Tomographic imaging of flow and chromophore concentrations in biological tissue

了解大脑的功能构成是神经科学的圣杯，成像工具在实现这一目标方面发挥着重要作用。功能成像是一个比解剖成像更困难的目标，因为它依赖于建立与生理功能相关的对比机制，并且可以以良好的精度和分辨率进行测量。光学技术非常有吸引力，因为在许多不同分子的吸收光谱中编码了丰富的信息，但由于在通过身体不同组织时发生的高度散射，它们难以大规模使用。漫射光学断层扫描（DOT）通过对来自多种照明模式的光传播进行时间分辨测量，可以产生吸收和散射特性的低分辨率图像，并将这些图像去关联，从而产生大脑和其他器官的氧合图。与此同时，漫射相关光谱学（DCS）检查了相干光在与时间比较时从自身去相关的方式。由于内源性散射粒子的布朗运动和血流，这种去相关自然发生。相干光学技术因此允许对血流进行无创监测，并提供病理性大脑自动调节的指示，例如中风。直到最近，相干检测技术的局限性阻碍了弥散相关断层扫描（DCT）的重大发展，其中可以产生血流的体积图像。在这个项目中，我们的目标是在一个设备中开发一个DCT和时间分辨DOT系统。这将使两种技术结合在一起，首次提供脑血流量和脑氧提取的脑代谢率的图像。我们建议发展理论和实验方法，这将使新一代便携式光学仪器的发展，低成本，连续同时监测血流和发色团浓度。我们的系统产生的丰富图像有潜力极大地提高我们对潜在神经过程和病理的理解，并允许在靶向治疗中有效利用稀缺资源。

Understanding the functional makeup of the brain is a holy grail of neuroscience, and imaging tools play a significant role in achieve this aim. Functional imaging is a more difficult goal than anatomical imaging because it depends on establishing a contrast mechanism that relates to physiological function and also can be measured with good accuracy and resolution. Optical techniques are very attractive because of the rich information encoded in the absorption spectra of many different molecules, but they are difficult to use at large scale because of the high degree of scattering that occurs in passing through different tissues of the body. By using time-resolved measurements of the propagation of light from multiple illumination patterns, diffuse optical tomography (DOT) can produced low-resolution images of absorption and scattering properties, and decorrelate these to produce maps of oxygenation in the brain and other organs. At the same time, diffuse correlation spectroscopy (DCS) examines the way in which coherent light is decorrelated from itself when compared over time. This decorrelation naturally occurs due to the Brownian motion of endogenous scattering particles, and blood flow. Coherent optical techniques thus allow the non-invasive monitoring of blood flow and provide an indication of pathological cerebral auto-regulation during, e.g., stroke. Until recently, limitations in coherent detection technology have prevented significant developments towards diffuse correlation tomography (DCT), wherein volumetric images of blood flow can be produced.In this project we aim to develop a system for DCT and time-resolved DOT in one device. This will bring the two techniques together to provide images of cerebral blood flow and cerebral metabolic rate of oxygen extraction in the brain for the first time. We propose the development of theoretical and experimental methods which will enable the development of a new generation of optical instruments for portable, low-cost, continuous simultaneous monitoring of blood flow and chromophore concentrations. The rich images produced by our system have the potential to vastly improve our understanding of underlying neurological processes and pathology, and to allow the efficient use of scarce resources in targeted treatments.