Bone marrow adipose tissue content in Latino adolescents with prediabetes and obesity.

OBJECTIVE: This study aimed to examine whether total, regional, and organ fat predicts bone marrow adipose tissue (BMAT) fat content and to explore whether BMAT fat content differs by sex among Latino youth. METHODS: Latino youth (n = 86; age 13.6 [1.4] years, 62% male) with obesity (BMI percentile = 98.5% [1.2%]) underwent a dual-energy x-ray absorptiometry scan to assess body composition and a magnetic resonance imaging scan to determine abdominal adiposity, liver fat, and vertebral BMAT fat content in the thoracic (average of T8-T12) and lumbar (average of L1-L5) spine. RESULTS: Male youth exhibited significantly greater thoracic (male youth = 30.8% [1.4%] vs. female youth = 24.5% [2.1%], p = 0.027) and lumbar (male youth = 36.3% [1.5%] vs. female youth = 30.2% [2.2%], p = 0.038) BMAT fat content compared with female youth. Visceral adipose tissue was a significant predictor of thoracic (ß = 0.434, t[86] = 3.016, p = 0.003) and lumbar (ß = 0.389, t[86] = 2.677, p = 0.009) BMAT fat content, explaining 8.9% and 6.9% of the variance, respectively. Liver fat was a significant predictor of both thoracic (ß = 0.487, t[86] = 4.334, p < 0.001) and lumbar (ß = 0.436, t[86] = 3.793, p < 0.001) BMAT fat content, explaining 17.6% and 13.8% of the variance, respectively. CONCLUSIONS: Male youth had significantly greater thoracic and lumbar BMAT fat content than female youth. Greater BMAT fat content is associated with greater liver fat and visceral adipose tissue among youth with obesity. Further investigation of the mechanistic underpinnings of BMAT may help to differentiate its metabolic and bone-related functions.

Multidelay Arterial Spin Labeling MRI in the Assessment of Cerebral Blood Flow: Preliminary Clinical Experience in Pediatrics.

OBJECTIVES: We attempted to demonstrate the clinical applicability and utility of a three-dimensional multidelay arterial spin labeling magnetic resonance imaging technique in pediatric neuroimaging through a series of case studies. METHODS: Whole-brain three-dimensional multidelay arterial spin labeling data were acquired in five pediatric patients with different neurological conditions using 3 mm to 4 mm slices and a scan time of six to seven minutes. RESULTS: Three-dimensional multidelay arterial spin labeling provided complementary diagnostic information via quantitative cerebral blood flow and arterial transit time maps. CONCLUSIONS: Three-dimensional multidelay arterial spin labeling sequence provides simultaneous quantification of cerebral blood flow and arterial transit time and is feasible for pediatric patients.

2-D magnetic resonance spectroscopic imaging of the pediatric brain using compressed sensing.

BACKGROUND: Magnetic resonance spectroscopic imaging helps to determine abnormal brain tissue conditions by evaluating metabolite concentrations. Although a powerful technique, it is underutilized in routine clinical studies because of its long scan times. OBJECTIVE: In this study, we evaluated the feasibility of scan time reduction in metabolic imaging using compressed-sensing-based MR spectroscopic imaging in pediatric patients undergoing routine brain exams. MATERIALS AND METHODS: We retrospectively evaluated compressed-sensing reconstructions in MR spectroscopic imaging datasets from 20 pediatric patients (11 males, 9 females; average age: 5.4±4.5 years; age range: 3 days to 16 years). We performed retrospective under-sampling of the MR spectroscopic imaging datasets to simulate accelerations of 2-, 3-, 4-, 5-, 7- and 10-fold, with subsequent reconstructions in MATLAB. Metabolite maps of N-acetylaspartate, creatine, choline and lactate (where applicable) were quantitatively evaluated in terms of the root-mean-square error (RMSE), peak amplitudes and total scan time. We used the two-tailed paired t-test along with linear regression analysis to statistically compare the compressed-sensing reconstructions at each acceleration with the fully sampled reference dataset. RESULTS: High fidelity was maintained in the compressed-sensing MR spectroscopic imaging reconstructions from 50% to 80% under-sampling, with the RMSE not exceeding 3% in any dataset. Metabolite intensities and ratios evaluated on a voxel-by-voxel basis showed no statistically significant differences and mean metabolite intensities showed high correlation compared to the fully sampled reference dataset up to an acceleration factor of 5. CONCLUSION: Compressed-sensing MR spectroscopic imaging has the potential to reduce MR spectroscopic imaging scan times for pediatric patients, with negligible information loss.

Post-contrast T1-weighted spine 3T MRI in children using a golden-angle radial acquisition.

PURPOSE: MRI methods that have reduced sensitivity to motion are attractive in pediatric applications. In spine imaging, physiologic motion such as respiration and cerebrospinal fluid pulsation can hamper diagnostic image quality. We compare a 3D T1-weighted non-Cartesian radial acquisition with a conventional Cartesian 2D turbo-spin-echo (TSE) acquisition in axial post-contrast spine imaging at 3T. METHODS: Thirty-two patients (mean age 12.2 ± 5.3 years) scheduled for routine clinical spine exams with contrast were enrolled. Three pediatric neuroradiologists compared the two sequences and assessed the presence of motion, the conspicuity of nerve roots, and whether one of the sequences was preferred in visualizing pathology using Likert scales. RESULTS: The Fleiss' kappa statistic for inter-rater agreement was 0.29 (95% confidence interval, 0.15-0.43) for the presence of motion, 0.30 (0.21-0.38) for conspicuity, and 0.37 (0.19-0.55) for sequence preference. Radial images were less sensitive to motion than TSE (p < 0.01). Motion and consequent artifacts were present in all TSE cases, while it was absent in 51% of the radial cases. In depicting nerve roots, radial images were superior in the cervical (p < 0.05), thoracic (p < 0.01), and lumbar spines (p < 0.01). Lastly, in 28 of the 32 patients who demonstrated contrast-enhancing pathology, radial images were preferred in 51% of the cases, while both sequences were equally preferred in 41% of the cases. CONCLUSION: We demonstrate the potential utility of radial MRI in post-contrast spine imaging. The free-breathing method is robust in generating diagnostic image quality and is superior in visualizing nerve roots and extramedullary metastases than traditional Cartesian TSE acquisitions.

Measurement of vertebral bone marrow proton density fat fraction in children using quantitative water-fat MRI.

OBJECTIVES: To investigate the feasibility of employing a 3D time-interleaved multi-echo gradient-echo (TIMGRE) sequence to measure the proton density fat fraction (PDFF) in the vertebral bone marrow (VBM) of children and to examine cross-sectional changes with age and intra-individual variations from the lumbar to the cervical region in the first two decades of life. MATERIALS AND METHODS: Quantitative water-fat imaging of the spine was performed in 93 patients (49 girls; 44 boys; age median 4.5 years; range 0.1-17.6 years). For data acquisition, a six-echo 3D TIMGRE sequence was used with phase correction and complex-based water-fat separation. Additionally, single-voxel MR spectroscopy (MRS) was performed in the L4 vertebrae of 37 patients. VBM was manually segmented in the midsagittal slice of each vertebra. Univariable and multivariable linear regression models were calculated between averaged lumbar, thoracic and cervical bone marrow PDFF and age with adjustments for sex, height, weight, and body mass index percentile. RESULTS: Measured VBM PDFF correlated strongly between imaging and MRS (R 2 = 0.92, slope = 0.94, intercept = -0.72%). Lumbar, thoracic and cervical VBM PDFF correlated significantly (all p < 0.001) with the natural logarithm of age. Differences between female and male patients were not significant (p > 0.05). CONCLUSION: VBM development in children showed a sex-independent cross-sectional increase of PDFF correlating with the natural logarithm of age and an intra-individual decrease of PDFF from the lumbar to the cervical region in all age groups. The present results demonstrate the feasibility of using a 3D TIMGRE sequence for PDFF assessment in VBM of children.

Brown fat in humans: consensus points and experimental guidelines.

As part of a current worldwide effort to understand the physiology of human BAT (hBAT) and whether its thermogenic activity can be manipulated to treat obesity, the workshop "Exploring the Roles of Brown Fat in Humans" was convened at the National Institutes of Health on February 25-26, 2014. Presentations and discussion indicated that hBAT and its physiological roles are highly complex, and research is needed to understand the health impact of hBAT beyond thermogenesis and body weight regulation, and to define its interactions with core physiological processes like glucose homeostasis, cachexia, physical activity, bone structure, sleep, and circadian rhythms.

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.

Brown adipose tissue and its relationship to bone structure in pediatric patients.

CONTEXT: Emerging evidence suggests a possible link between brown adipose tissue (BAT) and bone metabolism. OBJECTIVE: The objective of this study was to examine the relationships between BAT and bone cross-sectional dimensions in children and adolescents. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at a pediatric referral center. PATIENTS: Patients included 40 children and teenagers (21 males and 19 females) successfully treated for pediatric malignancies. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: The volume of BAT was determined by fluorodeoxyglucose-positron emission tomography/computed tomography. Measures of the cross-sectional area and cortical bone area and measures of thigh musculature and sc fat were determined at the midshaft of the femur. RESULTS: Regardless of sex, there were significant correlations seen between BAT volume and the cross-sectional dimensions of the bone (r values between 0.68 and 0.77; all P ≤ 0 .001). Multiple regression analyses indicated that the volume of BAT predicted femoral cross-sectional area and cortical bone area, even after accounting for height, weight, and gender. The addition of muscle as an independent variable increased the predictive power of the model but significantly decreased the contribution of BAT. CONCLUSIONS: The volume of BAT is positively associated with the amount of bone and the cross-sectional size of the femur in children and adolescents. This relation between BAT and bone structure could, at least in part, be mediated by muscle.

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.

Inverse association between brown adipose tissue activation and white adipose tissue accumulation in successfully treated pediatric malignancy.

BACKGROUND: Although the accumulation of white adipose tissue (WAT) is a risk factor for disease, brown adipose tissue (BAT) has been suggested to have a protective role against obesity. OBJECTIVE: We studied whether changes in BAT were related to changes in the amounts of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in children treated for malignancy. DESIGN: We examined the effect of BAT activity on weight, SAT, and VAT in 32 pediatric patients with cancer whose positron emission tomography-computed tomography (PET-CT) scans at diagnosis showed no BAT activity. Changes in weight, SAT, and VAT from diagnosis to remission for children with metabolically active BAT at disease-free follow-up (BAT+) were compared with those in children without visualized BAT when free of disease (BAT-). RESULTS: Follow-up PET-CT studies (4.7 ± 2.4 mo later) after successful treatment of the cancer showed BAT+ in 19 patients but no active BAT (BAT-) in 13 patients. BAT+ patients, in comparison with BAT- patients, gained significantly less weight (3.3 ± 6.6% compared with 11.0 ± 11.6%; P = 0.02) and had significantly less SAT (18.2 ± 26.5% compared with 67.4 ± 71.7%; P = 0.01) and VAT (22.6 ± 33.5% compared with 131.6 ± 171.8%; P = 0.01) during treatment. Multiple regression analysis indicated that the inverse relations between BAT activation and measures of weight, SAT, and VAT persisted even after age, glucocorticoid treatment, and the season when the PET-CT scans were obtained were accounted for. CONCLUSION: The activation of BAT in pediatric patients undergoing treatment of malignancy is associated with significantly less adipose accumulation. This trial was registered at clinicaltrials.gov as NCT01517581.

CT fluoroscopy-guided biopsy of the lung or upper abdomen with a breath-hold monitoring and feedback system: a prospective randomized controlled clinical trial.

PURPOSE: To prospectively determine the clinical effectiveness of a breath-hold monitoring and feedback system in computed tomographic (CT) fluoroscopy-guided biopsies in which respiratory motion is a problem. MATERIALS AND METHODS: Institutional review board approval and oral and written informed consent were obtained. This study was HIPAA compliant. A bellows-based system was used to monitor respiration and provide patient feedback. A randomized controlled clinical trial compared intermittent mode CT fluoroscopy-guided biopsies of the lung or upper abdomen performed with (n = 56) and without (n = 57) the bellows system. Inclusion criteria for 113 patients were lesions 6 cm or smaller in maximum dimension that were not affixed to the chest or abdominal wall. Primary outcome measurements were CT fluoroscopy exposure time and patient dose. Wilcoxon rank sum, chi(2), and Fisher exact tests were used for statistical analysis. RESULTS: Median CT fluoroscopy exposure time was 12.6 seconds (range, 2.4-44.4 seconds) for the bellows group and 18.0 seconds (range, 6.0-118.0 seconds) for the nonbellows group (P = .004). Patient dose was decreased in the bellows group (median dose, 29.5 mGy; range, 4.7-135.8 mGy) versus the nonbellows group (median, 41.3 mGy; range, 11.8-155.9 mGy) (P = .01). Lesions were accessed successfully with one needle puncture attempt in 43 of 56 patients (77%) in the bellows group and 30 of 57 patients (53%) in the nonbellows group (P = .007). Pneumothorax developed in 11 of 50 patients (22%) in the bellows group who underwent lung biopsy compared with 16 of 50 (32%) patients in the nonbellows group. CONCLUSION: A breath-hold monitoring and feedback system allows depiction of mobile target lesions throughout CT fluoroscopy-guided biopsy of the lung and upper abdomen.

Intermittent-mode CT fluoroscopy-guided biopsy of the lung or upper abdomen with breath-hold monitoring and feedback: system development and feasibility.

A bellows-based breath-hold monitoring and feedback system was developed and evaluated for use in intermittent-mode computed tomographic (CT) fluoroscopy-guided biopsy procedures in the lung or upper abdomen. The bellows system is described, and its feasibility is demonstrated in studies with a respiratory phantom and human volunteers. Results are reported for seven patients who underwent bellows-assisted biopsy. Breath-hold monitoring and feedback with the bellows system allow the patient to perform reliable breath holding at a preselected level. This optimizes intermittent-mode CT fluoroscopy-guided biopsies by allowing consistent visualization of the target lesion throughout the procedure.