Optimising the generation of human structural connectome: the development of a novel diffusion MRI fibre tracking framework with surface-based anatomical priors

The considerable investment and continuous effort in the “Human Connectome Project” internationally have prompted flourishing research activities in the emerging brain connectomics field. Connectomics aims at understanding the structural and functional connectivity of the human brain and at discovering the neural substrates underlying cognition and behaviour in either healthy or diseased states. Diffusion magnetic resonance imaging (MRI) is the primary method of choice for the identification of the macro-scale structural connectome, i.e. the comprehensive white matter fibre connections among distinct brain areas, as it is currently the only non-invasive neuroimaging technique available for providing such information in living human brains using so-called fibre tracking or tractography.Brain connectomics approach has been widely employed in neuroscience research. However, recent studies have demonstrated that inappropriate design of a connectome construction pipeline can bias the resultant connectome significantly, thereby making subsequent connectomic analysis and inferences hard to be justified. The generation of a tractography-based structural connectome from raw diffusion MRI data involves a series of complicated data processing steps with a wide range of practical decisions to make. Notably, a significant source of bias in connectome quantification in fact results primarily from the ill-posed nature of diffusion MRI tractography methods per se, which is a critical universal issue that researchers seek to resolve.This research proposal constitutes an opportunity to achieve a great advance in a highly active area by the technical expertise in MRI methods. This will require the implementation of cutting-edge methods, as well as the development and testing of novel technical advances. Specifically, new methods are required to optimise structural connectome generation of the human brain via the creation of a novel tractography framework, in which accurate anatomical priors from high-resolution surface modelling of brain tissues will be employed to ensure biologically plausible cortico-cortical fibre connections. Since tractography represents the current state-of-the-art for in vivo measurement of fibre connectivity, the advancement of such a technique is of crucial importance. The resultant advance in our knowledge of how to optimise brain connectome generation would have widespread implications for neuroscience, in particular through its fundamental relevance to the multiple human connectome projects currently underway internationally. It will advance understanding of brain circuitry and provide information for development of imaging and post-processing methods to measure brain connectivity and related metrics. This research project would also be beneficial for future investigations of such as the developing or ageing brain, and new technologies that are based on structural neuroimaging may reveal relationships of pathophysiology in disease models with a mild, pre-dementia symptom. And last but not least, development of new technologies outlined in this project can be combined with the existing neuroimaging modalities where the information can be measured natively on the brain cortical surface, such as cortical folding and thickness, and brain activity using electroencephalography (EEG), functional MRI (fMRI), or positron emission tomography (PET). These neuroimaging techniques can be combined to quantify in vivo functional-structural changes to understand underlying mechanisms of early neurological development.

Project ID:PB10909-0021
External Project ID:MOST109-2222-E182-001-MY3