Eur J Nucl Med (1982) 7:526-527 European M I i r ' , l~,-~r Journal of I ~lUN~,lE;;r._4/

Medicine © Springer-Verlag 1982

Short Communication

Measurement of Hepatic Blood Flow with Diethyl-Ida in Man Comparison with Indocyanine Green

Cristina Mufioz, Laurence Blanchet, and Didier Lebrec Unit~ de Recherches de Physiopathologie H6patique (INSERM), H6pital Beaujon, F-92118 Clichy, France

Abstract. Hepatic blood flow was estimated by the method based on the hepatic clearance. The substances removed by hepatocytes were indocyanine green and 99mTc-diethyl- Ida. Hepatic blood flow was estimated in 3 normal patients and 14 patients with cirrhosis. The mean values of hepatic blood flow did not significantly differ when calculated with indocyanine green or with diethyl-Ida: 1,504 +_ 491 ml/min (mean+SD) and 1,562_+ 525 ml/min, respectively ( P > 0.70). The relatively high extraction of diethyMda in pa- tients with cirrhosis suggests that this substance could be used in patients with reduced liver uptake rate.

Introduction

It is generally admitted that Fick's principle is the best method for estimating hepatic blood flow. In man, this method is largely used with indocyanine green, using clear- ance and extraction of this substance (Caesar et al. 1961). The purpose of the present study was to describe a tech- nique for assessing hepatic blood flow in man using frac- tional clearance and extraction of diethyl-Ida and to compare the results with those obtained with indocyanine green.

Patients and Methods

A series of 14 adult patients with histologically proven cir- rhosis was investigated. These patients were admitted to H6pital Beaujon for an episode of gastrointestinal bleeding due to ruptured esophageal varices. Three other patients with abdominal angina were also investigated.

The hemodynamic investigation was performed after an overnight fast. The patients were placed in a supine position in a vascular catheterism room in the morning. Under local anesthesia, a catheter was introduced through a polypropy- lene sheath (Desilets, Vygon, Ecouen, France) into the lumen of the fight internal jugular vein according to the Seldinger technique. Then, the catheter was advanced into a right hepatic vein under fluoroscopic visualization. Dur-

Offprint requests to: Dr. D. Lebrec

ing this investigation, hepatic blood flow was assessed by the indocyanine green continuous infusion method (Caesar et al. 1961). Peripheral and hepatic venous blood samples were collected 20, 22, 24, 26, 28, and 30 rain after a bolus injection of 6 mg followed by a continuous IV infusion of 0.2 mg/min indocyanine green (Vert d'indocyanine, S.E.R.B., Paris, France). Hepatic blood flow is equal to [ (Q/min) /Cp-Ch)] / ( l -Ht ) , where Q/min is the amount of indocyanine green infused per min, Cp and Ch the plateau concentration of indocyanine green in peripheral and hepatic venous plasma, and Ht the hematocrit. Simulta- neously, fractional hepatic blood flow was estimated using fractional clearance of 99mTc-diethyMda (Laboratoire Solco Nuclear France, Coutras, France). The injected dose was 500 gCi. Blood samples were simultaneously drawn from a peripheral vein and a hepatic vein through the cathe- ter 2, 4, 6, and 8 rain after the injection. Diethyl-Ida activity in the blood samples was counted in a well-type scintillation counter (Nuclear Chicago, Illinois, USA). The activities. were expressed in cpm per ml blood. Hepatic blood flow (HBF) was estimated from diethyl-Ida fractional clearance (K), and from the extraction (E) of this substance using the equation: HBF = K-V/E, where V is total blood volume, as determined from an injection of 5 gCi albumin labeled with 125I following hepatic blood flow estimation. K was calculated by the method of least squares and E was calcu- lated according to the formula: (Cp-Ch) /Cp, with Cp and Ch being the 99mTc-diethyl-Ida activities in peripheral and hepatic blood samples.

The Student's t test for dependent data was used for statistical comparisons.

Results

The values for the fractional clearance and extraction of diethyl-Ida, the clearance and extraction of indocyanine green, and hepatic blood flow estimated either with diethyl- Ida or indocyanine green are set out in Table 1. Hepatic extraction of diethyl-Ida was higher than hepatic extraction of indocyanine green in all patients. The mean value for diethyl-Ida extraction was significantly higher than the mean value of indocyanine green extraction in patients with cirrhosis. The mean value for hepatic blood flow did not significantly differ when calculated with diethyMda or with indocyanine green (Table 1).

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Table 1. lndocyanine green and diethyl-Ida clearance and extraction and hepatic blood flow in 14 patients with cirrhosis and in 3 patients without liver disease

527

Patients with cirrhosis

Indocyanine green Diethyl-Ida

Clearance Extraction Hepatic Fractional Extraction Hepatic blood flow clearance blood flow

(ml/min) (%) (ml/min) (min - 1) (%) (ml/min)

1 101 9.7 1,581 0.100 26.3 1,780 2 147 12.0 1,008 0.134 34.5 1,955 3 125 12.0 1,679 0.145 30.3 1,873 4 132 13.0 1,541 0.111 26.9 1,730 5 226 13.3 2,780 0.098 18.7 2,941 6 133 15.2 1,384 0.084 25.3 1,399 7 157 18.5 1,220 0.109 62.2 1,188 8 223 19.0 1,459 0.256 61.0 1,653 9 125 20.2 1,069 0.080 31.0 1,013

10 214 25.6 1,254 0.188 48.0 1,332 11 171 26.7 889 0.113 51.9 1,025 12 196 36.0 850 0.099 53.3 699 13 518 36.5 2,040 0.160 50.0 1,808 14 342 43.2 1,366 0.188 69.7 1,479 Mean_+SD 201+106 21.5_+10.2 1,504_+491 0.133_+0.048 42.1_+15.7 ~ 1,562_+525 b

without liver disease

1 324 41.7 1,272 0.276 72.0 1,505 2 304 44.1 1,190 0.252 87.1 1,168 3 267 49.0 1,211 0.315 83.5 1,481

a Significantly different from the indocyanine green extraction (P < 0.001) b Not significantly different from the mean value of hepatic blood flow estimated by indocyanine green

(P > 0.70)

Discussion

Hepat ic b lood flow can be assessed by several different methods. The me thod that is the most commonly used in man is based on the measurement of b lood clearance and removal efficiency of a substance taken up by the liver. The validi ty of this hepatic clearance method depends upon several assumptions (Bradley et al. 1945); these assump- tions appear to be valid for diethyl-Ida. In part icular , this substance, largely used to visualize the hepatobi l iary tree (Wistow et al. 1977; Pauwels et al. 1980), is removed from the b lood almost exclusively by the liver. Howmeer, the mechanism by which d ie thyMda is removed by hepatocytes is not well established (Joshi et al. 1981). In patients with liver disease, it has been demonst ra ted that die thyl-Ida un- dergoes minimal extract ion by the kidneys (Gelius et al. 1981). In fact, this extrahepat ic removal is very small in the first 10 rain after the injection of the substance (Gelius et al. 1981) and therefore can be est imated to be negligible.

In the present study, the values of hepatic b lood flow est imated with d i e thyMda are similar to those obta ined with indocyanine green which is the substance usually used to estimate hepatic b lood flow (Caesar et al. 1961). These results were found both in normal and in patients with cirrhosis.

The clearance method to est imate hepatic b lood flow is known to be less sat isfactory in patients with low removal efficiency; in this case, hepat ic b lood flow could be overesti- mated. This s tudy shows that the mean value o f extract ion of die thyl-Ida is twice that of extract ion of indocyanine

green. In other words, in patients with liver disease or with hepatic dysfunction, and in whom indocyanine green ex- t ract ion is too low for calculat ion of b lood flow, diethyl-Ida could be a useful substitute.

Acknowledgements. We thank Dr. G. Tissier from Laboratoire Solco-Nuclear-France for providing diethyl-Ida.

References

Bradley SE, Ingelfinger F J, Bradley GP, Curry JJ (1945) The esti- mation of hepatic blood flow in man. J Clin Invest 24 : 890-897

Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S (1961) The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 21:43-57

Gelius L, Skreting A, Aas M (1981) A mathematical model for the liver uptake and excretion of 99Tc-diethyl-Ida. Eur J Nucl Med 6:139-142

Joshi SN, George EA, Perillo RP (1981) Quantitative temporal analysis of 99mtechnetium-p-isopropyl-iminodiacetic acid (PIPIDA) as a measure of hepatic function in health and dis- ease. Gastroenterology 81 : 1045-1051

Pauwels S, Piret L, Schontens A, Vandermoten G, Beckers C (1980) Tc-99m-diethyl-Ida imaging: clinical evaluation in jaundiced patients. JNM 21 : 1022-1028

Wistow BW, Subramanian G, Van Hertum RL, Henderson RW, Gagne GM, Hall RC, McAfee JG (1977) An evaluation of 99'~Tc-labeled hepatobiliary agents. JNM 18:455~461

Received June 7, 1982