Towards optimal diffusion MRI tractography and validation

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The connectome, a novel term for the neuronal map of connections, is at the heart of modern neuroimaging. It is in fact creating a new field of Computer Science called neuroinformatics. Neurodegenerative diseases, developmental disorders, brain tumors and traumatic brain injuries affect a large proportion of the Canadian population. It remains unknown how fiber connections in the white matter are altered, degenerated and damaged by these disorders. Diffusion magnetic resonance imaging (dMRI) is the only non-invasive technique able to image the neural architecture of the white matter and better understand how the brain is wired. Diffusion MRI is thus a tool to measure the connectome for short and long distances connections at the millimeter scale. ***A crucial part of mapping the white matter connectome are measurements computed from dMRI tractography. Tractography is the computerized process of reconstructing white matter fiber bundles. Unfortunately, current tractography techniques do not control for invalid tracts produced by algorithms. As of today, the lack of accuracy in published works using tractography is well known but has mostly been overlooked because there are no public databases to validate techniques. There is mounting evidence that tractography errors can lead to wrong connectivity interpretations.***The main objective of my research program is thus to develop a state-of-the-art diffusion MRI processing pipeline to improve the reproducibility and accuracy of tractography. A short-term objective is to propose a unique validation mechanism with new datasets, from phantom ex vivo datasets and scan/rescan real datasets, added on the Tractometer, a novel online evaluation system that will include innovative connectivity metrics. A mid-term objective is to develop a novel global tractography framework based on state-of-the-art processing steps. This optimized diffusion MRI processing pipeline will integrate all steps from acquisition, image correction and preprocessing, local modeling, fiber tractography and visualization tools to study anatomical connectivity and tissue microstructure. As a long-term objective, I will propose new micro-tractography techniques to validate fiber tractography methods using novel realistic phantom simulations, new MRI and optical coherence tomography acquisitions on ex vivo and in vivo small animal models dedicated to image white matter at the microscopic scale.***The potential value of having a mechanism for validation of tractography protocols is very high. This will have a significant impact on neurosciences at large. Students under my supervision will be in a multi-disciplinary area, surrounded by state-of-the-art equipment, rich local and international collaborations at the frontiers of Computer Science and Medecine.**