Presenter Status
Fellow
Abstract Type
Research
Primary Mentor
Dr . Sherwin Chan
Start Date
12-5-2023 12:30 PM
End Date
12-5-2023 12:45 PM
Presentation Type
Oral Presentation
Description
Background: Physiologically based pharmacokinetic models for simulating drug pharmacokinetics are useful to guide drug dosing for pediatric patients. Hepatic blood flow could be a useful variable to use in these models.
Objectives/Goal: In this study, we explored 2-D phase contrast non-invasive magnetic resonance imaging (MRI) to measure hepatic blood flow in children with and without obesity.
Methods/Design: In this IRB-approved study, we imaged pediatric patients with abdominal MRI with 2D phase contrast imaging of the descending aorta (AO) at the diaphragm, the inferior vena cava (IVC) at the right atrium, and inferior to hepatic drainage above the renal vein confluence (IVCinf). We measured liver volume and hepatic fat fraction. We calculated body mass index (BMI) Z-score for each patient. We calculated hepatic flow (Hflow) with Circle Cardiovascular Imaging (Hflow = AO - IVCinf). We used AO instead of IVC because the IVC measurements were less reliable due to difficulty getting an accurate imaging plane. We used t-tests to compare Hflow between the three groups: normal weight (BMI Z-score < 1), overweight (1 =< BMI Z-score < 2) and obese (BMI Z-score >= 2). Hflow was correlated using multivariate regression to age, weight, height, liver volume, BMI Z-score, and hepatic fat fraction.
Results: Sixty-nine patients were enrolled in this study. Age ranged from 8-21 years. Body mass index (BMI) was 15.0 to 49.7 kg/m2. BMI Z-scores for age and sex ranged from -1.53 to 3.2. Hflow varied from 0.62 to 3.38 Liters/minute. T-tests showed that Hflow was significantly different between normal weight and obese children (p=0.02); and overweight and obese children (p=0.04); but not different between normal weight and overweight children (p=0.58). A trend toward higher Hflow with increasing BMI z-score was observed (p=0.064). Hflow correlated significantly with height (rho=0.431, p=0.000), weight (rho=0.430, p=0.000), hepatic fat fraction (rho=0.378, p=0.001) and liver volume (rho=0.408, p=0.001). Hflow did not correlate significantly with age.
Conclusions: Variability in hepatic blood flow may be important to consider for pediatric PBPK modeling. We successfully measured hepatic blood flow using MRI. In pediatric patients, hepatic blood flow is correlated with weight, height, hepatic fat fraction, and liver volume. Liver blood flow was also higher in obese children compared with normal weight and overweight children.
MeSH Keywords
Pediatric; Physiology; Liver
Included in
Higher Education and Teaching Commons, Medical Education Commons, Pediatrics Commons, Pharmaceutics and Drug Design Commons, Physiological Processes Commons, Science and Mathematics Education Commons
Magnetic Resonance Image-Based Estimates of Hepatic Blood Flow In Children with and without Obesity; Implications For Physiologically-Based Pharmacokinetic Models
Background: Physiologically based pharmacokinetic models for simulating drug pharmacokinetics are useful to guide drug dosing for pediatric patients. Hepatic blood flow could be a useful variable to use in these models.
Objectives/Goal: In this study, we explored 2-D phase contrast non-invasive magnetic resonance imaging (MRI) to measure hepatic blood flow in children with and without obesity.
Methods/Design: In this IRB-approved study, we imaged pediatric patients with abdominal MRI with 2D phase contrast imaging of the descending aorta (AO) at the diaphragm, the inferior vena cava (IVC) at the right atrium, and inferior to hepatic drainage above the renal vein confluence (IVCinf). We measured liver volume and hepatic fat fraction. We calculated body mass index (BMI) Z-score for each patient. We calculated hepatic flow (Hflow) with Circle Cardiovascular Imaging (Hflow = AO - IVCinf). We used AO instead of IVC because the IVC measurements were less reliable due to difficulty getting an accurate imaging plane. We used t-tests to compare Hflow between the three groups: normal weight (BMI Z-score < 1), overweight (1 =< BMI Z-score < 2) and obese (BMI Z-score >= 2). Hflow was correlated using multivariate regression to age, weight, height, liver volume, BMI Z-score, and hepatic fat fraction.
Results: Sixty-nine patients were enrolled in this study. Age ranged from 8-21 years. Body mass index (BMI) was 15.0 to 49.7 kg/m2. BMI Z-scores for age and sex ranged from -1.53 to 3.2. Hflow varied from 0.62 to 3.38 Liters/minute. T-tests showed that Hflow was significantly different between normal weight and obese children (p=0.02); and overweight and obese children (p=0.04); but not different between normal weight and overweight children (p=0.58). A trend toward higher Hflow with increasing BMI z-score was observed (p=0.064). Hflow correlated significantly with height (rho=0.431, p=0.000), weight (rho=0.430, p=0.000), hepatic fat fraction (rho=0.378, p=0.001) and liver volume (rho=0.408, p=0.001). Hflow did not correlate significantly with age.
Conclusions: Variability in hepatic blood flow may be important to consider for pediatric PBPK modeling. We successfully measured hepatic blood flow using MRI. In pediatric patients, hepatic blood flow is correlated with weight, height, hepatic fat fraction, and liver volume. Liver blood flow was also higher in obese children compared with normal weight and overweight children.
