在11.7 T下重新审视小鼠脑中的双扩散编码MRS：我们对哪些微结构特征敏感？
Revisiting double diffusion encoding MRS in the mouse brain at 11.7T: which microstructural features are we sensitive to?
摘要：
脑代谢物，如N-乙酰天冬氨酸或肌醇，在扩散作用下不断探测其局部细胞环境。因此，扩散加权核磁共振光谱法提供了无与伦比的潜力，产生细胞类型的具体微观结构信息。双扩散编码（DDE）依赖于两个扩散块，其相对方向描述了实验过程中的变化角度。与单扩散编码不同，在长混合时间下的DDE测量显示信号幅度的一些角度调制，其反映了隔室形状各向异性，同时需要相对低的梯度强度。这种角度依赖性以前已被用来量化细胞纤维直径使用模型的各向同性取向的无限圆柱体。然而，很少有人探讨细胞微观结构的其他特征，如细胞体直径，纤维长度和分支也可能影响DDE信号。在这里，我们使用冷冻探针以及最先进的后处理技术，在11.7 T下对小鼠大脑进行了高精度和高精度的DDE采集。然后，我们将我们的结果与在各种3D细胞模型中获得的模拟DDE数据集进行比较，以确定细胞形态的哪些特征可能影响DDE信号的角度依赖性。虽然无限圆柱体模型不符合我们的实验数据，我们表明，将分支纤维结构在我们的模型是至关重要的合理解释DDE信号。最后，在短混合时间制度的实验和模拟表明，细胞体直径的一些敏感性可能会被收回，虽然需要额外的实验，以进一步支持这一说法。
英文摘要：
Brain metabolites, such as N-acetylaspartate or myo-inositol, are constantly probing their local cellular environment under the effect of diffusion. Diffusion-weighted NMR spectroscopy therefore presents unparalleled potential to yield cell-type specific microstructural information. Double diffusion encoding (DDE) relies on two diffusion blocks which relative directions describe a varying angle during the course of the experiment. Unlike single diffusion encoding, DDE measurements at long mixing time display some angular modulation of the signal amplitude which reflects compartment shape anisotropy, while requiring relatively low gradient strength. This angular dependence has been formerly used to quantify cell fiber diameter using a model of isotropically oriented infinite cylinders. However, it has been little explored how additional features of the cell microstructure, such as cell body diameter, fiber length and branching may also influence the DDE signal. Here, we used a cryoprobe as well as state-of-the-art post-processing to perform DDE acquisitions with high accuracy and precision in the mouse brain at 11.7 T. We then compared our results to simulated DDE datasets obtained in various 3D cell models in order to pinpoint which features of cell morphology may influence the most the angular dependence of the DDE signal. While the infinite cylinder model poorly fits our experimental data, we show that incorporating branched fiber structure in our model is paramount to sensibly interpret the DDE signal. Lastly, experiments and simulations in the short mixing time regime suggest that some sensitivity to cell body diameter might be retrieved, although additional experiments would be required to further support this statement.
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