Abstract

The recent discovery of active brown fat in human adults has led to renewed interest in the role of this key metabolic tissue. This is particularly true for neurodegenerative conditions like Huntington disease (HD), an adult-onset heritable disorder with a prominent energy deficit phenotype. Current methods for imaging brown adipose tissue (BAT) are in limited use because they are equipment-wise demanding and often prohibitively expensive. This prompted us to explore how a standard MRI set-up can be modified to visualize BAT in situ by taking advantage of its characteristic fat/water content ratio to differentiate it from surrounding white fat. We present a modified MRI protocol for use on an 11.7 T small animal MRI scanner to visualize and quantify BAT in wild-type and disease model laboratory mice. In this application study using the R6/2 transgenic mouse model of HD we demonstrate a significantly reduced BAT volume in HD mice vs. matched controls (n = 5 per group). This finding provides a plausible structural explanation for the previously described temperature phenotype of HD mice and underscores the significance of peripheral tissue pathology for the HD phenotype. On a more general level, the results demonstrate the feasibility of MR-based BAT imaging in rodents and open the path towards transferring this imaging approach to human patients. Future studies are needed to determine if this method can be used to track disease progression in HD and other disease entities associated with BAT abnormalities, including metabolic conditions such as obesity, cachexia, and diabetes.

Highlights

  • Brown adipose tissue (BAT) is a key tissue for the regulation of whole-body energy metabolism [1]

  • Since BAT is expected to show an almost equal magnetization of fat- and water spins, BAT presents as bright signal intensity in the final 2PM images

  • Since the approach is based on a conventional FLASH technique, it can be readily used on any conventional MRI scanner without further modification of acquisition methods

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Summary

Introduction

Brown adipose tissue (BAT) is a key tissue for the regulation of whole-body energy metabolism [1]. A series of breakthrough positron emission tomography (PET) and computed tomography (CT) imaging studies has recently shown BAT deposits even in adult humans [2,3,4,5]. This resulted in a renewed interest in the role of BAT especially for metabolic conditions such as obesity and cachexia, thereby creating the need for appropriate imaging technologies [6]. Large-scale studies aiming at the structural and functional characterization of BAT by PET/CT in human adults are still scarce [4,6,7]. Factors contributing to this limitation include the high costs for the required tracers, safety concerns about the radiation involved, and the required activation of BAT either via cold-exposure or pharmacologically

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