Toward noninvasive quantification of adipose tissue oxygenation with MRI

Background: Molecular oxygen (O₂) plays a key role in normal and pathological adipose tissue function, yet technologies to measure its role in adipose tissue function are limited. O₂ is paramagnetic and, in principle, directly influences the magnetic resonance (MR) ¹H longitudinal relaxation rate constant of lipids, R₁; thus, we hypothesize that MR imaging (MRI) can directly measure adipose O₂ via a simple measure of R₁. Methods: R₁ was measured in a 4.7T preclinical MRI system at discrete oxygen partial pressure (pO₂) levels. These measures were made in vitro in an idealized system and in vivo in subcutaneous and visceral white adipose of rodents. pO₂ was determined using an invasive fiber-optic oxygen monitor. From the MRI and fiber optic data we determined the “relaxivity” of O₂ in lipid, a critical parameter in converting the MRI-based R₁ measurement into pO₂. We used breathing gas challenge to estimate the changes in lipid pO₂ (ΔpO₂). Results: The relaxivity of O₂ in lipid was determined to be 1.7·10⁻³ ± 4·10⁻⁴ mmHg⁻¹s⁻¹ at 4.7T and 37 °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 ΔpO₂ for in vivo visceral and subcutaneous fat depots in rodents. Conclusion: This study lays the foundation for a direct, noninvasive measure of adipose pO₂ using MRI and will allow for noninvasive measurement of O₂ 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.