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

OBJECTIVES: In 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 METHODS: Male 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). RESULTS: PVL 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. CONCLUSION: The 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

Demonstration of metabolic and cellular effects of portal vein ligation using multi-modal PET/MRI measurements in healthy rat liver.

OBJECTIVES: In 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 METHODS: Male 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). RESULTS: PVL 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. CONCLUSION: The 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

Changes in weight and volume of the liver after portal vein ligation.

<p>A: The macroscopic appearance of liver by post mortem examinations and three dimensional MRI reconstruction preoperatively (0), as well as 1, 2, 3 and 7 days after portal vein ligation (PVL). Changes in weight (B) and volume (C) of total liver, ligated and non-ligated liver lobes at the examined time points. The alteration in liver weight showed a significant positive correlation with the volume change (r = 0.842, P<0.001; tested by Spearman’s method). Values are expressed as mean ± S.D. Each column represents the average of 6 animals. a =  superior right lateral lobe; b =  inferior right lateral lobe; c =  median lobe; d =  left lateral lobe.</p

Histomorphological characteristics of the liver after portal vein ligation.

<p>A: Histomorphological characteristics of the ligated lobes 1 day after portal vein ligation (PVL). Wide necrotic areas were seen around the central vein. At the boundary between the necrotic and non-necrotic areas (white line) apoptosis was frequently present (black arrows). B: The extent of necrotic areas and the number of apoptotic cell death significantly increased in ligated lobes compared with that seen in non-ligated liver lobes. C: Ki-67 labeling in non-ligated lobes on 2^nd day after surgery. Ki-67 antibody reacts with the nuclear structure present exclusively in the proliferative phase of the cell cycle. In the non-ligated liver lobes immunohistochemistry (brown stain) show a high expression level of Ki-67 in cell nuclei, which represent an increased mitotic activity of the hepatocytes. D: Mitotic activity of hepatocytes significantly increased in non-ligated liver lobes, with the peak response on day 2. In contrast, the Ki-67 positivity of ligated lobes did not change significantly throughout the experiment. Values are expressed as mean ± S.D. Each column presents the average of 6 animals. PV =  portal vein; CV =  central vein; * =  p<0.05 versus non-ligated lobes; # =  p<0.05 versus ligated lobes.</p

Glycogen content of cells.

<p>Glycogen content of ligated lobes (striped column) decreased markedly after portal vein ligation and it reached the baseline level at postoperative day 7. In non-ligated lobes (black column), the PAS staining did not show any significant alteration throughout the experiment. Values are expressed as mean ± S.D. Each column represents the average of 6 animals. * =  p<0.05 versus the baseline level (0 day) of the corresponding lobes.</p

Tracer biodistribution in ligated and non-ligated liver lobes.

<p>A:Representative coregistered PET and MRI image of rat liver before (top) and 3 days after (bottom) portal vein ligation (PVL). The PET reconstruction is based on frame 21 (at 15–19 minutes). The top inset picture shows a homogeneous liver FDG uptake pattern in both liver lobes. The small inhomogeneity is related to the morphology of liver. After PVL the liver shows inhomogeneous tracer distribution with significantly increased FDG uptake in ligated lobes, while the tracer uptake in cardiac left ventricle (*) remain constant. B: The ratio of mean SUV of ligated (striped column) and non-ligated (black column) liver lobes to mean liver SUV. The SUV_VOI/SUV_Liver significantly increased in ligated liver lobes compared to the non-ligated lobes after PVL with the peak response on day 2. Values are expressed as mean ± S.D. Each column represents the average of 6 animals. ** =  p<0.01 versus non-ligated lobes.</p

The ratio of mean SUV of ligated and non-ligated lobes to cardiac left ventricle SUV.

<p>The FDG uptake significantly increased in ligated (striped column) liver lobes, with maximal value on 2^nd postoperative day and returned to near to the baseline 7 day after portal vein ligation. In non-ligated (black column) lobes the tracer uptake also increased, but significantly lower extent compared to the ligated lobes. Values are expressed as mean ± S.D. Each column represents the average of 6 animals. * =  p<0.05 versus the baseline level (0 day) of the corresponding lobes; # =  p<0.05 versus non-ligated lobes; ## =  p<0.01 versus non-ligated lobes.</p

Time activity curves of ligated and non-ligated lobes at different time points.

<p>After portal vein ligation (PVL) the characteristics of curves showed altered tracer kinetics in both ligated (gray; dotted line) and non-ligated (black; solid line) liver lobes, but these changes in ligated lobes were more pronounced. The most significant alterations can be seen on 2^nd postoperative day, then 7 days after the operation the curves characteristic showed similar appearance to the pre-PVL data.</p