Optical cerebral blood flow monitoring of mice to men

This thesis describes cerebral hemodynamic monitoring with the optical techniques of diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS). DOS and DCS both employ near-infrared light to investigate tissue physiology millimeters to centimeters below the tissue surface. DOS is a static technique that analyzes multispectral tissue-scattered light intensity signals with a photon diffusion approach (Chapter 2) or a Modified Beer-Lambert law approach (Chapter 3) to derive tissue oxy- and deoxy-hemoglobin concentrations, which are in turn used to compute tissue oxygen saturation and blood volume (Section 2.13). DCS is a qualitatively different dynamic technique that analyzes rapid temporal fluctuations in tissue-scattered light with a correlation diffusion approach to derive tissue blood flow (Chapter 4). Further, in combination these measurements of blood flow and blood oxygenation provide access to tissue oxygen metabolism (Section 7.6). The new contributions of my thesis to the diffuse optics field are a novel analysis technique for the DCS signal (Chapter 5), and a novel approach for separating cerebral hemodynamic signals from extra-cerebral artifacts (Chapter 6). The DCS analysis technique extends the Modified Beer-Lambert approach for DOS to the DCS measurement. This new technique has some useful advantages compared to the correlation diffusion approach. It facilitates real-time flow monitoring in complex tissue geometries, provides a novel route for increasing DCS measurement speed, and can be used to probe tissues wherein light transport is non-diffusive (Chapter 5). It also can be used to filter signals from superficial tissues. For separation of cerebral hemodynamic signals from extra-cerebral artifacts, the Modified Beer-Lambert approach is employed in a pressure modulation scheme, which determines subject-specific contributions of extra-cerebral and cerebral tissues to the DCS/DOS signals by utilizing probe pressure modulation to induce variations in extra-cerebral hemodynamics while cerebral hemodynamics remain constant (Chapter 6). In another novel contribution, I used optical techniques to characterize neurovascular coupling at several levels of cerebral ischemia in a rat model (Chapter 7). Neurovascular coupling refers to the relationship between increased blood flow and oxygen metabolism and increased neuronal activity in the brain. In the rat, localized neuronal activity was increased from functional forepaw stimulation. Under normal flow levels, I (and others) observed that the increase in cerebral blood flow (surrogate for oxygen delivery) from forepaw stimulation exceeded the increase in cerebral oxygen metabolism by about a factor of 2. My measurements indicate that this mismatch between oxygen delivery and consumption are more balanced during ischemia (Chapter 7). In Chapters 2 and 3, I review the underlying theory for the photon diffusion model and the Modified Beer-Lambert law for DOS analysis. I also review the correlation diffusion approach for analyzing DCS signals in Chapter 4. My hope is that readers new to the field will find these background chapters helpful