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Jo S, Suh CH, Lee S, Lee J, Yoon M, Heo H, Shim WH, Kim SJ, Kim EY, Chung SJ. Susceptibility map-weighted MRI can distinguish tremor-dominant Parkinson's disease from essential tremor. Sci Rep 2025; 15:823. [PMID: 39755717 PMCID: PMC11700172 DOI: 10.1038/s41598-024-81089-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 11/25/2024] [Indexed: 01/06/2025] Open
Abstract
Distinguishing between Parkinson's disease (PD) and essential tremor (ET) can be challenging sometimes. Although positron emission tomography can confirm PD diagnosis, its application is limited by high cost and exposure to radioactive isotopes. Patients with PD exhibit loss of the dorsal nigral hyperintensity on brain magnetic resonance imaging (MRI). Novel MRI-based approaches, including susceptibility map-weighted imaging (SMwI), allow visualization of the dorsal nigral hyperintensity at an increased resolution. Herein, we investigated the diagnostic accuracy of dorsal nigral hyperintensity evaluation on SMwI for distinguishing tremor-dominant PD from ET. Consecutive patients with tremor who underwent SMwI and were diagnosed with tremor-dominant PD or ET between July 2021 and July 2022 were enrolled. The dorsal nigral hyperintensity loss on SMwI was compared between the PD and ET groups. All 143 patients (100%) with tremor-dominant PD showed unilateral or bilateral dorsal nigral hyperintensity loss. Among 136 patients with ET, 131 (96.3%) exhibited an intact dorsal nigral hyperintensity, while 5 (3.7%) showed unilateral/bilateral dorsal nigral hyperintensity loss. SMwI discriminated between tremor-dominant PD and ET with a sensitivity and specificity of 100% and 96.3%, respectively. 18F-FP-CIT PET revealed normal findings in 4/5 patients with ET who had false-positive results on SMwI. These results indicate that dorsal nigral hyperintensity loss on SMwI could differentiate between tremor-dominant PD and ET with high accuracy.
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Affiliation(s)
- Sungyang Jo
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Chong Hyun Suh
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
| | - Sangjin Lee
- Department of Neurology, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Jihyun Lee
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - MyungKi Yoon
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hwon Heo
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Woo Hyun Shim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang Joon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eung Yeop Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sun Ju Chung
- Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
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Sato T, Sawai S, Shimada N. Comparison of the ability of different quantitative indices in 123I-FP-CIT single-photon emission computed tomography to differentiate dopaminergic neurodegenerative disease. Jpn J Radiol 2025; 43:78-90. [PMID: 39235674 PMCID: PMC11717878 DOI: 10.1007/s11604-024-01648-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 08/21/2024] [Indexed: 09/06/2024]
Abstract
PURPOSE By imaging dopamine transporter (DAT) uptake in the striatum, 123I-FP-CIT SPECT can differentiate dopaminergic neurodegenerative disease (dNDD) and non-dNDD, which differ in pathophysiology and clinical management. Our aim was to compare and validate the diagnostic abilities of various 123I-FP-CIT SPECT quantitative indices for dNDD. MATERIALS AND METHODS Distribution volume ratio (DVR) and binding ratio (BR), measures of DAT uptake capacity, were measured by analyzing clinical 123I-FP-CIT SPECT images of 29 patients with dNDD, including dementia with Lewy bodies and Parkinson's disease, and 18 patients with non-dNDD, using Montreal Neurological Institute space-based anatomical standardization and an atlas template, which utilizes statistical parametric mapping. Additionally, we computed the specific binding ratio (SBR) based on Bolt's method and the maximum and mean standardized uptake values (SUVmax and SUVmean, respectively). RESULTS The caudate-to-occipital lobe, putamen-to-occipital lobe, and striatum-to-occipital lobe ratios (COR, POR, and SOR, respectively) on DVR and POR and SOR on BR were significantly lower in dNDD than in non-dNDD, with areas under the ROC curve (AUCs) of 0.941-0.960, showing high diagnostic accuracy for dNDD. However, the AUC of COR on BR was 0.839, indicating lower diagnostic performance. SBR had an AUC of 0.921, while SUVmax and SUVmean had AUCs of 0.906 and 0.900, respectively. Although striatal asymmetry on both DVR and BR exhibited AUCs of 0.728 and 0.734 and asymmetry on SBR showed an AUC of 0.757, the ratio-based DAT quantitative indices were superior. There were strong positive correlations of DVR with BR, DVR with SBR or SUVmax, BR with SBR or SUVmax, and SBR with SUVmax. CONCLUSION COR, POR, and SOR on DVR and POR and SOR on BR were the most useful DAT quantitative indices. These indices can be compared with SBR and SUV, suggesting that comprehensive evaluation improves the diagnostic accuracy of dNDD.
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Affiliation(s)
- Tomohiro Sato
- Department of Radiology, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
- Department of Radiology, Chiba Aoba Municipal Hospital, 1273-2 Aoba-cho, Chuo-ku, Chiba City, Chiba, 260-0852, Japan.
| | - Setsu Sawai
- Department of Neurology, Chiba Aoba Municipal Hospital, 1273-2 Aoba-cho, Chuo-ku, Chiba City, Chiba, 260-0852, Japan
| | - Naokazu Shimada
- Department of Radiology, Chiba Aoba Municipal Hospital, 1273-2 Aoba-cho, Chuo-ku, Chiba City, Chiba, 260-0852, Japan
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Mizumura S, Tamamura N, Ebina J, Watanabe H, Hori M. Quantitative evaluation of striatal uptake ratios using an adaptive template registration method for 123I-ioflupane dopamine transporter SPECT. Ann Nucl Med 2024; 38:943-959. [PMID: 39158826 PMCID: PMC11538170 DOI: 10.1007/s12149-024-01968-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 08/07/2024] [Indexed: 08/20/2024]
Abstract
INTRODUCTION 123I-FP-CIT (123I-Ioflupane) SPECT shows strong accumulation in the striatum, but morphological standardization is challenging due to low accumulation outside the striatum, particularly in subjects with marked striatal decline. In this study, morphological standardization without MRI was achieved using the adaptive template registration (ATR) method to create a subject-specific optimized template with weighted images of normal-type and egg-shape-type templates. The accuracy of a quantitative method for calculating the ratio with nonspecific accumulation in the occipital lobe was evaluated by placing voxels-of-interest (VOI) on standardized images, particularly targeting the striatum. METHODS The average images of eight subjects, demonstrating normal-type and egg-shape-type tracer accumulation in 123I-Ioflupane SPECT, were utilized as normal and disease templates, respectively. The study included 300 subjects that underwent both 123I-Ioflupane SPECT and MRI for the diagnosis of suspected Parkinson's disease or for exclusion diagnosis. Morphological standardization of SPECT images using structural MRI (MRI-based method) was considered the standard of truth (SOT). Three morphological standardizations without MRI were conducted. The first involved conventional morphological standardization using a normal template (fixed template method), the second employed the ATR method, with a weighted template, and the third used the split-ATR method, processing the left and right striatum separately to address asymmetrical accumulation. VOIs were set on the striatum, caudate, putamen as regions of specific accumulation, and on the occipital lobe as a reference region for nonspecific accumulation. RESULTS Results showed significant and robust linearity in the striatal accumulation ratios for all templates when compared with the occipital lobe accumulation ratio when using the MRI-based method. Comparing intra-class correlations for different linearities, the ATR method and split-ATR method demonstrated higher linearity in the striatum, caudate, and putamen. The split-ATR method showed similar improvements, although more linearity than some of the ATR methods; the effectiveness of the Split-ATR method may vary by image quality, and further validation of its effectiveness in diverse asymmetric accumulation cases seemed warranted. CONCLUSION The use of optimized templates, such as the ATR and split-ATR methods, improved reproducibility in fully automated processing and demonstrated superior linearity compared to that of MRI-based method, in the ratio to the occipital lobe. The ATR method, which enables morphological standardization when using SPECT images only, proved highly reproducible for clinical quantitative analysis of striatal accumulation, facilitating its clinical use.
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Affiliation(s)
- Sunao Mizumura
- Department of Radiology, Toho University Omori Medical Center, 1‑1‑5, Omori‑nishi, Ota‑ku, Tokyo, 143‑8541, Japan.
| | - Naoyuki Tamamura
- Nihon Medi-Physics Co., Ltd., 3‑4‑10, Shinsuna, Koto‑ku, Tokyo, 136‑0075, Japan
| | - Junya Ebina
- Department of Neurology, Toho University Omori Medical Center, 1-1-5 Omori‑nishi, Ota‑ku, Tokyo, Japan
| | - Hikaru Watanabe
- Department of Radiology, Toho University Omori Medical Center, 1‑1‑5, Omori‑nishi, Ota‑ku, Tokyo, 143‑8541, Japan
| | - Masaaki Hori
- Department of Radiology, Toho University Omori Medical Center, 1‑1‑5, Omori‑nishi, Ota‑ku, Tokyo, 143‑8541, Japan
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Ahn JH, Kim MH, Lee K, Oh K, Lim H, Kil HS, Kwon SJ, Choi JY, Chi DY, Lee YJ. Preclinical evaluation of [ 18F]FP-CIT, the radiotracer targeting dopamine transporter for diagnosing Parkinson's disease: pharmacokinetic and efficacy analysis. EJNMMI Res 2024; 14:59. [PMID: 38958796 PMCID: PMC11222350 DOI: 10.1186/s13550-024-01121-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 06/14/2024] [Indexed: 07/04/2024] Open
Abstract
BACKGROUND N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (FP-CIT), the representative cocaine derivative used in dopamine transporter imaging, is a promising biomarker, as it reflects the severity of Parkinson's disease (PD). 123I- and 18F-labeled FP-CIT has been used for PD diagnosis. However, preclinical studies evaluating [18F]FP-CIT as a potential diagnostic biomarker are scarce. Among translational research advancements from bench to bedside, translating preclinical findings into clinical practice is one-directional. The aim of this study is to employ a circular approach, beginning back from the preclinical stage, progressing to the supplementation of [18F]FP-CIT, and subsequently returning to clinical application. We investigated the pharmacokinetic properties of [18F]FP-CIT and its efficacy for PD diagnosis using murine models. RESULTS Biodistribution, metabolite and excretion analyses were performed in mice and PD models were induced in rats using 6-hydroxydopamine (6-OHDA). The targeting efficiency of [18F]FP-CIT for the dopamine receptor was assessed through animal PET/CT imaging. Subsequently, correlation analysis was conducted between animal PET/CT imaging results and immunohistochemistry (IHC) targeting tyrosine hydroxylase. Rapid circulation was confirmed after [18F]FP-CIT injection. [18F]FP-CIT reached the highest uptake of 23.50 ± 12.46%ID/g in the striatum 1 min after injection, and it was rapidly excreted within 60 min. The major metabolic organs of [18F]FP-CIT were confirmed to be the intestines, liver, and kidneys. Its uptake in the intestine was approximately 5% ID/g. The uptake in the liver gradually increased, with excretion beginning after reaching a maximum after 60 min. The kidneys exhibited rapid elimination after 10 min. In the excretion study, rapid elimination was verified, with 21.46 ± 9.53% of the compound excreted within a 6 h period. Additionally, the efficacy of [18F]FP-CIT PET was demonstrated in the PD model, with a high correlation with IHC for both the absolute value (R = 0.803, p = 0.0017) and the ratio value (R = 0.973, p = 0.0011). CONCLUSIONS This study fills the gap regarding insufficient preclinical studies on [18F]FP-CIT, including its ADME, metabolites, and efficiency. The pharmacological results, including accurate diagnosis, rapid circulation, and [18F]FP-CIT excretion, provide complementary evidence that [18F]FP-CIT can be used safely and efficiently to diagnose PD in clinics, although it is already used in clinics.
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Affiliation(s)
- Jae Hun Ahn
- Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, 01812, Korea
- Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, 03080, Korea
| | - Min Hwan Kim
- Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd., Seoul, 04793, Korea
| | - Kyongkyu Lee
- Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd., Seoul, 04793, Korea
| | - Keumrok Oh
- Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd., Seoul, 04793, Korea
| | - Hyunwoo Lim
- Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd., Seoul, 04793, Korea
| | - Hee Seup Kil
- Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd., Seoul, 04793, Korea
| | - Soon Jeong Kwon
- Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd., Seoul, 04793, Korea
| | - Jae Yong Choi
- Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, 01812, Korea
- Radiological and Medico-Oncological Sciences, University of Science and Technology (UST), Seoul, Korea
| | - Dae Yoon Chi
- Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd., Seoul, 04793, Korea.
| | - Yong Jin Lee
- Division of Applied RI, Korea Institute of Radiological and Medical Sciences (KIRAMS), Seoul, 01812, Korea.
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Lee C, Yoon SY, Lee SW, Jeong SY, Park E, Hwang JH, Park KS, Kang K. Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus Patient With Parkinson's Disease-Compatible Findings on Dopamine Transporter Scans. Dement Neurocogn Disord 2024; 23:161-163. [PMID: 39113751 PMCID: PMC11300687 DOI: 10.12779/dnd.2024.23.3.161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/03/2024] [Accepted: 06/06/2024] [Indexed: 08/10/2024] Open
Affiliation(s)
- Chaejin Lee
- Department of Neurosurgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Sang-Youl Yoon
- Department of Neurosurgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Sang-Woo Lee
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Shin Young Jeong
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Eunhee Park
- Department of Rehabilitation Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jeong-Hyun Hwang
- Department of Neurosurgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Ki-Su Park
- Department of Neurosurgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Kyunghun Kang
- Department of Neurology, School of Medicine, Kyungpook National University, Daegu, Korea
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Nakata T, Shimada K, Iba A, Oda H, Terashima A, Koide Y, Kawasaki R, Yamada T, Ishii K. Differential diagnosis of MCI with Lewy bodies and MCI due to Alzheimer's disease by visual assessment of occipital hypoperfusion on SPECT images. Jpn J Radiol 2024; 42:308-318. [PMID: 37861956 DOI: 10.1007/s11604-023-01501-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/27/2023] [Indexed: 10/21/2023]
Abstract
PURPOSE Predicting progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD) or dementia with Lewy bodies (DLB) is important. We evaluated morphological and functional differences between MCI with Lewy bodies (MCI-LB) and MCI due to AD (MCI-AD), and a method for differentiating between these conditions using brain MRI and brain perfusion SPECT. METHODS A continuous series of 101 subjects, who had visited our memory clinic and met the definition of MCI, were enrolled retrospectively. They were consisted of 60 MCI-LB and 41 MCI-AD subjects. Relative cerebral blood flow (rCBF) on SPECT images and relative brain atrophy on MRI images were evaluated. We performed voxel-based analysis and visually inspected brain perfusion SPECT images for regional brain atrophy, occipital hypoperfusion and the cingulate island sign (CIS), for differential diagnosis of MCI-LB and MCI-AD. RESULTS MRI showed no significant differences in regional atrophy between the MCI-LB and MCI-AD groups. In MCI-LB subjects, occipital rCBF was significantly decreased compared with MCI-AD subjects (p < 0.01, family wise error [FWE]-corrected). Visual inspection of occipital hypoperfusion had sensitivity, specificity, and accuracy values of 100%, 73.2% and 89.1%, respectively, for differentiating MCI-LB and MCI-AD. Occipital hypoperfusion was offered higher diagnostic utility than the CIS. CONCLUSIONS The occipital lobe was the region with significantly decreased rCBF in MCI-LB compared with MCI-AD subjects. Occipital hypoperfusion on brain perfusion SPECT may be a more useful imaging biomarker than the CIS for visually differentiating MCI-LB and MCI-AD.
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Affiliation(s)
- Takashi Nakata
- Neurocognitive Disorders Medical Center, Hyogo Prefectural Harima-Himeji General Medical Center, 3-264 Kamiyacho, Himeji, Hyogo, 670-8560, Japan.
- Department of Radiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, Japan.
- Department of Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, 520 Saisho-Ko, Himji, Hyogo, Japan.
| | - Kenichi Shimada
- Neurocognitive Disorders Medical Center, Hyogo Prefectural Harima-Himeji General Medical Center, 3-264 Kamiyacho, Himeji, Hyogo, 670-8560, Japan
- Department of Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, 520 Saisho-Ko, Himji, Hyogo, Japan
| | - Akiko Iba
- Department of Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, 520 Saisho-Ko, Himji, Hyogo, Japan
- Department of Psychiatry, Hyogo Prefectural Harima-Himeji General Medical Center, 3-264 Kamiyacho, Himeji, Hyogo, Japan
- Hyogo Mental Health Center, 3 Noborio, Kamitanigami, Yamadacho, Kita-Ku, Kobe, Hyogo, Japan
| | - Haruhiko Oda
- Neurocognitive Disorders Medical Center, Hyogo Prefectural Harima-Himeji General Medical Center, 3-264 Kamiyacho, Himeji, Hyogo, 670-8560, Japan
- Department of Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, 520 Saisho-Ko, Himji, Hyogo, Japan
- Hyogo Mental Health Center, 3 Noborio, Kamitanigami, Yamadacho, Kita-Ku, Kobe, Hyogo, Japan
| | - Akira Terashima
- Neurocognitive Disorders Medical Center, Hyogo Prefectural Harima-Himeji General Medical Center, 3-264 Kamiyacho, Himeji, Hyogo, 670-8560, Japan
- Department of Aging Brain and Cognitive Disorders, Hyogo Brain and Heart Center, 520 Saisho-Ko, Himji, Hyogo, Japan
| | - Yutaka Koide
- Department of Diagnostic and Interventional Radiology, Hyogo Prefectural Harima-Himeji General Medical Center, 3-264 Kamiyacho, Himeji, Hyogo, Japan
- Department of Radiology and Nuclear Medicine, Hyogo Brain and Heart Center, 520 Saisho-Ko, Himeji, Hyogo, Japan
| | - Ryota Kawasaki
- Department of Diagnostic and Interventional Radiology, Hyogo Prefectural Harima-Himeji General Medical Center, 3-264 Kamiyacho, Himeji, Hyogo, Japan
- Department of Radiology and Nuclear Medicine, Hyogo Brain and Heart Center, 520 Saisho-Ko, Himeji, Hyogo, Japan
| | - Takahiro Yamada
- Department of Radiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, Japan
| | - Kazunari Ishii
- Department of Radiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, Japan
- Department of Diagnostic and Interventional Radiology, Hyogo Prefectural Harima-Himeji General Medical Center, 3-264 Kamiyacho, Himeji, Hyogo, Japan
- Department of Radiology and Nuclear Medicine, Hyogo Brain and Heart Center, 520 Saisho-Ko, Himeji, Hyogo, Japan
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Middleton JS, Hovren HL, Kha N, Medina MJ, MacLeod KR, Concha-Marambio L, Jensen KJ. Seed amplification assay results illustrate discrepancy in Parkinson's disease clinical diagnostic accuracy and error rates. J Neurol 2023; 270:5813-5818. [PMID: 37592136 PMCID: PMC10632284 DOI: 10.1007/s00415-023-11810-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 05/26/2023] [Accepted: 06/07/2023] [Indexed: 08/19/2023]
Abstract
Parkinson's disease (PD) may be misdiagnosed due to the clinical overlap between PD and atypical parkinsonism. The utility of α-Synuclein (αSyn) Seed Amplification Assay (SAA) as a diagnostic indicator for PD has been reported in numerous studies, but never when administered as a validated clinical laboratory test. This study compares results from αSyn-SAA validation testing performed using well-characterized cohorts from two biorepositories to better understand the accuracy of PD clinical diagnosis. Blinded cerebrospinal fluid (CSF) specimens from a repository that included cohorts of subjects clinically diagnosed as PD or healthy controls, both with confirmatory dopamine transporter single-photon emission computed tomography (DAT SPECT) imaging, and blinded CSF specimens from a repository that included cohorts of subjects clinically diagnosed as PD or healthy controls based on clinical diagnosis alone, were tested as part of the validation studies for the diagnostic αSyn-SAA test (SYNTap® Biomarker Test). Measured αSyn-SAA test accuracy was 83.9% using clinical diagnosis as comparator, and 93.6% using clinical diagnosis with confirmatory DAT- SPECT imaging as comparator. The statistically significant discordance between accuracy determinations using specimens classified using different diagnostic inclusion criteria indicates that there is some symbiosis between dopamine-weighted imaging and αSyn-SAA results, both of which are associated with higher accuracy compared with the clinical diagnosis alone.
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Affiliation(s)
| | | | - Nelson Kha
- Clinical Laboratory, Amprion Inc, San Diego, CA, USA
| | | | | | - Luis Concha-Marambio
- Research Laboratory, Amprion Inc, 10355 Science Center Drive, San Diego, CA, 92121, USA
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Ishizawa K, Fujita Y, Nagashima K, Nakamura T, Shibata M, Kasahara H, Makioka K, Taketomi-Takahashi A, Hirasawa H, Higuchi T, Tsushima Y, Ikeda Y. Striatal dopamine transporter binding differs between dementia with Lewy bodies and Parkinson's disease with dementia. J Neurol Sci 2023; 451:120713. [PMID: 37441875 DOI: 10.1016/j.jns.2023.120713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 07/15/2023]
Abstract
123I-ioflupane single-photon emission computed tomography (SPECT) is a highly sensitive and established neuroimaging technique for parkinsonian syndromes (PS). However, differentiating PS by visual inspection or analysis of regions of interest is challenging. To date, image analysis has not been able to differentiate dementia with Lewy bodies (DLB) from Parkinson's disease with dementia (PDD). This study aimed to differentiate PS based on the characteristics of striatal dopamine transporter (DAT) binding using voxel-based analysis. We acquired 123I-ioflupane SPECT data from patients with DLB (n = 30), Parkinson's disease (PD; n = 122), PDD (n = 19), multiple system atrophy with predominant parkinsonism (MSA-P; n = 18), and progressive supranuclear palsy (PSP; n = 45). DAT binding was reduced in the posterior striatum of patients with PD and PDD, whereas it was similar in MSA-P, PSP, and DLB. Hippocampal atrophy, visually evaluated by cerebral magnetic resonance imaging, did not affect striatal DAT binding in DLB. DAT binding in the anterior striatum was inversely correlated with the severity of parkinsonism in PD and PDD but not in DLB. Thus, the appearance of striatal DAT binding might indicate different pathological processes in DLB and PDD.
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Affiliation(s)
- Kunihiko Ishizawa
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Yukio Fujita
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Kazuaki Nagashima
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Takumi Nakamura
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Makoto Shibata
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Hiroo Kasahara
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Kouki Makioka
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Ayako Taketomi-Takahashi
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Hiromi Hirasawa
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Tetsuya Higuchi
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Yoshito Tsushima
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Yoshio Ikeda
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan.
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Ohba M, Kobayashi R, Iseki C, Kirii K, Morioka D, Otani K, Ohta Y, Sonoda Y, Suzuki K, Kanoto M. Effect of cerebrospinal fluid area mask correction on 123I-FP-CIT SPECT images in idiopathic normal pressure hydrocephalus. BMC Med Imaging 2023; 23:81. [PMID: 37312030 DOI: 10.1186/s12880-023-01038-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 05/30/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Cerebrospinal fluid (CSF) area mask correction reduces the influence of low [123I]-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) accumulation in the volume of interest (VOI) by CSF area dilatation on the specific binding ratio (SBR) calculated using the Southampton method. We assessed the effect of CSF area mask correction on the SBR for idiopathic normal pressure hydrocephalus (iNPH) characterized by CSF area dilatation. METHODS We enrolled 25 patients with iNPH who were assessed using 123I-FP-CIT single-photon emission computed tomography (SPECT) before shunt surgery or the tap test. The SBRs with and without CSF area mask correction were calculated, and changes in quantitative values were verified. Additionally, the number of voxels in the striatal and background (BG) VOI before and after CSF area mask correction were extracted. The number of voxels after correction was subtracted from that before correction, and the volume removed by the CSF area mask correction was calculated. The volumes removed from each VOI were compared to verify their effect on SBR. RESULTS The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF area mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively than those in the striatal region. CONCLUSIONS The SBR before and after CSF area mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results suggest that CSF area mask correction is effective in patients with iNPH. TRIAL REGISTRATION This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826. 11/07/2021.
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Affiliation(s)
- Makoto Ohba
- Department of Radiology, Yamagata University Hospital, Yamagata, Japan.
| | - Ryota Kobayashi
- Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan.
| | - Chifumi Iseki
- Division of Neurology and Clinical Neuroscience, Department of Internal Medicine III, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Kazukuni Kirii
- Division of Diagnostic Radiology, Department of Radiology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Daichi Morioka
- Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan
| | - Koichi Otani
- Department of Psychiatry, Yamagata University School of Medicine, Yamagata, Japan
| | - Yasuyuki Ohta
- Division of Neurology and Clinical Neuroscience, Department of Internal Medicine III, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Yukihiko Sonoda
- Department of Neurosurgery, Yamagata University School of Medicine, Yamagata, Japan
| | - Koji Suzuki
- Department of Radiology, Yamagata University Hospital, Yamagata, Japan
| | - Masafumi Kanoto
- Division of Diagnostic Radiology, Department of Radiology, Yamagata University Faculty of Medicine, Yamagata, Japan
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10
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Bae YJ, Choi BS, Kim JM, Ai WA, Yun I, Song YS, Nam Y, Cho SJ, Kim JH. Deep learning regressor model based on nigrosome MRI in Parkinson syndrome effectively predicts striatal dopamine transporter-SPECT uptake. Neuroradiology 2023:10.1007/s00234-023-03168-z. [PMID: 37209181 DOI: 10.1007/s00234-023-03168-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 05/15/2023] [Indexed: 05/22/2023]
Abstract
PURPOSE Nigrosome imaging using susceptibility-weighted imaging (SWI) and dopamine transporter imaging using 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT) single-photon emission computerized tomography (SPECT) can evaluate Parkinsonism. Nigral hyperintensity from nigrosome-1 and striatal dopamine transporter uptake are reduced in Parkinsonism; however, quantification is only possible with SPECT. Here, we aimed to develop a deep-learning-based regressor model that can predict striatal 123I-FP-CIT uptake on nigrosome magnetic resonance imaging (MRI) as a biomarker for Parkinsonism. METHODS Between February 2017 and December 2018, participants who underwent 3 T brain MRI including SWI and 123I-FP-CIT SPECT based on suspected Parkinsonism were included. Two neuroradiologists evaluated the nigral hyperintensity and annotated the centroids of nigrosome-1 structures. We used a convolutional neural network-based regression model to predict striatal specific binding ratios (SBRs) measured via SPECT using the cropped nigrosome images. The correlation between measured and predicted SBRs was evaluated. RESULTS We included 367 participants (203 women (55.3%); age, 69.0 ± 9.2 [range, 39-88] years). Random data from 293 participants (80%) were used for training. In the test set (74 participants [20%]), the measured and predicted 123I-FP-CIT SBRs were significantly lower with the loss of nigral hyperintensity (2.31 ± 0.85 vs. 2.44 ± 0.90) than with intact nigral hyperintensity (4.16 ± 1.24 vs. 4.21 ± 1.35, P < 0.01). The sorted measured 123I-FP-CIT SBRs and the corresponding predicted values were significantly and positively correlated (ρc = 0.7443; 95% confidence interval, 0.6216-0.8314; P < 0.01). CONCLUSION A deep learning-based regressor model effectively predicted striatal 123I-FP-CIT SBRs based on nigrosome MRI with high correlation using manually-measured values, enabling nigrosome MRI as a biomarker for nigrostriatal dopaminergic degeneration in Parkinsonism.
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Affiliation(s)
- Yun Jung Bae
- Departments of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Byung Se Choi
- Departments of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jong-Min Kim
- Departments of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173beon-gil, Bundang-gu, 13620, Seongnam, Republic of Korea.
| | - Walid Abdullah Ai
- Division of Computer Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea
| | - Ildong Yun
- Division of Computer Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea
| | - Yoo Sung Song
- Departments of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Yoonho Nam
- Division of Computer Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea
| | - Se Jin Cho
- Departments of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Jae Hyoung Kim
- Departments of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
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11
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Apostolova I, Schiebler T, Lange C, Mathies FL, Lehnert W, Klutmann S, Buchert R. Stereotactical normalization with multiple templates representative of normal and Parkinson-typical reduction of striatal uptake improves the discriminative power of automatic semi-quantitative analysis in dopamine transporter SPECT. EJNMMI Phys 2023; 10:25. [PMID: 36991245 DOI: 10.1186/s40658-023-00544-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 03/14/2023] [Indexed: 03/31/2023] Open
Abstract
BACKGROUND The specific binding ratio (SBR) of 123I-FP-CIT in the putamen is widely used to support the interpretation of dopamine transporter (DAT) SPECT. Automatic methods for computation of the putamen SBR often include stereotactical normalization of the individual DAT-SPECT image to an anatomical standard space. This study compared using a single 123I-FP-CIT template image as target for stereotactical normalization versus multiple templates representative of normal and different levels of Parkinson-typical reduction of striatal 123I-FP-CIT uptake. METHODS 1702 clinical 123I-FP-CIT SPECT images were stereotactically normalized (affine) to the anatomical space of the Montreal Neurological Institute (MNI) with SPM12 either using a single custom-made 123I-FP-CIT template representative of normal striatal uptake or using eight different templates representative of normal and different levels of Parkinson-typical reduction of striatal FP-CIT uptake with and without attenuation and scatter correction. In the latter case, SPM finds the linear combination of the multiple templates that best matches the patient's image. The putamen SBR was obtained using hottest voxels analysis in large unilateral regions-of-interest predefined in MNI space. The histogram of the putamen SBR in the whole sample was fitted by the sum of two Gaussians. The power to differentiate between reduced and normal SBR was estimated by the effect size of the distance between the two Gaussians computed as the differences between their mean values scaled to their pooled standard deviation. RESULTS The effect size of the distance between the two Gaussians was 3.83 with the single template versus 3.96 with multiple templates for stereotactical normalization. CONCLUSIONS Multiple templates representative of normal and different levels of Parkinson-typical reduction for stereotactical normalization of DAT-SPECT might provide improved separation between normal and reduced putamen SBR that could result in slightly improved power for the detection of nigrostriatal degeneration.
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Affiliation(s)
- Ivayla Apostolova
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Tassilo Schiebler
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Catharina Lange
- Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Franziska Lara Mathies
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Wencke Lehnert
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Susanne Klutmann
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Ralph Buchert
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
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12
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D’Elia A, Schiavi S, Manduca A, Rava A, Buzzelli V, Ascone F, Orsini T, Putti S, Soluri A, Galli F, Soluri A, Mattei M, Cicconi R, Massari R, Trezza V. FMR1 deletion in rats induces hyperactivity with no changes in striatal dopamine transporter availability. Sci Rep 2022; 12:22535. [PMID: 36581671 PMCID: PMC9800572 DOI: 10.1038/s41598-022-26986-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 12/22/2022] [Indexed: 12/30/2022] Open
Abstract
Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder emerging in early life characterized by impairments in social interaction, poor verbal and non-verbal communication, and repetitive patterns of behaviors. Among the best-known genetic risk factors for ASD, there are mutations causing the loss of the Fragile X Messenger Ribonucleoprotein 1 (FMRP) leading to Fragile X syndrome (FXS), a common form of inherited intellectual disability and the leading monogenic cause of ASD. Being a pivotal regulator of motor activity, motivation, attention, and reward processing, dopaminergic neurotransmission has a key role in several neuropsychiatric disorders, including ASD. Fmr1 Δexon 8 rats have been validated as a genetic model of ASD based on FMR1 deletion, and they are also a rat model of FXS. Here, we performed behavioral, biochemical and in vivo SPECT neuroimaging experiments to investigate whether Fmr1 Δexon 8 rats display ASD-like repetitive behaviors associated with changes in striatal dopamine transporter (DAT) availability assessed through in vivo SPECT neuroimaging. At the behavioral level, Fmr1 Δexon 8 rats displayed hyperactivity in the open field test in the absence of repetitive behaviors in the hole board test. However, these behavioral alterations were not associated with changes in striatal DAT availability as assessed by non-invasive in vivo SPECT and Western blot analyses.
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Affiliation(s)
- Annunziata D’Elia
- grid.5326.20000 0001 1940 4177Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), c/o International Campus “A. Buzzati-Traverso”, Via E. Ramarini, 32, 00015 Monterotondo Scalo (Rome), Italy ,grid.8509.40000000121622106Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy
| | - Sara Schiavi
- grid.8509.40000000121622106Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy
| | - Antonia Manduca
- grid.8509.40000000121622106Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy ,grid.417778.a0000 0001 0692 3437Neuroendocrinology, Metabolism and Neuropharmacology Unit, IRCSS Fondazione Santa Lucia, Rome, Italy
| | - Alessandro Rava
- grid.8509.40000000121622106Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy
| | - Valeria Buzzelli
- grid.8509.40000000121622106Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy
| | - Fabrizio Ascone
- grid.8509.40000000121622106Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy
| | - Tiziana Orsini
- grid.5326.20000 0001 1940 4177Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), c/o International Campus “A. Buzzati-Traverso”, Via E. Ramarini, 32, 00015 Monterotondo Scalo (Rome), Italy
| | - Sabrina Putti
- grid.5326.20000 0001 1940 4177Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), c/o International Campus “A. Buzzati-Traverso”, Via E. Ramarini, 32, 00015 Monterotondo Scalo (Rome), Italy
| | - Andrea Soluri
- grid.5326.20000 0001 1940 4177Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), c/o International Campus “A. Buzzati-Traverso”, Via E. Ramarini, 32, 00015 Monterotondo Scalo (Rome), Italy ,grid.9657.d0000 0004 1757 5329Unit of Molecular Neurosciences, University Campus Bio-Medico, Rome, Rome, Italy
| | - Filippo Galli
- grid.7841.aNuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, Rome, Italy
| | - Alessandro Soluri
- grid.5326.20000 0001 1940 4177Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), c/o International Campus “A. Buzzati-Traverso”, Via E. Ramarini, 32, 00015 Monterotondo Scalo (Rome), Italy
| | - Maurizio Mattei
- grid.6530.00000 0001 2300 0941Department of Biology and Centro di Servizi Interdipartimentale-Stazione per la Tecnologia Animale, “Tor Vergata” University, Rome, Italy
| | - Rosella Cicconi
- grid.6530.00000 0001 2300 0941Department of Biology and Centro di Servizi Interdipartimentale-Stazione per la Tecnologia Animale, “Tor Vergata” University, Rome, Italy
| | - Roberto Massari
- grid.5326.20000 0001 1940 4177Institute of Biochemistry and Cell Biology (IBBC), National Research Council of Italy (CNR), c/o International Campus “A. Buzzati-Traverso”, Via E. Ramarini, 32, 00015 Monterotondo Scalo (Rome), Italy
| | - Viviana Trezza
- grid.8509.40000000121622106Department of Science, Section of Biomedical Sciences and Technologies, Roma Tre University, Viale G. Marconi 446, 00146 Rome, Italy
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13
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Mathies F, Apostolova I, Dierck L, Jacobi J, Kuen K, Sauer M, Schenk M, Klutmann S, Forgács A, Buchert R. Multiple-pinhole collimators improve intra- and between-rater agreement and the certainty of the visual interpretation in dopamine transporter SPECT. EJNMMI Res 2022; 12:51. [PMID: 35976493 PMCID: PMC9385910 DOI: 10.1186/s13550-022-00923-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 08/08/2022] [Indexed: 11/10/2022] Open
Abstract
Background Multiple-pinhole (MPH) collimators improve the resolution–sensitivity trade-off compared to parallel-hole collimators. This study evaluated the impact of MPH collimators on intra- and between-rater agreement, and on the certainty of visual interpretation in dopamine transporter (DAT)-SPECT. Methods The study included 71 patients (62.1 ± 12.7 y). Two SPECT acquisitions were performed in randomized order after a single injection of 182 ± 9 MBq 123I-FP-CIT, one with MPH and one with low-energy–high-resolution–high-sensitivity (LEHRHS) collimators. MPH projections were reconstructed with an iterative 3d Monte Carlo algorithm. LEHRHS projections were reconstructed with filtered backprojection (FBP) or with ordered-subsets expectation–maximization and resolution recovery (OSEM). Images were visually evaluated twice by three independent raters with respect to presence/absence of Parkinson-typical reduction of striatal 123I-FP-CIT uptake using a Likert 6-score (− 3 = clearly normal, …, 3 = clearly reduced). In case of intra-rater discrepancy, an intra-rater consensus was obtained. Intra- and between-rater agreement with respect to the Likert score (6-score and dichotomized score) was characterized by Cohen’s kappa. Results Intra-rater kappa of visual scoring of MPH/LEHRHS-OSEM/LEHRHS-FBP images was 0.84 ± 0.12/0.73 ± 0.06/0.73 ± 0.08 (6-score, mean of three raters) and 1.00 ± 0.00/0.96 ± 0.04/0.97 ± 0.03 (dichotomized score). Between-rater kappa of visual scoring (intra-rater consensus) of MPH/LEHRHS-OSEM/LEHRHS-FBP images was 0.70 ± 0.06/0.63 ± 0.08/0.48 ± 0.05 (6-score, mean of three pairs of raters) and 1.00 ± 0.00/0.92 ± 0.04/0.90 ± 0.06 (dichotomized score). There was a decrease of (negative) Likert scores in normal DAT-SPECT by 0.87 ± 0.18 points from the LEHRHS-OSEM to the MPH setting. The (positive) Likert scores of reduced DAT-SPECT did not change on average. Conclusions MPH collimators improve intra- and between-rater agreement as well as the certainty of the visual interpretation of DAT-SPECT. Supplementary Information The online version contains supplementary material available at 10.1186/s13550-022-00923-w.
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Affiliation(s)
- Franziska Mathies
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Ivayla Apostolova
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Lena Dierck
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Janin Jacobi
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Katja Kuen
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Markus Sauer
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Michael Schenk
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Susanne Klutmann
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | | | - Ralph Buchert
- Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
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14
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Ito Y, Fujita N, Hara K, Tada T, Abe S, Katsuno M, Naganawa S, Kato K. Novel approach to semi-quantification of tracer accumulation in dopamine transporter scan. J Appl Clin Med Phys 2022; 23:e13626. [PMID: 35536775 PMCID: PMC9278684 DOI: 10.1002/acm2.13626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 03/23/2023] [Accepted: 04/07/2022] [Indexed: 11/25/2022] Open
Abstract
Purpose Accurate tracer accumulation evaluation is difficult owing to the partial volume effect (PVE). We proposed a novel semi‐quantitative approach for measuring the accumulation amount by examining the approximate image. Using a striatal phantom, we verified the validity of a newly proposed method to accurately evaluate the tracer accumulations in the caudate and putamen separately. Moreover, we compared the proposed method with the conventional methods. Methods The left and right caudate/putamen regions and the whole brain region as background were identified in computed tomography (CT) images obtained by single‐photon emission computed tomography (SPECT)/CT and acquired the positional information of each region. SPECT‐like images were generated by assigning assumed accumulation amounts to each region. The SPECT‐like image, approximated to the actual measured SPECT image, was examined by changing the assumed accumulation amounts assigned to each region. When the generated SPECT‐like image most approximated the actual measured SPECT image, the accumulation amounts assumed were determined as the accumulation amounts in each region. We evaluated the correlation between the count density calculated by the proposed method and the actual count density of the 123I solution filled in the phantom. Conventional methods (CT‐guide method, geometric transfer matrix [GTM] method, region‐based voxel‐wise [RBV] method, and Southampton method) were also evaluated. The significance of differences between the correlation coefficients of various methods (except the Southampton method) was evaluated. Results The correlation coefficients between the actual count density and the SPECT count densities were 0.997, 0.973, 0.951, 0.950, and 0.996 for the proposed method, CT‐guide method, GTM method, RBV method, and Southampton method, respectively. The correlation of the proposed method was significantly higher than those of the other methods. Conclusions The proposed method could calculate accurate accumulation amounts in the caudate and putamen separately, considering the PVE.
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Affiliation(s)
- Yoshinori Ito
- Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan
| | - Naotoshi Fujita
- Department of Radiological Technology, Nagoya University Hospital, Showa-ku, Nagoya, Japan
| | - Kazuhiro Hara
- Department of Neurology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan
| | - Tomohiro Tada
- Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan
| | - Shinji Abe
- Department of Radiological Technology, Nagoya University Hospital, Showa-ku, Nagoya, Japan
| | - Masahisa Katsuno
- Department of Neurology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan
| | - Shinji Naganawa
- Department of Radiology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan
| | - Katsuhiko Kato
- Functional Medical Imaging, Biomedical Imaging Sciences, Division of Advanced Information Health Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan
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15
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Otani RTV, Yamamoto JYS, Nunes DM, Haddad MS, Parmera JB. Magnetic resonance and dopamine transporter imaging for the diagnosis of Parkinson´s disease: a narrative review. ARQUIVOS DE NEURO-PSIQUIATRIA 2022; 80:116-125. [PMID: 35976320 PMCID: PMC9491424 DOI: 10.1590/0004-282x-anp-2022-s130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 04/29/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND the diagnosis of Parkinson's disease (PD) can be challenging, especially in the early stages, albeit its updated and validated clinical criteria. Recent developments on neuroimaging in PD, altogether with its consolidated role of excluding secondary and other neurodegenerative causes of parkinsonism, provide more confidence in the diagnosis across the different stages of the disease. This review highlights current knowledge and major recent advances in magnetic resonance and dopamine transporter imaging in aiding PD diagnosis. OBJECTIVE This study aims to review current knowledge about the role of magnetic resonance imaging and neuroimaging of the dopamine transporter in diagnosing Parkinson's disease. METHODS We performed a non-systematic literature review through the PubMed database, using the keywords "Parkinson", "magnetic resonance imaging", "diffusion tensor", "diffusion-weighted", "neuromelanin", "nigrosome-1", "single-photon emission computed tomography", "dopamine transporter imaging". The search was restricted to articles written in English, published between January 2010 and February 2022. RESULTS The diagnosis of Parkinson's disease remains a clinical diagnosis. However, new neuroimaging biomarkers hold promise for increased diagnostic accuracy, especially in earlier stages of the disease. CONCLUSION Future validation of new imaging biomarkers bring the expectation of an increased neuroimaging role in the diagnosis of PD in the following years.
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Affiliation(s)
- Rafael Tomio Vicentini Otani
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil
| | - Joyce Yuri Silvestre Yamamoto
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil
| | - Douglas Mendes Nunes
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departmento de Radiologia e Oncologia, Instituto de Radiologia, São Paulo SP, Brazil
| | - Mônica Santoro Haddad
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil
| | - Jacy Bezerra Parmera
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brazil
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Marzilli E, Cerniglia L, Tambelli R, Cimino S. Children’s ADHD and Dysregulation Problems, DAT1 Genotype and Methylation, and their Interplay with Family Environment. CHILD & YOUTH CARE FORUM 2022. [DOI: 10.1007/s10566-022-09687-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Abstract
Background
International literature has underlined the complex interplay between genetic and environmental variables in shaping children’s emotional-behavioral functioning.
Objective
This study aimed to explore the dynamic relationship between children’s Dopamine Transporter (DAT1) genotype and methylation, and maternal and paternal affective environment, on children’s Attention Deficit Hyperactivity Disorder (ADHD) problems and dysregulation problems.
Method
In a community sample of 76 families with school-aged children, we assessed children’s DAT1 genotype and methylation, their own ADHD problems and dysregulation profile (CBCL 6–18 DP), and maternal and paternal psychopathological risk, parenting stress, and marital adjustment. Hierarchical regressions were carried out to verify the possible moderation of children’s genotype on the relationship between children’s methylation and psychopathological risk, parental environment and children’s methylation, and parental environment and children’s psychopathological risk.
Results
The levels of methylation at M1 CpG significantly predicted ADHD problems among children with 10/10 genotype, whereas high levels of methylation at M6 CpG predicted low ADHD problems for children with 9/x genotype. High levels of methylation at M3 CpG were associated with high scores of CBCL DP. DAT1 genotype moderated the relationship between maternal and paternal variables with children’s methylation and psychopathological risk. The scores of maternal and paternal Dyadic Adjustment Scale showed indirect effects on children’s methylation and psychopathological risk in relation to those exerted by risk factors.
Conclusion
Our study has supported the emerging evidence on the complex nature of children’s emotional-behavioral functioning and the associated risk and protective factors, with important implications for the planning of preventive programs.
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Bae YJ, Kim JM, Choi BS, Song YS, Nam Y, Cho SJ, Kim JH, Kim SE. MRI Findings in Parkinson’s Disease: Radiologic Assessment of Nigrostriatal Degeneration. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2022; 83:508-526. [PMID: 36238511 PMCID: PMC9514534 DOI: 10.3348/jksr.2022.0044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 05/06/2022] [Accepted: 05/12/2022] [Indexed: 11/15/2022]
Abstract
파킨슨병은 중뇌 흑질에 위치한 도파민성 신경세포의 퇴행성 소실로 인해 발생하는 이상운동질환이다. 최근 다양한 자기공명영상기법의 발전으로 파킨슨병에서 일어나는 병리생태학적인 변화를 반영하는 여러 영상 소견들이 보고되었다. 여러 연구에서 이러한 영상 소견들은 파킨슨병의 진단 및 비정형 파킨슨증과의 감별 등에 유의미한 도움을 줄 수 있는 것이 밝혀졌다. 본 종설에서는, 파킨슨병에서 일어나는 흑질선조체 변성의 병태생리를 나타낼 수 있는 나이그로좀 영상 및 뉴로멜라닌 영상 등을 포함한 자기공명영상기법들과 각 영상에서 나타나는 소견에 대하여 자세히 다루었다.
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Affiliation(s)
- Yun Jung Bae
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jong-Min Kim
- Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Byung Se Choi
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yoo Sung Song
- Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yoonho Nam
- Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Korea
| | - Se Jin Cho
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jae Hyoung Kim
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sang Eun Kim
- Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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18
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Palermo G, Giannoni S, Bellini G, Siciliano G, Ceravolo R. Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review. Int J Mol Sci 2021; 22:11234. [PMID: 34681899 PMCID: PMC8538800 DOI: 10.3390/ijms222011234] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 11/16/2022] Open
Abstract
A major goal of current clinical research in Parkinson's disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts.
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Affiliation(s)
- Giovanni Palermo
- Unit of Neurology, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (G.P.); (S.G.); (G.B.); (G.S.)
| | - Sara Giannoni
- Unit of Neurology, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (G.P.); (S.G.); (G.B.); (G.S.)
- Unit of Neurology, San Giuseppe Hospital, 50053 Empoli, Italy
| | - Gabriele Bellini
- Unit of Neurology, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (G.P.); (S.G.); (G.B.); (G.S.)
| | - Gabriele Siciliano
- Unit of Neurology, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (G.P.); (S.G.); (G.B.); (G.S.)
| | - Roberto Ceravolo
- Unit of Neurology, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy; (G.P.); (S.G.); (G.B.); (G.S.)
- Center for Neurodegenerative Diseases, Unit of Neurology, Parkinson’s Disease and Movement Disorders, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
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19
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Herborg F, Jensen KL, Tolstoy S, Arends NV, Posselt LP, Shekar A, Aguilar JI, Lund VK, Erreger K, Rickhag M, Lycas MD, Lonsdale MN, Rahbek-Clemmensen T, Sørensen AT, Newman AH, Løkkegaard A, Kjaerulff O, Werge T, Møller LB, Matthies HJ, Galli A, Hjermind LE, Gether U. Dominant-negative actions of a dopamine transporter variant identified in patients with parkinsonism and neuropsychiatric disease. JCI Insight 2021; 6:e151496. [PMID: 34375312 PMCID: PMC8492322 DOI: 10.1172/jci.insight.151496] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 07/28/2021] [Indexed: 11/17/2022] Open
Abstract
Dysfunctional dopaminergic neurotransmission is central to movement disorders and mental diseases. The dopamine transporter (DAT) regulates extracellular dopamine levels, but the genetic and mechanistic link between DAT function and dopamine-related pathologies is not clear. Particularly, the pathophysiological significance of monoallelic missense mutations in DAT is unknown. Here, we use clinical information, neuroimaging, and large-scale exome-sequencing data to uncover the occurrence and phenotypic spectrum of a DAT coding variant, DAT-K619N, which localizes to the critical C-terminal PSD-95/Discs-large/ZO-1 homology–binding motif of human DAT (hDAT). We identified the rare but recurrent hDAT-K619N variant in exome-sequenced samples of patients with neuropsychiatric diseases and a patient with early-onset neurodegenerative parkinsonism and comorbid neuropsychiatric disease. In cell cultures, hDAT-K619N displayed reduced uptake capacity, decreased surface expression, and accelerated turnover. Unilateral expression in mouse nigrostriatal neurons revealed differential effects of hDAT-K619N and hDAT-WT on dopamine-directed behaviors, and hDAT-K619N expression in Drosophila led to impairments in dopamine transmission with accompanying hyperlocomotion and age-dependent disturbances of the negative geotactic response. Moreover, cellular studies and viral expression of hDAT-K619N in mice demonstrated a dominant-negative effect of the hDAT-K619N mutant. Summarized, our results suggest that hDAT-K619N can effectuate dopamine dysfunction of pathological relevance in a dominant-negative manner.
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Affiliation(s)
- Freja Herborg
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Kathrine L Jensen
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Sasha Tolstoy
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Natascha V Arends
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Leonie P Posselt
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Aparna Shekar
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States of America
| | - Jenny I Aguilar
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States of America
| | - Viktor K Lund
- Departmetn of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Kevin Erreger
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, United States of America
| | - Mattias Rickhag
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Matthew D Lycas
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Markus N Lonsdale
- Department of Clinical Physiology and Nuclear Medicine, Bispebjerg Hospital, Copenhagen, Denmark
| | - Troels Rahbek-Clemmensen
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Andreas T Sørensen
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Amy H Newman
- National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, Baltimore, United States of America
| | | | - Ole Kjaerulff
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Werge
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Lisbeth B Møller
- Center for Applied Human Genetics, Kennedy Center, Glostrup, Denmark
| | - Heinrich Jg Matthies
- Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
| | - Aurelio Galli
- Department of Surgery, University of Alabama at Birmingham, Birmingham, United States of America
| | - Lena E Hjermind
- Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark
| | - Ulrik Gether
- Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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20
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Bae YJ, Kim JM, Sohn CH, Choi JH, Choi BS, Song YS, Nam Y, Cho SJ, Jeon B, Kim JH. Imaging the Substantia Nigra in Parkinson Disease and Other Parkinsonian Syndromes. Radiology 2021; 300:260-278. [PMID: 34100679 DOI: 10.1148/radiol.2021203341] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Parkinson disease is characterized by dopaminergic cell loss in the substantia nigra of the midbrain. There are various imaging markers for Parkinson disease. Recent advances in MRI have enabled elucidation of the underlying pathophysiologic changes in the nigral structure. This has contributed to accurate and early diagnosis and has improved disease progression monitoring. This article aims to review recent developments in nigral imaging for Parkinson disease and other parkinsonian syndromes, including nigrosome imaging, neuromelanin imaging, quantitative iron mapping, and diffusion-tensor imaging. In particular, this article examines nigrosome imaging using 7-T MRI and 3-T susceptibility-weighted imaging. Finally, this article discusses volumetry and its clinical importance related to symptom manifestation. This review will improve understanding of recent advancements in nigral imaging of Parkinson disease. Published under a CC BY 4.0 license.
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Affiliation(s)
- Yun Jung Bae
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Jong-Min Kim
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Chul-Ho Sohn
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Ji-Hyun Choi
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Byung Se Choi
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Yoo Sung Song
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Yoonho Nam
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Se Jin Cho
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Beomseok Jeon
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
| | - Jae Hyoung Kim
- From the Departments of Radiology (Y.J.B., B.S.C., S.J.C., J.H.K.), Neurology (J.M.K., J.H.C.), and Nuclear Medicine (Y.S.S.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, 173-82 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea; Departments of Radiology (C.H.S.) and Neurology (B.J.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; and Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Republic of Korea (Y.N.)
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21
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Abstract
Two pathologically distinct neurodegenerative conditions, progressive supranuclear palsy and corticobasal degeneration, share in common deposits of tau proteins that differ both molecularly and ultrastructurally from the common tau deposits diagnostic of Alzheimer disease. The proteinopathy in these disorders is characterized by fibrillary aggregates of 4R tau proteins. The clinical presentations of progressive supranuclear palsy and of corticobasal degeneration are often confused with more common disorders such as Parkinson disease or subtypes of frontotemporal lobar degeneration. Neither of these 4R tau disorders has effective therapy, and while there are emerging molecular imaging approaches to identify patients earlier in the course of disease, there are as yet no reliably sensitive and specific approaches to diagnoses in life. In this review, aspects of the clinical syndromes, neuropathology, and molecular biomarker imaging studies applicable to progressive supranuclear palsy and to corticobasal degeneration will be presented. Future development of more accurate molecular imaging approaches is proposed.
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Affiliation(s)
- Kirk A Frey
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, The University of Michigan Health System, Ann Arbor, MI.
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22
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Han SW, Park YH, Ryoo N, Kim K, Pyun JM, Kim S. Pearls & Oy-sters: Idiopathic Normal Pressure Hydrocephalus With Synucleinopathy: Diagnosis and Treatment. Neurology 2021; 97:196-199. [PMID: 33931530 DOI: 10.1212/wnl.0000000000012099] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Sang-Won Han
- From the Department of Neurology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Republic of Korea
| | - Young Ho Park
- From the Department of Neurology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Republic of Korea.
| | - Nayoung Ryoo
- From the Department of Neurology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Republic of Korea
| | - Kitae Kim
- From the Department of Neurology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Republic of Korea
| | - Jung-Min Pyun
- From the Department of Neurology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Republic of Korea
| | - SangYun Kim
- From the Department of Neurology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Republic of Korea
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23
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Bae YJ, Song YS, Kim JM, Choi BS, Nam Y, Choi JH, Lee WW, Kim JH. Determining the Degree of Dopaminergic Denervation Based on the Loss of Nigral Hyperintensity on SMWI in Parkinsonism. AJNR Am J Neuroradiol 2021; 42:681-687. [PMID: 33509919 DOI: 10.3174/ajnr.a6960] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/21/2021] [Indexed: 01/23/2023]
Abstract
BACKGROUND AND PURPOSE Nigrostriatal dopaminergic function in patients with Parkinson disease can be assessed using 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropan dopamine transporter (123I-FP-CIT) SPECT, and a good correlation has been demonstrated between nigral status on SWI and dopaminergic denervation on 123I-FP-CIT SPECT. Here, we aim to correlate quantified dopamine transporter attenuation on 123I-FP-CIT SPECT with nigrosome-1 status using susceptibility map-weighted imaging (SMWI). MATERIALS AND METHODS Between May 2017 and January 2018, consecutive patients with idiopathic Parkinson disease (n = 109) and control participants (n = 29) who underwent 123I-FP-CIT SPECT with concurrent 3T SWI were included. SMWI was generated from SWI. Two neuroradiologists evaluated nigral hyperintensity from nigrosome-1 on each side of the substantia nigra. Using consensus reading, we compared the 123I-FP-CIT-specific binding ratio according to nigral hyperintensity status and the 123I-FP-CIT specific binding ratio threshold to confirm the loss of nigral hyperintensity was determined using receiver operating characteristic curve analysis. RESULTS The concordance rate between SMWI and 123I-FP-CIT SPECT was 65.9%. The 123I-FP-CIT-specific binding ratios in the striatum, caudate nucleus, and putamen were significantly lower when nigral hyperintensity in the ipsilateral substantia nigra was absent than when present (all, P < .001). The 123I-FP-CIT-specific binding ratio threshold values for the determination of nigral hyperintensity loss were 2.56 in the striatum (area under the curve, 0.890), 3.07 in the caudate nucleus (0.830), and 2.36 in the putamen (0.887). CONCLUSIONS Nigral hyperintensity on SMWI showed high positive predictive value and low negative predictive value with dopaminergic degeneration on 123I-FP-CIT SPECT. In patients with Parkinson disease, the loss of nigral hyperintensity is prominent in patients with lower striatal specific binding ratios.
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Affiliation(s)
- Y J Bae
- From the Department of Radiology (Y.J.B., B.S.C., J.H.K.)
| | - Y S Song
- Nuclear Medicine (Y.S.S., W.W.L.)
| | - J-M Kim
- Neurology (J.-M.K., J.-H.C.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - B S Choi
- From the Department of Radiology (Y.J.B., B.S.C., J.H.K.)
| | - Y Nam
- Division of Biomedical Engineering (Y.N.), Hankuk University of Foreign Studies, Gyeonggi-do, Republic of Korea
| | - J-H Choi
- Neurology (J.-M.K., J.-H.C.), Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - W W Lee
- Nuclear Medicine (Y.S.S., W.W.L.)
- Medical Research Center, Institute of Radiation Medicine (W.W.L.), Seoul National University, Seoul, Republic of Korea
| | - J H Kim
- From the Department of Radiology (Y.J.B., B.S.C., J.H.K.)
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24
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Frey KA, Bohnen NILJ. Molecular Imaging of Neurodegenerative Parkinsonism. PET Clin 2021; 16:261-272. [PMID: 33589385 DOI: 10.1016/j.cpet.2020.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Advances in molecular PET imaging of neurodegenerative parkinsonism are reviewed with focus on neuropharmacologic radiotracers depicting terminals of selectively vulnerable neurons in these conditions. Degeneration and losses of dopamine, norepinephrine, serotonin, and acetylcholine imaging markers thus far do not differentiate among the parkinsonian conditions. Recent studies performed with [18F]fluorodeoxyglucose PET are limited by the need for automated image analysis tools and by lack of routine coverage for this imaging indication in the United States. Ongoing research engages use of novel molecular modeling and in silico methods for design of imaging ligands targeting these specific proteinopathies.
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Affiliation(s)
- Kirk A Frey
- Department of Radiology (Nuclear Medicine and Molecular Imaging), University of Michigan, 1500 East Medical Center Drive, Room B1-G505 UH, Ann Arbor, MI 48109-5028, USA; Department of Neurology, University of Michigan, 1500 East Medical Center Drive, Room B1-G505 UH, Ann Arbor, MI 48109-5028, USA.
| | - Nicolaas I L J Bohnen
- Department of Radiology (Nuclear Medicine and Molecular Imaging), University of Michigan, 24 Frank Lloyd Wright Drive, Box 362, Ann Arbor, MI 48105, USA; Department of Neurology, University of Michigan, 24 Frank Lloyd Wright Drive, Box 362, Ann Arbor, MI 48105, USA; Ann Arbor Veterans Administration Medical Center, Ann Arbor, MI, USA
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25
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Honma M, Murakami H, Yabe Y, Kuroda T, Futamura A, Sugimoto A, Terao Y, Masaoka Y, Izumizaki M, Kawamura M, Ono K. Stopwatch training improves cognitive functions in patients with Parkinson's disease. J Neurosci Res 2021; 99:1325-1336. [PMID: 33594677 DOI: 10.1002/jnr.24812] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 01/09/2021] [Accepted: 01/31/2021] [Indexed: 12/20/2022]
Abstract
Parkinson's disease (PD) impairs various cognitive functions, including time perception. Dysfunctional time perception in PD is poorly understood, and no study has investigated the rehabilitation of time perception in patients with PD. We aimed to induce the recovery of time perception in PD patients and investigated the potential relationship between recovery and cognitive functions/domains other than time perception. Sixty patients with PD (27 females) and 20 healthy controls (10 females) were recruited. The participants underwent a feedback training protocol for 4 weeks to improve the accuracy of subjective spatial distance or time duration using a ruler or stopwatch, respectively. They participated in three tests at weekly intervals, each comprising 10 types of cognitive tasks and assessments. After duration feedback training for 1 month, performance on the Go/No-go task, Stroop task, and impulsivity assessment improved in patients with PD, while no effect was observed after distance feedback training. Additionally, the effect of training on duration production correlated with extended reaction time and improved accuracy in the Go/No-go and Stroop tasks. These findings suggest that time perception is functionally linked to inhibitory systems. If the feedback training protocol can modulate and maintain time perception, it may improve various cognitive/psychiatric functions in patients with PD. It may also be useful in the treatment of diseases other than PD that cause dysfunctions in temporal processing.
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Affiliation(s)
- Motoyasu Honma
- Department of Physiology, Showa University School of Medicine, Shinagawa-ku, Japan
| | - Hidetomo Murakami
- Division of Neurology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Japan
| | - Yoshiko Yabe
- Kashino Diverse Brain Research Laboratory, NTT Communication Science Laboratories, Atsugi-Shi, Japan
| | - Takeshi Kuroda
- Division of Neurology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Japan
| | - Akinori Futamura
- Division of Neurology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Japan
| | - Azusa Sugimoto
- Division of Neurology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Japan
| | - Yasuo Terao
- Department of Medical Physiology, Kyorin University School of Medicine, Mitaka-Shi, Japan
| | - Yuri Masaoka
- Department of Physiology, Showa University School of Medicine, Shinagawa-ku, Japan
| | - Masahiko Izumizaki
- Department of Physiology, Showa University School of Medicine, Shinagawa-ku, Japan
| | - Mitsuru Kawamura
- Division of Neurology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Japan
| | - Kenjiro Ono
- Division of Neurology, Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Japan
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NAKAJIMA M, YAMADA S, MIYAJIMA M, ISHII K, KURIYAMA N, KAZUI H, KANEMOTO H, SUEHIRO T, YOSHIYAMA K, KAMEDA M, KAJIMOTO Y, MASE M, MURAI H, KITA D, KIMURA T, SAMEJIMA N, TOKUDA T, KAIJIMA M, AKIBA C, KAWAMURA K, ATSUCHI M, HIRATA Y, MATSUMAE M, SASAKI M, YAMASHITA F, AOKI S, IRIE R, MIYAKE H, KATO T, MORI E, ISHIKAWA M, DATE I, ARAI H, The research committee of idiopathic normal pressure hydrocephalus. Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus. Neurol Med Chir (Tokyo) 2021; 61:63-97. [PMID: 33455998 PMCID: PMC7905302 DOI: 10.2176/nmc.st.2020-0292] [Citation(s) in RCA: 288] [Impact Index Per Article: 72.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Accepted: 10/13/2020] [Indexed: 01/18/2023] Open
Abstract
Among the various disorders that manifest with gait disturbance, cognitive impairment, and urinary incontinence in the elderly population, idiopathic normal pressure hydrocephalus (iNPH) is becoming of great importance. The first edition of these guidelines for management of iNPH was published in 2004, and the second edition in 2012, to provide a series of timely, evidence-based recommendations related to iNPH. Since the last edition, clinical awareness of iNPH has risen dramatically, and clinical and basic research efforts on iNPH have increased significantly. This third edition of the guidelines was made to share these ideas with the international community and to promote international research on iNPH. The revision of the guidelines was undertaken by a multidisciplinary expert working group of the Japanese Society of Normal Pressure Hydrocephalus in conjunction with the Japanese Ministry of Health, Labour and Welfare research project. This revision proposes a new classification for NPH. The category of iNPH is clearly distinguished from NPH with congenital/developmental and acquired etiologies. Additionally, the essential role of disproportionately enlarged subarachnoid-space hydrocephalus (DESH) in the imaging diagnosis and decision for further management of iNPH is discussed in this edition. We created an algorithm for diagnosis and decision for shunt management. Diagnosis by biomarkers that distinguish prognosis has been also initiated. Therefore, diagnosis and treatment of iNPH have entered a new phase. We hope that this third edition of the guidelines will help patients, their families, and healthcare professionals involved in treating iNPH.
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Affiliation(s)
- Madoka NAKAJIMA
- Department of Neurosurgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Shigeki YAMADA
- Department of Neurosurgery, Shiga University of Medical Science, Ohtsu, Shiga, Japan
| | - Masakazu MIYAJIMA
- Department of Neurosurgery, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
| | - Kazunari ISHII
- Department of Radiology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan
| | - Nagato KURIYAMA
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Kyoto, Japan
| | - Hiroaki KAZUI
- Department of Neuropsychiatry, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan
| | - Hideki KANEMOTO
- Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takashi SUEHIRO
- Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kenji YOSHIYAMA
- Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Masahiro KAMEDA
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan
| | - Yoshinaga KAJIMOTO
- Department of Neurosurgery, Division of Surgery, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Mitsuhito MASE
- Department of Neurosurgery, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Aichi, Japan
| | - Hisayuki MURAI
- Department of Neurosurgery, Chibaken Saiseikai Narashino Hospital, Narashino, Chiba, Japan
| | - Daisuke KITA
- Department of Neurosurgery, Noto General Hospital, Nanao, Ishikawa, Japan
| | - Teruo KIMURA
- Department of Neurosurgery, Kitami Red Cross Hospital, Kitami, Hokkaido, Japan
| | - Naoyuki SAMEJIMA
- Department of Neurosurgery, Tokyo Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Tokyo, Japan
| | - Takahiko TOKUDA
- Department of Functional Brain Imaging Research, National Institute of Radiological Science, National Institutes for Quantum and Radiological Science and Technology, Chiba, Chiba, Japan
| | - Mitsunobu KAIJIMA
- Department of Neurosurgery, Hokushinkai Megumino Hospital, Eniwa, Hokkaido, Japan
| | - Chihiro AKIBA
- Department of Neurosurgery, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
| | - Kaito KAWAMURA
- Department of Neurosurgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Masamichi ATSUCHI
- Normal Pressure Hydrocephalus Center, Jifukai Atsuchi Neurosurgical Hospital, Kagoshima, Kagoshima, Japan
| | - Yoshihumi HIRATA
- Department of Neurosurgery, Kumamoto Takumadai Hospital, Kumamoto, Kumamoto, Japan
| | - Mitsunori MATSUMAE
- Department of Neurosurgery at Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | - Makoto SASAKI
- Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Yahaba, Iwate, Japan
| | - Fumio YAMASHITA
- Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Yahaba, Iwate, Japan
| | - Shigeki AOKI
- Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Ryusuke IRIE
- Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroji MIYAKE
- Nishinomiya Kyoritsu Rehabilitation Hospital, Nishinomiya, Hyogo, Japan
| | - Takeo KATO
- Division of Neurology and Clinical Neuroscience, Department of Internal Medicine III, Yamagata University School of Medicine, Yamagata, Yamagata, Japan
| | - Etsuro MORI
- Department of Behavioral Neurology and Neuropsychiatry, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan
| | - Masatsune ISHIKAWA
- Department of Neurosurgery and Normal Pressure Hydrocephalus Center, Rakuwakai Otowa Hospital, Kyoto, Kyoto, Japan
| | - Isao DATE
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan
| | - Hajime ARAI
- Department of Neurosurgery, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - The research committee of idiopathic normal pressure hydrocephalus
- Department of Neurosurgery, Juntendo University Faculty of Medicine, Tokyo, Japan
- Department of Neurosurgery, Shiga University of Medical Science, Ohtsu, Shiga, Japan
- Department of Neurosurgery, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
- Department of Radiology, Kindai University Faculty of Medicine, Osakasayama, Osaka, Japan
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Kyoto, Japan
- Department of Neuropsychiatry, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan
- Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan
- Department of Neurosurgery, Division of Surgery, Osaka Medical College, Takatsuki, Osaka, Japan
- Department of Neurosurgery, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Aichi, Japan
- Department of Neurosurgery, Chibaken Saiseikai Narashino Hospital, Narashino, Chiba, Japan
- Department of Neurosurgery, Noto General Hospital, Nanao, Ishikawa, Japan
- Department of Neurosurgery, Kitami Red Cross Hospital, Kitami, Hokkaido, Japan
- Department of Neurosurgery, Tokyo Kyosai Hospital, Federation of National Public Service Personnel Mutual Aid Associations, Tokyo, Japan
- Department of Functional Brain Imaging Research, National Institute of Radiological Science, National Institutes for Quantum and Radiological Science and Technology, Chiba, Chiba, Japan
- Department of Neurosurgery, Hokushinkai Megumino Hospital, Eniwa, Hokkaido, Japan
- Normal Pressure Hydrocephalus Center, Jifukai Atsuchi Neurosurgical Hospital, Kagoshima, Kagoshima, Japan
- Department of Neurosurgery, Kumamoto Takumadai Hospital, Kumamoto, Kumamoto, Japan
- Department of Neurosurgery at Tokai University School of Medicine, Isehara, Kanagawa, Japan
- Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Yahaba, Iwate, Japan
- Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan
- Nishinomiya Kyoritsu Rehabilitation Hospital, Nishinomiya, Hyogo, Japan
- Division of Neurology and Clinical Neuroscience, Department of Internal Medicine III, Yamagata University School of Medicine, Yamagata, Yamagata, Japan
- Department of Behavioral Neurology and Neuropsychiatry, Osaka University United Graduate School of Child Development, Suita, Osaka, Japan
- Department of Neurosurgery and Normal Pressure Hydrocephalus Center, Rakuwakai Otowa Hospital, Kyoto, Kyoto, Japan
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Pozzi NG, Brumberg J, Todisco M, Minafra B, Zangaglia R, Bossert I, Trifirò G, Ceravolo R, Vitali P, Isaias IU, Fasano A, Pacchetti C. Striatal Dopamine Deficit and Motor Impairment in Idiopathic Normal Pressure Hydrocephalus. Mov Disord 2020; 36:124-132. [PMID: 33151012 DOI: 10.1002/mds.28366] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 09/24/2020] [Accepted: 09/30/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear. OBJECTIVES To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls. METHODS We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [123 I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane and single-photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l-dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. All patients completed a 2-year follow-up. RESULTS A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus. CONCLUSIONS Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Nicoló Gabriele Pozzi
- Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy.,Neurology Department, University Hospital and Julius Maximilian University of Würzburg, Würzburg, Germany
| | - Joachim Brumberg
- Nuclear Medicine Department, University Hospital Würzburg, Würzburg, Germany
| | - Massimiliano Todisco
- Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy.,Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
| | - Brigida Minafra
- Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy
| | - Roberta Zangaglia
- Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy
| | - Irene Bossert
- Nuclear Medicine Unit, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy
| | - Giuseppe Trifirò
- Nuclear Medicine Unit, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, Pavia, Italy
| | - Roberto Ceravolo
- Unit of Neurology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Paolo Vitali
- Neuroradiology Unit, IRCCS Mondino Foundation, Pavia, Italy
| | - Ioannis Ugo Isaias
- Neurology Department, University Hospital and Julius Maximilian University of Würzburg, Würzburg, Germany
| | - Alfonso Fasano
- Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.,Division of Neurology, University of Toronto, Toronto, Ontario, Canada.,Krembil Brain Institute, Toronto, Ontario, Canada.,CenteR for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
| | - Claudio Pacchetti
- Parkinson's Disease and Movement Disorders Unit, IRCCS Mondino Foundation, Pavia, Italy
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Shen B, Wei S, Ge J, Peng S, Liu F, Li L, Guo S, Wu P, Zuo C, Eidelberg D, Wang J, Ma Y. Reproducible metabolic topographies associated with multiple system atrophy: Network and regional analyses in Chinese and American patient cohorts. NEUROIMAGE-CLINICAL 2020; 28:102416. [PMID: 32987300 PMCID: PMC7520431 DOI: 10.1016/j.nicl.2020.102416] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 08/29/2020] [Accepted: 09/03/2020] [Indexed: 11/18/2022]
Abstract
This study produced reliable metabolic brain networks for multiple system atrophy. Network scores discriminated this disorder from other major forms of Parkinsonism. Network scores correlated with clinical stages and motor symptoms in this disorder. The network was highly reproducible across Chinese and American patient cohorts. Network scores provided a clinically useful biomarker in a multi-center setting. Purpose Multiple system atrophy (MSA) is an atypical parkinsonian syndrome and often difficult to discriminate clinically from progressive supranuclear palsy (PSP) and Parkinson's disease (PD) in early stages. Although a characteristic metabolic brain network has been reported for MSA, it is unknown whether this network can provide a clinically useful biomarker in different centers. This study was aimed to identify and cross-validate MSA-related brain network and assess its ability for differential diagnosis and clinical correlations in Chinese and American patient cohorts. Methods We included 18F-FDG PET scans retrospectively from 128 clinically diagnosed parkinsonian patients (34 MSA, 34 PSP and 60 PD) and 40 normal subjects in China and in the USA. Using PET images from 20 moderate-stage MSA patients of parkinsonian subtype and 20 normal subjects in both centers, we reproduced MSA-related pattern (MSAPRP) of spatial covariance and estimated its reliability. MSAPRP scores were evaluated in assessing differential diagnosis among moderate- and early-stage MSA, PSP or PD patients and clinical correlations with disease severity. Regional metabolic differences were detected using statistical parameter mapping analysis. MSA-related network and regional topographies of metabolic abnormality were cross-validated between the Chinese and American cohorts. Results We generated a highly reliable MSAPRP characterized by decreased loading in inferior frontal cortex, striatum and cerebellum, and increased loading in sensorimotor, parietal and occipital cortices. MSAPRP scores discriminated between normal, MSA, PSP and PD subjects and correlated with standardized ratings of clinical stages and motor symptoms in MSA. High similarities in MSAPRPs, network scores and corresponding maps of metabolic abnormality were observed between two different cohorts. Conclusion We have demonstrated reproducible metabolic topographies associated with MSA at both network and regional levels in two independent patient cohorts. Moreover, MSAPRP scores are sensitive for evaluating disease discrimination and clinical correlates. This study supports differential diagnosis of MSA regardless of different patient populations, PET scanners and imaging protocols.
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Affiliation(s)
- Bo Shen
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Sidi Wei
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jingjie Ge
- PET Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Shichun Peng
- Center for Neurosciences, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA
| | - Fengtao Liu
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ling Li
- PET Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Sisi Guo
- Department of Neurology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ping Wu
- PET Center, Huashan Hospital, Fudan University, Shanghai, China
| | - Chuantao Zuo
- PET Center, Huashan Hospital, Fudan University, Shanghai, China
| | - David Eidelberg
- Center for Neurosciences, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA
| | - Jian Wang
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Yilong Ma
- Center for Neurosciences, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
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Schmitz-Steinkrüger H, Lange C, Apostolova I, Amthauer H, Lehnert W, Klutmann S, Buchert R. Impact of the size of the normal database on the performance of the specific binding ratio in dopamine transporter SPECT. EJNMMI Phys 2020; 7:34. [PMID: 32435936 PMCID: PMC7239986 DOI: 10.1186/s40658-020-00304-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 05/05/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND This study investigated the impact of the size of the normal database on the classification performance of the specific binding ratio (SBR) in dopamine transporter (DAT) SPECT with [123I]FP-CIT in different settings. METHODS The first subject sample comprised 645 subjects from the Parkinson's Progression Marker Initiative (PPMI), 207 healthy controls (HC), and 438 Parkinson's disease (PD) patients. The second sample comprised 372 patients from clinical routine patient care, 186 with non-neurodegenerative parkinsonian syndrome (PS) and 186 with neurodegenerative PS. Single-photon emission computed tomography (SPECT) images of the clinical sample were reconstructed with two different reconstruction algorithms (filtered backprojection, iterative ordered subsets expectation maximization (OSEM) reconstruction with resolution recovery). The putaminal specific binding ratio (SBR) was computed using an anatomical region of interest (ROI) predefined in standard (MNI) space in the Automated Anatomic Labeling (AAL) atlas or using hottest voxels (HV) analysis in large predefined ROIs. SBR values were transformed to z-scores using mean and standard deviation of the SBR in a normal database of varying sizes (n = 5, 10, 15,…, 50) randomly selected from the HC subjects (PPMI sample) or the patients with non-neurodegenerative PS (clinical sample). Accuracy, sensitivity, and specificity for identifying patients with PD or neurodegenerative PS were determined as performance measures using a predefined fixed cutoff on the z-score. This was repeated for 10,000 randomly selected normal databases, separately for each size of the normal database. Mean and 5th percentile of the performance measures over the 10,000 realizations were computed. Accuracy, sensitivity, and specificity when using the whole set of HC or non-neurodegenerative PS subjects as normal database were used as benchmark. RESULTS Mean loss of accuracy of the putamen SBR z-score was below 1% when the normal database included at least 15 subjects, independent of subject sample (PPMI or clinical), reconstruction method (filtered backprojection or OSEM), and ROI method (AAL or HV). However, the variability of the accuracy of the putamen SBR z-score decreased monotonically with increasing size of normal database and was still considerable at size 15. In order to achieve less than 5% "maximum" loss of accuracy (defined by the 5th percentile) in all settings required at least 25 to 30 subjects in the normal database. Reduction of mean and "maximum" loss of accuracy of the putamen SBR z-score by further increasing the size of the normal database was very small beyond size 40. CONCLUSIONS The results of this study suggest that 25 to 30 is the minimum size of the normal database to reliably achieve good performance of semi-quantitative analysis in dopamine transporter (DAT) SPECT, independent of the algorithm used for image reconstruction and the ROI method used to estimate the putaminal SBR.
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Affiliation(s)
- Helen Schmitz-Steinkrüger
- Department for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Catharina Lange
- Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Ivayla Apostolova
- Department for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Holger Amthauer
- Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Wencke Lehnert
- Department for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Susanne Klutmann
- Department for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Ralph Buchert
- Department for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany
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A Novel Automatic Approach for Calculation of the Specific Binding Ratio in [I-123]FP-CIT SPECT. Diagnostics (Basel) 2020; 10:diagnostics10050289. [PMID: 32397547 PMCID: PMC7277984 DOI: 10.3390/diagnostics10050289] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 05/07/2020] [Accepted: 05/07/2020] [Indexed: 11/22/2022] Open
Abstract
A fully automatic method for specific binding ratio (SBR) calculation in [123I]ioflupane single-photon emission computed tomography (SPECT) studies was proposed by creating volumes of interest of the striatum (VOIst) and reference region (VOIref) without manual handling to avoid operator-induced variability. The study involved 105 patients (72 ± 10 years) suspected of parkinsonian syndrome (PS) who underwent [123I]ioflupane SPECT. The 200 images from our previous study were used for evaluation and validation of the new program. All patients were classified into PS and non-PS groups according to the results of clinical follow-up. A trapezoidal volume of interest (VOIt) containing all striatal intensive counts was created automatically, followed by VOIst setting using the previous method. SBR values were calculated from the mean values of VOIst and VOIref determined by the whole brain outside of VOIt. The low count voxels in the VOIref were excluded using an appropriate threshold. The SBR values from the new method were compared with the previous semi-automatic method and the Tossici–Bolt (TB) method. The SBRs from the semi- and fully automatic methods showed a good linear correlation (r > 0.98). The areas under the curves (AUCs) of receiver operating characteristic analysis showed no significant difference between the two methods for both our previous (AUC > 0.99) and new (AUC > 0.95) data. The diagnostic accuracy of the two methods showed similar results (>92%), and both were better than the TB method. The proposed method successfully created the automatic VOIs and calculated SBR rapidly (9 ± 1 s/patient), avoiding operator-induced variability and providing objective SBR results.
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Fahmi R, Platsch G, Sadr AB, Gouttard S, Thobois S, Zuehlsdorff S, Scheiber C. Single-site 123I-FP-CIT reference values from individuals with non-degenerative parkinsonism-comparison with values from healthy volunteers. Eur J Hybrid Imaging 2020; 4:5. [PMID: 34191214 PMCID: PMC8218096 DOI: 10.1186/s41824-020-0074-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 01/29/2020] [Indexed: 11/24/2022] Open
Abstract
Purpose Iodine 123-radiolabeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) SPECT can be performed to distinguish degenerative forms of movement disorders/parkinsonism/tremor from other entities such as idiopathic tremor or drug-induced parkinsonism. For equivocal cases, semi-quantification and comparison to reference values are a necessary addition to visual interpretation of 123I-FP-CIT scans. To overcome the challenges of multi-center recruitment and scanning of healthy volunteers, we generated 123I-FP-CIT reference values from individuals with various neurological conditions but without dopaminergic degeneration, scanned at a single center on the same SPECT-CT system following the same protocol, and compared them to references from a multi-center database built using healthy volunteers’ data. Methods From a cohort of 1884 patients, we identified 237 subjects (120 men, 117 women, age range 16–88 years) through a two-stage selection process. Every patient had a final clinical diagnosis after a mean follow-up of 4.8 ± 1.3 years. Images were reconstructed using (1) Flash3D with scatter and CT-based attenuation corrections (AC) and (2) filtered back projection with Chang AC. Volume-of-interest analysis was performed using a commercial software to calculate specific binding ratios (SBRs), caudate-to-putamen ratios, and asymmetry values on different striatal regions. Generated reference values were assessed according to age and gender and compared with those from the ENC-DAT study, and their robustness was tested against a cohort of patients with different diagnoses. Results Age had a significant negative linear effect on all SBRs. Overall, the reduction rate per decade in SBR was between 3.80 and 5.70%. Women had greater SBRs than men, but this gender difference was only statistically significant for the Flash3D database. Linear regression was used to correct for age-dependency of SBRs and to allow comparisons to age-matched reference values and “normality” limits. Generated regression parameters and their 95% confidence intervals (CIs) were comparable to corresponding European Normal Control Database of DaTscan (ENC-DAT) results. For example, 95% CI mean slope for the striatum in women is − 0.015 ([− 0.019, − 0.011]) for the Flash3D database versus − 0.015 ([− 0.021, − 0.009]) for ENC-DAT. Caudate-to-putamen ratios and asymmetries were not influenced by age or gender. Conclusion The generated 123I-FP-CIT references values have similar age-related distribution, with no increase in variance due to comorbidities when compared to values from a multi-center study with healthy volunteers. This makes it possible for sites to build their 123I-FP-CIT references from scans acquired during routine clinical practice.
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Affiliation(s)
- Rachid Fahmi
- Siemens Medical Solutions USA, Inc., Molecular Imaging, Knoxville, TN, USA
| | | | | | | | - Stephane Thobois
- Movement Disorder Clinic, Pierre Wertheimer Neurologic Hospital, Hospices Civils de Lyon, 69500, Bron, France.,Faculté de Médecine Lyon Sud, Université Claude Bernard Lyon 1, Lyon, France.,Institut des Sciences Cognitives Marc Jeannerod, UMR 5229, CNRS, Bron, France
| | - Sven Zuehlsdorff
- Siemens Medical Solutions USA, Inc., Molecular Imaging, Knoxville, TN, USA
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Li H, Hirano S, Furukawa S, Nakano Y, Kojima K, Ishikawa A, Tai H, Horikoshi T, Iimori T, Uno T, Matsuda H, Kuwabara S. The Relationship Between the Striatal Dopaminergic Neuronal and Cognitive Function With Aging. Front Aging Neurosci 2020; 12:41. [PMID: 32184717 PMCID: PMC7058549 DOI: 10.3389/fnagi.2020.00041] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 02/06/2020] [Indexed: 12/03/2022] Open
Abstract
Both cognitive function and striatal dopamine function decline by normal aging. However, the relationship among these three factors remains unclear. The aim of this study was to elucidate the association among age-related changes in the striatal dopamine transporter (DAT) and cognitive function in healthy subjects. The 30 healthy volunteers were enrolled in this research, the age ranged from 41 to 82 (64.5 ± 11.5, mean ± SD). All subjects were scanned with both T1-weighted magnetic resonance imaging (MRI) and 123I-FP-CIT single-photon emission computed tomography (SPECT) images. The Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) was used to evaluate cognitive function. Six spherical regions of interest (ROI) using 10 mm in diameter on the caudate nucleus, anterior putamen and posterior putamen were manually drawn on MRI image which was applied onto SPECT image. The relationship between striatal occipital ratio (SOR) values and WAIS-III subscore were analyzed by multiple regression analysis. Subscores which was significant were further analyzed by path analyses. Full intelligence quotient (IQ), verbal IQ, verbal comprehension were all positively correlated with age-adjusted striatal DAT binding (P < 0.01). Multiple regression analyses revealed that the coding digit symbol correlated with all striatal regions except for the left caudate (P < 0.04). Picture completion and right caudate, similarities and left caudate also showed a positive correlation (P < 0.04). Path analysis found that the right caudate and picture completion; the left caudate and similarities were correlated independently from age, whereas the models of coding digit symbol were not significant. These results suggest that age-based individual diversity of striatal DAT binding was associated with verbal function, and the caudate nucleus plays an important role in this association.
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Affiliation(s)
- Hongliang Li
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shigeki Hirano
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shogo Furukawa
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.,Department of Neurology, Japanese Red Cross Narita Hospital, Chiba, Japan
| | - Yoshikazu Nakano
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Kazuho Kojima
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.,Department of Neurology, Chiba Rosai Hospital, Chiba, Japan
| | - Ai Ishikawa
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.,Department of Neurology, JR Tokyo General Hospital, Tokyo, Japan
| | - Hong Tai
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takuro Horikoshi
- Diagnostic Radiology and Radiation Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Takashi Iimori
- Department of Radiology, Chiba University Hospital, Chiba, Japan
| | - Takashi Uno
- Diagnostic Radiology and Radiation Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroshi Matsuda
- Integrative Brain Imaging Center, National Center of Neurology and Psychiatry, Tokyo, Japan
| | - Satoshi Kuwabara
- Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Wenzel M, Milletari F, Krüger J, Lange C, Schenk M, Apostolova I, Klutmann S, Ehrenburg M, Buchert R. Automatic classification of dopamine transporter SPECT: deep convolutional neural networks can be trained to be robust with respect to variable image characteristics. Eur J Nucl Med Mol Imaging 2019; 46:2800-2811. [DOI: 10.1007/s00259-019-04502-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 08/22/2019] [Indexed: 01/29/2023]
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Molecular Imaging of the Dopamine Transporter. Cells 2019; 8:cells8080872. [PMID: 31405186 PMCID: PMC6721747 DOI: 10.3390/cells8080872] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 08/07/2019] [Accepted: 08/09/2019] [Indexed: 02/06/2023] Open
Abstract
Dopamine transporter (DAT) single-photon emission tomography (SPECT) with (123)Ioflupane is a widely used diagnostic tool for patients with suspected parkinsonian syndromes, as it assists with differentiating between Parkinson’s disease (PD) or atypical parkinsonisms and conditions without a presynaptic dopaminergic deficit such as essential tremor, vascular and drug-induced parkinsonisms. Recent evidence supports its utility as in vivo proof of degenerative parkinsonisms, and DAT imaging has been proposed as a potential surrogate marker for dopaminergic nigrostriatal neurons. However, the interpretation of DAT-SPECT imaging may be challenged by several factors including the loss of DAT receptor density with age and the effect of certain drugs on dopamine uptake. Furthermore, a clear, direct relationship between nigral loss and DAT decrease has been controversial so far. Striatal DAT uptake could reflect nigral neuronal loss once the loss exceeds 50%. Indeed, reduction of DAT binding seems to be already present in the prodromal stage of PD, suggesting both an early synaptic dysfunction and the activation of compensatory changes to delay the onset of symptoms. Despite a weak correlation with PD severity and progression, quantitative measurements of DAT binding at baseline could be used to predict the emergence of late-disease motor fluctuations and dyskinesias. This review addresses the possibilities and limitations of DAT-SPECT in PD and, focusing specifically on regulatory changes of DAT in surviving DA neurons, we investigate its role in diagnosis and its prognostic value for motor complications as disease progresses.
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Optimizing the Diagnosis of Parkinsonian Syndromes With 123I-Ioflupane Brain SPECT. AJR Am J Roentgenol 2019; 213:243-253. [DOI: 10.2214/ajr.19.21088] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Ikeda K, Ebina J, Kawabe K, Iwasaki Y. Dopamine Transporter Imaging in Parkinson Disease: Progressive Changes and Therapeutic Modification after Anti-parkinsonian Medications. Intern Med 2019; 58:1665-1672. [PMID: 30799370 PMCID: PMC6630131 DOI: 10.2169/internalmedicine.2489-18] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022] Open
Abstract
Parkinson disease (PD) is a slowly progressive neurodegenerative disease characterized by the loss of dopaminergic neurons and terminals in the nigrostriatal system. Dopamine transporter (DAT) imaging is widely performed for the differential diagnosis of PD and other degenerative parkinsonism from essential tremor, vascular parkinsonism, and drug-induced parkinsonism. DAT is the plasma membrane carrier specific to dopamine neurons that are responsible for re-uptaking dopamine from the synaptic cleft back into the nerve ending. DAT binding might reflect striatal presynaptic dysfunction or DAT expression in PD patients. Longitudinal studies of DAT imaging have reported progressive changes from early PD patients. This imaging may be used as a progressive biomarker. Follow-up DAT imaging for therapeutic interventions has been applied for several anti-parkinsonian drugs. We herein review the progressive changes and therapeutic modification of DAT binding by anti-PD medications in early PD patients.
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Affiliation(s)
- Ken Ikeda
- Department of Neurology, Toho University Omori Medical Center, Japan
| | - Junya Ebina
- Department of Neurology, Toho University Omori Medical Center, Japan
| | - Kiyokazu Kawabe
- Department of Neurology, Toho University Omori Medical Center, Japan
| | - Yasuo Iwasaki
- Department of Neurology, Toho University Omori Medical Center, Japan
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Buchert R, Lange C, Spehl TS, Apostolova I, Frings L, Jonsson C, Meyer PT, Hellwig S. Diagnostic performance of the specific uptake size index for semi-quantitative analysis of I-123-FP-CIT SPECT: harmonized multi-center research setting versus typical clinical single-camera setting. EJNMMI Res 2019; 9:37. [PMID: 31065816 PMCID: PMC6505020 DOI: 10.1186/s13550-019-0506-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 04/15/2019] [Indexed: 11/30/2022] Open
Abstract
Introduction The specific uptake size index (SUSI) of striatal FP-CIT uptake is independent of spatial resolution in the SPECT image, in contrast to the specific binding ratio (SBR). This suggests that the SUSI is particularly appropriate for multi-site/multi-camera settings in which camera-specific effects increase inter-subject variability of spatial resolution. However, the SUSI is sensitive to inter-subject variability of striatum size. Furthermore, it might be more sensitive to errors of the estimate of non-displaceable FP-CIT binding. This study compared SUSI and SBR in the multi-site/multi-camera (MULTI) setting of a prospective multi-center study and in a mono-site/mono-camera (MONO) setting representative of clinical routine. Methods The MULTI setting included patients with Parkinson’s disease (PD, n = 438) and healthy controls (n = 207) from the Parkinson Progression Marker Initiative. The MONO setting included 122 patients from routine clinical patient care in whom FP-CIT SPECT had been performed with the same double-head SPECT system according to the same acquisition and reconstruction protocol. Patients were categorized as “neurodegenerative” (n = 84) or “non-neurodegenerative” (n = 38) based on follow-up data. FP-CIT SPECTs were stereotactically normalized to MNI space. SUSI and SBR were computed for caudate, putamen, and whole striatum using unilateral ROIs predefined in MNI space. SUSI analysis was repeated in native patient space in the MONO setting. The area (AUC) under the ROC curve for identification of PD/“neurodegenerative” cases was used as performance measure. Results In both settings, the highest AUC was achieved by the putamen (minimum over both hemispheres), independent of the semi-quantitative method (SUSI or SBR). The putaminal SUSI provided slightly better performance with ROI analysis in MNI space compared to patient space (AUC = 0.969 vs. 0.961, p = 0.129). The SUSI (computed in MNI space) performed slightly better than the SBR in the MULTI setting (AUC = 0.993 vs. 0.991, p = 0.207) and slightly worse in the MONO setting (AUC = 0.969 vs. AUC = 0.976, p = 0.259). There was a trend toward larger AUC difference between SUSI and SBR in the MULTI setting compared to the MONO setting (p = 0.073). Variability of voxel intensity in the reference region was larger in misclassified cases compared to correctly classified cases for both SUSI and SBR (MULTI setting: p = 0.007 and p = 0.012, respectively). Conclusions The SUSI is particularly useful in MULTI settings. SPECT images should be stereotactically normalized prior to SUSI analysis. The putaminal SUSI provides better diagnostic performance than the SUSI of the whole striatum. Errors of the estimate of non-displaceable count density in the reference region can cause misclassification by both SUSI and SBR, particularly in borderline cases. These cases might be identified by visual checking FP-CIT uptake in the reference region for particularly high variability.
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Affiliation(s)
- Ralph Buchert
- Department for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
| | - Catharina Lange
- Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.
| | - Timo S Spehl
- Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Ivayla Apostolova
- Department for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany
| | - Lars Frings
- Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Cathrine Jonsson
- Medical Radiation Physics and Nuclear Medicine, Imaging and Physiology, Karolinska University Hospital, Stockholm, Sweden
| | - Philipp T Meyer
- Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Sabine Hellwig
- Department of Nuclear Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Patel A, Simon S, M Elangoven I, Amalchandran J, S. Jain A, S T. Dopamine Transporter maging with Tc-99m TRODAT-1 SPECT in Parkinson's isease and its orrelation with linical isease everity. ASIA OCEANIA JOURNAL OF NUCLEAR MEDICINE & BIOLOGY 2019; 7:22-28. [PMID: 30705908 PMCID: PMC6352051 DOI: 10.22038/aojnmb.2018.30356.1208] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 06/27/2018] [Accepted: 06/28/2018] [Indexed: 11/06/2022]
Abstract
OBJECTIVES To evaluate the role of Tc-99m TRODAT-1 Single Photon Emission Computed Tomography (SPECT) in Parkinson's Disease (PD) by assessing the correlation of clinical disease severity, disease duration and age at onset of disease with specific uptake ratio of Tc-99m TRODAT-1 in striatum. METHODS The study included 63 patients in age range of 40-72 years with clinical diagnosis of PD and nine controls. Clinical history of patients was obtained regarding age at onset of disease and disease duration. Disease severity in each patient was assessed using H and Y stage and UPDRS. Tc-99m TRODAT-1 SPECT was performed and specific uptake ratios were calculated for six regions in bilateral striata, caudate nuclei and putamina. Difference in specific uptake ratios between different stages of disease was analyzed for statistical significance. Specific uptake ratios were correlated with UPDRS, motor score of UPDRS, duration of disease and age at onset of disease using Pearson's correlation co-efficient. RESULTS Median specific uptake ratio was found to be least in contralateral putamen for all H and Y stages. There was a statistically significant difference between specific uptake ratios of controls vs stage 1, stage 1 vs 2, 1 vs 3, 1 vs 4, and 2 vs 4 for all 6 regions. The difference in uptake ratio between 3 and 4 H and Y stages was significant only for contralateral regions. There was no significant difference in uptake ratio between 2 and 3 H and Y stages. The uptake ratios showed a strong negative correlation with UPDRS and motor score, a weak negative correlation with duration of disease and no significant correlation with age at onset of disease. CONCLUSION We conclude that Tc-99m TRODAT-1 SPECT can be used to assess the disease severity in PD patients.
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Affiliation(s)
- Asra Patel
- Department of Nuclear Medicine and PET-CT, Apollo Hospitals, Chennai, India
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Suh M, Lee DS. Brain Theranostics and Radiotheranostics: Exosomes and Graphenes In Vivo as Novel Brain Theranostics. Nucl Med Mol Imaging 2018; 52:407-419. [PMID: 30538772 PMCID: PMC6261865 DOI: 10.1007/s13139-018-0550-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 09/10/2018] [Accepted: 10/05/2018] [Indexed: 12/17/2022] Open
Abstract
Brain disease is one of the greatest threats to public health. Brain theranostics is recently taking shape, indicating the treatments of stroke, inflammatory brain disorders, psychiatric diseases, neurodevelopmental disease, and neurodegenerative disease. However, several factors, such as lack of endophenotype classification, blood-brain barrier (BBB), target determination, ignorance of biodistribution after administration, and complex intercellular communication between brain cells, make brain theranostics application difficult, especially when it comes to clinical application. So, a more thorough understanding of each aspect is needed. In this review, we focus on recent studies regarding the role of exosomes in intercellular communication of brain cells, therapeutic effect of graphene quantum dots, transcriptomics/epitranscriptomics approach for target selection, and in vitro/in vivo considerations.
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Affiliation(s)
- Minseok Suh
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, 03080 Republic of Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 03080 Republic of Korea
| | - Dong Soo Lee
- Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, 03080 Republic of Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 03080 Republic of Korea
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Vetel S, Sérrière S, Vercouillie J, Vergote J, Chicheri G, Deloye JB, Dollé F, Bodard S, Tronel C, Nadal-Desbarats L, Lefèvre A, Emond P, Chalon S. Extensive exploration of a novel rat model of Parkinson's disease using partial 6-hydroxydopamine lesion of dopaminergic neurons suggests new therapeutic approaches. Synapse 2018; 73:e22077. [DOI: 10.1002/syn.22077] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 10/12/2018] [Accepted: 10/15/2018] [Indexed: 12/24/2022]
Affiliation(s)
- Steven Vetel
- UMR 1253, iBrain, Université de Tours, Inserm; Tours France
| | | | - Johnny Vercouillie
- UMR 1253, iBrain, Université de Tours, Inserm; Tours France
- INSERM CIC 1415, University Hospital; Tours France
| | - Jackie Vergote
- UMR 1253, iBrain, Université de Tours, Inserm; Tours France
| | | | | | - Frédéric Dollé
- CEA, Institut des Sciences du Vivant Frédéric Joliot, Service hospitalier Frédéric Joliot, Université Paris-Saclay; Orsay France
| | - Sylvie Bodard
- UMR 1253, iBrain, Université de Tours, Inserm; Tours France
| | - Claire Tronel
- UMR 1253, iBrain, Université de Tours, Inserm; Tours France
| | | | | | - Patrick Emond
- UMR 1253, iBrain, Université de Tours, Inserm; Tours France
- CHRU Tours; Tours France
| | - Sylvie Chalon
- UMR 1253, iBrain, Université de Tours, Inserm; Tours France
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Abstract
PURPOSE We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists. METHODS An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software. RESULTS When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7%, ĸ = 0.75) compared to semiquantification (86.2%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found. CONCLUSIONS In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment.
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Kuo PH, Eshghi N, Tinaz S, Blumenfeld H, Louis ED, Zubal G. Optimization of Parameters for Quantitative Analysis of 123I-Ioflupane SPECT Images for Monitoring Progression of Parkinson Disease. J Nucl Med Technol 2018; 47:70-74. [PMID: 30139881 DOI: 10.2967/jnmt.118.213181] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 08/14/2018] [Indexed: 11/16/2022] Open
Abstract
Quantitative assessment of dopamine transporter imaging can aid in diagnosing Parkinson disease (PD) and assessing disease progression in the context of therapeutic trials. Previously, the software program SBRquant was applied to 123I-ioflupane SPECT images acquired on healthy controls and subjects with PD. Earlier work on optimization of the parameters for differentiating between controls and subjects with dopaminergic deficits is extended here for maximizing change measurements associated with disease progression on longitudinally acquired scans. Methods: Serial 123I-ioflupane SPECT imaging for 51 subjects with PD (conducted approximately 1 y apart) were downloaded from the Parkinson Progression Markers Initiative database. The software program SBRquant calculates the striatal binding ratio (SBR) separately for the left and right caudates and putamen regions of interest (ROIs). Parameters were varied to evaluate the number of summed transverse slices and the positioning of the striatal ROIs for determining the signal-to-noise ratio associated with their annual rate of change in SBR. The parameters yielding the largest change in the lowest putamen's SBR from scan 1 to scan 2 were determined. Results: From scan 1 to scan 2 in the 51 subjects, the largest annual change was observed when the putamen ROI was placed 3 pixels away from the caudate and by summing 5 central striatal slices. This resulted in an 11.2% ± 4.3% annual decrease in the lowest putamen SBR for the group. Conclusion: Quantitative assessment of dopamine transporter imaging for assessing progression of PD requires specific, optimal parameters different from those for diagnostic accuracy.
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Affiliation(s)
- Phillip H Kuo
- Department of Medical Imaging, Banner University Medical Center, Tucson, Arizona.,Department of Medicine, Banner University Medical Center, Tucson, Arizona.,Department of Biomedical Engineering, University of Arizona, Tucson, Arizona
| | | | - Sule Tinaz
- Department of Neurology, Yale School of Medicine, New Haven, Connecticut
| | - Hal Blumenfeld
- Department of Neurology, Yale School of Medicine, New Haven, Connecticut
| | - Elan D Louis
- Department of Neurology, Yale School of Medicine, New Haven, Connecticut.,Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.,Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, New Haven, Connecticut
| | - George Zubal
- Department of Neurology, Yale School of Medicine, New Haven, Connecticut.,Departments of Medical Imaging, Medicine, and Biomedical Engineering, University of Arizona Health Sciences, Tucson, Arizona; and.,Z-Concepts LLC, New Haven, Connecticut
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Quantitative Intensity Harmonization of Dopamine Transporter SPECT Images Using Gamma Mixture Models. Mol Imaging Biol 2018; 21:339-347. [PMID: 29987621 DOI: 10.1007/s11307-018-1217-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
PURPOSE Differences in site, device, and/or settings may cause large variations in the intensity profile of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) images. However, the current standard to evaluate these images, the striatal binding ratio (SBR), does not efficiently account for this heterogeneity and the assessment can be unequivalent across distinct acquisition pipelines. In this work, we present a voxel-based automated approach to intensity normalize such type of data that improves on cross-session interpretation. PROCEDURES The normalization method consists of a reparametrization of the voxel values based on the cumulative density function (CDF) of a Gamma distribution modeling the specific region intensity. The harmonization ability was tested in 1342 SPECT images from the PPMI repository, acquired with 7 distinct gamma camera models and at 24 different sites. We compared the striatal quantification across distinct cameras for raw intensities, SBR values, and after applying the Gamma CDF (GDCF) harmonization. As a proof-of-concept, we evaluated the impact of GCDF normalization in a classification task between controls and Parkinson disease patients. RESULTS Raw striatal intensities and SBR values presented significant differences across distinct camera models. We demonstrate that GCDF normalization efficiently alleviated these differences in striatal quantification and with values constrained to a fixed interval [0, 1]. Also, our method allowed a fully automated image assessment that provided maximal classification ability, given by an area under the curve (AUC) of AUC = 0.94 when used mean regional variables and AUC = 0.98 when used voxel-based variables. CONCLUSION The GCDF normalization method is useful to standardize the intensity of DAT SPECT images in an automated fashion and enables the development of unbiased algorithms using multicenter datasets. This method may constitute a key pre-processing step in the analysis of this type of images.
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Semiquantitative analysis using standardized uptake value in 123I-FP-CIT SPECT/CT. Clin Imaging 2018; 52:57-61. [PMID: 29909364 DOI: 10.1016/j.clinimag.2018.06.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 05/02/2018] [Accepted: 06/10/2018] [Indexed: 11/22/2022]
Abstract
PURPOSE To evaluate potential of a semiquantitative method using standardized uptake value (SUV) in 123I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) single photon emission computed tomography/computed tomography (SPECT/CT) compared with specific binding ratio (SBR). MATERIALS AND METHODS First, we performed a phantom study to validate the accuracy of measuring SUV. 52 patients (25 male, 27 female; mean age of 75.1-year-old; 40 and 12 patients with neurodegenerative diseases with or without presynaptic dopaminergic deficits, respectively) were enrolled in a retrospective study. We measured SBR, maximum SUV, peak SUV, mean SUV, and striatum-to-background ratio of SUV (SUVratio) for striatum with lower 123I-FP-CIT uptake using commercial software. We calculated Pearson's correlation coefficient between SBR and SUV. We also calculated the sensitivity, specificity, and accuracy of each parameter for differential diagnosis. RESULTS The phantom study revealed errors of <10% between theoretical and actual SUVs. Although there were significant correlations between SBR and all SUV-based parameters, SUVratio showed the most strong correlation with SBR (r = 0.877, p < 0.001). However, diagnostic capability of SUVratio (cutoff = 2.35) yielded to that of SBR (cutoff = 3.90) for diagnosing neurodegenerative diseases with presynaptic dopaminergic deficits (sensitivity of 85.0% vs 92.5%, specificity of 100% vs 91.7%, and accuracy of 88.5% vs 92.3%, respectively). CONCLUSION SBR is a promising parameter to aid differential diagnosis of neurodegenerative diseases with or without presynaptic dopaminergic deficit. Although technically acceptable, SUV may not be superior to SBR when clinically applied in 123I-FP-CIT SPECT/CT.
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Ikeda K, Yanagihashi M, Miura K, Ishikawa Y, Hirayama T, Takazawa T, Kano O, Kawabe K, Mizumura N, Iwasaki Y. Zonisamide cotreatment delays striatal dopamine transporter reduction in Parkinson disease: A retrospective, observational cohort study. J Neurol Sci 2018; 391:5-9. [PMID: 30103971 DOI: 10.1016/j.jns.2018.05.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 03/31/2018] [Accepted: 05/16/2018] [Indexed: 11/19/2022]
Abstract
This study examined whether zonisamide (ZNS) cotreatment delays dopamine transporter (DAT) reduction on SPECT in Parkinson disease (PD) patients. The study participants met the following criteria: (i) age ≥ 40 years; (ii) HY stage = 2 or 3; (iii) average specific binding ratio (SBR) ≥2.00; (iv) levodopa administration without a prior history of ZNS use before the first DAT-SPECT (baseline). Attending physicians initially determined whether ZNS (25 mg/day) should be used or not. Levodopa and other anti-PD medications were not restricted. The second DAT-SPECT (endpoint) was conducted 1.2 ± 0.2 years after the first DAT-SPECT. Clinicoradiological changes of HY stage, UPDRS parts II to IV, dyskinesia subscore, and SBR were calculated. Statistical differences were analyzed by Student's t-test, ANOVA, or multilogistic analysis. ZNS cotreatment improved wearing off and prevented the development of dyskinesia without additional administration of selegiline, entacapone, and dopamine receptor agonists. The endpoint SBR reduced significantly in the non-ZNS group compared to the baseline (P < .01). The SBR decline rate reduced significantly in the ZNS group (P < .01). ZNS was an independent preventive factor for SBR reduction. These results suggested a beneficial potential that ZNS preserves striatal presynaptic DAT expression and slows disease progression in early-stage PD.
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Affiliation(s)
- Ken Ikeda
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan.
| | - Masaru Yanagihashi
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan
| | - Ken Miura
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan
| | - Yuichi Ishikawa
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan
| | - Takehisa Hirayama
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan
| | - Takanori Takazawa
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan
| | - Osamu Kano
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan
| | - Kiyokazu Kawabe
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan
| | - Nao Mizumura
- Department of Radiology, Toho University Omori Medical Center, Tokyo, Japan
| | - Yasuo Iwasaki
- Department of Neurology, Toho University Omori Medical Center, Tokyo, Japan
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Tinaz S, Chow C, Kuo PH, Krupinski EA, Blumenfeld H, Louis ED, Zubal G. Semiquantitative Analysis of Dopamine Transporter Scans in Patients With Parkinson Disease. Clin Nucl Med 2018; 43:e1-e7. [PMID: 29112012 DOI: 10.1097/rlu.0000000000001885] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Dopamine transporter (DaT) imaging is an adjunct diagnostic tool in parkinsonian disorders. Interpretation of DaT scans is based on visual reads. SBRquant is an automated method that measures the striatal binding ratio (SBR) in DaT scans, but has yet to be optimized. We aimed to (1) optimize SBRquant parameters to distinguish between patients with Parkinson disease (PD) and healthy controls using the Parkinson's Progression Markers Initiative (PPMI) database and (2) test the validity of these parameters in an outpatient cohort. METHODS For optimization, 336 DaT scans (215 PD patients and 121 healthy controls) from the PPMI database were used. Striatal binding ratio was calculated varying the number of summed transverse slices (N) and positions of the striatal regions of interest (d). The resulting SBRs were evaluated using area under the receiver operating characteristic curve. The optimized parameters were then applied to 77 test patients (35 PD and 42 non-PD patients). Striatal binding ratios were also correlated with clinical measures in the PPMI-PD group. RESULTS The optimal parameters discriminated the training groups in the PPMI cohort with 95.8% sensitivity and 98.3% specificity (lowest putamen SBR threshold, 1.037). The same parameters discriminated the groups in the test cohort with 97.1% sensitivity and 100% specificity (lowest putamen SBR threshold, 0.875). A significant negative correlation (r = -0.24, P = 0.0004) was found between putamen SBRs and motor severity in the PPMI-PD group. CONCLUSIONS SBRquant discriminates DaT scans with high sensitivity and specificity. It has a high potential for use as a quantitative diagnostic aid in clinical and research settings.
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Improvement in the measurement error of the specific binding ratio in dopamine transporter SPECT imaging due to exclusion of the cerebrospinal fluid fraction using the threshold of voxel RI count. Ann Nucl Med 2018; 32:288-296. [PMID: 29546633 DOI: 10.1007/s12149-018-1249-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 03/04/2018] [Indexed: 10/17/2022]
Abstract
OBJECTIVE In Japan, the Southampton method for dopamine transporter (DAT) SPECT is widely used to quantitatively evaluate striatal radioactivity. The specific binding ratio (SBR) is the ratio of specific to non-specific binding observed after placing pentagonal striatal voxels of interest (VOIs) as references. Although the method can reduce the partial volume effect, the SBR may fluctuate due to the presence of low-count areas of cerebrospinal fluid (CSF), caused by brain atrophy, in the striatal VOIs. We examined the effect of the exclusion of low-count VOIs on SBR measurement. METHODS We retrospectively reviewed DAT imaging of 36 patients with parkinsonian syndromes performed after injection of 123I-FP-CIT. SPECT data were reconstructed using three conditions. We defined the CSF area in each SPECT image after segmenting the brain tissues. A merged image of gray and white matter images was constructed from each patient's magnetic resonance imaging (MRI) to create an idealized brain image that excluded the CSF fraction (MRI-mask method). We calculated the SBR and asymmetric index (AI) in the MRI-mask method for each reconstruction condition. We then calculated the mean and standard deviation (SD) of voxel RI counts in the reference VOI without the striatal VOIs in each image, and determined the SBR by excluding the low-count pixels (threshold method) using five thresholds: mean-0.0SD, mean-0.5SD, mean-1.0SD, mean-1.5SD, and mean-2.0SD. We also calculated the AIs from the SBRs measured using the threshold method. We examined the correlation among the SBRs of the threshold method, between the uncorrected SBRs and the SBRs of the MRI-mask method, and between the uncorrected AIs and the AIs of the MRI-mask method. RESULTS The intraclass correlation coefficient indicated an extremely high correlation among the SBRs and among the AIs of the MRI-mask and threshold methods at thresholds between mean-2.0D and mean-1.0SD, regardless of the reconstruction correction. The differences among the SBRs and the AIs of the two methods were smallest at thresholds between man-2.0SD and mean-1.0SD. CONCLUSION The SBR calculated using the threshold method was highly correlated with the MRI-SBR. These results suggest that the CSF correction of the threshold method is effective for the calculation of idealized SBR and AI values.
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Honma M, Masaoka Y, Kuroda T, Futamura A, Shiromaru A, Izumizaki M, Kawamura M. Impairment of cross-modality of vision and olfaction in Parkinson disease. Neurology 2018; 90:e977-e984. [PMID: 29438044 DOI: 10.1212/wnl.0000000000005110] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 12/07/2017] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVE To determine whether Parkinson disease (PD) affects cross-modal function of vision and olfaction because it is known that PD impairs various cognitive functions, including olfaction. METHODS We conducted behavioral experiments to identify the influence of PD on cross-modal function by contrasting patient performance with age-matched normal controls (NCs). We showed visual effects on the strength and preference of odor by manipulating semantic connections between picture/odorant pairs. In addition, we used brain imaging to identify the role of striatal presynaptic dopamine transporter (DaT) deficits. RESULTS We found that odor evaluation in participants with PD was unaffected by visual information, while NCs overestimated smell when sniffing odorless liquid while viewing pleasant/unpleasant visual cues. Furthermore, DaT deficit in striatum, for the posterior putamen in particular, correlated to few visual effects in participants with PD. CONCLUSIONS These findings suggest that PD impairs cross-modal function of vision/olfaction as a result of posterior putamen deficit. This cross-modal dysfunction may serve as the basis of a novel precursor assessment of PD.
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Affiliation(s)
- Motoyasu Honma
- From the Departments of Neurology (M.H., T.K., A.F., A.S., M.K.) and Physiology (Y.M., M.I.), Showa University School of Medicine, Tokyo, Japan.
| | - Yuri Masaoka
- From the Departments of Neurology (M.H., T.K., A.F., A.S., M.K.) and Physiology (Y.M., M.I.), Showa University School of Medicine, Tokyo, Japan
| | - Takeshi Kuroda
- From the Departments of Neurology (M.H., T.K., A.F., A.S., M.K.) and Physiology (Y.M., M.I.), Showa University School of Medicine, Tokyo, Japan
| | - Akinori Futamura
- From the Departments of Neurology (M.H., T.K., A.F., A.S., M.K.) and Physiology (Y.M., M.I.), Showa University School of Medicine, Tokyo, Japan
| | - Azusa Shiromaru
- From the Departments of Neurology (M.H., T.K., A.F., A.S., M.K.) and Physiology (Y.M., M.I.), Showa University School of Medicine, Tokyo, Japan
| | - Masahiko Izumizaki
- From the Departments of Neurology (M.H., T.K., A.F., A.S., M.K.) and Physiology (Y.M., M.I.), Showa University School of Medicine, Tokyo, Japan
| | - Mitsuru Kawamura
- From the Departments of Neurology (M.H., T.K., A.F., A.S., M.K.) and Physiology (Y.M., M.I.), Showa University School of Medicine, Tokyo, Japan.
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Neuroimaging in Parkinson's disease: focus on substantia nigra and nigro-striatal projection. Curr Opin Neurol 2018; 30:416-426. [PMID: 28537985 DOI: 10.1097/wco.0000000000000463] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW The diagnosis of Parkinson disease is based on clinical features; however, unmet need is an imaging signature for Parkinson disease and the early differential diagnosis with atypical parkinsonisms. A summary of the molecular imaging and MRI recent evidences for Parkinson disease diagnosis will be presented in this review. RECENT FINDINGS The nigro-striatal dysfunction explored by dopamine transporter imaging is not a mandatory diagnostic criterion for Parkinson disease, recent evidence supported its utility as in-vivo proof of degenerative parkinsonisms, and there might be compensatory mechanisms leading to an early overestimation. The visualization of abnormalities in substantia nigra by MRI has been recently described as sensitive and specific tool for Parkinson disease diagnosis, even in preclinical conditions, whereas it is not useful for distinguishing between Parkinson disease and atypical parkinsonisms. The relationship between the nigral anatomical changes, evaluated as structural alterations or neuromelanin signal decrease and the dopaminergic nigro-striatal function needs to be further clarified. SUMMARY With the hopeful advent of potential neuroprotective drugs for PD, it is crucial to have imaging measures that are able to detect at risk subjects. Moreover it is desirable to increase the knowledge about which measure better predicts the probability and the time of clinical conversion to PD.
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Utility of Follow-up Dopamine Transporter SPECT With 123I-FP-CIT in the Diagnostic Workup of Patients With Clinically Uncertain Parkinsonian Syndrome. Clin Nucl Med 2018; 42:589-594. [PMID: 28574876 DOI: 10.1097/rlu.0000000000001696] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE Dopamine transporter SPECT with I-FP-CIT is registered for detection (or exclusion) of nigrostriatal degeneration to support the etiologic classification of parkinsonian syndromes. In case of uncertainty in the interpretation of SPECT findings or unexpected clinical course, follow-up SPECT might be useful. However, the utility of follow-up FP-CIT SPECT has not yet been clarified. METHODS One hundred forty-one patients (65.1 ± 10.4 years) from 3 sites with follow-up FP-CIT SPECT 22.4 ± 13.7 months after baseline SPECT were included. Retrospective visual interpretation of FP-CIT SPECT scans was performed by 2 experienced readers according to the following 7-point score: "normal," some minor degree of uncertainty due to "mild asymmetry" or mild to moderate "uniform reduction," "Parkinson disease (PD) reduction type 1/2/3," and "atypical reduction." RESULTS Normal FP-CIT SPECT or PD characteristic reduction was confirmed by follow-up SPECT in all cases (n = 58). Among patients with some minor degree of uncertainty at baseline (n = 65), the majority (72%) did now show abnormalities in follow-up SPECT, but 20% showed clear progression suggesting nigrostriatal degeneration. The latter was very rare at age younger than 60 years. The final categorization as normal or neurodegenerative was not affected by the time delay between baseline and follow-up SPECT. CONCLUSIONS Follow-up FP-CIT SPECT cannot be generally recommended in case of completely normal baseline SPECT or PD characteristic reduction. It also cannot be recommended in patients younger than 60 years, even in case of some minor degree of uncertainty in the baseline SPECT. There is no evidence to delay follow-up FP-CIT SPECT longer than 12 months.
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