Tandem 7: Molecular Imaging of Liver Metabolic Pathways after Partial Hepatectomy: Indicators of Liver Failure?

Short Summary:

Using multi-modal molecular imaging techniques, the liver metabolism of glucose, pyruvate and ATP is characterized during liver regeneration after partial hepatectomy. Currently, we test which biomarker of molecular imaging is best suited to provide a quantitative measure for developing post-hepatectomy liver failure.

Scope:

Post-hepatectomy liver failure (PLF) is an often fatal complication after partial hepatectomy. Key events in the development of PLF are an inadequate quantity or quality of residual liver mass (small-forsize syndrome), ischemia-reperfusion injury, and parenchymal congestion (van den Broek et al., 2008). Within the community, there is no consensual definition of PLF, which is typically characterized by failure of at least one or more of the hepatic synthetic functions including hyperbilirubinaemia, hypoalbuminia and prolonged prothrombin time. Although, PLF is associated with a failure of liver regeneration, the molecular mechanisms of PLF have not been elucidated yet (Clavien et al., 2010).

Specific Aims:

Using multi-modal molecular imaging techniques, the liver metabolism of glucose, pyruvate and ATP will be characterized during liver regeneration in a well-established mouse model of partial hepatectomy. Different risk factors such as small remnant liver volume, liver cirrhosis, cholestasis or ischemia-reperfusion injury will be assessed regarding the impact on metabolism of regenerating liver parenchyma. We will test which biomarker of molecular imaging is best suited to provide a quantitative measure for developing PLF. Furthermore, we aim at gaining deeper insights in the pathophysiology of PLF.

Molecular imaging techniques used:

Probing of metabolic pathways in regenerating liver will be performed using hybrid positron-emission-tomography (PET)/magnetic resonance imaging techniques. Liver ATPsynthesis will be measured with 31P-magnetic resonance spectroscopy (Schmid et al., 2008), pyruvatelactate metabolism with hyperpolarized [1-13C]pyruvate spectroscopy (Hu et al., 2009), and glucose metabolism with dynamic 18F-fluorodeoxyglucose (FDG) PET.

Mouse liver is assessed by multimodal MR imaging techniques before and after partial hepatectomy in order to monitor liver regeneration and to detect developing complications using the mouse model of common (70% PH) and extensive partial hepatectomy (86% PH), the latter representing the animal model for small-for size syndrome leading frequently to PLF. Shown here, representative T1-parametric (A) and T2-parametric maps (B) of the mouse liver prior partial hepatectomy.

Added value of KFSP for this specific tandem project:

In this tandem project, expertise from clinical liver surgeons and imaging scientist will be focused in a joint project. The frame of the KFSP will provide further expertise in multi-modal molecular imaging strategies for potential assessment of additional aspects of liver regeneration such as tissue oxygenation and perfusion and for identifying protective strategies.

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