A Z Lau1, A P Chen2, Y Gu3, M Ladouceur-Wodzak3, K S Nayak4, C H Cunningham1. 1. 1] Department of Medical Biophysics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada [2] Department of Imaging Research, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 2. GE Healthcare, Toronto, Ontario, Canada. 3. Department of Medical Biophysics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 4. Department of Electrical Engineering, University of Southern California, Los Angeles, CA, USA.
Abstract
OBJECTIVE: The recent identification of functional depots of brown adipose tissue (BAT) in adult humans has potential implications for the treatment of obesity. In order to evaluate new therapies aimed at inducing the production of more BAT or activating BAT in humans, it will be important to develop noninvasive methods to assess the functional state of the tissue in vivo. In this study, we investigate the feasibility of using hyperpolarized (13)C imaging to noninvasively identify functional, activated BAT in an in vivo rodent model, in less than 1 min, following an infusion of pre-polarized [1-(13)C] pyruvate. DESIGN: Hyperpolarized (13)C imaging was used to monitor BAT metabolic conversion of pre-polarized [1-(13)C] pyruvate in rats during baseline and norepinephrine (NE)-stimulated conditions. RESULTS: Activated BAT, stimulated by NE injection, can be detected in rats by increased conversion of pre-polarized [1-(13)C] pyruvate into its downstream products (13)C bicarbonate and [1-(13)C] lactate. The colocalization of the (13)C signal to interscapular BAT was validated using hematoxylin-eosin histological staining. CONCLUSION: The radiation-free nature and recent translation into the clinic of the hyperpolarized (13)C-imaging test may potentially facilitate trials of therapeutics targeting BAT activation in humans.
OBJECTIVE: The recent identification of functional depots of brown adipose tissue (BAT) in adult humans has potential implications for the treatment of obesity. In order to evaluate new therapies aimed at inducing the production of more BAT or activating BAT in humans, it will be important to develop noninvasive methods to assess the functional state of the tissue in vivo. In this study, we investigate the feasibility of using hyperpolarized (13)C imaging to noninvasively identify functional, activated BAT in an in vivo rodent model, in less than 1 min, following an infusion of pre-polarized [1-(13)C] pyruvate. DESIGN: Hyperpolarized (13)C imaging was used to monitor BAT metabolic conversion of pre-polarized [1-(13)C] pyruvate in rats during baseline and norepinephrine (NE)-stimulated conditions. RESULTS: Activated BAT, stimulated by NE injection, can be detected in rats by increased conversion of pre-polarized [1-(13)C] pyruvate into its downstream products (13)C bicarbonate and [1-(13)C] lactate. The colocalization of the (13)C signal to interscapular BAT was validated using hematoxylin-eosin histological staining. CONCLUSION: The radiation-free nature and recent translation into the clinic of the hyperpolarized (13)C-imaging test may potentially facilitate trials of therapeutics targeting BAT activation in humans.
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