Demonstration of Metabolic and Cellular Effects of Portal Vein Ligation Using Multi-Modal PET/MRI Measurements in Healthy Rat Liver

Abstract

ObjectivesIn the early recognition of portal vein ligation (PVL) induced tumor progression, positron emission tomography and magnetic resonance imaging (PET/MRI) could improve diagnostic accuracy of conventionally used methods. It is unknown how PVL affects metabolic patterns of tumor free hepatic tissues. The aim of this preliminary study is to evaluate the effect of PVL on glucose metabolism, using PET/MRI imaging in healthy rat liver.Materials and MethodsMale Wistar rats (n = 30) underwent PVL. 2-deoxy-2-(18F)fluoro-D-glucose (FDG) PET/MRI imaging (nanoScan PET/MRI) and morphological/histological examination were performed before (Day 0) and 1, 2, 3, and 7 days after PVL. Dynamic PET data were collected and the standardized uptake values (SUV) for ligated and non-ligated liver lobes were calculated in relation to cardiac left ventricle (SUVVOI/SUVCLV) and mean liver SUV (SUVVOI/SUVLiver).ResultsPVL induced atrophy of ligated lobes, while non-ligated liver tissue showed compensatory hypertrophy. Dynamic PET scan revealed altered FDG kinetics in both ligated and non-ligated liver lobes. SUVVOI/SUVCLV significantly increased in both groups of lobes, with a maximal value at the 2nd postoperative day and returned near to the baseline 7 days after the ligation. After PVL, ligated liver lobes showed significantly higher tracer uptake compared to the non-ligated lobes (significantly higher SUVVOI/SUVLiver values were observed at postoperative day 1, 2 and 3). The homogenous tracer biodistribution observed before PVL reappeared by 7th postoperative day.ConclusionThe observed alterations in FDG uptake dynamics should be taken into account during the assessment of PET data until the PVL induced atrophic and regenerative processes are completed.

Determination of Pathophysiological Mechanisms of ALPPS in an Animal Model Using Molecular and Functional Imagings

“…Moreover, as longitudinal imaging studies could easily be performed with this model and changes in tumor volume has been used as a standard therapeutic response marker to estimate tumor growth [28], this study showed that the metabolic tumor volume (MTV) was signi cantly higher in the ALPPS model than in Sham animals, suggesting that ALPPS accelerated tumor growth. These results are consistent with previous data obtained after PVL and PVE [29,30]. Importantly, the 18 F-FDG uptake in tumor revealed that alterations in metabolism preceded volume changes.This nding was con rmed by immunocytochemistry with GLUT1.…”

Isoform-Dependent Changes in Cytochrome P450-Mediated Drug Metabolism after Portal Vein Ligation in the Rat

“…Eventually, the LL undergoes atrophy and underlying necroapoptotic cell death, meanwhile the NLL displays an intensive cellular proliferation and hypertrophy [21, 29], which was repeatedly proven by the literature [2, 5, 29, 30] and previous reports of our workgroup [20, 21, 31]. In the present study, it was similarly reflected by liver lobe weights, thereby validating the standard application of the PVL model, and allowing further, more sophisticated analysis.…”

“…injection of 75 mg/body weight [bw] kg ketamine and 7.5 mg/bw kg xylazine in 1.5 mL saline), rats underwent median laparotomy and PVL affecting approximately 80% of the total liver parenchyma ( n = 20), as previously described by our workgroup [20, 21]. After abdominal saline lavage, antibiotic (10 mg/bw kg metronidazol i.p.)…”

Triggered Liver Regeneration: From Experimental Model to Clinical Implications

“…As a result, in the pericentral region - the region farthest away from the portal triad -, severe hypoxia (ischemia) occurs, leading to an impairment of the mitochondrial ATP production and consequently to necrosis [36]. In parallel, the incidence of apoptotic cell death also increases, mainly at the boundary between the necrotic and intact areas (intermediate zone) [37]. The location of the apoptotic cells suggests that apoptosis is also caused by hypoxia; severe ischemia induces necrosis, while mild ischemia induces apoptosis [35].…”