Contribution of oxygenation to BOLD contrast in exercising muscle

The potential physiological and therapeutic applications of functional MRI (fMRI) in skeletal muscle will depend on our ability to identify factors that may contribute to fluctuations in the BOLD signal. Until now, interpretations of signal changes in fMRI studies of muscle have mostly relied on the increase in muscle T 2 associated with osmotically driven fluid shifts. However, recent studies have documented increases in BOLD signal intensity (SI) after single contractions, coinciding with increases in muscle hemoglobin saturation. In this study, the factors that contribute to variations in the intensity of the BOLD signal in exercising muscle are further addressed. For this purpose, BOLD imaging was performed during and after a moderate electrical stimulation was applied to the sciatic nerve in mice. In addition, oxygen pressure (pO 2 ), blood flow, and skeletal muscle T 2 (fast and slow components: T 2 and T   2 ′ , respectively) were monitored. A comparison between mice lacking eNOS (eNOS −/− mice) and their wild‐type (WT) littermates was performed. In WT mice, the BOLD SI, as well as muscle oxygenation and T   2 ′ , were significantly increased for a prolonged time in response to this moderate exercise protocol. Blood flow immediately dropped after the electrical stimulation was stopped. In eNOS −/− mice, the high BOLD SI did not persist after the exercise protocol ended. This finding correlates well with the evolution of muscle oxygenation, which progressively decreases after stimulation in eNOS −/− mice. However, T   2 ′remained high for a prolonged time after stimulation. We therefore concluded that the maintenance of BOLD SI in moderately exercising skeletal muscle depends mainly on changes in pO 2 , rather than on blood flow or T 2 effects. Magn Reson Med 52:391–396, 2004. © 2004 Wiley‐Liss, Inc.