Measurement Of Liver Blood Flow Research Articles

Assessment of Global Liver Blood Flow With Quantitative Dynamic Contrast-Enhanced Ultrasound

This study assessed the potential of quantitative analysis of contrast bolus kinetics to reflect global liver blood flow. A dynamic contrast-enhanced ultrasound flow phantom was developed. A peristaltic pump established constant volume flow ranging between 16.5 and 49.5 mL/min (2-mm tube) and 85.5 and 256.5 mL/min (5-mm tube). After bolus injection of 2 doses of a contrast agent, a region of interest was drawn over the cross section of the tube used for a particular acquisition; the rise time, peak intensity, and wash-in slope were derived from time-intensity curves. Twenty healthy volunteers and 25 patients with biopsy-proven colorectal liver metastases were scanned with dynamic contrast-enhanced ultrasound. The rise time, peak intensity, and wash-in slope were derived from hepatic artery and portal vein time-intensity curves. Hepatic artery/portal vein ratios of the parameters were also calculated. In the in vitro experiment, the rise time decreased while the peak intensity and wash-in slope increased with increasing volume flow for both tube diameters and contrast bolus volumes. In the clinical study, the rise time was lowered in the hepatic artery but elevated in the portal vein, and the peak intensity and wash-in slope were elevated in the hepatic artery but lowered in the portal vein in patients with colorectal liver metastases compared with healthy volunteers, although not in a statistically significant manner. This finding was consistent with an increase in hepatic artery blood flow, a decrease in portal vein blood flow, or both in patients with colorectal liver metastases compared with healthy volunteers. Only the 3 hepatic artery/portal vein ratios of the parameters achieved statistical significance in differentiating healthy volunteers from patients with colorectal liver metastases (P < .05). Surrogate measurements of liver blood flow may be derived from quantitative analysis of dynamic contrast-enhanced ultrasound studies. They may have potential for quick and easy assessment of altered hepatic hemodynamics.

A comparison of xenon-133 clearance with electromagnetic flowmeters and an indicator dilution method for the measurement of liver blood flow

Measurement of liver blood flow has been carried out by three different methods in 14 dogs to assess the accuracy of xenon-133 clearance following portal vein injection. Electromagnetic flowmetry with flow probes on the hepatic artery and portal vein resulted in a mean value of 121.9 +/- 39.3 ml min-1 100 g-1. An indicator dilution study utilizing chromium-51-labelled red cells gave a mean value of 119.4 +/- 31.4 ml min-1 100 g-1 and the xenon-133 clearance following portal vein injection, 120.3 +/- 33.8 ml min-1 100 g-1. One-way analysis of variance showed no statistically significant variation between these three groups. There was a close correlation between xenon-133 clearance and electromagnetic flowmetry and between xenon-133 clearance and the indicator dilution technique. These data suggest that xenon-133 clearance following portal vein injection gives an accurate assessment of liver blood flow and this technique (as well as direct parenchymal injection) can be adapted for clinical use.

An isotope clearance method for measurement of liver blood flow during portasystemic shunt in man.

The clearance from the surface of the liver of krypton 85 following its injection into the portal vein was measured in 10 patients. Six control patients (i.e. those not suffering from portal hypertension) averaged flow values of 142 ml per 100 g liver weight per min. A repeat flow estimation in these patients was not significantly different. Four patients with portal hypertension were studied. In 2 with congenital hepatic fibrosis the portal vein was temporarily occluded to allow prediction of the degree of hepatic perfusion likely to be achieved by the hepatic artery alone after portal deviation. The flow after portal venous clamping was unaffected in one of these cases but reduced by 45 per cent in the other. In a patient undergoing a Warren distal splenorenal shunt there was no change in flow after the procedure. If measurements are performed before and during temporary portal vein occlusion, an assessment of the flow reduction to be expected after a shunt procedure can be made. We suggest that a knowledge of liver tissue perfusion might influence the choice of operative procedure.

A priori identifiability of a one-compartment model with two input functions for liver blood flow measurements

An extended dual-input Kety–Schmidt model can be applied to positron emission tomography data for the quantification of local arterial (fa) and local portal-venous blood flow (fp) in the liver by freely diffusible tracers (e.g., [15O]H2O). We investigated the a priori identifiability of the three-parameter model (fa, fp and distribution volume (Vd)) under ideal (noise-free) conditions. The results indicate that the full identifiability of the model depends on the form of the portal-venous input function (cp(t)), which is assumed to be a sum of m exponentials convolved with the arterial input function (ca(t)). When m ⩾ 2, all three-model parameters are uniquely identifiable. For m = 1 identifiability of fp fails if cp(t) coincides with tissue concentration (q(t)/Vd), which occurs if cp(t) is generated from an intestinal compartment with transit time Vd/fa. Any portal input, fp cp(t), is balanced by the portal contribution, fp q(t)/Vd, to the liver efflux, leaving q(t) unchanged by fp and only fa and Vd are a priori uniquely identifiable. An extension to this condition of unidentifiability is obtained if we leave the assumption of a generating intestinal compartment system and allow for an arbitrary proportionality constant between cp(t) and q(t). In this case, only fa remains a priori uniquely identifiable. These findings provide important insights into the behaviour and identifiability of the model applied to the unique liver environment.

The measurement of liver blood flow: a review of experimental and clinical methods

Changes in hepatic blood flow reflect adaptive responses of the liver to injury, regeneration, and the development of disease states. The measurement of hepatic blood flow is, however, technically challenging and although theoretically useful has not become routine in clinical work. The different techniques that have been developed for quantitative measurement of hepatic blood flow require careful interpretation of the results obtained but are frequently applied without careful considerations of their technical limitations. In particular, many noninvasive techniques depend on good hepatocellular function and are thus irrelevant under most clinical conditions. Many other potentially useful techniques are poorly validated and standardized and there is a need for further research into smethodology. This review summarizes the salient technical features of the different techniques for quantitative measurement of hepatic blood flow. The techniques are divided into invasive, minimally invasive, and noninvasive categories and the relevance of each technique to both routine clinical application or research is discussed.

Hepatic arterial blood flow in large hepatocellular carcinoma with or without portal vein thrombosis: assessment by transcutaneous duplex Doppler sonography.

As liver cirrhosis progresses, the portal venous blood (PVBF) flow decreases, accompanied by an increase in hepatic arterial blood flow. Large hepatocellular carcinoma is a hypervascular tumour with a rapid growth, which seems to require an increase of the tumoral arterial blood flow. Furthermore, hepatocellular carcinoma is frequently associated with portal vein thrombosis, which subsequently impedes portal blood supply. The purpose of our study was to estimate alterations in the hepatic arterial blood flow in large hepatocellular carcinomas occurring in liver cirrhosis, in comparison with liver cirrhosis and controls. Liver blood flow measurements were determined by duplex Doppler sonography in 47 patients with large hepatocellular carcinomas (13 with portal vein thrombosis and 34 without this thrombosis), 42 liver cirrhosis patients and 30 controls. The Doppler perfusion index was calculated as the ratio of hepatic arterial blood flow to total hepatic blood flow. The patients with liver cirrhosis had a significant increase of hepatic arterial blood flow as compared to controls (P < 0.001), accompanied by a significant reduction in PVBF (P < 0.005). As a result, the Doppler perfusion index was increased in patients with liver cirrhosis as compared to controls (P < 0.001). The hepatic arterial blood flow was increased in patients with hepatocellular carcinoma but without portal vein thrombosis as compared to the cirrhotic patients (P < 0.001), with a significant reduction of PVBF (P < 0.001). Hepatic arterial blood flow was also increased in patients with both hepatocellular carcinoma and portal vein thrombosis as compared to the patients without this thrombosis (P < 0.001). These results suggest that in large hepatocellular carcinomas there is a decreased PVBF, accompanied by an increased hepatic arterial blood flow. The hepatic arterial buffer response seems to be active in hepatocellular carcinomas and maintains liver perfusion to adequate levels.

Is it feasible to monitor total hepatic blood flow by use of transesophageal echography? An experimental study in pigs.

Total hepatic venous blood flow is determined by the common hepatic arterial blood flow and the venous outflow from stomach, spleen, pancreas, small intestine, and bowel, collected by the portal vein, and thus represents overall splanchnic perfusion. We investigated whether transesophageal echography (TEE) can provide a method for bedside assessment of hepatic venous blood flow useful as a noninvasive method for measuring splanchnic perfusion in clinical practice. Experimental study in 15 anesthetized and ventilated pigs in an animal research laboratory. TEE-derived calculations of hepatic venous blood flow were compared with liver blood flow measurements using perivascular ultrasound flow probes surgically positioned on portal vein and common hepatic artery. Parameters were determined at baseline and after modulating splanchnic perfusion by either PEEP maneuver (15 cmH2O) or intravenous epinephrine (0.1 microgram kg-1 min-1). Diameter (d) and velocity time integral (VTI) of all three hepatic veins were determined by TEE, heart rate (HR) was derived from electrocardiography and flow subsequently calculated as Q = pi.(d/2)(2).0.57.VTI.HR. Regression analysis of matched TEE and flow probe values showed a significant linear relationship (r2 = 0.698). Bias analysis revealed a systematic underestimation of liver blood flow by TEE, possibly due to use of 0.57 as correction factor for mean velocity, while changes in liver blood flow were reliably detected. TEE offers a noninvasive approach for monitoring hepatic perfusion and may be used in patients.

Hepatic blood flow changes in chronic hepatitis C measured by duplex Doppler color sonography: relationship to histological features.

Our aim was to determine if portal vein and hepatic artery blood flow indices are a noninvasive index of severity of liver disease in chronic hepatitis C. The effect of interferon-alpha treatment on liver blood flow was also studied. Liver blood flow measurements were recorded by duplex Doppler color sonography in 39 patients with chronic hepatitis C, 50 healthy controls, and a single patient with hepatocellular carcinoma. Doppler perfusion index (DPI) (calculated as the ratio of hepatic artery flow to total hepatic flow) and the congestive index of the portal vein (area/velocity) were calculated. Liver biopsies were scored for hepatic inflammation and fibrosis. Hepatic arterial flow (415.7+/-329.1 ml/min vs 195.1+/-103.5 ml/min) and DPI (0.27+/-0.14 vs. 0.17+/-0.06) were elevated in chronic hepatitis C patients compared to controls (P = 0.0002 and 0.0003, respectively) while portal vein flow and total hepatic flow were similar. Portal vein congestive index was similar in chronic hepatitis C (0.106+/-0.05) compared to controls (0.125+/-0.08) P 0.52. Hepatic blood flow indices were not related to the grade of hepatic inflammation or the stage of hepatic fibrosis. Twelve weeks of treatment with interferon-alpha had no effect on liver blood flow. In conclusion, patients with chronic hepatitis C have elevated hepatic artery blood flow. Hepatic blood flow indices have no relationship to the severity of histological liver injury in chronic hepatitis C, and these flow indices are unaffected by a 12-week course of interferon-alpha.

Liver metastases from colorectal carcinoma: detection with Doppler US-guided measurements of liver blood flow--past, present, future.

HomeRadiologyVol. 195, No. 1 PreviousNext Liver metastases from colorectal carcinoma: detection with Doppler US-guided measurements of liver blood flow--past, present, future.W P ShumanW P ShumanW P ShumanPublished Online:Apr 1 1995https://doi.org/10.1148/radiology.195.1.7892500MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Article HistoryPublished in print: 1995 FiguresReferencesRelatedDetailsCited ByEuropean Journal of Nuclear Medicine and Molecular Imaging, Vol. 39, No. 10World Journal of Surgery, Vol. 29, No. 6Journal of Ultrasound in Medicine, Vol. 24, No. 7Clinics in Liver Disease, Vol. 6, No. 1, Vol. 109Radiologic Clinics of North America, Vol. 36, No. 2Surgical Oncology, Vol. 6, No. 1Recommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 195, No. 1 Metrics Altmetric Score PDF download

Flow measurement using duplex Doppler ultrasound: haemodynamic changes in patients with colorectal liver metastases.

Duplex Doppler ultrasound has been used to make measurements of liver blood flow. The relationship between time average velocity as measured using pulsed Doppler and the true mean velocity was determined using a flow phantom. Correction factors were applied to measured time average velocities of blood in the hepatic artery and portal vein. Blood flow was calculated from the product of corrected velocities and the cross-sectional area of the vessels. There was no significant difference in total liver blood flow for patients with colorectal liver metastases when compared with controls. However, the ratio of the hepatic arterial flow to the sum of the portal and hepatic arterial flows (Doppler perfusion index, DPI) was markedly elevated (P < 0.0001) in the patients with metastases when compared with the controls. The DPI values for a third group of subjects who had undergone resection for colonic cancer but who had no proven liver metastases overlapped the values for the other two groups. When attention is paid to technique, the procedure can detect and quantify the changes in liver blood flow which occur in the presence of metastases.

Experimental and clinical evaluation of capsular and parenchymal total liver perfusion. Liver microcirculation.

Liver blood flow measurements obtained from both the liver surface and deep within the parenchyma, were correlated in an effort to assess the usefulness of laser-Doppler flowmetry for non-invasive monitoring of total liver blood flow, the probe being positioned on either the surface or within the liver parenchyma. In 23 Wistar rats and 10 biliary surgery patients, anaesthetized prior to gallbladder removal, liver microcirculation was measured at 4 points on the capsular surface, and consequently at 4 points deep within the parenchyma, using probes connected to a laser-Doppler flowmeter. The findings revealed that laser-Doppler measurements on the liver surface and within the parenchyma were well correlated, as no statistically significant differences were found either in rats or humans. It is concluded that laser- Doppler flowmetry for monitoring of total liver perfusion can be applied either on the capsular surface or within the hepatic parenchyma.

Detection of Hepatic Metastases Using Duplex/Color Doppler Sonography

Current imaging modalities are unable to detect small liver metastases because of limited resolution and contrast differentiation. The association between liver metastases and altered liver blood flow has been demonstrated by dynamic scintigraphy, but the clinical feasibility of this test has been questioned. In this study a novel approach to detecting liver metastases was assessed by measurement of liver blood flow using a duplex/color Doppler System. Hepatic arterial and portal venous blood flows were measured in 16 controls, 50 patients with gastrointestinal cancer, and 6 patients with breast cancer. The ratio of hepatic arterial to total liver blood flow (Doppler perfusion index, DPI) and the ratio of hepatic arterial: portal venous blood flow (Doppler flow ratio, DFR) were calculated. The DPI and DFR values of controls and patients with overt liver metastases were clearly separated (p less than 0.0001). The results suggest that duplex/color Doppler ultrasound measurement of hepatic perfusion changes may be of value in the detection of liver metastases.

Galactose clearance measurements and liver blood flow

Galactose clearance, measured during low galactose infusion and calculated as infusion rate divided by peripheral galactose concentration (systemic clearance), has been proposed as a measure of liver blood flow. This requires nearly complete hepatic extraction as well as negligible extrahepatic elimination. The purpose of the study was to examine if these assumptions are fulfilled in subjects with no liver disease, and to compare the galactose clearance measurement with an independent measurement of liver blood flow. Liver blood flow was measured in 6 subjects by means of a constant indocyanine green infusion, indocyanine green concentration measurements in a peripheral artery and a hepatic vein, and calculation according to Fick's principle. The mean (± SEM) blood flow rate was 1.2 ± 0.1 L/min. Galactose was given at a constant infusion rate of 142 ± 10 μmmol/min, and steady-state concentrations were measured in the peripheral artery (A) and the hepatic vein (V). The hepatic extraction fraction [(A − V)/A] was 0.91 ± 0.03. The hepatic galactose elimination rate [(A − V) × flow] was 101 ± 12 μmol/min; this is about two-thirds of the total elimination rate (viz., infusion rate). Urinary excretion was negligible. This indicates an extrahepatic galactose elimination of ~41 μmmol/ min. Systemic galactose clearance, calculated as mentioned above, was 1.5 ± 0.1 L blood/min. It was significantly higher than the liver blood flow in each subject (paired t-test, each p < 0.02), on average 133% of the flow. Thus the systemic galactose clearance value overestimates liver blood flow, probably due to a small, but in this context quantitatively important, extrahepatic galactose elimination.

Comparison of bolus and infusion methods for estimating hepatic blood flow in patients with liver disease using indocyanine green

A non-invasive method of estimating liver blood flow by a two-compartment pharmacokinetic model of the plasma clearance of indocyanine green has been previously described in normal animals and patients without liver disease. This non-invasive technique has been compared with the conventional method of measuring liver blood flow by hepatic vein catheterisation in 25 patients with liver disease. There was good correlation between the values for indocyanine green clearance, with the infusion method tending to produce slightly higher results. However, there was poor agreement in the measurement of liver blood flow, as the non-invasive technique over-estimated the hepatic extraction ratio and thus underestimated liver blood flow. Therefore, in patients with liver disease the non-invasive method cannot be relied upon or replace hepatic vein catheterisation for the measurement of liver blood flow.

Liver blood flow measured by indocyanine green in conscious unrestrained miniature pigs.

For studies in physiology and biochemistry of the liver the measurement of hepatic blood flow is a fundamental precondition. Therefore, the least invasive method, the measurement of liver blood flow by indocyanine green (ICG) dye elimination, was re-evaluated for the miniature pig, an animal model of increasing interest. The accuracy of spectrophotometric determination of ICG was enhanced by addition of 5% of desoxycholic acid. It was shown that ICG was eliminated exclusively by the liver. An extraction rate of 30%-50% was found in mini-pigs, but an insufficient rate of 5%-10% in pigs of German landrace. A liver blood flow ranging from 70 to 160 ml/100 g X min-1 was measured. These values are in good accordance with datas from simultaneous estimation of blood flow by 133Xenon washout. As shown for a starvation/refeeding cycle, liver blood flow measurement by ICG combined with permanently implanted catheters is a practicable tool for studies of the metabolic and pharmacologic fate of substances resorbed from the gut.

A modification of the 133Xe inhalation method for the measurement of liver blood flow in man.

The 133Xe inhalation technique for liver blood flow measurements was modified by using a gamma camera for data acquisition. Desaturation curves were derived from regions of interest (ROIs) over different parts of the liver, the lung and that lung area overlapping the liver, the liver hilus, and the splanchnic area. An additional liver scan with 99mTc-sulfur colloid facilitated the choice of these regions and allowed the estimation of the total liver volume. Thirteen healthy volunteers were examined under baseline conditions. Uncorrected blood flow values derived from the 133Xe-washout curves over the liver (40 +/- 10 ml/min/100 g liver) were lower than those found with other methods. A multicompartment model, based on the input functions calculated from the lung and splanchnic curves, gave values in accordance with those reported in the literature (94 +/- 20 ml/min/100 g or 1,356 +/- 382 ml/min/liver; mean liver volume: 1,475 +/- 227 g). Some methodologic limitations are shared with other invasive or noninvasive techniques.

CHANGES IN LIVER BLOOD FLOW WITH DEVELOPMENT OF BILIARY OBSTRUCTION IN THE RAT

As well as causing retention of biliary secretory products, bile duct obstruction is associated with other hepatic and systemic effects which are poorly understood. These latter changes contribute to the increased morbidity and mortality associated with surgery for biliary obstruction. This study examines the changes in liver blood flow occurring after common bile duct (CBD) ligation in the belief that relative hepatic ischaemia may contribute to dysfunction. A new method for measuring liver blood flow (LBF) based on the clearance of 133Xe from the liver following injection into the portal vein is described. With this new development, serial measurements of LBF can be performed in the conscious, unfasted rat. With the development of jaundice, a highly significant reduction in LBF is seen which is first evident 36 hours after CBD ligation. By the third day after ligation, LBF is only 54% of the control value. No fall in LBF is seen in rats subjected to sham ligation. The mechanism for the reduction in LBF is uncertain, but the delayed onset makes any relfex autonomic reaction unlikely.

Methods of the assessment of the effect of drugs on liver blood flow in man.

The liver is the central metabolic organ of the body and therefore the volume and the composition of the blood perfusing the liver are undoubtedly major determinants of hepatocellular function. In the past the amount of liver blood flow and its regulation was mainly investigated by physiologists and most of the work was done in animals (Bradley, 1963; Greenway and Stark, 1971). In recent years clinicians and pharmacologists have paid more attention to the problem of liver blood flow measurements as it was found that drug metabolism can be influenced by changes in liver blood flow under certain experimental conditions (Ohnhaus, Thorgeirsson, Davies and Breckenridge, 1971; Branch, Shand, Wilkinson and Nies, 1974). Based on these findings a physiological approach to hepatic drug clearance has been developed which seems very useful in predicting changes in drug kinetics produced by variations in the biological determinants of drug disposition (Wilkinson, 1975; Wilkinson and Shand, 1975). In addition, as surgeons started to treat portal hypertension occurring in liver disease such as cirrhosis by portocaval or similar anastomoses, liver blood flow was assessed with other parameters of liver function to select appropriate patients for surgery (Bircher, Blankart, Halpern, Hacki, Laissue and Preisig, 1973). These facts have increased tremendously the interest of clinical pharmacologists and clinicians in the methods for liver blood flow measurement and their limitations in order to investigate changes in drug metabolism under certain clinical and experimental conditions and the clinical outcome of liver disease following different operating procedures.

Measurement of liver blood flow in the dog using krypton-85 clearance: A comparison with electromagnetic flowmeter measurements

Blood flow in the superficial liver tissue was measured by recording the clearance rate of the β emissions of 85Kr following its injection into the portal vein. The flow values calculated from monoexponential clearance curves were compared to portal venous blood flow simultaneously recorded with a calibrated electromagnetic flow probe in six dogs whose hepatic artery had been ligated. The liver: blood partition coefficient of 85Kr was measured in these dogs and was found to be 0.91. There was a close correlation ( r = 0.95) between the blood flow values obtained from the two techniques over a wide range of flow values. This shows that measurement of liver blood flow in the surface layers of the liver using the 85Kr clearance method provides a true reflection of the blood flow in the liver tissue as a whole.

Measurement of liver blood flow by means of a single injection of bromosulphthalein, without hepatic venous catheterization.

1. A method is described for the measurement of liver blood flow without hepatic venous catheterization by the injection of the a single dose of bromosulphthalein and the analysis of the graph of the plasma disappearance of the indicator. 2. The rationale of the method was tested in three systems which covered a wide range of flow rates. The first system was a physical model with a haemodialyser in which the calculated flow could be compared with the flow measured directly. The second was in anesthetized dogs, in which the calculated flow was compared with that measured by continuous infusion and hepatic venous catheterization, based on the Fick principle. The third system was in unanaesthetized turkeys, in which metabolism of bromosulphthalein does not occur. The calculated flow was compared with the flow measured simultaneously by the uptake of collodial particles by the Kupffer cells. 3. In all three systems the correspondence between the two methods of measuring liver blood flow was good, the differences between them being not statistically significant. 4. The method has been applied to measurements of liver blood flow in man and animals and gives results comparable with those reported by other workers.