Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland.
Center for Biomedical Imaging, New York University School of Medicine, New York, NY, USA.
Nat Commun. 2021 May 19;12(1):2941. doi: 10.1038/s41467-021-22719-7.
Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin's nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method's sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.
髓鞘为神经元轴突提供绝缘，并促进快速信号传递，是大脑发育、衰老和疾病的关键组成部分。然而，对宏观样本的髓鞘特异性成像仍然是一个挑战。在这里，我们利用髓鞘的纳米结构周期性，使用小角 X 射线散射张量断层扫描（SAXS-TT）技术，同时定量分析神经组织中的髓鞘水平、纳米结构完整性和轴突取向。在整个小鼠大脑、小鼠脊髓以及人类白质和灰质样本中进行了原理验证。通过 2D/3D 组织学和与对髓鞘和轴突取向敏感的 MRI 测量结果进行比较，对结果进行了验证。通过对具有不同周期性的不同髓鞘类型进行同时成像，证明了该方法对纳米结构的特异性。最后，我们通过定量分析脱髓鞘小鼠大脑中的髓鞘改变，说明了该方法对与髓鞘相关疾病的敏感性。这种非破坏性、无染色的分子成像方法能够在发育、衰老、疾病和治疗过程中对样本内和样本间的髓鞘形成进行定量研究，并且适用于其他有序生物分子或纳米结构。
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