Saturation-Recovery T1 (SR-T1) Method: A Dynamic Neuroimaging Tool for Assessment of Perfusion Change

Abstract

A working brain requires continuous oxygen and nutrition supply through the circulation of Cerebral Blood Flow (CBF). CBF and its change closely reflect the energy demand of neuron activity and are highly related to variety of cerebral diseases as well. It is of great importance to noninvasively and reliably mapping CBF and its change under physiological and pathological conditions. The goal of this research is to develop a sensitive, reliable and noninvasive MRI neuroimaging technique based on Saturation-recovery longitudinal relaxation time (SR-T1) method to imaging CBF change and Blood Oxygen-Level Dependent (BOLD) signal simultaneously. First, the theoretical and mathematical model of SR-T1 method is derived and MRI sequence design is described. This technique is tested on physiological and pathological rat models at 9.4T and is validated by indirect Laser Doppler Flowmetry (LDF) and direct Continuous Arterial Spin Labeling (CASL) CBF approaches. Some technical confounding factors are also investigated and discussed (Chapter 2 to 4). Second, the SR-T1 method of imaging CBF change is applied at two different magnetic fields (9.4T and 16.4T) to examine the notion that T1 is field dependent whereas CBF change in response to physiological or pathological perturbation is field independent (Chapter 5). Third, the SR-T1 method is performed to quantitatively investigate the perfusion contribution to the total functional MRI (fMRI) signal using a rat model with mild hypercapnia at 9.4T and human subjects with visual stimulation at 4T. It reveals that an improved fMRI contrast-to-noise ratio and spatial specificity for mapping brain activity and physiology changes could benefit from appropriately choosing the MRI parameters in enhancing perfusion contribution to the total fMRI signal (Chapter 6). Fourth, the SR-T1 method is carried out on Middle Cerebral Artery Occlusion (MCAO) rat model at 1 day and 7 days of post-ischemia and then is compared to the CBF change measured by the CASL technique in varied lesion regions of rat brain. The comparison reveals a good correlation of CBF change measured with these two perfusion techniques. A variety of MR imaging modalities, such as Apparent Diffusion Coefficient (ADC) images and Cerebral Vascular Reactivity (CVR) images as well as histology are also performed on the MCAO rat brain to longitudinally study the reperfusion injury (Chapter 7). Finally, the major conclusions are summarized and the future prospects are discussed and proposed in Chapter 8. In conclusion, the SR-T1 method developed and applied in this thesis should provide an alternative, noninvasive and reliable neuroimaging tool to study CBF change and BOLD under both physiological and pathological conditions.