Auer, Dorothee P.

Abstract Advanced molecular and pathophysiologic characterization of primary central nervous system lymphoma (PCNSL) has revealed insights into promising targeted therapeutic approaches. Medical imaging plays a fundamental role in PCNSL diagnosis, staging, and response assessment. Institutional imaging variation and inconsistent clinical trial reporting diminishes the reliability and reproducibility of clinical response assessment. In this context, we aimed to: (1) critically review the use of advanced positron emission tomography (PET) and magnetic resonance imaging (MRI) in the setting of PCNSL; (2) provide results from an international survey of clinical sites describing the current practices for routine and advanced imaging, and (3) provide biologically based recommendations from the International PCNSL Collaborative Group (IPCG) on adaptation of standardized imaging practices. The IPCG provides PET and MRI consensus recommendations built upon previous recommendations for standardized brain tumor imaging protocols (BTIP) in primary and metastatic disease. A biologically integrated approach is provided to addresses the unique challenges associated with the imaging assessment of PCNSL. Detailed imaging parameters facilitate the adoption of these recommendations by researchers and clinicians. To enhance clinical feasibility, we have developed both “ideal” and “minimum standard” protocols at 3T and 1.5T MR systems that will facilitate widespread adoption.

Abstract Glioblastomas (GBMs) are known to be complex tumors comprising multiple subpopulations of genetically-distinct cancer cells; it is thought that this genetic variation is a major factor in the lack of observed survival benefit of treatment regimes that target one of these subpopulations. The field of radiogenomics seeks to study correlations between MRI patterns and genetic features of GBM tumors. Spatial radiogenomic maps produced using machine-learning (ML) methods that are trained against information from image-localized patient biopsies identify regions where particular cancer sub-populations are predicted to occur within a GBM, thus non-invasively characterizing the regional genetic variability of these tumors. These tumor subpopulations may also interact with one another, in ways which may be of a competitive or cooperative nature to varying degrees. It is important to ascertain the nature of these interactions, as they may have implications for treatment response to targeted therapies, and characterization of the spatio-temporal dynamics of these co-evolving sub-populations will shed light on why some therapies fail. Here we combine mathematical modeling techniques and spatially-resolved radiogenomic maps to study the nature of these interactions between molecularly-distinct GBM subpopulations. We model the interactions between cell populations using a partial differential equation based formalism. The model is parameterized using radiogenomic ML maps from which we infer the nature of interactions between subpopulations. Furthermore, using maps as inputs, the model turns static maps into dynamic information, thus providing insight into how these subpopulations composing the tumor change over time and the effect this has on observed treatment response for individual patients.