Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee.
Am J Physiol Heart Circ Physiol. 2013 Oct 15;305(8):H1168-80. doi: 10.1152/ajpheart.00362.2013. Epub 2013 Aug 16.
The mouse hind limb ischemia (HLI) model is well established for studying collateral vessel formation and testing therapies for peripheral arterial disease, but there is a lack of quantitative techniques for intravitally analyzing blood vessel structure and function. To address this need, non-invasive, quantitative optical imaging techniques were developed to assess the time-course of recovery in the mouse HLI model. Hyperspectral imaging and optical coherence tomography (OCT) were used to non-invasively image hemoglobin oxygen saturation and microvessel morphology plus blood flow, respectively, in the anesthetized mouse after induction of HLI. Hyperspectral imaging detected significant increases in hemoglobin saturation in the ischemic paw as early as 3 days after femoral artery ligation (P < 0.01), and significant increases in distal blood flow were first detected with OCT 14 days postsurgery (P < 0.01). Intravital OCT images of the adductor muscle vasculature revealed corkscrew collateral vessels characteristic of the arteriogenic response to HLI. The hyperspectral imaging and OCT data significantly correlated with each other and with laser Doppler perfusion imaging (LDPI) and tissue oxygenation sensor data (P < 0.01). However, OCT measurements acquired depth-resolved information and revealed more sustained flow deficits following surgery that may be masked by more superficial measurements (LDPI, hyperspectral imaging). Therefore, intravital OCT may provide a robust biomarker for the late stages of ischemic limb recovery. This work validates non-invasive acquisition of both functional and morphological data with hyperspectral imaging and OCT. Together, these techniques provide cardiovascular researchers an unprecedented and comprehensive view of the temporal dynamics of HLI recovery in living mice.
小鼠后肢缺血（HLI）模型是研究侧支血管形成和测试外周动脉疾病治疗方法的成熟模型，但缺乏用于活体分析血管结构和功能的定量技术。为了解决这一需求，开发了非侵入性、定量的光学成像技术，以评估小鼠 HLI 模型中恢复的时间过程。高光谱成像和光相干断层扫描（OCT）分别用于在诱导 HLI 后对麻醉小鼠进行非侵入性血红蛋白氧饱和度和微血管形态加血流成像。高光谱成像检测到，在股动脉结扎后 3 天，缺血足的血红蛋白饱和度显著增加（P < 0.01），并且在手术后 14 天首次用 OCT 检测到远端血流量增加（P < 0.01）。内活体 OCT 图像显示了内收肌血管的螺旋状侧支血管，这是对 HLI 的动脉生成反应的特征。高光谱成像和 OCT 数据与彼此以及激光多普勒灌注成像（LDPI）和组织氧传感器数据显著相关（P < 0.01）。然而，OCT 测量获得了深度分辨信息，并揭示了手术后更持续的血流不足，这可能被更浅表的测量（LDPI、高光谱成像）掩盖。因此，内活体 OCT 可能为缺血肢体恢复的晚期提供一个强大的生物标志物。这项工作验证了高光谱成像和 OCT 非侵入性地获取功能和形态数据。这些技术共同为心血管研究人员提供了一种前所未有的、全面的活体小鼠 HLI 恢复的时间动态视图。
