Magnetic resonance imaging of the cerebral metabolic rate of oxygen (CMRO₂)

Abstract

Oxygen consumption is an essential process of the functioning brain. The rate at which the brain consumes oxygen is known as the cerebral metabolic rate of oxygen (CMRO₂). CMRO₂ is intimately related to brain health and function, and will change in settings of disease and functional activation. Accurate CMRO₂ measurement will enable detailed investigation of neuropathology and facilitate our understanding of the brain's underlying functional architecture. Despite the importance of CMRO₂ in both clinical and basic neuroscience settings, a robust CMRO₂ mapping technique amenable to functional and clinical MRI has not been established. To address this issue, a novel method called QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption, or QUIXOTIC, is introduced. The key innovation in QUIXOTIC is the use of velocity-selective spin labeling to isolate MR signal exclusively from post-capillary venular blood on a voxel-by-voxel basis. This isolated signal can be related to venular oxygen saturation, oxygen extraction fraction, and ultimately CMRO₂. This thesis first explores fundamental theory behind the QUIXOTIC technique, including design of a novel MRI pulse sequence, explanation of the principal sequence parameters, and results from initial human experiences. A human trial follows, in which QUIXOTIC is used to measure cortical gray matter CMRO₂ in ten healthy volunteers.

(cont.) QUIXOTIC-measured CMRO₂ is found to be within the expected physiological range and is comparable to values reported by other techniques. QUIXOTIC is then applied to evaluate CMRO₂ response to carbon-dioxide-induced hypercapnia in awake humans. In this study, CMRO₂ is observed to decrease in response to mild hypercapnia. Finally, pilot studies that show feasibility of QUIXOTIC-based functional MRI (fMRI) and so-called "turbo" QUIXOTIC are presented and discussed.