JOURNAL OF NUCLEAR MEDICINE 5: , 1964

Transcription

1 JOURNAL OF NUCLEAR MEDICINE 5: , 1964 The Use of Radioactive Isotopes to Study the Hemodynamic Pattern, Function and Morphology of the Liver in Hepato-Splenic Bilharziasis ( Schistosomiasis )â Muhammad Abdel Razzak, M.D.23 Bilharziasis, which is endemic in our country, is famous for its hepato-splenic affection. The disease is caused by an intravascular parasite that inhabits the portal venous system, leading to hepatic fibrosis, portal hypertension and very late involvement of the liver parenchyma. The aim of this work is to apply radioisotopic techniques for the study of the hemodynamic pattern, function and morphology of the liver in hepato-sple@ic bilharziasis; a syndrome that is commonly met with among our Egyptian peasants. MATERIALS AND METHODS The present work deals with the findings obtained in a group of 60 patients suffering from hepato-splenic bilharziasis and representing different grades of this disease (Table I). The first grade is preclinical, asymptomatic, with slight enlargment of spleen and/or liver and having history or evidence of bilharzial infection. In the second grade, there is definite enlargment of the liver and spleen. The third grade is characterized by the presence of oesophogeal varices indi cating the appearance of portal hypertension. In the fourth grade, ascites is de tectable with or without varices. The diagnosis in these cases was made on clin ical grounds, helped by liver biopsy, liver function tests, examination of excreta for bilharzia ova, full blood picture and barium swallow for evidence of oesopho geal varices. ithis work was partly presented at the Tenth Annual Meeting, Society of Nuclear Medi chic, June 27, 1963, Montreal, Canada. 2Medical Unit and Section of Nuclear Medicine, Faculty of Medicine, Cairo University. 3Medical Unit of Atomic Energy Establishment, U.A.R. 125

2 126 MUHAMMAD ABDELRAZZAK The tests that were performed during this study were: ( 1 ) Hepatic uptake of radioactive colloidal gold' Au'Â 8 (1) and rose bengal tagged1 with 1131 using 20 microcuries of each. ( 2) Modified cardioportal circulation time using 10 microcuries of human serum albumin tagged' with 1131 (2). (3) Photoscanning of the liver using 200 microcuries of radiogold' (3). CALCULATIONS For estimation of hepatic blood flow, the disappearance hall-time for radio gold is calculated from the hepatic uptake tracing ( Fig. 1 ). Then the clearance rate constant ( K) is obtained by dividing by the disappearance half-time. Finally, ( K ) is multiplied by the total blood volume to give the hepatic blood flow ( HBF ). In the present work, the clearance rate constant will be expressed as percentage of total blood volume that passes through the liver per minute. It is well known that hepatic uptake of trace amounts of radiogold de pends primarily on the hepatic blood flow, while that of radioactive rose bengal depends on both the blood flow and the integrity of liver cells. Therefore, con sideration of the disappearance half-time of radiogold (TX C) and rose bengal (TXR.B), together with the removal efficiency of rose bengal that is obtained by calculating the ratio between these two disappearance half-times (TX C : TX R.B) will enable differentiation of combinations of normal or decreased hepatic blood flow with normal or impaired liver cell function (4). 1Different lots of radioisotopes were used, and were obtained from Amersham (U.K.) and Atomic Energy Establishment (U.A.R.) TABLE I THE CLINIco-I@DIoLoGIc BASIS USED FOR THE CLASSIFICATION OF CASES OF HEPATO-SPLENIC BIUIARzIAsIs INTO 4 GRADES. GradeNumber scites1 of casesspleenliveroesophogcal II III IV or to++++ â to or++ +or â - - Present. Present or (@Absent.- - â Present. â : not palpable (spleen), shrunken (liver), absent (ascites and varices). +: 1 to 2 fingers breadth below costal margin in midclavicular plane. ++: 2 to4 fingers. +++: down to umbilicus : lowerpoleofspleenfeltbelowumbilicus.

3 USE OF ISOTOPES IN THE STUDY OF LIVER 127 The cardioportal circulation time ( CPCT) begins from the peak of activity over the left heart in a radiocardiographic tracing and ends when radioactivity reaches a peak over the liver in a simultaneously drawn uptake curve. RESULTS Patients from first grade hepato-splenic bilharziasis had normal disappear ance half-times for both radiogold and rose bengal; mean TX C being 3.2 ±0.6 minutes and that for rose bengal 6.1 ±0.5 minutes, with a removal efficiency of rose bengal of 0.52 ±0.1. In this group the clearance rate constant for radiogold was 22 per cent ( Table II ). In contradistinction, from the second grade onwards, the disappearance half-times were usually longer than normal, and consequently the clearance rate constants were smaller than normal. In the 14 patients repre senting grade II, TX C amounted to 4.0 ±0.8 minutes, and TX R.B was 8.9 ±2.7 minutes, with a removal efficiency of rose bengal of 0.44 ±0.1. These patients had a clearance rate constant for radiogold of 17 per cent. In grade III cases, the average TX C was 7.0 minutes, TX R.B being 15.7 minutes, with a removal efficiency of rose bengal of 0.44 ±0.1. The clearance rate constant of radiogold in these patients was 10 per cent. Lastly, the disappearance half-times for subjects having ascites were 6.8 and 21.5 minutes for gold and rose bengal respectively. Thus, the removal efficiency for rose bengal was 0.32 ±0.1 and the clearance rate constant for gold was 10 per cent. id 7 Mean of 20 Normals. Hepaic uptake. U3 I @ i6' 1@ 26 Minutes after Fig.1.The mean curveforhepaticuptakeof colloidalgold Au198 in 20 normal subjects. Dose used was 20 microcuries. The value of (K) is calculated by substraction of the original curve C 00 (1 â ekt) from the activity level reached in infinite time C 00,thusconvertingtheintegralcurveintoa ratecurveof accumulationc ekt. The value of (K) = O.639/T112.

4 128 MUHAMMAD ABDEL RAZZAK The cardioportal circulation time was measured in 25 of the bilharzial sub jects included in the present study (Table III ). In grade I, CPCT was within normal limits, ranging between 20 and 32 seconds, with an average of 26 ±7 see onds ( Mean ± 1 S.D. ). Cases from the second and third grades usually had prolonged CPCT, amounting to 33 ±7 and 29 ±9 seconds in the two groups respectively. The results in patients having ascites were variable, being either nor mal, prolonged or shorter than normal. In this particular group, CPCT ranged between 16 and 35 seconds, with an average of 24 ±7 seconds. Photoscanning of the liver was performed on 10 bilharzial patients using radioactive colloidal gold (Table IV). The scan was completely normal in pa tients from grade I. Grade II cases showed slight diminution in the intensity of the scan picture together with some mottling. These effects were much more marked in grade III (Fig. 2). Lastly, in patients from fourth grade these changes were still more marked and diminution in the size of the liver was noticed. All figures in this section are Mean ±1 S.D. DISCUSSION Razzak and Wagner (5) concluded that in normal subjects, serial blood sam pling was better than external measurement of hepatic radioactivity for the de termination of hepatic blood flow using radiogold. This was because with serial blood sampling, the clearance of gold exhibit an exponential function with time (Fig. 3), allowing accurate calculation of the clearance rate constant, which could be multiplied by the total blood volume to get the hepatic blood flow. Un fortunately, when this method of serial blood sampling was applied to cases of bilharzial hepatic fibrosis, radiogold disappearance was found to be a complex I Fig. 2. Radioisotope photoscan of a patient from grade III hepatosplenic bilharziasis.

5 USE OF ISOTOPES IN THE STUDY OF LIVER 129 exponential function of time. Thus losing its advantage over the easier and less harmful external techniques. Therefore, it was decided to use methods based on surface counting in estimation of hepatic blood flow in hepato-splenic bil harziasis. In earlier experiments of this work, disappearance rate constant was calculated from a hepatic uptake tracing (Fig. 1 ) and a radioactivity clearance curve ( Fig. 4). These were obtained by the simultanous application of two col limated detectors; one over the right eighth intercostal space in the midaxillary line and the other centered over the temple. In normal subjects, the disappear ance half-time was nearly the same when calculated by both methods. On the other hand, in bilharzial hepatic fibrosis TX hepatic uptake was usually greater than that obtained from the simultanously drawn clearance curve specially in the presence of huge splenic enlargment. This is to be expected from consideration of the pathology of the bilharzial spleen which is characterized by reticular TABLE II THE DISAPPEARANCE HALF-TIMES FOR COLLOIDAL RADIOGOLD (T112 C) AND RADIOACTIVE ROSE BENGAL (T112 R.B), REMOVAL EFFICIENCY FOR ROSE BENGAL (R@@TIo BETWEEN T112 G AND T,12 R.B) AND DISAPPEARANCE RATE CONSTANT OF Au'98 (K) IN BILHARZIASIS. Type and number of bengalgradel casest,12 G (minutes)t11, R.B (minutes)removal efficiency of K rose 0.122%Range2.6â ± ± 9 casesmean3.2â± 26.6Gradell â â 0.69@ 15.8â 0.117%Range3.0â 14 casesmean4.0â± 23.1Grade ± ± â â â Ill 110%â ± casesmean Grade Range3.0â â â â IV 25casesMean ± 0.110% Range3.2â â â â Normals 20 CasesMean3. 1 ± ± ± % Range2.0â â â â 34.7 Meaii values are Mean ±1 S.D.

6 130 MUHAMMAD ABDEL RAZZAK hyperplasia and very marked engorgement of sinusoids (6), thus enabling the bilharzial spleen to capture and retain a good amount of the injected radioactivity. Therefore, we relied on the hepatic uptake technique for the determination of hepatic blood flow in this study of hepato-splenic bilharziasis. From the results of the present work, it can be seen that the percentage of total blood volume passing through the liver per minute was within normal limits in first grade cases, and usually diminished in other grades of hepato-splenic bil harziasis, the diminution being directly related to the severity of the condition. This was not always the case, since some cases even of the fourth grade with ascites had a normal clearance rate constant. Previous reports dealing with the HBF in bilharziasis are few. Bradley et at (7) found that hepatic blood flow as estimated by bromsulphalein (BSP) was normal in 2 cases and very low in another 2 patients suffering from bilharzial cirrhosis. Using the same technique, Badawi & Nomeir (8) after a study of 16 patients having bilharzial hepatic fibrosis, reported that the estimated hepatic blood flow was reduced in these pa tients and that the degree of reduction was related to the degree of fibrosis and the size of the liver but not related to the height of portal pressure. This correla tion between the HBF and the size of the liver was not evident in the present series of cases. Lastly, Benhamou et al (9) using radiogold found slight reduction in the fractional hepatic blood flow in two patients with hepatic schistosomiasis. Mean of 5 cases. Blood sampling 2 I Y2 4 2 fr@ I', I Mmulesafter inject@n. Fig. 3. Clearance of 20 microcuries of colloidal gold particles from circulation as measured by serial blood sampling in normal subjects.

7 USE OF ISOTOPES IN THE STUDY OF LIVER 131 TABLE THE CARDIOPORTAL CIRCULATION TIME IN HEPATO-SPLENIC BILHARZ!ASIS lii secondsmeancpct in Type of casenumber of casesthe S.D.RangeNormal5026 ±1 ±518 â 31 Bilharzial I826±7II533±7III529±9IV724±7 20â 32 22â 38 20â 37 16â 35 As regards the hepatic uptake of rose bengal, results of the present study demonstrate that the disappearance half-time of radio-iodinated rose bengal was usually longer in bilharzial patients than in normal subjects; and that this pro longation was related to the severity of the hepato-splenic affection. In this re spect, Sallam et al ( 10) examined 19 bilharzial patients using the same radio active substance, taking counts every 5 minutes to draw an uptake excretion curve and they found no appreciable difference between normal subjects and bilharzial patients in the hepatic uptake of rose bengal; the only difference being in the excretion portion of the curve. Furthermore, these authors did not ob serve any difference in the hepatic uptake of rose bengal between members of the various grades of hepato-splenic bilharziasis. The effect of bilharzial hepatic fibrosis on the removal efficiency of rose bengal was noticed to depend on the grade of the disease. Thus, it was completely normal in first grade cases, and markedly reduced in patients having ascites de TABLE IV RADIOISOTOPE PHOTOSCANNING OF TIlE LIVER IN HEPATOSPLENIC BILHARZIASIS USING Au'98. GradeNumber photoscani of casesinterpretation of II III IV Normal. Slight diminution of intensity and mottling. Diminution of intensity and scattered diffuse mottling. Shrunken liver image, marked diminution in intensity and diffuse mottling

8 132 MUHAMMAD ABDEL RAZZAK noting parenchymal involvement. Between these two extremes, the clearance of radiogold was impaired to approximately the same degree as that of rose bengal in the second and third grades. This agrees with the well known concept con cerning the very late involvement of liver parenchyma in hepato-splenic hil harziasis ( 1 1 ). Nevertheless, this lowered removal efficiency of rose bengal was not constant in all late cases, and was occasionally seen in moderate cases. This is expected from a non-homogenous group of patients as evidenced by liver biopsy, which showed that some of these cases were pure bilharzial, while in others there was evidence of an additional element of infective or nutritional origin. The cardioportal circulation time was normal in grade I cases, and usually prolonged in patients of the second and third grades. This prolongation in CPCT is most probably due to the effect of periportal bilharzial fibrosis. The results in cases with ascites were variable, being either prolonged, normal or even shorter than normal. This might be due to the presence of arteriovenous portal collateral anastomotic channels. Hepatic photoscans of patients representing the first grade of hepato-splenic bilharziasis proved to be completely normal. In more advanced cases, diminution in the intensity of the scan picture together with scattered mottling were seen; this being due to the periportal fibrosis, portal hypertension and reduced hepatic blood flow that were present in these patients. These factors may be aided by the presence of ascites in fourth grade cases. SUMMARY Patients having hepato-splenic bilharziasis (schistosomiasis) can be classified into 4 grades: preclinical; mild; cases with oesophogeal varices indicating the presence of portal hypertension and those having ascites. 7 5 Mean of 20 Normals. Bbod dis@pearance using head counts. 03 -v I â 3 10 S I--- â --@â Minttes after.15 injection. 20 Fig. 4. Clearance of colloidal gold particles from the circulation in normal subjects as meas ured by a detector over the right temple. Dose used was 20 microcuries.

9 USE OF ISOTOPES IN THE STUDY OF LIVER 133 Radioactive isotopes were used to study the hemodynamic pattern, function and morphology of the liver in a group of 60 patients suffering from this disease. The radioisotopic technique applied showed that the hemodynamics, cell function and morphology of the liver in grade I cases were normal. In the sec ond grade, there was a slight diminution in hepatic blood flow (HBF), definite prolongation of cardioportal circulation time ( CPCT ) and some change in morphology as shown by photoscanning. Patients having oesophogeal varices without ascites had marked reduction in HBF and occasionally showed evidence of parenchymal affection. In the same group of cases, the CPCT was prolonged and scan picture distorted. Lastly, those with ascites had diminished HBF and marked affection of liver parenchyma. The photoscan was severely distorted and shrunken and CPCT was variable. However, it should be remembered that these findings were not constant in all cases from the same grade. ACKNOWLEDGEMENT I wish to record my thanks to The Atomic Energy Establishment of U.A.R. for supplying the radioactive material and apparatus used in this work. REFERENCES 1. I,o, M., KAMEDA,H. ANDUEDA,H.: The Study of Hepatic Blood Flow Determination by Au198 Colloid Using Deviced Recording Method. Japanese Heart I. 1: 17, R@.zz@uc, M. A.: SimultanousDetermination of Pulmonary and Cardioportal Circulation Times by Radio-iodinated Human Serum Albumin. I. of Trop. Med. and Hyg. 66:109, WAGNER,H. N., MCAFEE, J. C. ANDMOZLEY,J. M. : Diagnosis of Liver Disease by Radio isotope Scanning. Arch. Inter. Med. 107:324, MACINTYRE,W. J., KOCH-WESSER, D., CHRISTIE,J. H. ANDCRESPO,G. C. : The Clear ance of Labelled Compounds as a Measurement of Hepatic Flow Versus Function. I. of Nuclear Med. 2:133, RAZZAK,M. A. ANDWAGNER, H. N.: Measurement of Hepatic Blood Flow by Colloidal Gold Clearance. I. Applied Physiology 16:1133, HASHEM, M.: The Pathogenesis of the Spleenomegaly Associated with Bilharzial Fibrosis. The Gazette of Kasr El Aini Faculty of Med. 23:57, BRADLEY, S. E., INGELFINGER, F. J. AND BRADLEY, G. P.: Hepatic Circulation in Cirrhosis of the Liver. Circulation 5:410, BADAWI,H. S. AND N0MEIR, A. M.: Hepatic Blood Flow in Bilharzial Fibrosis. Alex. Med. J. 8:220, BENHAMOIJ,J. P., NICOLLO, F., GIROND, C., TRIc0T, R., LECER, L. AND FAUVERT, R.: Etudes sur L'hemodynamique Portohepatique. Rev. Franc. Etudes Clin. et Biol. 7:83, SALLAM,F., DAW, H., MAHMOUD,K. A., MAMOUN,A., HAZZAA,I. ANDZAK!, F. C.: The Value of Rose Bengal 1131 as a Liver Function Test in Hepatic Bilharziasis. Second U.N. Internat. Conference on the Peaceful Uses of Atomic Energy. 26:150, EFFAT, S.: Portal Hypertension. The Gazette of Kasr El Aini Faculty of Med. 21:

10 The Use of Radioactive Isotopes to Study the Hemodynamic Pattern, Function and Morphology of the Liver in Hepato-Splenic Bilharziasis (Schistosomiasis) Muhammad Abdel Razzak J Nucl Med. 1964;5: This article and updated information are available at: Information about reproducing figures, tables, or other portions of this article can be found online at: Information about subscriptions to JNM can be found at: The Journal of Nuclear Medicine is published monthly. SNMMI Society of Nuclear Medicine and Molecular Imaging 1850 Samuel Morse Drive, Reston, VA (Print ISSN: , Online ISSN: X) Copyright 1964 SNMMI; all rights reserved.