Molecular Imaging of Brown Adipose Tissue Mass

Abstract

Brown adipose tissue (BAT), a uniquely thermogenic tissue that plays an important role in metabolism and energy expenditure, has recently become a revived target in the fight against metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD). Different from white adipose tissue (WAT), the brown adipocytes have distinctive features including multilocular lipid droplets, a large number of mitochondria, and a high expression of uncoupling protein-1 (UCP-1), as well as abundant capillarity. These histologic characteristics provide an opportunity to differentiate BAT from WAT using imaging modalities, such as PET/CT, SPECT/CT, MRI, NIRF and Ultrasound. However, most of the reported imaging methods were BAT activation dependent, and the imaging signals could be affected by many factors, including environmental temperatures and the states of the sympathetic nervous system. Accurate BAT mass detection methods that are independent of temperature and hormone levels have the capacity to track the development and changes of BAT throughout the lifetime of mammals, and such methods could be very useful for the investigation of potential BAT-related therapies. In this review, we focus on molecular imaging modalities that can detect and quantify BAT mass. In addition, their detection mechanism and limitations will be discussed as well.

Keywords: TSPO; activation-independent; brown adipose tissue; metabolic disorders; molecular imaging; rest state; tissue mass quantification.

Figure 1

BAT imaging with ¹¹C-MRB and ¹⁸F-FDG under room and cold temperature in male subject. ¹⁸F-FDG and ¹¹C-MRB are scaled from SUV 0 (black) to SUV 2 (white). ¹¹C-MRB images are computed from the average of frames acquired between 40 to 60 min post-injection. Original data with permission from reference [54].

Figure 2

BAT imaging with TSPO PET tracer: ⁶⁴Cu-Dis and ¹⁸F-F-DPA. (a) PET imaging with ⁶⁴Cu-Dis in mouse under room temperature. (b) Representative coronal image under a cold exposure condition. (c) Quantitative analysis of (a,b). There was no significant difference in uptake between control and cold-treated groups (p = 0.359). (d) PET imaging with ¹⁸F-F-DPA in a mouse under room temperature. (e) Representative coronal image under a cold exposure condition. (f) Quantitative analysis of (d,e). There was no significant difference in uptake between control and cold treated groups (p = 0.356).

Figure 3

BAT imaging with TSPO PET tracer: ¹¹C-PBR28. Representative images of a healthy volunteer who underwent PET/MRI using ¹¹C-PBR28. The images were obtained 60–90 min after 14 m Ci of ¹¹C-PBR28 injection. The supraclavicular BAT depots are indicated with arrows. Reproduced data with permission from reference [64].

Figure 4

BAT imaging with TSPO PET tracer ¹⁸F-F-DPA: (a) PET imaging with ¹⁸F-F-DPA in mouse under room temperature. (b) Representative coronal image under light anesthesia for 30 min before tracer injection. (c) Quantitative analysis of (a,b). There was a significant difference in uptake between the control and anesthesia treated groups.

Figure 5

Example of image registration and a reconstructed fat fraction map before and after cooling. The first column shows thermoneutral and post-cooling images (one slice from the first echo in the acquisition). In the second column, the overlay of the same images before (top) and after registration (bottom) is shown. The images are colored orange (thermoneutral) and blue (post-cooling) for better visualization of differences between the scans. The third column shows the thermoneutral and post-cooling fat fraction maps of the supraclavicular adipose depot, overlaid on the corresponding images. Lipid content in the supraclavicular region is color-mapped over a 30–100% fat fraction range. Reprinted with permission from reference [85]. Copyright © 2021 Abreu-Vieira, Sardjoe Mishre, Burakiewicz, Janssen, Nahon, van der Eijk, Riem, Boon, Dzyubachyk, Webb, Rensen and Kan.

Figure 6

BAT imaging with micellar SRFluor680. (A) Representative PET/CT with ¹⁸F-FDG in a single living SKH1 mouse. (B,C) Fluorescence/X-ray images of the same SKH1 mouse with micellar SRFluor680. (D) Effect of BAT metabolic activation on probe accumulation. Representative fluorescence images of the excised BAT are shown above each of the bars. Note: n.s. (not significant), ** (p < 0.01). Reproduced from reference [103] with permission from the Royal Society of Chemistry.