Measuring oxygenation in vivo with MRS/MRI--from gas exchange to the cell

Oxygen plays a major role as a substrate in metabolic processes in numerous signaling pathways, in redox metabolism, and in free radical metabolism. To study the role of oxygen in normal and pathophysiological states, methods that can be used noninvasively are required. This review examines the potential of nuclear magnetic resonance techniques to study tissue oxygenation. It is written from a systems perspective, looking at detection methods with respect to the path that oxygen takes in the mammalian system-from the lungs, through the vascular system, into the interstitial space, and finally into the cell. Methods discussed range from those that are quantifiable, such as the assessment of spin lattice relaxation time in fluorocarbon solutions, to those that are more correlative, such as assessment of lactate and high energy phosphates. Since the methods vary in their site of application, sensitivity, and specificity to the quantification of oxygen, this review provides examples of how each method has been applied. This may facilitate the reader's understanding of how to optimally apply different methods to study specific biomedical problems.