title: DEMARCATE: Density-based magnetic resonance image clustering for assessing tumor heterogeneity in cancer.
abstract: Tumor heterogeneity is a crucial area of cancer research wherein inter- and intra-tumor differences are investigated to assess and monitor disease development and progression, especially in cancer. The proliferation of imaging and linked genomic data has enabled us to evaluate tumor heterogeneity on multiple levels. In this work, we examine magnetic resonance imaging (MRI) in patients with brain cancer to assess image-based tumor heterogeneity. Standard approaches to this problem use scalar summary measures (e.g., intensity-based histogram statistics) that do not adequately capture the complete and finer scale information in the voxel-level data. In this paper, we introduce a novel technique, DEMARCATE (DEnsity-based MAgnetic Resonance image Clustering for Assessing Tumor hEterogeneity) to explore the entire tumor heterogeneity density profiles (THDPs) obtained from the full tumor voxel space. THDPs are smoothed representations of the probability density function of the tumor images. We develop tools for analyzing such objects under the Fisher-Rao Riemannian framework that allows us to construct metrics for THDP comparisons across patients, which can be used in conjunction with standard clustering approaches. Our analyses of The Cancer Genome Atlas (TCGA) based Glioblastoma dataset reveal two significant clusters of patients with marked differences in tumor morphology, genomic characteristics and prognostic clinical outcomes. In addition, we see enrichment of image-based clusters with known molecular subtypes of glioblastoma multiforme, which further validates our representation of tumor heterogeneity and subsequent clustering techniques.
authors.affiliation: Department of Statistics, The Ohio State University, United States.
authors.forename: Abhijoy
authors.initials: A
authors.lastname: Saha
authors.affiliation: Operations Management and Quantitative Techniques Area, Indian Institute of Management Indore, India.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Statistics, The Ohio State University, United States.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kurtek
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, United States.
authors.forename: Shivali
authors.initials: S
authors.lastname: Narang
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, United States.
authors.forename: Joonsang
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, United States.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Rao
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, United States.
authors.forename: Juan
authors.initials: J
authors.lastname: Martinez
authors.affiliation: School of Mathematical Sciences, The University of Nottingham, United Kingdom.
authors.forename: Karthik
authors.initials: K
authors.lastname: Bharath
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, United States.
authors.forename: Arvind U K
authors.initials: AU
authors.lastname: Rao
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, United States.
authors.forename: Veerabhadran
authors.initials: V
authors.lastname: Baladandayuthapani
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D016000:Cluster Analysis; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged
keywords: Clustering; Density estimation; Fisher–Rao metric; Glioblastoma; Medical imaging; Tumor heterogeneity