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Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography.

ABSTRACT: Detection and quantification of brown adipose tissue (BAT) mass remains a major challenge, as current tomographic imaging techniques are either nonspecific or lack the necessary resolution to quantify BAT mass, especially in obese phenotypes, in which this tissue may be present but inactive. Here, we report quantification of BAT mass by xenon-enhanced computed tomography. We show that, during stimulation of BAT thermogenesis, the lipophilic gas xenon preferentially accumulates in BAT, leading to a radiodensity enhancement comparable to that seen in the lungs. This enhancement is mediated by a selective reduction in BAT vascular resistance, which greatly increases vascular perfusion of BAT. This enhancement enables precise identification and quantification of BAT mass not only in lean, but also in obese, mouse phenotypes, in which this tissue is invisible to conventional tomographic imaging techniques. The method is developed and validated in rodents and then applied in macaques to assess its feasibility in larger species.

SUBMITTER: Branca RT

PROVIDER: S-EPMC5776810 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography.

Branca Rosa T RT McCallister Andrew A Yuan Hong H Aghajanian Amir A Faber James E JE Weimer Nicholas N Buchanan Riley R Floyd Carlos S CS Antonacci Michael M Zhang Le L Burant Alex A

Proceedings of the National Academy of Sciences of the United States of America 20171218 1

Detection and quantification of brown adipose tissue (BAT) mass remains a major challenge, as current tomographic imaging techniques are either nonspecific or lack the necessary resolution to quantify BAT mass, especially in obese phenotypes, in which this tissue may be present but inactive. Here, we report quantification of BAT mass by xenon-enhanced computed tomography. We show that, during stimulation of BAT thermogenesis, the lipophilic gas xenon preferentially accumulates in BAT, leading to ...[more]

PMID: 29255046

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Project description:ObjectivesObesity and its distribution pattern are important factors for the prediction of the onset of diabetes in humans. Since several mouse models are suitable to study the pathophysiology of type 2 diabetes the aim was to validate a novel computed tomograph model (Aloka-Hitachi LCT-200) for the quantification of visceral, subcutaneous, brown and intrahepatic fat depots in mice.MethodsDifferent lean and obese mouse models (C57BL/6, B6.V-Lep(ob), NZO) were used to determine the most adequate scanning parameters for the detection of the different fat depots. The data were compared with those obtained after preparation and weighing the fat depots. Liver fat content was determined by biochemical analysis.ResultsThe correlations between weights of fat tissues on scale and weights determined by CT were significant for subcutaneous (r(2) = 0.995), visceral (r(2) = 0.990) and total white adipose tissue (r(2) = 0.992). Moreover, scans in the abdominal region, between lumbar vertebrae L4 to L5 correlated with whole-body fat distribution allowing experimenters to reduce scanning time and animal exposure to radiation and anesthesia. Test-retest reliability and measurements conducted by different experimenters showed a high reproducibility in the obtained results. Intrahepatic fat content estimated by CT was linearly related to biochemical analysis (r(2) = 0.915). Furthermore, brown fat mass correlated well with weighted brown fat depots (r(2) = 0.952). In addition, short-term cold-expose (4 °C, 4 hours) led to alterations in brown adipose tissue attributed to a reduction in triglyceride content that can be visualized as an increase in Hounsfield units by CT imaging.ConclusionThe 3D imaging of fat by CT provides reliable results in the quantification of total, visceral, subcutaneous, brown and intrahepatic fat in mice. This non-invasive method allows the conduction of longitudinal studies of obesity in mice and therefore enables experimenters to investigate the onset of complex diseases such as diabetes and obesity.

Project description:BACKGROUND:Positron emission tomography (PET) is increasingly applied for in vivo brown adipose tissue (BAT) research in healthy volunteers. To limit the radiation exposure, the injected 18F-FDG tracer dose should be as low as possible. With simultaneous PET/MR imaging, the radiation exposure due to computed tomography (CT) can be avoided, but more importantly, the PET acquisition time can often be increased to match the more extensive magnetic resonance (MR) imaging protocol. The potential gain in detected coincidence counts, due to the longer acquisition time, can then be applied to decrease the injected tracer dose. The aim of this study was to investigate the minimal 18F-FDG dose for a 10-min time-of-flight (TOF) PET/MR acquisition that would still allow accurate quantification of supraclavicular BAT volume and activity. METHODS:Twenty datasets from 13 volunteers were retrospectively included from a prospective clinical study. PET emission datasets were modified to simulate step-wise reductions of the original 75?MBq injected dose. The resulting PET images were visually and quantitatively assessed and compared to a 4-min reference scan. For the visual assessment, the image quality and artifacts were scored using a 5-point and a 3-point Likert scale. For the quantitative analysis, image noise and artifacts, BAT metabolic activity, BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were investigated. RESULTS:The visual assessment showed still good image quality for the 35%, 30%, and 25% activity reconstructions with no artifacts. Quantitatively, the background noise was similar to the reference for the 35% and 30% activity reconstructions and the artifacts started to increase significantly in the 25% and lower activity reconstructions. There was no significant difference in supraclavicular BAT metabolic activity, BMV, and TBG between the reference and the 35% to 20% activity reconstructions. CONCLUSIONS:This study indicates that when the PET acquisition time is matched to the 10-min MRI protocol, the injected 18F-FDG tracer dose can be reduced to approximately 19?MBq (25%) while maintaining image quality and accurate supraclavicular BAT quantification. This could decrease the effective dose from 1.4?mSv to 0.36?mSv.

Project description:Background Recent studies have reported the association between pericoronary inflammation assessed by pericoronary adipose tissue attenuation (PCATA) on computed tomography angiography and worse outcomes in patients with coronary artery disease. We investigated the determinants predicting increased PCATA in patients with known or suspected coronary artery disease. Methods and Results A total of 540 patients who underwent computed tomography angiography and invasive coronary angiography were studied. Mean computed tomography attenuation values of PCAT (-190 to -30 Hounsfield units) (PCATA) were assessed at the proximal 40-mm segments of all 3 major coronary arteries by crude analysis. Univariable and multivariable analyses were performed to determine the predictors of increased PCATA surrounding the proximal right coronary artery. Mean right coronary artery-PCATA was -72.22±8.47 Hounsfield units and the average of 3-vessel PCATA was -70.24±6.60 Hounsfield units. Multivariable linear regression analysis revealed that the independent determinants of right coronary artery-PCATA were male (β coefficient=4.965, P<0.001), left ventricular mass index (β coefficient=0.040, P=0.025), and angiographically significant stenosis (diameter stenosis >50%) (β coefficient=2.418, P=0.008). Sex-related determinants were NT-proBNP level (N-terminal pro-B-type natriuretic peptide; β coefficient <0.001, P=0.026), Agatston score (β coefficient=-0.002, P=0.010), left ventricular mass index (β coefficient=0.041, P=0.028), and significant stenosis (β coefficient=4.006, P<0.001) in male patients and left ventricular ejection fraction (β coefficient=-0.217, P=0.010) and significant stenosis (β coefficient=3.835, P=0.023) in female patients. Conclusions Right coronary artery-PCATA was associated with multiple clinical characteristics, established risk factors, and the presence of significant stenosis. Our results suggest that clinically significant factors such as sex, left ventricular hypertrophy, ejection fraction, calcification, and epicardial stenosis should be taken into account in the assessment of pericoronary inflammation using computed tomography angiography.

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Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography.

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Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography.

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