1
|
Zhang L, Meng Z, Huang C, Xian J. Combined average standard uptake value and rate constant can predict expression of EGFR in hypopharyngeal squamous cell carcinoma: A pilot study with integrated PET/MRI. Eur J Radiol 2024; 172:111326. [PMID: 38280301 DOI: 10.1016/j.ejrad.2024.111326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 11/09/2023] [Accepted: 01/17/2024] [Indexed: 01/29/2024]
Abstract
PURPOSE To investigate whether the quantitative multiparameters of 18F-FDG PET/MRI can predict expression of epidermal growth factor receptor (EGFR) of hypopharyngeal squamous cell carcinoma (HSCC). METHODS Twenty-one patients with HSCC confirmed by biopsy underwent neck integrated 18F-FDG PET/MRI and EGFR expression detection. Quantitative parameters derived from 18F-FDG PET, difusion-weighted imaging (DWI), and dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) were measured. The efficacies of quantitative multiparameters derived from 18F-FDG PET/MRI for predicting the expression of EGFR of HSCC were evaluated. RESULTS The patients were divided into positive expression group (PEG, n = 14) and negative expression group (NEG, n = 7). Mann-Whitney U nonparametric test showed that SUVmean and Kep had statistical difference between PEG and NPG, while other parameters had no statistical difference. Using 14.50 and 2.10 min-1 as the threshold values, areas under the curve (AUCs) for SUVmean and Kep were 0.786 with specificity of 92.9 % and sensitivity of 57.1 %. The combined use of SUVmean and Kep had better efficacy to evaluate the expression of EGFR with AUC of 0.980, sensitivity of 92.9 %, and specificity of 100.0 %. CONCLUSION Combined use of SUVmean and Kep showed good performance in predicting the expression of EGFR in HSCC. Integrated 18F-FDG PET/MRI enables simultaneous acquisition of SUVmean and Kep, so it represents as a powerful tool to noninvasively and repeatably evaluate the expression of EGFR during the management of HSCC.
Collapse
Affiliation(s)
- Lingyu Zhang
- Department of Radiology, Beijing Tongren Hospital, Capital Medical University, No. 1, DongJiaoMinXiang Street, Dongcheng District, Beijing 100730, China
| | - Zhaoting Meng
- Department of Nuclear Medicine, Beijing Universal Medical Imaging Diagnostic Center, Beijing 100071, China
| | - Caiyun Huang
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning 530022, China
| | - Junfang Xian
- Department of Radiology, Beijing Tongren Hospital, Capital Medical University, No. 1, DongJiaoMinXiang Street, Dongcheng District, Beijing 100730, China.
| |
Collapse
|
2
|
Surov A, Pech M, Eckert A, Arens C, Grosser O, Wienke A. 18F-FDG PET cannot predict expression of clinically relevant histopathological biomarkers in head and neck squamous cell carcinoma: a meta-analysis. Acta Radiol 2022; 63:166-175. [PMID: 33541089 DOI: 10.1177/0284185121988973] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is a common cancer. Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is a widely used imaging modality in HNSCC. PURPOSE To provide evident data about associations between 18F-FDG PET and histopathology in HNSCC. MATERIAL AND METHODS The MEDLINE database was screened for associations between maximum standard uptake values (SUVmax) derived from 18F-FDG PET and histopathological features in HNSCC up to May 2020. Only papers containing correlation coefficients between SUVmax and histopathology were acquired. Overall, 23 publications were collected. RESULTS The following correlations were calculated: KI 67: 12 studies (345 patients), pooled correlation coefficient (PCC): 0.23 (95% confidence interval [CI] 0.06-0.40); hypoxia-inducible factor-1α: eight studies (240 patients), PCC: 0.24 (95% CI 0.06-0.42); microvessel density: three studies (64 patients), PCC: 0.33 (95% CI 0.02-0.65); vascular endothelial growth factor: two studies (59 cases), PCC: 0.27 (95% CI 0.02-0.51); tumor suppressor protein p53: four studies (159 patients), PCC: 0.05 (95% CI -0.41 to 0.51); epidermal growth factor receptor: two studies (124 patients), PCC: 0.21 (95% CI 0.05-0.37); tumor cell count: three studies (67 patients), PCC: 0.18 (95% CI -0.06 to 0.42); tumor cell apoptosis: two studies (40 patients), PCC: 0.07 (95% CI = -0.85 to 0.99); B-cell lymphoma-2 protein: two studies (118 patients); PCC: 0.04 (95% CI -0.65 to 0.74); glucose-transporter 1: 10 studies (317 patients), PCC: 0.20 (95% CI 0.10-0.30). CONCLUSION SUVmax derived from 18F-FDG PET cannot reflect relevant histopathological features in HNSCC.
Collapse
Affiliation(s)
- Alexey Surov
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Maciej Pech
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Alexander Eckert
- Oral and Plastic Maxillofacial Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany
| | - Christoph Arens
- Department of Otorhinolaryngology, Head and Neck Surgery, Magdeburg University Hospital, Magdeburg, Germany
| | - Oliver Grosser
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Magdeburg, Magdeburg, Germany
| | - Andreas Wienke
- Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| |
Collapse
|
3
|
Does multiparametric imaging with 18F-FDG-PET/MRI capture spatial variation in immunohistochemical cancer biomarkers in head and neck squamous cell carcinoma? Br J Cancer 2020; 123:46-53. [PMID: 32382113 PMCID: PMC7341803 DOI: 10.1038/s41416-020-0876-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 04/07/2020] [Accepted: 04/15/2020] [Indexed: 11/18/2022] Open
Abstract
Background The purpose of this study is to test if functional multiparametric imaging with 18F-FDG-PET/MRI correlates spatially with immunohistochemical biomarker status within a lesion of head and neck squamous cell carcinoma (HNSCC), and also whether a biopsy with the highest FDG uptake was more likely to have the highest PD-L1 expression or the highest percentage of vital tumour cells (VTC) compared with a random biopsy. Methods Thirty-one patients with HNSCC were scanned on an integrated PET/MRI scanner with FDG prior to surgery in this prospective study. Imaging was quantified with SUV, ADC and Ktrans. A 3D-morphometric MRI scan of the specimen was used to co-register the patient and the specimen scans. All specimens were sectioned in consecutive slices, and slices from six different locations were selected randomly from each tumour. Core biopsies were performed to construct TMA blocks for IHC staining with the ten predefined biomarkers. The spatial correlation was assessed with a partial correlation analysis. Results Twenty-eight patients with a total of 33 lesions were eligible for further analysis. There were significant correlations between the three imaging biomarkers and some of the IHC biomarkers. Moreover, a biopsy taken from the most FDG-avid part of the tumour did not have a statistically significantly higher probability of higher PD-L1 expression or VTC, compared with a random biopsy. Conclusion We found statistically significant correlations between functional imaging parameters and key molecular cancer markers.
Collapse
|
4
|
Vidiri A, Gangemi E, Ruberto E, Pasqualoni R, Sciuto R, Sanguineti G, Farneti A, Benevolo M, Rollo F, Sperati F, Spasiano F, Pellini R, Marzi S. Correlation between histogram-based DCE-MRI parameters and 18F-FDG PET values in oropharyngeal squamous cell carcinoma: Evaluation in primary tumors and metastatic nodes. PLoS One 2020; 15:e0229611. [PMID: 32119697 PMCID: PMC7051076 DOI: 10.1371/journal.pone.0229611] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 02/10/2020] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVES To investigate the correlation between histogram-based Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI) parameters and positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG-PET) values in oropharyngeal squamous cell carcinoma (OPSCC), both in primary tumors (PTs) and in metastatic lymph nodes (LNs). METHODS 52 patients with a new pathologically-confirmed OPSCC were included in the present retrospective cohort study. Imaging including DCE-MRI and 18F-FDG PET/CT scans were acquired in all patients. Both PTs and the largest LN, if present, were volumetrically contoured. Quantitative parameters, including the transfer constants, Ktrans and Kep, and the volume of extravascular extracellular space, ve, were calculated from DCE-MRI. The percentiles (P), P10, P25, P50, P75, P90, and skewness, kurtosis and entropy were obtained from the histogram-based analysis of each perfusion parameter. Standardized uptake values (SUV), SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated applying a SUV threshold of 40%. The correlations between all variables were investigated with the Spearman-rank correlation test. To exclude false positive results under multiple testing, the Benjamini-Hockberg procedure was applied. RESULTS No significant correlations were found between any parameters in PTs, while significant associations emerged between Ktrans and 18F-FDG PET parameters in LNs. CONCLUSIONS Evident relationships emerged between DCE-MRI and 18F-FDG PET parameters in OPSCC LNs, while no association was found in PTs. The complex relationships between perfusion and metabolic biomarkers should be interpreted separately for primary tumors and lymph-nodes. A multiparametric approach to analyze PTs and LNs before treatment is advisable in head and neck squamous cell carcinoma (HNSCC).
Collapse
Affiliation(s)
- Antonello Vidiri
- Radiology and Diagnostic Imaging Department, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Emma Gangemi
- Radiology and Diagnostic Imaging Department, IRCCS Regina Elena National Cancer Institute, Rome, Italy
- Departmental Faculty of Medicine and Surgery, Center for Integrated Research, University Campus Bio-Medico of Rome, Rome, Italy
- * E-mail:
| | - Emanuela Ruberto
- Radiology and Diagnostic Imaging Department, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Rosella Pasqualoni
- Department of Nuclear Medicine, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Rosa Sciuto
- Department of Nuclear Medicine, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Giuseppe Sanguineti
- Department of Radiotherapy, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Alessia Farneti
- Department of Radiotherapy, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Maria Benevolo
- Department of Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Francesca Rollo
- Department of Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Francesca Sperati
- Biostatistics-Scientific Direction, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Filomena Spasiano
- Department of Radiotherapy, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Raul Pellini
- Department of Otolaryngology & Head and Neck Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Simona Marzi
- Medical Physics Laboratory, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| |
Collapse
|
5
|
Yamagishi Y, Koiwai T, Yamasaki T, Einama T, Fukumura M, Hiratsuka M, Kono T, Hayashi K, Ishida J, Ueno H, Tsuda H. Dual time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging ( 18F-FDG PET/CT) in primary breast cancer. BMC Cancer 2019; 19:1146. [PMID: 31775675 PMCID: PMC6882358 DOI: 10.1186/s12885-019-6315-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Accepted: 10/31/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To evaluate the clinicopathological and prognostic significance of the percentage change between maximum standardized uptake value (SUVmax) at 60 min (SUVmax1) and SUVmax at 120 min (SUVmax2) (ΔSUVmax%) using dual time point 18F-fluorodeoxyglucose emission tomography/computed tomography (18F-FDG PET/CT) in breast cancer. METHODS Four hundred and sixty-four patients with primary breast cancer underwent 18F-FDG PET/CT for preoperative staging. ΔSUVmax% was defined as (SUVmax2 - SUVmax1) / SUVmax1 × 100. We explored the optimal cutoff value of SUVmax parameters (SUVmax1 and ΔSUVmax%) referring to the event of relapse by using receiver operator characteristic curves. The clinicopathological and prognostic significances of the SUVmax1 and ΔSUVmax% were analyzed by Cox's univariate and multivariate analyses. RESULTS The optimal cutoff values of SUVmax1 and ΔSUVmax% were 3.4 and 12.5, respectively. Relapse-free survival (RFS) curves were significantly different between high and low SUVmax1 groups (P = 0.0003) and also between high and low ΔSUVmax% groups (P = 0.0151). In Cox multivariate analysis for RFS, SUVmax1 was an independent prognostic factor (P = 0.0267) but ΔSUVmax% was not (P = 0.152). There was a weak correlation between SUVmax1 and ΔSUVmax% (P < 0.0001, R2 = 0.166). On combining SUVmax1 and ΔSUVmax%, the subgroups of high SUVmax1 and high ΔSUVmax% showed significantly worse prognosis than the other groups in terms of RFS (P = 0.0002). CONCLUSION Dual time point 18F-FDG PET/CT evaluation can be a useful method for predicting relapse in patients with breast cancer. The combination of SUVmax1 and ΔSUVmax% was able to identify subgroups with worse prognosis more accurately than SUVmax1 alone.
Collapse
Affiliation(s)
- Yoji Yamagishi
- Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.,Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Tomomi Koiwai
- Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Tamio Yamasaki
- Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Takahiro Einama
- Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Makiko Fukumura
- Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Miyuki Hiratsuka
- Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Takako Kono
- Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Katsumi Hayashi
- Department of Radiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Jiro Ishida
- Tokorozawa PET Diagnostic Imaging Clinic, 7-5 Higashisumiyoshi, Tokorozawa, Saitama, 359-1124, Japan
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan
| | - Hitoshi Tsuda
- Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
| |
Collapse
|
6
|
Bădan MI, Bonci EA, Piciu D. A review on immunohistochemical and histopathologic validation in PET-CT findings with consideration to microRNAs. Med Pharm Rep 2019; 92:337-345. [PMID: 31750432 PMCID: PMC6853049 DOI: 10.15386/mpr-1341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Accepted: 06/20/2019] [Indexed: 12/24/2022] Open
Abstract
Purpose This review provides an overview of some of the most recent clinical trials which investigated various types of cancer and other diseases, through the use of PET-CT imaging, highlighting the use of immunohistochemical stains or conventional histopathology for the validation or contradiction of their hypothesis. Furthermore, we investigate a potential new direction of research by analyzing the upcoming role of microRNAs in disease confirmation. Methods An extensive search of MEDLINE/PubMed and SCOPUS electronic databases was made, using the MeSH terms "positron emission tomography computed tomography" and "immunohistochemistry" as well as "SUV" and "immunohistochemistry", restricting the search by clinical trials and time period. Further searches were made for articles regarding Ki-67 and microRNAs in correlation with metabolic PET-CT uptake. Results Out of all 389 initial search results, 27 original articles were found relevant to the topic. Their contents were synthesized and discussed regarding the matter at hand. No relevant clinical trials involving microRNAs were found. Conclusions Immunohistochemical and histopathologic results remain widely used and indispensable in modern research, concerning PET-CT validation. Possible candidates for diagnosis confirmation, in future research, may reside in the further development of microRNAs.
Collapse
Affiliation(s)
- Marius-Ioan Bădan
- Department of Morphological Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Eduard-Alexandru Bonci
- Department of Morphological Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Doina Piciu
- Department of Morphological Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.,Department of Endocrinology and Nuclear Medicine, "Prof. Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca, Romania
| |
Collapse
|
7
|
Abstract
BACKGROUND FDG-PET might be able to reflect histopathology features of tumors. Ki 67 in head and neck carcinomas (HNSCC). The present study sought to elucidate the association between Ki 67 index and SUVmax based upon a large patient sample. METHODS PubMed database was screened for studies analyzed the relationship between Ki 67 and SUV in HNSCC. Nine studies comprising 211 patients were suitable for analysis. RESULTS SUVmax increased with tumor grade and was statistically significant different between G1, G2, and G3 tumors. The ROC analysis for discrimination between G1/G2 and G3 tumors revealed an area under curve of 0.71. In the overall patient sample, SUVmax correlated statistically significant with Ki 67 index (r = 0.154, P = .032). CONCLUSION The present study identified a weak correlation between SUV values and proliferation index Ki 67 index in HNSCC in a large patient sample. Therefore, SUVmax cannot be used as surrogate parameter for proliferation activity in HNSCC.
Collapse
Affiliation(s)
- Hans-Jonas Meyer
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig
| | - Peter Gundermann
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig
| | - Alexey Surov
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig
- Department of Diagnostic and Interventional Radiology, University of Ulm, Ulm, Germany, Germany
| |
Collapse
|
8
|
Surov A, Meyer HJ, Höhn AK, Winter K, Sabri O, Purz S. Associations Between [ 18F]FDG-PET and Complex Histopathological Parameters Including Tumor Cell Count and Expression of KI 67, EGFR, VEGF, HIF-1α, and p53 in Head and Neck Squamous Cell Carcinoma. Mol Imaging Biol 2019; 21:368-374. [PMID: 29931433 DOI: 10.1007/s11307-018-1223-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
PURPOSE Head and neck squamous cell carcinoma (HNSCC) is one of common cancers worldwide. Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is increasingly used for diagnosing and staging, as well as for monitoring of treatment of HNSCC. PET parameters like maximum and mean standard uptake values (SUVmax, SUVmean) can predict the behavior of HNSCC. The purpose of this study was to analyze possible associations between these PET parameters and clinically relevant histopathological features in patients with HNSCC. PROCEDURES Overall, 22 patients, mean age, 55.2 ± 11.0 years, with different HNSCC were acquired. Low grade (G1/2) tumors were diagnosed in 10 cases (45 %) and high grade (G3) tumor in 12 (55 %) patients. In all cases, whole body PET was performed. For this study, the following specimen stainings were performed: MIB-1 staining (KI 67 expression), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, hypoxia-inducible factor (HIF)-1α, and human papilloma virus (p16 expression). All stained specimens were digitalized and analyzed by using the ImageJ software 1.48v. Spearman's correlation coefficient (ρ) was used to analyze associations between investigated parameters. P values <0.05 were taken to indicate statistical significance. RESULTS P16-negative tumors showed statistically significant higher SUVmax (ρ = 0.006) and SUVmean values (ρ = 0.002) in comparison to p16-positive carcinomas. No significant differences were identified in the analyzed parameters between poorly and moderately/well-differentiated tumors. In overall sample, there were no statistically significant correlations between the [18F]FDG-PET and histopathological parameters. Also, in G1/2 tumors, no significant correlations were identified. In G3 carcinomas, cell count correlated statistical significant with SUVmax (p = 0.580, P = 0.048) and SUVmean (ρ = 0.587, P = 0.045). CONCLUSION Associations between [18F]FDG-PET parameters and different histopathological features in HNSCC depend significantly on tumor grading. In G1/2 carcinomas, there were no significant correlations between [18F]FDG-PET parameters and histopathology. In G3 lesions, SUVmax and SUVmean reflect tumor cellularity.
Collapse
Affiliation(s)
- Alexey Surov
- Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany.
| | - Hans Jonas Meyer
- Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany
| | - Anne-Kathrin Höhn
- Department of Pathology, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany
| | - Karsten Winter
- Institute of Anatomy, University Hospital of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany
| | - Osama Sabri
- Department of Nuclear Medicine, University Hospital of Leipzig, Liebigstraße 18, 04103, Leipzig, Germany
| | - Sandra Purz
- Department of Nuclear Medicine, University Hospital of Leipzig, Liebigstraße 18, 04103, Leipzig, Germany
| |
Collapse
|
9
|
Radiogenomics of breast cancer using dynamic contrast enhanced MRI and gene expression profiling. Cancer Imaging 2019; 19:48. [PMID: 31307537 PMCID: PMC6628478 DOI: 10.1186/s40644-019-0233-5] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 06/24/2019] [Indexed: 12/27/2022] Open
Abstract
Background Imaging techniques can provide information about the tumor non-invasively and have been shown to provide information about the underlying genetic makeup. Correlating image-based phenotypes (radiomics) with genomic analyses is an emerging area of research commonly referred to as “radiogenomics” or “imaging-genomics”. The purpose of this study was to assess the potential for using an automated, quantitative radiomics platform on magnetic resonance (MR) breast imaging for inferring underlying activity of clinically relevant gene pathways derived from RNA sequencing of invasive breast cancers prior to therapy. Methods We performed quantitative radiomic analysis on 47 invasive breast cancers based on dynamic contrast enhanced 3 Tesla MR images acquired before surgery and obtained gene expression data by performing total RNA sequencing on corresponding fresh frozen tissue samples. We used gene set enrichment analysis to identify significant associations between the 186 gene pathways and the 38 image-based features that have previously been validated. Results All radiomic size features were positively associated with multiple replication and proliferation pathways and were negatively associated with the apoptosis pathway. Gene pathways related to immune system regulation and extracellular signaling had the highest number of significant radiomic feature associations, with an average of 18.9 and 16 features per pathway, respectively. Tumors with upregulation of immune signaling pathways such as T-cell receptor signaling and chemokine signaling as well as extracellular signaling pathways such as cell adhesion molecule and cytokine-cytokine interactions were smaller, more spherical, and had a more heterogeneous texture upon contrast enhancement. Tumors with higher expression levels of JAK/STAT and VEGF pathways had more intratumor heterogeneity in image enhancement texture. Other pathways with robust associations to image-based features include metabolic and catabolic pathways. Conclusions We provide further evidence that MR imaging of breast tumors can infer underlying gene expression by using RNA sequencing. Size and shape features were appropriately correlated with proliferative and apoptotic pathways. Given the high number of radiomic feature associations with immune pathways, our results raise the possibility of using MR imaging to distinguish tumors that are more immunologically active, although further studies are necessary to confirm this observation. Electronic supplementary material The online version of this article (10.1186/s40644-019-0233-5) contains supplementary material, which is available to authorized users.
Collapse
|
10
|
Schillaci O, Scimeca M, Toschi N, Bonfiglio R, Urbano N, Bonanno E. Combining Diagnostic Imaging and Pathology for Improving Diagnosis and Prognosis of Cancer. CONTRAST MEDIA & MOLECULAR IMAGING 2019; 2019:9429761. [PMID: 31354394 PMCID: PMC6636452 DOI: 10.1155/2019/9429761] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 06/12/2019] [Indexed: 02/08/2023]
Abstract
In the era of personalized medicine, the management of oncological patients requires a translational and multidisciplinary approach. During early phases of cancer development, biochemical alterations of cell metabolism occur much before the formation of detectable tumour masses. Current molecular imaging techniques, targeted to the study of molecular kinetics, employ molecular tracers capable of detecting cancer lesions with both high sensitivity and specificity while also providing essential information for both prognosis and therapy. On the contrary, complementary and crucial information is provided by histopathological examination and ancillary techniques such as immunohistochemistry. Thus, the successful collaboration between diagnostic imaging and anatomic pathology can represent a fundamental step in the "tortuous" but decisive path towards personalized medicine.
Collapse
Affiliation(s)
- Orazio Schillaci
- Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Via Montpellier 1, Rome 00133, Italy
- IRCCS Neuromed, Pozzilli, Italy
| | - Manuel Scimeca
- Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Via Montpellier 1, Rome 00133, Italy
- University of San Raffaele, Via di Val Cannuta 247, 00166 Rome, Italy
- Fondazione Umberto Veronesi (FUV), Piazza Velasca 5, 20122 Milano, Italy
| | - Nicola Toschi
- Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Via Montpellier 1, Rome 00133, Italy
- Martinos Center for Biomedical Imaging, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Rita Bonfiglio
- Department of Experimental Medicine, University “Tor Vergata”, Via Montpellier 1, Rome 00133, Italy
| | | | - Elena Bonanno
- Department of Experimental Medicine, University “Tor Vergata”, Via Montpellier 1, Rome 00133, Italy
- IRCCS Neuromed Lab, “Diagnostica Medica”, “Villa dei Platani”, Avellino, Italy
| |
Collapse
|
11
|
Fujima N, Shimizu Y, Yoshida D, Kano S, Mizumachi T, Homma A, Yasuda K, Onimaru R, Sakai O, Kudo K, Shirato H. Machine-Learning-Based Prediction of Treatment Outcomes Using MR Imaging-Derived Quantitative Tumor Information in Patients with Sinonasal Squamous Cell Carcinomas: A Preliminary Study. Cancers (Basel) 2019; 11:cancers11060800. [PMID: 31185611 PMCID: PMC6627127 DOI: 10.3390/cancers11060800] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 06/02/2019] [Accepted: 06/06/2019] [Indexed: 02/06/2023] Open
Abstract
The purpose of this study was to determine the predictive power for treatment outcome of a machine-learning algorithm combining magnetic resonance imaging (MRI)-derived data in patients with sinonasal squamous cell carcinomas (SCCs). Thirty-six primary lesions in 36 patients were evaluated. Quantitative morphological parameters and intratumoral characteristics from T2-weighted images, tumor perfusion parameters from arterial spin labeling (ASL) and tumor diffusion parameters of five diffusion models from multi-b-value diffusion-weighted imaging (DWI) were obtained. Machine learning by a non-linear support vector machine (SVM) was used to construct the best diagnostic algorithm for the prediction of local control and failure. The diagnostic accuracy was evaluated using a 9-fold cross-validation scheme, dividing patients into training and validation sets. Classification criteria for the division of local control and failure in nine training sets could be constructed with a mean sensitivity of 0.98, specificity of 0.91, positive predictive value (PPV) of 0.94, negative predictive value (NPV) of 0.97, and accuracy of 0.96. The nine validation data sets showed a mean sensitivity of 1.0, specificity of 0.82, PPV of 0.86, NPV of 1.0, and accuracy of 0.92. In conclusion, a machine-learning algorithm using various MR imaging-derived data can be helpful for the prediction of treatment outcomes in patients with sinonasal SCCs.
Collapse
Affiliation(s)
- Noriyuki Fujima
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo 060-8638, Hokkaido, Japan.
| | - Yukie Shimizu
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo 060-8638, Hokkaido, Japan.
| | - Daisuke Yoshida
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo 060-8638, Hokkaido, Japan.
| | - Satoshi Kano
- Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan.
| | - Takatsugu Mizumachi
- Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan.
| | - Akihiro Homma
- Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan.
| | - Koichi Yasuda
- Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan.
| | - Rikiya Onimaru
- Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan.
| | - Osamu Sakai
- Departments of Radiology, Otolaryngology-Head and Neck Surgery, and Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA 02118, USA.
| | - Kohsuke Kudo
- Department of Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo 060-8638, Hokkaido, Japan.
| | - Hiroki Shirato
- Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan.
- The Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education, Sapporo 060-0808, Hokkaido, Japan.
| |
Collapse
|
12
|
Meyer HJ, Hamerla G, Höhn AK, Surov A. CT Texture Analysis-Correlations With Histopathology Parameters in Head and Neck Squamous Cell Carcinomas. Front Oncol 2019; 9:444. [PMID: 31192138 PMCID: PMC6546809 DOI: 10.3389/fonc.2019.00444] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 05/10/2019] [Indexed: 12/26/2022] Open
Abstract
Introduction: Texture analysis is an emergent imaging technique to quantify heterogeneity in radiological images. It is still unclear whether this technique is capable to reflect tumor microstructure. The present study sought to correlate histopathology parameters with texture features derived from contrast-enhanced CT images in head and neck squamous cell carcinomas (HNSCC). Materials and Methods: Twenty-eight patients with histopathological proven HNSCC were retrospectively analyzed. In every case EGFR, VEGF, Hif1-alpha, Ki67, p53 expression derived from immunhistochemical specimen were semiautomatically calculated. Furthermore, mean cell count was estimated. Texture analysis was performed on contrast-enhanced CT images as a whole lesion measurement. Spearman's correlation analysis was performed, adjusted with Benjamini-Hochberg correction for multiple tests. Results: Several texture features correlated with histopathological parameters. After correction only CT texture joint entropy and CT entropy correlation with Hif1-alpha expression remained statistically significant (ρ = −0.60 and ρ = −0.50, respectively). Conclusions: CT texture joint entropy and CT entropy were associated with Hif1-alpha expression in HNSCC and might be able to reflect hypoxic areas in this entity.
Collapse
Affiliation(s)
- Hans-Jonas Meyer
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany
| | - Gordian Hamerla
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany
| | | | - Alexey Surov
- Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany
| |
Collapse
|
13
|
Surov A, Meyer HJ, Höhn AK, Wienke A, Sabri O, Purz S. 18F-FDG-PET Can Predict Microvessel Density in Head and Neck Squamous Cell Carcinoma. Cancers (Basel) 2019; 11:cancers11040543. [PMID: 30991696 PMCID: PMC6521262 DOI: 10.3390/cancers11040543] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 04/04/2019] [Accepted: 04/11/2019] [Indexed: 12/19/2022] Open
Abstract
Aim: Positron emission tomography (PET) with 18F-fluordeoxyglucose (18F-FDG) plays an essential role in the staging and tumor monitoring of head and neck squamous cell carcinoma (HNSCC). Microvessel density (MVD) is one of the clinically important histopathological features in HNSCC. The purpose of this study was to analyze possible associations between 18F-FDG-PET findings and MVD parameters in HNSCC. Materials and Methods: Overall, 22 patients with a mean age of 55.2 ± 11.0 and with different HNSCC were acquired. In all cases, whole-body 18F-FDG-PET was performed. For each tumor, the maximum and mean standardized uptake values (SUVmax; SUVmean) were determined. The MVD, including stained vessel area and total number of vessels, was estimated on CD105 stained specimens. All specimens were digitalized and analyzed by using ImageJ software 1.48v. Spearman's correlation coefficient (r) was used to analyze associations between investigated parameters. p-values of <0.05 were taken to indicate statistical significance. Results: SUVmax correlated with vessel area (r = 0.532, p = 0.011) and vessel count (r = 0.434, p = 0.043). Receiver operating characteristic analysis identified a threshold SUVmax of 15 to predict tumors with high MVD with a sensitivity of 72.7% and specificity of 81.8%, with an area under the curve of 82.6%. Conclusion: ⁸F-FDG-PET parameters correlate statistically significantly with MVD in HNSCC. SUVmax may be used for discrimination of tumors with high tumor-related MVD.
Collapse
Affiliation(s)
- Alexey Surov
- Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany.
| | - Hans Jonas Meyer
- Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany.
| | - Anne-Kathrin Höhn
- Department of Pathology, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany.
| | - Andreas Wienke
- Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 8, 06097 Halle, Germany.
| | - Osama Sabri
- Department of Nuclear Medicine, University Hospital of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany.
| | - Sandra Purz
- Department of Nuclear Medicine, University Hospital of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany.
| |
Collapse
|
14
|
Martens RM, Noij DP, Koopman T, Zwezerijnen B, Heymans M, de Jong MC, Hoekstra OS, Vergeer MR, de Bree R, Leemans CR, de Graaf P, Boellaard R, Castelijns JA. Predictive value of quantitative diffusion-weighted imaging and 18-F-FDG-PET in head and neck squamous cell carcinoma treated by (chemo)radiotherapy. Eur J Radiol 2019; 113:39-50. [PMID: 30927958 DOI: 10.1016/j.ejrad.2019.01.031] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 12/28/2018] [Accepted: 01/29/2019] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND PURPOSE In head and neck squamous cell carcinoma (HNSCC) (chemo)radiotherapy is increasingly used to preserve organ functionality. The purpose of this study was to identify predictive pretreatment DWI- and 18F-FDG-PET/CT-parameters for treatment failure (TF), locoregional recurrence (LR) and death in HNSCC patients treated by (chemo)radiotherapy. MATERIALS AND METHODS We retrospectively included 134 histologically proven HNSCC patients treated with (chemo)radiotherapy between 2012-2017. In 58 patients pre-treatment DWI and 18F-FDG-PET/CT were performed, in 31 patients DWI only and in 45 patients 18F-FDG-PET/CT only. Primary tumor (PT) and largest lymph node (LN) metastasis were quantitatively assessed for TF, LR and death. Multivariate analysis was performed for 18F-FDG-PET/CT and DWI separately and thereafter combined. In patients with both imaging modalities, positive and negative predictive value in TF and differences in LR and death, were assessed. RESULTS Mean follow-up was 25.6 months (interquartile-range; 14.0-37.1 months). Predictors of treatment failure, corrected for TNM-stage and HPV-status, were SUVmax-PT, ADCmax-PT, total lesion glycolysis (TLG-LN), ADCp20-LN (P = 0.049, P = 0.024, P = 0.031, P = 0.047, respectively). TLG-PT was predictive for LR (P = 0.003). Metabolic active tumor volume (MATV-PT) (P = 0.003), ADCGTV-PT (P < 0.001), ADCSD (P = 0.048) were significant predictors for death. In patients with both imaging modalities SUVmax-PT remained predictive for treatment failure (P = 0.049), TLG-LN for LR (P = 0.003) and ADCGTV-PT for death (P < 0.001). Higher predictive value for treatment failure was found for the combination of SUVmax-PT and ADCmax-PT, compared to either one separately. CONCLUSION Both DWI- and 18F-FDG-PET/CT-parameters appear to have predictive value for treatment failure, locoregional recurrence and death. Combining SUVmax-PT and ADCmax-PT resulted in better prediction of treatment failure compared to single parameter assessment.
Collapse
Affiliation(s)
- Roland M Martens
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
| | - Daniel P Noij
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Thomas Koopman
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Ben Zwezerijnen
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Martijn Heymans
- Department of Epidemiology and Biostatistics, the Netherlands
| | - Marcus C de Jong
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Otto S Hoekstra
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Marije R Vergeer
- Department of Radiation Oncology, VU University Medical Center, Amsterdam, the Netherlands
| | - Remco de Bree
- Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, Amsterdam, the Netherlands; Department of Head and Neck Surgical Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - C René Leemans
- Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, Amsterdam, the Netherlands
| | - Pim de Graaf
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Ronald Boellaard
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Jonas A Castelijns
- Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands
| |
Collapse
|
15
|
Can the Efficacy of [ 18F]FDG-PET/CT in Clinical Oncology Be Enhanced by Screening Biomolecular Profiles? Pharmaceuticals (Basel) 2019; 12:ph12010016. [PMID: 30678034 PMCID: PMC6469153 DOI: 10.3390/ph12010016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 01/03/2019] [Accepted: 01/14/2019] [Indexed: 12/22/2022] Open
Abstract
Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncology. Over the years the sensitivity and specificity of PET has improved with the advent of specific radiotracers, increased technical accuracy of PET scanners and incremental experience of Radiologists. However, significant limitations exist—most notably false positives and false negatives. Additionally, the accuracy of PET varies between cancer types and in some cancers, is no longer considered a standard imaging modality. This review considers the relative influence of macroscopic tumour features such as size and morphology on 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG) uptake by tumours which, though well described in the literature, lacks a comprehensive assessment of biomolecular features which may influence [18F]FDG uptake. The review aims to discuss the potential influence of individual molecular markers of glucose transport, glycolysis, hypoxia and angiogenesis in addition to the relationships between these key cellular processes and their influence on [18F]FDG uptake. Finally, the potential role for biomolecular profiling of individual tumours to predict positivity on PET imaging is discussed to enhance accuracy and clinical utility.
Collapse
|
16
|
Associations between Histogram Analysis Parameters Derived from DCE-MRI and Histopathological Features including Expression of EGFR, p16, VEGF, Hif1-alpha, and p53 in HNSCC. CONTRAST MEDIA & MOLECULAR IMAGING 2019; 2019:5081909. [PMID: 30718984 PMCID: PMC6334376 DOI: 10.1155/2019/5081909] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 12/05/2018] [Indexed: 12/14/2022]
Abstract
Background Our purpose was to elucidate possible correlations between histogram parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) with several histopathological features in head and neck squamous cell carcinomas (HNSCC). Methods Thirty patients with primary HNSCC were prospectively acquired. Histogram analysis was derived from the DCE-MRI parameters: Ktrans, Kep, and Ve. Additionally, in all cases, expression of human papilloma virus (p16) hypoxia-inducible factor-1-alpha (Hif1-alpha), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and tumor suppressor protein p53 were estimated. Results Kep kurtosis was significantly higher in p16 tumors, and Ve min was significantly lower in p16 tumors compared to the p16 negative tumors. In the overall sample, Kep entropy correlated well with EGFR expression (p=0.38, P=0.04). In p16 positive carcinomas, Ktrans max correlated with VEGF expression (p=0.46, P=0.04), Ktrans kurtosis correlated with Hif1-alpha expression (p=0.46, P=0.04), and Ktrans entropy correlated with EGFR expression (p=0.50, P=0.03). Regarding Kep parameters, mode correlated with VEGF expression (p=0.51, P=0.02), and entropy correlated with Hif1-alpha expression (p=0.47, P=0.04). In p16 negative carcinomas, Kep mode correlated with Her2 expression (p=−0.72, P=0.03), Ve max correlated with p53 expression (p=−0.80, P=0.009), and Ve p10 correlated with EGFR expression (p=0.68, P=0.04). Conclusion DCE-MRI can reflect several histopathological features in HNSCC. Associations between DCE-MRI and histopathology in HNSCC depend on p16 status. Kep kurtosis and Ve min can differentiate p16 positive and p16 negative carcinomas.
Collapse
|
17
|
Subramaniam N, Balasubramanian D, Sundaram PS, Murthy S, Thankappan K, Iyer S. Role of pretreatment fluorodeoxyglucose positron emission tomography quantitative parameters in prognostication of head-and-neck squamous cell carcinoma. Indian J Med Paediatr Oncol 2019. [DOI: 10.4103/ijmpo.ijmpo_253_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Abstract
In spite of the good organ preservation strategies available for locally advanced head-and-neck squamous cell carcinoma (HNSCC), failure rates have been reported to be as high as 35%–50%. There has been an increasing interest in predicting response to treatment, to aid early intervention and better outcomes. Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is a standard modality for posttreatment evaluation; however, it is still underutilized as a pretreatment investigative modality. Several articles have described quantitative parameters in pretreatment FDG-PET to prognosticate patients and determine the likelihood of response to treatment; however, they are still not used commonly. This article was a review of the literature available on pretreatment FDG-PET quantitative parameters and their value in predicting failure. A thorough review of literature from MEDLINE and EMBASE was performed on pretreatment quantitative parameters in HNSCC. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were reliable parameters to predict response to organ preservation therapy, disease-free survival, and overall survival. Maximum SUV (SUVmax) was an inconsistent parameter. MTV and TLG may help predict poor response to organ preservation to initiate early surgical salvage or modify therapeutic decisions to optimize clinical outcomes. Routine use may provide additional information over SUVmax alone.
Collapse
Affiliation(s)
- Narayana Subramaniam
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Deepak Balasubramanian
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - P Shanmuga Sundaram
- Department of Nuclear Medicine, Amrita Institute of Medical Sciences, Amrita Vidya Vidyapeetham, Kochi, Kerala, Indias
| | - Samskruthi Murthy
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Krishnakumar Thankappan
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Subramania Iyer
- Department of Head and Neck Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| |
Collapse
|
18
|
Meyer HJ, Leifels L, Hamerla G, Höhn AK, Surov A. Histogram Analysis Parameters Derived from Conventional T1- and T2-Weighted Images Can Predict Different Histopathological Features Including Expression of Ki67, EGFR, VEGF, HIF-1α, and p53 and Cell Count in Head and Neck Squamous Cell Carcinoma. Mol Imaging Biol 2018; 21:740-746. [DOI: 10.1007/s11307-018-1283-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
19
|
Surov A, Meyer HJ, Höhn AK, Sabri O, Purz S. Combined Metabolo-Volumetric Parameters of 18F-FDG-PET and MRI Can Predict Tumor Cellularity, Ki67 Level and Expression of HIF 1alpha in Head and Neck Squamous Cell Carcinoma: A Pilot Study. Transl Oncol 2018; 12:8-14. [PMID: 30240972 PMCID: PMC6143720 DOI: 10.1016/j.tranon.2018.08.018] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 08/25/2018] [Accepted: 08/29/2018] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND: Our purpose was to evaluate associations of combined 18F-FDG-PET and MRI parameters with histopathological features in head and neck squamous cell carcinoma (HNSCC). METHODS: Overall, 22 patients with HNSCC were acquired (10 with G1/2 tumors and 12 with G3 tumors).18F-FDG-PET/CT and MRI was performed and maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) were estimated. Neck MRI was obtained on a 3 T scanner. Diffusion weighted imaging was performed with estimation of apparent diffusion coefficient (ADC). Perfusion parameters Ktrans,Ve, and Kep were derived from dynamic contrast-enhanced (DCE) imaging. Different combined PET/MRI parameters were calculated as ratios: PET parameters divided by ADC or DCE MRI parameters. The following histopathological features were estimated: Ki 67, EGFR, VEGF, p53, hypoxia-inducible factor (HIF)-1α, and cell count. Spearman's correlation coefficient (p) was used for correlation analysis. P < .05 was taken to indicate statistical significance. RESULTS: In overall sample, cellularity correlated with SUVmax/ADCmin (P = .558, P = .007), TLG/ADCmin (P = .546, P = .009), and MTV/ADCmin (P = .468, P = .028). MTV/Kep correlated with expression of HIF-1α (P = .450, P = 0,047). In G1/2 tumors, SUVmax/ADCmin correlated with HIF-1α (P = −.648, P = .043); MTV/Kep (P = −.669, P = .034) and TLG/Kep (P = −.644, P = .044) with Ki67. In G3 tumors, cellularity correlated with SUVmax/ADCmin (P = .832, P = .001), SUVmax/ADCmean (P = .741, P = .006), and TLG/ADCmin (P = .678, P = .015). MTV/ADCmin and TLG/ADCmin tended to correlate with HIF-1α. CONCLUSION: Combined parameters of 18F-FDG-PET and MRI can reflect Ki 67, tumor cellularity and expression of HIF-1α in HNSCC. Associations between parameters of 18F-FDG-PET and MRI and histopathology depend on tumor grading.
Collapse
Affiliation(s)
- Alexey Surov
- Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany.
| | - Hans Jonas Meyer
- Department of Diagnostic and Interventional Radiology, University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Anne Kathrin Höhn
- Department of Pathology University Hospital of Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany
| | - Osama Sabri
- Department of Nuclear Medicine, University Hospital of Leipzig, Liebigstraße 18, 04103 Leipzig, Germany
| | - Sandra Purz
- Department of Nuclear Medicine, University Hospital of Leipzig, Liebigstraße 18, 04103 Leipzig, Germany
| |
Collapse
|
20
|
Rasmussen JH, Håkansson K, Rasmussen GB, Vogelius IR, Friborg J, Fischer BM, Bentzen SM, Specht L. A clinical prognostic model compared to the newly adopted UICC staging in an independent validation cohort of P16 negative/positive head and neck cancer patients. Oral Oncol 2018; 81:52-60. [PMID: 29884414 DOI: 10.1016/j.oraloncology.2018.04.009] [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: 09/01/2017] [Revised: 01/29/2018] [Accepted: 04/10/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVES A previously published prognostic model in patients with head and neck squamous cell carcinoma (HNSCC) was validated in both a p16-negative and a p16-positive independent patient cohort and the performance was compared with the newly adopted 8th edition of the UICC staging system. MATERIALS AND METHODS Consecutive patients with HNSCC treated at a single institution from 2005 to 2012 were included. The cohort was divided in three. 1.) Training cohort, patients treated from 2005 to 2009 excluding patients with p16-positive oropharyngeal squamous cell carcinomas (OPSCC); 2.) A p16-negative validation cohort and 3.) A p16-positive validation cohort. A previously published prognostic model (clinical model) with the significant covariates (smoking status, FDG uptake, and tumor volume) was refitted in the training cohort and validated in the two validation cohorts. The clinical model was used to generate four risk groups based on the predicted risk of disease recurrence after 2 years and the performance was compared with UICC staging 8th edition using concordance index. RESULTS Overall 568 patients were included. Compared to UICC the clinical model had a significantly better concordance index in the p16-negative validation cohort (AUC = 0.63 for UICC and AUC = 0.73 for the clinical model; p = 0.003) and a borderline significantly better concordance index in the p16-positive cohort (AUC = 0.63 for UICC and 0.72 for the clinical model; p = 0.088). CONCLUSION The validated clinical model provided a better prognostication of risk of disease recurrence than UICC stage in the p16-negative validation cohort, and similar prognostication as the newly adopted 8th edition of the UICC staging in the p16-positive patient cohort.
Collapse
Affiliation(s)
- Jacob H Rasmussen
- Department of Otorhinolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Denmark.
| | - Katrin Håkansson
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Denmark.
| | - Gregers B Rasmussen
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Denmark.
| | - Ivan R Vogelius
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Denmark.
| | - Jeppe Friborg
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Denmark.
| | - Barbara M Fischer
- Department of Clinical Physiology, Nuclear Medicine & PET, PET & Cyclotron Unit, Rigshospitalet University of Copenhagen, Denmark.
| | - Søren M Bentzen
- Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, USA.
| | - Lena Specht
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Denmark.
| |
Collapse
|
21
|
Surov A, Meyer HJ, Wienke A. Can Imaging Parameters Provide Information Regarding Histopathology in Head and Neck Squamous Cell Carcinoma? A Meta-Analysis. Transl Oncol 2018; 11:498-503. [PMID: 29510360 PMCID: PMC5884190 DOI: 10.1016/j.tranon.2018.02.004] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 02/02/2018] [Accepted: 02/09/2018] [Indexed: 11/29/2022] Open
Abstract
OBJECT Our purpose was to provide data regarding relationships between different imaging and histopathological parameters in HNSCC. METHODS MEDLINE library was screened for associations between different imaging parameters and histopathological features in HNSCC up to December 2017. Only papers containing correlation coefficients between different imaging parameters and histopathological findings were acquired for the analysis. RESULTS Associations between 18F-FDG positron emission tomography (PET) and KI 67 were reported in 8 studies (236 patients). The pooled correlation coefficient was 0.20 (95% CI = [-0.04; 0.44]). Furthermore, in 4 studies (64 patients), associations between 18F-fluorothymidine PET and KI 67 were analyzed. The pooled correlation coefficient between SUVmax and KI 67 was 0.28 (95% CI = [-0.06; 0.94]). In 2 studies (23 patients), relationships between KI 67 and dynamic contrast-enhanced magnetic resonance imaging were reported. The pooled correlation coefficient between Ktrans and KI 67 was -0.68 (95% CI = [-0.91; -0.44]). Two studies (31 patients) investigated correlation between apparent diffusion coefficient (ADC) and KI 67. The pooled correlation coefficient was -0.61 (95% CI = [-0.84; -0.38]). In 2 studies (117 patients), relationships between 18F-FDG PET and p53 were analyzed. The pooled correlation coefficient was 0.0 (95% CI = [-0.87; 0.88]). There were 3 studies (48 patients) that investigated associations between ADC and tumor cell count in HNSCC. The pooled correlation coefficient was -0.53 (95% CI = [-0.74; -0.32]). Associations between 18F-FDG PET and HIF-1α were investigated in 3 studies (72 patients). The pooled correlation coefficient was 0.44 (95% CI = [-0.20; 1.08]). CONCLUSIONS ADC may predict cell count and proliferation activity, and SUVmax may predict expression of HIF-1α in HNSCC. SUVmax cannot be used as surrogate marker for expression of KI 67 and p53.
Collapse
Affiliation(s)
- Alexey Surov
- Department of Diagnostic and Interventional Radiology, University of Leipzig.
| | - Hans Jonas Meyer
- Department of Diagnostic and Interventional Radiology, University of Leipzig
| | - Andreas Wienke
- Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg
| |
Collapse
|
22
|
Grau C, Høyer M, Poulsen PR, Muren LP, Korreman SS, Tanderup K, Lindegaard JC, Alsner J, Overgaard J. Rethink radiotherapy - BIGART 2017. Acta Oncol 2017; 56:1341-1352. [PMID: 29148908 DOI: 10.1080/0284186x.2017.1371326] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Cai Grau
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Morten Høyer
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | | | - Ludvig Paul Muren
- Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark
| | | | - Kari Tanderup
- Department of Medical Physics, Aarhus University Hospital, Aarhus, Denmark
| | | | - Jan Alsner
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Jens Overgaard
- Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark
| |
Collapse
|
23
|
Rasmussen GB, Håkansson KE, Vogelius IR, Rasmussen JH, Friborg JT, Fischer BM, Schumaker L, Cullen K, Therkildsen MH, Bentzen SM, Specht L. Immunohistochemical and molecular imaging biomarker signature for the prediction of failure site after chemoradiation for head and neck squamous cell carcinoma. Acta Oncol 2017; 56:1562-1570. [PMID: 28840766 DOI: 10.1080/0284186x.2017.1364870] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To identify a failure site-specific prognostic model by combining immunohistochemistry (IHC) and molecular imaging information to predict long-term failure type in squamous cell carcinoma of the head and neck. PATIENT AND METHODS Tissue microarray blocks of 196 head and neck squamous cell carcinoma cases were stained for a panel of biomarkers using IHC. Gross tumor volume (GTV) from the PET/CT radiation treatment planning CT scan, maximal Standard Uptake Value (SUVmax) of fludeoxyglucose (FDG) and clinical information were included in the model building using Cox proportional hazards models, stratified for p16 status in oropharyngeal carcinomas. Separate models were built for time to locoregional failure and time to distant metastasis. RESULTS Higher than median p53 expression on IHC tended toward a risk factor for locoregional failure but was protective for distant metastasis, χ2 for difference p = .003. The final model for locoregional failure included p53 (HR: 1.9; p: .055), concomitant cisplatin (HR: 0.41; p: .008), β-tubulin-1 (HR: 1.8; p: .08), β-tubulin-2 (HR: 0.49; p: .057) and SUVmax (HR: 2.1; p: .046). The final model for distant metastasis included p53 (HR: 0.23; p: .025), Bcl-2 (HR: 2.6; p: .08), SUVmax (HR: 3.5; p: .095) and GTV (HR: 1.7; p: .063). CONCLUSIONS The models successfully distinguished between risk of locoregional failure and risk of distant metastasis, which is important information for clinical decision-making. High p53 expression has opposite prognostic effects for the two endpoints; increasing risk of locoregional failure, but decreasing the risk of metastatic failure, but external validation of this finding is needed.
Collapse
Affiliation(s)
- Gregers Brünnich Rasmussen
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Katrin E. Håkansson
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Ivan R. Vogelius
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jacob H. Rasmussen
- Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jeppe T. Friborg
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Barbara M. Fischer
- Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Lisa Schumaker
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA
| | - Kevin Cullen
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA
| | | | - Søren M. Bentzen
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA
- Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Lena Specht
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| |
Collapse
|
24
|
Håkansson K, Rasmussen JH, Rasmussen GB, Friborg J, Gerds TA, Fischer BM, Andersen FL, Bentzen SM, Specht L, Vogelius IR. A failure-type specific risk prediction tool for selection of head-and-neck cancer patients for experimental treatments. Oral Oncol 2017; 74:77-82. [PMID: 29103755 DOI: 10.1016/j.oraloncology.2017.09.018] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Revised: 09/08/2017] [Accepted: 09/17/2017] [Indexed: 01/16/2023]
Abstract
OBJECTIVES The objective of this work was to develop a tool for decision support, providing simultaneous predictions of the risk of loco-regional failure (LRF) and distant metastasis (DM) after definitive treatment for head-and-neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS Retrospective data for 560HNSCC patients were used to generate a multi-endpoint model, combining three cause-specific Cox models (LRF, DM and death with no evidence of disease (death NED)). The model was used to generate risk profiles of patients eligible for/included in a de-intensification study (RTOG 1016) and a dose escalation study (CONTRAST), respectively, to illustrate model predictions versus classic inclusion/exclusion criteria for clinical trials. The model is published as an on-line interactive tool (https://katrin.shinyapps.io/HNSCCmodel/). RESULTS The final model included pre-selected clinical variables (tumor subsite, T stage, N stage, smoking status, age and performance status) and one additional variable (tumor volume). The treatment failure discrimination ability of the developed model was superior of that of UICC staging, 8th edition (AUCLRF=72.7% vs 64.2%, p<0.001 and AUCDM=70.7% vs 58.8%, p<0.001). Using the model for trial inclusion simulation, it was found that 14% of patients eligible for the de-intensification study had>20% risk of tumor relapse. Conversely, 9 of the 15 dose escalation trial participants had LRF risks<20%. CONCLUSION A multi-endpoint model was generated and published as an on-line interactive tool. Its potential in decision support was illustrated by generating risk profiles for patients eligible for/included in clinical trials for HNSCC.
Collapse
Affiliation(s)
- Katrin Håkansson
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - Jacob H Rasmussen
- Department of Otorhinolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - Gregers B Rasmussen
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - Jeppe Friborg
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - Thomas A Gerds
- Department of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen, Denmark.
| | - Barbara Malene Fischer
- Department of Clinical Physiology, Nuclear Medicine & PET, PET & Cyclotron Unit, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - Flemming L Andersen
- Department of Clinical Physiology, Nuclear Medicine & PET, PET & Cyclotron Unit, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - Søren M Bentzen
- Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center and Department of Epidemiology and Public Health, University of Maryland School of Medicine, 655 W Baltimore Street, Baltimore MD21201, USA.
| | - Lena Specht
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| | - Ivan R Vogelius
- Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
| |
Collapse
|
25
|
Mena E, Thippsandra S, Yanamadala A, Redy S, Pattanayak P, Subramaniam RM. Molecular Imaging and Precision Medicine in Head and Neck Cancer. PET Clin 2016; 12:7-25. [PMID: 27863568 DOI: 10.1016/j.cpet.2016.08.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The concept of using tumor genomic profiling information has revolutionized personalized cancer treatment. Head and neck (HN) cancer management is being influenced by recent discoveries of activating mutations in epidermal growth factor receptor and related targeted therapies with tyrosine kinase inhibitors, targeted therapies for Kristen Rat Sarcoma, and MET proto-oncogenes. Molecular imaging using PET plays an important role in assessing the biologic behavior of HN cancer with the goal of delivering individualized cancer treatment. This review summarizes recent genomic discoveries in HN cancer and their implications for functional PET imaging in assessing response to targeted therapies, and drug resistance mechanisms.
Collapse
Affiliation(s)
- Esther Mena
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Johns Hopkins University, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Shwetha Thippsandra
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Johns Hopkins University, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Anusha Yanamadala
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Johns Hopkins University, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Siddaling Redy
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Johns Hopkins University, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Puskar Pattanayak
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Johns Hopkins University, 601 North Caroline Street, Baltimore, MD 21287, USA
| | - Rathan M Subramaniam
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Johns Hopkins University, 601 North Caroline Street, Baltimore, MD 21287, USA; Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8896, USA; Department of Clinical Sciences, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9096, USA; Department of Biomedical Engineering, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8896, USA; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390-8896, USA.
| |
Collapse
|