Myelin damage and abnormal myelination frequently accompany various pathological processes in the central nervous system at different stages of neurodevelopment. The availability of a technology capable to non- invasively visualize and quantify myelin in CNS would substantially enrich both clinical and fundamental neuroscience research. A newly emerged quantitative MRI method enables fast and robust in vivo mapping of the brain and spinal cord myelination based on the physical principle of measuring macromolecular proton fraction (MPF). MPF is a biophysical parameter that describes the amount of macromolecular protons involved into magnetization exchange with free water protons in biological systems. During past decade, MPF has attracted remarkable attention as a quantitative biomarker of myelin due to its high sensitivity to demyelination in normal-appearing white and gray matter and strong correlations between MPF and histologically determined myelin content. However, widespread applications of MPF have been limited due to the absence of methods allowing fast and reliable in vivo measurements of this parameter. A recently developed fast MPF mapping method has introduced a principally new approach for MPF measurements, achieved critical improvement in time efficiency, and greatly simplified image acquisition and processing. In its current state, fast MPF mapping fully addresses the unmet need of the neuroscience research community in a reliable, quantitative, and simple imaging biomarker of the myelin content in neural tissues. The ultimate goals of the proposed R24 resource are to make MPF mapping easily accessible to the users of most widely available human and animal MRI equipment based on standard manufacturers' software, employ it in a wide range of neuroscience research projects, and enable clinical translation. To achieve these goals, the following specific aims will be accomplished: (1) standardize fast MPF mapping for most widely used human and animal MRI platforms based on a set of ready-for-use protocols for human whole-body 1.5T and 3T MRI systems manufactured by Philips, Siemens, and General Electric and animal 7T, 9.4T, 11.7T, 14T, and 16.4T MRI systems manufactured by Bruker and Varian/Agilent with a post-processing algorithm for correction of potential platform-dependent biases in MPF maps; (2) enable widespread distribution of the MPF mapping technology based on a standard user package that will include electronic versions of MPF mapping protocols, standalone reconstruction software, standard operating procedures for protocol execution and image processing, quality assurance phantom, and training materials; and (3) deploy the fast MPF mapping technology at 17 or more national and international sites to be applied in a broad range of clinical and preclinical neuroscience research. The project activities will be carried out during four years, involve comprehensive metrological assessment of the MPF mapping technology in humans and animals, and will be guided by the Steering Committee representing senior investigators from the University of Washington and collaborating institutions.
The proposed resource will enable a previously unavailable measurement capability targeted at the assessment of myelination that is one of most clinically and physiologically relevant brain tissue characteristics. The widespread use of new technology will result in gaining new fundamental knowledge about the central nervous system and applications of this knowledge to reduce the burden of neurological disease, specifically, by introducing a new biomarker that could facilitate the development of new therapies and diagnostic criteria. Such applications include all primary demyelinating diseases, traumatic brain injury, stroke, neurodegenerative and other diseases where myelin damage may occur, as well as normal or abnormal pre- and post-natal brain development.
