Combining P-H 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 (H) exclusively to generate contrast. Phosphorus (P) 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, P may provide richer and more specific ways to probe the myelin bilayers. Key experiments aimed at developing MRI compatible probes of myelin P are demonstrated. First, a solid-state NMR technique, cross polarization (CP) is compared with single pulse excitation in white matter. The H-P CP spectrum retains the morphology sensitive P powder pattern of the single-pulse spectrum, but lacks the aqueous P peak. Second, by combining magnetization transfer (MT) with CP, we observe bi-directional polarization exchange between myelin P and surrounding water, apparently proceeding through a unique H pool that is distinct from the H that typically dominates MT. Pulsed magnetic field gradients are used to isolate magnetization that originates from myelin P and transferred to aqueous H. This small signal, approximately 1/68,000 that of the H 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 P 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.