DEMARCATE: density-based magnetic resonance image clustering for assessing tumor heterogeneity in cancer

Saha, Abhijoy; Banerjee, Sayantan; Kurtek, Sebastian; Narang, Shivali; Lee, Joonsang; Rao, Ganesh; Martinez, Juan; Bharath, Karthik; Baladandayuthapani, Veerabhadran

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.

Citation

Saha, A., Banerjee, S., Kurtek, S., Narang, S., Lee, J., Rao, G., …Baladandayuthapani, V. (in press). DEMARCATE: density-based magnetic resonance image clustering for assessing tumor heterogeneity in cancer. NeuroImage: Clinical, 12, https://doi.org/10.1016/j.nicl.2016.05.012

• Journal Article Type: Article
• Acceptance Date: May 25, 2016
• Online Publication Date: May 27, 2016
• Deposit Date: Aug 15, 2017
• Publicly Available Date: Aug 15, 2017
• Journal: NeuroImage: Clinical
• Electronic ISSN: 2213-1582
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 12
• DOI: https://doi.org/10.1016/j.nicl.2016.05.012
• Keywords: Glioblastoma; Medical imaging; Tumor heterogeneity; Density estimation; Clustering; Fisher–Rao metric
• Public URL: https://nottingham-repository.worktribe.com/output/788405
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S2213158216300882
• Contract Date: Aug 15, 2017