Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function
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 indi...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:7964686b269548f4b959bfdab7888e902021-11-18T08:16:57ZHepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function1664-042X10.3389/fphys.2021.733868https://doaj.org/article/7964686b269548f4b959bfdab7888e902021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.733868/fullhttps://doaj.org/toc/1664-042XLiver 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.Bruno ChristMaximilian CollatzMaximilian CollatzMaximilian CollatzUta DahmenKarl-Heinz HerrmannSebastian HöpflMatthias KönigLena LambersManja MarzDaria MeyerNicole RaddeJürgen R. ReichenbachTim RickenHans-Michael TautenhahnFrontiers Media S.A.articlemulti-scale modelingliver regenerationliver surgeryliver perfusionperfusion/function relationshipmechanoperceptionPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021) |
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| topic |
multi-scale modeling liver regeneration liver surgery liver perfusion perfusion/function relationship mechanoperception Physiology QP1-981 |
| spellingShingle |
multi-scale modeling liver regeneration liver surgery liver perfusion perfusion/function relationship mechanoperception Physiology QP1-981 Bruno Christ Maximilian Collatz Maximilian Collatz Maximilian Collatz Uta Dahmen Karl-Heinz Herrmann Sebastian Höpfl Matthias König Lena Lambers Manja Marz Daria Meyer Nicole Radde Jürgen R. Reichenbach Tim Ricken Hans-Michael Tautenhahn Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function |
| description |
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. |
| format |
article |
| author |
Bruno Christ Maximilian Collatz Maximilian Collatz Maximilian Collatz Uta Dahmen Karl-Heinz Herrmann Sebastian Höpfl Matthias König Lena Lambers Manja Marz Daria Meyer Nicole Radde Jürgen R. Reichenbach Tim Ricken Hans-Michael Tautenhahn |
| author_facet |
Bruno Christ Maximilian Collatz Maximilian Collatz Maximilian Collatz Uta Dahmen Karl-Heinz Herrmann Sebastian Höpfl Matthias König Lena Lambers Manja Marz Daria Meyer Nicole Radde Jürgen R. Reichenbach Tim Ricken Hans-Michael Tautenhahn |
| author_sort |
Bruno Christ |
| title |
Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function |
| title_short |
Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function |
| title_full |
Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function |
| title_fullStr |
Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function |
| title_full_unstemmed |
Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function |
| title_sort |
hepatectomy-induced alterations in hepatic perfusion and function - toward multi-scale computational modeling for a better prediction of post-hepatectomy liver function |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/7964686b269548f4b959bfdab7888e90 |
| work_keys_str_mv |
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