The Fontan circulation and the liver: A magnetic resonance diffusion-weighted imaging study

Wolff, Djoeke; Melle, Joost P. van; Dijkstra, Hildebrand; Bartelds, Beatrijs; Willems, Tineke P.; Hillege, Hans L.; Berg, Aad P. van den; Ebels, Tjark; Sijens, Paul E.; Berger, Rolf M. F.

doi:10.1016/j.ijcard.2015.09.088

Cited by 35 publications

(29 citation statements)

References 34 publications

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“…15, the hepatic exclusion leads to larger relative changes in the splanchnic circulation, most strikingly in flow and pressure in the common hepatic vein and hepatic portal vein. This drop in pressure highlights the effectiveness of this modification in combating venous and portal venous congestion, thought to be factors potentially leading to complications in the Fontan physiology [2,68,69]. …”

Section: Discussionmentioning

confidence: 99%

A computational study of the Fontan circulation with fenestration or hepatic vein exclusion

Puelz

Acosta

Rivière

et al. 2017

Computers in Biology and Medicine

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Fontan patients may undergo additional surgical modifications to mitigate complications like protein–losing enteropathy, liver cirrhosis, and other issues in their splanchnic circulation. Recent case reports show promise for several types of modifications, but the subtle effects of these surgeries on the circulation are not well understood. In this paper, we employ mathematical modeling of blood flow to systematically quantify the impact of these surgical changes on extracardiac Fontan hemodynamics. We investigate two modifications: (1) the fenestrated Fontan and (2) the Fontan with hepatic vein exclusion. Closed–loop hemodynamic models are used, which consist of one–dimensional networks for the major vessels and zero–dimensional models for the heart and organ beds. Numerical results suggest the hepatic vein exclusion has the greatest overall impact on the hemodynamics, followed by the largest sized fenestration. In particular, the hepatic vein exclusion drastically lowers portal venous pressure while the fenestration decreases pulmonary artery pressure. Both modifications increase flow to the intestines, a finding consistent with their utility in clinical practice for combating complications in the splanchnic circulation.

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Section: Discussionmentioning

confidence: 99%

A computational study of the Fontan circulation with fenestration or hepatic vein exclusion

Puelz

Acosta

Rivière

et al. 2017

Computers in Biology and Medicine

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“…Between January 2012 and October 2013, consecutive patients with a functionally univentricular heart treated with a Fontan operation (further referred to as Fontan patients) were scheduled for cardiac MRI including diffusion-weighted imaging (DWI) of the liver [21]. Inclusion criteria were: age 10 years or older.…”

Section: Methodsmentioning

confidence: 99%

“…This resulted in 59 patients, 32 children and 27 adults (29 men; mean-age, 19.1 years; age-range, 9.6–44.7 years). All 59 patients have been previously reported [21]. This prior article dealt with the association between the ADC and functional liver parameters; whereas in this manuscript we apply IVIM modeling to explain the previously observed decreased ADC in Fontan livers by measuring the microperfusion and molecular diffusion in each of eight liver segments.…”

Section: Methodsmentioning

confidence: 99%

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Diminished liver microperfusion in Fontan patients: A biexponential DWI study

et al. 2017

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It has been demonstrated that hepatic apparent diffusion coefficients (ADC) are decreasing in patients with a Fontan circulation. It remains however unclear whether this is a true decrease of molecular diffusion, or rather reflects decreased microperfusion due to decreased portal blood flow. The purpose of this study was therefore to differentiate diffusion and microperfusion using intravoxel incoherent motion (IVIM) modeled diffusion-weighted imaging (DWI) for different liver segments in patients with a Fontan circulation, compare to a control group, and relate with liver function, chronic hepatic congestion and hepatic disease. For that purpose, livers of 59 consecutively included patients with Fontan circulation (29 men; mean-age, 19.1 years) were examined (Oct 2012─Dec 2013) with 1.5T MRI and DWI (b = 0,50,100,250,500,750,1500,1750 s/mm2). IVIM (Dslow, Dfast, ffast) and ADC were calculated for eight liver segments, compared to a control group (19 volunteers; 10 men; mean-age, 32.9 years), and correlated to follow-up duration, clinical variables, and laboratory measurements associated with liver function. The results demonstrated that microperfusion was reduced (p<0.001) in Fontan livers compared to controls with ─38.1% for Dfast and ─32.6% for ffast. Molecular diffusion (Dslow) was similar between patients and controls, while ADC was significantly lower (─14.3%) in patients (p<0.001). ADC decreased significantly with follow-up duration after Fontan operation (r = ─0.657). Dslow showed significant inverse correlations (r = ─0.591) with follow-up duration whereas Dfast and ffast did not. From these results it was concluded that the decreasing ADC values in Fontan livers compared with controls reflect decreases in hepatic microperfusion rather than any change in molecular diffusion. However, with the time elapsed since the Fontan operation molecular diffusion and ADC decreased while microperfusion remained stable. This indicates that after Fontan operation initial blood flow effects on the liver are followed by intracellular changes preceding the formation of fibrosis and cirrhosis.

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“…Diffusion weighted imaging (DWI) is a magnetic resonance technique that quantifies the diffusion of water molecules in tissues that can be quantified as apparent diffusion coefficient (ADC). Collagen fibers in the liver would inhibit water diffusion thereby leading to a decrease in ADC and therefore can be quantitatively used to assess liver fibrosis, but the technique has limitations since factors like steatosis can also affect ADC [35]. Dynamic contrast-enhanced MR imaging (DCE-MRI) and MR perfusion weighted imaging (MR-PWI) rely on the intravenous administration of MR contrast agents that can more precisely reveal hepatic hemodynamic changes [36–38].…”

Section: Assessment Of Liver Fibrosismentioning

confidence: 99%

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

Bansal

Nagórniewicz

Prakash

2016

Mediators of Inflammation

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Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis.

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The Fontan circulation and the liver: A magnetic resonance diffusion-weighted imaging study

Cited by 35 publications

References 34 publications

A computational study of the Fontan circulation with fenestration or hepatic vein exclusion

A computational study of the Fontan circulation with fenestration or hepatic vein exclusion

Diminished liver microperfusion in Fontan patients: A biexponential DWI study

Clinical Advancements in the Targeted Therapies against Liver Fibrosis

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