Imaging changes in the rodent brain using diffusion weighted multiple boli arterial spin labelling

[摘要] This thesis combines the quantification of a new arterial spin labelling (ASL) sequence, and the development of a diffusion weighted ASL (DWASL) sequence, to examine blood brain barrier (BBB) impairment. The blood brain barrier maintains the delicate neuroenvironment in the brain by controlling influx and efflux of cells and molecules. Many neurological disorders are effected by an impairment of the BBB. Current magnetic resonance imaging (MRI) methods to image BBB dysfunction involve the use of a contrast agent, which is invasive and not sensitive to subtle changes in BBB permeability. Non-invasive MR methods such as ASL, are able to measure perfusion and produce cerebral blood flow (CBF) maps of the brain. ASL however has an inherently low signal and therefore development of high signal-tonoise ratio (SNR) sequences are needed. Multiple boli ASL (mbASL) is a high SNR sequence that would be suitable for producing CBF maps but lacks quantification. Human African trypanosomiasis (HAT), a parasitic disease native to Africa, results in a progressive diffuse impairment of the BBB throughout the disease course. A murine model of HAT was used to examine water exchange and cerebral blood flow changes with DWASL.Chapter 1 outlines the current literature on the blood brain barrier, HAT and splenomegaly. Chapter 2 introduces the theory of MRI, which is the imaging method used throughout the thesis. Chapter 3 provides a literature review of the ASL sequence and subsequent development of diffusion weighted ASL. The review outlines the main ASL sequences and introduces multiple boli ASL, followed by diffusion weighted ASL. These two sequences are used throughout this thesis. Chapter 4, the first results chapter, experimentally validates the quantification of the mbASL sequence. Chapter 5 outlines the development of diffusion weighted mbASL which could potentially image changes in water exchange across the BBB. Chapter 6 and Chapter 7 use the HAT mouse model first to examine changes in the water exchange in the brain and then to serially image changes in spleen volume.

[发布机构] University:University of Glasgow;Department:Institute of Neuroscience and Psychology

[关键词] Brain, Blood brain barrier, MRI, Arterial spin labelling, ASL, DWASL, Diffusion weighted arterial spin labelling, human African trypanosomiasis, sleeping sickness.