Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-12, Vol.111 (50), p.18001-18006
• Main Authors: Branca, Rosa Tamara, He, Ting, Le Zhang, Floyd, Carlos S., Freeman, Matthew, White, Christian, Burant, Alex
• Format: Article
• Language: English
• Subjects: Adipose Tissue, Brown - blood supply; Adipose Tissue, Brown - physiology; Animals; Biological Sciences; Body fat; Brown adipose tissue; Chemical equilibrium; Genotype & phenotype; Imaging; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Mice; Norepinephrine; Obesity; Protein folding; Rodents; Spectrum Analysis; Temperature; Temperature measurement; Temperature probes; Thermogenesis; Thermogenesis - physiology; Tissues; Weight control; Xenon; Xenon Isotopes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1403697111

Significance In recent years, there has been a growing interest in brown adipose tissue (BAT), a tissue specialized in nonshivering thermogenesis and considered to be the next therapeutic target against obesity and diabetes. However, the detection of this very sparse tissue still represents a major challenge. To our knowledge, we report the first in vivo detection of BAT and thermogenic activity by hyperpolarized xenon gas MRI. We show that during thermogenic activity a more than 15-fold enhancement in xenon uptake by BAT enables us to clearly differentiate this tissue from the surrounding tissue and to thereby overcome the major limitations of conventional imaging methods. We also use lipid-dissolved hyperpolarized xenon chemical shift to demonstrate direct in vivo MR thermometry of BAT. The study of brown adipose tissue (BAT) in human weight regulation has been constrained by the lack of a noninvasive tool for measuring this tissue and its function in vivo. Existing imaging modalities are nonspecific and intrinsically insensitive to the less active, lipid-rich BAT of obese subjects, the target population for BAT studies. We demonstrate noninvasive imaging of BAT in mice by hyperpolarized xenon gas MRI. We detect a greater than 15-fold increase in xenon uptake by BAT during stimulation of BAT thermogenesis, which enables us to acquire background-free maps of the tissue in both lean and obese mouse phenotypes. We also demonstrate in vivo MR thermometry of BAT by hyperpolarized xenon gas. Finally, we use the linear temperature dependence of the chemical shift of xenon dissolved in adipose tissue to directly measure BAT temperature and to track thermogenic activity in vivo.