In Vivo Optical Imaging of Interscapular Brown Adipose Tissue with ¹⁸F-FDG via Cerenkov Luminescence Imaging

<div><p>Objective</p><p>Brown adipose tissue (BAT), a specialized tissue for thermogenesis, plays important roles for metabolism and energy expenditure. Recent studies validated BAT’s presence in human adults, making it an important re-emerging target for various pathologies. During this validation, PET images with ¹⁸F-FDG showed significant uptake of ¹⁸F-FDG by BAT under certain conditions. Here, we demonstrated that Cerenkov luminescence imaging (CLI) using ¹⁸F-FDG could be utilized for <i>in vivo</i> optical imaging of BAT in mice.</p><p>Methods</p><p>Mice were injected with ¹⁸F-FDG and imaged 60 minutes later with open filter and 2 minute acquisition. <i>In vivo</i> activation of BAT was performed by norepinephrine and cold treatment under isoflurane or ketamine anesthesia. Spectral unmixing and 3D imaging reconstruction were conducted with multiple-filter CLI images.</p><p>Results</p><p>1) It was feasible to use CLI with ¹⁸F-FDG to image interscapular BAT in mice, with the majority of the signal (>85%) at the interscapular site originating from BAT; 2) The method was reliable because excellent correlations between <i>in vivo</i> CLI, <i>ex vivo</i> CLI, and <i>ex vivo</i> radioactivity were observed; 3) CLI could be used for monitoring BAT activation under different conditions; 4) CLI signals from the group under short-term isoflurane anesthesia were significantly higher than that from the group under long-term anesthesia; 5) The CLI spectrum of ¹⁸F-FDG with a peak at 640 nm in BAT after spectral unmixing reflected the actual context of BAT; 6) Finally 3D reconstruction images showed excellent correlation between the source of the light signal and the location and physical shape of BAT.</p><p>Conclusion</p><p>CLI with ¹⁸F-FDG is a feasible and reliable method for imaging BAT in mice. Compared to PET imaging, CLI is significantly cheaper, faster for 2D planar imaging and easier to use. We believe that this method could be used as an important tool for researchers investigating BAT.</p>