Toward noninvasive quantification of adipose tissue oxygenation with MRI

Abstract

Background Molecular oxygen (O-2) plays a key role in normal and pathological adipose tissue function, yet technologies to measure its role in adipose tissue function are limited. O-2 is paramagnetic and, in principle, directly influences the magnetic resonance (MR) H-1 longitudinal relaxation rate constant of lipids, R-1; thus, we hypothesize that MR imaging (MRI) can directly measure adipose O-2 via a simple measure of R-1. Methods R-1 was measured in a 4.7T preclinical MRI system at discrete oxygen partial pressure (pO(2)) levels. These measures were made in vitro in an idealized system and in vivo in subcutaneous and visceral white adipose of rodents. pO(2) was determined using an invasive fiber-optic oxygen monitor. From the MRI and fiber optic data we determined the "relaxivity" of O-2 in lipid, a critical parameter in converting the MRI-based R-1 measurement into pO(2). We used breathing gas challenge to estimate the changes in lipid pO(2) (Delta pO(2)). Results The relaxivity of O-2 in lipid was determined to be 1.7 center dot 10(-3) +/- 4 center dot 10(-4) mmHg(-1)s(-1) at 4.7T and 37 degrees C, and was consistent between in vitro and in vivo adipose tissue. There was a strong, significant correlation between MRI- and gold standard OxyLite-based measurements of lipid Delta pO(2) for in vivo visceral and subcutaneous fat depots in rodents. Conclusion This study lays the foundation for a direct, noninvasive measure of adipose pO(2) using MRI and will allow for noninvasive measurement of O-2 flux in adipose tissue. The proposed approach would be of particular importance in the interrogation of the pathogenesis of type 2 diabetes, where it has been suggested that adipose tissue hypoxia is an independent driver of insulin resistance pathway.