Assessment of hepatic microvascular flow and density in patients undergoing preoperative portal vein embolization

Uz, Zühre; İnce, Can; Rassam, Fadi; Ergin, Bülent; Lienden, Krijn P. van; Gulik, Thomas M. van

doi:10.1016/j.hpb.2018.07.002

Cited by 8 publications

(5 citation statements)

References 45 publications

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“…The high microvascular density (TVD and PVD) in the nonembolized hypertrophic lobes compared to the atrophic lobes described in this study is compatible with the findings of a clinical study in which the hepatic microcirculation was assessed intraoperatively after approximately 6 weeks of (permanent) PVE [29]. This study in patients undergoing liver resection also showed that the hypertrophic lobes revealed a higher microvascular density compared to the atrophic lobes.…”

Section: Discussion/conclusionsupporting

confidence: 90%

Increased Hepatic Microvascular Density, Oxygenation, and VEGF in the Hypertrophic Lobe following Portal Vein Embolization in Rabbits

Ergin

Shen

et al. 2021

Eur Surg Res

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Introduction: The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We aimed to assess the changes in hepatic microvascular perfusion and neo-angiogenesis after experimental PVE. Methods: PVE of the cranial liver lobes was performed in 12 New Zealand White rabbits divided into 2 groups of permanent (P-PVE) and reversible PVE (R-PVE), respectively. Hepatobiliary scintigraphy and CT were used to evaluate hepatic function and volume. Hepatic microcirculation was assessed using a handheld vital microscope (Cytocam) to measure microvascular density (total vessel density; TVD) before PVE, right after PVE, and 20 min after PVE, as well as at 14 days (D14 post-PVE) and 35 days (D35 post-PVE). Additionally, on D35, microvascular PO2 and liver parenchymal VEGF were assessed. Results: Eleven rabbits were included after PVE (R-PVE, n = 5; P-PVE, n = 6). TVD in the nonembolized (hypertrophic) lobes was higher than in the embolized (atrophic) lobes of the P-PVE group at D35 post-PVE (36.7 ± 7.2 vs. 23.4 ± 4.9 mm/mm2; p < 0.05). In the R-PVE group, TVD in the nonembolized lobes was not increased at D35. Function and volume were increased in the nonembolized lobes of the P-PVE group compared to the embolized lobes, but not in the R-PVE group. Likewise, the mmicrovascular PO2 and VEGF staining rate were higher in the nonembolized lobes of the P-PVE group at D35 post-PVE. Discussion/Conclusion: Successful volumetric and functional hypertrophy of the nonembolized lobe was accompanied by microvascular alterations featuring increased neo-angiogenesis, microvascular density, and microvascular oxygen pressure following P-PVE.

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Section: Discussion/conclusionsupporting

confidence: 90%

Increased Hepatic Microvascular Density, Oxygenation, and VEGF in the Hypertrophic Lobe following Portal Vein Embolization in Rabbits

Ergin

Shen

et al. 2021

Eur Surg Res

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“…The areas in the liver where 99mTc mebrofenin accumulates (high uptake) is indicative of regional and global function. There is also potential to quantitatively assess liver function before and after surgical intervention (Rassam et al, 2019b ; Uz et al, 2019 ) such as HEF, mebrofenin uptake rate or hepatic extraction rate (Gupta et al, 2018 ; Rassam et al, 2019a ). The advantage of this method compared to ICG and LiMAx is the spatial resolution, albeit very coarse.…”

Section: Clinical and Experimental Partmentioning

confidence: 99%

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function

et al. 2021

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Liver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties and cellular function. Changes in blood flow impose compression, tension and shear forces on the liver tissue. These forces are perceived by mechanosensors on parenchymal and non-parenchymal cells of the liver and regulate cell-cell and cell-matrix interactions as well as cellular signaling and metabolism. These interactions are key players in tissue growth and remodeling, a prerequisite to restore tissue function after PHx. Their dysregulation is associated with metabolic impairment of the liver eventually leading to liver failure, a serious post-hepatectomy complication with high morbidity and mortality. Though certain links are known, the overall functional change after liver surgery is not understood due to complex feedback loops, non-linearities, spatial heterogeneities and different time-scales of events. Computational modeling is a unique approach to gain a better understanding of complex biomedical systems. This approach allows (i) integration of heterogeneous data and knowledge on multiple scales into a consistent view of how perfusion is related to hepatic function; (ii) testing and generating hypotheses based on predictive models, which must be validated experimentally and clinically. In the long term, computational modeling will (iii) support surgical planning by predicting surgery-induced perfusion perturbations and their functional (metabolic) consequences; and thereby (iv) allow minimizing surgical risks for the individual patient. Here, we review the alterations of hepatic perfusion, biomechanical properties and function associated with hepatectomy. Specifically, we provide an overview over the clinical problem, preoperative diagnostics, functional imaging approaches, experimental approaches in animal models, mechanoperception in the liver and impact on cellular metabolism, omics approaches with a focus on transcriptomics, data integration and uncertainty analysis, and computational modeling on multiple scales. Finally, we provide a perspective on how multi-scale computational models, which couple perfusion changes to hepatic function, could become part of clinical workflows to predict and optimize patient outcome after complex liver surgery.

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“…A weak correlation was identified between an increase in RBC velocity and volume of liver resected. To date, the only paper published on the use of IDFI in the liver is by Uz et al [27], who measured liver microcirculation in 18 patients undergoing major hepatectomy with and without preoperative unilateral portal vein embolization. They found a significantly higher hepatic microvascular density in the non-embolized lobe when compared to the embolized lobe, as the result of angiogenesis occurring in the hypertrophic, non-embolized lobe after portal vein embolization [27].…”

Section: Handheld Vital Microscopymentioning

confidence: 99%

“…Therefore, information of whole liver perfusion will require scanning of the liver surface. With a maximum of 500 µm focus depth, only surface perfusion information can be gathered from HVM, although in most pathological conditions, this is sufficient to focus through the liver capsule and capture the sinusoidal microcirculation [27].…”

Section: Handheld Vital Microscopymentioning

confidence: 99%

Intraoperative Imaging Techniques to Visualize Hepatic (Micro)Perfusion: An Overview

Shen

Milstein

et al. 2020

Eur Surg Res

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The microcirculation plays a crucial role in the distribution of perfusion to organs. Studies have shown that microcirculatory dysfunction is an independent predictor of morbidity and mortality. Hence, assessment of liver perfusion offers valuable information on the (patho)physiological state of the liver. The current review explores techniques in perfusion imaging that can be used intraoperatively. Available modalities include dynamic contrast-enhanced ultrasound, handheld vital microscopes, indocyanine green fluorescence angiography, and laser contrast speckle imaging. Dynamic contrast-enhanced ultrasound relays information on deep tissue perfusion and is a commonly used technique to assess tumor perfusion. Handheld vital microscopes provide direct visualization of the sinusoidal architectural structure of the liver, which is a unique feature of this technique. Intraoperative fluorescence imaging uses indocyanine green, a dye that is administered intravenously to visualize microvascular perfusion when excited using near-infrared light. Laser speckle contrast imaging produces non-contact large surface-based tissue perfusion imaging free from movement-or pressure-related artefacts. In this review, we discuss the intrinsic advantages and disadvantages of these techniques and their clinical and/or scientific applications.

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Assessment of hepatic microvascular flow and density in patients undergoing preoperative portal vein embolization

Abstract: The non-embolized lobe has a significantly higher microvascular density, however without differences in microvascular flow. These findings indicate increased angiogenesis in the hypertrophic lobe.

Cited by 8 publications

References 45 publications

Increased Hepatic Microvascular Density, Oxygenation, and VEGF in the Hypertrophic Lobe following Portal Vein Embolization in Rabbits

Increased Hepatic Microvascular Density, Oxygenation, and VEGF in the Hypertrophic Lobe following Portal Vein Embolization in Rabbits

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function

Intraoperative Imaging Techniques to Visualize Hepatic (Micro)Perfusion: An Overview

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