Novel MRI deformation-heterogeneity radiomic features are associated with molecular subgroups and overall survival in pediatric medulloblastoma: Preliminary findings from a multi-institutional study

Sukanya Iyer; Marwa Ismail; Benita Tamrazi; Ralph Salloum; Peter de Blank; Ashley Margol; Ramon Correa; Jonathan Chen; Kaustav Bera; Volodymyr Statsevych; Mai-Lan Ho; Pranjal Vaidya; Ruchika Verma; Debra Hawes; Alexander Judkins; Pingfu Fu; Anant Madabhushi; Pallavi Tiwari

doi:10.3389/fonc.2022.915143

Novel MRI deformation-heterogeneity radiomic features are associated with molecular subgroups and overall survival in pediatric medulloblastoma: Preliminary findings from a multi-institutional study

Front Oncol. 2022 Dec 21:12:915143. doi: 10.3389/fonc.2022.915143. eCollection 2022.

Authors

Sukanya Iyer¹, Marwa Ismail², Benita Tamrazi³, Ralph Salloum⁴, Peter de Blank⁵, Ashley Margol³, Ramon Correa¹, Jonathan Chen¹, Kaustav Bera¹, Volodymyr Statsevych⁶, Mai-Lan Ho⁷, Pranjal Vaidya¹, Ruchika Verma¹, Debra Hawes³, Alexander Judkins³, Pingfu Fu⁸, Anant Madabhushi⁸, Pallavi Tiwari²

Affiliations

¹ Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, United States.
² Department of Radiology and Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States.
³ Department of Pathology, Children's Hospital Los Angeles, Los Angeles, CA, United States.
⁴ Division of Hematology, Oncology & Bone Marrow Transplant, Nationwide Children's Hospital, Columbus, OH, United States.
⁵ Division of Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
⁶ Department of Neuroradiology, Imaging Institute, Cleveland Clinic, Cleveland, OH, United States.
⁷ Department of Radiology, Nationwide Children's Hospital, Columbus, OH, United States.
⁸ Radiology and Imaging Sciences, Biomedical Informatics (BMI) and Pathology, Georgia Institute of Technology and Emory University, Atlanta, GA, United States.

Abstract

Introduction: Medulloblastoma (MB) is a malignant, heterogenous brain tumor. Advances in molecular profiling have led to identifying four molecular subgroups of MB (WNT, SHH, Group 3, Group 4), each with distinct clinical behaviors. We hypothesize that (1) aggressive MB tumors, growing heterogeneously, induce pronounced local structural deformations in the surrounding parenchyma, and (b) these local deformations as captured on Gadolinium (Gd)-enhanced-T1w MRI are independently associated with molecular subgroups, as well as overall survival in MB patients.

Methods: In this work, a total of 88 MB studies from 2 institutions were analyzed. Following tumor delineation, Gd-T_1w scan for every patient was registered to a normal age-specific T_1w-MRI template via deformable registration. Following patient-atlas registration, local structural deformations in the brain parenchyma were obtained for every patient by computing statistics from deformation magnitudes obtained from every 5mm annular region, 0 < d < 60 mm, where d is the distance from the tumor infiltrating edge.

Results: Multi-class comparison via ANOVA yielded significant differences between deformation magnitudes obtained for Group 3, Group 4, and SHH molecular subgroups, observed up to 60-mm outside the tumor edge. Additionally, Kaplan-Meier survival analysis showed that the local deformation statistics, combined with the current clinical risk-stratification approaches (molecular subgroup information and Chang's classification), could identify significant differences between high-risk and low-risk survival groups, achieving better performance results than using any of these approaches individually.

Discussion: These preliminary findings suggest there exists significant association of our tumor-induced deformation descriptor with overall survival in MB, and that there could be an added value in using the proposed radiomic descriptor along with the current risk classification approaches, towards more reliable risk assessment in pediatric MB.

Keywords: LASSO; deformation; medulloblastoma; molecular subgroups; survival.

Grants and funding

Research reported in this publication was supported by the National Cancer Institute under award numbers 1U24CA199374-01, R01CA249992-01A1, R01CA202752-01A1, R01CA208236-01A1, R01CA216579-01A1, R01CA220581-01A1, R01CA257612-01A1, 1U01CA239055-01, 1U01CA248226-01, 1U54CA254566-01, National Heart, Lung and Blood Institute 1R01HL15127701A1, National Institute of Biomedical Imaging and Bioengineering 1R43EB028736-01, National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program (W81XWH-19-1-0668), the Prostate Cancer Research Program (W81XWH-15-1-0558, W81XWH-20-1-0851), the Lung Cancer Research Program (W81XWH-18-1-0440, W81XWH-20-1-0595), the Peer Reviewed Cancer Research Program (W81XWH-18-1-0404), the Kidney Precision Medicine Project (KPMP) Glue Grant, the Ohio Third Frontier Technology Validation Fund, the Clinical and Translational Science Collaborative of Cleveland (UL1TR0002548) from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, The Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering at Case Western Reserve University. Sponsored research agreements from Bristol Myers-Squibb, Boehringer-Ingelheim, and Astrazeneca.