In vivo oxygen detection using exogenous hemoglobin as a contrast agent in magnetic resonance microscopy

In this work we show that exogenous molecular hemoglobin (Hb) is an effective indicator of relative local oxygen tension in magnetic resonance (MR) microscopy studies in vivo. This approach is more sensitive than other MRI oximetry methods; it can be used at higher resolutions and in specimens with no blood oxygen level-dependent (BOLD) effects. Using injection studies in flies, we show that Hb can permeate through relatively dense neural tissue, and that it is not obviously disruptive to physiology. Hb-injected flies show large changes in signal intensity (40-50%) when external O(2) levels are manipulated artificially from 0% to 21%. Oxygen-dependent contrast changes produced by exogenous Hb are detected in T(2)-weighted imaging experiments, and can be roughly calibrated if necessary. These studies demonstrate the feasibility of a contrast agent technique that may be useful for functional MRI (fMRI) studies of metabolism at tens of microns resolution.