Combining 31P-1H Cross Polarization With Magnetization Transfer: A Novel Approach for Myelin Investigation.

MRI is a crucial tool for studying white matter, which is primarily composed of myelin, a phospholipid-rich sheath surrounding nerve fibers. Myelin damage leads to disrupted neurological function, which is a prominent feature in neurodegenerative diseases like multiple sclerosis. Current MRI techniques for detecting myelin use hydrogen nuclei (1H) exclusively to generate contrast. Phosphorus (31P) is highly concentrated in myelin phospholipids relative to other brain structures. Due to sensitivity of the anisotropic chemical shifts and dipolar couplings to structure and dynamics, 31P may provide richer and more specific ways to probe the myelin bilayers. Key experiments aimed at developing MRI compatible probes of myelin 31P are demonstrated. First, a solid-state NMR technique, cross polarization (CP) is compared with single pulse excitation in white matter. The 1H-31P CP spectrum retains the morphology sensitive 31P powder pattern of the single-pulse spectrum, but lacks the aqueous 31P peak. Second, by combining magnetization transfer (MT) with CP, we observe bi-directional polarization exchange between myelin 31P and surrounding water, apparently proceeding through a unique 1H pool that is distinct from the 1H that typically dominates MT. Pulsed magnetic field gradients are used to isolate magnetization that originates from myelin 31P and transferred to aqueous 1H. This small signal, approximately 1/68,000 that of the 1H water signal, could offer access to structural and dynamic information from the membrane/water interface not previously available. This two-step transfer process opens new possibilities for understanding myelin and white matter disease and injury. These proof-of-principle findings may have broad implications for both basic neuroscience and clinical imaging. By leveraging 31P as a myelin probe, this approach offers a novel tool for studying myelin and could aid in detection and treatment monitoring of white matter disease and injury. Future work will investigate the translation of this technique to MRI.