MuSIC: Multi-Sequential Interactive Co-Registration for Cancer Imaging Data based on Segmentation Masks

In gynecologic cancer imaging, multiple magnetic resonance imaging (MRI) sequences are acquired per patient to reveal different tissue characteristics. However, after image acquisition, the anatomical structures can be misaligned in the various sequences due to changing patient location in the scanner and organ movements. The co-registration process aims to align the sequences to allow for multi-sequential tumor imaging analysis. However, automatic co-registration often leads to unsatisfying results. To address this problem, we propose the web-based application MuSIC (Multi-Sequential Interactive Co-registration). The approach allows medical experts to co-register multiple sequences simultaneously based on a pre-defined segmentation mask generated for one of the sequences. Our contributions lie in our proposed workflow. First, a shape matching algorithm based on dual annealing searches for the tumor position in each sequence. The user can then interactively adapt the proposed segmentation positions if needed. During this procedure, we include a multi-modal magic lens visualization for visual quality assessment. Then, we register the volumes based on the segmentation mask positions. We allow for both rigid and deformable registration. Finally, we conducted a usability analysis with seven medical and machine learning experts to verify the utility of our approach. Our participants highly appreciate the multi-sequential setup and see themselves using MuSIC in the future. Best Paper Honorable Mention at VCBM2022publishedVersio

Patient-derived organoids reflect the genetic profile of endometrial tumors and predict patient prognosis

Background: A major hurdle in translational endometrial cancer (EC) research is the lack of robust preclinical models that capture both inter- and intra-tumor heterogeneity. This has hampered the development of new treatment strategies for people with EC. Methods: EC organoids were derived from resected patient tumor tissue and expanded in a chemically defined medium. Established EC organoids were orthotopically implanted into female NSG mice. Patient tissue and corresponding models were characterized by mor- phological evaluation, biomarker and gene expression and by whole exome sequencing. A gene signature was defined and its prognostic value was assessed in multiple EC cohorts using Mantel-Cox (log-rank) test. Response to carboplatin and/or paclitaxel was measured in vitro and evaluated in vivo. Statistical difference between groups was calculated using paired t-test. Results: We report EC organoids established from EC patient tissue, and orthotopic organoid-based patient-derived xenograft models (O-PDXs). The EC organoids and O-PDX models mimic the tissue architecture, protein biomarker expression and genetic profile of the original tissue. Organoids show heterogenous sensitivity to conventional chemotherapy, and drug response is reproduced in vivo. The relevance of these models is further supported by the identification of an organoid-derived prognostic gene signature. This signature is vali- dated as prognostic both in our local patient cohorts and in the TCGA endometrial cancer cohort. Conclusions: We establish robust model systems that capture both the diversity of endo- metrial tumors and intra-tumor heterogeneity. These models are highly relevant preclinical tools for the elucidation of the molecular pathogenesis of EC and identification of potential treatment strategies.publishedVersio

Patient-derived organoids reflect the genetic profile of endometrial tumors and predict patient prognosis

Background: A major hurdle in translational endometrial cancer (EC) research is the lack of robust preclinical models that capture both inter- and intra-tumor heterogeneity. This has hampered the development of new treatment strategies for people with EC. Methods: EC organoids were derived from resected patient tumor tissue and expanded in a chemically defined medium. Established EC organoids were orthotopically implanted into female NSG mice. Patient tissue and corresponding models were characterized by mor- phological evaluation, biomarker and gene expression and by whole exome sequencing. A gene signature was defined and its prognostic value was assessed in multiple EC cohorts using Mantel-Cox (log-rank) test. Response to carboplatin and/or paclitaxel was measured in vitro and evaluated in vivo. Statistical difference between groups was calculated using paired t-test. Results: We report EC organoids established from EC patient tissue, and orthotopic organoid-based patient-derived xenograft models (O-PDXs). The EC organoids and O-PDX models mimic the tissue architecture, protein biomarker expression and genetic profile of the original tissue. Organoids show heterogenous sensitivity to conventional chemotherapy, and drug response is reproduced in vivo. The relevance of these models is further supported by the identification of an organoid-derived prognostic gene signature. This signature is vali- dated as prognostic both in our local patient cohorts and in the TCGA endometrial cancer cohort. Conclusions: We establish robust model systems that capture both the diversity of endo- metrial tumors and intra-tumor heterogeneity. These models are highly relevant preclinical tools for the elucidation of the molecular pathogenesis of EC and identification of potential treatment strategies