Anatomy-Driven Brain Connectivity Mapping

The connectome, the comprehensive map of neural connections in the human brain, is unique in every individual. Even identical twins differ at the level of neural connectivity. Mapping the human connectome and its variability across individuals is essential in getting insight into the unknown cognitive aspects of brain function, but also into identifying dysfunctional features of the diseased brain.
For these reasons, understanding the human brain, its organisation and ultimately its function, is amongst the key scientific challenges of the 21st century. Magnetic resonance imaging (MRI) has revolutionised neuroscience by uniquely allowing both brain anatomy and function to be probed in living humans. Even if MRI allows only macroscopic features to be recovered (at the level of relatively large tissue regions, rather than individual neuronal cells), its non-invasive and in-vivo application has opened tremendous possibilities for brain research. Diffusion-weighted MRI (dMRI) is a particular modality that uniquely allows the mapping of fibre bundles, the underlying connection pathways that mediate information flow between different brain regions. The connection mapping is performed indirectly by processing dMRI images via computational algorithms referred to as tractography.
Tractography has already provided fundamental new insights into brain anatomy. The importance of brain connectivity to our understanding of the brain along, with the great potential revealed by tractography algorithms have led to large initiatives from both sides of the Atlantic. These utilise dMRI to collect state-of-the-art datasets of the healthy adult and the developing brain and map the structural connectome through tractography. They include the $30M NIH Human Connectome Project, the 15M Euros ERC Developing Human Connectome Project and the £30M UK funded Biobank Imaging. However, without state-of-the-art analysis methods, and new ways of analysing dMRI data, researchers will fail to get the most out of this vast wealth of upcoming data.
In this project, we propose new frameworks for tractography methods centred on neuroanatomy. We particularly focus on problems arising from ambiguous mapping of complex geometries (which are very common in the brain) to the dMRI measurements. These pose significant limits to the accuracy of existing approaches. We propose wholesale changes through computational and algorithmic solutions that will allow connections to be measured in-vivo with unprecedented detail, whole brain organization to be studied at a much finer scale and anatomical features -invisible to existing techniques- to be revealed. These advances will open new possibilities for neuroanatomical studies, but also set the foundations for new basic research in MRI processing and connectivity mapping. We will illustrate their potential using compelling demonstrator applications from basic and clinical neuroscience, including the assessment of benefits from using the new technology in assisting neurosurgical planning.

This research provides the technological innovation that is essential for understanding and modelling human brain as an integrated network. The research output will have a transformative impact on science, from basic neuroscience to neurology, psychology and psychiatry, on pharmaceutical industry, and ultimately on the society as a whole, from the wellbeing of an individual to the care of patients suffering from neurological disorders.
There will be immediate impact on clinical and basic neuroscience researchers worldwide. The proposed advances to brain connectivity mapping open new, exciting possibilities for in vivo studies of neuroanatomy and neuropathology. For instance, differences in connectivity patterns can be used to identify functionally segregated regions; the anatomical substrate of behavior/cognition can be explored; connectivity changes may serve as disease biomarkers. Our two groups are the authors of the two leading software packages for diffusion imaging, FSL and CAMINO, ensuring the successful and timely realisation of this impact.
The impact on clinical and basic neuroscience will lead to additional impact on the downstream disciplines such as neurology, psychology and psychiatry. A better understanding of the organisation of the brain network is prerequisite to the investigation into the alteration of this network in diseased states from various brain and mental disorders. This will lead to a deeper understanding of the aetiology of these disorders.
The impact on neurology, psychology and psychiatry will in turn benefit pharmaceutical industry. Improved understanding of the aetiology of the various brain and mental disorders will allow the identification of new therapeutic approaches and targets. This creates opportunities to develop novel disease-modifying treatments.
Ultimately, the combinations of these advances will benefit the society as well. A deeper understanding of the inner workings of our brain will allow individuals to take preventive measures to ensure the long-term wellbeing of their minds. New and improved treatments for brain and mental disorders will improve patient outcome and the quality of living of themselves and their carers.