PWI-003 - MAGNETIC RESONANCE IMAGE-BASED ESTIMATES OF HEPATIC BLOOD FLOW IN CHILDREN WITH AND WITHOUT OBESITY; IMPLICATIONS FOR PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODELS.

Y. Cho^1,2, S. Chan^3,2, C. Friesen⁴, V. Shakhnovich^1,2,5; ¹Children's Mercy Kansas City, Kansas City, MO, USA, ²University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA, ³Children's Mercy Kansas City, Kansas City, MO, USA, ⁴University of Kansas, Kansas City, KS, USA, ⁵Center for Children's Healthy Lifestyles and Nutrition, Kansas City, MO, USA.

Background: Physiologically-based pharmacokinetic models (PBPK) are powerful tools for simulating drug pharmacokinetics (PK) in understudied populations, but they are limited by the physiology data available. In this pilot, we explored non-invasive magnetic resonance imaging (MRI) to estimate hepatic blood flow (important for PK of high extraction drugs) in children with and without obesity.

Methods: Abdominal MRI (n=20) with phase contrast flow measurements at the descending aorta (AO), the inferior vena cave (IVC) at the right atrium, and inferior to hepatic drainage above the renal vein confluence (IVCinf), was performed. Hepatic volume and percent liver fat were also measured, and elastography used to confirm normal liver stiffness (i.e., no fibrosis) . Hepatic flow (Hflow) was calculated as Hflow = IVCinf – AO. Using non-parametric tests, Hflow was compared across weight groups and correlations (rho) explored with patient characteristics; SPSSv24, α=0.05.

Results: Hflow in 10-20 year-old youths with body mass index (BMI) 17.7 to 49.7 kg/m2 (BMI z-score for age and sex -1.1 to 2.8) varied from 0.6 to 2.7 Liters/minute. A trend toward higher Hflow with increasing BMI z-score was observed, but did not reach statistical significance (p=0.26). Hflow correlated most significantly with height (rho=0.46, p=0.04). Adjusting Hflow for body surface area, total body weight, fat free body weight, liver volume or lean liver volume did not change the results.

Conclusion: Variability in Hflow may be important to consider for pediatric PBPK modeling. Our pilot dataset suggests that Hflow may be estimated using non-invasive, non-contrast MRI technology. In pediatric patients, Hflow appears to correlate with height, independent of obesity status; however, our sample size is small and MRI data analysis from additional subjects is under way.