Intermolecular zero-quantum MRI for imaging Brown Adipose Tissue

Obesity is rapidly spreading across most developed countries and is thought to be more harmful to health than alcohol or smoking because of its association with many other medical conditions. At a fundamental level, obesity is the result of an imbalance between energy intake and energy expenditure. 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. BAT is considered to be the ‘‘good fat’’ that, unlike the white ‘‘bad fat’’, burns calories to produce heat through a process known as non-shivering thermogenesis. Until recently, BAT was thought to exist in humans only in infancy and early childhood. However, combined 18F fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and CT scans have identified active BAT in adults and shown a strong correlation between BAT activity and the basal metabolic rate. As it turned out, BAT was previously missed in adult humans because of its diffuse anatomical distribution: the tissue is present only in scattered amounts in the neck and chest areas, around major blood vessels, muscles or white fat. Nevertheless, it is estimated that BAT activity could account for up to 20% of daily energy expenditure in an adult human.

However, clinical investigation of BAT is currently limited by the lack of non-invasive tools for measuring mass and function of this tissue in humans. Although BAT tissue is a clear target for obesity treatments, the current modality of choice for imaging metabolically active BAT in humans, 18F PET/CT, has significant limitations. BAT metabolism relies on fatty acid consumption, not glucose consumption, so 18F-FDG-PET is highly nonspecific. Moreover, confounding factors such as blood glucose levels and room temperature conditions may affect glucose uptake in BAT.

To meet this challenge, a group from the University of North Carolina at Chapel Hill, North Carolina, USA have recently described the development of a new magnetic resonance imaging method based on the normally invisible intermolecular multiple-quantum coherence 1H MR signal (Branca RT et al In Vivo Noninvasive Detection of Brown Adipose Tissue through Intermolecular Zero-Quantum MRI. PLOS One Sept 2013 e7420). The 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 the group showed that they could exploit the characteristic cellular structure of BAT to selectively image it, even when (as in humans) it is intimately mixed with other tissues. The researchers demonstrated and validated the method in mice using PET scans and histology and compared the methodology with conventional 1H MR fat fraction methods. The group also investigated its feasibility for the detection of BAT in humans.

The group conclude that although more experiments are needed to validate the methodology in humans, the possibility to detect BAT with MR, independently from its activity, is an important feature that will inherently lead to fewer false negative results than 18F-FDGPET scans. This should facilitate future studies in which the true prevalence of this tissue can be determined in the adult  human population and its metabolic dysfunction detected.

http://tinyurl.com/Branca-et-al-paper