title: Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome.
abstract: Tumors exhibit genomic and phenotypic heterogeneity, which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as CT density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks using PET, MRI, and other emerging molecular imaging techniques. These methods can establish whether one tumor is more or less heterogeneous than another and can identify subregions with differing biology. In this article, we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, instead of being developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care.
authors.affiliation: CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, University of Manchester, Manchester, United Kingdom. Department of Radiology, Christie Hospital, Manchester, United Kingdom. james.o'connor@manchester.ac.uk.
authors.forename: James P B
authors.initials: JP
authors.lastname: O'Connor
authors.affiliation: CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, University of Manchester, Manchester, United Kingdom.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Rose
authors.affiliation: CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, University of Manchester, Manchester, United Kingdom. R&D Personalised Healthcare and Biomarkers, AstraZeneca, Macclesfield, United Kingdom.
authors.forename: John C
authors.initials: JC
authors.lastname: Waterton
authors.affiliation: Biomedical Imaging Department, Genentech, Inc., South San Francisco, California.
authors.forename: Richard A D
authors.initials: RA
authors.lastname: Carano
authors.affiliation: CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, University of Manchester, Manchester, United Kingdom.
authors.forename: Geoff J M
authors.initials: GJ
authors.lastname: Parker
authors.affiliation: CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester, University of Manchester, Manchester, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Jackson
mesh_terms: D000818:Animals; D003952:Diagnostic Imaging; D018740:Genetic Heterogeneity; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*