A trans-ethnic genome-wide association study identifies gender-specific loci influencing pediatric aBMD and BMC at the distal radius.

Childhood fractures are common, with the forearm being the most common site. Genome-wide association studies (GWAS) have identified more than 60 loci associated with bone mineral density (BMD) in adults but less is known about genetic influences specific to bone in childhood. To identify novel genetic factors that influence pediatric bone strength at a common site for childhood fractures, we performed a sex-stratified trans-ethnic genome-wide association study of areal BMD (aBMD) and bone mineral content (BMC) Z-scores measured by dual energy X-ray absorptiometry at the one-third distal radius, in a cohort of 1399 children without clinical abnormalities in bone health. We tested signals with P < 5 × 10(-6) for replication in an independent, same-age cohort of 486 Caucasian children. Two loci yielded a genome-wide significant combined P-value: rs7797976 within CPED1 in females [P = 2.4 × 10(-11), ß =- 0.30 standard deviations (SD) per T allele; aBMD-Z] and rs7035284 at 9p21.3 in males (P = 1.2 × 10(-8), ß = 0.28 SD per G allele; BMC-Z). Signals at the CPED1-WNT16-FAM3C locus have been previously associated with BMD at other skeletal sites in adults and children. Our result at the distal radius underscores the importance of this locus at multiple skeletal sites. The 9p21.3 locus is within a gene desert, with the nearest gene flanking each side being MIR31HG and MTAP, neither of which has been implicated in BMD or BMC previously. These findings suggest that genetic determinants of childhood bone accretion at the radius, a skeletal site that is primarily cortical bone, exist and also differ by sex.

BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures.

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait.

Changes in Brown Adipose Tissue and Muscle Development during Infancy.

OBJECTIVE: To examine the relationship between brown adipose tissue (BAT) and muscle development, two tissues that derive from a common cell lineage, during the first 6 months of postnatal life. STUDY DESIGN: Thirty healthy term infants (15 males and females) underwent whole-body magnetic resonance imaging examinations. Measurements of BAT in the supraclavicular area as well as measures of trunk musculature and subcutaneous adiposity were obtained at birth and at 6 months of age. RESULTS: Paraspinous musculature and subcutaneous white adipose tissue (WAT) increased, and the proportion of BAT in the supraclavicular area decreased during infancy. Although measures of BAT did not correlate with paraspinous musculature through the first 6 months of life (r = -0.35; P = .09), BAT was a significant predictor of paraspinous musculature after adjusting for weight, body length, and WAT (P = .002); infants with the smallest decreases in BAT had the greatest gains in musculature. In contrast, changes in BAT did not predict increases in subcutaneous WAT (P = .25) during infancy, which were primarily determined by body weight. CONCLUSIONS: Changes in BAT are associated with muscle development but not WAT accumulation in healthy infants. Studies are needed to determine the mechanism(s) by which BAT could facilitate muscle growth, and the degree to which decreased muscle mass, such as in preterm and low birth weight infants, is related to a deficiency of BAT.

Small vertebral cross-sectional area and tall intervertebral disc in adolescent idiopathic scoliosis.

BACKGROUND: When compared to boys, girls have smaller vertebral cross-sectional area, which conveys a greater spinal flexibility, and a higher prevalence of adolescent idiopathic scoliosis. OBJECTIVE: To test the hypothesis that small vertebral cross-sectional area and tall intervertebral disc height are structural characteristics of patients with adolescent idiopathic scoliosis. MATERIALS AND METHODS: Using multiplanar imaging techniques, measures of vertebral cross-sectional area, vertebral height and intervertebral disc height in the lumbar spine were obtained in 35 pairs of girls and 11 pairs of boys with and without adolescent idiopathic scoliosis of the thoracic spine matched for age, height and weight. RESULTS: Compared to adolescents without spinal deformity, girls and boys with adolescent idiopathic scoliosis had, on average, 9.8% (6.68 ± 0.81 vs. 7.40 ± 0.99 cm(2); P = 0.0007) and 13.9% (8.22 ± 0.84 vs. 9.55 ± 1.61 cm(2); P = 0.009) smaller vertebral cross-sectional dimensions, respectively. Additionally, patients with adolescent idiopathic scoliosis had significantly greater values for intervertebral disc heights (9.06 ± 0.85 vs. 7.31 ± 0.62 mm and 9.09 ± 0.87 vs. 7.61 ± 1.00 mm for girls and boys respectively; both P ≤ 0.011). Multiple regression analysis indicated that the presence of scoliosis was negatively associated with vertebral cross-sectional area and positively with intervertebral disc height, independent of sex, age and body mass index. CONCLUSION: We provide new evidence that girls and boys with adolescent idiopathic scoliosis have significantly smaller vertebral cross-sectional area and taller intervertebral disc heights - two major structural determinants that influence trunk flexibility. With appropriate validation, these findings may have implications for the identification of children at the highest risk for developing scoliosis.

Comparative analysis of microRNA expression in mouse and human brown adipose tissue.

BACKGROUND: In small mammals brown adipose tissue (BAT) plays a predominant role in regulating energy expenditure (EE) via adaptive thermogenesis. New-born babies require BAT to control their body temperature, however its relevance in adults has been questioned. Active BAT has recently been observed in adult humans, albeit in much lower relative quantities than small mammals. Comparing and contrasting the molecular mechanisms controlling BAT growth and development in mice and humans will increase our understanding or how human BAT is developed and may identify potential therapeutic targets to increase EE. MicroRNAs are molecular mechanisms involved in mouse BAT development however, little is known about the miRNA profile in human BAT. The aims of this study were to establish a mouse BAT-enriched miRNA profile and compare this with miRNAs measured in human BAT. To achieve this we firstly established a mouse BAT enriched-miRNA profile by comparing miRNAs expressed in mouse BAT, white adipose tissue and skeletal muscle. Following this the BAT-enriched miRNAs predicted to target genes potentially involved in growth and development were identified. METHODS: MiRNA levels were measured using PCR-based miRNA arrays. Results were analysed using ExpressionSuite software with the global mean expression value of all expressed miRNAs in a givensample used as the normalisation factor. Bio-informatic analyses was used to predict gene targets followed by Ingenuity Pathway Analysis. RESULTS: We identified 35 mouse BAT-enriched miRNAs that were predicted to target genes potentially involved in growth and development. We also identified 145 miRNAs expressed in both mouse and human BAT, of which 25 were enriched in mouse BAT. Of these 25 miRNAs, miR-20a was predicted to target MYF5 and PPARγ, two important genes involved in brown adipogenesis, as well as BMP2 and BMPR2, genes involved in white adipogenesis. For the first time, 69 miRNAs were identified in human BAT but absent in mouse BAT, and 181 miRNAs were expressed in mouse but not in human BAT. CONCLUSION: The present study has identified a small sub-set of miRNAs common to both mouse and human BAT. From this sub-set bioinformatics analysis suggested a potential role of miR-20a in the control of cell fate and this warrants further investigation. The large number of miRNAs found only in mouse BAT or only in human BAT highlights the differing molecular profile between species that is likely to influence the functional role of BAT across species. Nevertheless the BAT-enriched miRNA profiles established in the present study suggest targets to investigate in the control BAT development and EE.

Sexual Dimorphism in Newborn Vertebrae and Its Potential Implications.

OBJECTIVE: To examine whether the sex-related differences in vertebral cross-sectional area (CSA) found in children and at the timing of peak bone mass-a major determinant of osteoporosis and future fracture risk-are also present at birth. STUDY DESIGN: Vertebral CSA, vertebral height, and intervertebral disc height were measured using magnetic resonance imaging in 70 healthy full-term newborns (35 males and 35 females). The length and CSA of the humerus, musculature, and adiposity were measured as well. RESULTS: Weight, body length, and head and waist circumferences did not differ significantly between males and females (P ≥ .06 for all). Compared with newborn boys, girls had significantly smaller mean vertebral cross-sectional dimensions (1.47 ± 0.11 vs 1.31 ± 0.12; P < .0001). Multiple linear regression analysis identified sex as a predictor of vertebral CSA independent of gestational age, birth weight, and body length. In contrast, the sexes were monomorphic with regard to vertebral height, intervertebral disc height, and spinal length (P ≥ .11 for all). There were also no sex differences in the length or cross-sectional dimensions of the humerus or in measures of musculature and adiposity (P ≥ .10 for all). CONCLUSION: Factors related to sex influence fetal development of the axial skeleton. The smaller vertebral CSA in females is associated with greater flexibility of the spine, which could represent the human adaptation to fetal load. Unfortunately, it also imparts a mechanical disadvantage that increases stress within the vertebrae for all physical activities and increases the susceptibility to fragility fractures later in life.

Effectiveness of diffusion tensor imaging in assessing disease severity in Duchenne muscular dystrophy: preliminary study.

BACKGROUND: There is currently a lack of suitable objective endpoints to measure disease progression in Duchenne muscular dystrophy (DMD). Emerging research suggests that diffusion tensor imaging (DTI) has potential as an outcome measure for the evaluation of skeletal muscle injury. OBJECTIVE: The objective of this study was to evaluate the potential of DTI as quantitative magnetic resonance imaging (MRI) markers of disease severity in DMD. MATERIALS AND METHODS: Thirteen consecutive boys (8.9 years ± 3.0 years) with DMD were evaluated using DTI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were compared with clinical outcome measures of manual muscle testing and MRI determinations of muscle fat fraction (MFF) in the right lower extremity. RESULTS: Both MRI measures of FA and ADC strongly correlated with age and muscle strength. Values for FA positively correlated with age and negatively correlated with muscle strength (r = 0.78 and -0.96; both P ≤ 0.002) while measures of ADC negatively correlated age, but positively correlated with muscle strength (r = -0.87 and 0.83; both P ≤ 0.0004). Additionally, ADC and FA strongly correlated with MFF (r = -0.891 and 0.894, respectively; both P ≤ 0.0001). Mean MMF was negatively correlated with muscle strength (r = -0.89, P = 0.0001). CONCLUSION: DTI measures of muscle structure strongly correlated with muscle strength and adiposity in boys with DMD in this pilot study, although these markers may be more reflective of fat replacement rather than muscle damage in later stages of the disease. Further studies in presymptomatic younger children are needed to assess the ability of DTI to detect early changes in DMD.

Can Subclinical Rickets Cause SCFE? A Prospective, Pilot Study.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a common disorder of the growing hip; however, its etiology remains unknown. Vitamin D (25-OH) is a major regulator of bone homeostasis and calcium metabolism. Vitamin D deficiency is one of the major causes of rickets, and rickets has been associated with SCFE. Increased body mass index (BMI) has been linked to SCFE and obese children are known to have lower vitamin D levels. Therefore, we hypothesize that children who develop SCFE may have subclinical rickets predisposing them to the development of physeal disease. METHODS: This was a pilot, prospective study designed to determine the relationship between vitamin D, bone, muscle, and fat in patients with SCFE. We enrolled 20 consecutive patients with idiopathic SCFE aged 9 to 14 years. Upon diagnosis, vitamin D, PTH, T4, and thyroid-stimulating hormone blood levels were obtained. A single-slice computed tomography was used to measure cortical bone density (CBD) of the femur. Demographics, BMI, and the results obtained were compared to generate a relationship between vitamin D levels and SCFE. RESULTS: Twenty patients were enrolled, 13 males and 7 females, at an average age of 12 years (range, 9 to 14 y), and mean BMI% was 93.9 (range, 81.3 to 99.5). There were 15 stable and 5 unstable SCFE. Overall, mean and SD values for vitamin D, 25-OH were within the normal range (43.9 ± 13.5). We found no difference in values in vitamin D between nonobese (BMI < 95%) and obese (BMI ≥ 95%) subjects (34.8 ± 16.8 vs. 51.6 ± 22.4, P = 0.144). Moreover, we found no difference in CBD between these 2 groups (1126 ± 33.1 vs. 1147 ± 41.2, P = 0.333). There was no relation between blood values of vitamin D and measures of CBD. CONCLUSIONS: Although obese children are known to have lower levels of vitamin D and a higher prevalence of SCFE, we found no correlation between low vitamin D and the development of SCFE in this subset of patients.

Longitudinal tracking of dual-energy X-ray absorptiometry bone measures over 6 years in children and adolescents: persistence of low bone mass to maturity.

OBJECTIVES: Early assessment of bone mass may be useful for predicting future osteoporosis risk if bone measures "track" during growth. This prospective longitudinal multicenter study examined tracking of bone measures in children and adolescents over 6 years to sexual and skeletal maturity. STUDY DESIGN: A total of 240 healthy male and 293 healthy female patients, ages 6-17 years, underwent yearly evaluations of height, weight, body mass index, skeletal age, Tanner stage, and dual-energy x-ray absorptiometry (DXA) bone measurements of the whole body, spine, hip, and forearm for 6 years. All subjects were sexually and skeletally mature at final follow-up. Correlation was performed between baseline and 6-year follow-up measures, and change in DXA Z-scores was examined for subjects who had baseline Z < -1.5. RESULTS: DXA Z-scores (r = 0.66-0.87) had similar tracking to anthropometric measures (r = 0.64-0.74). Tracking was stronger for bone mineral density compared with bone mineral content and for girls compared with boys. Tracking was weakest during mid- to late puberty but improved when Z-scores were adjusted for height. Almost all subjects with baseline Z < -1.5 had final Z-scores below average, with the majority remaining less than -1.0. CONCLUSIONS: Bone status during childhood is a strong predictor of bone status in young adulthood, when peak bone mass is achieved. This suggests that bone mass measurements in children and adolescents may be useful for early identification of individuals at risk for osteoporosis later in life.

Repeatability of chemical-shift-encoded water-fat MRI and diffusion-tensor imaging in lower extremity muscles in children.

OBJECTIVE: The purpose of this study was to assess the repeatability of water-fat MRI and diffusion-tensor imaging (DTI) as quantitative biomarkers of pediatric lower extremity skeletal muscle. SUBJECTS AND METHODS: MRI at 3 T of a randomly selected thigh and lower leg of seven healthy children was studied using water-fat separation and DTI techniques. Muscle-fat fraction, apparent diffusion coefficient (ADC), and fractional anisotropy (FA) values were calculated. Test-retest and interrater repeatability were assessed by calculating the Pearson correlation coefficient, intraclass correlation coefficient, and Bland-Altman analysis. RESULTS: Bland-Altman plots show that the mean difference between test-retest and interrater measurements of muscle-fat fraction, ADC, and FA was near 0. The correlation coefficients and intraclass correlation coefficients were all between 0.88 and 0.99 (p < 0.05), suggesting excellent reliability of the measurements. Muscle-fat fraction measurements from water-fat MRI exhibited the highest intraclass correlation coefficient. Interrater agreement was consistently better than test-retest comparisons. CONCLUSION: Water-fat MRI and DTI measurements in lower extremity skeletal muscles are objective repeatable biomarkers in children. This knowledge should aid in the understanding of the number of participants needed in clinical trials when using these determinations as an outcome measure to noninvasively monitor neuromuscular disease.

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes.

BACKGROUND: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. RESULTS: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. CONCLUSION: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single "optimal" pubertal growth pattern.

Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI.

PURPOSE: To compare fat-signal fractions (FFs) and T2* values between brown (BAT) and white (WAT) adipose tissue located within the supraclavicular fossa and subcutaneous depots, respectively. MATERIALS AND METHODS: Twelve infants and 39 children were studied. Children were divided into lean and overweight/obese subgroups. Chemical-shift-encoded water-fat magnetic resonance imaging (MRI) was used to quantify FFs and T2* metrics in the supraclavicular and adjacent subcutaneous adipose tissue depots. Linear regression and t-tests were performed. RESULTS: Infants had lower supraclavicular FFs than children (P < 0.01) but T2* values were similar (P = 0.5). Lean children exhibited lower supraclavicular FFs and T2* values than overweight children (P < 0.01). In each individual infant and child, supraclavicular FFs were consistently lower than adjacent subcutaneous FFs. Supraclavicular T2* values were consistently lower than subcutaneous T2* values in children, but not in infants. FFs in both depots were positively correlated with age and weight in infants (P < 0.01). In children, they were correlated with weight and body mass index (BMI) (P < 0.01), but not age. Correlations between T2* and anthropometric variables existed in children (P < 0.01), but were absent in infants. CONCLUSION: Cross-sectional comparisons suggest variations in FF and T2* values in the supraclavicular and subcutaneous depots of infants and children, which are potentially indicative of physiological differences in adipose tissue fat content, amount, and metabolic activity.

Relevance of brown adipose tissue in infancy and adolescence.

Brown adipose tissue (BAT) was thought to disappear after infancy. Recent findings of BAT in patients undergoing positron emission tomography/computed tomography (PET/CT) have renewed the interest in deciphering the relevance of this tissue in humans. Available data suggest that BAT is more prevalent in children than in adults and that its activation during adolescence is associated with significantly lower gains in weight and adiposity. Data also show that pediatric patients with metabolically active BAT on PET/CT examinations have significantly greater muscle volume than patients without identifiable BAT. Both the activity and the amount of BAT increase during puberty. The magnitude of the increase is higher in boys as compared with girls and is closely related to gains in muscle volume. Hence, concurrent with the gains in skeletal muscle during infancy and puberty, all infants and adolescents accumulate large amounts of BAT. These observations are consistent with in vitro investigations suggesting close interactions between brown adipocytes, white adipocytes, and myocytes. In this review, we discuss the potential role of this tissue in regulating weight and musculoskeletal development in children.

Characterization of human brown adipose tissue by chemical-shift water-fat MRI.

OBJECTIVE: The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS: A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS: Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION: We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.

Changes in brown adipose tissue in boys and girls during childhood and puberty.

OBJECTIVE: To characterize the changes in brown adipose tissue (BAT) occurring during puberty in boys and girls. STUDY DESIGN: We examined the prevalence and the volume of BAT at different stages of sexual development in 73 pediatric patients who underwent positron emission tomography (PET)/computed tomography (CT) studies. RESULTS: Of the 73 patients studied, 43 (59%) had BAT depicted on PET/CT. The presence of BAT was detected significantly less frequently on PET/CT in prepubertal subjects (Tanner stage 1) than in pubertal subjects (Tanner stages 2-5) (15% vs 75%). BAT volume also increased during puberty, with a significantly greater magnitude of the increase in the final 2 stages of puberty (Tanner stages 4 and 5) than in earlier stages (Tanner stages 1-3) (boys: 499 ± 246 vs 50 ± 36, P < .0001; girls: 286 ± 139 vs 36 ± 29, P = .024). Changes in BAT volume were also significantly greater in boys than in girls (P = .004) and were closely related to muscle volume (r = 0.52, P < .01 for boys; r = 0.64, P < .01 for girls). CONCLUSION: The presence and volume of BAT increase rapidly during puberty. Metabolic and hormonal events related to the achievement of sexual maturity are likely responsible for this increase.

Racial disparity in fracture risk between white and nonwhite children in the United States.

OBJECTIVES: To examine risk factors for fracture in a racially diverse cohort of healthy children in the US. STUDY DESIGN: A total of 1470 healthy children, aged 6-17 years, underwent yearly evaluations of height, weight, body mass index, skeletal age, sexual maturation, calcium intake, physical activity levels, and dual-energy x-ray absorptiometry (DXA) bone and fat measurements for up to 6 years. Fracture information was obtained at each annual visit, and risk factors for fracture were examined using the time-dependent Cox proportional hazards model. RESULTS: The overall fracture incidence was 0.034 fracture per person-year with 212 children reporting a total of 257 fractures. Being white (hazard ratio [HR] = 2.1), being male (HR = 1.8), and having skeletal age of 10-14 years (HR = 2.2) were the strongest risk factors for fracture (all P ≤ .001). Increased sports participation (HR = 1.4), lower body fat percentage (HR = 0.97), and previous fracture in white girls (HR = 2.1) were also significant risk factors (all P ≤ .04). Overall, fracture risk decreased with higher DXA z scores, except in white boys, who had increased fracture risk with higher DXA z scores (HR = 1.7, P < .001). CONCLUSIONS: Boys and girls of European descent had double the fracture risk of children from other backgrounds, suggesting that the genetic predisposition to fractures seen in elderly adults also manifests in children.

Unequivocal identification of brown adipose tissue in a human infant.

We report the unique depiction of brown adipose tissue (BAT) by magnetic resonance imaging (MRI) and computed tomography (CT) in a human 3-month-old infant. Based on cellular differences between BAT and more lipid-rich white adipose tissue (WAT), chemical-shift MRI and CT were both capable of generating distinct signal contrasts between the two tissues and against surrounding anatomy, utilizing fat-signal fraction metrics in the former and x-ray attenuation values in the latter. While numerous BAT imaging experiments have been performed previously in rodents, the identification of BAT in humans has only recently been described with fusion positron emission and computed tomography in adults. The imaging of BAT in children has not been widely reported and, furthermore, MRI of human BAT in general has not been demonstrated. In the present work, large bilateral supraclavicular BAT depots were clearly visualized with MRI and CT. Tissue identity was subsequently confirmed by histology. BAT has important implications in regulating energy metabolism and nonshivering thermogenesis and has the potential to combat the onset of weight gain and the development of obesity. Current findings suggest that BAT is present in significant amounts in children and that MRI and CT can differentiate BAT from WAT based on intrinsic tissue properties.

The depiction of brown adipose tissue is related to disease status in pediatric patients with lymphoma.

OBJECTIVE: The objective of our study was to determine whether the depiction of brown adipose tissue (BAT) in PET/CT studies of pediatric patients with lymphoma is related to disease status. MATERIALS AND METHODS: The PET/CT studies of 31 pediatric patients (17 boys and 14 girls) with Hodgkin or non-Hodgkin lymphoma were reviewed, and the prevalence of metabolically active BAT at diagnosis and the prevalence of BAT when there was no evidence of disease were compared. RESULTS: The percentage of PET/CT studies depicting BAT was greater when there was no evidence of disease than at diagnosis (10% vs 77%, respectively; p < 0.001). The McNemar test indicated a strong inverse correlation between the presence of disease and the presence of BAT (p < 0.001). This correlation was noted when all subjects were examined together and when subjects with Hodgkin lymphoma and those with non-Hodgkin lymphoma were analyzed separately (p < 0.001 and < 0.05, respectively). When baseline and follow-up PET/CT scans for all patients were analyzed for the presence of BAT using conditional logistic regression, both the season when the study was performed and disease status independently predicted BAT: The winter months positively predicted BAT and the presence of lymphoma was negatively correlated with the depiction of BAT on PET/CT. Age, sex, treatment, and weight did not provide additional information when added to the model. CONCLUSION: The knowledge that BAT is a predictor of disease status should contribute to the correct analysis of PET/CT studies in children with lymphoma.

Quantitative computed tomography assessment of transfusional iron overload.

Quantitative computed tomography (QCT) has been proposed for iron quantification for more than 30 years, however there has been little clinical validation. We compared liver attenuation by QCT with magnetic resonance imaging (MRI)-derived estimates of liver iron concentration (LIC) in 37 patients with transfusional siderosis. MRI and QCT measurements were performed as clinically indicated monitoring of LIC and vertebral bone-density respectively, over a 6-year period. Mean time difference between QCT and MRI studies was 14 d, with 25 studies performed on the same day. For liver attenuation outside the normal range, attenuation values rose linearly with LIC (r(2) = 0·94). However, intersubject variability in intrinsic liver attenuation prevented quantitation of LIC <8 mg/g dry weight of liver, and was the dominant source of measurement uncertainty. Calculated QCT and MRI accuracies were equivalent for LIC values approaching 22 mg/g dry weight, with QCT having superior performance at higher LIC's. Although not suitable for monitoring patients with good iron control, QCT may nonetheless represent a viable technique for liver iron quantitation in patients with moderate to severe iron in regions where MRI resources are limited because of its low cost, availability, and high throughput.