MRI and Structural Connectivity

Structure and function are linked; this wide-spread connection is true in many aspects of nature as well as in the brain. Indeed, one of the basic concepts in neuroscience is the circular relationship between behavioral performance, brain functionality and neuronal micro- and macro-structural architecture (structural connectivity). The field of brain mapping has evolved tremendously since the introduction of non-invasive imaging techniques (i.e. MRI). Functional MRI (fMRI) revolutionized our understanding on the brain regional localization of specific cognitive domains and fine behavioral processes. However, a missing component in non-invasive brain mapping is the assessment of structural connectivity at different spatial scales (micron level to the whole brain) – this is the core of the CONNECT project.

In recent years, diffusion MRI has become an extremely popular tool for studying the morphology of brain tissue, as it provides unique insights into both its macrostructure and microstructure. The technique measures scattering of water molecules through diffusion within tissue. Since the microstructure of the tissue determines the water mobility, the measured scatter pattern supports inferences about the tissue microstructure. White matter, for example, is the brain’s connective cabling and contains bundles of parallel axon fibres. Water molecules move preferentially along the bundle and diffusion MRI reveals the dominant orientation of the axons very clearly. This particular unique piece of microstructural information leads to unique macrostructural information about white matter organization and the connectivity of the brain: tractography (fibre tracking) algorithms follow fibre orientation estimates from point to point to reconstruct the white matter pathways and reveal the global connectivity of the brain. This unique insight into both tissue microstructure and connectivity has enormous potential value. Changes in tissue microstructure are often the earliest signs of disease or the effect of a treatment, but are mostly only measurable using microscopy on excised tissue samples. Detailed knowledge of the brain’s structural connectivity has the potential to revolutionize neuroscience, but can only be established otherwise through painstaking tracer studies on post-mortem tissue. However, development of diffusion MRI paradigms and processing algorithms is at an early stage and the reliability and accuracy of the information they provide remain unclear.

Quantification of brain micro-structural features is currently only achieved through invasive histological techniques. The CONNECT project will develop diffusion MRI into a true microstructural probe that will enable virtual biopsy and virtual dissection of the human brain in-vivo reliably and non-invasively. As such the main impact of the Consortium will be to develop diffusion-based MRI to such an extent that it becomes a robust and reliable tool with which to investigate white matter and its connections both in routine clinical and neuroscience research settings. This unprecedented insight into white matter will open up new realms of possibilities in terms of both diagnostic and therapeutic strategies, as well as providing fundamental new insights to the connectivity and workings of the brain. By being able to probe white matter to this new level of detail, and combined with detailed assessment of brain function, we will obtain an unparalleled holistic view of the brain.