Dataset Information

A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models.

ABSTRACT:

Purpose

Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma.

Experimental design

Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data glioblastoma patients (n = 93) and orthotopic xenografts (OX; n = 40). Tumor phenotypes were segmented, and radiomic-features extracted using the developed radiome-sequencing pipeline. Patients and animals were dichotomized on the basis of Periostin (POSTN) expression levels. RNA and protein levels confirmed RNAi-mediated POSTN knockdown in OX. Total RNA of tumor cells isolated from mouse brains (knockdown and control) was used for microarray-based expression profiling. Radiomic-features were utilized to predict POSTN expression status in patient, mouse, and interspecies.

Results

Our robust pipeline consists of segmentation, radiomic-feature extraction, feature normalization/selection, and predictive modeling. The combination of skull stripping, brain-tissue focused normalization, and patient-specific normalization are unique to this study, providing comparable cross-platform, cross-institution radiomic features. POSTN expression status was not associated with qualitative or volumetric MRI parameters. Radiomic features significantly predicted POSTN expression status in patients (AUC: 76.56%; sensitivity/specificity: 73.91/78.26%) and OX (AUC: 92.26%; sensitivity/specificity: 92.86%/91.67%). Furthermore, radiomic features in OX were significantly associated with patients with similar POSTN expression levels (AUC: 93.36%; sensitivity/specificity: 82.61%/95.74%; P = 02.021E-15).

Conclusions

We determined causality between radiomic texture features and POSTN expression levels in a preclinical model with clinical validation. Our biologically validated radiomic pipeline also showed the potential application for human-mouse matched coclinical trials.

SUBMITTER: Zinn PO

PROVIDER: S-EPMC6538261 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models.

Zinn Pascal O PO Singh Sanjay K SK Kotrotsou Aikaterini A Hassan Islam I Thomas Ginu G Luedi Markus M MM Elakkad Ahmed A Elshafeey Nabil N Idris Tagwa T Mosley Jennifer J Gumin Joy J Fuller Gregory N GN de Groot John F JF Baladandayuthapani Veera V Sulman Erik P EP Kumar Ashok J AJ Sawaya Raymond R Lang Frederick F FF Piwnica-Worms David D Colen Rivka R RR

Clinical cancer research : an official journal of the American Association for Cancer Research 20180727 24

<h4>Purpose</h4>Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma.<h4>Experimental design</h4>Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular ...[more]

PMID: 30054278

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Project description:Background and purposeSemantic imaging features have been used for molecular subclassification of high-grade gliomas. Radiomics-based prediction of molecular subgroups has the potential to strategize and individualize therapy. Using MRI texture features, we propose to distinguish between IDH wild type and IDH mutant type high grade gliomas.MethodsBetween 2013 and 2020, 100 patients were retrospectively analyzed for the radiomics study. Immunohistochemistry of the pathological specimen was used to initially identify patients for the IDH mutant/wild phenotype and was then confirmed by Sanger's sequencing. Image texture analysis was performed on contrast-enhanced T1 (T1C) and T2 weighted (T2W) MR images. Manual segmentation was performed on MR image slices followed by single-slice multiple sampling image augmentation. Both whole tumor multislice segmentation and single-slice multiple sampling approaches were used to arrive at the best model. Radiomic features were extracted, which included first-order features, second-order (GLCM-Grey level co-occurrence matrix), and shape features. Feature enrichment was done using LASSO (Least Absolute Shrinkage and Selection Operator) regression, followed by radiomic classification using Support Vector Machine (SVM) and a 10-fold cross-validation strategy for model development. The area under the Receiver Operator Characteristic (ROC) curve and predictive accuracy were used as diagnostic metrics to evaluate the model to classify IDH mutant and wild-type subgroups.ResultsMultislice analysis resulted in a better model compared to the single-slice multiple-sampling approach. A total of 164 MR-based texture features were extracted, out of which LASSO regression identified 14 distinctive GLCM features for the endpoint, which were used for further model development. The best model was achieved by using combined T1C and T2W MR images using a Quadratic Support Vector Machine Classifier and a 10-fold internal cross-validation approach, which demonstrated a predictive accuracy of 89% with an AUC of 0.89 for each IDH mutant and IDH wild subgroup.ConclusionA machine learning classifier of radiomic features extracted from multiparametric MRI images (T1C and T2w) provides important diagnostic information for the non-invasive prediction of the IDH mutant or wild-type phenotype of high-grade gliomas and may have potential use in either escalating or de-escalating adjuvant therapy for gliomas or for using targeted agents in the future.

Project description:Background: Parkinson's disease (PD) is a neurodegenerative disease in which the neostriatum, including the caudate nucleus (CN) and putamen (PU), has an important role in the pathophysiology. However, conventional magnetic resonance imaging (MRI) lacks sufficient specificity to diagnose PD. Therefore, the study's aim was to investigate the feasibility of using a radiomics approach to distinguish PD patients from healthy controls on T2-weighted images of the neostriatum and provide a basis for the clinical diagnosis of PD. Methods: T2-weighted images from 69 PD patients and 69 age- and sex-matched healthy controls were obtained on the same 3.0T MRI scanner. Regions of interest (ROIs) were manually placed at the CN and PU on the slices showing the largest respective sizes of the CN and PU. We extracted 274 texture features from each ROI and then used the least absolute shrinkage and selection operator regression to perform feature selection and radiomics signature building to identify the CN and PU radiomics signatures consisting of optimal features. We used a receiver operating characteristic curve analysis to assess the diagnostic performance of two radiomics signatures in a training group and estimate the generalization performance in the test group. Results: There were no significant differences in the demographic and clinical characteristics between the PD patients and healthy controls. The CN and PU radiomics signatures were built using 12 and 7 optimal features, respectively. The performance of the two radiomics signatures to distinguish PD patients from healthy controls was good. In the training and test groups, the AUCs of the CN radiomics signatures were 0.9410 (95% confidence interval [CI]: 0.8986-0.9833) and 0.7732 (95% CI: 0.6292-0.9173), respectively, and the AUCs of the PU radiomics signature were 0.8767 (95% CI: 0.8066-0.9469) and 0.7143 (95% CI: 0.5540-0.8746), respectively. Vertl_GlevNonU_R appeared simultaneously in both the CN and PU radiomics signatures as an optimal feature. A t-test analysis revealed significantly higher levels of texture values of the CN and PU in the PD patients than healthy controls (P < 0.05). Conclusion: Neostriatum radiomics signatures achieved good diagnostic performance for PD and potentially could serve as a basis for the clinical diagnosis of PD.

Dataset Information

A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models.

Purpose

Experimental design

Results

Conclusions

Publications

A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models.

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