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Semmineh NB, Guha I, Healey D, Chandrasekharan A, Quarles CC, Boxerman JL. Imaging Intravoxel Vessel Size Distribution in the Brain Using Susceptibility Contrast Enhanced MRI. ARXIV 2025:arXiv:2503.17600v2. [PMID: 40196141 PMCID: PMC11975306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 04/09/2025]
Abstract
Vascular remodelling is inherent to the pathogenesis of many diseases including cancer, neurodegeneration, fibrosis, hypertension, and diabetes. In this paper, a new susceptibility-contrast based MRI approach is established to non-invasively image intravoxel vessel size distribution (VSD), enabling a more comprehensive and quantitative assessment of vascular remodelling. The approach utilizes high-resolution light-sheet fluorescence microscopy images of rodent brain vasculature, simulating gradient echo sampling of free induction decay and spin echo (GESFIDE) MRI signals for the three-dimensional vascular networks, and training a deep learning model to predict cerebral blood volume (CBV) and VSD from GESFIDE signals. The results from ex vivo experiments demonstrated strong correlation (r = 0.96) between the true and predicted CBV. High similarity between true and predicted VSDs was observed (mean Bhattacharya Coefficient = 0.92). With further in vivo validation, intravoxel VSD imaging could become a transformative preclinical and clinical tool for interrogating disease and treatment induced vascular remodelling.
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Affiliation(s)
- Natenael B Semmineh
- Department of Cancer Systems Imaging, Cancer Neuroscience Program, Neuroimaging Innovations to Transform Cancer Care (NeuroCare) Program, The University of Texas MD Anderson Cancer Center, Houston, TX, 77025, USA
| | - Indranil Guha
- Department of Cancer Systems Imaging, Cancer Neuroscience Program, Neuroimaging Innovations to Transform Cancer Care (NeuroCare) Program, The University of Texas MD Anderson Cancer Center, Houston, TX, 77025, USA
| | - Deborah Healey
- Department of Cancer Systems Imaging, Cancer Neuroscience Program, Neuroimaging Innovations to Transform Cancer Care (NeuroCare) Program, The University of Texas MD Anderson Cancer Center, Houston, TX, 77025, USA
| | - Anagha Chandrasekharan
- Department of Cancer Systems Imaging, Cancer Neuroscience Program, Neuroimaging Innovations to Transform Cancer Care (NeuroCare) Program, The University of Texas MD Anderson Cancer Center, Houston, TX, 77025, USA
| | - C Chad Quarles
- Department of Cancer Systems Imaging, Cancer Neuroscience Program, Neuroimaging Innovations to Transform Cancer Care (NeuroCare) Program, The University of Texas MD Anderson Cancer Center, Houston, TX, 77025, USA
| | - Jerrold L Boxerman
- Department of Diagnostic Imaging, Rhode Island Hospital, Providence, RI, 02903, USA
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Zhou X, Wang F, Yu L, Yang F, Kang J, Cao D, Xing Z. Prediction of PD-L1 and Ki-67 status in primary central nervous system diffuse large B-cell lymphoma by diffusion and perfusion MRI: a preliminary study. BMC Med Imaging 2024; 24:222. [PMID: 39187807 PMCID: PMC11348779 DOI: 10.1186/s12880-024-01409-y] [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: 02/29/2024] [Accepted: 08/22/2024] [Indexed: 08/28/2024] Open
Abstract
OBJECTIVE To assess whether diffusion and perfusion MRI derived parameters could non-invasively predict PD-L1 and Ki-67 status in primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). METHODS We retrospectively analyzed DWI, DSC-PWI, and morphological MRI (mMRI) in 88 patients with PCNS-DLBCL. The mMRI features were compared using chi-square tests or Fisher exact test. Minimum ADC (ADCmin), mean ADC(ADCmean), relative minimum ADC (rADCmin), relative mean ADC (rADCmean), and relative maximum CBV (rCBVmax) values were compared in PCNS-DLBCL with different molecular status by using the Mann-Whitney U test. The diagnostic performances were evaluated by receiver operating characteristic curves. RESULTS PCNS-DLBCL with high PD-L1 expression demonstrated a significantly higher ADCmin value than those with low PD-L1. The ADCmean and rADCmean values were significantly lower in PCNS-DLBCL with high Ki-67 status compared with those in low Ki-67 status. Other ADC, CBV parameters, and mMRI features did not show any association with these molecular statuses The diagnostic efficacy of ADC values in assessing PD-L1 and Ki-67 status was relatively low, with area under the curves (AUCs) values less than 0.7. CONCLUSIONS DWI-derived ADC values can provide some relevant information about PD-L1 and Ki-67 status in PCNS-DLBCL, but may not be sufficient to predict their expression due to the rather low diagnostic performance.
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Affiliation(s)
- Xiaofang Zhou
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, 20 Cha-Zhong Road, Fuzhou, 350005, Fujian, P.R. China
- Department of Radiology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China
| | - Feng Wang
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, 20 Cha-Zhong Road, Fuzhou, 350005, Fujian, P.R. China
- Department of Radiology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China
| | - Lan Yu
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, 20 Cha-Zhong Road, Fuzhou, 350005, Fujian, P.R. China
- Department of Radiology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China
| | - Feiman Yang
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, 20 Cha-Zhong Road, Fuzhou, 350005, Fujian, P.R. China
- Department of Radiology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China
| | - Jie Kang
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, 20 Cha-Zhong Road, Fuzhou, 350005, Fujian, P.R. China
- Department of Radiology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China
| | - Dairong Cao
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, 20 Cha-Zhong Road, Fuzhou, 350005, Fujian, P.R. China.
- Department of Radiology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China.
- Department of Radiology, Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
- Key Laboratory of Radiation Biology of Fujian Higher Education Institutions, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
| | - Zhen Xing
- Department of Radiology, The First Affiliated Hospital of Fujian Medical University, 20 Cha-Zhong Road, Fuzhou, 350005, Fujian, P.R. China.
- Department of Radiology, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China.
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Malik V, Kesavadas C, Thomas B, N. DA, K. KK. Diagnostic Utility of Integration of Dynamic Contrast-Enhanced and Dynamic Susceptibility Contrast MR Perfusion Employing Split Bolus Technique in Differentiating High-Grade Glioma. Indian J Radiol Imaging 2024; 34:382-389. [PMID: 38912247 PMCID: PMC11188723 DOI: 10.1055/s-0043-1777742] [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] [Indexed: 06/25/2024] Open
Abstract
Background : Despite documented correlation between glioma grades and dynamic contrast-enhanced (DCE) magnetic resonance (MR) perfusion-derived parameters, and its inherent advantages over dynamic susceptibility contrast (DSC) perfusion, the former remains underutilized in clinical practice. Given the inherent spatial heterogeneity in high-grade diffuse glioma (HGG) and assessment of different perfusion parameters by DCE (extravascular extracellular space volume [Ve] and volume transfer constant in unit time [k-trans]) and DSC (rCBV), integration of the two into a protocol could provide a holistic assessment. Considering therapeutic and prognostic implications of differentiating WHO grade 3 from 4, we analyzed the two grades based on a combined DCE and DSC perfusion. Methods : Perfusion sequences were performed on 3-T MR. Cumulative dose of 0.1 mmol/kg of gadodiamide, split into two equal boluses, was administered with an interval of 6 minutes between the DCE and DSC sequences. DCE data were analyzed utilizing commercially available GenIQ software. Results : Of the 41 cases of diffuse gliomas analyzed, 24 were WHO grade III and 17 grade IV gliomas (2016 WHO classification). To differentiate grade III and IV gliomas, Ve cut-off value of 0.178 provided the best combination of sensitivity (88.24%) and specificity (87.50%; AUC: 0.920; p < 0.001). A relative cerebral blood volume (rCBV) of value 3.64 yielded a sensitivity of 70.59% and specificity of 62.50% ( p = 0.018). The k-trans value, although higher in grade III than in grade IV gliomas, did not reach statistical significance ( p = 0.108). Conclusion : Uniqueness of employed combined perfusion technique, treatment naïve patients at imaging, user-friendly postprocessing software utilization, and ability of Ve and rCBV to differentiate between grade III and IV gliomas ( p < 0.05) are the strengths of the present study, contributing to the existing literature and moving a step closer to achieving accurate MR perfusion-based glioma grading.
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Affiliation(s)
| | - Chandrasekharan Kesavadas
- Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Bejoy Thomas
- Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Deepti A. N.
- Department of Pathology, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
| | - Krishna Kumar K.
- Department of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram, India
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Sawlani V, Jen JP, Patel M, Jain M, Haq H, Ughratdar I, Wykes V, Nagaraju S, Watts C, Pohl U. Multiparametric MRI and T2/FLAIR mismatch complements the World Health Organization 2021 classification for the diagnosis of IDH-mutant 1p/19q non-co-deleted/ATRX-mutant astrocytoma. Clin Radiol 2024; 79:197-204. [PMID: 38101998 DOI: 10.1016/j.crad.2023.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 10/14/2023] [Accepted: 11/14/2023] [Indexed: 12/17/2023]
Abstract
AIM To investigate whether T2-weighted imaging-fluid-attenuated inversion recovery (T2/FLAIR) mismatch, T2∗ dynamic susceptibility contrast (DSC) perfusion, and magnetic resonance spectroscopy (MRS) correlated with the histological diagnosis and grading of IDH (isocitrate dehydrogenase)-mutant, 1p/19q non-co-deleted/ATRX (alpha-thalassemia mental retardation X-linked)-mutant astrocytoma. MATERIALS Imaging of 101 IDH-mutant diffuse glioma cases of histological grades 2-3 (2019-2021) were analysed retrospectively by two neuroradiologists blinded to the molecular diagnosis. T2/FLAIR mismatch sign is used for radio-phenotyping, and pre-biopsy multiparametric MRI images were assessed for grading purposes. Cut-off values pre-determined for radiologically high-grade lesions were relative cerebral blood volume (rCBV) ≥2, choline/creatine ratio (Cho/Cr) ≥1.5 (30 ms echo time [TE]), Cho/Cr ≥1.8 (135 ms TE). RESULTS Sixteen of the 101 cases showed T2/FLAIR mismatch, all of which were histogenetically confirmed IDH-mutant 1p/19q non-co-deleted/ATRX mutant astrocytomas; 50% were grade 3 (8/16) and 50% grade 2 (8/16). None showed contrast enhancement. Nine of the 16 had adequate multiparametric MRI for analysis. Any positive value by combining rCBV ≥2 with Cho/Cr ≥1.5 (30 ms TE) or Cho/Cr ≥1.8 (135 ms TE) predicted grade 3 histology with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%. CONCLUSION The T2/FLAIR mismatch sign detected diffuse astrocytomas with 100% specificity. When combined with high Cho/Cr and raised rCBV, this predicted histological grading with high accuracy. The future direction for imaging should explore a similar integrated layered approach of 2021 classification of central nervous system (CNS) tumours combining radio-phenotyping and grading from structural and multiparametric imaging.
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Affiliation(s)
- V Sawlani
- Department of Neuroradiology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK; Department of Imaging, Neurosurgery and Neuropathology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK.
| | - J P Jen
- Department of Neuroradiology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
| | - M Patel
- Department of Neuroradiology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK; Department of Imaging, Neurosurgery and Neuropathology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
| | - M Jain
- Department of Neuroradiology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
| | - H Haq
- Department of Neuroradiology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
| | - I Ughratdar
- Department of Imaging, Neurosurgery and Neuropathology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK; Department of Neurosurgery, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
| | - V Wykes
- Department of Imaging, Neurosurgery and Neuropathology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK; Department of Neurosurgery, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
| | - S Nagaraju
- Department of Neuropathology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
| | - C Watts
- Department of Imaging, Neurosurgery and Neuropathology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK; Department of Neurosurgery, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
| | - U Pohl
- Department of Neuropathology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS FT, Birmingham, UK
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Porte C, Lisson T, Kohlen M, von Maltzahn F, Dencks S, von Stillfried S, Piepenbrock M, Rix A, Dasgupta A, Koczera P, Boor P, Stickeler E, Schmitz G, Kiessling F. Ultrasound Localization Microscopy for Breast Cancer Imaging in Patients: Protocol Optimization and Comparison with Shear Wave Elastography. ULTRASOUND IN MEDICINE & BIOLOGY 2024; 50:57-66. [PMID: 37805359 DOI: 10.1016/j.ultrasmedbio.2023.09.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 07/25/2023] [Accepted: 09/02/2023] [Indexed: 10/09/2023]
Abstract
OBJECTIVE Ultrasound localization microscopy (ULM) has gained increasing attention in recent years because of its ability to visualize blood vessels at super-resolution. The field of oncology, in particular, could benefit from detailed vascular characterization, for example, for diagnosis and therapy monitoring. This study was aimed at refining ULM for breast cancer patients by optimizing the measurement protocol, identifying translational challenges and combining ULM and shear wave elastography. METHODS We computed ULM images of 11 patients with breast cancer by recording contrast-enhanced ultrasound (CEUS) sequences and post-processing them in an offline pipeline. For CEUS, two different doses and injection speeds of SonoVue were applied. The best injection protocol was determined based on quantitative parameters derived from so-called occurrence maps. In addition, a suitable measurement time window was determined, also considering the occurrence of motion. ULM results were compared with shear wave elastography and histological vessel density. RESULTS At the higher dose and injection speed, the highest number of microbubbles, number of tracks and vessel coverage were achieved, leading to the most detailed representation of tumor vasculature. Even at the highest concentration, no significant overlay of microbubble signals occurred. Motion significantly reduced the number of usable frames, thus limiting the measurement window to 3.5 min. ULM vessel coverage was comparable to the histological vessel fraction and correlated significantly with mean tumor elasticity. CONCLUSION The settings for microbubble injection strongly influence ULM images, thus requiring optimized protocols for different indications. Patient and examiner motion was identified as the main translational challenge for ULM.
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Affiliation(s)
- Céline Porte
- Institute for Experimental Molecular Imaging, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Thomas Lisson
- Department of Electrical Engineering and Information Technology, Ruhr University Bochum, Bochum, Germany
| | - Matthias Kohlen
- Department of Gynecology and Obstetrics, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Finn von Maltzahn
- Institute for Experimental Molecular Imaging, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Stefanie Dencks
- Department of Electrical Engineering and Information Technology, Ruhr University Bochum, Bochum, Germany
| | - Saskia von Stillfried
- Institute of Pathology, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Marion Piepenbrock
- Department of Electrical Engineering and Information Technology, Ruhr University Bochum, Bochum, Germany
| | - Anne Rix
- Institute for Experimental Molecular Imaging, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Anshuman Dasgupta
- Institute for Experimental Molecular Imaging, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Patrick Koczera
- Institute for Experimental Molecular Imaging, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Peter Boor
- Institute of Pathology, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Elmar Stickeler
- Department of Gynecology and Obstetrics, University Clinic Aachen, RWTH Aachen University, Aachen, Germany
| | - Georg Schmitz
- Department of Electrical Engineering and Information Technology, Ruhr University Bochum, Bochum, Germany
| | - Fabian Kiessling
- Institute for Experimental Molecular Imaging, University Clinic Aachen, RWTH Aachen University, Aachen, Germany; Fraunhofer Institute for Digital Medicine MEVIS, Aachen, Germany.
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Agrawal I, Bano S, Chaudhary A, Ahuja A. Role of Permeability Surface Area Product in Grading of Brain Gliomas using CT Perfusion. Asian J Neurosurg 2023; 18:751-760. [PMID: 38161609 PMCID: PMC10756843 DOI: 10.1055/s-0043-1774820] [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] [Indexed: 01/03/2024] Open
Abstract
Purpose The aim of this study was to evaluate the role of permeability surface area product in grading brain gliomas using computed tomography (CT) perfusion Materials and Methods CT perfusion was performed on 33 patients with brain glioma diagnosed on magnetic resonance imaging. Of these, 19 had high-grade glioma and 14 had low-grade glioma on histopathological follow-up. CT perfusion values were obtained and first compared between the tumor region and normal brain parenchyma. Then the relative values of perfusion parameters were compared between high- and low-grade gliomas. Cut-off values, sensitivity, specificity, and strength of agreement for each parameter were calculated and compared subsequently. A conjoint factor (permeability surface area product + cerebral blood volume) was also evaluated since permeability surface area product and cerebral blood volume are considered complimentary factors for tumor vascularity. Results All five perfusion parameters namely permeability surface area product, cerebral blood volume, cerebral blood flow, mean transit time, and time to peak were found significantly higher in the tumor region than normal brain parenchyma. Among these perfusion parameters, only relative permeability surface area product and relative cerebral blood volume were found significant in differentiating high- and low-grade glioma. Moreover, relative permeability surface area product was significantly better than all other perfusion parameters with highest sensitivity and specificity (97.74 and 100%, respectively, at a cut-off of 9.0065). Relative permeability surface area product had a very good agreement with the histopathology grade. The conjoint factor did not yield any significant diagnostic advantage over permeability surface area product. Conclusion Relative permeability surface area product and relative cerebral blood volume were helpful in differentiating high- and low-grade glioma; however, relative permeability surface area product was significantly better than all other perfusion parameters. Grading brain gliomas using relative permeability surface area product can add crucial value in their management and prognostication; hence, it should be evaluated in the routine CT perfusion imaging protocol.
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Affiliation(s)
- Ira Agrawal
- Department of Radiodiagnosis, PGIMER, Dr. RML Hospital, New Delhi, India
| | - Shahina Bano
- Department of Radiodiagnosis, PGIMER, Dr. RML Hospital, New Delhi, India
| | - Ajay Chaudhary
- Department of Neurosurgery, PGIMER, Dr. RML Hospital, New Delhi, India
| | - Arvind Ahuja
- Department of Pathology, PGIMER, Dr. RML Hospital, New Delhi, India
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Chiu FY, Yen Y. Imaging biomarkers for clinical applications in neuro-oncology: current status and future perspectives. Biomark Res 2023; 11:35. [PMID: 36991494 DOI: 10.1186/s40364-023-00476-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 03/16/2023] [Indexed: 03/31/2023] Open
Abstract
Biomarker discovery and development are popular for detecting the subtle diseases. However, biomarkers are needed to be validated and approved, and even fewer are ever used clinically. Imaging biomarkers have a crucial role in the treatment of cancer patients because they provide objective information on tumor biology, the tumor's habitat, and the tumor's signature in the environment. Tumor changes in response to an intervention complement molecular and genomic translational diagnosis as well as quantitative information. Neuro-oncology has become more prominent in diagnostics and targeted therapies. The classification of tumors has been actively updated, and drug discovery, and delivery in nanoimmunotherapies are advancing in the field of target therapy research. It is important that biomarkers and diagnostic implements be developed and used to assess the prognosis or late effects of long-term survivors. An improved realization of cancer biology has transformed its management with an increasing emphasis on a personalized approach in precision medicine. In the first part, we discuss the biomarker categories in relation to the courses of a disease and specific clinical contexts, including that patients and specimens should both directly reflect the target population and intended use. In the second part, we present the CT perfusion approach that provides quantitative and qualitative data that has been successfully applied to the clinical diagnosis, treatment and application. Furthermore, the novel and promising multiparametric MR imageing approach will provide deeper insights regarding the tumor microenvironment in the immune response. Additionally, we briefly remark new tactics based on MRI and PET for converging on imaging biomarkers combined with applications of bioinformatics in artificial intelligence. In the third part, we briefly address new approaches based on theranostics in precision medicine. These sophisticated techniques merge achievable standardizations into an applicatory apparatus for primarily a diagnostic implementation and tracking radioactive drugs to identify and to deliver therapies in an individualized medicine paradigm. In this article, we describe the critical principles for imaging biomarker characterization and discuss the current status of CT, MRI and PET in finiding imaging biomarkers of early disease.
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Affiliation(s)
- Fang-Ying Chiu
- Center for Cancer Translational Research, Tzu Chi University, Hualien City, 970374, Taiwan.
- Center for Brain and Neurobiology Research, Tzu Chi University, Hualien City, 970374, Taiwan.
- Teaching and Research Headquarters for Sustainable Development Goals, Tzu Chi University, Hualien City, 970374, Taiwan.
| | - Yun Yen
- Center for Cancer Translational Research, Tzu Chi University, Hualien City, 970374, Taiwan.
- Ph.D. Program for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei City, 110301, Taiwan.
- Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei City, 110301, Taiwan.
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei City, 110301, Taiwan.
- Cancer Center, Taipei Municipal WanFang Hospital, Taipei City, 116081, Taiwan.
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Sequential and Hybrid PET/MRI Acquisition in Follow-Up Examination of Glioblastoma Show Similar Diagnostic Performance. Cancers (Basel) 2022; 15:cancers15010083. [PMID: 36612079 PMCID: PMC9817523 DOI: 10.3390/cancers15010083] [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: 10/28/2022] [Revised: 12/09/2022] [Accepted: 12/20/2022] [Indexed: 12/25/2022] Open
Abstract
Both positron emission tomography (PET) and magnetic resonance imaging (MRI), including dynamic susceptibility contrast perfusion (DSC-PWI), are crucial for treatment monitoring of patients with high-grade gliomas. In clinical practice, they are usually conducted at separate time points. Whether this affects their diagnostic performance is presently unclear. To this end, we retrospectively reviewed 38 patients with pathologically confirmed glioblastoma (IDH wild-type) and suspected tumor recurrence after radiotherapy. Only patients who received both a PET−MRI (where DSC perfusion was acquired simultaneously with a FET-PET) and a separate MRI exam (including DSC perfusion) were included. Tumors were automatically segmented into contrast-enhancing tumor (CET), necrosis, and edema. To compare the simultaneous as well as the sequential DSC perfusion to the FET-PET, we calculated Dice overlap, global mutual information as well as voxel-wise Spearman correlation of hotspot areas. For the joint assessment of PET and MRI, we computed logistic regression models for the differentiation between true progression (PD) and treatment-related changes (TRC) using simultaneously or sequentially acquired images as input data. We observed no significant differences between Dice overlap (p = 0.17; paired t-test), mutual information (p = 0.18; paired t-test) and Spearman correlation (p = 0.90; paired t-test) when comparing simultaneous PET−MRI and sequential PET/MRI acquisition. This also held true for the subgroup of patients with >14 days between exams. Importantly, for the diagnostic performance, ROC analysis showed similar AUCs for differentiation of PD and TRC (AUC simultaneous PET: 0.77; AUC sequential PET: 0.78; p = 0.83, DeLong’s test). We found no relevant differences between simultaneous and sequential acquisition of FET-PET and DSC perfusion, also regarding their diagnostic performance. Given the increasing attention to multi-parametric assessment of glioma treatment response, our results reassuringly suggest that sequential acquisition is clinically and scientifically acceptable.
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Bredno J, Venn O, Chen X, Freese P, Ofman JJ. Circulating Tumor DNA Allele Fraction: A Candidate Biological Signal for Multicancer Early Detection Tests to Assess the Clinical Significance of Cancers. THE AMERICAN JOURNAL OF PATHOLOGY 2022; 192:1368-1378. [PMID: 35948080 DOI: 10.1016/j.ajpath.2022.07.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 06/02/2022] [Accepted: 07/07/2022] [Indexed: 05/28/2023]
Abstract
Current imaging-based cancer screening approaches provide useful but limited prognostic information. Complementary to existing screening tests, cell-free DNA-based multicancer early detection (MCED) tests account for cancer biology [manifested through circulating tumor allele fraction (cTAF)], which could inform prognosis and help assess the cancer's clinical significance. This review discusses the factors affecting circulating tumor DNA (ctDNA) levels and cTAF, and their correlation with the cancer's clinical significance. Furthermore, it discusses the influence of cTAF on MCED test performance, which could help inform prognosis. Clinically significant cancers show higher ctDNA levels quantified by cTAF than indolent phenotype cancers within each stage. This is because more frequent mitosis and cell death combined with increased trafficking of cell-free DNA into circulation leads to greater vascularization and depth of tumor invasion. cTAF has been correlated with biomarkers for cancer aggressiveness and overall survival; cancers with lower cTAF had better survival when compared with cancers as determined by the higher cTAF and Surveillance, Epidemiology, and End Results-based survival for that cancer type at each stage. MCED-detected cancers in case-control studies had comparable survival to Surveillance, Epidemiology, and End Results-based survival at each stage. Because many MCED tests use ctDNA as an analyte, cTAF could provide a common metric to compare performance. The prognostic value of cTAF may allow MCED tests to preferentially detect clinically significant cancers at early stages when outcomes are favorable and this may avoid overdiagnosis.
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Affiliation(s)
- Joerg Bredno
- GRAIL, LLC, a subsidiary of Illumina, Inc., Menlo Park, California
| | - Oliver Venn
- GRAIL, LLC, a subsidiary of Illumina, Inc., Menlo Park, California.
| | - Xiaoji Chen
- GRAIL, LLC, a subsidiary of Illumina, Inc., Menlo Park, California
| | - Peter Freese
- GRAIL, LLC, a subsidiary of Illumina, Inc., Menlo Park, California
| | - Joshua J Ofman
- GRAIL, LLC, a subsidiary of Illumina, Inc., Menlo Park, California
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The new era of bio-molecular imaging with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) in neurosurgery of gliomas. Clin Transl Imaging 2022. [DOI: 10.1007/s40336-022-00509-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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Kamimura K, Nakajo M, Gohara M, Kawaji K, Bohara M, Fukukura Y, Uchida H, Tabata K, Iwanaga T, Akamine Y, Keupp J, Fukami T, Yoshiura T. Differentiation of hemangioblastoma from brain metastasis using MR amide proton transfer imaging. J Neuroimaging 2022; 32:920-929. [PMID: 35731178 DOI: 10.1111/jon.13019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/18/2022] [Accepted: 06/06/2022] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND AND PURPOSE Differentiation between hemangioblastoma and brain metastasis remains a challenge in neuroradiology using conventional MRI. Amide proton transfer (APT) imaging can provide unique molecular information. This study aimed to evaluate the usefulness of APT imaging in differentiating hemangioblastomas from brain metastases and compare APT imaging with diffusion-weighted imaging and dynamic susceptibility contrast perfusion-weighted imaging. METHODS This retrospective study included 11 patients with hemangioblastoma and 20 patients with brain metastases. Region-of-interest analyses were employed to obtain the mean, minimum, and maximum values of APT signal intensity, apparent diffusion coefficient (ADC), and relative cerebral blood volume (rCBV), and these indices were compared between hemangioblastomas and brain metastases using the unpaired t-test and Mann-Whitney U test. Their diagnostic performances were evaluated using receiver operating characteristic (ROC) analysis and area under the ROC curve (AUC). AUCs were compared using DeLong's method. RESULTS All MRI-derived indices were significantly higher in hemangioblastoma than in brain metastasis. ROC analysis revealed the best performance with APT-related indices (AUC = 1.000), although pairwise comparisons showed no significant difference between the mean ADC and mean rCBV. CONCLUSIONS APT imaging is a useful and robust imaging tool for differentiating hemangioblastoma from metastasis.
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Affiliation(s)
- Kiyohisa Kamimura
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Masanori Nakajo
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Misaki Gohara
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kodai Kawaji
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Manisha Bohara
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Yoshihiko Fukukura
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Hiroyuki Uchida
- Department of Neurosurgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Kazuhiro Tabata
- Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Takashi Iwanaga
- Department of Radiological Technology, Kagoshima University Hospital, Kagoshima, Japan
| | | | | | | | - Takashi Yoshiura
- Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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12
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Grading of IDH-mutant astrocytoma using diffusion, susceptibility and perfusion-weighted imaging. BMC Med Imaging 2022; 22:105. [PMID: 35644621 PMCID: PMC9150301 DOI: 10.1186/s12880-022-00832-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 05/24/2022] [Indexed: 01/16/2023] Open
Abstract
Background The accurate grading of IDH-mutant astrocytoma is essential to make therapeutic strategies and assess the prognosis of patients. The purpose of this study was to investigate the usefulness of DWI, SWI and DSC-PWI in grading IDH-mutant astrocytoma. Methods One hundred and seven patients with IDH-mutant astrocytoma who underwent DWI, SWI and DSC-PWI were retrospectively reviewed. Minimum apparent diffusion coefficient (ADCmin), intratumoral susceptibility signal intensity(ITSS) and maximum relative cerebral blood volume (rCBVmax) values were assessed. ADCmin, ITSS and rCBVmax values were compared between grade 2 vs. grade 3, grade 3 vs. grade 4 and grade 2 + 3 vs. grade 4 tumors. Logistic regression, tenfold cross-validation,and receiver operating characteristic (ROC) curve analyses were used to assess their diagnostic performances. Results Grade 4 IDH-mutant astrocytomas showed significantly lower ADCmin and higher rCBVmax as compared to grade 3 tumors (adjusted P < 0.001). IDH-mutant grade 3 astrocytomas showed significantly lower ITSS levels as compared with grade 4 tumors (adjusted P < 0.001). ITSS levels between IDH-mutant grade 2 and grade 3 astrocytomas were significantly different (adjusted P = 0.002). Combined the ADCmin, ITSS and rCBVmax resulted in the highest AUC for differentiation grade 2 and grade 3 tumors from grade 4 tumors. Conclusion ADCmin, rCBVmax and ITSS can be used for grading the IDH-mutant astrocytomas. The combination of ADCmin, ITSS and rCBVmax could improve the diagnostic performance in grading of IDH-mutant astrocytoma.
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13
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Woodall RT, Sahoo P, Cui Y, Chen BT, Shiroishi MS, Lavini C, Frankel P, Gutova M, Brown CE, Munson JM, Rockne RC. Repeatability of tumor perfusion kinetics from dynamic contrast-enhanced MRI in glioblastoma. Neurooncol Adv 2022; 3:vdab174. [PMID: 34988454 PMCID: PMC8715899 DOI: 10.1093/noajnl/vdab174] [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] [Indexed: 11/14/2022] Open
Abstract
Background Dynamic contrast-enhanced MRI (DCE-MRI) parameters have been shown to be biomarkers for treatment response in glioblastoma (GBM). However, variations in analysis and measurement methodology complicate determination of biological changes measured via DCE. The aim of this study is to quantify DCE-MRI variations attributable to analysis methodology and image quality in GBM patients. Methods The Extended Tofts model (eTM) and Leaky Tracer Kinetic Model (LTKM), with manually and automatically segmented vascular input functions (VIFs), were used to calculate perfusion kinetic parameters from 29 GBM patients with double-baseline DCE-MRI data. DCE-MRI images were acquired 2-5 days apart with no change in treatment. Repeatability of kinetic parameters was quantified with Bland-Altman and percent repeatability coefficient (%RC) analysis. Results The perfusion parameter with the least RC was the plasma volume fraction (v p ), with a %RC of 53%. The extra-cellular extra-vascular volume fraction (v e ) %RC was 82% and 81%, for extended Tofts-Kety Model (eTM) and LTKM respectively. The %RC of the volume transfer rate constant (K trans ) was 72% for the eTM, and 82% for the LTKM, respectively. Using an automatic VIF resulted in smaller %RCs for all model parameters, as compared to manual VIF. Conclusions As much as 72% change in K trans (eTM, autoVIF) can be attributable to non-biological changes in the 2-5 days between double-baseline imaging. Poor K trans repeatability may result from inferior temporal resolution and short image acquisition time. This variation suggests DCE-MRI repeatability studies should be performed institutionally, using an automatic VIF method and following quantitative imaging biomarkers alliance guidelines.
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Affiliation(s)
- Ryan T Woodall
- Division of Mathematical Oncology, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA
| | - Prativa Sahoo
- Division of Mathematical Oncology, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA
| | - Yujie Cui
- Division of Biostatistics, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA
| | - Bihong T Chen
- Department of Diagnostic Radiology, City of Hope, Duarte, California, USA
| | - Mark S Shiroishi
- Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Cristina Lavini
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam, the Netherlands
| | - Paul Frankel
- Division of Biostatistics, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA
| | - Margarita Gutova
- Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA
| | - Christine E Brown
- Department of Hematology & Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope, Duarte, California, USA.,Department of Immuno-Oncology, Beckman Research Institute, City of Hope, Duarte, California, USA
| | - Jennifer M Munson
- Department of Biomedical Engineering & Mechanics, Fralin Biomedical Research Institute, Virginia Tech, Roanoke, Virginia, USA
| | - Russell C Rockne
- Division of Mathematical Oncology, Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA
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14
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Yang X, Lin Y, Xing Z, She D, Su Y, Cao D. Predicting 1p/19q codeletion status using diffusion-, susceptibility-, perfusion-weighted, and conventional MRI in IDH-mutant lower-grade gliomas. Acta Radiol 2021; 62:1657-1665. [PMID: 33222488 DOI: 10.1177/0284185120973624] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Isocitrate dehydrogenase (IDH)-mutant lower-grade gliomas (LGGs) are further classified into two classes: with and without 1p/19q codeletion. IDH-mutant and 1p/19q codeleted LGGs have better prognosis compared with IDH-mutant and 1p/19q non-codeleted LGGs. PURPOSE To evaluate conventional magnetic resonance imaging (cMRI), diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) for predicting 1p/19q codeletion status of IDH-mutant LGGs. MATERIAL AND METHODS We retrospectively reviewed cMRI, DWI, SWI, and DSC-PWI in 142 cases of IDH mutant LGGs with known 1p/19q codeletion status. Features of cMRI, relative ADC (rADC), intratumoral susceptibility signals (ITSSs), and the value of relative cerebral blood volume (rCBV) were compared between IDH-mutant LGGs with and without 1p/19q codeletion. Receiver operating characteristic curve and logistic regression were used to determine diagnostic performances. RESULTS IDH-mutant and 1p/19q non-codeleted LGGs tended to present with the T2/FLAIR mismatch sign and distinct borders (P < 0.001 and P = 0.038, respectively). Parameters of rADC, ITSSs, and rCBVmax were significantly different between the 1p/19q codeleted and 1p/19q non-codeleted groups (P < 0.001, P = 0.017, and P < 0.001, respectively). A combination of cMRI, SWI, DWI, and DSC-PWI for predicting 1p/19q codeletion status in IDH-mutant LGGs resulted in a sensitivity, specificity, positive predictive value, negative predictive value, and an AUC of 80.36%, 78.57%, 83.30%, 75.00%, and 0.88, respectively. CONCLUSION 1p/19q codeletion status of IDH-mutant LGGs can be stratified using cMRI and advanced MRI techniques, including DWI, SWI, and DSC-PWI. A combination of cMRI, rADC, ITSSs, and rCBVmax may improve the diagnostic performance for predicting 1p/19q codeletion status.
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Affiliation(s)
- Xiefeng Yang
- Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China
| | - Yu Lin
- Department of Radiology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, PR China
| | - Zhen Xing
- Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China
| | - Dejun She
- Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China
| | - Yan Su
- Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China
| | - Dairong Cao
- Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, PR China
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15
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Wang K, Li Y, Cheng H, Li S, Xiang W, Ming Y, Chen L, Zhou J. Perfusion CT detects alterations in local cerebral flow of glioma related to IDH, MGMT and TERT status. BMC Neurol 2021; 21:460. [PMID: 34814870 PMCID: PMC8611974 DOI: 10.1186/s12883-021-02490-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 11/12/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The aim of this study was to investigate the relationship between tumor biology and values of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), time to peak (TTP), permeability surface (PS) of tumor in patients with glioma. METHODS Forty-six patients with glioma were involved in the study. Histopathologic and molecular pathology diagnoses were obtained by tumor resection, and all patients accepted perfusion computed tomography (PCT) before operation. Regions of interests were placed manually at tumor and contralateral normal-appearing thalamus. The parameters of tumor were divided by those of contralateral normal-appearing thalamus to normalize at tumor (relative [r] CBV, rCBF, rMTT, rTTP, rPS). The relationships of the parameters, world health organization (WHO) grade, molecular pathological findings were analysed. RESULTS The rCBV, rMTT and rPS of patients are positively related to the pathological classification (P < 0.05). The values of rCBV and rPS in IDH mutated patients were lower than those IDH wild-type. The values of rCBF in patients with MGMT methylation were lower than those MGMT unmethylation (P < 0.05). The MVD of TERT wild-type group was lower than TERT mutated group (P < 0.05). The values of rCBV were significant difference in the four molecular groups divided by the combined IDH/TERT classification (P < 0.05). The progression free survival (PFS) and overall survival (OS) were significant difference in the four molecular groups divided by the combined IDH/TERT classification (P < 0.05). CONCLUSIONS Our study introduces and supports the changes of glioma flow perfusion may be closely related to its biological characteristics.
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Affiliation(s)
- Ke Wang
- Department of Neurosurgery, Affliated Hospital of Southwest Medical University, Luzhou, China.,Department of Neurosurgery, The General Hospital of Western Theater Command PLA, Chengdu, China
| | - Yeming Li
- Department of Neurosurgery, Affliated Hospital of Southwest Medical University, Luzhou, China.,Neurosurgery Clinical Medical Research Center of Sichuan Province, Lu Zhou, China.,Neurological Diseases and Brain Function Laboratory, Luzhou, China
| | | | - Shenjie Li
- Department of Neurosurgery, Affliated Hospital of Southwest Medical University, Luzhou, China.,Neurosurgery Clinical Medical Research Center of Sichuan Province, Lu Zhou, China.,Neurological Diseases and Brain Function Laboratory, Luzhou, China
| | - Wei Xiang
- Department of Neurosurgery, Affliated Hospital of Southwest Medical University, Luzhou, China.,Neurosurgery Clinical Medical Research Center of Sichuan Province, Lu Zhou, China.,Neurological Diseases and Brain Function Laboratory, Luzhou, China
| | - Yang Ming
- Department of Neurosurgery, Affliated Hospital of Southwest Medical University, Luzhou, China.,Neurosurgery Clinical Medical Research Center of Sichuan Province, Lu Zhou, China.,Neurological Diseases and Brain Function Laboratory, Luzhou, China
| | - Ligang Chen
- Department of Neurosurgery, Affliated Hospital of Southwest Medical University, Luzhou, China.,Neurosurgery Clinical Medical Research Center of Sichuan Province, Lu Zhou, China.,Neurological Diseases and Brain Function Laboratory, Luzhou, China
| | - Jie Zhou
- Department of Neurosurgery, Affliated Hospital of Southwest Medical University, Luzhou, China. .,Neurosurgery Clinical Medical Research Center of Sichuan Province, Lu Zhou, China. .,Neurological Diseases and Brain Function Laboratory, Luzhou, China.
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Nicolas-Jilwan M, Wintermark M. Automated Brain Perfusion Imaging in Acute Ischemic Stroke: Interpretation Pearls and Pitfalls. Stroke 2021; 52:3728-3738. [PMID: 34565174 DOI: 10.1161/strokeaha.121.035049] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Recent advancements in computed tomography technology, including improved brain coverage and automated processing of the perfusion data, have reinforced the use of perfusion computed tomography imaging in the routine evaluation of patients with acute ischemic stroke. The DAWN (Diffusion Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trials have established the benefit of endovascular thrombectomy in patients with acute ischemic stroke with anterior circulation large vessel occlusion up to 24 hours of last seen normal, using perfusion imaging-based patient selection. The compelling data has prompted stroke centers to increasingly introduce automated perfusion computed tomography imaging in the routine evaluation of patients with acute ischemic stroke. We present a comprehensive overview of the acquisition and interpretation of automated perfusion imaging in patients with acute ischemic stroke with a special emphasis on the interpretation pearls, pitfalls, and stroke mimicking conditions.
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Affiliation(s)
- Manal Nicolas-Jilwan
- Division of Neuroradiology, Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia (M.N.-J.)
| | - Max Wintermark
- Division of Neuroimaging and Neurointervention, Department of Radiology, Stanford Healthcare, CA (M.W.)
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Fully automated analysis combining [ 18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression. Eur J Nucl Med Mol Imaging 2021; 48:4445-4455. [PMID: 34173008 PMCID: PMC8566389 DOI: 10.1007/s00259-021-05427-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 05/24/2021] [Indexed: 12/15/2022]
Abstract
Purpose To evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma. Material and methods At suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier’s performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments. Results In 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77–0.93 (sensitivity 0.91, 95% CI 0.81–0.97; specificity 0.71, 95% CI 0.44–0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72–0.9), 0.81 for [18F]-FET-PET (95% CI 0.7–0.89), and 0.81 for expert consensus (95% CI 0.7–0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities. Conclusion Automated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas. Supplementary Information The online version contains supplementary material available at 10.1007/s00259-021-05427-8.
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Overcast WB, Davis KM, Ho CY, Hutchins GD, Green MA, Graner BD, Veronesi MC. Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors. Curr Oncol Rep 2021; 23:34. [PMID: 33599882 PMCID: PMC7892735 DOI: 10.1007/s11912-021-01020-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/11/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW This review will explore the latest in advanced imaging techniques, with a focus on the complementary nature of multiparametric, multimodality imaging using magnetic resonance imaging (MRI) and positron emission tomography (PET). RECENT FINDINGS Advanced MRI techniques including perfusion-weighted imaging (PWI), MR spectroscopy (MRS), diffusion-weighted imaging (DWI), and MR chemical exchange saturation transfer (CEST) offer significant advantages over conventional MR imaging when evaluating tumor extent, predicting grade, and assessing treatment response. PET performed in addition to advanced MRI provides complementary information regarding tumor metabolic properties, particularly when performed simultaneously. 18F-fluoroethyltyrosine (FET) PET improves the specificity of tumor diagnosis and evaluation of post-treatment changes. Incorporation of radiogenomics and machine learning methods further improve advanced imaging. The complementary nature of combining advanced imaging techniques across modalities for brain tumor imaging and incorporating technologies such as radiogenomics has the potential to reshape the landscape in neuro-oncology.
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Affiliation(s)
- Wynton B. Overcast
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 550 N University Blvd. Room 0663, Indianapolis, IN 46202 USA
| | - Korbin M. Davis
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 550 N University Blvd. Room 0663, Indianapolis, IN 46202 USA
| | - Chang Y. Ho
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Goodman Hall, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202 USA
| | - Gary D. Hutchins
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Research 2 Building (R2), Room E124, 920 W. Walnut Street, Indianapolis, IN 46202-5181 USA
| | - Mark A. Green
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Research 2 Building (R2), Room E124, 920 W. Walnut Street, Indianapolis, IN 46202-5181 USA
| | - Brian D. Graner
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Goodman Hall, 355 West 16th Street, Suite 4100, Indianapolis, IN 46202 USA
| | - Michael C. Veronesi
- Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Research 2 Building (R2), Room E174, 920 W. Walnut Street, Indianapolis, IN 46202-5181 USA
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Soliman MA, Guccione J, Reiter AM, Moawad AW, Etchison A, Kamel S, Khatchikian AD, Elsayes KM. Current Concepts in Multi-Modality Imaging of Solid Tumor Angiogenesis. Cancers (Basel) 2020; 12:cancers12113239. [PMID: 33153067 PMCID: PMC7692820 DOI: 10.3390/cancers12113239] [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: 09/28/2020] [Revised: 10/15/2020] [Accepted: 10/19/2020] [Indexed: 12/11/2022] Open
Abstract
Simple Summary The recent increase in the use of targeted molecular therapy including anti-angiogenetic agents in cancer treatment necessitate the use of robust tools to assess and guide treatment. Angiogenesis, the formation of new disorganized blood vessels, is used by tumor cells to grow and spread using different mechanisms that could be targeted by anti-angiogenetic agents. In this review, we discuss the biological principles of tumor angiogenesis and the imaging modalities that could provide information beyond gross tumor size and morphology to capture the efficacy of anti-angiogenetic therapeutic response. Abstract There have been rapid advancements in cancer treatment in recent years, including targeted molecular therapy and the emergence of anti-angiogenic agents, which necessitate the need to quickly and accurately assess treatment response. The ideal tool is robust and non-invasive so that the treatment can be rapidly adjusted or discontinued based on efficacy. Since targeted therapies primarily affect tumor angiogenesis, morphological assessment based on tumor size alone may be insufficient, and other imaging modalities and features may be more helpful in assessing response. This review aims to discuss the biological principles of tumor angiogenesis and the multi-modality imaging evaluation of anti-angiogenic therapeutic responses.
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Affiliation(s)
- Moataz A. Soliman
- Department of Diagnostic Radiology, Northwestern University, Evanston, IL 60201, USA;
| | - Jeffrey Guccione
- Department of Diagnostic and Interventional Imaging, The University of Texas Health Sciences Center at Houston, Houston, TX 77030, USA;
| | - Anna M. Reiter
- School of Medicine, University of Texas Southwestern, Dallas, TX 75390, USA;
| | - Ahmed W. Moawad
- Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA;
| | - Ashley Etchison
- Department of Diagnostic Radiology, Baylor College of Medicine, Houston, TX 76798, USA;
| | - Serageldin Kamel
- Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA;
| | - Aline D. Khatchikian
- Department of Diagnostic Radiology, McGill University, Montreal, QC H3G 1A4, Canada;
| | - Khaled M. Elsayes
- Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA;
- Correspondence:
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Comparison of Conventional, Diffusion, and Perfusion MRI Between Low-Grade and Anaplastic Extraventricular Ependymoma. AJR Am J Roentgenol 2020; 215:978-984. [PMID: 32809860 DOI: 10.2214/ajr.20.22764] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE. The purpose of this study was to investigate and compare conventional MRI, DWI, and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) characteristics between low-grade and anaplastic extraventricular ependymomas. MATERIALS AND METHODS. Twenty-six patients with extraventricular ependymomas (19 anaplastic and seven low-grade) who underwent preoperative MRI were enrolled in this retrospective study. Conventional MRI and DWI were performed in all patients; DSCPWI was performed in 15 patients (11 with anaplastic ependymoma and four with low-grade ependymoma). Demographics, conventional MRI features, minimum relative apparent diffusion coefficient (rADCmin), and maximum relative cerebral blood volume (rCBVmax) of the low-grade and anaplastic ependymomas were compared. Diagnostic performance with optimal cutoff values was determined. RESULTS. Anaplastic extraventricular ependymomas were more likely to be located in the superficial supratentorial cerebral hemisphere (p = 0.026) and to present with pial and cortical involvement (p = 0.028 and 0.013, respectively) and necrotic degeneration (p = 0.014). The mean rADCmin ± SD of anaplastic ependymoma was significantly lower than that of low-grade ependymoma (0.8 ± 0.2 vs 1.2 ± 0.3, p = 0.002). The mean rCBVmax of anaplastic ependymoma was significantly higher than that of low-grade ependymoma (15.7 ± 5.3 vs 9.0 ± 4.4, p = 0.042). The cutoff values in grading extraventricular ependymoma were 1.02 for rADCmin and 10.43 for rCBVmax. Combining conventional MRI, DWI, and DSC-PWI allowed the best differentiation of low-grade and anaplastic ependymoma (AUC = 1.00). CONCLUSION. Conventional MRI, DWI, and DSC-PWI techniques may aid in assessing and grading extraventricular ependymomas.
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Schön S, Cabello J, Liesche-Starnecker F, Molina-Romero M, Eichinger P, Metz M, Karimov I, Preibisch C, Keupp J, Hock A, Meyer B, Weber W, Zimmer C, Pyka T, Yakushev I, Gempt J, Wiestler B. Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas. Eur J Nucl Med Mol Imaging 2020; 47:1468-1475. [PMID: 31953672 PMCID: PMC7188730 DOI: 10.1007/s00259-019-04677-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Accepted: 12/30/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas. METHODS Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging. RESULTS In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET. CONCLUSIONS We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.
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Affiliation(s)
- S Schön
- Department of Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - J Cabello
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - F Liesche-Starnecker
- Department of Neuropathology, Institute of Pathology, Technical University of Munich, Munich, Germany
| | - M Molina-Romero
- Image-based Biomedical Modeling, Technical University of Munich, Munich, Germany
| | - P Eichinger
- Department of Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - M Metz
- Department of Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - I Karimov
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - C Preibisch
- Department of Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - J Keupp
- Philips Research, Hamburg, Germany
| | - A Hock
- Philips Health Systems, Zurich, Switzerland
| | - B Meyer
- Department of Neurosurgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - W Weber
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - C Zimmer
- Department of Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - T Pyka
- Department of Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany
| | - I Yakushev
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - J Gempt
- Department of Neurosurgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - B Wiestler
- Department of Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
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Kiang KMY, Zhang P, Li N, Zhu Z, Jin L, Leung GKK. Loss of cytoskeleton protein ADD3 promotes tumor growth and angiogenesis in glioblastoma multiforme. Cancer Lett 2020; 474:118-126. [PMID: 31958485 DOI: 10.1016/j.canlet.2020.01.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2019] [Revised: 01/08/2020] [Accepted: 01/13/2020] [Indexed: 12/20/2022]
Abstract
Adducin 3 (ADD3) is a crucial assembly factor in the actin cytoskeleton and has been found to be aberrantly expressed in various cancers, including glioblastoma multiforme (GBM). It has previously been studied in array-based studies with controversial findings as to its functional role in glioma. In microarray analyses of 452 glioma specimens, we found significant downregulation of ADD3 in GBM, but not in less malignant gliomas, compared to normal brain tissue, which suggests that its downregulation might underlie critical events during malignant progression. We also found that ADD3 was functionally dependent on cell-matrix interaction. In our in vivo study, the proliferative and angiogenic capacity of ADD3-depleted GBM cells was promoted, possibly through PCNA, while p53 and p21 expression was suppressed, and pro-angiogenic signals were induced through VEGF-VEGFR-2-mediated activation in endothelial cells. With correlative in vitro, in vivo, and clinical data, we provide compelling evidence on the putative tumor-suppressive role of ADD3 in modulating GBM growth and angiogenesis. As a preclinical study, our research offers a better understanding of the pathogenesis of glioma malignant progression for the benefit of future investigations.
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Affiliation(s)
- Karrie Mei-Yee Kiang
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Pingde Zhang
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Ning Li
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Zhiyuan Zhu
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Lei Jin
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Gilberto Ka-Kit Leung
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
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Daboudi M, Papadaki E, Vakis A, Chlouverakis G, Makrakis D, Karageorgou D, Simos P, Koukouraki S. Brain SPECT and perfusion MRI: do they provide complementary information about the tumour lesion and its grading? Clin Radiol 2019; 74:652.e1-652.e9. [PMID: 31164195 DOI: 10.1016/j.crad.2019.03.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 03/22/2019] [Indexed: 10/26/2022]
Abstract
AIM To evaluate the relative and combined utility of 99mTc-tetrofosmin (99mTc-TF) brain single-photon-emission computed tomography (SPECT) and dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) in grading brain gliomas. MATERIALS AND METHODS Thirty-six patients with clinically suspected brain tumours were assessed by 99mTc-TF SPECT and DSC-MRI. Brain tumour malignancy was confirmed in all patients at histopathology. On both techniques brain lesions were evaluated via visual and semi-quantitative analysis methods (deriving tetrofosmin index [T-index] and relative cerebral blood volume [rCBV] ratios, respectively). RESULTS 99mTc-TF SPECT showed abnormally elevated tracer uptake in 31/36 patients whereas MRI detected the brain tumour in all patients. Optimal cut-off values of each index for discriminating between low- and high-grade gliomas were obtained through receiver operating characteristic (ROC) analyses. A T-index cut-off of 6.35 ensured 82% sensitivity and 71% specificity for discriminating between high- and low-grade gliomas, whereas a relative rCBV ratio cut-off of 1.80 achieved 91% sensitivity and 100% specificity. Requiring a positive result on either technique to characterise a high-grade glioma was associated with similar specificity and slightly increased sensitivity. CONCLUSION Both imaging techniques, 99mTF SPECT and DSC MRI, may provide complementary indices of tumour grade and have an independent diagnostic value for high-risk tumours.
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Affiliation(s)
- M Daboudi
- Department of Nuclear Medicine, School of Medicine, University of Crete, Heraklion, Crete, Greece.
| | - E Papadaki
- Department of Radiology, School of Medicine, University of Crete, Heraklion, Crete, Greece; Institute of Computer Science, Foundation of Research and Technology, Heraklion, Crete, Greece
| | - A Vakis
- Department of Neurosurgery, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - G Chlouverakis
- Biostatistics Lab., Department of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - D Makrakis
- Department of Radiology, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - D Karageorgou
- Department of Radiology, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - P Simos
- Institute of Computer Science, Foundation of Research and Technology, Heraklion, Crete, Greece; Department of Psychiatry, School of Medicine, University of Crete, Heraklion, Crete, Greece
| | - S Koukouraki
- Department of Nuclear Medicine, School of Medicine, University of Crete, Heraklion, Crete, Greece
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MR imaging phenotype correlates with extent of genome-wide copy number abundance in IDH mutant gliomas. Neuroradiology 2019; 61:1023-1031. [PMID: 31134296 DOI: 10.1007/s00234-019-02219-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 04/29/2019] [Indexed: 12/15/2022]
Abstract
PURPOSE There is variability in survival within IDH mutant gliomas determined by chromosomal events. Copy number variation (CNV) abundance associated with survival in low-grade and IDH mutant astrocytoma has been reported. Our purpose was to correlate the extent of genome-wide CNV abundance in IDH mutant astrocytomas with MRI features. METHODS Presurgical MRI and CNV plots derived from Illumina 850k EPIC DNA methylation arrays of 18 cases of WHO grade II-IV IDH mutant astrocytomas were reviewed. IDH mutant astrocytomas were divided into CNV stable group (CNV-S) with ≤ 3 chromosomal gains or losses and lack of focal gene amplifications and CNV unstable group (CNV-U) with > 3 large chromosomal gains/losses and/or focal amplifications. The associations between MR features, relative cerebral blood volume (rCBV), CNV abundance, and time to progression were assessed. Tumor rCBV estimates were obtained using DSC T2* perfusion analysis. RESULTS There were nine (50%) CNV-S and nine (50%) CNV-U IDH mutant astrocytomas. CNV-U tumors showed larger mean tumor size (P = 0.004) and maximum diameter on FLAIR (P = 0.004) and also demonstrated significantly higher median rCBV than CNV-S tumors (2.62 vs 0.78, P = 0.019). CNV-U tumors tended to have shorter time to progression although without statistical significance (P = 0.393). CONCLUSIONS Larger size/diameter and higher rCBVs were seen associated CNV-U astrocytomas, suggesting a correlation of aggressive imaging phenotype with unstable and aggressive genotype in IDH mutant astrocytomas.
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Demené C, Payen T, Dizeux A, Barrois G, Gennisson JL, Bridal L, Tanter M. 3-D Longitudinal Imaging of Tumor Angiogenesis in Mice in Vivo Using Ultrafast Doppler Tomography. ULTRASOUND IN MEDICINE & BIOLOGY 2019; 45:1284-1296. [PMID: 30799125 DOI: 10.1016/j.ultrasmedbio.2018.12.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 11/09/2018] [Accepted: 12/17/2018] [Indexed: 06/09/2023]
Abstract
Angiogenesis, the formation of new vessels, is one of the key mechanisms in tumor development and an appealing target for therapy. Non-invasive, high-resolution, high-sensitivity, quantitative 3-D imaging techniques are required to correctly depict tumor heterogeneous vasculature over time. Ultrafast Doppler was recently introduced and provides an unprecedented combination of resolution, penetration depth and sensitivity without requiring any contrast agents. The technique was further extended to three dimensions with ultrafast Doppler tomography (UFD-T). In this work, UFD-T was applied to the monitoring of tumor angiogenesis in vivo, providing structural and functional information at different stages of development. UFD-T volume renderings revealed that our murine model's vasculature stems from pre-existing vessels and sprouts to perfuse the whole volume as the tumor grows until a critical size is reached. Then, as the network becomes insufficient, the tumor core is no longer irrigated because the vasculature is concentrated mainly in the periphery. In addition to spatial distribution and growth patterns, UFD-T allowed a quantitative analysis of vessel size and length, revealing that the diameter distribution of vessels remained relatively constant throughout tumor growth. The network is dominated by small vessels at all stages of tumor development, with more than 74% of the vessels less than 200 µm in diameter. This study also found that cumulative vessel length is more closely related to tumor radius than volume, indicating that the vascularization becomes insufficient when a critical mass is reached. UFD-T was also compared with dynamic contrast-enhanced ultrasound and found to provide complementary information regarding the link between structure and perfusion. In conclusion, UFD-T is capable of in vivo quantitative assessment of the development of tumor vasculature (vessels with blood speed >1 mm/s [sensitivity limit] assessed with a resolution limit of 80 µm) in 3 dimensions. The technique has very interesting potential as a tool for treatment monitoring, response assessment and treatment planning for optimal drug efficiency.
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Affiliation(s)
- Charlie Demené
- Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Paris, France; Inserm Accélérateur de Recherche Technologique en Ultrasons biomédicaux, Paris, France.
| | - Thomas Payen
- Sorbonnne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France
| | - Alexandre Dizeux
- Sorbonnne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France
| | - Guillaume Barrois
- Sorbonnne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France
| | - Jean-Luc Gennisson
- Physics for Medicine Paris, Inserm, ESPCI Paris, CNRS, PSL Research University, Paris, France
| | - Lori Bridal
- Sorbonnne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France
| | - Mickael Tanter
- Inserm Accélérateur de Recherche Technologique en Ultrasons biomédicaux, Paris, France
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Kasenene A, Baidya A, Shams S, Xu HB. Evaluation of tumor response to antiangiogenic therapy in patients with recurrent gliomas using contrast-enhanced perfusion-weighted magnetic resonance imaging techniques: A meta-analysis. World J Meta-Anal 2019; 7:51-65. [DOI: 10.13105/wjma.v7.i2.51] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/07/2019] [Accepted: 02/14/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tumor. However, the treatment response is observed only in a fraction of patients due to the partial radiological response secondary to stabilization of abnormal vessels which does not essentially indicate a true antitumor effect. Perfusion-weighted magnetic resonance imaging (PW-MRI) techniques have shown implicitness as a strong imaging biomarker for gliomas since they give hemodynamic information of blood vessels. Hence, there is a rapid expansion of PW-MRI related studies and clinical applications.
AIM To determine the diagnostic performance of PW-MRI techniques including: (A) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); and (B) dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) for evaluating response to antiangiogenic therapy in patients with recurrent gliomas.
METHODS Databases such as PubMed (MEDLINE included), EMBASE, and Google Scholar were searched for relevant original articles. The included studies were assessed for methodological quality with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Medical imaging follow-up or histopathological analysis was used as the reference standard. The data were extracted by two reviewers independently, and then the sensitivity, specificity, summary receiver operating characteristic curve, area under the curve (AUC), and heterogeneity were calculated using Meta-Disc 1.4 software.
RESULTS This study analyzed a total of six articles. The overall sensitivity for DCE-MRI and DSC-MRI was 0.69 [95% confidence interval (CI): 0.53-0.82], and the specificity was 0.99 (95%CI: 0.93-1) by a random effects model (DerSimonianee-Laird model). The likelihood ratio (LR) +, LR-, and diagnostic odds ratio (DOR) were 12.84 (4.54-36.28), 0.35 (0.22-0.53), and 24.44 (7.19-83.06), respectively. The AUC (± SE) was 0.9921 (± 0.0120), and the Q* index (± SE) was 0.9640 (± 0.0323). For DSC-MRI, the sensitivity was 0.73, the specificity was 0.98, the LR+ was 7.82, the LR- was 0.32, the DOR was 31.65, the AUC (± SE) was 0.9925 (± 0.0132), and the Q* index was 0.9649 (± 0.0363). For DCE-MRI, the sensitivity was 0.41, the specificity was 0.97, the LR+ was 5.34, the LR- was 0.71, the DOR was 8.76, the AUC (± SE) was 0.9922 (± 0.2218), and the Q* index was 0.8935 (± 0.3037).
CONCLUSION This meta-analysis demonstrated a beneficial value of PW-MRI (DSC-MRI and DCE-MRI) in monitoring the response of recurrent gliomas to antiangiogenic therapy, with reasonable sensitivity, specificity, +LR, and -LR.
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Affiliation(s)
- Akanganyira Kasenene
- Department of Radiology and Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Aju Baidya
- Department of Radiology and Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Salman Shams
- Department of Radiology and Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China
| | - Hai-Bo Xu
- Department of Radiology and Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China
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Macrovascular Networks on Contrast-Enhanced Magnetic Resonance Imaging Improves Survival Prediction in Newly Diagnosed Glioblastoma. Cancers (Basel) 2019; 11:cancers11010084. [PMID: 30646519 PMCID: PMC6356693 DOI: 10.3390/cancers11010084] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Revised: 12/17/2018] [Accepted: 12/20/2018] [Indexed: 12/30/2022] Open
Abstract
A higher degree of angiogenesis is associated with shortened survival in glioblastoma. Feasible morphometric parameters for analyzing vascular networks in brain tumors in clinical practice are lacking. We investigated whether the macrovascular network classified by the number of vessel-like structures (nVS) visible on three-dimensional T1-weighted contrast–enhanced (3D-T1CE) magnetic resonance imaging (MRI) could improve survival prediction models for newly diagnosed glioblastoma based on clinical and other imaging features. Ninety-seven consecutive patients (62 men; mean age, 58 ± 15 years) with histologically proven glioblastoma underwent 1.5T-MRI, including anatomical, diffusion-weighted, dynamic susceptibility contrast perfusion, and 3D-T1CE sequences after 0.1 mmol/kg gadobutrol. We assessed nVS related to the tumor on 1-mm isovoxel 3D-T1CE images, and relative cerebral blood volume, relative cerebral flow volume (rCBF), delay mean time, and apparent diffusion coefficient in volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter. We also assessed Visually Accessible Rembrandt Images scoring system features. We used ROC curves to determine the cutoff for nVS and univariate and multivariate cox proportional hazards regression for overall survival. Prognostic factors were evaluated by Kaplan-Meier survival and ROC analyses. Lesions with nVS > 5 were classified as having highly developed macrovascular network; 58 (60.4%) tumors had highly developed macrovascular network. Patients with highly developed macrovascular network were older, had higher volumeCEL, increased rCBFCEL, and poor survival; nVS correlated negatively with survival (r = −0.286; p = 0.008). On multivariate analysis, standard treatment, age at diagnosis, and macrovascular network best predicted survival at 1 year (AUC 0.901, 83.3% sensitivity, 93.3% specificity, 96.2% PPV, 73.7% NPV). Contrast-enhanced MRI macrovascular network improves survival prediction in newly diagnosed glioblastoma.
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Di N, Cheng W, Jiang X, Liu X, Zhou J, Xie Q, Chu Z, Chen H, Wang B. Can dynamic contrast-enhanced MRI evaluate VEGF expression in brain glioma? An MRI-guided stereotactic biopsy study. J Neuroradiol 2018; 46:186-192. [PMID: 29752976 DOI: 10.1016/j.neurad.2018.04.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Revised: 02/16/2018] [Accepted: 04/21/2018] [Indexed: 12/18/2022]
Abstract
PURPOSE To investigate whether pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to evaluate vascular endothelial growth factor (VEGF) expression in brain glioma based on a point-to-point basis. MATERIALS AND METHODS Forty-seven patients with treatment-naïve glioma received preoperative DCE-MRI before stereotactic biopsy. We histologically quantified VEGF from section of stereotactic biopsies, and co-registered biopsy locations with localized measurements of DCE-MRI parameters including volume transfer coefficient (Ktrans), reverse reflux rate constant (Kep), extracellular extravascular volume fraction (Ve) and blood plasma volume (Vp). The correlations between DCE-MRI parameters (Ktrans, Kep, Ve and Vp) and VEGF were determined using Spearman correlation coefficient. P≤.05 was considered statistically significant. RESULTS Seventy-nine biopsy samples were obtained and graded into 45 high-grade gliomas (HGGs) and 34 low-grade gliomas (LGGs). Ktrans showed a significant positive correlation with VEGF expression in HGGs group (ρ=0.505, P<0.001) and in combined group (LGGs+HGGs) (ρ=0.549, P<0.001), but not in LGGs group (P>0.05). Kep, Ve or Vp was not correlated with VEGF even though a positive trend showed (P>0.05). CONCLUSIONS DCE-MRI is a useful, non-invasive imaging technique for quantitative evaluation of VEGF, and its parameter Ktrans other than Kep, Ve or Vp may be used as a surrogate for VEGF expression in brain gliomas.
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Affiliation(s)
- Ningning Di
- Department of Radiology, Binzhou Medical University Hospital, 661, Huanghe road, 256600 Binzhou, China; Department of Radiology, Huashan Hospital Fudan University, 12, Wulumuqi road Middle, 200040 Shanghai, China.
| | - Wenna Cheng
- Department of Pharmacy, Binzhou Medical University Hospital, 661, Huanghe road, 256600 Binzhou, China.
| | - Xingyue Jiang
- Department of Radiology, Binzhou Medical University Hospital, 661, Huanghe road, 256600 Binzhou, China.
| | - Xinjiang Liu
- Department of Radiology, Binzhou Medical University Hospital, 661, Huanghe road, 256600 Binzhou, China.
| | - Jinliang Zhou
- Department of Radiology, Binzhou Medical University Hospital, 661, Huanghe road, 256600 Binzhou, China.
| | - Qian Xie
- Department of Radiology, Huashan Hospital Fudan University, 12, Wulumuqi road Middle, 200040 Shanghai, China.
| | - Zhihui Chu
- Department of Radiology, Binzhou Medical University Hospital, 661, Huanghe road, 256600 Binzhou, China.
| | - Huacheng Chen
- Department of Radiology, Weifang Traditional Chinese Hospital, 1055, Weizhou road, 256600 Weifang, China.
| | - Bin Wang
- Department of Medical Imaging and Nuclear, Binzhou Medical University, 346, Guanhai road, 264000 Yantai, China.
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Di N, Yao C, Cheng W, Ren Y, Qu J, Wang B, Yao Z. Correlation of dynamic contrast-enhanced MRI derived volume transfer constant with histological angiogenic markers in high-grade gliomas. J Med Imaging Radiat Oncol 2018; 62:464-470. [PMID: 29330968 DOI: 10.1111/1754-9485.12701] [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: 08/16/2016] [Accepted: 12/12/2017] [Indexed: 11/30/2022]
Abstract
INTRODUCTION To ascertain if the volume transfer constant (Ktrans ) derived from T1 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlates with the immunohistological markers of angiogenesis in high-grade gliomas. METHODS Fifty-one image-guided biopsy specimens in 34 patients with newly presenting high-grade gliomas (grade III = 16; grade IV = 18) underwent preoperative imaging (conventional imaging and T1 DCE-MRI). We correlated vascular endothelial growth factor (VEGF) expression and the microvessel density (MVD) of MRI-guided biopsy specimens with the corresponding DCE-derived Ktrans . Histological sections were stained with VEGF and CD34, and examined under light microscopy. These histological and molecular markers of angiogenesis were correlated with the Ktrans of the region of interest corresponding to the biopsy specimen. RESULTS The Ktrans showed a significant positive correlation with VEGF expression (ρ = 0.582, P = 0.001) but not with MVD stained with CD34 antibody (ρ = 0.328, P = 0.072). CONCLUSION The Ktrans derived from DCE-MRI can reflect the VEGF expression of high-grade gliomas but not the MVD.
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Affiliation(s)
- Ningning Di
- Department of Radiology, Binzhou Medical University Hospital, Binzhou, China
- Department of Radiology, Huashan Hospital Fudan University, Shanghai, China
| | - Chenjun Yao
- Department of Neurosurgery, Huashan Hospital Fudan University, Shanghai, China
| | - Wenna Cheng
- Department of Pharmacy, Binzhou Medical University Affiliated Hospital, Binzhou, China
| | - Yan Ren
- Department of Radiology, Huashan Hospital Fudan University, Shanghai, China
| | | | - Bin Wang
- Department of Medical Imaging and Nuclear Medicine, Binzhou Medical University, Yantai, China
| | - Zhenwei Yao
- Department of Radiology, Huashan Hospital Fudan University, Shanghai, China
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Verburg N, Hoefnagels FWA, Barkhof F, Boellaard R, Goldman S, Guo J, Heimans JJ, Hoekstra OS, Jain R, Kinoshita M, Pouwels PJW, Price SJ, Reijneveld JC, Stadlbauer A, Vandertop WP, Wesseling P, Zwinderman AH, De Witt Hamer PC. Diagnostic Accuracy of Neuroimaging to Delineate Diffuse Gliomas within the Brain: A Meta-Analysis. AJNR Am J Neuroradiol 2017; 38:1884-1891. [PMID: 28882867 DOI: 10.3174/ajnr.a5368] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 05/30/2017] [Indexed: 12/25/2022]
Abstract
BACKGROUND Brain imaging in diffuse glioma is used for diagnosis, treatment planning, and follow-up. PURPOSE In this meta-analysis, we address the diagnostic accuracy of imaging to delineate diffuse glioma. DATA SOURCES We systematically searched studies of adults with diffuse gliomas and correlation of imaging with histopathology. STUDY SELECTION Study inclusion was based on quality criteria. Individual patient data were used, if available. DATA ANALYSIS A hierarchic summary receiver operating characteristic method was applied. Low- and high-grade gliomas were analyzed in subgroups. DATA SYNTHESIS Sixty-one studies described 3532 samples in 1309 patients. The mean Standard for Reporting of Diagnostic Accuracy score (13/25) indicated suboptimal reporting quality. For diffuse gliomas as a whole, the diagnostic accuracy was best with T2-weighted imaging, measured as area under the curve, false-positive rate, true-positive rate, and diagnostic odds ratio of 95.6%, 3.3%, 82%, and 152. For low-grade gliomas, the diagnostic accuracy of T2-weighted imaging as a reference was 89.0%, 0.4%, 44.7%, and 205; and for high-grade gliomas, with T1-weighted gadolinium-enhanced MR imaging as a reference, it was 80.7%, 16.8%, 73.3%, and 14.8. In high-grade gliomas, MR spectroscopy (85.7%, 35.0%, 85.7%, and 12.4) and 11C methionine-PET (85.1%, 38.7%, 93.7%, and 26.6) performed better than the reference imaging. LIMITATIONS True-negative samples were underrepresented in these data, so false-positive rates are probably less reliable than true-positive rates. Multimodality imaging data were unavailable. CONCLUSIONS The diagnostic accuracy of commonly used imaging is better for delineation of low-grade gliomas than high-grade gliomas on the basis of limited evidence. Improvement is indicated from advanced techniques, such as MR spectroscopy and PET.
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Affiliation(s)
- N Verburg
- From the Neurosurgical Center Amsterdam (N.V., F.W.A.H., W.P.V., P.C.D.W.H.)
| | - F W A Hoefnagels
- From the Neurosurgical Center Amsterdam (N.V., F.W.A.H., W.P.V., P.C.D.W.H.)
| | - F Barkhof
- Departments of Radiology and Nuclear Medicine (F.B., R.B., O.S.H.)
- Institutes of Neurology and Healthcare Engineering (F.B.), University College London, London, UK
| | - R Boellaard
- Departments of Radiology and Nuclear Medicine (F.B., R.B., O.S.H.)
| | - S Goldman
- Service of Nuclear Medicine and PET/Biomedical Cyclotron Unit (S.G.), l'université libre de Bruxelles-Hôpital Erasme, Brussels, Belgium
| | - J Guo
- Shanghai Medical College (J.G.), Fudan University, Shanghai, China
| | | | - O S Hoekstra
- Departments of Radiology and Nuclear Medicine (F.B., R.B., O.S.H.)
| | - R Jain
- Department of Radiology (R.J.), New York University School of Medicine, New York, New York
| | - M Kinoshita
- Department of Neurosurgery (M.K.), Osaka University Graduate School of Medicine, Osaka, Japan
| | | | - S J Price
- Academic Neurosurgery Division (S.J.P.), Department of Clinical Neurosciences, Addenbrooke's Hospital, Cambridge, UK
| | | | - A Stadlbauer
- Department of Neurosurgery (A.S.), University of Erlangen-Nuremberg, Erlangen, Germany
| | - W P Vandertop
- From the Neurosurgical Center Amsterdam (N.V., F.W.A.H., W.P.V., P.C.D.W.H.)
| | - P Wesseling
- Pathology (P.W.), VU University Medical Center, Amsterdam, the Netherlands
- Department of Pathology (P.W.), Radboud University Medical Centre, Nijmegen, the Netherlands
| | - A H Zwinderman
- Department of Clinical Epidemiology and Biostatistics (A.H.Z.), Academic Medical Center, University of Amsterdam, the Netherlands
| | - P C De Witt Hamer
- From the Neurosurgical Center Amsterdam (N.V., F.W.A.H., W.P.V., P.C.D.W.H.)
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Prah MA, Al-Gizawiy MM, Mueller WM, Cochran EJ, Hoffmann RG, Connelly JM, Schmainda KM. Spatial discrimination of glioblastoma and treatment effect with histologically-validated perfusion and diffusion magnetic resonance imaging metrics. J Neurooncol 2017; 136:13-21. [PMID: 28900832 DOI: 10.1007/s11060-017-2617-3] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 09/04/2017] [Indexed: 11/30/2022]
Abstract
The goal of this study is to spatially discriminate tumor from treatment effect (TE), within the contrast-enhancing lesion, for brain tumor patients at all stages of treatment. To this end, the diagnostic accuracy of MRI-derived diffusion and perfusion parameters to distinguish pure TE from pure glioblastoma (GBM) was determined utilizing spatially-correlated biopsy samples. From July 2010 through June 2015, brain tumor patients who underwent pre-operative DWI and DSC-MRI and stereotactic image-guided biopsy were considered for inclusion in this IRB-approved study. MRI-derived parameter maps included apparent diffusion coefficient (ADC), normalized cerebral blood flow (nCBF), normalized and standardized relative cerebral blood volume (nRCBV, sRCBV), peak signal-height (PSR) and percent signal-recovery (PSR). These were co-registered to the Stealth MRI and median values extracted from the spatially-matched biopsy regions. A ROC analysis accounting for multiple subject samples was performed, and the optimal threshold for distinguishing TE from GBM determined for each parameter. Histopathologic diagnosis of pure TE (n = 10) or pure GBM (n = 34) was confirmed in tissue samples from 15 consecutive subjects with analyzable data. Perfusion thresholds of sRCBV (3575; SN/SP% = 79.4/90.0), nRCBV (1.13; SN/SP% = 82.1/90.0), and nCBF (1.05; SN/SP% = 79.4/80.0) distinguished TE from GBM (P < 0.05), whereas ADC, PSR, and PH could not (P > 0.05). The thresholds for CBF and CBV can be applied to lesions with any admixture of tumor or treatment effect, enabling the identification of true tumor burden within enhancing lesions. This approach overcomes current limitations of averaging values from both tumor and TE for quantitative assessments.
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Affiliation(s)
- Melissa A Prah
- Department of Radiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA
| | - Mona M Al-Gizawiy
- Department of Radiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA
| | - Wade M Mueller
- Department of Neurosurgery, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI, 53226, USA
| | - Elizabeth J Cochran
- Department of Pathology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI, 53226, USA
| | - Raymond G Hoffmann
- Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA
| | - Jennifer M Connelly
- Department of Neurology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI, 53226, USA
| | - Kathleen M Schmainda
- Department of Radiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA. .,Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI, 53226, USA.
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32
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Xing Z, Yang X, She D, Lin Y, Zhang Y, Cao D. Noninvasive Assessment of IDH Mutational Status in World Health Organization Grade II and III Astrocytomas Using DWI and DSC-PWI Combined with Conventional MR Imaging. AJNR Am J Neuroradiol 2017; 38:1138-1144. [PMID: 28450436 DOI: 10.3174/ajnr.a5171] [Citation(s) in RCA: 98] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2016] [Accepted: 02/06/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND PURPOSE Isocitrate dehydrogenase (IDH) has been shown to have both diagnostic and prognostic implications in gliomas. The purpose of this study was to examine whether DWI and DSC-PWI combined with conventional MR imaging could noninvasively predict IDH mutational status in World Health Organization grade II and III astrocytomas. MATERIALS AND METHODS We retrospectively reviewed DWI, DSC-PWI, and conventional MR imaging in 42 patients with World Health Organization grade II and III astrocytomas. Minimum ADC, relative ADC, and relative maximum CBV values were compared between IDH-mutant and wild-type tumors by using the Mann-Whitney U test. Receiver operating characteristic curve and logistic regression were used to assess their diagnostic performances. RESULTS Minimum ADC and relative ADC were significantly higher in IDH-mutated grade II and III astrocytomas than in IDH wild-type tumors (P < .05). Minimum ADC with the cutoff value of ≥1.01 × 10-3 mm2/s could differentiate the mutational status with a sensitivity, specificity, positive predictive value, and negative predictive value of 76.9%, 82.6%, 91.2%, and 60.5%, respectively. The threshold value of <2.35 for relative maximum CBV in the prediction of IDH mutation provided a sensitivity, specificity, positive predictive value, and negative predictive value of 100.0%, 60.9%, 85.6%, and 100.0%, respectively. A combination of DWI, DSC-PWI, and conventional MR imaging for the identification of IDH mutations resulted in a sensitivity, specificity, positive predictive value, and negative predictive value of 92.3%, 91.3%, 96.1%, and 83.6%. CONCLUSIONS A combination of conventional MR imaging, DWI, and DSC-PWI techniques produces a high sensitivity, specificity, positive predictive value, and negative predictive value for predicting IDH mutations in grade II and III astrocytomas. The strategy of using advanced, semiquantitative MR imaging techniques may provide an important, noninvasive, surrogate marker that should be studied further in larger, prospective trials.
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Affiliation(s)
- Z Xing
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China
| | - X Yang
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China
| | - D She
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China
| | - Y Lin
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China
| | - Y Zhang
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China
| | - D Cao
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China.
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Zhang J, Liu H, Tong H, Wang S, Yang Y, Liu G, Zhang W. Clinical Applications of Contrast-Enhanced Perfusion MRI Techniques in Gliomas: Recent Advances and Current Challenges. CONTRAST MEDIA & MOLECULAR IMAGING 2017; 2017:7064120. [PMID: 29097933 PMCID: PMC5612612 DOI: 10.1155/2017/7064120] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 02/23/2017] [Indexed: 01/12/2023]
Abstract
Gliomas possess complex and heterogeneous vasculatures with abnormal hemodynamics. Despite considerable advances in diagnostic and therapeutic techniques for improving tumor management and patient care in recent years, the prognosis of malignant gliomas remains dismal. Perfusion-weighted magnetic resonance imaging techniques that could noninvasively provide superior information on vascular functionality have attracted much attention for evaluating brain tumors. However, nonconsensus imaging protocols and postprocessing analysis among different institutions impede their integration into standard-of-care imaging in clinic. And there have been very few studies providing a comprehensive evidence-based and systematic summary. This review first outlines the status of glioma theranostics and tumor-associated vascular pathology and then presents an overview of the principles of dynamic contrast-enhanced MRI (DCE-MRI) and dynamic susceptibility contrast-MRI (DSC-MRI), with emphasis on their recent clinical applications in gliomas including tumor grading, identification of molecular characteristics, differentiation of glioma from other brain tumors, treatment response assessment, and predicting prognosis. Current challenges and future perspectives are also highlighted.
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Affiliation(s)
- Junfeng Zhang
- Department of Radiology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China
| | - Heng Liu
- Department of Radiology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Haipeng Tong
- Department of Radiology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China
| | - Sumei Wang
- Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Yizeng Yang
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Gang Liu
- State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Weiguo Zhang
- Department of Radiology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China
- Chongqing Clinical Research Center for Imaging and Nuclear Medicine, Chongqing 400042, China
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Eidel O, Burth S, Neumann JO, Kieslich PJ, Sahm F, Jungk C, Kickingereder P, Bickelhaupt S, Mundiyanapurath S, Bäumer P, Wick W, Schlemmer HP, Kiening K, Unterberg A, Bendszus M, Radbruch A. Tumor Infiltration in Enhancing and Non-Enhancing Parts of Glioblastoma: A Correlation with Histopathology. PLoS One 2017; 12:e0169292. [PMID: 28103256 PMCID: PMC5245878 DOI: 10.1371/journal.pone.0169292] [Citation(s) in RCA: 115] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 12/14/2016] [Indexed: 11/18/2022] Open
Abstract
PURPOSE To correlate histopathologic findings from biopsy specimens with their corresponding location within enhancing areas, non-enhancing areas and necrotic areas on contrast enhanced T1-weighted MRI scans (cT1). MATERIALS AND METHODS In 37 patients with newly diagnosed glioblastoma who underwent stereotactic biopsy, we obtained a correlation of 561 1mm3 biopsy specimens with their corresponding position on the intraoperative cT1 image at 1.5 Tesla. Biopsy points were categorized as enhancing (CE), non-enhancing (NE) or necrotic (NEC) on cT1 and tissue samples were categorized as "viable tumor cells", "blood" or "necrotic tissue (with or without cellular component)". Cell counting was done semi-automatically. RESULTS NE had the highest content of tissue categorized as viable tumor cells (89% vs. 60% in CE and 30% NEC, respectively). Besides, the average cell density for NE (3764 ± 2893 cells/mm2) was comparable to CE (3506 ± 3116 cells/mm2), while NEC had a lower cell density with 2713 ± 3239 cells/mm2. If necrotic parts and bleeds were excluded, cell density in biopsies categorized as "viable tumor tissue" decreased from the center of the tumor (NEC, 5804 ± 3480 cells/mm2) to CE (4495 ± 3209 cells/mm2) and NE (4130 ± 2817 cells/mm2). DISCUSSION The appearance of a glioblastoma on a cT1 image (circular enhancement, central necrosis, peritumoral edema) does not correspond to its diffuse histopathological composition. Cell density is elevated in both CE and NE parts. Hence, our study suggests that NE contains considerable amounts of infiltrative tumor with a high cellularity which might be considered in resection planning.
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Affiliation(s)
- Oliver Eidel
- Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany
- Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), Radiology, Heidelberg, Germany
| | - Sina Burth
- Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany
- Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), Radiology, Heidelberg, Germany
| | - Jan-Oliver Neumann
- Department of Neurosurgery, Division Stereotactic Neurosurgery, University of Heidelberg Medical Center, Heidelberg, Germany
| | - Pascal J. Kieslich
- Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany
| | - Felix Sahm
- Department of Neuropathology, University of Heidelberg Medical Center, Heidelberg, Germany
| | - Christine Jungk
- Department of Neurosurgery, Division Stereotactic Neurosurgery, University of Heidelberg Medical Center, Heidelberg, Germany
| | - Philipp Kickingereder
- Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany
| | | | - Sibu Mundiyanapurath
- Department of Neurology, University of Heidelberg Medical Center, Heidelberg, Germany
| | - Philipp Bäumer
- Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Wolfgang Wick
- Department of Neurology, University of Heidelberg Medical Center, Heidelberg, Germany
| | | | - Karl Kiening
- Department of Neurosurgery, Division Stereotactic Neurosurgery, University of Heidelberg Medical Center, Heidelberg, Germany
| | - Andreas Unterberg
- Department of Neurosurgery, Division Stereotactic Neurosurgery, University of Heidelberg Medical Center, Heidelberg, Germany
| | - Martin Bendszus
- Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany
| | - Alexander Radbruch
- Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany
- Department of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), Radiology, Heidelberg, Germany
- * E-mail:
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35
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Perfusion imaging of brain gliomas using arterial spin labeling: correlation with histopathological vascular density in MRI-guided biopsies. Neuroradiology 2016; 59:51-59. [DOI: 10.1007/s00234-016-1756-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2016] [Accepted: 10/17/2016] [Indexed: 11/25/2022]
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36
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Saito T, Sugiyama K, Ikawa F, Yamasaki F, Ishifuro M, Takayasu T, Nosaka R, Nishibuchi I, Muragaki Y, Kawamata T, Kurisu K. Permeability Surface Area Product Using Perfusion Computed Tomography Is a Valuable Prognostic Factor in Glioblastomas Treated with Radiotherapy Plus Concomitant and Adjuvant Temozolomide. World Neurosurg 2016; 97:21-26. [PMID: 27693246 DOI: 10.1016/j.wneu.2016.09.072] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 09/14/2016] [Accepted: 09/16/2016] [Indexed: 11/28/2022]
Abstract
OBJECTIVE The current standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). We hypothesized that the permeability surface area product (PS) from a perfusion computed tomography (PCT) study is associated with sensitivity to TMZ. The aim of this study was to determine whether PS values were correlated with prognosis of GBM patients who received the standard treatment protocol. METHODS This study included 36 patients with GBM that were newly diagnosed between October 2005 and September 2014 and who underwent preoperative PCT study and the standard treatment protocol. We measured the maximum value of relative cerebral blood volume (rCBVmax) and the maximum PS value (PSmax). We statistically examined the relationship between PSmax and prognosis using survival analysis, including other clinicopathologic factors (age, Karnofsky performance status [KPS], extent of resection, O6-methylguanine-DNA methyltransferase [MGMT] status, second-line use of bevacizumab, and rCBVmax). RESULTS Log-rank tests revealed that age, KPS, MGMT status, and PSmax were significantly correlated with overall survival. Multivariate analysis using the Cox regression model showed that PSmax was the most significant prognostic factor. Receiver operating characteristic curve analysis showed that PSmax had the highest accuracy in differentiating longtime survivors (LTSs) (surviving more than 2 years) from non-LTSs. At a cutoff point of 8.26 mL/100 g/min, sensitivity and specificity were 90% and 70%, respectively. CONCLUSIONS PSmax from PCT study can help predict survival time in patients with GBM receiving the standard treatment protocol. Survival may be related to sensitivity to TMZ.
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Affiliation(s)
- Taiichi Saito
- Department of Neurosurgery, Graduate School of Biomedical and Health Science, Hiroshima University, Minami-ku, Hiroshima, Japan.
| | - Kazuhiko Sugiyama
- Department of Clinical Oncology and Neuro-oncology Program, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan
| | - Fusao Ikawa
- Department of Neurosurgery, Graduate School of Biomedical and Health Science, Hiroshima University, Minami-ku, Hiroshima, Japan
| | - Fumiyuki Yamasaki
- Department of Neurosurgery, Graduate School of Biomedical and Health Science, Hiroshima University, Minami-ku, Hiroshima, Japan
| | - Minoru Ishifuro
- Department of Diagnostic Imaging, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan
| | - Takeshi Takayasu
- Department of Neurosurgery, Graduate School of Biomedical and Health Science, Hiroshima University, Minami-ku, Hiroshima, Japan
| | - Ryo Nosaka
- Department of Neurosurgery, Graduate School of Biomedical and Health Science, Hiroshima University, Minami-ku, Hiroshima, Japan
| | - Ikuno Nishibuchi
- Department of Radiation Oncology, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan
| | - Yoshihiro Muragaki
- Department of Neurosurgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Takakazu Kawamata
- Department of Neurosurgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Kaoru Kurisu
- Department of Neurosurgery, Graduate School of Biomedical and Health Science, Hiroshima University, Minami-ku, Hiroshima, Japan
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Huang RY, Wen PY. Response Assessment in Neuro-Oncology Criteria and Clinical Endpoints. Magn Reson Imaging Clin N Am 2016; 24:705-718. [PMID: 27742111 DOI: 10.1016/j.mric.2016.06.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The Response Assessment in Neuro-Oncology (RANO) Working Group is an international multidisciplinary group whose goal is to improve response criteria and define endpoints for neuro-oncology trials. The RANO criteria for high-grade gliomas attempt to address the issues of pseudoprogression, pseudoresponse, and nonenhancing tumor progression. Incorporation of advanced MR imaging may eventually help improve the ability of these criteria to define enhancing and nonenhancing disease better. The RANO group has also developed criteria for neurologic response and evaluation of patients receiving immunologic therapies. RANO criteria have been developed for brain metastases and are in progress for meningiomas, leptomeningeal disease, spinal tumors, and pediatric tumors.
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Affiliation(s)
- Raymond Y Huang
- Division of Neuroradiology, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
| | - Patrick Y Wen
- Division of Neuro-Oncology, Department of Neurology, Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA
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38
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Nguyen TB, Cron GO, Bezzina K, Perdrizet K, Torres CH, Chakraborty S, Woulfe J, Jansen GH, Thornhill RE, Zanette B, Cameron IG. Correlation of Tumor Immunohistochemistry with Dynamic Contrast-Enhanced and DSC-MRI Parameters in Patients with Gliomas. AJNR Am J Neuroradiol 2016; 37:2217-2223. [PMID: 27585700 DOI: 10.3174/ajnr.a4908] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Accepted: 07/01/2016] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND PURPOSE Tumor CBV is a prognostic and predictive marker for patients with gliomas. Tumor CBV can be measured noninvasively with different MR imaging techniques; however, it is not clear which of these techniques most closely reflects histologically-measured tumor CBV. Our aim was to investigate the correlations between dynamic contrast-enhanced and DSC-MR imaging parameters and immunohistochemistry in patients with gliomas. MATERIALS AND METHODS Forty-three patients with a new diagnosis of glioma underwent a preoperative MR imaging examination with dynamic contrast-enhanced and DSC sequences. Unnormalized and normalized cerebral blood volume was obtained from DSC MR imaging. Two sets of plasma volume and volume transfer constant maps were obtained from dynamic contrast-enhanced MR imaging. Plasma volume obtained from the phase-derived vascular input function and bookend T1 mapping (Vp_Φ) and volume transfer constant obtained from phase-derived vascular input function and bookend T1 mapping (Ktrans_Φ) were determined. Plasma volume obtained from magnitude-derived vascular input function (Vp_SI) and volume transfer constant obtained from magnitude-derived vascular input function (Ktrans_SI) were acquired, without T1 mapping. Using CD34 staining, we measured microvessel density and microvessel area within 3 representative areas of the resected tumor specimen. The Mann-Whitney U test was used to test for differences according to grade and degree of enhancement. The Spearman correlation was performed to determine the relationship between dynamic contrast-enhanced and DSC parameters and histopathologic measurements. RESULTS Microvessel area, microvessel density, dynamic contrast-enhanced, and DSC-MR imaging parameters varied according to the grade and degree of enhancement (P < .05). A strong correlation was found between microvessel area and Vp_Φ and between microvessel area and unnormalized blood volume (rs ≥ 0.61). A moderate correlation was found between microvessel area and normalized blood volume, microvessel area and Vp_SI, microvessel area and Ktrans_Φ, microvessel area and Ktrans_SI, microvessel density and Vp_Φ, microvessel density and unnormalized blood volume, and microvessel density and normalized blood volume (0.44 ≤ rs ≤ 0.57). A weaker correlation was found between microvessel density and Ktrans_Φ and between microvessel density and Ktrans_SI (rs ≤ 0.41). CONCLUSIONS With dynamic contrast-enhanced MR imaging, use of a phase-derived vascular input function and bookend T1 mapping improves the correlation between immunohistochemistry and plasma volume, but not between immunohistochemistry and the volume transfer constant. With DSC-MR imaging, normalization of tumor CBV could decrease the correlation with microvessel area.
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Affiliation(s)
- T B Nguyen
- From the Departments of Radiology (T.B.N., G.O.C., C.H.T., R.E.T., I.G.C., S.C.)
| | - G O Cron
- From the Departments of Radiology (T.B.N., G.O.C., C.H.T., R.E.T., I.G.C., S.C.)
| | - K Bezzina
- Psychiatry (K.B.), The Ottawa Hospital, University of Ottawa, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | | | - C H Torres
- From the Departments of Radiology (T.B.N., G.O.C., C.H.T., R.E.T., I.G.C., S.C.)
| | - S Chakraborty
- From the Departments of Radiology (T.B.N., G.O.C., C.H.T., R.E.T., I.G.C., S.C.)
| | | | | | - R E Thornhill
- From the Departments of Radiology (T.B.N., G.O.C., C.H.T., R.E.T., I.G.C., S.C.)
| | - B Zanette
- Department of Medical Biophysics (B.Z.), University of Toronto, Toronto, Ontario, Canada
| | - I G Cameron
- From the Departments of Radiology (T.B.N., G.O.C., C.H.T., R.E.T., I.G.C., S.C.).,Medical Physics (I.G.C.)
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Intravoxel Incoherent Motion Metrics as Potential Biomarkers for Survival in Glioblastoma. PLoS One 2016; 11:e0158887. [PMID: 27387822 PMCID: PMC4936699 DOI: 10.1371/journal.pone.0158887] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Accepted: 06/23/2016] [Indexed: 01/03/2023] Open
Abstract
Objective Intravoxel incoherent motion (IVIM) is an MRI technique with potential applications in measuring brain tumor perfusion, but its clinical impact remains to be determined. We assessed the usefulness of IVIM-metrics in predicting survival in newly diagnosed glioblastoma. Methods Fifteen patients with glioblastoma underwent MRI including spin-echo echo-planar DWI using 13 b-values ranging from 0 to 1000 s/mm2. Parametric maps for diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) were generated for contrast-enhancing regions (CER) and non-enhancing regions (NCER). Regions of interest were manually drawn in regions of maximum f and on the corresponding dynamic susceptibility contrast images. Prognostic factors were evaluated by Kaplan-Meier survival and Cox proportional hazards analyses. Results We found that fCER and D*CER correlated with rCBFCER. The best cutoffs for 6-month survival were fCER>9.86% and D*CER>21.712 x10−3mm2/s (100% sensitivity, 71.4% specificity, 100% and 80% positive predictive values, and 80% and 100% negative predictive values; AUC:0.893 and 0.857, respectively). Treatment yielded the highest hazard ratio (5.484; 95% CI: 1.162–25.88; AUC: 0.723; P = 0.031); fCER combined with treatment predicted survival with 100% accuracy. Conclusions The IVIM-metrics fCER and D*CER are promising biomarkers of 6-month survival in newly diagnosed glioblastoma.
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She D, Yang X, Xing Z, Cao D. Differentiating Hemangioblastomas from Brain Metastases Using Diffusion-Weighted Imaging and Dynamic Susceptibility Contrast-Enhanced Perfusion-Weighted MR Imaging. AJNR Am J Neuroradiol 2016; 37:1844-1850. [PMID: 27173365 DOI: 10.3174/ajnr.a4809] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Accepted: 03/18/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND PURPOSE On DWI and DSC-PWI, hemangioblastomas and brain metastases may exhibit different signal intensities depending on their cellularity and angiogenesis. The purpose of this study was to evaluate whether a hemangioblastoma can be differentiated from a single brain metastasis with DWI and DSC-PWI. MATERIALS AND METHODS We retrospectively reviewed DWI, DSC-PWI, and conventional MR imaging of 21 patients with hemangioblastomas and 30 patients with a single brain metastasis. Variables of minimum ADC and relative ADC were acquired by DWI and the parameter of relative maximum CBV, by DSC-PWI. Minimum ADC, relative ADC, and relative maximum CBV values were compared between hemangioblastomas and brain metastases by using the nonparametric Mann-Whitney test. The sensitivity, specificity, positive and negative predictive values, accuracy, and the area under the receiver operating characteristic curve were determined. RESULTS Both the minimum ADC values and relative ADC ratios were significantly higher in hemangioblastomas compared with brain metastases (P < .001 for both minimum ADC values and relative ADC ratios). The same was true for the relative maximum CBV ratio (P < .002). The threshold value of ≥6.59 for relative maximum CBV provided sensitivity, specificity, and accuracy of 95.24%, 53.33%, and 70.59%, respectively, for differentiating hemangioblastomas from brain metastases. Compared with relative maximum CBV, relative ADC had high sensitivity (95.24%), specificity (96.67%), and accuracy (96.08%) using the threshold value of ≥1.54. The optimal threshold value for minimum ADC was ≥1.1 × 10-3 mm2/s. CONCLUSIONS DWI and DSC-PWI are helpful in the characterization and differentiation of hemangioblastomas from brain metastases. DWI appears to be the most efficient MR imaging technique for providing a distinct differentiation of the 2 tumor types.
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Affiliation(s)
- D She
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China
| | - X Yang
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China
| | - Z Xing
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China
| | - D Cao
- From the Department of Radiology, First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China.
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Rao A, Manyam G, Rao G, Jain R. Integrative Analysis of mRNA, microRNA, and Protein Correlates of Relative Cerebral Blood Volume Values in GBM Reveals the Role for Modulators of Angiogenesis and Tumor Proliferation. Cancer Inform 2016; 15:29-33. [PMID: 27053917 PMCID: PMC4814129 DOI: 10.4137/cin.s33014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 11/29/2016] [Accepted: 12/07/2015] [Indexed: 12/12/2022] Open
Abstract
Dynamic susceptibility contrast-enhanced magnetic resonance imaging is routinely used to provide hemodynamic assessment of brain tumors as a diagnostic as well as a prognostic tool. Recently, it was shown that the relative cerebral blood volume (rCBV), obtained from the contrast-enhancing as well as -nonenhancing portion of glioblastoma (GBM), is strongly associated with overall survival. In this study, we aim to characterize the genomic correlates (microRNA, messenger RNA, and protein) of this vascular parameter. This study aims to provide a comprehensive radiogenomic and radioproteomic characterization of the hemodynamic phenotype of GBM using publicly available imaging and genomic data from the Cancer Genome Atlas GBM cohort. Based on this analysis, we identified pathways associated with angiogenesis and tumor proliferation underlying this hemodynamic parameter in GBM.
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Affiliation(s)
- Arvind Rao
- Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ganiraju Manyam
- Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ganesh Rao
- Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rajan Jain
- Department of Radiology, NY University School of Medicine, New York, NY, USA
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Chin SC, Lin CY, Huang BS, Tsang NM, Fan KH, Ku YK, Hsu CL, Chan SC, Huang SF, Li CH, Tseng HJ, Liao CT, Liu HL, Sung K. Pretreatment Dynamic Contrast-Enhanced MRI Improves Prediction of Early Distant Metastases in Patients With Nasopharyngeal Carcinoma. Medicine (Baltimore) 2016; 95:e2567. [PMID: 26871776 PMCID: PMC4753871 DOI: 10.1097/md.0000000000002567] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The identification of early distant metastases (DM) in patients with newly diagnosed, previously untreated nasopharyngeal carcinoma (NPC) plays an important role in selecting the most appropriate treatment approach. Here, we sought to investigate the predictive value of distinct MRI parameters for the detection of early DM.Between November 2010 and June 2011, a total of 51 newly diagnosed NPC patients were included. All of the study participants were followed until December 2014 at a single institution after completion of therapy. DM was defined as early when they were detected on pretreatment FDG-PET scans or within 6 months after initial diagnosis. The following parameters were tested for their ability to predict early DM: pretreatment FDG-PET standardized uptake value (SUV), MRI-derived AJCC tumor staging, tumor volume, and dynamic contrast-enhanced (DCE) values. The DCE-derived ve was defined as the volume fraction of the extravascular, extracellular space.Compared with patients without early DM, patients with early DM had higher SUV, tumor volume, DCE mean (median) ve, ve skewness, ve kurtosis, and the largest mean ve selected among sequential slices (P < 0.05). No differences were identified when early DM were defined only according to the results of pretreatment FDG-PET. Among different quantitative DCE parameters, the mean ve had the highest area under curve (AUC, 0.765). However, the AUCs of SUV, tumor volume, mean ve, ve skewness, ve kurtosis, or the largest mean ve selected among the sequential slices did not differ significantly from one another (P = 0.82).Taken together, our results suggest that DCE-derived ve may be a useful parameter in combination with SUV and tumor volume for predicting early DM. Dynamic contrast-enhanced MRI may be complementary to FDG-PET for selecting the most appropriate treatment approach in NPC patients.
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Affiliation(s)
- Shy-Chyi Chin
- From the Department of Medical Imaging and Intervention (C-SC, K-YK); Department of Radiation Oncology (L-CY, H-BS, T-NM, F-KH); Division of Medical Oncology, Department of Internal Medicine (H-CL); Molecular Imaging Center and Department of Nuclear Medicine (C-SC); Department of Otorhinolaryngology, Head and Neck Surgery, Linkou Chang Gung Memorial Hospital and Chang Gung University (H-SF, L-CT), Taoyuan; Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University (L-CH), Hsinchu; Biostatistical Center for Clinical Research, Linkou Chang Gung Memorial Hospital and Chang Gung University (T-HJ), Taoyuan, Taiwan, ROC; Department of Imaging Physics, University of Texas MD Anderson Cancer Center (L-HL), Houston, TX; and Department of Radiological Sciences, University of California (S-K), Los Angeles, CA
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Dynamic perfusion CT in brain tumors. Eur J Radiol 2015; 84:2386-92. [DOI: 10.1016/j.ejrad.2015.02.012] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2014] [Accepted: 02/15/2015] [Indexed: 11/22/2022]
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High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study. Neuroradiology 2015; 58:17-26. [PMID: 26438560 DOI: 10.1007/s00234-015-1599-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 09/21/2015] [Indexed: 01/04/2023]
Abstract
INTRODUCTION The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. METHODS Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. RESULTS Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). CONCLUSIONS Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival.
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Barajas R, Phillips J, Vandenberg S, McDermott M, Berger M, Dillon W, Cha S. Pro-angiogenic cellular and genomic expression patterns within glioblastoma influences dynamic susceptibility weighted perfusion MRI. Clin Radiol 2015; 70:1087-95. [DOI: 10.1016/j.crad.2015.03.006] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 11/19/2014] [Accepted: 03/19/2015] [Indexed: 12/15/2022]
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Lee SH, Hayano K, Zhu AX, Sahani DV, Yoshida H. Water-Exchange-Modified Kinetic Parameters from Dynamic Contrast-Enhanced MRI as Prognostic Biomarkers of Survival in Advanced Hepatocellular Carcinoma Treated with Antiangiogenic Monotherapy. PLoS One 2015; 10:e0136725. [PMID: 26366997 PMCID: PMC4569468 DOI: 10.1371/journal.pone.0136725] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 08/08/2015] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND To find prognostic biomarkers in pretreatment dynamic contrast-enhanced MRI (DCE-MRI) water-exchange-modified (WX) kinetic parameters for advanced hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy. METHODS Twenty patients with advanced HCC underwent DCE-MRI and were subsequently treated with sunitinib. Pretreatment DCE-MRI data on advanced HCC were analyzed using five different WX kinetic models: the Tofts-Kety (WX-TK), extended TK (WX-ETK), two compartment exchange, adiabatic approximation to tissue homogeneity (WX-AATH), and distributed parameter (WX-DP) models. The total hepatic blood flow, arterial flow fraction (γ), arterial blood flow (BFA), portal blood flow, blood volume, mean transit time, permeability-surface area product, fractional interstitial volume (vI), extraction fraction, mean intracellular water molecule lifetime (τC), and fractional intracellular volume (vC) were calculated. After receiver operating characteristic analysis with leave-one-out cross-validation, individual parameters for each model were assessed in terms of 1-year-survival (1YS) discrimination using Kaplan-Meier analysis, and association with overall survival (OS) using univariate Cox regression analysis with permutation testing. RESULTS The WX-TK-model-derived γ (P = 0.022) and vI (P = 0.010), and WX-ETK-model-derived τC (P = 0.023) and vC (P = 0.042) were statistically significant prognostic biomarkers for 1YS. Increase in the WX-DP-model-derived BFA (P = 0.025) and decrease in the WX-TK, WX-ETK, WX-AATH, and WX-DP-model-derived vC (P = 0.034, P = 0.038, P = 0.028, P = 0.041, respectively) were significantly associated with an increase in OS. CONCLUSIONS The WX-ETK-model-derived vC was an effective prognostic biomarker for advanced HCC treated with sunitinib.
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Affiliation(s)
- Sang Ho Lee
- 3D Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Koichi Hayano
- Division of Abdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Andrew X. Zhu
- Massachusetts General Hospital Cancer Center, Boston, Massachusetts, United States of America
| | - Dushyant V. Sahani
- Division of Abdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
| | - Hiroyuki Yoshida
- 3D Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
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Arevalo-Perez J, Thomas AA, Kaley T, Lyo J, Peck KK, Holodny AI, Mellinghoff IK, Shi W, Zhang Z, Young RJ. T1-Weighted Dynamic Contrast-Enhanced MRI as a Noninvasive Biomarker of Epidermal Growth Factor Receptor vIII Status. AJNR Am J Neuroradiol 2015; 36:2256-61. [PMID: 26338913 DOI: 10.3174/ajnr.a4484] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 04/30/2015] [Indexed: 01/02/2023]
Abstract
BACKGROUND AND PURPOSE Epidermal growth factor receptor variant III is a common mutation in glioblastoma, found in approximately 25% of tumors. Epidermal growth factor receptor variant III may accelerate angiogenesis in malignant gliomas. We correlated T1-weighted dynamic contrast-enhanced MR imaging perfusion parameters with epidermal growth factor receptor variant III status. MATERIALS AND METHODS Eighty-two consecutive patients with glioblastoma and known epidermal growth factor receptor variant III status who had dynamic contrast-enhanced MR imaging before surgery were evaluated. Volumes of interest were drawn around the entire enhancing tumor on contrast T1-weighted images and then were transferred onto coregistered dynamic contrast-enhanced MR imaging perfusion maps. Histogram analysis with normalization was performed to determine the relative mean, 75th percentile, and 90th percentile values for plasma volume and contrast transfer coefficient. A Wilcoxon rank sum test was applied to assess the relationship between baseline perfusion parameters and positive epidermal growth factor receptor variant III status. The receiver operating characteristic method was used to select the cutoffs of the dynamic contrast-enhanced MR imaging perfusion parameters. RESULTS Increased relative plasma volume and increased relative contrast transfer coefficient parameters were both significantly associated with positive epidermal growth factor receptor variant III status. For epidermal growth factor receptor variant III-positive tumors, relative plasma volume mean was 9.3 and relative contrast transfer coefficient mean was 6.5; for epidermal growth factor receptor variant III-negative tumors, relative plasma volume mean was 3.6 and relative contrast transfer coefficient mean was 3.7 (relative plasma volume mean, P < .001, and relative contrast transfer coefficient mean, P = .008). The predictive powers of relative plasma volume histogram metrics outperformed those of the relative contrast transfer coefficient histogram metrics (P < = .004). CONCLUSIONS Dynamic contrast-enhanced MR imaging shows greater perfusion and leakiness in epidermal growth factor receptor variant III-positive glioblastomas than in epidermal growth factor receptor variant III-negative glioblastomas, consistent with the known effect of epidermal growth factor receptor variant III on angiogenesis. Quantitative evaluation of dynamic contrast-enhanced MR imaging may be useful as a noninvasive tool for correlating epidermal growth factor receptor variant III expression and related tumor neoangiogenesis. This potential may have implications for monitoring response to epidermal growth factor receptor variant III-targeted therapies.
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Affiliation(s)
- J Arevalo-Perez
- From the Departments of Radiology (J.A.-P., J.L., A.I.H., R.J.Y.)
| | | | - T Kaley
- Neurology (A.A.T., T.K., I.K.M.) the Brain Tumor Center (T.K., J.L., A.I.H., R.J.Y.), Memorial Sloan Kettering Cancer Center, New York, New York
| | - J Lyo
- From the Departments of Radiology (J.A.-P., J.L., A.I.H., R.J.Y.) the Brain Tumor Center (T.K., J.L., A.I.H., R.J.Y.), Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - A I Holodny
- From the Departments of Radiology (J.A.-P., J.L., A.I.H., R.J.Y.) the Brain Tumor Center (T.K., J.L., A.I.H., R.J.Y.), Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - W Shi
- Epidemiology and Biostatistics (W.S., Z.Z.)
| | - Z Zhang
- Epidemiology and Biostatistics (W.S., Z.Z.)
| | - R J Young
- From the Departments of Radiology (J.A.-P., J.L., A.I.H., R.J.Y.) the Brain Tumor Center (T.K., J.L., A.I.H., R.J.Y.), Memorial Sloan Kettering Cancer Center, New York, New York.
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Sunwoo L, Choi SH, Yoo RE, Kang KM, Yun TJ, Kim TM, Lee SH, Park CK, Kim JH, Park SW, Sohn CH, Won JK, Park SH, Kim IH. Paradoxical perfusion metrics of high-grade gliomas with an oligodendroglioma component: quantitative analysis of dynamic susceptibility contrast perfusion MR imaging. Neuroradiology 2015; 57:1111-20. [PMID: 26232204 DOI: 10.1007/s00234-015-1569-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Accepted: 07/15/2015] [Indexed: 11/26/2022]
Abstract
INTRODUCTION The aim of this study is to investigate perfusion characteristics of glioblastoma with an oligodendroglioma component (GBMO) compared with conventional glioblastoma (GBM) using dynamic susceptibility contrast (DSC) perfusion magnetic resonance (MR) imaging and microvessel density (MVD). METHODS The study was approved by the institutional review board. Newly diagnosed high-grade glioma patients were enrolled (n = 72; 20 GBMs, 14 GBMOs, 19 anaplastic astrocytomas (AAs), 13 anaplastic oligodendrogliomas (AOs), and six anaplastic oligoastrocytomas (AOAs)). All participants underwent preoperative MR imaging including DSC perfusion MR imaging. Normalized cerebral blood volume (nCBV) values were analyzed using a histogram approach. Histogram parameters were subsequently compared across each tumor subtype and grade. MVD was quantified by immunohistochemistry staining and correlated with perfusion parameters. Progression-free survival (PFS) was assessed according to the tumor subtype. RESULTS GBMO displayed significantly reduced nCBV values compared with GBM, whereas grade III tumors with oligodendroglial components (AO and AOA) exhibited significantly increased nCBV values compared with AA (p < 0.001). MVD analyses revealed the same pattern as nCBV results. In addition, a positive correlation between MVD and nCBV values was noted (r = 0.633, p < 0.001). Patients with oligodendroglial tumors exhibited significantly increased PFS compared with patients with pure astrocytomas in each grade. CONCLUSION In contrast to grade III tumors, the presence of oligodendroglial components in grade IV tumors resulted in paradoxically reduced perfusion metrics and MVD. In addition, patients with GBMO exhibited a better clinical outcome compared with patients with GBM.
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Affiliation(s)
- Leonard Sunwoo
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, Korea
| | - Seung Hong Choi
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
- Center for Nanoparticle Research, Institute for Basic Science, and School of Chemical and Biological Engineering, Seoul National University, Seoul, Korea.
| | - Roh-Eul Yoo
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
| | - Koung Mi Kang
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
| | - Tae Jin Yun
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
| | - Tae Min Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Se-Hoon Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Chul-Kee Park
- Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea
| | - Ji-Hoon Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
| | - Sun-Won Park
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul, Korea
| | - Chul-Ho Sohn
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
| | - Jae-Kyung Won
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Sung-Hye Park
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Il Han Kim
- Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea
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Jain R, Griffith B, Alotaibi F, Zagzag D, Fine H, Golfinos J, Schultz L. Glioma Angiogenesis and Perfusion Imaging: Understanding the Relationship between Tumor Blood Volume and Leakiness with Increasing Glioma Grade. AJNR Am J Neuroradiol 2015. [PMID: 26206809 DOI: 10.3174/ajnr.a4405] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND PURPOSE The purpose of this study was to investigate imaging correlates to the changes occurring during angiogenesis in gliomas. This was accomplished through in vivo assessment of vascular parameters (relative CBV and permeability surface-area product) and their changing relationship with increasing glioma grade. MATERIALS AND METHODS Seventy-six patients with gliomas underwent preoperative perfusion CT and assessment of relative CBV and permeability surface-area product. Regression analyses were performed to assess the rate of change between relative CBV and permeability surface-area product and to test whether these differed for distinct glioma grades. The ratio of relative CBV to permeability surface-area product was also computed and compared among glioma grades by using analysis of variance methods. RESULTS The rate of change in relative CBV with respect to permeability surface-area product was highest for grade II gliomas followed by grade III and then grade IV (1.64 versus 0.91 versus 0.27, respectively). The difference in the rate of change was significant between grade III and IV (P = .003) and showed a trend for grades II and IV (P = .098). Relative CBV/permeability surface-area product ratios were the highest for grade II and lowest for grade IV. The pair-wise difference among all 3 groups was significant (P < .001). CONCLUSIONS There is an increase in relative CBV more than permeability surface-area product in lower grade gliomas, whereas in grade III and especially grade IV gliomas, permeability surface-area product increases much more than relative CBV. The rate of change of relative CBV with respect to permeability surface-area product and relative CBV/permeability surface-area product ratio can serve as an imaging correlate to changes occurring at the tumor microvasculature level.
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Affiliation(s)
- R Jain
- From the Departments of Radiology (R.J.)
| | | | | | - D Zagzag
- Pathology (F.A., D.Z.) Neurosurgery (D.Z., J.G.)
| | - H Fine
- Medicine (H.F.), New York University School of Medicine, New York, New York
| | | | - L Schultz
- Public Health Sciences (L.S.), Henry Ford Hospital, Detroit, Michigan
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Yeung TPC, Wang Y, He W, Urbini B, Gafà R, Ulazzi L, Yartsev S, Bauman G, Lee TY, Fainardi E. Survival prediction in high-grade gliomas using CT perfusion imaging. J Neurooncol 2015; 123:93-102. [PMID: 25862005 DOI: 10.1007/s11060-015-1766-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 04/02/2015] [Indexed: 11/24/2022]
Abstract
Patients with high-grade gliomas usually have heterogeneous response to surgery and chemoirradiation. The objectives of this study were (1) to evaluate serial changes in tumor volume and perfusion imaging parameters and (2) to determine the value of these data in predicting overall survival (OS). Twenty-nine patients with World Health Organization grades III and IV gliomas underwent magnetic resonance (MR) and computed tomography (CT) perfusion examinations before surgery, and 1, 3, 6, 9, and 12 months after radiotherapy. Serial measurements of tumor volumes and perfusion parameters were evaluated by receiver operating characteristic analysis, Cox proportional hazards regression, and Kaplan-Meier survival analysis to determine their values in predicting OS. Higher trends in blood flow (BF), blood volume (BV), and permeability-surface area product in the contrast-enhancing lesions (CEL) and the non-enhancing lesions (NEL) were found in patients with OS < 18 months compared to those with OS ≥ 18 months, and these values were significant at selected time points (P < 0.05). Only CT perfusion parameters yielded sensitivities and specificities of ≥ 70% in predicting 18 and 24 months OS. Pre-surgery BF in the NEL and BV in the CEL and NEL 3 months after radiotherapy had sensitivities and specificities >80% in predicting 24 months OS in patients with grade IV gliomas. Our study indicated that CT perfusion parameters were predictive of survival and could be useful in assessing early response and in selecting adjuvant treatment to prolong survival if verified in a larger cohort of patients.
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