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Monday, April 9 • 2:00pm - 2:15pm
SYMPOSIA-03: Imaging of Habitats in Cancer: Life at the Edge

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AUTHORS: Robert Gillies, H. Lee Moffitt Cancer Center and Research Institute

ABSTRACT: Cells in solid tumors are heterogeneous in mutational load, gene expression, and phenotype. This heterogeneity is a key driver in the emergence of resistance to therapy. Evolutionary dynamical models predict that microenvironment differences in acid-base balance and oxygen levels drive somatic evolution and genetic heterogeneity. Importantly, tools exist that can quantitatively image solid tumors and map the extent and types of microenvironments (“habitats”). An emerging analytical tool uses multi-parametric magnetic resonance imaging (mpMRI) to identify and classify physiologically distinct habitats in solid tumors. In general, these approaches require the co-registration of images acquired from different pulse sequences that interrogate different physiological parameters, such as blood flow, cell packing density, infrastructural organization, etc.. Overlaying these data sets creates “hyper-voxels” that contain specific combinations of normalized data from multiple inputs. Clustering algorithms identify hyper-voxels with similar features, and these are used to generate spatial maps of similar clusters. Notably, this procedure yields clusters that are spatially distinct, leading us to see them as “habitats”. An example is the combination of Apparent Diffusion coefficient (ADC), related to tissue density, with post-pre contrast T1 images, related to tumor blood flow. By combining these, four different habitats are observable with high or low cellularity and/or flow, respectively. In animal models of cancers, these imaged habitats can be co-registered with microscopic analyses to identify the underling physiologic properties of the individual cancer cells and their environment. The cores of tumors and their invasive edges differ in cell composition and protein expression patterns. The magnitude of these differences are prognostic. Larger differences portend poorer outcomes. One protein of interest is carbonic anhydrase 9, CA-IX. It may acidify the local extracellular microenvironment and promote invasion into the surrounding stroma. Therapies to reduce tumor acidity reduce this invasion, and can lead to improved tumor control.

Monday April 9, 2018 2:00pm - 2:15pm CDT
Spire Parlor