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Adipocyte and Cell Biology

Toward noninvasive quantification of adipose tissue oxygenation with MRI

Abstract

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.

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Fig. 1: The system used for lard phantom preparation.
Fig. 2: MR spectra of fat specimens at 4.7T.
Fig. 3: \({r}_{1,{\mathrm{pO}}_2}\) determination and the utility of the \({r}_{1,{\mathrm{pO}}_2}\) in measuring short-time oxygen flux in adipose tissue.
Fig. 4: Comparison between \({r}_{1,{\mathrm{pO}}_2}\) and R1,0 of lard and adipose depots.

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Acknowledgements

The authors would like to thank their colleagues Drs Joseph J.H. Ackerman and Joel R. Garbow for their invaluable input. These MR experiments were conducted in the Small Animal Magnetic Resonance Facility in the Washington University School of Medicine.

Funding

This work was supported by NIH grants K01 DK109119 and P30 DK020579.

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Correspondence to Scott C. Beeman.

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Morozov, D., Quirk, J.D. & Beeman, S.C. Toward noninvasive quantification of adipose tissue oxygenation with MRI. Int J Obes 44, 1776–1783 (2020). https://doi.org/10.1038/s41366-020-0567-x

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