Myelin plays a critical role in neuronal signal conduction across the brain as an insulating layer of phospholipid membranes around axons. Myelin formation begins shortly after birth, continuing well into the 5th decade of life in humans, and is the basis for long range neural networks. The degree of myelination and its structure is also a key feature of many neurological disorders, especially demyelinating diseases such as multiple sclerosis, leukodystrophies, and neruodegeneration. In this project, we propose to develop a new MRI method for non-invasive imaging of myelin. It is based on a previously unexplored source of myelin contrast that has been shown in recent ex vivo studies to be originating from protons in the myelin phospholipid membranes. This source of contrast is not exploited by any current MRI methods for imaging myelin because it has a rapid decay rate (ultrashort-T2), meaning its signal has decayed by the time data is acquired using conventional approaches. We will use methods based on ultra- short echo time (UTE) MRI that leverage specialized excitations, acquisitions, and reconstructions in order to detect such rapidly decaying components. While current MRI methods for imaging myelin, including magnetization transfer, diffusion, and myelin water fractions, rely on detection of signal from protons in water, this new source of contrast comes directly from protons in the myelin phospholipid membranes. We believe that this could provide more specific imaging of myelin and thus could provide a more specific imaging biomarker of myelination, demyelination, dysmyelination, and remyelination. As a more specific biomarker, imaging this membrane component could improving our understanding of brain development as well as be applied for diagnosis, localization, surgical planning, and monitoring response to treatment in many disorders. As this source of contrast is largely unexplored, we first propose to characterize its MRI properties in human studies, both in healthy volunteers of various ages as well as multiple sclerosis patients with previously identified demyelinating lesions. This will provide an initial evaluation of this largely unexplored source of contrast in normal appearing gray and white matter as well as in demyelinated lesions. Since these complete characterization studies will require long scan times, we will also develop SNR and contrast efficient imaging methods based on UTE MRI in order to enable widespread measurements of this source of contrast in future clinical evaluation studies.
In this project we propose to explore a new source of contrast for imaging myelin, which plays a critical role in neuronal networks throughout the brain. We will develop and apply novel ultra-short echo time magnetic resonance imaging (MRI) methods to provide new information that maybe extremely valuable for studying brain development as well as diagnosis, localization, surgical planning, and monitoring response to treatment in many neurodegenerative disorders, such as multiple sclerosis, leukodystrophies, and Alzheimers disease. This project will also explore the clinical potential of these novel methods through studies in multiple sclerosis patients with known demyelinating lesions.
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