Endoscopic ultrasound-guided sampling and profiling of portal circulation in human patients for metabolic research studies and biomarker assessment.

Portal and hepatic circulation can now be safely accessed using endoscopic ultrasound (EUS). EUS-guided needle access of the portal vein is performed clinically at select tertiary centers for measurement of portal pressure gradients in patients with chronic liver disease and sampling of portal venous thrombus to diagnose malignancy. We propose that this novel clinical technique can be applied in research studies to allow blood collection from and profiling of portal and hepatic circulation. In this technical report, we present and highlight the technical aspects, feasibility, and safety of EUS: guided portal venous blood collection. As a proof of the concept and the utility of this technique in metabolic research and biomarker assessment and discovery, we present a pilot metabolite profiling study of portal venous blood in a small cohort of patients with cirrhosis and a comparison with a group without cirrhosis. Despite the very small diameter of the endoscopic needle used for the blood collection, the portal samples have the same quality as those collected from systemic circulation, and they can be used for the same downstream applications. Finally, we propose an analytical workflow to screen for promising metabolites that could qualify for further studies to determine their utility as sensitive, early candidate biomarkers of hepatic fibrosis, portal shunt, and hypertension. We hope that this report could stimulate and facilitate the widespread use of EUS-guided techniques for the profiling of portal circulation, which could potentially open a new field of scientific inquiry.NEW & NOTEWORTHY The technical aspects, feasibility, and safety of endoscopic ultrasound (EUS)-guided needle access for portal venous blood collection are presented in this technical report. Despite the very small diameter of the endoscopic needle, portal blood samples have the same quality as those collected from systemic circulation. As a proof of the concept and the utility of this technique in metabolic research and biomarker assessment and discovery, we present a pilot metabolite profiling study of portal venous blood in a small cohort of patients with cirrhosis and a comparison with a group without cirrhosis.

Assessment of hepatic microvascular flow and density in patients undergoing preoperative portal vein embolization.

BACKGROUND: The microvascular effects occurring after unilateral preoperative portal vein embolization (PVE) are poorly understood. The aim of this study was to assess the microvascular changes in the embolized and the non-embolized lobes after right PVE. METHODS: Videos of the hepatic microcirculation in patients undergoing right hemihepatectomy following PVE were recorded using a handheld vital microscope (Cytocam) based on incident dark field imaging. Hepatic microcirculation was measured in the embolized and the non-embolized lobes at laparotomy, 3-6 weeks after PVE. The following microcirculatory parameters were assessed: total vessel density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel (PPV), perfused vessel density (PVD), sinusoidal diameter (SinD) and the absolute red blood cell velocity (RBCv). RESULTS: 16 patients after major liver resection were included, 8 with and 8 without preoperative PVE. Microvascular density parameters were higher in the non-embolized lobes when compared to the embolized lobes (TVD: 40.3 ± 8.9 vs. 26.8 ± 4.6 mm/mm2 (p < 0.003), PVD: 40.3 ± 8.8 vs. 26.7 ± 4.7 mm/mm2 (p < 0.002), SinD: 9.2 ± 1.7 vs. 6.3 ± 0.8 µm (p < 0.040)). RBCv, PPV and the MFI were not significantly different. CONCLUSION: The non-embolized lobe has a significantly higher microvascular density, however without differences in microvascular flow. These findings indicate increased angiogenesis in the hypertrophic lobe.

Celiac axis stenosis due to median arcuate ligament compression in a patient who underwent pancreatoduodenectomy; intraoperative assessment of hepatic arterial flow using Doppler ultrasonography: a case report.

BACKGROUND: Celiac axis stenosis due to compression by the median arcuate ligament has been reported in patients undergoing pancreaticoduodenectomy; it leads to the development of major collateral pathways that feed the hepatic artery. Dividing these important collaterals during pancreaticoduodenectomy can cause ischemic complications which may lead to a high mortality rate. To prevent these complications, it is necessary to assess intrahepatic arterial flow. CASE PRESENTATION: A 71-year-old Japanese man with anorexia was referred to us for the treatment of alcoholic chronic pancreatitis. Computed tomography revealed a pancreatic head tumor with a calculus, associated with the dilatation of the main pancreatic duct and intrahepatic bile duct. Three-dimensional imaging demonstrated focal narrowing in the proximal celiac axis due to median arcuate ligament compression and a prominent gastroduodenal artery that fed the common hepatic artery. The preoperative diagnosis was alcoholic chronic pancreatitis with common bile duct obstruction and celiac axis stenosis due to median arcuate ligament compression. Pancreaticoduodenectomy with median arcuate ligament release was scheduled. Before the division of the median arcuate ligament, the peak flow velocity and resistive index of his intrahepatic artery measured with Doppler ultrasonography decreased from 37.7 cm/second and 0.510, respectively, to 20.6 cm/second and 0.508 respectively, when his gastroduodenal artery was clamped. However, these values returned to baseline levels after the division of the median arcuate ligament. These findings suggested that pancreaticoduodenectomy could be performed safely. Our patient was discharged on postoperative day 17 without significant complications. CONCLUSION: The intraoperative quantitative evaluation of intrahepatic arterial blood flow using Doppler ultrasonography was useful in a patient who underwent pancreaticoduodenectomy, who had celiac axis stenosis due to compression by the median arcuate ligament.

Assessment of Advanced Liver Fibrosis and the Risk for Hepatic Decompensation in Patients With Congestive Hepatopathy.

Congestive hepatopathy (CH) arises from chronically elevated right-sided heart pressures transmitted to the liver by passive venous congestion. Over time, CH can lead to hepatic bridging fibrosis, decompensated cirrhosis, and hepatocellular carcinoma. Currently, there are no evidence-based guidelines to direct appropriate screening or management of patients with CH, partly because of the inability of current clinical tools (serum tests, imaging studies, liver stiffness measurements, and liver biopsy) to accurately estimate hepatic fibrosis or the risk for hepatic decompensation. The Model for End-Stage Liver Disease excluding international normalized ratio (MELD-XI) score is the only validated serum-based test to predict clinical outcomes in CH. Noninvasive liver stiffness measurements are proving to be of minimal utility as all patients with CH have elevated values that currently cannot differentiate between congestion and fibrosis. In addition, fibrosis staging by liver biopsy is difficult to standardize because of heterogeneous collagen deposition in CH. Moreover, liver biopsy results have little predictive value for post-heart transplant hepatic outcomes in patients with CH. Evaluating liver nodules and masses is also complicated in CH as the finding of delayed venous washout in nodules is not specific for hepatocellular carcinoma in the background of a congested liver, and these lesions may require biopsy to confirm the diagnosis. The lack of effective clinical tools for predicting liver fibrosis and liver function suggests the need for the development of novel biomarkers in patients with CH to assist in the management of this complicated disease. (Hepatology 2018; 00:000-000).

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion.

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours of normothermic machine perfusion.

Normothermic machine perfusion (NMP) is an emerging technology to preserve liver allografts more effectively than cold storage (CS). However, little is known about the effect of NMP on steatosis and the markers indicative of hepatic quality during NMP. To address these points, we perfused 10 discarded human livers with oxygenated NMP for 24 hours after 4-6 hours of CS. All livers had a variable degree of steatosis at baseline. The perfusate consisted of packed red blood cells and fresh frozen plasma. Perfusate analysis showed an increase in triglyceride levels from the 1st hour (median, 127 mg/dL; interquartile range [IQR], 95-149 mg/dL) to 24th hour of perfusion (median, 203 mg/dL; IQR, 171-304 mg/dL; P = 0.004), but tissue steatosis did not decrease. Five livers produced a significant amount of bile (≥5 mL/hour) consistently throughout 24 hours of NMP. Lactate in the perfusate cleared to <3 mmol/L in most livers within 4-8 hours of NMP, which was independent of bile production rate. This is the first study to characterize the lipid profile and functional assessment of discarded human livers at 24 hours of NMP. Liver Transplantation 24 233-245 2018 AASLD.

Assessment of liver perfusion and function by indocyanine green in the perioperative setting and in critically ill patients.

Indocyanine green (ICG) is a water-soluble dye that is bound to plasma proteins when administered intravenously and nearly completely eliminated from the blood by the liver. ICG elimination depends on hepatic blood flow, hepatocellular function and biliary excretion. ICG elimination is considered as a useful dynamic test describing liver function and perfusion in the perioperative setting, i.e., in liver surgery and transplantation, as well as in critically ill patients. ICG plasma disappearance rate (ICG-PDR) which can be measured today by transcutaneous systems at the bedside is a valuable method for dynamic assessment of liver function and perfusion, and is regarded as a valuable prognostic tool in predicting survival of critically ill patients, presenting with sepsis, ARDS or acute liver failure.

Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

An Assessment of Fetal Cerebral and Hepatic Perfusion in Normal Pregnancy and Pre-Eclampsia Using Three-Dimensional Ultrasound.

BACKGROUND: Pre-eclampsia and placental causes of intrauterine growth restriction (IUGR) are part of the same spectrum of disorders. In IUGR, there is preferential shunting of blood to the fetal brain at the expense of other organs. We wanted to demonstrate that this also occurs in pre-eclampsia using three dimensional (3D) ultrasound. The 3D indices of perfusion are: flow index (FI), vascular index (VI) and vascularisation flow index (VFI) which reflect tissue vascularity and flow intensity. METHODS: Fourteen normal pregnant women and 14 with diagnosed pre-eclampsia were recruited. Scanning was conducted by 2 observers using a Voluson E8 machine. Perfusion was measured at a pre-defined position within the fetal brain and fetal liver. The power Doppler signals were quantified using the 'histogram facility' to generate 3 indices of vascularity: FI, VI and VFI. The unpaired t-test was used to compare differences between groups. The hypothesis was that fetal brain FI, VI and VFI would be similar between women with normal pregnancy and women with pre-eclampsia, but measurements would be reduced in the fetal liver in women with pre-eclampsia. RESULTS: Maternal characteristics of age, body mass index and gestation were not different between groups. The depth of insonnation did not differ between groups. Fetal cerebral perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 22.4 (5.7) vs. 21.1 (4.3) respectively (p=0.49). For VI, the mean (SD) was as 64.7 (40.4) vs. 79.1 (27.4) respectively (p=0.28). For VFI, the mean (SD) was 14.8 (10.3) vs. 16.1 (5.5) respectively (p = 0.66). Fetal hepatic perfusion was not different between women with a normal pregnancy compared to women with pre-eclampsia. The mean (SD) for FI was 34.4 (19.9) vs. 27.8 (11.0) respectively (p = 0.28). For VI, mean (SD) was 67.6 (36.0) vs. 87.3 (25.8) respectively (p=0.11). For VFI, the mean (SD) was 19.6 (11.6) vs. 23.1 (10.6) respectively (p=0.42). CONCLUSION: Using 3D ultrasound, we were not able to demonstrate preferential shunting of blood to the fetal brain at the expense of the fetal liver. Due to the high variability of our data, no definite conclusions can be derived from this work. A larger study may be required.

Dynamic Contrast-Enhanced Magnetic Resonance Imaging With Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid for Quantitative Assessment of Vascular Effects on Hepatocellular-Carcinoma Lesions Treated by Transarterial Chemoembolization or Radiofrequency Ablation.

PURPOSE: The aim of this study was to investigate the role of dynamic contrast-enhanced magnetic resonance imaging (MRI) in evaluation of blood flow changes related to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) procedures in patients with hepatocellular carcinoma (HCC) lesions. METHODS: Fifty-four patients, with biopsy-proven HCC, who underwent TACE or RFA, were evaluated, 1 month after treatment, with upper abdominal MRI examination. Multiplanar T2-weighted, T1-weighted, and dynamic contrast-enhanced sequences were acquired. Dedicated perfusion software (T1 Perfusion Package, Viewforum; Philips Medical Systems, The Netherlands) was used to generate color permeability maps. After placing regions of interest in normal hepatic parenchyma, in successfully treated lesions, and in area of recurrence, the following perfusion parameters were calculated and statistically analyzed: relative arterial, venous, and late enhancement; maximum enhancement; maximum relative enhancement, and time to peak. RESULTS: Twenty-one of 54 patients had residual disease, and perfusion parameters values measured within tumor tissue were: relative arterial enhancement median, 42%; relative venous enhancement median, 69%; relative late enhancement median, 57.7%; maximum enhancement median, 749.6%; maximum relative enhancement median, 69%; time to peak median, 81.1 seconds. As for all the evaluated parameters, a significant difference (P < 0.05) was found between residual viable tumor tissue and effective treated lesions. CONCLUSIONS: Dynamic contrast-enhanced MRI represents a complementary noninvasive tool that may offer quantitative and qualitative information about HCC lesions treated with TACE and RFA.

[ASSESSMENT OF LIVER FUNCTION WITH TRANSESOPHAGEAL ECHOCARDIOGRAPHY HEART SURGERY WITH CARDIOPULMONARY BYPASS].

AIM OF THE STUDY: evaluation of arterial and venous liver circulation during cardiopulmonary bypass (CPB) using the method of transesophageal echocardiography (TEE). MATERIALS AND METHODS: 62 patients undergoing reconstructive cardiac surgery with CPB were analyzed. During all the stages of treatment we performed monitoring of mean arterial pressure, heart rate and central venous pressure. TEE was performed using specialized Philips iE-33 3-D matrix multifrequency probe X7-2t in transgastral position. Ultrasonic and dopplerographic measuring of blood flow in hepatic artery and veins was performed before sternotomy, in 30 minutes after starting CPB and after stopping CPB during sternal closure. The speed of bloodflow in hepatic artery, hepatic veins, biochemical blood analysis was evaluated, i.e. lactate level, AST ALT ratio before the intervention, during CPD and in early postoperative period RESULTS: Correlation between blood flow in liver vessels and dynamics of biochemical analysis. It is considered to that this change during procedures with CPB may be linked with liver insufficiency during first hours of evaluation. In other words reduced blood flow in liver vessels may be one of the liver insufficiency early symptoms and is one of factors that require correction during operative and early postoperative period. So dynamic follow-up of hepatic circulation may be used as a method of early diagnostics of functional organ disorders.

Preclinical Assessment of the Efficacy of Anti-Angiogenic Therapies in Hepatocellular Carcinoma.

Diffuse hepatocellular carcinoma (HCC) is a complex affliction in which comorbidities can bias global outcome of cancer therapy. Better methods are thus warranted to directly assess effects of therapy on tumor angiogenesis and growth. As tumor angiogenesis is invariably associated with changes in local blood flow, we assessed the utility of ultrasound imaging in evaluation of the efficacy of anti-angiogenic therapy in a spontaneous transgenic mouse model of HCC. Blood flow velocities were measured monthly in the celiac trunk before and after administration of sorafenib or bevacizumab at doses corresponding to those currently used in clinical practice. Concordant with clinical experience, sorafenib, but not bevacizumab, reduced microvascular density and suppressed tumor growth relative to controls. Evolution of blood flow velocities correlated with microvascular density and with the evolution of tumor size. Ultrasound imaging thus provides a useful non-invasive tool for preclinical evaluation of new anti-angiogenic therapies for HCC.

Intravital Microscopy Imaging of the Liver following Leishmania Infection: An Assessment of Hepatic Hemodynamics.

Intravital microscopy (IVM) is a powerful optical imaging technique that has made possible the visualization, monitoring and quantification of various biological events in real time and in live animals. This technology has greatly advanced our understanding of physiological processes and pathogen-mediated phenomena in specific organs. In this study, IVM is applied to the mouse liver and protocols are designed to image in vivo the circulatory system of the liver and measure red blood cell (RBC) velocity in individual hepatic vessels. To visualize the different vessel subtypes that characterize the hepatic organ and perform blood flow speed measurements, C57Bl/6 mice are intravenously injected with a fluorescent plasma reagent that labels the liver-associated vasculature. IVM enables in vivo, real time, measurement of RBC velocity in a specific vessel of interest. Establishing this methodology will make it possible to investigate liver hemodynamics under physiological and pathological conditions. Ultimately, this imaging-based methodology will be important for studying the influence of L. donovani infection on hepatic hemodynamics. This method can be applied to other infectious models and mouse organs and might be further extended to pre-clinical testing of a drug's effect on inflammation by quantifying its effect on blood flow.

Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis.

AIM: To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound (CEUS) in a canine model. METHODS: Liver fibrosis was established in adult canines (Beagles; n = 14) by subcutaneous injection of carbon tetrachloride (CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases (Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures (FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Qp/Qa and Ip/Ia. RESULTS: Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0 (n = 3), F1 (n = 12), F2 (n = 14), F3 (n = 11), and F4 (n = 2). There were significant differences in the measurements of Qp/Qa (19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia (1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively (all P < 0.001). There were statistically significant negative correlations between FPP and Qp/Qa (r = -0.707, P < 0.001), and between FPP and Ip/Ia (r = -0.759, P < 0.001) in the canine fibrosis model. Prediction of elevated FPP based on Qp/Qa and Ip/Ia was highly sensitive, as assessed by the area under the receiver operating curve (0.866 and 0.895, respectively). CONCLUSION: CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.

Assessment of Liver Perfusion by IntraVoxel Incoherent Motion (IVIM) Magnetic Resonance-Diffusion-Weighted Imaging: Correlation With Phase-Contrast Portal Venous Flow Measurements.

OBJECTIVES: To prospectively verify, in vivo, Le Bihan's model of signal decay in magnetic resonance/diffusion-weighted imaging (intravoxel incoherent motion) in healthy liver parenchyma. METHODS: Informed consent and institutional board approval were obtained. To measure both underfasting and postprandial conditions, apparent, slow, and fast diffusion (D*) coefficients and perfusion fraction of liver parenchyma, 40 healthy volunteers (19 women and 21 men) underwent a 3.0-T magnetic resonance imaging examination, including portal venous flow measurements by a 2-dimensional phase-contrast sequence, and multi-b diffusion-weighted imaging acquired before and 30 minutes after a 600-Kcal meal. Parameters were measured by fitting procedure with regions of interest drawn on the right liver lobe. Paired-sample t test was performed to search for any statistically significant difference between preprandial and postprandial values of each parameter and of portal flow. Pearson correlation coefficients were calculated to evaluate the relationship between portal flow increase and diffusion-weighted imaging parameter changes in postprandial conditions. Interobserver agreement for measurement of the intravoxel incoherent motion parameters was determined, both for preprandial and postprandial values. RESULTS: Mean increase in postprandial portal flow was 98% (P < 0.0009). The t test did not show any statistically significant difference between the preprandial and postprandial values for apparent, slow diffusion coefficients and perfusion fraction (P ≥ 0.05), whereas a statistically significant postprandial increase (P < 0.01) of D* was detected. Correlation with portal venous flow increase at Pearson test was statistically significant for D* (P = 0.04) and nonsignificant for the other parameters. All the parameters showed wide variability, with a higher percent coefficient of variation for D*. Interobserver agreement was always greater than 0.70. CONCLUSIONS: This study verifies Le Bihan's theory, confirming that in the liver, D* is influenced by perfusional changes related to portal venous flow.

K-t GRAPPA-accelerated 4D flow MRI of liver hemodynamics: influence of different acceleration factors on qualitative and quantitative assessment of blood flow.

OBJECTIVE: We sought to evaluate the feasibility of k-t parallel imaging for accelerated 4D flow MRI in the hepatic vascular system by investigating the impact of different acceleration factors. MATERIALS AND METHODS: k-t GRAPPA accelerated 4D flow MRI of the liver vasculature was evaluated in 16 healthy volunteers at 3T with acceleration factors R = 3, R = 5, and R = 8 (2.0 × 2.5 × 2.4 mm(3), TR = 82 ms), and R = 5 (TR = 41 ms); GRAPPA R = 2 was used as the reference standard. Qualitative flow analysis included grading of 3D streamlines and time-resolved particle traces. Quantitative evaluation assessed velocities, net flow, and wall shear stress (WSS). RESULTS: Significant scan time savings were realized for all acceleration factors compared to standard GRAPPA R = 2 (21-71 %) (p < 0.001). Quantification of velocities and net flow offered similar results between k-t GRAPPA R = 3 and R = 5 compared to standard GRAPPA R = 2. Significantly increased leakage artifacts and noise were seen between standard GRAPPA R = 2 and k-t GRAPPA R = 8 (p < 0.001) with significant underestimation of peak velocities and WSS of up to 31 % in the hepatic arterial system (p <0.05). WSS was significantly underestimated up to 13 % in all vessels of the portal venous system for k-t GRAPPA R = 5, while significantly higher values were observed for the same acceleration with higher temporal resolution in two veins (p < 0.05). CONCLUSION: k-t acceleration of 4D flow MRI is feasible for liver hemodynamic assessment with acceleration factors R = 3 and R = 5 resulting in a scan time reduction of at least 40 % with similar quantitation of liver hemodynamics compared with GRAPPA R = 2.

Quantitative assessment of hepatic blood flow in the diagnosis and management of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most important gastrointestinal emergency in the neonatal period and early detection is very important for its management. Bowel ischemia-hypoperfusion is one of the main etiological factors. In the literature, a few studies have focused on arterial Doppler ultrasonography (DUS) features of splanchnic arteries; however, their clinical implications are not clear. OBJECTIVE: In this study, we aimed to quantitatively evaluate the blood flow features in the hepatic portal vein (PV) and hepatic veins (HVs) by using DUS in newborns with NEC. Patient-Method: Enrolled subjects were divided into two groups as patient (suspected/confirmed NEC, n = 24), and control group (n = 25). Daily serial DUS examinations were performed after the onset of the suspicion of NEC and continued until the initial day of the enteral feeding. Portal blood flow (PBF) and "hepatic blood flow ratio" (RHBF) were calculated manually by using DUS findings. Two groups were compared with respect to their PBF and RoHBF values. RESULTS: PBF and RHBF levels were significantly lower in patient group than those in control group. Clinical improvement in patients with NEC was associated with improvement in the PBF and RHBF. Cut-off level of the RHBF for the diagnosis of NEC was 0.66. CONCLUSION: DUS seems to be useful for the diagnosis and follow-up of NEC by providing quantitative information on liver blood flow. Daily measurements of the PBF and RoHBF in newborns with NEC may be beneficial to make the decision of starting enteral feeding.

Safety assessment of liver-targeted hydrodynamic gene delivery in dogs.

Evidence in support of safety of a gene delivery procedure is essential toward gene therapy. Previous studies using the hydrodynamics-based procedure primarily focus on gene delivery efficiency or gene function analysis in mice. The current study focuses on an assessment of the safety of computer-controlled and liver-targeted hydrodynamic gene delivery in dogs as the first step toward hydrodynamic gene therapy in clinic. We demonstrate that the impacts of the hydrodynamic procedure were limited in the injected region and the influences were transient. Histological examination and the hepatic microcirculation measurement using reflectance spectrophotometry reveal that the liver-specific impact of the procedure involves a transient expansion of the liver sinusoids. No systemic damage or toxicity was observed. Physiological parameters, including electrocardiogram, heart rate, blood pressure, oxygen saturation, and body temperature, remained in normal ranges during and after hydrodynamic injection. Body weight was also examined to assess the long-term effects of the procedure in animals who underwent 3 hydrodynamic injections in 6 weeks with 2-week time interval in between. Serum biochemistry analysis showed a transient increase in liver enzymes and a few cytokines upon injection. These results demonstrate that image-guided, liver-specific hydrodynamic gene delivery is safe.

Laser speckle contrast imaging for assessment of abdominal visceral microcirculation in acute peritonitis: does sequential impairments exist?

OBJECTIVE: It is believed that the microcirculation of multiple organs is impaired during acute peritonitis, however whether distinct susceptibilities of visceral microvasculature exist is still unknown. The present study aims to verify whether the microcirculatory alterations occur sequentially among multiple abdominal viscera during acute peritonitis. MATERIALS AND METHODS: Acute peritonitis was achieved on 29 Sprague-Dawley rats through colon ascendens stent peritonitis (CASP) model. With laser speckle contrast imaging (LSCI), the microcirculation of the liver, ileum and renal cortex was monitored in each rat at baseline before CASP sepsis and continued monitoring at 4h, 8h, or 12h after the surgery. Another 9 rats served for sham operation. One-way analysis of variance with a post hoc Dunnett's test was used for analysis. RESULTS: The ileum microcirculation was impaired earliest from 342.1±61.0 laser speckle perfusion unit (LSPU) at baseline to 271.7±74.0 LSPU at 4h (P<0.05), while the decline of renal microcirculation was not obvious until 8h after peritonitis (289.1±111.2 vs 376.2±53.4, P<0.05). However hepatic microcirculation was not significantly changed during 12h of observation period. CONCLUSION: The microcirculation of various viscera has shown distinct susceptibilities to acute peritonitis: the ileum is more susceptible than the kidney, while the hepatic microcirculation seems to be the most resistant to peritonitis.