Laboratory for Structural NMR Imaging, Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9605-10. doi: 10.1073/pnas.1115107109. Epub 2012 May 24.
Magnetic resonance imaging has previously demonstrated its potential for indirectly mapping myelin density, either by relaxometric detection of myelin water or magnetization transfer. Here, we investigated whether myelin can be detected and possibly quantified directly. We identified the spectrum of myelin in the spinal cord in situ as well as in myelin lipids extracted via a sucrose gradient method, and investigated its spectral properties. High-resolution solution NMR spectroscopy showed the extract composition to be in agreement with myelin's known chemical make-up. The 400-MHz (1)H spectrum of the myelin extract, at 20 °C (room temperature) and 37 °C, consists of a narrow water resonance superimposed on a broad envelope shifted ∼3.5 ppm upfield, suggestive of long-chain methylene protons. Superimposed on this signal are narrow components resulting from functional groups matching the chemical shifts of the constituents making up myelin lipids. The spectrum could be modeled as a sum of super-Lorentzians with a T(2)* distribution covering a wide range of values (0.008-26 ms). Overall, there was a high degree of similarity between the spectral properties of extracted myelin lipids and those found in neural tissue. The normalized difference spectrum had the hallmarks of membrane proteins, not present in the myelin extract. Using 3D radially ramp-sampled proton MRI, with a combination of adiabatic inversion and echo subtraction, the feasibility of direct myelin imaging in situ is demonstrated. Last, the integrated signal from myelin suspensions is shown, both spectroscopically and by imaging, to scale with concentration, suggesting the potential for quantitative determination of myelin density.
磁共振成像先前已经证明了其通过弛豫检测髓磷脂水或磁化转移来间接绘制髓磷脂密度图的潜力。在这里,我们研究了是否可以直接检测和可能定量髓磷脂。我们在脊髓原位和通过蔗糖梯度法提取的髓磷脂脂质中鉴定了髓磷脂的光谱,并研究了其光谱特性。高分辨率溶液 NMR 光谱显示提取物的组成与髓磷脂的已知化学组成一致。髓磷脂提取物的 400-MHz(1)H 光谱,在 20°C(室温)和 37°C,由一个窄的水共振叠加在一个宽的包络上,向上场移动约 3.5 ppm,提示长链亚甲基质子。在这个信号上叠加了窄的组件,这些组件来自与构成髓磷脂脂质的成分的化学位移匹配的官能团。该光谱可以建模为具有覆盖广泛值范围(0.008-26ms)的 T(2)*分布的超洛伦兹的总和。总体而言,提取的髓磷脂脂质的光谱特性与神经组织中的那些非常相似。归一化差谱具有膜蛋白的特征,不存在于髓磷脂提取物中。使用具有绝热反转和回波相减的 3D 径向斜坡采样质子 MRI,证明了在原位直接成像髓磷脂的可行性。最后,展示了髓磷脂悬浮液的积分信号,无论是通过光谱还是成像,都与浓度成比例,表明髓磷脂密度定量测定的潜力。