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.