Ensworth Alex G, Knight Cariad A, Laule Cornelia, MacKay Alex L, Michal Carl A
Department of Physics & Astronomy, The University of British Columbia, Vancouver, Canada.
International Collaboration on Repair Discoveries (ICORD), The University of British Columbia, Vancouver, Canada.
NMR Biomed. 2025 Aug;38(8):e70086. doi: 10.1002/nbm.70086.
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.
磁共振成像（MRI）是研究白质的关键工具，白质主要由髓磷脂组成，髓磷脂是一种富含磷脂的围绕神经纤维的鞘。髓磷脂损伤会导致神经功能紊乱，这是多发性硬化症等神经退行性疾病的一个突出特征。目前用于检测髓磷脂的MRI技术仅使用氢核（H）来产生对比度。相对于其他脑结构，磷（P）在髓磷脂磷脂中高度浓缩。由于各向异性化学位移和偶极耦合对结构和动力学的敏感性，P可能提供更丰富、更具体的方法来探测髓磷脂双层。展示了旨在开发与MRI兼容的髓磷脂P探针的关键实验。首先，将一种固态核磁共振技术——交叉极化（CP）与白质中的单脉冲激发进行比较。H-P CP谱保留了单脉冲谱中对形态敏感的P粉末图案，但没有水相P峰。其次，通过将磁化传递（MT）与CP相结合，我们观察到髓磷脂P与周围水之间的双向极化交换，显然是通过一个独特的H池进行的，这个H池与通常主导MT的H不同。脉冲磁场梯度用于分离源自髓磷脂P并转移到水相H的磁化。这个小信号约为H水信号的1/68000，可能提供从膜/水界面获取以前无法获得的结构和动力学信息的途径。这个两步转移过程为理解髓磷脂以及白质疾病和损伤开辟了新的可能性。这些原理验证结果可能对基础神经科学和临床成像都有广泛的影响。通过利用P作为髓磷脂探针，这种方法为研究髓磷脂提供了一种新颖的工具，并有助于白质疾病和损伤的检测及治疗监测。未来的工作将研究这种技术向MRI的转化。
