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Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution., A combined modelling and tumour analysis approach is used to study the temporal and spatial patterns of subclone evolution in the TRACERx renal study. Studying the tumour shape and spatial features of clonal diversity in early-stage tumours may allow the prediction of tumour progression and patterns of subclone diversification over time.

Purpose: XNAT is an informatics software platform to support imaging research, particularly in the context of large, multicentre studies of the type that are essential to validate quantitative imaging biomarkers. XNAT provides import, archiving, processing and secure distribution facilities for image and related study data. Until recently, however, modern data visualisation and annotation tools were lacking on the XNAT platform. We describe the background to, and implementation of, an integration of the Open Health Imaging Foundation (OHIF) Viewer into the XNAT environment. We explain the challenges overcome and discuss future prospects for quantitative imaging studies. Materials and methods: The OHIF Viewer adopts an approach based on the DICOM web protocol. To allow operation in an XNAT environment, a data-routing methodology was developed to overcome the mismatch between the DICOM and XNAT information models and a custom viewer panel created to allow navigation within the viewer between different XNAT projects, subjects and imaging sessions. Modifications to the development environment were made to allow developers to test new code more easily against a live XNAT instance. Major new developments focused on the creation and storage of regions-of-interest (ROIs) and included: ROI creation and editing tools for both contour- and mask-based regions; a “smart CT” paintbrush tool; the integration of NVIDIA’s Artificial Intelligence Assisted Annotation (AIAA); the ability to view surface meshes, fractional segmentation maps and image overlays; and a rapid image reader tool aimed at radiologists. We have incorporated the OHIF microscopy extension and, in parallel, introduced support for microscopy session types within XNAT for the first time. Results: Integration of the OHIF Viewer within XNAT has been highly successful and numerous additional and enhanced tools have been created in a programme started in 2017 that is still ongoing. The software has been downloaded more than 3700 times during the course of the development work reported here, demonstrating the impact of the work. Conclusions: The OHIF open-source, zero-footprint web viewer has been incorporated into the XNAT platform and is now used at many institutions worldwide. Further innovations are envisaged in the near future.

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Purpose\ud \ud To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations.\ud \ud \ud Materials and Methods\ud \ud Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups.\ud \ud \ud Results\ud CoV aggregated across all studies was 4.1% (range for each study, 1.7%–6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = −0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies—a difference that did not persist after the study with the largest tumors was excluded.\ud \ud \ud Conclusion\ud \ud ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations.

International audience; Synchrotron microbeam radiation therapy (MRT) is an advanced form of radiotherapy for which it is extremely difficult to provide adequate quality assurance. This may delay or limit its clinical uptake, particularly in the paediatric patient populations for whom it could be especially suitable. This study investigates the extent to which new developments in 3D dosimetry using optical computed tomography (CT) can visualise MRT dose distributions, and assesses what further developments are necessary before fully quantitative 3D measurements can be achieved. Two experiments are reported. In the first cylindrical samples of the radiochromic polymer PRESAGE (R) were irradiated with different complex MRT geometries including multiport treatments of collimated 'pencil' beams, interlaced microplanar arrays and a multiport treatment using an anthropomorphic head phantom. Samples were scanned using transmission optical CT. In the second experiment, optical CT measurements of the biologically important peak-to-valley dose ratio (PVDR) were compared with expected values from Monte Carlo simulations. The depth-of-field (DOF) of the optical CT system was characterised using a knife-edge method and the possibility of spatial resolution improvement through deconvolution of a measured point spread function (PSF) was investigated. 3D datasets from the first experiment revealed excellent visualisation of the 50 mu m beams and various discrepancies from the planned delivery dose were found. The optical CT PVDR measurements were found to be consistently 30% of the expected Monte Carlo values and deconvolution of the microbeam profiles was found to lead to increased noise. The reason for the underestimation of the PVDR by optical CT was attributed to lack of spatial resolution, supported by the results of the DOF characterisation. Solutions are suggested for the outstanding challenges and the data are shown already to be useful in identifying potential treatment anomalies