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 recent discovery of active Brown Adipose Tissue (BAT) in adult humans has opened new avenues for obesity research and treatment, as reduced BAT activity seem to be implicated in human energy imbalance, diabetes, and hypertension. However, clinical applications are currently limited by the lack of non-invasive tools for measuring mass and function of this tissue in humans. Here we present a new magnetic resonance imaging method based on the normally invisible intermolecular multiple-quantum coherence ¹H MR signal. This method, which doesn’t require special hardware modifications, can be used to overcome partial volume effect, the major limitation of MR-based approaches that are currently being investigated for the detection of BAT in humans. With this method we can exploit the characteristic cellular structure of BAT to selectively image it, even when (as in humans) it is intimately mixed with other tissues. We demonstrate and validate this method in mice using PET scans and histology. We compare this methodology with conventional ¹H MR fat fraction methods. Finally, we investigate its feasibility for the detection of BAT in humans.

Significance: The search for new obesity drug targets and the rediscovery of active brown fat (brown adipose tissue; BAT) in adult humans has triggered a BAT renaissance. However, the assumption that this tissue plays a key role in energy balance in humans, as it does in rodents, is still a matter of debate. This is because BAT mass cannot be correctly quantified by current imaging techniques, as these are either nonspecific or lack the necessary sensitivity to detect BAT, especially in obese phenotypes. Here, we show that xenon-enhanced computed tomography can accurately quantify BAT mass, especially in obese mouse phenotypes in which extensive BAT hypertrophy hampers the detection of this tissue by current tomographic imaging techniques.