Context Acromegaly presents a unique pattern of lower adiposity and insulin resistance in active disease but reduction in insulin resistance despite a rise in adiposity after surgery. Depot-specific adipose tissue masses and ectopic lipid are important predictors of insulin resistance in other populations, but whether they are in acromegaly is unknown. Long-term persistence of body composition changes after surgery is unknown. Objective To determine how depot-specific body composition and ectopic lipid relate to insulin resistance in active acromegaly and whether their changes with surgery are sustained long-term. Methods Cross-sectional study in patients with active acromegaly and longitudinal study in newly diagnosed patients studied before and in long-term follow-up, 3 (1-8) years (median, range), after surgery. Seventy-one patients with active acromegaly studied cross-sectionally and 28 with newly diagnosed acromegaly studied longitudinally. Main outcome measures were visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue masses by whole-body magnetic resonance imaging; intrahepatic lipid (IHL) by proton magnetic resonance spectroscopy; insulin resistance measures derived from fasting; and oral glucose tolerance test insulin and glucose levels. Results SAT and insulin-like growth factor 1 level, but not VAT or IHL, were independent predictors of insulin resistance in active acromegaly. VAT, SAT, and IHL gains were sustained long-term after surgery. VAT mass rise with surgery correlated inversely with rise in QUICKI while SAT rise correlated with fall in the Homeostatic Model Assessment score. Conclusion SAT and disease activity are important predictors of insulin resistance in active acromegaly. Adiposity gains are sustained long-term after surgical treatment and impact on the accompanying improvement in insulin resistance.

BACKGROUND Sustained calorie restriction (CR) promises to extend the lifespan. The effect of CR on changes in body mass across tissues and organs is unclear. OBJECTIVES We used whole-body MRI to evaluate the effect of 2 y of CR on changes in body composition. METHODS In an ancillary study of the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, 43 healthy adults [25-50 y; BMI (kg/m2): 22-28] randomly assigned to 25% CR (n = 28) or ad libitum (AL) eating (n = 15) underwent whole-body MRI at baseline and month 24 to measure adipose tissue in subcutaneous, visceral, and intermuscular depots (SAT, VAT, and IMAT, respectively); skeletal muscle; and organs including brain, liver, spleen, and kidneys but not heart. RESULTS The CR group lost more adipose tissue and lean tissue than controls (P < 0.05). In the CR group, at baseline, total tissue volume comprised 32.1%, 1.9%, and 1.0% of SAT, VAT, and IMAT, respectively. The loss of total tissue volume over 24 mo comprised 68.4%, 7.4%, and 2.2% of SAT, VAT, and IMAT, respectively, demonstrating preferential loss of fat vs. lean tissue. Although there is more muscle loss in CR than AL (P < 0.05), the loss of muscle over 24 mo in the CR group comprised only 17.2% of the loss of total tissue volume. Changes in organ volumes were not different between CR and AL. The degree of CR (% decrease in energy intake vs. baseline) significantly (P < 0.05) affected changes in VAT, IMAT, muscle, and liver volume (standardized regression coefficient ± standard error of estimates: 0.43 ± 0.15 L, 0.40 ± 0.19 L, 0.55 ± 0.17 L, and 0.45 ± 0.18 L, respectively). CONCLUSIONS Twenty-four months of CR (intended, 25%; actual, 13.7%) in young individuals without obesity had effects on body composition, including a preferential loss of adipose tissue, especially VAT, over the loss of muscle and organ tissue. This trial was registered at www.clinicaltrials.gov as NCT02695511.

Context: In active acromegaly, the lipolytic and insulin antagonistic effects of growth hormone (GH) excess alter adipose tissue (AT) deposition, reduce body fat, and increase insulin resistance. This pattern reverses with surgical therapy. Pegvisomant treats acromegaly by blocking GH receptor (GHR) signal transduction and lowering insulin-like growth factor 1 (IGF-1) levels. The long-term effects of GHR antagonist treatment of acromegaly on body composition have not been studied. Methods: We prospectively studied 21 patients with active acromegaly who were starting pegvisomant. Body composition was examined by whole body magnetic resonance imaging, proton magnetic resonance spectroscopy of liver and muscle and dual-energy x-ray absorptiometry, and endocrine and metabolic markers were measured before and serially during 1.0 to 13.4 years of pegvisomant therapy. The data of patients with acromegaly were compared with predicted and to matched controls. Results: Mass of visceral AT (VAT) increased to a peak of 187% (1.56-229%) (P < .001) and subcutaneous AT (SAT) to 109% (-17% to 57%) (P = .04) of baseline. These remained persistently and stably increased, but did not differ from predicted during long-term pegvisomant therapy. Intrahepatic lipid rose from 1.75% to 3.04 % (P = .04). Although lean tissue mass decreased significantly, skeletal muscle (SM) did not change. IGF-1 levels normalized, and homeostasis model assessment insulin resistance and HbA1C were lowered. Conclusion: Long-term pegvisomant therapy is accompanied by increases in VAT and SAT mass that do not differ from predicted, stable SM mass and improvements in glucose metabolism. Long-term pegvisomant therapy does not produce a GH deficiency-like pattern of body composition change.

10532 Background: Obesity, as defined by elevated BMI, correlates with prognosis in some cancers but not Hodgkin lymphoma (HL). Potential explanations include 1) BMI cannot differentiate lean from fat tissue, especially visceral adipose tissue (VAT), a depot that is linked to cardiovascular diseases; 2) HL with B symptoms usually experience weight loss. In this study we use clinically collected PET-CT scans to measure VAT and muscle mass in HL. Methods: In a subsample (n = 101) of the COG AHOD0031 study cohort, we matched (same gender, age ±2yrs, height ±5cm, weight ±5kg) cases with controls for 13 out of 17 subjects with B symptoms, and 9 out of 14 with subsequent HL relapse. Multi-slice CT from head to mid-thigh were analyzed for VAT, subcutaneous adipose tissue (SAT) and muscle mass (sliceOmatic, Tomovision). Results: Among 13 patients with B symptoms at diagnosis (age, 15.7±2.7 yrs, muscle: 10.5±3.1 kg), borderline significantly less muscle (P = .08) was observed compared to the group without B symptoms (age 15.6±2.7 yrs, muscle 11.7±3.4 kg). We detected significant changes of VAT, SAT and borderline significant changes of muscle mass between baseline and after 6 weeks of chemotherapy (Table). Among 9 patients who subsequently developed a relapse, a non-significant trend towards more VAT was observed compared to the group who did not relapse (P = .17). The relapse group also showed a non-significant trend towards more VAT (P = .16) and SAT (P = .23) increases than the group w/o relapse. Conclusions: Significant increases in VAT and SAT and borderline significant decreases in muscle were noted after 6 weeks of chemotherapy in a small pediatric HL cohort using routine PET-CT. HL with B symptoms tends to have less muscle than those without B symptoms. Our small HL sample only shows a non-significant weak trend towards more VAT and SAT in the relapse group. Assessment of the full AHOD0031 cohort will allow further discrimination of the impact of body composition on relapse risk and toxicity in pediatric HL. Relapse (BL) Relapse Free (BL) Relapse (Δ 6wks) Relapse free (Δ 6wks) VAT, kg 1.9±1.2 1.4±1.9 0.5±0.4* 0.3±0.2* SAT, kg 8.8±6.5 7.6±6.1 1.1±1.1* 0.5±0.8† Muscle, kg 9.8±3.3 10.1±3.7 -0.3±0.5† -0.1±0.7 BL, baseline;*, P < .05; †, .05 < P < .10 for 6 wks vs. BL

In this brief review, introductory concepts in animal and human adipose tissue segmentation using proton magnetic resonance imaging (MRI) and computed tomography are summarized in the context of obesity research. Adipose tissue segmentation and quantification using spin relaxation-based (e.g., T1-weighted, T2-weighted), relaxometry-based (e.g., T1-, T2-, T2*-mapping), chemical-shift selective, and chemical-shift encoded water–fat MRI pulse sequences are briefly discussed. The continuing interest to classify subcutaneous and visceral adipose tissue depots into smaller sub-depot compartments is mentioned. The use of a single slice, a stack of slices across a limited anatomical region, or a whole body protocol is considered. Common image post-processing steps and emerging atlas-based automated segmentation techniques are noted. Finally, the article identifies some directions of future research, including a discussion on the growing topic of brown adipose tissue and related segmentation considerations.

Previous studies have shown an inverse correlation between bone marrow adipose tissue and bone mineral density in cancellous bone; however, such relationships in cortical bone are less studied, especially in children. A total of 185 healthy children and adolescents (76 females and 109 males, aged 5-18 years) were included in this study. Right femoral bone marrow adipose tissue area (BMA), right femoral cortical bone area (CBA), subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle were accessed by whole-body magnetic resonance imaging. In regression analysis with CBA as the dependent variable and BMA as the independent variable, BMA negatively contributed to CBA after adjusting for weight and total body fat or subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle (β = -0.201 to -0.272, p < 0.001). These results suggest an inverse relationship between BMA and CBA in children and adolescents after adjustment of body weight or body composition. The data support the hypothesis that a competitive relationship exists between bone and marrow fat in cortical bone and is consistent with a similar finding in cancellous bone in previous studies. Future research is needed to clarify the role of marrow fat in childhood fractures that are related to cortical bone quality.

Several large-scale studies have reported the presence of an inverse relationship between bone mineral density (BMD) and bone marrow adipose tissue (BMAT) in adults. We aim to determine if there is an inverse relationship between pelvic volumetric BMD (vBMD) and pelvic BMAT in children and to compare this relationship in children and adults. Pelvic BMAT and bone volume (BV) was evaluated in 181 healthy children (5–17yr) and 495 healthy adults (≥18yr) with whole-body magnetic resonance imaging (MRI). Pelvic vBMD was calculated using whole-body dual-energy X-ray absorptiometry to measure pelvic bone mineral content and MRI-measured BV. An inverse correlation was found between pelvic BMAT and pelvic vBMD in both children (r=−0.374, p<0.001) and adults (r=−0.650, p<0.001). In regression analysis with pelvic vBMD as the dependent variable and BMAT as the independent variable, being a child or adult neither significantly contribute to the pelvic BMD (p=0.995) nor did its interaction with pelvic BMAT (p=0.415). The inverse relationship observed between pelvic vBMD and pelvic BMAT in children extends previous findings that found the inverse relationship to exist in adults and provides further support for a reciprocal relationship between adipocytes and osteoblasts.

Earlier cross‐sectional studies found that a single magnetic resonance imaging (MRI) slice predicts total visceral and subcutaneous adipose tissue (VAT and SAT) volumes well. We sought to investigate the accuracy of trunk single slice imaging in estimating changes of total VAT and SAT volume in 123 overweight and obese subjects who were enrolled in a 24‐week CB‐1R inverse agonist clinical trial (weight change, −7.7 ± 5.3 kg; SAT change, −5.4 ± 4.9 l, VAT change, −0.8 ± 1.0 l). VAT and SAT volumes at baseline and 24 weeks were derived from whole‐body MRI images. The VAT area 5–10 cm above L 4 —L 5 (A +5–10 ) ( R 2 = 0.59–0.70, P < 0.001) best predicted changes in VAT volume but the strength of these correlations was significantly lower than those at baseline ( R 2 = 0.85–0.90, P < 0.001). Furthermore, the L 4 —L 5 slice poorly predicted VAT volume changes ( R 2 = 0.24–0.29, P < 0.001). Studies will require 44–69% more subjects if (A +5–10 ) is used and 243–320% more subjects if the L 4 —L 5 slice is used for equivalent power of multislice total volume measurements of VAT changes. Similarly, single slice imaging predicts SAT loss less well than cross‐sectional SAT ( R 2 = 0.31–0.49 vs. R 2 = 0.52–0.68, P < 0.05). Results were the same when examined in men and women separately. A single MRI slice 5–10 cm above L 4 —L 5 is more powerful than the traditionally used L 4 —L 5 slice in detecting VAT changes, but in general single slice imaging poorly predicts VAT and SAT changes during weight loss. For certain study designs, multislice imaging may be more cost‐effective than single slice imaging in detecting changes for VAT and SAT.

CONTEXT An increasing number of studies suggest that bone marrow adipose tissue (BMAT) might play a role in the pathogenesis of osteoporosis. Our previous study of Caucasian women demonstrated that there is an inverse relationship between BMAT and whole-body bone mineral density (BMD). It is unknown whether visceral adipose tissue (VAT), sc adipose tissue (SAT), and skeletal muscle had an effect on the relationship between BMAT and BMD. OBJECTIVE In the present study we investigated the relationship between pelvic, hip, and lumbar spine BMAT with hip and lumbar spine BMD in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) sample with adjustment for whole-body magnetic resonance imaging (MRI)-measured VAT, SAT, and skeletal muscle. DESIGN T1-weighted MRI was acquired for 210 healthy African-American and Caucasian men and women (age 38-52 yr). Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. RESULTS Pelvic, hip, and lumbar spine BMAT had negative correlations with hip and lumbar spine BMD (r = -0.399 to -0.550, P < 0.001). The inverse associations between BMAT and BMD remained strong after adjusting for demographics, weight, skeletal muscle, SAT, VAT, total adipose tissue (TAT), menopausal status, lifestyle factors, and inflammatory markers (standardized regression coefficients = -0. 296 to -0.549, P < 0.001). Among body composition measures, skeletal muscle was the strongest correlate of BMD after adjusting for BMAT (standardized regression coefficients = 0.268-0.614, P < 0.05), with little additional contribution from weight, SAT, VAT, or total adipose tissue. CONCLUSION In this middle-aged population, a negative relationship existed between MRI-measured BMAT and hip and lumbar spine BMD independent of demographics and body composition. These observations support the growing evidence linking BMAT with low bone density.

Magnetic Resonance Imaging (MRI) is increasingly being used in children to quantify adipose tissue (AT) and skeletal muscle (SM) in vivo. It is unclear whether the every 5 cm whole body MRI protocol used in adults is appropriate when applied in children. Whole body MRI continuous 1 cm thick slices were acquired in 73, aged 5-17-year-old healthy children. Images were segmented into subcutaneous (SAT), visceral (VAT), intermuscular AT (IMAT), and SM. The percentage difference between volumes measured by the continuous protocol and volumes estimated with protocols of different between-slice intervals (i.e., interval = 2, 3, 4 and 5 cm) was larger with an increase in interval size, depot size, weight and body mass index percentile. For group comparisons, studies will require less than 5.4% more subjects if an every 5 cm protocol is used for equivalent power as the every 1 cm protocol. For individual subject comparisons, interval protocols can be used to reliably distinguish between subjects who differ in SM or SAT volume by 0.14 to 0.64 L (i.e., 1 to 5% of SM or SAT volume) or more, or in VAT or IMAT volume by 0.06 to 0.21 L (i.e., 10 to 30% of VAT or IMAT volume) or more. The every 5 cm image acquisition protocol can be considered as accurate as the contiguous protocol for group comparisons in children, as well as for comparison of SM and SAT among individual children. However, a smaller slice interval protocol would be more accurate for comparison of VAT or IMAT among individual children.

Despite increasing research and clinical significance, limited information is available on how the visceral and subcutaneous adipose tissue (VAT and SAT) compartments develop during growth and maturation and then vary in volume across the adult lifespan. The present study aimed at exploring how adipose tissue compartments partition across the lifespan.

In vivo adipose tissue quantification is an important tool to characterize phenotypes of obesity, especially in the human. The amount and distribution of adipose tissue is associated with many of the adverse consequences of obesity. Recent studies suggest that adipose tissue is not a single homogeneous compartment. Regional adipose tissue depots vary in biological functions and individual adipose tissue compartments have stronger associations with metabolic conditions than does total adipose tissue mass. Currently there is intense and increasing interest in regional adipose tissue compartments. Computed tomography and magnetic resonance imaging often are used to quantify adipose tissue volumes or cross-sectional adipose tissue areas. Other modalities, including dual-energy absorptiometry and magnetic resonance spectroscopy, provide whole-body or regional fat measures instead of adipose tissue mass quantification.