Faculty Bibliography

The rates of diabetes, obesity, and metabolic disease have reached epidemic proportions worldwide. In recent years there has been renewed interest in combating these diseases not only by modifying energy intake and lifestyle factors, but also by inducing endogenous energy expenditure. This approach has largely been stimulated by the recent recognition that brown adipose tissue (BAT)-long known to promote heat production and energy expenditure in infants and hibernating mammals-also exists in adult humans. This landmark finding relied on the use of clinical fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography, and imaging techniques continue to play a crucial and increasingly central role in understanding BAT physiology and function. Herein, the authors review the origins of BAT imaging, discuss current preclinical and clinical strategies for imaging BAT, and discuss imaging methods that will provide crucial insight into metabolic disease and how it may be treated by modulating BAT activity. (©) RSNA, 2016.

OBJECTIVE:To determine body composition predictors of skeletal integrity in overweight/obese subjects using dual energy X-ray absorptiometry (DXA). We hypothesized that visceral adiposity would be negatively, and lean mass positively, associated with DXA measures of skeletal integrity in obesity. MATERIALS AND METHODS/METHODS:Our study was institutional review board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPAA)-compliant and written informed consent was obtained. We studied 82 overweight or obese, but otherwise healthy premenopausal women and men of similar age who were part of a clinical trial (mean age: 37 ± 10 years, mean BMI: 34 ± 7 kg/m(2)). All subjects underwent DXA of the spine and hip for assessment of bone mineral density (BMD), trabecular bone score (TBS), and hip structural analysis (HSA), and of the whole body for the assessment of body composition, including estimated visceral adipose tissue (VAT). RESULTS:Sixty-three subjects (77 %) had normal BMD and 19 subjects (23 %) had osteopenia. There were strong age-, sex-, and BMD-independent positive associations between lean mass and HSA parameters (r = 0.50 to r = 0.81, p < 0.0001), whereas there was no association with TBS. There were strong age-, sex- and BMD-independent inverse associations between total fat and VAT mass and TBS (r = -0.60 and r = -0.72, p < 0.0001 for both correlations), whereas there were no associations with HSA parameters. CONCLUSION/CONCLUSIONS:Lean mass is a positive predictor of hip geometry, whereas fat and VAT mass are negative predictors of trabecular microarchitecture in overweight/obese subjects.

OBJECTIVE:Growth hormone (GH) administration reduces abdominal, but not lower body, fat mass. To gain insight into the underlying mechanisms, this study examined the expression of the GH receptor (GHR) and some of its targets in abdominal and gluteal adipose tissue. METHODS:GHR and GH targets in the lipolytic pathway were assessed (quantitative PCR/Western blotting) in adipose aspirates from premenopausal women [n = 15, age 26.9 ± 6.1 years, body mass index (BMI) 28.0 ± 6.8 kg/m(2) ] and men (n = 28, age 29.2 ± 7.0 years, BMI 26.9 ± 3.7 kg/m(2) ). RESULTS:GHR mRNA expression was lower in the gluteal depot when compared with the abdominal depot (P = 0.01). Abdominal GHR correlated negatively with age and BMI, whereas gluteal GHR was associated with lower waist-to-hip ratio (WHR), that is, pear shape. In both sites, GHR mRNA correlated strongly with genes important for the regulation of lipolysis: adipose tissue triglyceride lipase (ATGL), hormone-sensitive lipase, perilipin, and CIDEA (all P < 0.001), independently of BMI, WHR, age, and sex. GHR protein was lower in the gluteal fat when compared with the abdominal fat (P = 0.03) and correlated with ATGL protein in the gluteal depot (P < 0.001). CONCLUSIONS:GHR levels correlate with levels of lipases and lipid droplet-associated proteins crucial for lipolysis. Thus, higher GHR expression in the abdominal depot when compared with the gluteal depot may underlie the in vivo effect of GH to specifically reduce abdominal adipose tissue mass.

OBJECTIVE:To determine the association between adiposity, hormones, and cognition in young men with abdominal obesity. METHODS:In this cross-sectional observational study, 53 nondiabetic men with abdominal obesity (mean body mass index, 37.3 kg/m(2) ; age, 22-45 years) and normal intelligence underwent detailed measures of body composition, hormonal profiles, and cognition. Age- and education-adjusted performance in five cognitive domains was examined. RESULTS:Total fat percentage was negatively associated with visuospatial skills (P = 0.002) and visual memory (P = 0.012). Insulin resistance (homeostatic model assessment of insulin resistance) was also negatively associated with these domains (P = 0.05 and trend, P = 0.06, respectively). Total testosterone levels were negatively associated with executive function and verbal learning and memory (P = 0.04 for each), but free testosterone was not. Sex hormone-binding globulin (SHBG) was also inversely associated with performance in these domains (P = 0.015 and trend, P = 0.09, respectively). In a stepwise regression model including percentage fat, homeostatic model assessment of insulin resistance, SHBG, and free testosterone, SHBG was the only variable selected for executive function (P = 0.05) and showed a trend for verbal learning and memory (P = 0.09). CONCLUSIONS:Adiposity and insulin resistance were associated with worse function in visual domains. An unexpected negative association is reported between SHBG and cognitive measures, which seemed to be independent of free testosterone levels.

PURPOSE/OBJECTIVE:To investigate the composition, cross-sectional area (CSA), and hormonal correlates of different fat depots in women with anorexia nervosa (AN) and control subjects with normal weights to find out whether patients with AN have lower fat CSA but higher attenuation than did control subjects and whether these changes may be mediated by gonadal steroids, cortisol, and thyroid hormones. MATERIALS AND METHODS/METHODS:This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Forty premenopausal women with AN and 40 normal-weight women of comparable age (mean age ± standard deviation, 26 years ± 5) were studied. All individuals underwent computed tomography of the abdomen and thigh with a calibration phantom. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), thigh SAT, and thigh intermuscular adipose tissue CSA and attenuation were quantified. Serum estradiol, thyroid hormones, and urinary free cortisol levels were assessed. Variables were compared by using analysis of variance. Associations were examined by using linear regression analysis. RESULTS:Women with AN had higher fat attenuation than did control subjects (-100.1 to -46.7 HU vs -117.6 to -61.8 HU, P < .0001), despite lower fat CSA (2.0-62.8 cm(2) vs 5.5-185.9 cm(2), P < .0001). VAT attenuation but not CSA was inversely associated with lowest prior lifetime body mass index in AN (r = -0.71, P = .006). Serum estradiol levels were inversely associated with fat attenuation (r = -0.34 to -0.61, P = .03 to <.0001) and were positively associated with fat CSA of all compartments (r = 0.42-0.64, P = .007 to <.0001). Thyroxine levels and urinary free cortisol levels were positively associated with thigh SAT attenuation (r = 0.64 [P = .006] and r = 0.68 [P = .0004], respectively) and were inversely associated with abdominal SAT and VAT CSA (r = -0.44 to -0.58, P = .04 to .02). CONCLUSION/CONCLUSIONS:Women with AN have differences in fat composition, with higher fat attenuation than that of control subjects, as well as low fat mass. VAT attenuation but not CSA is inversely associated with lowest prior lifetime body mass index, suggesting that fat attenuation may serve as a biomarker of prior and current disease status in AN.

PURPOSE/OBJECTIVE:To compare the lateral mortise and anterior midline approaches to fluoroscopically guided tibiotalar joint injections with respect to successful intra-articular needle placement, fluoroscopy time, radiation dose, and dose area product (DAP). MATERIALS AND METHODS/METHODS:This retrospective study was IRB-approved and HIPAA-compliant. 498 fluoroscopically guided tibiotalar joint injections were performed or supervised by one of nine staff radiologists from 11/1/2010-12/31/2013. The injection approach was determined by operator preference. Images were reviewed on a PACS workstation to determine the injection approach (lateral mortise versus anterior midline) and to confirm intra-articular needle placement. Fluoroscopy time (minutes), radiation dose (mGy), and DAP (μGy-m(2)) were recorded and compared using the student's t-test (fluoroscopy time) or the Wilcoxon rank sum test (radiation dose and DAP). RESULTS:There were 246 lateral mortise injections and 252 anterior midline injections. Two lateral mortise injections were excluded from further analysis because no contrast was administered. Intra-articular location of the needle tip was documented in 242/244 lateral mortise injections and 252/252 anterior midline injections. Mean fluoroscopy time was shorter for the lateral mortise group than the anterior midline group (0.7 ± 0.5 min versus 1.2 ± 0.8 min, P < 0.0001). Mean radiation dose and DAP were less for the lateral mortise group than the anterior midline group (2.1 ± 3.7 mGy versus 2.5 ± 3.5 mGy, P = 0.04; 11.5 ± 15.3 μGy-m(2) versus 13.5 ± 17.3 μGy-m(2), P = 0.006). CONCLUSION/CONCLUSIONS:Both injection approaches resulted in nearly 100% rates of intra-articular needle placement, but the lateral mortise approach used approximately 40% less fluoroscopy time and delivered 15% lower radiation dose and DAP to the patient.

BACKGROUND:Surgery with high-dose radiation and high-dose radiation alone for sacral chordomas have shown promising local control rates. However, we have noted frequent sacral insufficiency fractures and perceived this rate to be higher than previously reported. QUESTIONS/PURPOSES/OBJECTIVE:We wished (1) to characterize the incidence of sacral insufficiency fractures in patients with chordomas of the sacrum who received high-dose radiation, and (2) to determine whether patients treated with surgery plus high-dose radiation or high-dose radiation alone are more likely to experience a sacral fracture, and to compare time to fracture in these groups. METHODS:Sixty-two patients who received high-dose radiation for sacral chordomas with (n = 44) or without surgical resection (n = 18) between 1992 and 2013 were included in this retrospective study. At our institution, sacral chordomas generally are treated by preoperative radiotherapy, followed by en bloc resection, and postoperative radiotherapy. Radiation alone, with an intent to cure, is offered to patients who otherwise are not good surgical candidates or patients who elect radiotherapy based on tumor location and the anticipated morbidity after surgery (such as sexual, bowel, or bladder dysfunction). MRI and CT scans were evaluated for evidence of sacral insufficiency fractures. Complete followup was available at a minimum of 2 years (or until fracture or death) for all 18 patients who underwent radiation alone, whereas 14% (six of 44 patients) in the surgery plus radiation group (9% [three of 33] after high sacrectomy and 27% [three of 11] after low sacrectomy) were lost to followup before 2 years. RESULTS:Sacral insufficiency fractures occurred in 29 of the 62 patients (47%). A total of 25 of 33 patients (76%) with high sacrectomy had fractures develop compared with zero of 11 (0%) after low sacrectomy, and four of the 18 patients (22%) who had high-dose radiation alone (p < 0.001). The fracture rate was greater in the high sacrectomy group than in the low sacrectomy group (p < 0.001) and the radiation only group (p < 0.001). There was no difference with the numbers evaluated in fracture probability between patients in the low-sacrectomy group and those treated with radiation alone (p = 0.112). The fracture-free survival probability was 0.99 for the low sacrectomy group at all times as there were no insufficiency fractures in this group; the 1-year fracture-free survival probability was 0.53 (95% CI, 0.35-0.69) after high sacrectomy, 0.83 (95% CI, 0.57-0.94) after radiation alone; the 2-year fracture-free survival probability was 0.36 (95% CI, 0.19-0.52) after high sacrectomy and 0.77 (95% CI, 0.50-0.91) after radiation alone; and the 5-year fracture-free survival probability was 0.14 (95% CI, 0.04-0.30) after high sacrectomy and 0.77 (95% CI, 0.50-0.91) after radiation alone. CONCLUSIONS:Acknowledging the limitations of potential differences in baseline and followup among treatment groups in our study, we found that almost ½ of our patients experienced an insufficiency fracture. We found that the fracture rate was greater in the surgery group compared with the radiation alone group and that high sacrectomy accounted for all fractures in the surgery group. These findings can be used to inform patients and also support the need for further research to elucidate the influence of high-dose radiation on bone quality. LEVEL OF EVIDENCE/METHODS:Level III, therapeutic study.

OBJECTIVE:To assess short- and long-term reproducibility of marrow adipose tissue (MAT) quantification by 1H-MR spectroscopy. MATERIALS AND METHODS/METHODS:Our study was IRB-approved and HIPAA compliant. Written informed consent was obtained. We studied 20 overweight/obese but otherwise healthy subjects (12 female, 8 male) with a mean age of 37 ± 6 years. All subjects underwent proton magnetic resonance spectroscopy (1H-MRS) of the fourth lumbar vertebral body using a single-voxel point-resolved spatially localized spectroscopy sequence without water suppression at 3 T. Measurements were repeated after 6 weeks and 6 months using identical scanning protocols. The following clinical parameters were collected, weight, BMI, exercise status, and trabecular bone mineral density (BMD), by quantitative computed tomography. Short- (baseline, 6 weeks) and long-term (baseline, 6 months) reproducibility of MAT was assessed by the coefficient of variance (CV), standard deviation (SD), and interclass correlation coefficients (ICCs). Short- and long-term changes in clinical parameters were assessed by paired t-test. RESULTS:For short-term reproducibility between baseline and 6-week scans, the CV was 9.9 %, SD was 0.08, and ICC was 0.97 (95 % CI 0.94-099). For long-term reproducibility between baseline and 6-month scans, the CV was 12.0 %, SD was 0.10, and ICC was 0.95 (95 % CI 0.88 to 0.98). There was no significant short- or long-term change in clinical parameters (weight, BMI, exercise status, BMD) (p > 0.2). CONCLUSION/CONCLUSIONS:1H-MRS is a reproducible method for short- and long-term quantification of MAT. Our results can guide sample size calculations for interventional and longitudinal studies.

Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross-sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L4 in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual-energy X-ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT (R = -[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load-to-strength ratio helps explain increased fracture risk in both low-weight and obese women.