Neuroimaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
Neuroimaging Laboratory, Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA.
Neuroimage. 2019 Aug 15;197:657-667. doi: 10.1016/j.neuroimage.2017.08.046. Epub 2017 Aug 16.
Contrast-enhanced cerebral blood volume-weighted (CBVw) fMRI response peaks are specific to the layer of evoked synaptic activity (Poplawsky et al., 2015), but the spatial resolution limit of CBVw fMRI is unknown. In this study, we measured the laminar spread of the CBVw fMRI evoked response in the external plexiform layer (EPL, 265 ± 65 μm anatomical thickness, mean ± SD, n = 30 locations from 5 rats) of the rat olfactory bulb during electrical stimulation of the lateral olfactory tract and examined its potential vascular source. First, we obtained the evoked CBVw fMRI responses with a 55 × 55 μm in-plane resolution and a 500-μm thickness at 9.4 T, and found that the fMRI signal peaked predominantly in the inner half of EPL (136 ± 54 μm anatomical thickness). The mean full-width at half-maximum of these fMRI peaks was 347 ± 102 μm and the functional spread was approximately 100 or 200 μm when the effects of the laminar thicknesses of EPL or inner EPL were removed, respectively. Second, we visualized the vascular architecture of EPL from a different rat using a Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue hYdrogel (CLARITY)-based tissue preparation method and confocal microscopy. Microvascular segments with an outer diameter of <11 μm accounted for 64.3% of the total vascular volume within EPL and had a mean segment length of 55 ± 40 μm (n = 472). Additionally, vessels that crossed the EPL border had a mean segment length outside of EPL equal to 73 ± 61 μm (n = 28), which is comparable to half of the functional spread (50-100 μm). Therefore, we conclude that dilation of these microvessels, including capillaries, likely dominate the CBVw fMRI response and that the biological limit of the fMRI spatial resolution is approximately the average length of 1-2 microvessel segments, which may be sufficient for examining sublaminar circuits.
对比增强脑血容量加权（CBVw）fMRI 响应峰值与诱发突触活动的层有关（Poplawsky 等人，2015 年），但 CBVw fMRI 的空间分辨率限制尚不清楚。在这项研究中，我们在大鼠嗅球外侧嗅束电刺激期间测量了外丛状层（EPL）中 CBVw fMRI 诱发反应的层展度（265±65μm 解剖厚度，平均值±标准差，n=5 只大鼠的 30 个位置），并检查了其潜在的血管来源。首先，我们在 9.4T 下获得了具有 55×55μm 面内分辨率和 500-μm 厚度的诱发 CBVw fMRI 响应，发现 fMRI 信号主要在 EPL 的内半部分达到峰值（136±54μm 解剖厚度）。这些 fMRI 峰值的半峰全宽平均值为 347±102μm，当去除 EPL 或内 EPL 的层厚影响时，功能扩散分别约为 100 或 200μm。其次，我们使用基于 Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue hYdrogel（CLARITY）的组织制备方法和共聚焦显微镜从另一只大鼠中可视化了 EPL 的血管结构。外直径<11μm 的微血管段占 EPL 总血管体积的 64.3%，平均段长为 55±40μm（n=472）。此外，跨越 EPL 边界的血管在 EPL 之外的平均段长等于 73±61μm（n=28），与功能扩散的一半（50-100μm）相当。因此，我们得出结论，这些微血管的扩张，包括毛细血管，可能主导 CBVw fMRI 响应，而 fMRI 空间分辨率的生物学限制约为 1-2 个微血管段的平均长度，这可能足以检查亚层电路。
