Capturing Tumor Heterogeneity in Hepatocellular Carcinoma- A Radiomics Approach Systematically Tested in Transgenic Mice

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Radiomics seem to offer great solutions for many as of yet unsolved tasks in medicine. Integrating multimodality data from genetic and molecular analyses with high-end diagnostic imaging methods will revolutionize disease diagnosis to a great extent. Thus, Radiomics could open the door for entry of precision medicine into clinical routine by linking tumor heterogeneity with outcome prediction, a prerequisite for individualized treatment. However, since this methodology is at the very beginning of clinical evaluation with various influencing factors, some of which are not yet well-understood, standardized testing is required to evaluate its potential and to uncover any currently unknown limitations. Moreover, in contrast to our today`s clinical workflow Radiomics will require highly transdisciplinary teams with a strong focus on mathematics and informatics.With this research proposal we submit a highly multidisciplinary approach for the implementation of Radiomics to study hepatocellular cancer. Due to the limitations of standard diagnostic procedures in both primary diagnosis of HCC as well as treatment response assessment, the purpose of this proposal is to develop a radiomics approach for advanced molecular diagnosis of HCC that captures the complexity of (intra-)tumoral heterogeneity and treatment response patterns induced by an established Multi Kinase Inhibitor. The ultimate goal is to identify imaging and non-imaging based biomarkers by a systematic radiomics analysis that can identify and predict treatment response. We hypothesize that radiomics could offer a promising approach for both, (i) an advanced characterization of primary hepatocellular carcinoma based on innovative imaging that involves molecular as well as genetic correlates and (ii) the delineation of cellular/molecular processes affected by MKI treatment. Testing radiomics systematically under the standardized conditions of established animal models will control experimental variance of the entire system to an extent that is not possible in humans.To adress this complex topic the work programme will be performed by a highly transdisciplinary research team, consisting of five principal investigators from radiology, biochemistry, medical physics, instrumental bioanalytics and applied computer science.