Investigating the biomechanics and biochemistry underlying MRI measures of neuronal function

This thesis investigates the biophysical mechanisms underlying functional magnetic resonance imaging (fMRI) measures of brain activity. Diffusion-weighted fMRI (DWfMRI) has been suggested as an alternative to the established Blood Oxygenation Level Dependent (BOLD) method. It is speculated to be sensitive to transient microstructural changes within active brain tissue, which could provide a more direct measure of neuronal activity than techniques relying on attendant haemodynamic changes. DWfMRI has yet to become widely accepted however, as the mechanism driving the observed signal is not well understood. Here, experimental and theoretical investigations of the fMRI signal are presented. As part of this work, a functional MRI study was undertaken to compare BOLD and DWfMRI responses to stimulated brain activity in human volunteers. The effect of different experimental protocols were explored, with an emphasis on stimulus design. Analysis methods and their potential impact on interpretation of the response are explored. Neuronal activation is accompanied by heamodynamic changes detectable with Optical Imaging Spectroscopy. Additionally, there is a growing base of evidence showing microstructural changes in excited neuronal tissue. This tortuosity change might be observable through the use of Spatial Frequency Domain Imaging (SFDI). These properties can be observed in the animal model and compared with fMRI to aid interpretation. The following work presents the development of in-vivo optical imaging techniques for the measurement of tissue optical property changes during brain activity. This includes theoretical explorations of the analysis pipeline, and of the potential limitations of these techniques and their sensitivity. A Monte Carlo simulation of light transport through tissue was written to provide calibration data for the optical imaging methods. The simulation was used to explore the impact of tissue parameters on the optical results and inform interpretation. The simulation was extended to explore tissue absorption in the context of biophotomodulation.