Lee Jennifer A, Kozikowski Raymond T, Sorg Brian S
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32610, USA.
Ventana Medical Systems, Inc., Tucson, AZ 85755, USA.
Microvasc Res. 2015 Mar;98:29-39. doi: 10.1016/j.mvr.2014.11.007. Epub 2014 Dec 10.
Abnormal or compromised microvascular function is a key component of various diseases. In vivo microscopy of microvessel function in preclinical models can be useful for the study of a disease state and effects of new treatments. Wide-field imaging of microvascular oxygenation via hemoglobin (Hb) saturation measurements has been applied in various applications alone and in combination with other measures of microvessel function, such as blood flow. However, most current combined imaging methods of microvessel function do not provide direct information on microvessel network connectivity or changes in connections and blood flow pathways. First-pass fluorescence (FPF) imaging of a systemically administered fluorescent contrast agent can be used to directly image blood flow pathways and connections relative to a local supplying arteriole in a quantitative manner through measurement of blood supply time (BST). Here, we demonstrate the utility of information produced by the combination of Hb saturation measurements via spectral imaging with BST measurements via FPF imaging for correlation of microvessel oxygenation with blood flow pathways and connections throughout a local network. Specifically, we show network pathway effects on oxygen transport in normal microvessels, dynamic changes associated with wound healing, and pathological effects of abnormal angiogenesis in tumor growth and development.
微血管功能异常或受损是多种疾病的关键组成部分。临床前模型中微血管功能的体内显微镜检查对于研究疾病状态和新治疗方法的效果可能是有用的。通过血红蛋白（Hb）饱和度测量对微血管氧合进行的宽场成像已单独应用于各种应用中，并与微血管功能的其他测量方法（如血流）结合使用。然而，目前大多数微血管功能的联合成像方法无法提供关于微血管网络连通性或连接和血流途径变化的直接信息。全身给药的荧光造影剂的首过荧光（FPF）成像可用于通过测量供血时间（BST）以定量方式直接成像相对于局部供应小动脉的血流途径和连接。在此，我们证明了通过光谱成像进行的Hb饱和度测量与通过FPF成像进行的BST测量相结合所产生的信息对于局部网络中微血管氧合与血流途径和连接的相关性的实用性。具体而言，我们展示了网络途径对正常微血管中氧运输的影响、与伤口愈合相关的动态变化以及肿瘤生长和发展中异常血管生成的病理影响。
