Gethin Williams

Identification and importance of brown adipose tissue in adult humans.

BACKGROUND Obesity results from an imbalance between energy intake and expenditure. In rodents and newborn humans, brown adipose tissue helps regulate energy expenditure by thermogenesis mediated by the expression of uncoupling protein 1 (UCP1), but brown adipose tissue has been considered to have no physiologic relevance in adult humans. METHODS We analyzed 3640 consecutive (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans performed for various diagnostic reasons in 1972 patients for the presence of substantial depots of putative brown adipose tissue. Such depots were defined as collections of tissue that were more than 4 mm in diameter, had the density of adipose tissue according to CT, and had maximal standardized uptake values of (18)F-FDG of at least 2.0 g per milliliter, indicating high metabolic activity. Clinical indexes were recorded and compared with those of date-matched controls. Immunostaining for UCP1 was performed on biopsy specimens from the neck and supraclavicular regions in patients undergoing surgery. RESULTS Substantial depots of brown adipose tissue were identified by PET-CT in a region extending from the anterior neck to the thorax. Tissue from this region had UCP1-immunopositive, multilocular adipocytes indicating brown adipose tissue. Positive scans were seen in 76 of 1013 women (7.5%) and 30 of 959 men (3.1%), corresponding to a female:male ratio greater than 2:1 (P<0.001). Women also had a greater mass of brown adipose tissue and higher (18)F-FDG uptake activity. The probability of the detection of brown adipose tissue was inversely correlated with years of age (P<0.001), outdoor temperature at the time of the scan (P=0.02), beta-blocker use (P<0.001), and among older patients, body-mass index (P=0.007). CONCLUSIONS Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT. Most important, the amount of brown adipose tissue is inversely correlated with body-mass index, especially in older people, suggesting a potential role of brown adipose tissue in adult human metabolism.

Method for Decreasing Uptake of 18F-FDG by Hypermetabolic Brown Adipose Tissue on PET

OBJECTIVE The purpose of this study was to determine whether use of a high-fat, very-low-carbohydrate protocol for preparing patients for PET decreases the frequency of (18)F-FDG uptake by hypermetabolic brown adipose tissue (BAT) on PET scans. MATERIALS AND METHODS In this HIPAA-compliant retrospective study, 741 FDG PET/CT scans obtained during the winter months (October 1-April 30) for patients who prepared with a high-fat, very-low-carbohydrate, protein-permitted protocol were compared with 1,229 FDG PET scans obtained during the winter months for patients who prepared by fasting. FDG uptake on PET scans co-localized with regions of fat identified on the CT scans was assumed to represent hypermetabolic BAT. The categoric variables frequency of occurrence of hypermetabolic BAT (present or not) and the sex ratios of the groups before and after the change in preparation were compared by use of a chi-square test. The continuous variables of age and blood glucose level were compared by use of a two-tailed Students t test. RESULTS In this intention-to-treat analysis, there was no difference between the fasting (n = 1,229) and the high-fat, very-low-carbohydrate, protein-permitted diet (n = 741) groups in terms of age and sex. Patients who prepared with the high-fat diet had a significantly lower frequency of hypermetabolic BAT uptake on FDG PET scans during the winter months (p<0.0002) and had lower blood glucose levels (p<<0.001). CONCLUSION In this intention-to-treat analysis, use of a high-fat preparation protocol significantly lowered the frequency of uptake of FDG by hypermetabolic BAT on FDG PET studies. Use of this protocol has the potential to decrease the rate of false-positive findings on oncologic FDG PET scans.

Retrospective study of coronary uptake of 18F-fluorodeoxyglucose in association with calcification and coronary artery disease: a preliminary study.

ObjectiveTo determine whether focal 18F-fluorodeoxyglucose (FDG) uptake could be detected along the course of coronary arteries in patients with known coronary artery disease (CAD) and/or coronary artery calcification (CAC) by PET/computed tomography (CT) using a new patient preparation protocol that reduces background myocardial FDG uptake. Materials and methodsIn this retrospective, Health Insurance Portability and Accountability Act-compliant study approved by our institutional internal review board, 60 FDG-PET/CT studies performed for noncardiac indications were reviewed and CAC and focal FDG uptake were determined. Cardiac histories were obtained. Age range was 21–88 years (64±16 years); 35 women/25 men; six had CAD documented by myocardial perfusion imaging, cardiac catheterization, or history of percutaneous coronary intervention or coronary artery bypass grafting. Chi-square probabilities were calculated. ResultsFifteen of the 60 patients studied showed focal FDG uptake along the course of coronary arteries; fourteen of these showed significant CAC scores and four had documented CAD. The concordance of focal FDG coronary artery uptake was 58% with CAC, 77% with cardiac history, and 90% with extracardiac vascular focal FDG uptake. There were 20 focal FDG and coronary artery lesions in 15 patients and 11 of the 20 colocalized with calcification. No preferred anatomic location was found (junction, end of calcification or along coronary artery). ConclusionThis limited retrospective study shows that with a new patient preparation to reduce high FDG uptake by the myocardium on PET/CT scans, foci of increased FDG cardiac uptake can be seen in association with CAC and in patients with a history of CAD. These results provide initial evidence that it may be possible to use FDG-PET/CT to monitor sites of coronary plaque formation. Larger and invasive prospective studies will be necessary to fully determine the suitability of this technique for that purpose.