Characterizing Active and Inactive Brown Adipose Tissue in Adult Humans Using PET-CT and MR Imaging (original) (raw)
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EJNMMI Research
Background Brown adipose tissue (BAT) is a thermogenic tissue which can generate heat in response to mild cold exposure. As it constitutes a promising target in the fight against obesity, we need reliable techniques to quantify its activity in response to therapeutic interventions. The current standard for the quantification of BAT activity is [18F]FDG PET/CT. Various sequences in magnetic resonance imaging (MRI), including those measuring its relative fat content (fat fraction), have been proposed and evaluated in small proof-of-principle studies, showing diverging results. Here, we systematically compare the predictive value of adipose tissue fat fraction measured by MRI to the results of [18F]FDG PET/CT. Methods We analyzed the diagnostic reliability of MRI measured fat fraction (FF) for the estimation of human BAT activity in two cohorts of healthy volunteers participating in two prospective clinical trials (NCT03189511, NCT03269747). In both cohorts, BAT activity was stimulated...
Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using 18F-FDG PET/CT
Journal of Visualized Experiments, 2019
In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT's ability to expend energy has made it a potential target for novel therapies to ameliorate obesity and associated metabolic disorders in humans. Though this tissue has been well studied in small animals, BAT's thermogenic capacity in humans remains largely unknown due to the difficulties of measuring its volume, activity, and distribution. Identifying and quantifying active human BAT is commonly performed using 18 F-Fluorodeoxyglucose (18 F-FDG) positron emission tomography and computed tomography (PET/CT) scans following cold-exposure or pharmacological activation. Here we describe a detailed image-analysis approach to quantify total-body human BAT from 18 F-FDG PET/ CT scans using an open-source software. We demonstrate the drawing of user-specified regions of interest to identify metabolically active adipose tissue while avoiding common non-BAT tissues, to measure BAT volume and activity, and to further characterize its anatomical distribution. Although this rigorous approach is time-consuming, we believe it will ultimately provide a foundation to develop future automated BAT quantification algorithms.
Recent advances in the detection of brown adipose tissue in adult humans: a review
Clinical science (London, England : 1979), 2018
The activation of brown adipose tissue (BAT) is associated with reductions in circulating lipids and glucose in rodents and contributes to energy expenditure in humans indicating the potential therapeutic importance of targetting this tissue for the treatment of a variety of metabolic disorders. In order to evaluate the therapeutic potential of human BAT, a variety of methodologies for assessing the volume and metabolic activity of BAT are utilized. Cold exposure is often utilized to increase BAT activity but inconsistencies in the characteristics of the exposure protocols make it challenging to compare findings. The metabolic activity of BAT in response to cold exposure has most commonly been measured by static positron emission tomography of F-fluorodeoxyglucose in combination with computed tomography (F-FDG PET-CT) imaging, but recent studies suggest that under some conditions this may not always reflect BAT thermogenic activity. Therefore, recent studies have used alternative po...
Journal of Nuclear Medicine, 2013
For brown adipose tissue (BAT) to be effective at consuming calories, its blood flow must increase enough to provide sufficient fuel to sustain energy expenditure and also transfer the heat created to avoid thermal injury. Here we used a combination of human and rodent models to assess changes in BAT blood flow and glucose utilization. Methods: 99m Tc-methoxyisobutylisonitrile (MIBI) SPECT (n 5 7) and SPECT/CT (n 5 74) scans done in adult humans for parathyroid imaging were reviewed for uptake in regions consistent with human BAT. Site-directed biopsies of subcutaneous and deep neck fat were obtained for electron microscopy and gene expression profiling. In mice, tissue perfusion was measured with 99m Tc-MIBI (n 5 16) and glucose uptake with 18 F-FDG (n 5 16). Animals were kept fasting overnight, anesthetized with pentobarbital, and given intraperitoneally either the b 3adrenergic receptor agonist CL-316,243, 1 mg/kg (n 5 8), or saline (n 5 8) followed by radiotracer injection 5 min later. After 120 min, the mice were imaged using SPECT/CT or PET/CT. Vital signs were recorded over 30 min during the imaging. BAT, white adipose tissue (WAT), muscle, liver, and heart were resected, and tissue uptake of both 99m Tc-MIBI and 18 F-FDG was quantified by percentage injected dose per gram of tissue and normalized to total body weight. Results: In 5.4% of patients (4/74), 99m Tc-MIBI SPECT/CT showed increased retention in cervical and supraclavicular fat that displayed multilocular lipid droplets, dense capillary investment, and a high concentration of ovoid mitochondria. Expression levels of the tissue-specific uncoupling protein-1 were 180 times higher in BAT than in subcutaneous WAT (P , 0.001). In mice, BAT tissue perfusion increased by 61% (P , 0.01), with no significant changes in blood flow to WAT, muscle, heart, or liver. CL-316,243 increased glucose uptake in BAT even more, by 440% (P , 0.01). Conclusion: Pharmacologic activation of BAT requires increased blood flow to deliver glucose and oxygen for thermogenesis. However, the glucose consumption far exceeds the vascular response. These findings demonstrate that activated BAT increases glucose uptake beyond what might occur by increased blood flow alone and suggest that activated BAT likely uses glucose for nonthermogenic purposes.
Background Obesity and its metabolic consequences are a major cause of morbidity and mortality. Brown adipose tissue (BAT) utilises glucose and free fatty acids to produce heat, thereby increasing energy expenditure. Effective evaluation of human BAT stimulators is constrained by current standard BAT assessment methods as positron emission tomography-computed tomography (PET-CT) requires exposure to high doses of ionising radiation. Infrared thermography (IRT) is a potential non-invasive, safe alternative, although direct corroboration with PET-CT has not previously been established. Methods IRT and 18F-fluorodeoxyglucose (18F-FDG) PET-CT data from 8 healthy male participants subjected to water jacket cooling were directly compared. Thermal images (TIs) were geometrically transformed to overlay PET-CT-derived maximum intensity projection (MIP) images from each subject and the areas of greatest intensity of temperature and glucose-uptake within the supraclavicular regions compared. Relationships between supraclavicular temperatures from IRT (TSCR) and the maximum rate of glucose uptake (MR(gluc)) from PET-CT were determined. Results Glucose uptake on MR(gluc)MIP was positively correlated with change in TSCR relative to a reference region (r2 = 0.721; p=0.008). Spatial overlap between areas of maximal MR(gluc)MIP and maximal TSCR was 29.5±5.1%. Prolonged cooling to 60 minutes was associated with further TSCR rise compared with cooling to 10 minutes. Conclusions The supraclavicular hotspot identified on IRT closely corresponds to the area of maximal uptake on PET-CT-derived MR(gluc)MIP images. Greater increases in relative TSCR were associated with raised glucose uptake. IRT should now be considered a suitable method for measuring BAT activation, especially in populations where PET-CT is not feasible, practical or repeatable.
Obesity
This study aimed to compare the associations of positron emission tomography (PET), magnetic resonance (MR), and infrared thermography (IRT) imaging modalities with energy expenditure (EE) after brown adipose tissue (BAT) activation using capsinoid ingestion and cold exposure. Methods: Twenty participants underwent PET-MR, IRT imaging, and whole-body calorimetry after capsinoid ingestion and cold exposure. Standardized uptake values (SUV) and the fat fraction (FF) of the supraclavicular brown adipose tissue regions were estimated. The anterior supraclavicular temperature (Tscv) from IRT at baseline and postintervention was measured. Two-hour post-capsinoid ingestion EE and post-cold exposure EE served as a reference to correlate fluorodeoxyglucose uptake, FF, and Tscv for BAT assessment. IRT images were geometrically transformed to overlay on PET-MR for visualization of the hottest regions. Results: The supraclavicular hot spot identified on IRT closely corresponded to the area of maximal fluorodeoxyglucose uptake on PET images. Controlling for body weight, post-cold exposure Tscv was a significant variable associated with EE (P = 0.025). The SUV was significantly inversely correlated with FF (P = 0.012) and significantly correlated with peak of Tscv during cold exposure in BAT-positive participants (P = 0.022). Conclusions: Tscv correlated positively with EE and was also significantly correlated with SUV after cold exposure. Both IRT and MR FF are promising methods to study BAT activity noninvasively.
Cell Metabolism, 2016
Human brown adipose tissue (BAT) presence, metabolic activity, and estimated mass are typically measured by imaging [18F]fluorodeoxyglucose (FDG) uptake in response to cold exposure in regions of the body expected to contain BAT, using positron emission tomography combined with X-ray computed tomography (FDG-PET/CT). Efforts to describe the epidemiology and biology of human BAT are hampered by diverse experimental practices, making it difficult to directly compare results among laboratories. An expert panel was assembled by the National Institute of Diabetes and Digestive and Kidney Diseases on November 4, 2014 to discuss minimal requirements for conducting FDG-PET/CT experiments of human BAT, data analysis, and publication of results. This resulted in Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0). Since there are no fully validated best practices at this time, panel recommendations are meant to enhance comparability across experiments, but not to constrain experimental design or the questions that can be asked.
Mapping of human brown adipose tissue in lean and obese young men
Proceedings of the National Academy of Sciences of the United States of America, 2017
Human brown adipose tissue (BAT) can be activated to increase glucose uptake and energy expenditure, making it a potential target for treating obesity and metabolic disease. Data on the functional and anatomic characteristics of BAT are limited, however. In 20 healthy young men [12 lean, mean body mass index (BMI) 23.2 ± 1.9 kg/m(2); 8 obese, BMI 34.8 ± 3.3 kg/m(2)] after 5 h of tolerable cold exposure, we measured BAT volume and activity by (18)F-labeled fluorodeoxyglucose positron emission tomography/computerized tomography (PET/CT). Obese men had less activated BAT than lean men (mean, 130 vs. 334 mL) but more fat in BAT-containing depots (mean, 1,646 vs. 855 mL) with a wide range (0.1-71%) in the ratio of activated BAT to inactive fat between individuals. Six anatomic regions had activated BAT-cervical, supraclavicular, axillary, mediastinal, paraspinal, and abdominal-with 67 ± 20% of all activated BAT concentrated in a continuous fascial layer comprising the first three depots ...
Human brown fat radiodensity indicates underlying tissue composition and systemic metabolic health
The Journal of clinical endocrinology and metabolism, 2017
Metabolic imaging studying brown adipose tissue (BAT) physiology has increased, where computed tomography (CT) is commonly used as an anatomical reference for metabolic PET (positron emission tomography) imaging. However, the capacity of CT to provide metabolic information has been underexploited. To evaluate whether CT radiodensity of BAT could non-invasively estimate underlying tissue morphology, regarding amount of stored triglycerides. Further, could the alteration in tissue characteristics due to cold stimulus, as a marker for active BAT, be detected with radiodensity. And, whether BAT can be differentiated from white adipose tissue (WAT) solely using CT based measurements. A cross-sectional study evaluating sixty-six healthy human subjects with CT, PET and 1H-magnetic resonance spectroscopy (1H-MRS). BAT radiodensity was measured with CT. BAT stored triglyceride content was measured with 1H-MRS. Arterial blood volume in BAT, as a marker of tissue vascularity, was measured with...
Hybrid PET/MRI as a tool to detect brown adipose tissue: Proof of principle
Obesity Research & Clinical Practice, 2015
Objective: The purpose of this study was to assess the performance of 18 F-FDG hybrid PET/MRI to detect and localise the presence of metabolically active brown adipose tissue (BAT). Methods: We retrospectively analyzed 197 consecutive 18 F-flurodeoxyglucose ( 18 F-FDG) positron-emission tomographic (PET) and magnetic resonance imaging (MRI) images performed with a hybrid whole-body PET-MRI tomography in 192 patients. These patients were originally investigated mainly for oncological staging, in the absence of a cooling protocol. The presence of BAT was defined as a soft tissue structure that was larger than 4 mm in diameter, had the characteristics of fat tissue on MRI and had a maximal standardised uptake value (SUV) of 18 F-FDG of at least 2.0. No specific MRI sequences for BAT detection were acquired. Results: PET/MRI identified the presence of metabolically active BAT in 5 out of 192 patients (2.6%). BAT positive subjects were all female, significantly younger and with significantly lower body weight than BAT negative subjects. Conclusions: Whole body hybrid PET/MRI allowed for the identification of BAT, with a low prevalence, comparable to previous retrospective PET/CT studies realised in the absence of a cooling protocol. The main advantages of the PET/MRI hybrid