Investigating the temporal evolution of the cerebral hemodynamic response using diffuse optical tomography.

摘要

The primary goal of this dissertation is to provide evidence to support the hypothesis that near-infrared optical measurement of brain function relies upon similar neurovascular coupling mechanisms and measures the same hemodynamic changes as does functional magnetic resonance imaging. To test this assertion, instrumentation was constructed and methodologies were developed to replicate a sequence of rodent experiments in which an electrical stimulus to the forepaw elicited a spatially localized hemodynamic response within the somatosensory region of the cerebral cortex. The temporal evolution of this response, previously measured with functional magnetic resonance imaging, was then measured using diffuse optical tomography, and the results of both measurements are compared and discussed.;In order to perform these experiments, a number of technical issues had to be addressed. Instrumentation capable of acquiring noninvasive real-time imagery of vascular events within the cerebral cortex with minimal temporal distortion had to be designed and tested. This investigation led to the evolution of a series of optical tomography instruments and the development of a new optical source encoding technique, Pulse TDM, which provides for advanced capabilities like individualized gain control, while significantly reducing the degree of temporal skew in the optical data.;Special surgical and anesthetic techniques which maintained normal cerebral hemodynamic activity while providing sufficient analgesia for stereotactic headgear had to be learned and mastered. To meet this need, custom surgical, biomonitoring, anesthesia, and stimulus equipment was developed.;Although the temporal hemodynamic measurements themselves comprise the core of this dissertation, they represent only a small fraction of the work involved in reaching that goal. To emphasize this point, the dissertation includes chapters which discuss topics vital to biophysical experimentation, including vascular physiology, electro-optical instrument design, and anesthesia.;The ethical implications of experimentation with live subjects is a topic which is often eschewed by many researchers in the field of biophysics. Because this is an important topic, the ethical and legal responsibilities involved in animal and human experimentation are discussed in the Appendix.;Since some electronic components are common to many DOT instruments, a number of datasheets are included in the Appendix as a convenience for the more technically-minded readers. Likewise, complete schematics of the bioinstrumentation developed for these measurements is provided, in an effort to assist others in replicating this circuitry for their own research.