Changes In Liver Perfusion Research Articles

Using MRI to study the alterations in liver blood flow, perfusion, and oxygenation in response to physiological stress challenges: Meal, hyperoxia, and hypercapnia.

Noninvasive assessment of dynamic changes in liver blood flow, perfusion, and oxygenation using MRI may allow detection of subtle hemodynamic alterations in cirrhosis. To assess the feasibility of measuring dynamic liver blood flow, perfusion, and T2 * alterations in response to meal, hypercapnia, and hyperoxia challenges. Prospective. Ten healthy volunteers (HV) and 10 patients with compensated cirrhosis (CC). 3T; phase contrast, arterial spin labeling, and mapping. Dynamic changes in portal vein and hepatic artery blood flow (using phase contrast MRI), liver perfusion (using arterial spin labeling), and blood oxygenation ( mapping) following a meal challenge (660 kcal), hyperoxia (target PET O2 of 500 mmHg), and hypercapnia (target increase PET CO2 of ∼6 mmHg). Tests between baseline and each challenge were performed using a paired two-tailed t-test (parametric) or Wilcoxon-signed-ranks test (nonparametric). Repeatability and reproducibility were determined by the coefficient of variation (CoV). Portal vein velocity increased following the meal (70 ± 9%, P < 0.001) and hypercapnic (7 (5-11)%, P = 0.029) challenge, while hepatic artery flow decreased (-30 ± 18%, P = 0.005) following the meal challenge in HV. In CC patients, portal vein velocity increased (37 ± 13%, P = 0.012) without the decrease in hepatic artery flow following the meal. In both groups, the meal increased liver perfusion (HV: 82 ± 50%, P < 0.0001; CC: 27 (16-42)%, P = 0.011) with faster arrival time of blood (HV: -54 (-56-30)%, P = 0.074; CC: -42 ± 32%, P = 0.005). In HVs, increased after the meal and in response to hyperoxia, with a decrease in hypercapnia (6 ± 8% P = 0.052; 3 ± 5%, P = 0.075; -5 ± 6%, P = 0.073, respectively), but no change in CC patients. Baseline between-session CoV <15% for blood flow and <10% for measures. Dynamic changes in liver perfusion, blood flow, and oxygenation following a meal, hyperoxic, and hypercapnic challenges can be measured using noninvasive MRI and potentially be used to stratify patients with cirrhosis. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1577-1586.

MRI assessment of altered dynamic changes in liver haemodynamics following a meal challenge in compensated cirrhosis

BackgroundThe aim was to use magnetic resonance imaging (MRI) to dynamically assess postprandial changes in hepatic and collateral blood flow, liver perfusion and oxygenation in healthy participants and patients with liver disease with compensated cirrhosis (CC).MethodsWe evaluated blood flow in the portal vein, hepatic artery and azygos vein (using phase-contrast MRI), liver perfusion (using arterial spin labelling) and blood oxygenation (using transverse relaxation time [T2*] mapping). Measures were collected at baseline and at 6–7-min intervals from 20 to 65 min following a test meal (440 mL, 660 kcal) in 10 healthy participants and 10 patients with CC.ResultsIn healthy participants, we observed a significant postprandial increase in portal vein flow from baseline (+ 137 ± 26% (mean ± standard deviation), p < 0.001) coupled with a reduction in hepatic artery flow from baseline (− 30 ± 18%, p = 0.008), reflecting the hepatic artery buffer response. In patients with CC, a lower but still significant increase in portal vein flow (67 ± 50%, p = 0.014) was observed, without a clear hepatic artery buffer response. Healthy participants showed a significant increase in postprandial liver perfusion (138 ± 75%, p < 0.001), not observed in patients with CC. There was no change in liver T2* for either group.ConclusionsPostprandial changes in liver perfusion, oxygenation and hepatic and collateral circulation can be measured noninvasively using MRI. Differences between healthy participants and patients with CC were shown, which may help stratify liver cirrhosis in patients.

Changes in liver perfusion and function before and after percutaneous occlusion of spontaneous portosystemic shunt.

To evaluate changes in liver perfusion after occlusion of spontaneous portosystemic shunt and to analyze mechanisms of liver profile improvement. Liver function changes and portal venous and hepatic arterial blood flow were evaluated using perfusion CT before and after shunt occlusion in 23 patients who underwent percutaneous occlusion of spontaneous portosystemic shunt because of gastric varices (n=15) or hepatic encephalopathy (n=8). Portal venous blood flow was significantly higher at 1week (278.7ml/min, 92.7-636.7, p=0.012), 1month (290.0ml/min, 110.1-560.1, p<0.001) and 3months (299.6ml/min, 156.7-618.5, p=0.033) after shunt occlusion than the baseline (220.9ml/min, 49.5-566.7). Hepatic arterial liver blood flow became lower than the baseline (132.3ml/min, 47.9-622.3) after shunt occlusion, but a significant decrease was observed only at 1month later (107.9ml/min, 45.8-263.6 p=0.027). Serum albumin concentration became significantly higher than the baseline (3.4mg/dl, 1.9-4.5) at 1month (3.8mg/dl, 2.3-4.3, p=0.018) and 3months (3.9mg/dl, 2.6-4.3, p=0.024) after shunt occlusion. Shunt occlusion increases portal venous blood flow and decreases hepatic arterial blood flow, thereby improving the liver profile.

Hemodynamic response magnetic resonance imaging: application for renal hemodynamic characterization

The clinical use of iodinated radiocontrast agents or gadolinium for renal perfusion imaging is limited in the presence of renal dysfunction. We have previously demonstrated the feasibility of hemodynamic response imaging (HRI), a functional magnetic resonance imaging (MRI) method combined with hypercapnia and hypercapnic-hyperoxia, for monitoring changes in liver perfusion and hemodynamics. The aim of the present study was to evaluate the utility of HRI for monitoring changes in renal perfusion and hemodynamics. Renal HRI maps were acquired during graded hypercapnia (95% air + 5% CO2) and hypercapnic-hyperoxia (95% O2 + 5% CO2) in control mice. The utility of HRI for monitoring changes in renal perfusion and oxygenation was evaluated using pharmacological inhibition of nitric oxide synthase and cycloxygenase as well as in rhabdomyolysis-induced acute kidney injury (AKI) in mice. HRI results were further interpreted using Doppler ultrasound (US). Renal HRI maps revealed pronounced signal-intensity changes in response to both hypercapnia and hypercapnic-hyperoxia, reflecting intense vascular reactivity. These changes were significantly attenuated following the pharmacological intervention and during AKI, corresponding with hampered perfusion dynamics, as confirmed by Doppler US. The applicability of the non-invasive HRI method suggests its potential use for the evaluation of renal perfusion and vascular reactivity, excluding the need for contrast-agent administration.

LIVER RESPONSE TO HEMORRHAGIC SHOCK AND SUBSEQUENT RESUSCITATION

The liver is a target for injury in low flow states. Markers of liver injury are either invasive or not rapidly responding. Magnetic resonance imaging (MRI) may offer a noninvasive alternative to evaluate liver injury due to reduced perfusion. Recently, we reported an MRI method (functional MRI [fMRI]) that enables us to follow liver perfusion by changing the enrichment of inspired gas (air, air-5% carbon dioxide, 95% oxygen-5% carbon dioxide). Rats were subjected to hemorrhagic shock (HS) (bleeding to a MAP of 25 mmHg) and randomized to no resuscitation or resuscitation with Ringer lactate (RL) or adrenaline infusion targeted to a MAP of 50 mmHg or baseline. Significantly decreased fMRI responses to hyperoxia and hypercapnia were observed immediately after HS. Liver enzymes levels, liver histology, and apoptosis assessments were normal immediately after hemorrhage, however, showed significant changes after 6 h. Functional MRI revealed that adrenaline, but not RL infusion, significantly (P < 0.01) improved liver perfusion. Similarly, liver injury, as assessed by liver enzyme levels, liver histology, and apoptosis, was attenuated to a greater extent with adrenaline resuscitation. No significant differences in liver perfusion and injury were noted between resuscitation to low (50 mmHg) versus high (baseline) MAP. This study shows that fMRI enables early assessment of changes in liver perfusion, resulting in liver injury or recovery, and therefore, it may be considered as a noninvasive, rapidly responding tool for following liver outcome subsequent to hemorrhage and resuscitation. Using fMRI, we showed that adrenaline may be preferable to RL as an initial measure to attenuate liver injury after HS.

Functional MR Imaging during Hypercapnia and Hyperoxia: Noninvasive Tool for Monitoring Changes in Liver Perfusion and Hemodynamics in a Rat Model1

To prospectively assess functional magnetic resonance (MR) imaging during hypercapnia and hyperoxia for monitoring changes in liver perfusion and hemodynamics in rats. All experiments were performed with approval of an animal care and use committee. Functional T2*-weighted gradient-echo MR images of the rat liver were acquired during hyperoxia and graded hypercapnia (n=24). Additional images were acquired during portal vein ligation (n=4), induced hypovolemia (n=5), and 70% hepatectomy (n=5). Hypercapnic effects were confirmed with Doppler ultrasonography and with gadopentetate dimeglumine. Differences between groups were analyzed by using Wilcoxon rank sum test, except for the graded hypercapnia, for which one-way analysis of variance was used. Liver signal intensity (SI) increased due to hyperoxia; the percentage change in SI was seven times greater than that in muscle tissue; this reflects higher vascularity of the liver. Liver SI decreased due to hypercapnia; the percentage change in SI was negative in the liver but positive in the muscle (P<.001). Induced hypovolemia resulted in considerable decreases in functional MR imaging response; this reflects lower liver perfusion. Clinical applicability of the functional MR imaging method was proved by monitoring changes in liver perfusion that resulted from liver resection. In the liver, the magnitude of the percentage change in SI induced by hypercapnia and hyperoxia reflects changes in total blood volume; whereas percentage change in SI values induced by hypercapnia from a negative to a positive value reflects relative changes in portal-to-arterial blood flow ratio.

Early detection of occult colorectal hepatic metastases using duplex colour Doppler sonography.

Previous studies have shown that overt intrahepatic tumours are associated with subtle changes in liver perfusion that can be measured directly using duplex colour Doppler sonography (DCDS). This study assessed the predictive value of DCDS in the early detection of occult colorectal hepatic metastases. Hepatic arterial and portal venous blood flow was measured in 50 control subjects and 135 patients with colorectal cancer, 67 with overt liver metastases and 68 with an apparently disease-free liver on the basis of computed tomography and laparotomy findings. The Doppler perfusion index (DPI), defined as the ratio of hepatic arterial to total liver blood flow, was calculated. Clear separation of the DPI values of controls and those of patients with overt metastases was observed (P < 0.0001). Thirty-eight of the 68 patients with a disease-free liver also had an abnormally high DPI value. After 1 year of follow-up, 21 patients with an abnormally high DPI at the time of apparently curative primary resection had developed liver metastases and a further four had died without post-mortem examination. The 30 patients with normal DPI remain disease-free. The data suggest that DPI is of value in the early detection of occult liver metastases.

Portal Perfusion Measurement on Dynamic CT in Patients with Liver Cirrhosis

Portal Perfusion Measurement on Dynamic CT in Patients with Liver CirrhosisYoshito Tsushima and Keigo EndoAudio Available | Share

Vascular imaging and interventional procedures in hepatic cirrhosis

Changes in the vascularization of the cirrhotic liver are related to the progression of the disease. Knowledge of normal hepatic vascular anatomy and anatomic is essential for understanding the altered hepatic circulation seen in cirrhosis. We analyze the changes in liver perfusion with special interest in the anatomic features that are important in interventional procedures. The indications, technical notes, and complications of transjugular liver biopsy, transjugular intrahepatic portosystemic shunt (TIPS), and embolization of hepatocellular carcinoma, are reviewed.

Early changes in liver perfusion caused by occult metastases in rats: detection with quantitative CT.

To determine whether computed tomography (CT) can depict liver hemodynamic changes caused by occult hepatic micrometastases in rat. Liver micrometastases (mean diameter, 500 micrometer +/- 300) were produced in seven BD IX rats by injecting 10(7) DHDK12 PROb colorectal carcinoma cells into the spleen. Macrometastases (mean diameter, 7 mm +/- 3) were produced in four other rats. Five normal rats were studied as controls. CT images were obtained every 300 msec for 30 seconds during the injection of 1 mL per kilogram of body weight of contrast medium. The time-attenuation curves of the aorta, portal vein, and liver were used to calculate liver perfusion with a deconvolution model designed for the dual blood supply. Micrometastases in an apparently normal liver caused a 34% decrease in portal blood flow and a 25% increase in the mean transit time for the blood to pass through the liver. These findings suggest increased resistance in the sinusoidal capillaries. Similar but greater changes were found in the macrometastases. Occult liver micrometastases in rats generate changes in liver perfusion that can be detected with CT.

Thermodiffusion for Continuous Quantification of Hepatic Microcirculation—Validation and Potential in Liver Transplantation

Hepatic microcirculation is a main determinant of reperfusion injury and graft quality in liver transplantation. Methods available for the quantification of hepatic microcirculation are indirect, are invasive, or preclude postoperative application. The aim of this study was the validation of thermodiffusion in a new modification allowing long-term use in the clinical setting. In six pigs Doppler flowmeters were positioned around the hepatic artery and portal vein for the measurement of total liver blood flow. Liver perfusion was quantified by thermodiffusion and compared to H2 clearance as an established technique under baseline conditions, during different degrees of portal venous obstruction and during occlusion of the hepatic artery. Thermodiffusion measurements were recorded for five days postoperatively followed by histological evaluation of the hepatic puncture site. Perfusion data obtained by thermodiffusion were significantly correlated to H2 clearance (r = 0.94, P < 0.001) and to liver blood flow (r = 0.9, P < 0.05). The agreement between thermodiffusion and H2 clearance was excellent (mean difference −2.1 ml/100 g/min; limits of agreement −12.5 and 8.3 ml/100 g/min). Occlusion of the portal vein or hepatic artery was immediately detected by thermodiffusion, indicating a decrease of perfusion by 64 ± 7% or 27 ± 5% of baseline, respectively. Perfusion values at baseline and during vascular occlusion were reproducible during the entire observation period. Histological changes of the liver tissue adjacent to the thermodiffusion probes were minute and did not influence long-term measurements. In vivo validation proved that enhanced thermodiffusion is a minimally invasive technique for the continuous, real-time quantification of hepatic microcirculation. Changes in liver perfusion can be safely detected over several days postoperatively. The implication for liver transplantation has led to the clinical application of thermodiffusion.

Acute trauma alters morphine clearance.

Trauma is accompanied by changes in liver perfusion and acute phase proteins. Such changes have the potential to alter drug metabolism. There are few studies describing drug disposition in acute trauma. We determined the pharmacokinetics of an intermediate extraction drug, morphine, in trauma patients. Nine patients with an Injury Severity Score (ISS) > or = 16 were studied within 48 hours of trauma. Morphine 5 mg was given intravenously and serial blood and urine samples were drawn to derive pharmacokinetic parameters. Alpha acid glycoprotein (AAG) levels were determined. Total morphine clearance (CL) and volume of distribution (Vss) were decreased compared to established literature values. Area under the curve (AUC) and terminal half-life (T 1/2 alpha) were increased. AAG levels were higher than reference range. Elimination half-life was increased. The decrease we observed in Vss may be attributed to increased binding of morphine by AAG, which is increased after trauma as in our patients. Decreased clearance and increased half-life of an intermediate extraction drug may be explained by increased protein binding, decreased liver blood flow, and reduced hepatocellular function. Decreased clearance of the magnitude observed in these patients could result in drug accumulation. Better understanding of the effects of trauma on the pharmacokinetics of low, high, and intermediate extraction drugs will prevent excessive or suboptimal drug dosing.

D-Sorbitol plasma disappearance rate: An index to evaluate changes in liver circulation

The hepatic clearance of D-sorbitol was proven to be a reliable parameter for evaluating the functional liver plasma flow. Twenty-five normal subjects and 50 cirrhotic patients were studied in order to assess if the measure of the plasma disappearance rate of sorbitol can be used as a simpler procedure to evaluate changes in liver perfusion and to predict modifications of drug bioavailability due to circulatory events. The plasma disappearance rate was calculated between 10 and 20 min after intravenous administration of a 2-g dose because in this time interval plasma levels were in the optimum range for the chemical assay, and the plasma concentration/time curve fitted a decreasing exponential function. Plasma disappearance rate values were found to correlate significantly (r = 0.666, p less than 0.001) with sorbitol hepatic clearance, as calculated after the 2-h test. The test had a good day-to-day reproducibility both in normal subjects and cirrhotic patients. In 5 patients submitted to surgical side-to-side portacaval shunt, decreases of plasma disappearance rate and sorbitol hepatic clearance showed no significant difference. Mean values (+/- SD) of D-sorbitol plasma disappearance rate were 0.048 +/- 0.014 min-1 in cirrhotic patients, and 0.081 +/- 0.014 min-1 in normal subjects (p less than 0.001).