Imaging Metabolically Active Fat: A Literature Review and Mechanistic Insights

Figure 1. Summary of major physiological differences between white adipose tissue (WAT) and brown adipose tissue (BAT). A summary of major physiological differences relevant to imaging between WAT and BAT. FFA: free fatty acid, N: nucleus, M: mitochondria, β3-AR: beta-3 adrenergic receptor, G: glucose, L: lipid droplet, CD36: cluster of differentiation 36/fatty acid translocase, GLUT: glucose transporter.

Figure 2. CT showing different density and vascularity of BAT versus WAT. Subcutaneous WAT with a darker appearance on conventional display and fewer vessels (yellow circle) compared with BAT (blue circle).

Figure 3. MRI vs. FDG-PET/CT in detection of BAT. FDG-PET/CT and MRI of a healthy BAT-positive research subject. FDG uptake is visible in supraclavicular BAT with cold exposure on the PET maximum intensity projection (MIP; E, red arrows) and absent from the thermoneutral PET MIP (A). CT shows adipose tissue in the same region (B,F) and PET shows increased standardized uptake value there after exposure to cold (C,G). MRI-derived fat signal fraction from the same subject shows adipose tissue with relatively low levels of fat (white ovals) in the same region at thermoneutral and cold conditions (D,H). Image reproduced with permission from reference 41.

Figure 4. Change in blood oxygen level dependent MRI signal in human BAT with cold exposure. Change in blood oxygen level dependent MRI signal in supraclavicular BAT with cold exposure (13–16 °C) in healthy human research subjects. Images A, B, and C are representative images of 3 subjects. Image reproduced with permission from reference 47.

Figure 5. Example of variable iBAT uptake on FDG-PET/CT. FDG-PET/CT in a woman in her 20s showing marked BAT uptake in (A) November (yellow arrows) and no detectable BAT FDG uptake on a scan (B) 6 months later.

Figure 6. Variation of BAT FDG uptake in clinical patients. Fused coronal FDG-PET/CT, coronal CT, and fused axial FDG-PET/CT (A–C). (A) BAT FDG uptake in a woman with normal BMI. Note supraclavicular (yellow arrows), skull base (red arrow), paraesophageal (blue arrow), and perinephric (white arrow) uptake. (B) Supraclavicular BAT in an obese woman (yellow arrows). (C) Diffuse FDG uptake in subcutaneous WAT in a male patient (yellow arrows). (D) A male patient with extensive supraclavicular FDG uptake extending into the upper neck (yellow arrows) and paravertebral BAT activity (blue arrows).

Figure 7. BAT FTHA uptake in a healthy human subject. Transverse FTHA-PET (left panel), CT (middle panel) and fused PET/CT (right panel) in a healthy subject after 1 h of cold exposure. Supraclavicular BAT is shown in the red circle. Image reproduced with permission from reference 28.

Figure 8. BMIPP-SPECT/CT with and without beta-adrenergic stimulation. BMIPP-SPECT/CT scanning for the patterns of fatty acid uptake in the metabolic active fat tissues of adult mice at room temperature after 7 days of vehicle treatment (top) or 7 days of treatment with the β3-adrenergic agonist CL-316243 (bottom row). Treatment increased uptake in classical interscapular BAT cervical depots, and inducible anterior abdominal subcutaneous (arrow) and inguinal metabolically active fat tissue. Image reproduced with permission from reference 30.

Figure 9. 99mTc-MIBI uptake in iBAT on a clinical scan. Supraclavicular BAT uptake shown coronal and axial fused 99mTc-MIBI-SPECT/CT (yellow arrows). Salivary gland uptake (white arrows) is normal.

Figure 10. Hyperpolarized 13C-pyruvate MRI with cold exposure in a mouse. Hyperpolarized 13C-pyruvate MRI shows increased BAT activity in a mouse after cold exposure (solid arrow). The dashed arrows show the heart and large vessels and dotted arrow is a phantom. Image reproduced with permission from reference 92.

Figure 11. MSOT HbO2 map after norepinephrine treatment. MSOT image unmixed for HbO2 signal of murine interscapular BAT after treatment with norepinephrine (NE; top panel). BAT pads are shown in rectangles. The bottom panel shows the horizontal intensity profile with and without NE treatment. Image reproduced with permission from reference 95.

Figure 12. Physiological underpinnings of key imaging modalities for BAT research. The physiological basis for key imaging modalities in brown adipose tissue (BAT) research includes changes in inner action, vascularity, fat fraction, mitochondrial activity and key substrate transport and utilization. Comparison is made to white adipose tissue (WAT). N: nucleus, M: mitochondria, L: lipid droplet, FDG: 18F-Fluorodeoxyglucose, FTHA: 18F-Fluoro-6-Thia-Heptadecanoic Acid, BMIPP: 123I-Beta-Methyl-Iodophenyl-Pentadecanoic Acid.