Diffuse Light Imaging of Flow, Oxygen & Brain Metabolism

描述（申请人提供）：微血管系统中血细胞的浓度、氧合和流动特性深刻地影响周围组织的营养和热调节，这些量的异常水平将影响氧提取并可能损害周围组织，在-这些基本血液参数中的任何一个的原位测量提供了对许多生理现象的了解，功能异质性、内出血、肿瘤脉管系统和局部缺血。同时测量这些量中的一个以上提供了对基本组织生理学的更深入的了解，并提供了直接探测组织氧代谢的可能性。在这个提议中，我们关注的是大脑中这些量的测量，最终是人类大脑。到目前为止，广泛的非侵入性技术已被用于探测大脑皮层的活动。这项建议旨在为这一武器库增加一项新技术。特别地，我们提出构建和使用通用的多模态全光学成像探头，用于测量总血红蛋白浓度、血氧、血流量、脑氧代谢率（CMRO 2）及其在脑中的变化。该仪器的独特之处在于它结合了两种质量不同且互补的漫射光学成像模式：（1）用于计算血氧饱和度和总血红蛋白浓度的漫射反射光谱（DRS），以及（2）用于测量血流的漫射相关光谱（DCS）。我们预计该仪器及其变体将提供小动物大脑中这些特性的三维成像，并将提供人类大脑中类似的区域成像信息。这两种扩散光学成像方案是评价脑生理学的有吸引力的新方法。它们可以提供与磁共振成像（MRI）和正电子发射断层扫描（PET）互补的血流动力学和代谢成像对比，并具有用于人类连续无创床旁成像和动物密集采样纵向研究的独特潜力。

DESCRIPTION (provided by applicant): The concentration, oxygenation, and flow characteristics of blood cells in the microvasculature profoundly affect nourishment and thermal regulation of surrounding tissues, abdnormal levels of these quantities will affect oxygen extraction and can potentially compromise surrounding tissue, ln-situ measurements of any one of these basic blood parameters provide insight about many physiological phenomena including cerebral metabolism and functional heterogeneity, internal bleeding, tumor vasculature, and ischemia. Measurement of more than one of these quantities simultaneously provides even deeper insight into fundamental tissue physiology, and offers the possibility to directly probe tissue oxygen metabolism. In this proposal we are concerned with measurement of these quantities in brain, ultimately human brain. Thus far a broad range of non-invasive techniques has been used to probe activity in the cerebral cortex. This proposal seeks to add a new technique to this arsenal. In particular we propose to construct and use a versatile multi-modality all-optical imaging probe for measurement of total hemoglobin concentration, blood oxygenation, blood flow, the cerebral metabolic rate for oxygen (CMRO2) and changes thereof in brain. The instrument is unusual in that it combines two qualitately different and complementary diffuse optical imaging modalities: (1) Diffuse Reflection Spectroscopy (DRS) for computation of blood oxygen saturation and total hemoglobin concentration, and (2) Diffuse Correlation Spectroscopy (DCS) for measurement ot blood flow. We anticipate this instrument and its variants will provide three-dimensional imaging of these properties in small animal brain, and will provide similar regional imaging information in human brain. The two diffuse optical imaging schemes are attractive new approaches for evaluating cerebral physiology. They can provide hemodynamic and metabolic imaging contrasts complementary to those of Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET), and hold a unique potential for continous noninvasive bedside imaging in humans and densely sampled longitudinal studies in animals.