Differentiating brown and white adipose tissues by high-resolution diffusion NMR spectroscopy

Abstract

majority of body fat, which is utilized for energy storage, whereas BAT is a minor portion that is involved in thermogenesis, due to the presence of uncoupling protein 1 (UCP1) in the mitochondria. In addition to the differences in energy storage and expenditure, BAT is a highly heterogeneous, densely vascularized tissue with abundant oxygen, blood supply, and iron-rich mitochondria (6, 7). WAT is composed of unilocular lipid droplets, whereas BAT is composed of multilocular lipid droplets scattered throughout the cytoplasm and surrounded by mitochondria.Positron emission tomography (PET) has been the gold standard for imaging BAT (8, 9) because of a selective image contrast of activated BAT by the increased uptake of 18 F-deoxyglucose. However, PET is not suitable for longitudinal studies because it requires injection of exogenous radioactive tracers. Magnetic resonance (MR)-based methods are more promising for real-time and long-term observation of fat accumulation and consumption (10). Traditional MR-based approaches exploit the differences in the water content in WAT and BAT using chemical shift imaging or the Dixon technique (11-13). Imaging of water and fat permits quantitative assessment of the fat fraction. Additionally, the differences in iron content, perfusion, and vasculature have been exploited by T 2 and T 2 * relaxation techniques (14, 15). However, although WAT and BAT are manually separable by color and texture, they cannot be easily distinguished by MR because of the similarity in their magnetic and chemical characteristics (14,15).Applications of nontraditional MR methodologies for selectively detecting BAT have been attempted. Branca and Warren (16, 17) have studied focusing on intermolecular multiple-quantum coherences through dipolar Abstract There are two types of fat tissues, white adipose tissue (WAT) and brown adipose tissue (BAT), which essentially perform opposite functions in whole body energy metabolism. There is a large interest in identifying novel biophysical properties of WAT and BAT by a quantitative and easy-to-run technique. In this work, we used high-resolution pulsed field gradient diffusion NMR spectroscopy to study the apparent diffusion coefficient (ADC) of fat molecules in rat BAT and WAT samples. The ADC of fat in BAT and WAT from rats fed with a chow diet was compared with that of rats fed with a high-fat diet to monitor how the diffusion properties change due to obesity-associated parameters such as lipid droplet size, fatty acid chain length, and saturation. Feeding a high-fat diet resulted in increased saturation, increased chain lengths, and reduced ADC of fat in WAT. The ADC of fat was lower in BAT relative to WAT in rats fed both chow and high-fat diets. Diffusion of fat was restricted in BAT due to the presence of small multilocular lipid droplets. Our findings indicate that in vivo diffusion might be a potential way for better delineation of BAT and WAT in both lean and obese states.-Verma, S. K., K. Nagashima, J. Yaligar, N. Michael, S. S. Lee, T. Xianfeng, V...

Measuring large lipid droplet sizes by probing restricted lipid diffusion effects with diffusion‐weighted MRS at 3T

“…The present study proposes a methodology to measure lipid droplet sizes with DW‐MRS. The restricted diffusion effects in the DW‐MR measurements of lipid droplets have been reported previously for lipid droplets a few microns in size using the strong gradient hardware of preclinical MR scanners . The diffusion restriction effect induced by the lipid droplet boundary on the fat DW signal is reduced as the lipid droplet size increases, requires longer TEs as the gradient strength of gradient hardware decreases and can be confounded by scanner table vibrations and physiological motion due to the need of using high b‐values.…”

“…Previously published work has predominantly extracted an estimate for the restriction size by exploiting deviations from the monoexponential diffusion signal decay curve at a specific diffusion time . An estimate for the diffusion restriction size can also be obtained when investigating the dependency of the diffusion constant on the diffusion time assuming the short diffusion time limit (mean free path length is much smaller than the restriction barrier size).…”

“…Water signal was not detectable due to the strong diffusion‐weighting. Only the methylene peak area (at 1.3 ppm) was used to estimate the lipid droplet size, because the different fat peaks, in general, differ in diffusion coefficient and T 1 relaxation time …”

“…Recently, a high b‐value DW‐MRS has been applied to study myocellular lipid diffusion and to quantify the intramyocellular lipid droplet size by analyzing the ADC dependence on diffusion time . Diffusion restriction effects on the dependence of the DW signal on b‐value have also been reported in murine brown adipocytes ex vivo using a preclinical MR system with strong magnetic field gradients . Murine brown adipocytes enclose many lipid droplets with a diameter below 10 µm, whereas white adipocytes enclose a single lipid droplet with diameters between 50 and 150 µm.…”

Reduction of vibration‐induced signal loss by matching mechanical vibrational states: Application in high b‐value diffusion‐weighted MRS

“…Multiple research applications require particularly high b ‐values diffusion measurements, including high‐resolution diffusion tensor imaging of the brain or the assessment of fat microstructure with diffusion MRI . Specifically, measuring the diffusion properties of lipids has been proven to be challenging because fat has a diffusion coefficient approximately 2 orders of magnitude lower than water due to the large molecular size .…”