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Objective: Regorafenib demonstrated efficacy in patients with metastatic colorectal cancer (mCRC). Lack of predictive biomarkers, potential toxicities and cost-effectiveness concerns highlight the unmet need for better patient selection.\ud \ud Design: Patients with RAS mutant mCRC with biopsiable metastases were enrolled in this phase II trial. Dynamic contrast-enhanced (DCE) MRI was acquired pretreatment and at day 15 post-treatment. Median values of volume transfer constant (Ktrans), enhancing fraction (EF) and their product KEF (summarised median values of Ktrans× EF) were generated. Circulating tumour (ct) DNA was collected monthly until progressive disease and tested for clonal RAS mutations by digital-droplet PCR. Tumour vasculature (CD-31) was scored by immunohistochemistry on 70 sequential tissue biopsies.\ud \ud Results: Twenty-seven patients with paired DCE-MRI scans were analysed. Median KEF decrease was 58.2%. Of the 23 patients with outcome data, >70% drop in KEF (6/23) was associated with higher disease control rate (p=0.048) measured by RECIST V. 1.1 at 2 months, improved progression-free survival (PFS) (HR 0.16 (95% CI 0.04 to 0.72), p=0.02), 4-month PFS (66.7% vs 23.5%) and overall survival (OS) (HR 0.08 (95% CI 0.01 to 0.63), p=0.02). KEF drop correlated with CD-31 reduction in sequential tissue biopsies (p=0.04). RAS mutant clones decay in ctDNA after 8 weeks of treatment was associated with better PFS (HR 0.21 (95% CI 0.06 to 0.71), p=0.01) and OS (HR 0.28 (95% CI 0.07–1.04), p=0.06).\ud \ud Conclusions: Combining DCE-MRI and ctDNA predicts duration of anti-angiogenic response to regorafenib and may improve patient management with potential health/economic implications.

Despite the utility of tumour characterisation using quantitative parameter maps from multi-b-value diffusion-weighted MRI (DWI), clinicians often prefer the use of the image with highest diffusion-weighting (b-value), for instance for defining regions of interest (ROIs). However, these images are typically degraded by noise, as they do not utilize the information from the full acquisition. We present a principal component analysis (PCA) approach for model-free denoising of DWI data. PCA-denoising was compared to synthetic MRI, where a diffusion model is fitted for each voxel and a denoised image at a given b-value is generated from the model fit. A quantitative comparison of systematic and random errors was performed on data simulated using several diffusion models (mono-exponential, bi-exponential, stretched-exponential and kurtosis). A qualitative visual comparison was also performed for in vivo images in six healthy volunteers and three pancreatic cancer patients. In simulations, the reduction in random errors from PCA-denoising was substantial (up to 55%) and similar to synthetic MRI (up to 53%). Model-based synthetic MRI denoising resulted in substantial (up to 29% of signal) systematic errors, whereas PCA-denoising was able to denoise without introducing systematic errors (less than 2%). In vivo, the signal-to-noise ratio (SNR) and sharpness of PCA-denoised images were superior to synthetic MRI, resulting in clearer tumour boundaries. In the presence of motion, PCA-denoising did not cause image blurring, unlike image averaging or synthetic MRI. Multi-b-value MRI can be denoised model-free with our PCA-denoising strategy that reduces noise to a level similar to synthetic MRI, but without introducing systematic errors associated with the synthetic MRI method.

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.

This thesis presents technical and methodological developments aiming tooffer a viable alternative for the treatment of digestive cancers (rectum and esophagus). Compared to the standard methods of therapy, the high intensity contact ultrasound guided by MRI is a less invasive approach. MRI offers 2 advantages: good spatial resolution, and real-time temperature control. This treatment method requires efficacy and safety. Three prototypes of RF coil integrated with ultrasound transducers were built in order to increase the spatial and temporal resolution ofthe MR images, and the accuracy of the temperature measurement. The integrated coils showed a better sensitivity compared to a standard extracorporeal coil. Anatomical (voxel 0.4x0.4x5 mm3)and thermometry (voxel 0.75x0.75x8 mm3, 2s/image) high resolution MR images were acquired in-vivo. The temperature was measured, within a radius of 20 mm from the balloon, with a standard deviation, Cette thèse présente des développements techniques et méthodologiques visant une alternative viable pour le traitement des cancers digestifs (rectum, œsophage). Par rapport aux méthodes standards de thérapie, les ultrasons de contact de haute intensité sous guidage IRM sont une approche moins invasive. L’IRM offre 2 avantages: bonne résolution spatiale et contrôle en temps réel de la température. Cette méthode de traitement demande efficacité et sécurité. Trois prototypes d’antenne RF intégrées à des transducteurs ultrasonores ont été réalisés afin d’améliorer la résolution spatiale et temporelle des images IRM et la précision de la mesure de température. Les antennes intégrées ont montré une meilleure sensibilité par rapport à une antenne extra corporelle standard. Des images IRM haute résolution, anatomiques (voxel0.4x0.4x5 mm3) et de thermométrie (voxel 0.75x0.75x8 mm3, 2s/image) ont été acquises in-vivo.La température a été mesurée, dans un rayon de 20 mm au-delà du ballon, avec un écart type