Merkle Conrad W, Srinivasan Vivek J
Department of Biomedical Engineering, University of California at Davis 451 E. Health Sciences Dr. GBSF 2303 Davis CA 95616, USA.
Department of Biomedical Engineering, University of California at Davis 451 E. Health Sciences Dr. GBSF 2303 Davis CA 95616, USA.
Neuroimage. 2016 Jan 15;125:350-362. doi: 10.1016/j.neuroimage.2015.10.017. Epub 2015 Oct 20.
The transit time distribution of blood through the cerebral microvasculature both constrains oxygen delivery and governs the kinetics of neuroimaging signals such as blood-oxygen-level-dependent functional Magnetic Resonance Imaging (BOLD fMRI). However, in spite of its importance, capillary transit time distribution has been challenging to quantify comprehensively and efficiently at the microscopic level. Here, we introduce a method, called Dynamic Contrast Optical Coherence Tomography (DyC-OCT), based on dynamic cross-sectional OCT imaging of an intravascular tracer as it passes through the field-of-view. Quantitative transit time metrics are derived from temporal analysis of the dynamic scattering signal, closely related to tracer concentration. Since DyC-OCT does not require calibration of the optical focus, quantitative accuracy is achieved even deep in highly scattering brain tissue where the focal spot degrades. After direct validation of DyC-OCT against dilution curves measured using a fluorescent plasma label in surface pial vessels, we used DyC-OCT to investigate the transit time distribution in microvasculature across the entire depth of the mouse somatosensory cortex. Laminar trends were identified, with earlier transit times and less heterogeneity in the middle cortical layers. The early transit times in the middle cortical layers may explain, at least in part, the early BOLD fMRI onset times observed in these layers. The layer-dependencies in heterogeneity may help explain how a single vascular supply manages to deliver oxygen to individual cortical layers with diverse metabolic needs.
血液通过脑微血管系统的传输时间分布既限制了氧气输送,又决定了诸如血氧水平依赖性功能磁共振成像(BOLD fMRI)等神经成像信号的动力学。然而,尽管其很重要,但在微观层面全面且高效地量化毛细血管传输时间分布一直具有挑战性。在此,我们介绍一种名为动态对比光学相干断层扫描(DyC-OCT)的方法,它基于血管内示踪剂穿过视野时的动态横截面OCT成像。定量传输时间指标是从与示踪剂浓度密切相关的动态散射信号的时间分析中得出的。由于DyC-OCT不需要对光学焦点进行校准,即使在焦点光斑退化的高散射脑组织深处也能实现定量准确性。在用表面软脑膜血管中使用荧光血浆标记物测量的稀释曲线对DyC-OCT进行直接验证后,我们使用DyC-OCT研究小鼠体感皮层整个深度的微血管系统中的传输时间分布。确定了层状趋势,中间皮层的传输时间更早且异质性更小。中间皮层的早期传输时间可能至少部分解释了在这些层中观察到的早期BOLD fMRI起始时间。异质性中的层依赖性可能有助于解释单一血管供应如何设法向具有不同代谢需求的各个皮层层输送氧气。