Distribution Of Hepatic Blood Flow Research Articles

Abstract 13627: Hepatic Venous Return to Lungs in Fontan is Dependent on Age-Dependent Caval Flow Ratio

Introduction: The Fontan procedure is performed between 2-4 years of age and is a palliative technique for patients born with single ventricle defects. The Fontan physiology is the result of a total cavopulmonary connection between superior and inferior vena cava (SVC and IVC) and the hepatic veins to the pulmonary arteries (PA). Maldistribution of hepatic blood flow to the lungs can result in the formation of pulmonary arteriovenous malformations (PAVM) and resulting cyanosis. Hepatic blood flow distribution (HFD) to right and left lungs is highly dependent on the local flow dynamics. We sought to investigate the impact of SVC-to-IVC flow ratio and age on HFD. Methods: SVC and IVC flow data measured by cardiac MRI (CMR) from 81 Fontan patients were collected to establish the relationship between SVC: IVC flow ratio vs. age. 3D Patient-specific computational fluid dynamics (CFD) modeling was performed for 5 patients who underwent Fontan procedure with an extracardiac conduit to quantify the HFD to the right and left PAs. We evaluated the dependency of HFD on SVC: IVC flow ratio by quantifying HFD to different SVC: IVC flow ratios (2, 1.0, and 0.5) for a given Fontan anatomy. Results: SVC: IVC flow ratio inverted at ~10 years of age (n=81, Figure A) indicating a clear shift to lower body predominance in overall caval flow. CFD analysis (n=5) showed that the shift in SVC-IVC flow had a significant effect on the HFD (Fig. B-F). Change in HFD was more substantial as SVC: IVC flow ratio shifted from 2 to 1 [~5-10 years] with an average % change of 21±6 compared to the HFD change that occurred for a shift of 1 to 0.5 [9±11 for ~10-20 years] (Fig. B-F). Conclusion: Well-balanced distribution of HFD is essential to prevent PAVMs and to ensure long-term efficacy of a Fontan. This study highlights how SVC: IVC flow ratios change over time and can impact HFD to PAs. Interventions to address HFD maldistribution should not be considered in isolation and should incorporate predictions of SVC: IVC changes over time.

Virtual treatment planning in three patients with univentricular physiology using computational fluid dynamics-Pitfalls and strategies.

BackgroundUneven hepatic venous blood flow distribution (HFD) to the pulmonary arteries is hypothesized to be responsible for the development of intrapulmonary arteriovenous malformations (PAVM) in patients with univentricular physiology. Thus, achieving uniform distribution of hepatic blood flow is considered favorable. However, no established method for the prediction of the post-interventional hemodynamics currently exists. Computational fluid dynamics (CFD) offers the possibility to quantify HFD in patient-specific anatomies before and after virtual treatment. In this study, we evaluated the potential benefit of CFD-assisted treatment planning.Materials and methodsThree patients with total cavopulmonary connection (TCPC) and PAVM underwent cardiovascular magnetic resonance imaging (CMR) and computed tomography imaging (CT). Based on this imaging data, the patient-specific anatomy was reconstructed. These patients were considered for surgery or catheter-based intervention aiming at hepatic blood flow re-routing. CFD simulations were then performed for the untreated state as well as for different surgical and interventional treatment options. These treatment options were applied as suggested by treating cardiologists and congenital heart surgeons with longstanding experience in interventional and surgical treatment of patients with univentricular physiology. HFD was quantified for all simulations to identify the most viable treatment decision regarding redistribution of hepatic blood flow.ResultsFor all three patients, the complex TCPC anatomy could be reconstructed. However, due to the presence of metallic stent implants, hybrid models generated from CT as well as CMR data were required. Numerical simulation of pre-interventional HFD agreed well with angiographic assessment and physiologic considerations. One treatment option resulting in improvement of HFD was identified for each patient. In one patient follow-up data after treatment was available. Here, the virtual treatment simulation and the CMR flow measurements differed by 15%.ConclusionThe combination of modern computational methods as well as imaging methods for assessment of patient-specific anatomy and flow might allow to optimize patient-specific therapy planning in patients with pronounced hepatic flow mismatch and PAVM. In this study, we demonstrate that these methods can also be applied in patients with complex univentricular physiology and extensive prior interventions. However, in those cases, hybrid approaches utilizing information of different image modalities may be required.

Non-uniform mixing of hepatic venous flow and inferior vena cava flow in the Fontan conduit.

Fontan patients require a balanced hepatic blood flow distribution (HFD) to prevent pulmonary arteriovenous malformations. Currently, HFD is quantified by tracking Fontan conduit flow, assuming hepatic venous (HV) flow to be uniformly distributed within the Fontan conduit. However, this assumption may be unvalid leading to inaccuracies in HFD quantification with potential clinical impact. The aim of this study was to (i) assess the mixing of HV flow and inferior vena caval (IVC) flow within the Fontan conduit and (ii) quantify HFD by directly tracking HV flow and quantitatively comparing results with the conventional approach. Patient-specific, time-resolved computational fluid dynamic models of 15 total cavopulmonary connections were generated, including the HV and subhepatic IVC. Mixing of HV and IVC flow, on a scale between 0 (no mixing) and 1 (perfect mixing), was assessed at the caudal and cranial Fontan conduit. HFD was quantified by tracking particles from the caudal (HFDcaudal conduit) and cranial (HFDcranial conduit) conduit and from the hepatic veins (HFDHV). HV flow was non-uniformly distributed at both the caudal (mean mixing 0.66 ± 0.13) and cranial (mean 0.79 ± 0.11) level within the Fontan conduit. On a cohort level, differences in HFD between methods were significant but small; HFDHV (51.0 ± 20.6%) versus HFDcaudal conduit (48.2 ± 21.9%, p = 0.033) or HFDcranial conduit (48.0 ± 21.9%, p = 0.044). However, individual absolute differences of 8.2–14.9% in HFD were observed in 4/15 patients. HV flow is non-uniformly distributed within the Fontan conduit. Substantial individual inaccuracies in HFD quantification were observed in a subset of patients with potential clinical impact.

Technique for comprehensive fetal hepatic blood flow assessment in sheep using 4D flow MRI.

The comprehensive visualization and quantification of in vivo fetal hepatic haemodynamics, particularly the shunting of ductus venosus blood, has been elusive and is not yet fully understood. We introduce the combination of chronically instrumented fetal sheep and 4D flow MRI of the whole fetal liver, which allows retrospective blood flow measurement in all visible vessels as well as qualitative assessment. The applicability and usefulness of this technique is exhibited in normally grown fetal Merino sheep in mid- and late-gestation with detailed dynamic distribution of hepatic blood flow presented. The feasibility of this approach in clinical pathology is demonstrated in two growth-restricted fetuses at mid-gestation. Further exemplification of blood flow quantification is performed over major hepatic vessels. Although the fetal vasculature has been demarcated and well understood for several decades, the corresponding haemodynamics permitting oxygen- and nutrient-rich blood delivery to the fetal organs has been comparatively difficult to study. We married two well-established methods: 4D flow MRI, a volumetric and dynamic blood-flow measurement technique, and chronically instrumented sheep to broadly assess fetal hepatic circulation. We performed this technique in mid- and late-gestation fetal Merino sheep under normoxemic conditions and major hepatic vasculature was segmented to quantify blood flow and related parameters. Dynamic blood flow was visualized, exhibiting an acceleration of umbilical vein blood through the ductus venosus as well as spiralling into the inferior vena cava where its stream remained separate from that of the hepatic veins and lower body. Ductus venosus changes from mid- to late-gestation included larger diameter (mid: 5.8±0.9 vs. late: 7.1±1.1mm; P=0.003) and cross-sectional area (mid: 27.1±8.6 vs. late: 40.4±11.8mm2 ; P=0.003), and lower velocity averaged over the cardiac cycle (mid: 15.7±5.4 vs. late: 9.8±7.0cms-1 ; P=0.020). This resulted in higher magnitude blood flow (indexed to umbilical vein input) at mid-gestation in the ductus venosus (mid: 0.73±0.21; late: 0.46±0.21; P=0.008). The visualization and quantification results support the further use of this technique to better understand regional blood flow changes during normal or abnormal fetal growth, as well as to observe acute haemodynamic responses to physiological challenges or drug interventions.

Outcomes of Single Ventricle Patients Undergoing the Kawashima Procedure: Can We Do Better?

Current technology advances in virtual surgery modeling and computational flow dynamics allow preoperative individualized computer-based design of Fontan operation. To determine potential role of those innovations in patients undergoing hepatic vein incorporation (HVI) following Kawashima operation, we retrospectively examined historic cohort of patients who underwent HVI following Kawashima with focus on regression of pulmonary arteriovenous malformations (PAVMs). Twenty-two children with single ventricle and interrupted inferior vena cava underwent Kawashima operation (2002-12). Twenty-one (96%) patients had left atrial isomerism and 21 (96%) had undergone prior first-stage palliation. Clinical outcomes were examined. Mean O2 saturation (SaO2) increased from 77% ± 8% to 85% ± 6% ( P = .002) after Kawashima. Fifteen (68%) patients developed PAVMs. Eighteen patients underwent HVI (median age and interval from Kawashima: 4.4 and 3.7 years, respectively). Mean SaO2 prior to HVI was 77% ± 8% and increased to 81% ± 10% at the time of hospital discharge ( P = .250), with five patients requiring home oxygen. On follow-up, mean SaO2 increased to 95% ± 4% ( P < .001). Overall ten-year survival following Kawashima was 94%. A large number of patients develop PAVMs and subsequent cyanosis after Kawashima operation. Early following HVI, SaO2 is commonly low and insignificantly different from that prior to HVI. Although SaO2 will improve on follow-up in most patients, a number of patients continue to have low saturations, indicating incomplete resolution of PAVMs. Given the heterogeneity of those patients and lack of preoperative predictors for complete PAVM regression, our findings suggest a role for virtual surgery to determine optimal individual procedure design that would provide even distribution of hepatic blood flow to both pulmonary arteries.

A pulsatile hemodynamic evaluation of the commercially available bifurcated Y-graft Fontan modification and comparison with the lateral tunnel and extracardiac conduits

ObjectiveFontan completion, resulting in a total cavopulmonary connection, is accomplished using a lateral tunnel, extracardiac conduit, or bifurcated Y-graft. The use of Y-grafts is hypothesized to provide symmetric hepatic blood flow distribution to the lungs, a factor related to pulmonary arteriovenous malformations. The present study evaluates the hemodynamic performance of the largest commercially available Y-graft cohort to date, highlights 6 representative cases, and compares commercially available Y-graft performance with lateral tunnel/extracardiac conduit connections. MethodsA total of 30 patients with commercially available Y-grafts and 30 patients with lateral tunnel/extracardiac conduits were analyzed. Total cavopulmonary connection anatomies and flow waveforms were reconstructed using cardiac magnetic resonance images and phase-contrast cardiac magnetic resonance. Computational fluid dynamic simulations were performed to quantify total cavopulmonary connection power loss, resistance, and hepatic flow distribution. Comparisons between graft types were investigated. ResultsTotal cavopulmonary connection resistance was significantly higher for Y-grafts. Hepatic flow distribution was similar overall but showed discrepancies at extreme values with more unbalanced flow in the Y-graft cohort. Power loss was more sensitive to left pulmonary artery stenosis in the Y-graft cohort. Prediction of Y-graft hepatic flow distribution is multifactorial. ConclusionsCommercially available Y-grafts do not inherently provide more balanced hepatic flow distribution than lateral tunnel/extracardiac conduit connections, which are more energetically favorable and less sensitive to pulmonary artery stenosis. Graft type should be considered on an individual basis because hemodynamic performance is based on a combination of factors, including pulmonary flow distribution, pulmonary artery stenosis, and superior vena cava positioning.

Abstract 14364: Hemodynamic Evaluation of 30 Y-Graft Fontan Completions

Background: Fontan completion, resulting in a total cavopulmonary connection (TCPC), is accomplished using either a traditional baffle or bifurcated Y-graft. The use of Y-grafts was originally hypothesized to provide more even hepatic blood flow distribution to the lungs, a factor related to pulmonary arteriovenous malformations. This study evaluates the hemodynamic performance of the largest Y-graft cohort to date, compares those results with a traditional baffle, and highlights Y-graft cases that exhibit both favorable and poor performance. Methods: Thirty Y-graft and 30 traditional baffle Fontan patients were analyzed. TCPC anatomies and vessel flow waveforms were reconstructed using cardiac magnetic resonance (CMR) images and phase-contrast CMR. Computational fluid dynamic simulations were performed to quantify TCPC power loss, resistance, and hepatic flow distribution (HFD). Comparisons between graft types and subanalysis of favorable versus poor performing Y-grafts were investigated. Results: The TCPC resistance distribution, HFD distribution, and the effect of LPA stenosis on power loss for Y-grafts and traditional baffles are shown in Fig. 1A-1C. TCPC resistance was significantly lower in traditional baffle patients. HFD was similar overall, with median and range of 40 (1-77) and 51 (1-99) for the traditional baffle and Y-graft, but show a discrepancy at extreme values with more unbalanced flow in the Y-graft cohort. Power loss was more sensitive to LPA stenosis in the Y-graft cohort. Prediction of Y-graft HFD is multi-factorial and six representative cases are shown in Fig. 1D. Conclusions: Y-grafts do not inherently provide more balanced HFD than traditional baffles. Traditional baffles are more energetically favorable and less sensitive to PA stenosis. Graft type should be considered on an individual basis as hemodynamic performance is based on a combination of factors, including global flow distribution, PA stenosis and SVC positioning.

Flow simulations and validation for the first cohort of patients undergoing the Y-graft Fontan procedure

In this study, with the use of computational fluid dynamics, we evaluate the postoperative hemodynamic performance of the first cohort of patients undergoing a handcrafted Y-graft Fontan procedure and validate simulation predictions of hepatic blood flow distribution against invivo clinical data. An 18-12×2-mm handcrafted Y-graft modification of the Fontan procedure was performed in 6 patients. Early (at the time of discharge) and 6-month postoperative 3-dimensional magnetic resonance imaging data were collected. Patient-specific models were constructed for flow simulations. Hepatic blood flow distribution varied among patients. Lung perfusion data (n=3) showed good agreement with simulations. Postoperative asymmetry in hepatic blood flow distribution was reduced 6 months postoperatively. In 1 patient, low wall shear stress was found in the left limb of the Y-graft, corresponding to the location of subsequent thrombosis in the patient. The credibility and accuracy of simulation-based predictions of postoperative hepatic flow distribution for the Fontan surgery have been validated by invivo lung perfusion data. The performance of the Y-graft design is highly patient-specific. The anastomosis location is likely the most important factor influencing hepatic blood flow distribution. Although the development of thrombosis is multifactorial, the occurrence in 1 patient suggests that simulations should not solely consider the hepatic blood flow distribution but also aim to avoid low wall shear stress in the limbs.

Hepatic blood flow distribution and performance in conventional and novel Y-graft Fontan geometries: A case series computational fluid dynamics study

A novel Y-shaped baffle has been proposed for the Fontan operation with promising initial results. However, previous studies have relied either on idealized models or a single patient-specific model. The objective of this study is to comprehensively compare the hemodynamic performance and hepatic blood flow distribution of the Y-graft Fontan baffle with 2 current designs using multiple patient-specific models. Y-shaped and tube-shaped grafts were virtually implanted into 5 patient-specific Glenn models forming 3 types of Fontan geometries: Y-graft, T-junction, and offset. Unsteady flow simulations were performed at rest and at varying exercise conditions. The hepatic flow distribution between the right and left lungs was carefully quantified using a particle tracking method. Other physiologically relevant parameters such as energy dissipation, superior vena cava pressure, and wall shear stress were evaluated. The Fontan geometry significantly influences the hepatic flow distribution. The Y-graft design improves the hepatic flow distribution effectively in 4 of 5 patients, whereas the T-junction and offset designs may skew as much as 97% of hepatic flow to 1 lung in 2 cases. Sensitivity studies show that changes in pulmonary flow split can affect the hepatic flow distribution dramatically but that some Y-graft and T-junction designs are relatively less sensitive than offset designs. The Y-graft design offers moderate improvements over the traditional designs in power loss and superior vena cava pressure in all patients. The Y-graft Fontan design achieves overall superior hemodynamic performance compared with traditional designs. However, the results emphasize that no one-size-fits-all solution is available that will universally benefit all patients and that designs should be customized for individual patients before clinical application.

Hepatic blood flow distribution: consideration of gravity, liver surface, and norepinephrine on regional heterogeneity

Blood flow distribution within the livers of cats and dogs was assessed using 15-microns microspheres injected into the hepatic artery and portal vein. Representative vertical core samples (n = 11-18) were taken from the thickest part of each liver. Heterogeneity was assessed in several ways. The difference in total flow to different lobes was greater in dogs than in cats, and in dogs, those lobes with highest portal venous flow had lowest hepatic arterial flow. Overall flow variance was very high in both species, with adjacent surface samples in a single lobe showing variance of 15-22% for both vessels. The ratio of highest to lowest flow within core samples averaged 2.1-3.4 for both vessels in both species. The hepatic arterial flow was highest to the surface 2 mm of the liver. Portal flow most often (31% of all samples) showed a pattern of highest flow to the top, graduating down to lowest flow to the bottom (dorsal side) of the vertical cores. However, this pattern appeared much more frequently in the most ventral liver lobes and very seldom in the lobes lying beneath the liver mass. Norepinephrine reduced heterogeneity. Hepatic arterial occlusion for 10 min produced minor and inconsistent reduction of heterogeneity. Rotating cats from back to front and again to back disrupted patterns of distribution but not in a way that could be interpreted as due to effects of gravity. Flow patterns changed with time. The heterogeneity of perfusion appears to be under dynamic and multiple interacting forces.

Intrahepatic distribution of hepatic blood flow: double-input studies

ARTICLESIntrahepatic distribution of hepatic blood flow: double-input studiesN Lifson, DG Levitt, Griffen WO Jr, and CJ EllisN Lifson, DG Levitt, Griffen WO Jr, and CJ EllisPublished Online:01 May 1970https://doi.org/10.1152/ajplegacy.1970.218.5.1480MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByBlood Flows in Tributaries of the Portal Vein: Anatomical and Angiographic Studies in Normal Beagle Dogs7 November 2014 | Anatomia, Histologia, Embryologia, Vol. 44, No. 6Heterogeneity of the intrahepatic portal venous blood flow: Impact on hepatocyte transplantationMicrovascular Research, Vol. 86PKQuest: volatile solutes – application to enflurane, nitrous oxide, halothane, methoxyflurane and toluene pharmacokinetics15 August 2002 | BMC Anesthesiology, Vol. 2, No. 1PKQuest: measurement of intestinal absorption and first pass metabolism – application to human ethanol pharmacokinetics15 August 2002 | BMC Clinical Pharmacology, Vol. 2, No. 1PKQuest: a general physiologically based pharmacokinetic model. Introduction and application to propranolol15 August 2002 | BMC Clinical Pharmacology, Vol. 2, No. 1PKQuest: capillary permeability limitation and plasma protein binding – application to human inulin, dicloxacillin and ceftriaxone pharmacokinetics26 September 2002 | BMC Clinical Pharmacology, Vol. 2, No. 1Dependency of the [18f]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liverNuclear Medicine and Biology, Vol. 27, No. 8Use of a Two-Compartment Model to Assess the Pharmacokinetics of Human Ethanol MetabolismAlcoholism: Clinical and Experimental Research, Vol. 22, No. 8Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: Limitations of model descriptionEuropean Journal of Nuclear Medicine, Vol. 23, No. 2Patterns of colorectal liver metastases according to Couinaud's segmentsDiseases of the Colon & Rectum, Vol. 38, No. 3Role of the hepatic artery in the metabolism of phenacetin and acetaminophen: An intravital microscopic and multiple-indicator dilution study in perfused rat liverHepatology, Vol. 20, No. 3Marked Heterogeneity in the Intrahepatic Distribution of Quinidine in Rats: Implications in PharmacokineticsJournal of Pharmaceutical Sciences, Vol. 79, No. 9Residence time distributions of solutes in the perfused rat liver using a dispersion model of hepatic elimination: 1. Effect of changes in perfusate flow and albumin concentration on sucrose and taurocholate1 June 1990 | Journal of Pharmacokinetics and Biopharmaceutics, Vol. 18, No. 3Liver blood flowGastroenterology, Vol. 81, No. 1Functional zones in rat liver: The degree of overlapJournal of Theoretical Biology, Vol. 89, No. 2Flow dependence of first-order uptake of substances by heterogeneous perfused organsJournal of Theoretical Biology, Vol. 86, No. 2Heterogeneity of macroscopic and single villus blood flow in rabbit small intestineMicrovascular Research, Vol. 17, No. 2The distribution of RB86 in different parts of the liverPfl�gers Archiv European Journal of Physiology, Vol. 346, No. 2 More from this issue > Volume 218Issue 5May 1970Pages 1480-1488 Copyright & PermissionsCopyright © 1970 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1970.218.5.1480PubMed5438277History Published online 1 May 1970 Published in print 1 May 1970 Metrics

Intrahepatic distribution of hepatic blood flow: single-input studies.

Intrahepatic distribution of hepatic blood flow: single-input studies.