Patricia C. Aggabao

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

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.

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.

Presence of Brown Adipose Tissue in an Adolescent With Severe Primary Hypothyroidism

CONTEXT Brown adipose tissue (BAT) generates heat during adaptive thermogenesis in response to cold temperature. Thyroid hormone (TH) receptors, type 2 deiodinase, and TSH receptors are present on brown adipocytes, indicating that the thyroid axis regulates BAT. It is unknown whether absent TH in humans would down-regulate development of BAT and its thermogenic function. OBJECTIVE The objective of the study was to examine BAT by magnetic resonance imaging (MRI) and infrared thermal imaging (IRT) in a pediatric patient with severe primary hypothyroidism before and after TH treatment. DESIGN/SETTING This study was a case report with longitudinal follow-up in a tertiary center. MAIN OUTCOME MEASURES BAT fat fraction (FF) by MRI and skin temperature by IRT were measured. RESULTS An 11.5-year-old female was severely hypothyroid (TSH, 989 μIU/mL; free T4, 0.10 ng/dL; low thyroglobulin, 3.0 ng/mL). Low MRI measures of FF (56.1% ± 3.7%) indicated that BAT was abundantly present in the supraclavicular fossa. IRT showed higher supraclavicular temperature (36.0°C ±0.16°C) than the suprasternal area (34.3°C ± 0.19°C). After 2 months of TH replacement, she was euthyroid (TSH, 4.3 μIU/mL; free T4, 1.49 ng/dL; T3, 102 ng/dL) at which time supraclavicular BAT decreased (increased FF 60.7% ± 3.8%). IRT showed a higher, more homogeneous skin temperature throughout the upper thorax (supraclavicular, 37.1°C ± 0.23°C; suprasternal, 36.4°C ± 0.13°C). The overall size of the supraclavicular fat depot decreased from 84.79 cm(3) to 41.21 cm(3). CONCLUSIONS These findings document the presence of BAT and thermogenesis in profound hypothyroidism and suggest a role for TSH and/or TRH as a potential regulator of BAT.

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.

Brown Adipose Tissue in the Buccal Fat Pad during Infancy

Background The buccal fat pad (BFP) is an encapsulated mass of adipose tissue thought to enhance the sucking capabilities of the masticatory muscles during infancy. To date, no conclusive evidence has been provided as to the composition of the BFP in early postnatal life. Objective The purpose of this study was to examine whether the BFP of neonates and infants is primarily composed of white adipose tissue (WAT) or brown adipose tissue (BAT). Materials and Methods The percentage of fat in the BFP in 32 full-term infants (16 boys and 16 girls), aged one day to 10.6 months, was measured using magnetic resonance imaging (MRI) determinations of fat fraction. Results BFP fat fraction increased with age (r = 0.67; P<.0001) and neonates had significantly lower values when compared to older infants; 72.6±9.6 vs. 91.8±2.4, P<.0001. Multiple regression analysis indicated that the age-dependent relationship persisted after accounting for gender, gestational age, and weight percentile (P = .001). Two subjects (aged one and six days) depicted a change in the MRI characteristics of the BFP from primarily BAT to WAT at follow-up examinations two to six weeks later, respectively. Histological post-mortem studies of a 3 day and 1.1 month old revealed predominantly BAT and WAT in the BFP, respectively. Conclusion The BFP is primarily composed of BAT during the first weeks of life, but of WAT thereafter. Studies are needed to investigate the contributions of BAT in the BFP to infant feeding and how it is altered by postnatal nutrition.

Association between vertebral cross-sectional area and lumbar lordosis angle in adolescents

Lumbar lordosis (LL) is more prominent in women than in men, but the mechanisms responsible for this discrepancy are poorly defined. A recent study indicates that newborn girls have smaller vertebral cross-sectional area (CSA) when compared to boys—a difference that persists throughout life and is independent of body size. We determined the relations between vertebral cross-sectional area (CSA) and LL angle and whether sex differences in lumbar lordosis are related to sex differences in vertebral CSA. Using multi-planar magnetic resonance imaging (MRI), we measured vertebral cross-sectional area (CSA) and vertebral height of the spine of 40 healthy boys and 40 girls, ages 9–13 years. Measures of the CSA of the lumbar vertebrae significantly differed between sexes (9.38 ± 1.46 vs. 7.93 ± 0.69 in boys and girls, respectively; P < 0.0001), while the degree of LL was significantly greater in girls than in boys (23.7 ± 6.1 vs. 27.6 ± 8.0 in boys and girls, respectively; P = 0.02). When all subjects were analyzed together, values for LL angle were negatively correlated to vertebral CSA (r = -0.47; P < 0.0001); this was also true when boys and girls were analyzed separately. Multivariate regression analysis indicated that vertebral CSA was independently associated with LL, even after accounting for sex, age, height or vertebral height, and weight. Similar negative relations were present when thoracic vertebrae were analyzed (Model P < 0.0001, R2 = 0.37, thoracic vertebral CSA slope P < 0.0001), suggesting that deficient vertebral cross-sectional dimensions are not merely the consequence of the anterior lumbar curvature. We conclude that vertebral CSA is negatively associated with LL, and that the greater degree of LL in females could, at least in part, be due to smaller vertebral cross-sectional dimensions. Studies are needed to examine the potential relations between vertebral CSA and spinal conditions known to be associated with increased LL, such as spondylolysis and spondylolisthesis.

Association Between Vertebral Cross-sectional Area and Vertebral Wedging in Children and Adolescents: A Cross-sectional Analysis: VERTEBRAL CSA ASSOCIATED WITH VERTEBRAL WEDGING

A small vertebral cross‐sectional area (CSA) imparts a mechanical disadvantage that escalates the risk for vertebral fractures in elderly populations. We examined whether a small vertebral CSA is also associated with a greater degree of vertebral wedging in children. Measurements of vertebral CSA, lumbar lordosis (LL) or thoracic scoliosis angle, and vertebral wedging were obtained in 100 healthy adolescents (50 boys and 50 girls) and 25 girls with adolescent idiopathic scoliosis (AIS) using magnetic resonance imaging. Vertebral CSA of the lumbar vertebrae negatively correlated to the degree of posteroanterior vertebral wedging at L5 (r = –0.49; p < 0.0001); this was true whether all subjects were analyzed together or boys and girls independently. In contrast, we found a positive correlation between the degree of LL and vertebral wedging (r = 0.57; p < 0.0001). Multiple regression analysis showed that the association between vertebral CSA and wedging was independent of age and body mass index. In girls with AIS, vertebral CSA negatively correlated to the degree of lateral thoracic vertebral wedging (r = –0.66; p = 0.0004), an association that persisted even after accounting for age and body mass index. Additionally, Cobb angle positively correlated to lateral thoracic vertebral wedging (r = 0.46; p = 0.021). Our cross‐sectional results support the hypothesis that smaller vertebral CSA is associated with greater vertebral deformity during growth, as in adulthood.

Biomechanical Modeling of Spine Flexibility and Its Relationship to Spinal Range of Motion and Idiopathic Scoliosis

STUDY DESIGN Cross-sectional OBJECTIVE: To examine the relationships between spine morphology, spine flexibility, and idiopathic scoliosis. BACKGROUND Girls have a higher incidence of clinically significant scoliosis than boys, along with smaller vertebrae and greater flexibility. Based on biomechanical modeling, we hypothesized that smaller vertebral width relative to intervertebral disc (IVD) height would be associated with both greater lateral flexibility of the spine and with idiopathic scoliosis. METHODS Magnetic resonance imaging was used to measure IVD height, vertebral width, and paraspinous musculature in 22 girls with mild and moderate idiopathic scoliosis and 29 girls without scoliosis ages 9-13 years. Clinical measurement of maximum lateral bending was also performed in the girls without scoliosis. A simple biomechanical model was used to estimate bending angle from the ratio of IVD height to vertebral half-width for L1-L4. The average ratio (Ravg) and calculated total bending angle (α tot) for L1-L4 were compared to the clinical measurements of lateral bending flexibility in the control group. These measures were also compared between the scoliosis and control groups. RESULTS There was a significant positive relationship between clinical flexibility and both Ravg (p =.041) and αtot (p =.042) adjusting for skeletal age, height, body mass index, and paraspinous muscle area as covariates. The ratio was significantly higher (Ravg = 0.45 vs. 0.38, p <.0001) and the bending angle was significantly greater (αtot = 107° vs. 89°, p <.0001) for girls with scoliosis compared with controls. CONCLUSION These results suggest that differences in spine morphology and corresponding changes in spine flexibility may be related to idiopathic scoliosis. If these relationships can be corroborated in larger prospective studies, these easily measured morphologic traits may contribute to a better understanding of the etiology of idiopathic scoliosis and an improved ability to predict scoliosis progression. LEVEL OF EVIDENCE Level III.

Vertebral cross-sectional growth: A predictor of vertebral wedging in the immature skeleton

The degree of vertebral wedging, a key structural characteristic of spinal curvatures, has recently been found to be negatively related to vertebral cross-sectional area (CSA). The purpose of this longitudinal study was to examine the relation between vertebral cross-sectional growth and vertebral wedging progression within the immature lumbar spine. Using magnetic resonance imaging (MRI), we analyzed the potential association between increases in lumbar vertebral CSA and changes in L5 vertebral wedging in 27 healthy adolescent girls (ages 9–13 years) twice within a two-year period. Vertebral CSA growth was negatively associated with changes in posteroanterior vertebral wedging (r = -0.61; p = 0.001). Multiple regression analysis showed that this relation was independent of gains in age, height, and weight. When compared to the 14 girls whose vertebral wedging progressed, the 13 subjects whose vertebral wedging decreased had significantly greater vertebral cross-sectional growth (0.39 ± 0.25 vs. 0.75 ± 0.23 cm2; p = 0.001); in contrast, there were no significant differences in increases in age, height, or weight between the two groups. Changes in posteroanterior vertebral wedging and the degree of lumbar lordosis (LL) positively correlated (r = 0.56, p = 0.002)—an association that persisted even after adjusting for gains in age, height, and weight. We concluded that in the immature skeleton, vertebral cross-sectional growth is an important determinant of the plasticity of the vertebral body; regression of L5 vertebral wedging is associated with greater lumbar vertebral cross-sectional growth, while progression is the consequence of lesser cross-sectional growth.