Free-breathing 3-D quantification of infant body composition and hepatic fat using a stack-of-radial magnetic resonance imaging technique.

BACKGROUND: Body composition and hepatic fat correlate with future risk for metabolic syndrome. In children, many conventional techniques for quantifying body composition and hepatic fat have limitations. MRI is a noninvasive research tool to study body composition and hepatic fat in infants; however, conventional Cartesian MRI is sensitive to motion, particularly in the abdomen because of respiration. Therefore we developed a free-breathing MRI technique to quantify body composition and hepatic fat in infants. OBJECTIVE: In infants, we aimed to (1) compare the image quality between free-breathing 3-D stack-of-radial MRI (free-breathing radial) and 3-D Cartesian MRI in the liver and (2) determine the feasibility of using free-breathing radial MRI to quantify body composition and hepatic proton-density fat fraction (PDFF). MATERIALS AND METHODS: Ten infants ages 2-7 months were scanned with free-breathing radial (two abdominal; one head and chest) and Cartesian (one abdominal) MRI sequences. The median preparation and scan times were reported. To assess feasibility for hepatic PDFF quantification, a radiologist masked to the MRI technique scored abdominal scans for motion artifacts in the liver using a 3-point scale (1, or non-diagnostic, to 3, or no artifacts). Median visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and brown adipose tissue (BAT) volume and PDFF, and hepatic PDFF were measured using free-breathing radial MRI. We assessed repeatability of free-breathing radial hepatic PDFF (coefficient of repeatability) between back-to-back scans. We determined differences in the distribution of image-quality scores using McNemar-Bowker tests. P<0.05 was considered significant. RESULTS: Nine infants completed the entire study (90% completion). For ten infants, the median preparation time was 32 min and scan time was 24 min. Free-breathing radial MRI demonstrated significantly higher image-quality scores compared to Cartesian MRI in the liver (radial scan 1 median = 2 and radial scan 2 median = 3 vs. Cartesian median = 1; P=0.01). Median measurements using free-breathing radial were VAT=52.0 cm3, VAT-PDFF=42.2%, SAT=267.7 cm3, SAT-PDFF=87.1%, BAT=1.4 cm3, BAT-PDFF=26.1% and hepatic PDFF=3.4% (coefficient of repeatability <2.0%). CONCLUSION: In this study, free-breathing radial MRI in infants achieved significantly improved liver image quality compared to Cartesian MRI. It is feasible to use free-breathing radial MRI to quantify body composition and hepatic fat in infants.

Free-breathing Magnetic Resonance Imaging Assessment of Body Composition in Healthy and Overweight Children: An Observational Study.

OBJECTIVE: Conventional, breath-holding magnetic resonance imaging (MRI) assesses body composition by measuring fat volumes and proton density fat fraction (PDFF). However, breath-holding MRI is not always feasible in children. This study's objective was to use free-breathing MRI to quantify visceral and subcutaneous fat volumes and PDFFs and correlate these measurements with hepatic PDFF. METHODS: This was an observational, hypothesis-forming study that enrolled 2 groups of children (ages 6-17 years), healthy children and overweight children with presumed nonalcoholic fatty liver disease. Free-breathing MRI was used to measure visceral and subcutaneous fat volumes and PDFFs, and hepatic PDFF. Imaging biomarkers were compared between groups, and correlations coefficients (r) and coefficients of determination (R) were calculated. RESULTS: When compared with the control group (n = 10), the overweight group (n = 9) had greater mean visceral (1843 vs 329 cm, P < 0.001) and subcutaneous fat volumes (7663 vs 893 cm, P < 0.001), as well as greater visceral (80% vs 45%, p < 0.001) and subcutaneous fat PDFFs (89% vs 75%, P = 0.003). Visceral fat volume (r = 0.79, P < 0.001) and PDFF (r = 0.92, P < 0.001) correlated with hepatic PDFF. In overweight subjects, for each unit increase in visceral fat PDFF, hepatic PDFF increased by 2.64%; visceral fat PDFF explained 54% of hepatic PDFF variation (R = 0.54, P = 0.02). CONCLUSIONS: In this study, we used free-breathing MRI to measure body composition in children. Future studies are needed to investigate the possible value of subcutaneous and visceral fat PDFFs, and validate free-breathing MRI body composition biomarkers.

Umbilical cord blood bilirubins, gestational age, and maternal race predict neonatal hyperbilirubinemia.

OBJECTIVE: No validated biomarker at birth exists to predict which newborns will develop severe hyperbilirubinemia. This study's primary aim was to build and validate a prediction model for severe hyperbilirubinemia using umbilical cord blood bilirubins (CBB) and risk factors at birth in neonates at risk for maternal-fetal blood group incompatibility. This study's secondary aim was to compare the accuracy of CBB to the direct antigen titer. METHODS: Inclusion criteria for this prospective cohort study included: ≥35 weeks gestational age, mother with blood type O and/or Rh negative or positive antibody screen, and <24 hours of age. The primary outcome was severe hyperbilirubinemia, defined as phototherapy during the initial hospital stay. Secondary outcomes were a total serum bilirubin concentration >95th and >75th percentile during the initial hospital stay. The predictive performance and accuracy of the two tests (CBB and direct antigen titer) for each outcome was assessed using area under a receiver-operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: When compared to neonates who did not receive phototherapy (n = 463), neonates who received phototherapy (n = 36) had a greater mean CBB ± standard deviation (2.5 ± 0.7 vs. 1.6 ± 0.4 mg/dL, p<0.001). For every 0.3 mg/dL increase in CBB, a neonate was 3.20 (95% confidence interval, 2.31-4.45), 2.10 (1.63-2.70), and 3.12 (2.44-3.99) times more likely to receive phototherapy or have a total serum bilirubin concentration >95th and >75th percentile, respectively. The AUC ± standard error (95% confidence interval) for CBB for phototherapy and a total serum bilirubin concentration >95th and >75th percentile was 0.89 ± 0.03 (0.82-0.95), 0.81 ± 0.04 (0.73-0.90), and 0.84 ± 0.02 (0.80-0.89), respectively. However, the AUC for gestational age and maternal Asian race for these outcomes was only 0.55 ± 0.05 (0.45-0.66), 0.66 ± 0.05 (0.56-0.76), and 0.57 ± 0.04 (0.05-0.64), respectively. When the CBB was combined with gestational age and maternal Asian race, the AUC for a total serum bilirubin concentration >95th percentile improved to 0.87 ± 0.03 (0.81-0.92) (p = 0.034 vs. the model with CBB only and p<0.001 vs. the model with clinical risk factors only). In a sub-group of subjects (n = 189), the AUC for the direct antigen titer for phototherapy was 0.64 ± 0.06 (0.52-0.77) with a 52% sensitivity and 77% specificity. In contrast, a CBB cut-point of 1.85 mg/dL was 92% sensitive and 70% specific for phototherapy with an AUC of 0.87 ± 0.04 (0.80-0.95). CONCLUSION: CBB, in combination with gestational age and maternal race, may be a useful, non-invasive test to predict shortly after birth which neonates will develop severe hyperbilirubinemia.

Free-breathing quantification of hepatic fat in healthy children and children with nonalcoholic fatty liver disease using a multi-echo 3-D stack-of-radial MRI technique.

BACKGROUND: In adults, noninvasive chemical shift encoded Cartesian magnetic resonance imaging (MRI) and single-voxel magnetic resonance (MR) spectroscopy (SVS) accurately quantify hepatic steatosis but require breath-holding. In children, especially young and sick children, breath-holding is often limited or not feasible. Sedation can facilitate breath-holding but is highly undesirable. For these reasons, there is a need to develop free-breathing MRI technology that accurately quantifies steatosis in all children. OBJECTIVE: This study aimed to compare non-sedated free-breathing multi-echo 3-D stack-of-radial (radial) MRI versus standard breath-holding MRI and SVS techniques in a group of children for fat quantification with respect to image quality, accuracy and repeatability. MATERIALS AND METHODS: Healthy children (n=10, median age [±interquartile range]: 10.9 [±3.3] years) and overweight children with nonalcoholic fatty liver disease (NAFLD) (n=9, median age: 15.2 [±3.2] years) were imaged at 3 Tesla using free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS. Acquisitions were performed twice to assess repeatability (within-subject mean difference, MDwithin). Images and hepatic proton-density fat fraction (PDFF) maps were scored for image quality. Free-breathing and breath-holding PDFF were compared using linear regression (correlation coefficient, r and concordance correlation coefficient, ρc) and Bland-Altman analysis (mean difference). P<0.05 was considered significant. RESULTS: In patients with NAFLD, free-breathing radial MRI demonstrated significantly less motion artifacts compared to breath-holding Cartesian (P<0.05). Free-breathing radial PDFF demonstrated a linear relationship (P<0.001) versus breath-holding SVS PDFF and breath-holding Cartesian PDFF with r=0.996 and ρc=0.994, and r=0.997 and ρc=0.995, respectively. The mean difference in PDFF between free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS was <0.7%. Repeated free-breathing radial MRI had MDwithin=0.25% for PDFF. CONCLUSION: In this pediatric study, non-sedated free-breathing radial MRI provided accurate and repeatable hepatic PDFF measurements and improved image quality, compared to standard breath-holding MR techniques.