New methods to quantify axonal magnetic properties and myelin integrity using MRI

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Myelin is a key component of brain function and structure, specifically in white matter (WM). It is an insulating layer of lipids and proteins covering many of the brain's axons that aids in the transmission of action potentials. If compromised it disrupts the axons' ability to transmit information which reduces the brain's ability to function. Myelin is especially of interest when considering illnesses such as multiple sclerosis (MS), which involves the demyelination of nerves within the brain and spinal cord. Therefore developing methods to accurately quantify myelin status is of high clinical importance.Current methods of mapping myelin non-invasively using Magnetic Resonance Imaging (MRI) rely on the magnetic field inhomogeneities induced by myelin's paramagnetic properties. Susceptibility tensor imaging (STI) is a MRI technique that maps the magnetic field inhomogeneities induced by myelin, providing a non-invasive way of assessing myelination. However, STI requires a complex acquisition where a patient is physically rotated inside the scanner in order to obtain information about the myelin anisotropy and orientation. This means that STI is not always applicable to the wider clinical environment. An alternative approach is quantitative susceptibility mapping (QSM) which also maps the field inhomogeneities induced by myelin, but it cannot characterize the myelin anisotropy and orientation. This project will establish a novel paradigm by developing Magnetic Susceptibility Interference MRI (MSI): exploiting magnetic field gradients typically used to sensitize the MRI signal to water diffusion in conventional diffusion-weighted MRI (dMRI) to probe the microscopic magnetic field gradients induced by the local microstructure and distribution of myelin susceptibility. Our objectives are:(a) Developing MSI's core: a biophysical model describing the effects on measured dMRI signals of the interference of diffusion-sensitizing magnetic field gradients with the myelin-induced microscopic field inhomogeneities(b) Developing computational tools to estimate myelin anisotropic susceptibility by inverting the forward model in (a) using simulation-based/likelihood-free machine learning methods(c) Demonstrating MSI using a unique dataset of STI/dMRI data acquired in-vivo in healthy and demyelinating rat brains(d) Demonstrating MSI in humans by optimising the acquisition and analysing new data collected in healthy volunteers and MS patients at 7T in the Cardiff University Brain Research Imaging Centre (CUBRIC).The proposed research will develop brand new imaging techniques that will have a transformative impact on understanding key constituents of brain function and provide a whole new avenue of research programmes aimed at characterising tissue state in-vivo. A non-invasive methodology to quantify in-vivo the brain WM state, myelin formation during normal and abnormal development and myelin breakdown in disease will allow for new insights into the basic understanding of brain physiology. The unique dataset of dMRI/STI/MSI data will offer a precious resource for understanding and extracting new clinically relevant information from medical images, which is of great value to the Medical Imaging research area. Potential for accurate quantification of how and how much brain WM myelination changes over time due to disease or other factors has implications for medical diagnosis, precision medicine, disease-modifying drug discovery, personalized treatment, monitoring or a more in-depth understanding of how such factors affect the brain.