Magnetic Resonance Imaging of Human Brown Adipose Tissue : Methodological Development and Application

Sammanfattning: Brown adipose tissue (BAT) is a thermogenic organ with the main human depot located in the cervical-supraclavicular (sBAT) region. BAT is proposed as a potential therapeutic target for obesity and diabetes. This thesis aims to contribute to the development of magnetic resonance imaging (MRI)-based methods and to the application of these in studies of human BAT. Water-fat MRI enables separation of water and fat, the dominant contributors to the MR signal, and the quantification of fat fraction (FF) and effective transverse relaxation rate (R2'). FF and R2' are often used in studies of human BAT, e.g. for characterizing the tissue and distinguishing it from white adipose tissue. A Cooling-reheating protocol was introduced for studying changes in sBAT, related to lipid content and perfusion. sBAT FF decreased after cold exposure. The sustained low FF after reheating suggested lipid consumption as the primary cause. This conclusion was based on the assumption of a normalized perfusion after reheating. An automated method for segmentation of sBAT was developed. The method compared well with a semi-automated reference method with respect to segmentation overlap and estimated mean sBAT FF and R2'. A modified version of the automated method was applied to a large-scale study where an association between sBAT FF and glucose tolerance indicated a role for BAT in glucose metabolism, potentially linked to the risk of developing diabetes.  A Cooling-reheating protocol was evaluated with positron emission tomography measurements of perfusion and cold-stimulated BAT activity. Inverse correlations between sBAT FF and BAT activity suggested sBAT FF to predict cold-induced BAT activity. After reheating, the cold-induced increase in perfusion normalized and the cold-induced decrease in FF partially normalized. This suggested potential decreases in FF after reheating to mainly be due to lipid consumption and decreases in FF after cold exposure to possibly be influenced by perfusion.