Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Medical Biophysics


Dr. Ravi Menon

Second Advisor

Dr. Christopher Ellis

Third Advisor

Dr. Brian Corneil


Modem brain functional imaging techniques like functional magnetic resonance imaging (fMRI) mostly infer alterations of neuronal activities by mapping local changes in cerebral blood flow (CBF) or metabolism. The understanding of the relationship between neuronal activity and the hemodynamic responses, the so called neurovascular coupling, is critical for the interpretation of signals like the blood-oxygenation-level- dependent (BOLD) effect. The neurovascular regulation is modeled by a linear transform model in the fMRI experiments, which allows making an inverse inference from BOLD to neuron. Some recent reports suggest that the BOLD response is a nonlinear function in the time domain. Because changes in CBF underlie the BOLD effect, a separate assessment of the CBF response would be useful to gain more insight into this complicated relationship. This thesis concerns aspects of making quantitative CBF measurements in vivo. Avoiding the profound consequences caused by anesthesia, we addressed the relationship between CBF and neural activity by recording variations of the neural and induced hemodynamic signals in the primary visual cortex (Vl) in monkeys. The animals were trained to view a standard stimulus pattern whose duration could be varied. The extracellular field potentials and CBF responses were acquired by a microelectrode and laser Doppler probe through a recording chamber. Through a stable deconvolution analysis, a rapid biphasic and a slower monophasic hemodynamic response functions (HRFs) were identified to associate the transient and sustained components of the power spectral density of the local field potential (LFP) with the CBF responses, respectively. Beyond the implications for fMRI analysis and BOLD biophysical models, our findings suggest that there exist two distinctly tuned CBF regulatory mechanisms in primate cortex. One appears to support the high energy demands typical of the transient neuronal response and the other the more modest demands of a sustained neuronal response. The laser Doppler probe measures signals at one position on the cortex. To spatially resolve distinct hemodynamic responses evoked by complex neuronal activation requires an in-vivo flow imaging technique that can directly visualize changes of blood flow with sufficient spatial and temporal resolution. To this end, an optical imaging technique - laser speckle contrast imaging (LSCI) with superior spatiotemporal (at micrometer and millisecond level) was developed to gain in-depth knowledge of spatial regulation of local CBF responses. In order to optimize this method, a number of basic assumptions in LSCI were re-examined by theoretical analysis and an important strategy was proposed for in vivo applications. The detailed distribution of CBF responses to physiological manipulation was imaged with tens of micron spatial resolution in the exposed cortex and quantitatively compared to the laser Doppler measurements. Our results demonstrate that optimization of LSCI can achieve high specificity to assess cerebral microcirculation, and LSCI is a promising, quantitative, minimally invasive method to achieve in vivo high- resolution visualization of blood flow in exposed biological tissue.



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