Optical Imaging Of Tissue Physiology With Exogenous Contrast Agents

This thesis describes experiments and analyses which push the frontier per what one can learn from optically emitting exogenous contrast agents in living tissue. The first set of experiments concurrently measured cerebral blood flow and bothintravascular- and extravascular-tissue oxygen concentration in a rat brain during functional activation; the new instrumentation needed to collect this information used contrast agent phosphorescence lifetime to determine oxygen concentration and speckle contrast imaging to probe blood flow. The concurrent measurement of multiple physiological parameters with high temporal resolution (∼7 Hz) provided a unique opportunity to observe the interconnected dynamics of oxygen exchange, blood flow, and cerebral oxygen metabolism. The experiments showed that initial metabolic changes trigger a blood flow response; comprehensive theoretical modeling of the data exposed potential weaknesses of the well-known and often-used two-compartment oxygen diffusion model, and the experiments as a whole introduced a new tool for characterization of oxygen metabolism and neurovascular coupling in the brain. The second set of experiments developed instrumentation and a simple theoretical methodology for imaging fluorescent targets in turbid media such as tissue. This approach used the ideas of spatial frequency domain fluorescence diffuse optical tomography (SFD-FDOT). The new reconstruction algorithm modified the more complex SFD-FDOT reconstruction method to rapidly acquire the depth of fluorescent target(s) and then estimate the transverse margins of the fluorescent target(s). Tissue phantom experiments demonstrated the instrumentation and algorithm, and assessed limitations. The new methodology could be useful for image guidance during tumor resection surgery, and could also provide rapid and useful constraining information for more comprehensive fluorescent tomography.