The Experts below are selected from a list of 825 Experts worldwide ranked by ideXlab platform

Thomas M. Van Gulik - One of the best experts on this subject based on the ideXlab platform.

  • stress test of liver function using technetium 99m Mebrofenin hepatobiliary scintigraphy
    Nuclear Medicine Communications, 2019
    Co-Authors: Fadi Rassam, Thomas M. Van Gulik, Kasia P. Cieslak, Ulrich Beuers, R J Bennink
    Abstract:

    Technetium-99m (Tc) Mebrofenin hepatobiliary scintigraphy (HBS) enables a quantitative assessment of liver function. This is normally performed in a fasting state and might therefore reflect the resting liver function. We evaluated the change in liver function using HBS after stimulation with an oral metabolic challenge. Healthy volunteers aged 50-60 (n=12) or older than or equal to 75 (n=12) years underwent two sequential HBS. The first scan was performed after an overnight fast and the second scan was performed after the administration of chocolate milk. Hepatic Tc-Mebrofenin uptake rate (cMUR) was calculated and the difference was expressed as percentage. cMUR after fasting was 10.9±2.5%/min/m (mean±SD) and increased by 20% to 13.0±3.1%/min/m after stimulation with chocolate milk (P<0.001). cMUR increased markedly after the administration of an oral metabolic challenge in comparison with fasting. This may be a consequence of hepatocyte stimulation, reflecting the hepatic functional reserve capacity.

  • Stress test of liver function using technetium-99m-Mebrofenin hepatobiliary scintigraphy.
    Nuclear medicine communications, 2019
    Co-Authors: Fadi Rassam, Thomas M. Van Gulik, Kasia P. Cieslak, Ulrich Beuers, Roel J. Bennink
    Abstract:

    Technetium-99m (Tc) Mebrofenin hepatobiliary scintigraphy (HBS) enables a quantitative assessment of liver function. This is normally performed in a fasting state and might therefore reflect the resting liver function. We evaluated the change in liver function using HBS after stimulation with an oral metabolic challenge. Healthy volunteers aged 50-60 (n=12) or older than or equal to 75 (n=12) years underwent two sequential HBS. The first scan was performed after an overnight fast and the second scan was performed after the administration of chocolate milk. Hepatic Tc-Mebrofenin uptake rate (cMUR) was calculated and the difference was expressed as percentage. cMUR after fasting was 10.9±2.5%/min/m (mean±SD) and increased by 20% to 13.0±3.1%/min/m after stimulation with chocolate milk (P

  • Quantitative assessment of liver function using hepatobiliary scintigraphy: the effect of microcirculatory alterations after portal vein embolization.
    Nuclear medicine communications, 2019
    Co-Authors: Fadi Rassam, Roelof J. Bennink, Krijn P. Van Lienden, Can Ince, Thomas M. Van Gulik
    Abstract:

    ObjectivesHepatobiliary scintigraphy using technetium-99m Mebrofenin has been validated as a quantitative liver function test. Preoperative portal vein embolization (PVE) is performed in patients to increase future remnant liver function and volume. Changes in hepatic microcirculation after PVE remain largely unknown and may influence the uptake of Mebrofenin. The aim was to evaluate microcirculatory changes after PVE to examine differences in perfusion that might influence the uptake of Mebrofenin, and consequently, assessment of function.Patients and methodsPatients undergoing liver resection with or without preoperative PVE were included. Future remnant liver volume and function were measured before and after PVE. Hepatic microcirculation was measured in the embolized and the nonembolized lobes during resection. Microcirculatory flow index, perfused vessel density, sinusoidal diameter and red blood cell velocity were assessed.ResultsA total of 16 patients, eight with preoperative PVE and eight control patients without PVE, were included. After PVE, both function and volume of the nonembolized lobe were significantly increased, and the functional increase exceeded the increase in volume. Perfused vessel density and sinusoidal diameter were significantly higher in the nonembolized liver lobe (P

  • Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection
    HPB : the official journal of the International Hepato Pancreato Biliary Association, 2016
    Co-Authors: Kasia P. Cieslak, Wilmar De Graaf, Roelof J. Bennink, Krijn P. Van Lienden, Olivier R. Busch, Dirk J. Gouma, Marc G. Besselink, Thomas M. Van Gulik
    Abstract:

    Background 99mTc-Mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cut-off value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated.

  • Quantitative Assessment of Hepatic Function During Liver Regeneration in a Standardized Rat Model
    Journal of nuclear medicine : official publication Society of Nuclear Medicine, 2011
    Co-Authors: Wilmar De Graaf, Michal Heger, Roelof J. Bennink, Adrie Maas, Kora De Bruin, Thomas M. Van Gulik
    Abstract:

    Reliable assessment of hepatic function during liver regeneration is crucial after liver surgery or liver transplantation. Tc-99m-galactosyl human serum albumin (Tc-99m-GSA) scintigraphy, Tc-99m-Mebrofenin hepatobiliary scintigraphy (HBS), the indocyanine green (ICG) clearance test, and the galactose elimination capacity (GEC) are common quantitative liver function tests. However, to our knowledge, comparative analysis between these tests has never been performed during liver regeneration. The aim of this study was therefore to compare Tc-99m-GSA scintigraphy, Tc-99m-Mebrofenin HBS, the ICG clearance test, and GEC in the assessment of hepatic function during liver regeneration in rats. Methods: Rats were subjected to 70% partial hepatectomy (PHx). Liver function and functional volume were determined at predefined times after PHx and expressed as a percentage of baseline (pre-PHx) values. Results: During liver regeneration, functional liver volume measured by Tc-99m-GSA SPECT correlated strongly with conventional liver volume based on wet weight. One day after 70% PHx, conventional liver volume overestimated liver function as measured by Tc-99m-Mebrofenin uptake and excretion rates, Tc-99m-GSA uptake rate, and ICG clearance. On days 5 and 7, Tc-99m-Mebrofenin uptake and ICG clearance had recovered to levels similar to conventional liver volume, whereas Tc-99m-GSA uptake reflected a reduced liver function in relation to conventional liver volume and Tc-99m-Mebrofenin uptake. The GEC measurements consistently overestimated liver function during regeneration. Conclusion: Volumetric assessment of the liver should be complemented by liver function-specific assays. Functional regeneration is impaired, compared with volumetric regeneration, in the early phase of liver regeneration. In later stages of liver regeneration, Tc-99m-GSA uptake underestimates hepatic regeneration in comparison to liver volume and Tc-99m-Mebrofenin uptake. GEC is of less value because it is only minimally affected by 70% PHx and is influenced by factors not related to liver function. Tc-99m-Mebrofenin HBS has the advantage of providing visual and quantitative information regarding both uptake and excretory liver function

Kim L. R. Brouwer - One of the best experts on this subject based on the ideXlab platform.

  • Effect of Ritonavir on 99mTechnetium–Mebrofenin Disposition in Humans: A Semi‐PBPK Modeling and In Vitro Approach to Predict Transporter‐Mediated DDIs
    CPT: pharmacometrics & systems pharmacology, 2013
    Co-Authors: Nathan D. Pfeifer, S. L. Goss, Brandon Swift, Giulia Ghibellini, M. Ivanovic, William D. Heizer, L. M. Gangarosa, Kim L. R. Brouwer
    Abstract:

    A semiphysiologically based pharmacokinetic (semi-PBPK) model was developed to describe a unique blood, liver, and bile clinical data set for the hepatobiliary imaging agent (99m)Technetium-Mebrofenin ((99m)Tc-Mebrofenin), and to simulate sites/mechanisms of a (99m)Tc-Mebrofenin-ritonavir drug-drug interaction (DDI). The transport inhibitor ritonavir (multiple-dose: 2 × 300 mg) significantly increased systemic (99m)Tc-Mebrofenin exposure as compared with control (4,464 ± 1,861 vs. 1,970 ± 311 nCi min/ml; mean ± SD), without affecting overall hepatic exposure or biliary recovery. A novel extrahepatic distribution compartment was required to characterize (99m)Tc-Mebrofenin disposition. Ritonavir inhibited (99m)Tc-Mebrofenin accumulation in human sandwich-cultured hepatocytes (SCH) (half maximal inhibitory concentration (IC50) = 3.46 ± 1.53 µmol/l). Despite ritonavir accumulation in hepatocytes, intracellular binding was extensive (97. 6%), which limited interactions with multidrug resistance protein 2 (MRP2)-mediated biliary excretion. These in vitro data supported conclusions from modeling/simulation that ritonavir inhibited (99m)Tc-Mebrofenin hepatic uptake, but not biliary excretion, at clinically relevant concentrations. This integrated approach, utilizing modeling, clinical, and in vitro data, emphasizes the importance of hepatic and extrahepatic distribution, assessment of inhibitory potential in relevant in vitro systems, and intracellular unbound concentrations to assess transporter-mediated hepatic DDIs.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e20; doi:10.1038/psp.2012.21; advance online publication 2 January 2013.

  • effect of ritonavir on 99mtechnetium Mebrofenin disposition in humans a semi pbpk modeling and in vitro approach to predict transporter mediated ddis
    CPT: Pharmacometrics & Systems Pharmacology, 2013
    Co-Authors: Nathan D. Pfeifer, S. L. Goss, Brandon Swift, Giulia Ghibellini, M. Ivanovic, William D. Heizer, L. M. Gangarosa, Kim L. R. Brouwer
    Abstract:

    A semiphysiologically based pharmacokinetic (semi-PBPK) model was developed to describe a unique blood, liver, and bile clinical data set for the hepatobiliary imaging agent (99m)Technetium-Mebrofenin ((99m)Tc-Mebrofenin), and to simulate sites/mechanisms of a (99m)Tc-Mebrofenin-ritonavir drug-drug interaction (DDI). The transport inhibitor ritonavir (multiple-dose: 2 × 300 mg) significantly increased systemic (99m)Tc-Mebrofenin exposure as compared with control (4,464 ± 1,861 vs. 1,970 ± 311 nCi min/ml; mean ± SD), without affecting overall hepatic exposure or biliary recovery. A novel extrahepatic distribution compartment was required to characterize (99m)Tc-Mebrofenin disposition. Ritonavir inhibited (99m)Tc-Mebrofenin accumulation in human sandwich-cultured hepatocytes (SCH) (half maximal inhibitory concentration (IC50) = 3.46 ± 1.53 µmol/l). Despite ritonavir accumulation in hepatocytes, intracellular binding was extensive (97. 6%), which limited interactions with multidrug resistance protein 2 (MRP2)-mediated biliary excretion. These in vitro data supported conclusions from modeling/simulation that ritonavir inhibited (99m)Tc-Mebrofenin hepatic uptake, but not biliary excretion, at clinically relevant concentrations. This integrated approach, utilizing modeling, clinical, and in vitro data, emphasizes the importance of hepatic and extrahepatic distribution, assessment of inhibitory potential in relevant in vitro systems, and intracellular unbound concentrations to assess transporter-mediated hepatic DDIs.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e20; doi:10.1038/psp.2012.21; advance online publication 2 January 2013.

  • Evaluation of 99mTechnetium-Mebrofenin and 99mTechnetium-Sestamibi as Specific Probes for Hepatic Transport Protein Function in Rat and Human Hepatocytes
    Pharmaceutical research, 2010
    Co-Authors: Brandon Swift, Wei Yue, Kim L. R. Brouwer
    Abstract:

    Purpose This study characterized 99mTc-Mebrofenin (MEB) and 99mTc-Sestamibi (MIBI) hepatic transport and preferential efflux routes (canalicular vs. basolateral) in rat and human sandwich-cultured hepatocytes (SCH).

  • Use of Tc-99m Mebrofenin as a Clinical Probe to Assess Altered Hepatobiliary Transport: Integration of In Vitro, Pharmacokinetic Modeling, and Simulation Studies
    Pharmaceutical research, 2008
    Co-Authors: Giulia Ghibellini, Elaine M. Leslie, Gary M. Pollack, Kim L. R. Brouwer
    Abstract:

    Purpose Transport of the hepatobiliary scintigraphy agent Tc-99m Mebrofenin (MEB) was characterized and simulation studies were conducted to examine the effects of altered hepatic transport on MEB pharmacokinetics in humans.

  • A novel method for the determination of biliary clearance in humans
    The AAPS Journal, 2004
    Co-Authors: Giulia Ghibellini, William D. Heizer, Brendan M. Johnson, Richard J. Kowalsky, Kim L. R. Brouwer
    Abstract:

    Biliary excretion is an important route of elimination and the biliary tract is a potential site of toxicity for many drugs and xenobiotics. Quantification of biliary excretion in healthy human volunteers is logistically challenging and is rarely defined during drug development. The current study uses a novel oroenteric tube coupled with a specialized clinical protocol to examine the pharmacokinetics of^99mTechnetium (Tc-99m) Mebrofenin, a compound that undergoes rapid hepatic uptake and extensive biliary excretion. A custommade multilumen oroenteric tube was positioned in the duodenum of healthy human volunteers. Subjects were positioned under a gamma camera and 2.5 mCi of Tc-99m Mebrofenin was administered intravenously. Duodenal aspirates, blood samples, and urine were collected periodically for 3 hours. Two hours after Tc-99m Mebrofenin administration, the gallbladder was contracted with an intravenous infusion of cholecystokinin-8. Gamma scintigraphy was used to determine the gallbladder ejection fraction in each subject. Total systemic clearance of Tc-99m Mebrofenin approximated liver blood flow (Cl_total 17.3±1.7 mL/min/kg), and 35% to 84% of the Tc-99m Mebrofenin dose was recovered in bile. However, when the data were corrected for the gallbladder ejection fraction, 71% to 92% of the excreted Tc-99m Mebrofenin dose was recovered. This novel croenteric tube and clinical protocol provide a useful method to quantify biliary excretion of xenobiotics in healthy human volunteers.

Roel J. Bennink - One of the best experts on this subject based on the ideXlab platform.

  • Comparison between dynamic gadoxetate-enhanced MRI and 99m Tc-Mebrofenin hepatobiliary scintigraphy with SPECT for quantitative assessment of liver function
    European radiology, 2019
    Co-Authors: Fadi Rassam, Tian Zhang, K.p. Cieslak, Cristina Lavini, Jaap Stoker, Roel J. Bennink, T.m. Van Gulik, L.j. Van Vliet, Jurgen H. Runge, Franciscus M. Vos
    Abstract:

    To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-Mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-Mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: Mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p 

  • comparison between dynamic gadoxetate enhanced mri and 99m tc Mebrofenin hepatobiliary scintigraphy with spect for quantitative assessment of liver function
    European Radiology, 2019
    Co-Authors: Fadi Rassam, Tian Zhang, K.p. Cieslak, Cristina Lavini, Jaap Stoker, Roel J. Bennink, T.m. Van Gulik, L.j. Van Vliet, Jurgen H. Runge, Franciscus M. Vos
    Abstract:

    To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-Mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-Mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: Mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p < 0.001 respectively). There was a strong agreement between the functional share determined with both modalities (ICC = 0.944, 95% CI 0.863–0.978, n = 20). There was a significant negative correlation between liver aminotransferases and bilirubin for both MUR and Ki. Assessment of liver function with DHCE-MRI is comparable with that of 99mTc-Mebrofenin HBS and has the potential to be combined with diagnostic MRI imaging. This can therefore provide a one-stop-shop modality for the preoperative assessment of patients undergoing liver surgery. • Quantitative assessment of liver function using hepatobiliary scintigraphy is performed in the preoperative assessment of patients undergoing liver surgery in order to prevent posthepatectomy liver failure. • Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) is an emerging method to quantify liver function and can serve as a potential alternative to hepatobiliary scintigraphy. • Assessment of liver function with dynamic gadoxetate-enhanced MRI is comparable with that of hepatobiliary scintigraphy and has the potential to be combined with diagnostic MRI imaging.

  • Stress test of liver function using technetium-99m-Mebrofenin hepatobiliary scintigraphy.
    Nuclear medicine communications, 2019
    Co-Authors: Fadi Rassam, Thomas M. Van Gulik, Kasia P. Cieslak, Ulrich Beuers, Roel J. Bennink
    Abstract:

    Technetium-99m (Tc) Mebrofenin hepatobiliary scintigraphy (HBS) enables a quantitative assessment of liver function. This is normally performed in a fasting state and might therefore reflect the resting liver function. We evaluated the change in liver function using HBS after stimulation with an oral metabolic challenge. Healthy volunteers aged 50-60 (n=12) or older than or equal to 75 (n=12) years underwent two sequential HBS. The first scan was performed after an overnight fast and the second scan was performed after the administration of chocolate milk. Hepatic Tc-Mebrofenin uptake rate (cMUR) was calculated and the difference was expressed as percentage. cMUR after fasting was 10.9±2.5%/min/m (mean±SD) and increased by 20% to 13.0±3.1%/min/m after stimulation with chocolate milk (P

  • Hepatic regeneration and functional recovery following partial liver resection in an experimental model of hepatic steatosis treated with omega-3 fatty acids.
    The British journal of surgery, 2013
    Co-Authors: Hendrik A. Marsman, Michal Heger, Roel J. Bennink, W. De Graaf, R. F. Van Golen, F. J. W. Ten Kate, T.m. Van Gulik
    Abstract:

    Background Omega-3 fatty acids (FAs) have been shown to reduce experimental hepatic steatosis and protect the liver from ischaemia–reperfusion injury. The aim of this study was to examine the effects of omega-3 FAs on regeneration of steatotic liver. Methods Steatosis was induced in rats by a 3-week methionine/choline-deficient diet, which was continued for an additional 2 weeks in conjunction with oral administration of omega-3 FAs or saline solution. Steatosis was graded histologically and quantified by proton magnetic resonance spectroscopy (1H-MRS) before and after the diet/treatment. Liver function was determined by 99mTc-labelled Mebrofenin hepatobiliary scintigraphy (HBS). In separate experiments, the hepatic regenerative capacity and functional recovery of omega-3 FA-treated, saline-treated or non-steatotic (control) rats were investigated 1, 2, 3 and 5 days after partial (70 per cent) liver resection by measurement of liver weight change and hepatocyte proliferation (Ki-67) and HBS. Results Severe steatosis (over 66 per cent) in the saline group was reduced by omega-3 FAs to mild steatosis (less than 33 per cent), and hepatic fat content as assessed by 1H-MRS decreased 2·2-fold. 99mTc-Mebrofenin uptake in the saline group was more than 50 per cent lower than in the control group, confirming the functional effects of steatosis. 99mTc-Mebrofenin uptake and regenerated liver mass were significantly greater in the omega-3 group compared with the saline group on days 1 and 3. The posthepatectomy proliferation peak response was delayed until day 2 in saline-treated rats, compared with day 1 in the omega-3 and control groups. Conclusion Omega-3 FAs effectively reduced severe hepatic steatosis, which was associated with improved liver regeneration and functional recovery following partial hepatectomy.

  • Mild steatosis impairs functional recovery after liver resection in an experimental model
    The British journal of surgery, 2007
    Co-Authors: Reeta Veteläinen, Roel J. Bennink, A.k. Van Vliet, T.m. Van Gulik
    Abstract:

    Background: Mild steatosis has been thought not to affect outcome after liver resection. However, recent studies have reported impaired postoperative recovery of patients with mild steatosis. This study evaluated the recovery of hepatic functional reserve during regeneration in a rat model of mild steatosis and liver resection. Methods: Male Wistar rats had a standard methione- and choline-deficient diet to induce mild steatosis before 70 per cent liver resection. Evaluation of hepatobiliary function was by 99mTc-labelled Mebrofenin scintigraphy. Mebrofenin uptake rate, the time for maximum uptake (T peak) and the time required for peak activity to decrease by 50 per cent (T1/2 peak) were assessed 1, 2, 3 and 7 days after liver resection, along with regeneration of the remnant liver, hepatocellular and sinusoidal damage, and hepatic adenosine 5′-triphosphate (ATP) levels. Results: Liver regeneration and proliferative response in mild steatotic rats were no different from those in controls. However, the Mebrofenin uptake rate was lower (P < 0·050) and the recovery of hepatic ATP impaired (P < 0·050) in animals with mild steatosis. Hepatocellular damage was increased (P < 0·050) but sinusoidal endothelial cell function was not affected after liver resection in mildly steatotic rats. Conclusion: Mild steatosis impaired functional recovery and increased hepatocellular damage after liver resection. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Roelof J. Bennink - One of the best experts on this subject based on the ideXlab platform.

  • Quantitative assessment of liver function using hepatobiliary scintigraphy: the effect of microcirculatory alterations after portal vein embolization.
    Nuclear medicine communications, 2019
    Co-Authors: Fadi Rassam, Roelof J. Bennink, Krijn P. Van Lienden, Can Ince, Thomas M. Van Gulik
    Abstract:

    ObjectivesHepatobiliary scintigraphy using technetium-99m Mebrofenin has been validated as a quantitative liver function test. Preoperative portal vein embolization (PVE) is performed in patients to increase future remnant liver function and volume. Changes in hepatic microcirculation after PVE remain largely unknown and may influence the uptake of Mebrofenin. The aim was to evaluate microcirculatory changes after PVE to examine differences in perfusion that might influence the uptake of Mebrofenin, and consequently, assessment of function.Patients and methodsPatients undergoing liver resection with or without preoperative PVE were included. Future remnant liver volume and function were measured before and after PVE. Hepatic microcirculation was measured in the embolized and the nonembolized lobes during resection. Microcirculatory flow index, perfused vessel density, sinusoidal diameter and red blood cell velocity were assessed.ResultsA total of 16 patients, eight with preoperative PVE and eight control patients without PVE, were included. After PVE, both function and volume of the nonembolized lobe were significantly increased, and the functional increase exceeded the increase in volume. Perfused vessel density and sinusoidal diameter were significantly higher in the nonembolized liver lobe (P

  • Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection
    HPB : the official journal of the International Hepato Pancreato Biliary Association, 2016
    Co-Authors: Kasia P. Cieslak, Wilmar De Graaf, Roelof J. Bennink, Krijn P. Van Lienden, Olivier R. Busch, Dirk J. Gouma, Marc G. Besselink, Thomas M. Van Gulik
    Abstract:

    Background 99mTc-Mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cut-off value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated.

  • Quantitative Assessment of Hepatic Function During Liver Regeneration in a Standardized Rat Model
    Journal of nuclear medicine : official publication Society of Nuclear Medicine, 2011
    Co-Authors: Wilmar De Graaf, Michal Heger, Roelof J. Bennink, Adrie Maas, Kora De Bruin, Thomas M. Van Gulik
    Abstract:

    Reliable assessment of hepatic function during liver regeneration is crucial after liver surgery or liver transplantation. Tc-99m-galactosyl human serum albumin (Tc-99m-GSA) scintigraphy, Tc-99m-Mebrofenin hepatobiliary scintigraphy (HBS), the indocyanine green (ICG) clearance test, and the galactose elimination capacity (GEC) are common quantitative liver function tests. However, to our knowledge, comparative analysis between these tests has never been performed during liver regeneration. The aim of this study was therefore to compare Tc-99m-GSA scintigraphy, Tc-99m-Mebrofenin HBS, the ICG clearance test, and GEC in the assessment of hepatic function during liver regeneration in rats. Methods: Rats were subjected to 70% partial hepatectomy (PHx). Liver function and functional volume were determined at predefined times after PHx and expressed as a percentage of baseline (pre-PHx) values. Results: During liver regeneration, functional liver volume measured by Tc-99m-GSA SPECT correlated strongly with conventional liver volume based on wet weight. One day after 70% PHx, conventional liver volume overestimated liver function as measured by Tc-99m-Mebrofenin uptake and excretion rates, Tc-99m-GSA uptake rate, and ICG clearance. On days 5 and 7, Tc-99m-Mebrofenin uptake and ICG clearance had recovered to levels similar to conventional liver volume, whereas Tc-99m-GSA uptake reflected a reduced liver function in relation to conventional liver volume and Tc-99m-Mebrofenin uptake. The GEC measurements consistently overestimated liver function during regeneration. Conclusion: Volumetric assessment of the liver should be complemented by liver function-specific assays. Functional regeneration is impaired, compared with volumetric regeneration, in the early phase of liver regeneration. In later stages of liver regeneration, Tc-99m-GSA uptake underestimates hepatic regeneration in comparison to liver volume and Tc-99m-Mebrofenin uptake. GEC is of less value because it is only minimally affected by 70% PHx and is influenced by factors not related to liver function. Tc-99m-Mebrofenin HBS has the advantage of providing visual and quantitative information regarding both uptake and excretory liver function

  • Transporters involved in the hepatic uptake of (99m)Tc-Mebrofenin and indocyanine green
    Journal of hepatology, 2010
    Co-Authors: Wilmar De Graaf, Stephanie Häusler, Michal Heger, Tessa M. Van Ginhoven, Gert Van Cappellen, Roelof J. Bennink, Gerd A. Kullak-ublick, Rolf Hesselmann, Thomas M. Van Gulik, Bruno Stieger
    Abstract:

    Background & Aims 99m Tc-Mebrofenin hepatobiliary scintigraphy (HBS) and the indocyanine green (ICG) clearance test are used for the assessment of hepatic function before and after liver surgery. The hepatic uptake of 99m Tc-Mebrofenin and ICG is considered similar to the uptake of organic anions such as bilirubin and bile acids. Little is known about hepatic uptake mechanisms of both compounds and recent evidence suggests that the hepatic transporters for ICG and 99m Tc-Mebrofenin are distinct. The aim of this study was to identify the specific human hepatic transporters of 99m Tc-Mebrofenin and ICG. Methods The uptake of 99m Tc-Mebrofenin was investigated in cRNA-injected Xenopus laevis oocytes expressing human OATP1B1, OATP1B3, OATP2B1, or NTCP. Chinese hamster ovary (CHO) cells stably expressing OATP1B1, OATP1B3, OATP2B1, or NTCP were used as a mammalian expression system. ICG transport into CHO cells was additionally imaged with confocal microscopy. Results We demonstrated that OATP1B1 and OATP1B3 are involved in the transport of 99m Tc-Mebrofenin. OATP1B1 showed an approximately 1.5-fold higher affinity for 99m Tc-Mebrofenin compared to OATP1B3. ICG is transported by OATP1B3 and NTCP. Conclusions The transporter specificity of 99m Tc-Mebrofenin and ICG partially overlaps as both compounds are transported by OATP1B3. 99m Tc-Mebrofenin is also taken up by OATP1B1, whereas ICG is additionally transported by NTCP.

  • Quantitative assessment of liver function after ischemia-reperfusion injury and partial hepatectomy in rats.
    The Journal of surgical research, 2010
    Co-Authors: Wilmar De Graaf, Michal Heger, Roelof J. Bennink, Adrie Maas, Kora De Bruin, Onno Spruijt, Ruurdtje Hoekstra, Thomas M. Van Gulik
    Abstract:

    Background Liver function after hepatic ischemia-reperfusion (I/R) injury and partial liver resection (PHx) is influenced by the extent of PHx, hepatocellular damage, and liver regeneration. This study investigates the effect of minor PHx with increasing degrees of I/R-induced damage on postoperative liver function parameters and compares the indocyanine green (ICG) clearance test with 99mTc-Mebrofenin hepatobiliary scintigraphy (HBS) for quantitative measurement of hepatic function in a standardized rat model. Methods Rats were subjected to 70% partial liver I/R combined with resection of the nonischemic lobes. Various degrees of hepatic damage were induced by 0, 15, 30, 45, and 60 min ischemia. Prothrombin time and bilirubin were used as indirect parameters of liver function. 99mTc-Mebrofenin HBS and ICG clearance were used as dynamic quantitative liver function tests. Results After 24 h reperfusion hepatocellular damage increased with prolonged ischemia times. Hepatocellular damage and liver regeneration were closely interrelated. Moderate I/R-induced damage enhanced regeneration, while extensive damage debilitates the regenerative capacity. PHx alone resulted in no significant decrease in liver uptake function measured by HBS or ICG. Increasing severity of hepatic I/R injury had a differential effect on ICG clearance and 99mTc-Mebrofenin uptake and excretion. Conclusions The specific impact of 30% PHx combined with progressive ischemia times is different for each liver function test. Albeit 99mTc-Mebrofenin HBS and the ICG clearance test provide complementary quantitative information to biochemical parameters, they only quantify one or two components of liver function. ICG and 99mTc-Mebrofenin uptake profiles differed significantly, suggesting that the specific hepatic transporters may be distinct.

T.m. Van Gulik - One of the best experts on this subject based on the ideXlab platform.

  • Comparison between dynamic gadoxetate-enhanced MRI and 99m Tc-Mebrofenin hepatobiliary scintigraphy with SPECT for quantitative assessment of liver function
    European radiology, 2019
    Co-Authors: Fadi Rassam, Tian Zhang, K.p. Cieslak, Cristina Lavini, Jaap Stoker, Roel J. Bennink, T.m. Van Gulik, L.j. Van Vliet, Jurgen H. Runge, Franciscus M. Vos
    Abstract:

    To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-Mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-Mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: Mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p 

  • comparison between dynamic gadoxetate enhanced mri and 99m tc Mebrofenin hepatobiliary scintigraphy with spect for quantitative assessment of liver function
    European Radiology, 2019
    Co-Authors: Fadi Rassam, Tian Zhang, K.p. Cieslak, Cristina Lavini, Jaap Stoker, Roel J. Bennink, T.m. Van Gulik, L.j. Van Vliet, Jurgen H. Runge, Franciscus M. Vos
    Abstract:

    To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-Mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection. Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-Mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: Mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters. A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p < 0.001 respectively). There was a strong agreement between the functional share determined with both modalities (ICC = 0.944, 95% CI 0.863–0.978, n = 20). There was a significant negative correlation between liver aminotransferases and bilirubin for both MUR and Ki. Assessment of liver function with DHCE-MRI is comparable with that of 99mTc-Mebrofenin HBS and has the potential to be combined with diagnostic MRI imaging. This can therefore provide a one-stop-shop modality for the preoperative assessment of patients undergoing liver surgery. • Quantitative assessment of liver function using hepatobiliary scintigraphy is performed in the preoperative assessment of patients undergoing liver surgery in order to prevent posthepatectomy liver failure. • Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) is an emerging method to quantify liver function and can serve as a potential alternative to hepatobiliary scintigraphy. • Assessment of liver function with dynamic gadoxetate-enhanced MRI is comparable with that of hepatobiliary scintigraphy and has the potential to be combined with diagnostic MRI imaging.

  • Hepatic regeneration and functional recovery following partial liver resection in an experimental model of hepatic steatosis treated with omega-3 fatty acids.
    The British journal of surgery, 2013
    Co-Authors: Hendrik A. Marsman, Michal Heger, Roel J. Bennink, W. De Graaf, R. F. Van Golen, F. J. W. Ten Kate, T.m. Van Gulik
    Abstract:

    Background Omega-3 fatty acids (FAs) have been shown to reduce experimental hepatic steatosis and protect the liver from ischaemia–reperfusion injury. The aim of this study was to examine the effects of omega-3 FAs on regeneration of steatotic liver. Methods Steatosis was induced in rats by a 3-week methionine/choline-deficient diet, which was continued for an additional 2 weeks in conjunction with oral administration of omega-3 FAs or saline solution. Steatosis was graded histologically and quantified by proton magnetic resonance spectroscopy (1H-MRS) before and after the diet/treatment. Liver function was determined by 99mTc-labelled Mebrofenin hepatobiliary scintigraphy (HBS). In separate experiments, the hepatic regenerative capacity and functional recovery of omega-3 FA-treated, saline-treated or non-steatotic (control) rats were investigated 1, 2, 3 and 5 days after partial (70 per cent) liver resection by measurement of liver weight change and hepatocyte proliferation (Ki-67) and HBS. Results Severe steatosis (over 66 per cent) in the saline group was reduced by omega-3 FAs to mild steatosis (less than 33 per cent), and hepatic fat content as assessed by 1H-MRS decreased 2·2-fold. 99mTc-Mebrofenin uptake in the saline group was more than 50 per cent lower than in the control group, confirming the functional effects of steatosis. 99mTc-Mebrofenin uptake and regenerated liver mass were significantly greater in the omega-3 group compared with the saline group on days 1 and 3. The posthepatectomy proliferation peak response was delayed until day 2 in saline-treated rats, compared with day 1 in the omega-3 and control groups. Conclusion Omega-3 FAs effectively reduced severe hepatic steatosis, which was associated with improved liver regeneration and functional recovery following partial hepatectomy.

  • Mild steatosis impairs functional recovery after liver resection in an experimental model
    The British journal of surgery, 2007
    Co-Authors: Reeta Veteläinen, Roel J. Bennink, A.k. Van Vliet, T.m. Van Gulik
    Abstract:

    Background: Mild steatosis has been thought not to affect outcome after liver resection. However, recent studies have reported impaired postoperative recovery of patients with mild steatosis. This study evaluated the recovery of hepatic functional reserve during regeneration in a rat model of mild steatosis and liver resection. Methods: Male Wistar rats had a standard methione- and choline-deficient diet to induce mild steatosis before 70 per cent liver resection. Evaluation of hepatobiliary function was by 99mTc-labelled Mebrofenin scintigraphy. Mebrofenin uptake rate, the time for maximum uptake (T peak) and the time required for peak activity to decrease by 50 per cent (T1/2 peak) were assessed 1, 2, 3 and 7 days after liver resection, along with regeneration of the remnant liver, hepatocellular and sinusoidal damage, and hepatic adenosine 5′-triphosphate (ATP) levels. Results: Liver regeneration and proliferative response in mild steatotic rats were no different from those in controls. However, the Mebrofenin uptake rate was lower (P < 0·050) and the recovery of hepatic ATP impaired (P < 0·050) in animals with mild steatosis. Hepatocellular damage was increased (P < 0·050) but sinusoidal endothelial cell function was not affected after liver resection in mildly steatotic rats. Conclusion: Mild steatosis impaired functional recovery and increased hepatocellular damage after liver resection. Copyright © 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.