title: Two-point magnitude MRI for rapid mapping of brown adipose tissue and its application to the R6/2 mouse model of Huntington disease.
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.
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Katrin S
authors.initials: KS
authors.lastname: Lindenberg
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Weydt
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Müller
authors.affiliation: Department of Internal Medicine II, Ulm University, Ulm, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Bornstedt
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: G Bernhard
authors.initials: GB
authors.lastname: Landwehrmeyer
authors.affiliation: Department of Internal Medicine II, Ulm University, Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rottbauer
authors.affiliation: Department of Neurology, Ulm University, Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kassubek
authors.affiliation: Department of Internal Medicine II, Ulm University, Ulm, Germany; Core Facility Small Animal Imaging, Ulm University, Ulm, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Rasche
mesh_terms: D002001:Adipose Tissue, Brown / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006816:Huntington Disease / Q000175:diagnosis / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic