Clinical need for both scintigraphy with technetium-99m GSA and per-rectal portal scintigraphy in some patients with chronic liver disease

Scintigraphy with 99mTc-diethylenetriaminepentaacetate with galactosyl human serum albumin (99mTc-GSA) and per-rectal portal scintigraphy are useful for evaluating hepatic functional reserve and portal circulation, respectively. We did the procedures simultaneously in some patients to examine the relationship between hepatic functional reserve and portal circulation in chronic liver disease. Scintigraphy with 99mTc-GSA was done in 10 healthy subjects, 45 patients with chronic hepatitis, and 165 patients with cirrhosis. Fifty-seven patients (13 with hepatitis and 44 with cirrhosis) also underwent per-rectal portal scintigraphy with 99mTc-pertechnetate within two weeks. A receptor index was calculated by dividing the radioactivity of the liver region of interest (ROI) by that of the liver-plus-heart ROI at 15 min after the injection of 99mTc-GSA. The index of blood clearance was calculated by dividing the radioactivity of the heart ROI at 15 min by that of the heart ROI at 3 min. A solution containing 99mTc-pertechnetate was instilled into the rectum, and serial scintigrams were taken while radioactivity curves for the liver and heart were recorded sequentially. A per-rectal portal shunt index was determined by calculating the ratio of counts for the liver to counts for the heart integrated for 24 seconds immediately after the appearance of the liver time-activity curve. The median receptor index was lower for more severe liver disorders, increasing in the order of chronic hepatitis, compensated cirrhosis and decompensated cirrhosis, and the median index of blood clearance was higher. The median receptor index was significantly lower when a complication (varices, ascites, or encephalopathy) was present, and the median index of blood clearance was higher. The shunt index was correlated significantly with the two other indices, but these values for some one-third of the patients disagreed in either indices. Scintigraphy with 99mTc-GSA and per-rectal portal scintigraphy with 99mTc-pertechnetate are both needed for accurate assessment of the severity of chronic liver disease before treatment-making decisions, because in some patients, results are not correlated.     

A compartment model of Tc-99m-DTPA-galactosyl-human serum albumin for evaluating liver function]

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a new liver scintigraphy agent which binds to asialoglycoprotein receptor in hepatocyte. Studies were performed in three normal volunteers and 11 patients with liver cirrhosis. Time-activity curves for the heart and liver were obtained for 60 min following an i.v. injection of 99mTc-GSA (1 mg/185 MBq). We introduced five compartments to describe 99mTc-GSA: 1) extrahepatic blood, 2) hepatic blood, 3) receptor, 4) interstitial fluid and 5) urine. The %ID of 99mTc-GSA in blood and the hepatic blood volume were obtained from the extrapolation of the biexponential fitting for the heart and liver curves. Michaelis-Menten type saturation kinetics was applied to the process of receptor-ligand binding. Numerical analysis solved the simultaneous differential equations that were introduced from the compartment model. Hepatic blood flow was 1,651 +/- 131 ml/min, maximal removal rate for the ligand was 0.547 +/- 0.069 mg/min in normal controls. Both results were significantly decreased in patients with liver cirrhosis compared with normal controls. Present study may provide a novel method for the diagnosis of liver function that allows independent quantification of the hepatic blood flow and the receptor population.     

Phase II clinical study on 99mTc-GSA, a new agent for functional imaging of the liver]

Phase II study of 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a new radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes, was performed in 81 patients with liver diseases to validate its safety and possibility for the evaluation of hepatic function. None of adverse reactions, abnormal clinical laboratory findings and anti-99mTc-GSA antibody production due to 99mTc-GSA was recognized. Immediately after the injection of 99mTc-GSA, the dynamic data and serial hepatic images were obtained for 60 min. The indices for blood clearance and liver accumulation were calculated based on the counts in the regions of interest on the hearts and livers. In 54 patients with chronic hepatic disorders such as liver cirrhosis, the blood clearance and liver accumulation of 99mTc-GSA were retarded according to the progress of the hepatic disorders. The findings of 99mTc-GSA scintigraphy also reflected the hepatic functions of the patients with large hepatic tumors, obstructive jaundice and acute hepatitis. These results suggest that 99mTc-GSA has the clinical potentials to evaluate the liver functions in the patients with hepatic disorders.     

Clinical assessment of hepatic functional reserve using<Superscript>99m</Superscript>Tc DTPA galactosyl human serum albumin SPECT to prognosticate chronic hepatic diseases —Validation of the use of SPECT and a new indicator—

RATIONALE: It is generally known that scintigraphy of 99mTc diethylenetriamine pentaacetic acid-galactosyl human serum albumin (99mTc-GSA) is useful for assessing hepatic functional reserve. For hepatic functional indicators, the index of the calculated planar image has been used in previous studies. However, there have been few reports that suggest that the indicators calculated from static SPECT data would be useful for the assessment of hepatic function. The aims of this study were to establish a simple method for assessing hepatic functional reserve using the liver SPECT of 99mTc-GSA and to apply this method for rich stratification in patients with chronic hepatic diseases. METHODS: A liver phantom (a 50% concentration of 99mTc solution) was used to compare the planar and SPECT methods. According to the definition of the new indicator, the liver SPECT of 99mTc-GSA was divided by a syringe SPECT of 99mTc-GSA and was called the liver uptake ratio (LUR). We correlated the LUR and the liver uptake ratio calculated according to the blood-sampling method. 99mTc-GSA SPECT was performed in 137 patients with hepatic diseases, including chronic hepatic diseases, and 20 healthy volunteers. The LUR was correlated between the formed subtypes for all subjects. RESULTS: The acquired phantom-count ratio calculated by the SPECT method was more accurate than that acquired by the planar method. A good correlation was obtained between the LUR and the blood-sampling method (r = 0.971). The LUR was significantly lower in subjects with severe cirrhosis than in healthy subjects or those with chronic hepatitis and mild cirrhosis, and it was significantly lower in subjects with chronic hepatitis and mild cirrhosis than in healthy subjects. The LUR was significantly correlated with other hepatic function tests. Based on LUR, the chronic hepatic diseases were divided into two groups: Group A, with LURs 30% and higher, and Group B, with LURs below 30%. An LUR of 30% marked the 25th percentile of the mild-cirrhosis group. The cumulative survival rates were lower in Group B than in Group A. CONCLUSION: The SPECT method was superior to the planar method for assessing LURs. LUR was a suitable indicator of 99mTc-GSA clearance from the blood pool and of binding to the asialo-glycoprotein receptor. LUR is a simple and clinically useful indicator for the assessment of hepatic functional reserve in chronic hepatic diseases.     

A quantitative model of technetium-99m-DTPA-galactosyl-HSA for the assessment of hepatic blood flow and hepatic binding receptor.

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) was studied in normal volunteers and in patients with impaired liver function. The extrapolation approach originated the absolute dose of 99mTc-GSA in blood and the hepatic blood volume. The heart and liver regression curves were simultaneously fractionated into the three compartments (extrahepatic blood, hepatic blood and hepatocytes). Four differential equations were integrated with the six parameters as variables, and the smallest residual sum of squares was obtained by the damping Gauss-Newton method. The result of hepatic blood flow was 1603 +/- 144 (ml/min) in normal controls, which was compatible with previously reported values. Maximal removal rate (mg/min) showed statistically significant differences between the normal volunteers and patients with chronic hepatitis or liver cirrhosis. Our kinetic model of 99mTc-GSA can be used in the evaluation of liver function.     

Analysis of the early blood kinetics of 99mTc-GSA and its verification: new one-compartment model and regression equation.

Technetium-99m-galactosyl human serum albumin (99mTc-GSA) is a radiopharmaceutical that binds to asialoglycoprotein receptors in the hepatocyte membrane; the level of 99mTc-GSA accumulation in the liver correlates well with the parameters of hepatic function tests. We hypothesized that the early blood kinetics of 99mTc-GSA could be described by a simple one-compartment model expressed as an offset + a monoexponential function (y=y0 +Ae(-alpha)t). The aims of this study were to assess the validity of this hypothesis using sequentially measured blood levels of 99mTc-GSA, which were approximated by a regression expression, and to analyse the regression equation. 99mTc-GSA levels were measured in blood samples collected from 30 patients with liver disease. From sequential changes in radioactivity up to 30 min after injection, a regression equation expressed as an offset+ a monoexponential function was calculated and evaluated by multiple correlation coefficients and absolute deviations (% error). The liver uptake rate 15 min after injection of 99mTc-GSA (liver uptake rate 15, UTR 15) was calculated from the regression equation in each case. The respective relationships of this parameter to the coefficient [A] and gradient [alpha] were evaluated. In all cases, the measured values of radioactivity in blood samples could be fitted to an offset + a monoexponential function. The validity of our hypothesis was supported by examining regression equations calculated from blood 99mTc-GSA levels. Analysis of the regression equations suggested a potential for a new index of hepatic functional reserve.     

The utility of quantitative 99mTc-GSA liver scintigraphy in the evaluation of hepatic functional reserve: comparison with 99mTc-PMT and 99mTc-Sn colloid]

Using data from 17 patients with liver cirrhosis and 3 patients with fatty liver, we have compared the utility of 3 hepatic imaging agents in the evaluation of hepatic functional reserve. Evaluated here were 99mTc-galactosyl human serum albumin (GSA) which is a new ligand for hepatic binding protein, 99mTc-N-pyridoxyl-5-methyl tryptophan (PMT) of a hepatobiliary agent, and 99mTc-Sn colloid. In each patient, we performed these 3 imaging studies within a week and also examined hepatic function tests (indocyanine green test, hepaplastin test, choline-esterase, etc). In each imaging study, serial images and dynamic data were obtained after the injection of 99mTc-GSA (185 MBq/3 mg), 99mTc-PMT (185 MBq), or 99mTc-Sn colloid (185 MBq). Using the obtained dynamic data, we analyzed the liver kinetics of the 3 agents based on 1 compartment model with 3 parameters (hepatic clearance, hepatic excretion rate, non-specific volume of distribution). From fitting the liver and heart data to this model, three unknown parameters were determined. Patlak plot was also applied in order to estimate liver uptake rate. Both curve fitting and Patlak plot could determine appropriate parameters in every study. In 99mTc-GSA, a nonlinear 3 compartment model was also applied in order to estimate hepatic blood flow, liver receptor density, and affinity of receptor-GSA binding separately. Using the obtained parameters, we analyzed the correlations between the parameters and the results of hepatic function tests. In all of the parameters, those obtained from 99mTc-GSA imaging showed the most significant statistical correlation with the results of hepatic function tests. From the present results, 99mTc-GSA imaging was concluded to be the best for evaluation of hepatic functional reserve.     

Asialoglycoprotein receptor concentration in tumor-bearing livers and its fate early after their sectorial resection

The aim of the present study was to investigate asialoglycoprotein receptor (ASGP-R) status in tumor-bearing livers and early after their sectorial resection employing 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) dynamic SPECT. METHODS: Ten normal liver controls and 44 liver tumor patients who underwent sectorial hepatectomy were included in the study. 99mTc-GSA dynamic SPECT study was performed 7 +/- 3 d before (pre-operative) and 34 +/- 13 d after surgery (post-operative) in liver tumour patients. Pre- and post-operative parameters including hepatic functional volume and 99mTc-GSA clearance of unit hepatic functional volume, representing ASGP-R concentration, were measured. The sum of functional volume of the sectors uninvolved in hepatectomy was defined as residual functional volume. Subsequently, post-operative change in functional volume (the ratio of post-operative to residual functional volume), post-operative change in 99mTc-GSA clearance of unit hepatic functional volume (the ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional volume) and percent resection of functional volume were calculated. RESULTS: Pre-operative 99mTc-GSA clearance of unit hepatic functional volume in tumor-bearing livers was significantly lower than that in non-tumor bearing control liver. The ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional volume showed marked variation from 0.57 to 2.14, which negatively correlated with the percent resection of functional volume (r = -0.58, p < 0.0001). The ratio of post- to pre-operative 99mTc-GSA clearance of unit hepatic functional volume exhibited a negative correlation with the ratio of post-operative to estimated residual functional volume (r = -0.67, p < 0.0001). CONCLUSION: ASGP-R concentration is reduced in the presence of liver tumor. ASGP-R concentration reveals variable changes early after sectorial resection; the change negatively correlates with percent resection of hepatic functional volume. Post-operative change in ASGP-R concentration negatively correlates with change in functional volume.     

A new method for pharmacokinetic analysis of 99mTc-GSA using two-compartment and two-parameter model

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a liver scintigraphy agent which binds to asialoglycoprotein receptor in hepatocyte. Twenty-six patients with liver dysfunction were examined with 99mTc-GSA liver scintigraphy using two-compartment and two-parameter model (2C2P model). The 99mTc-GSA was assumed to move within two compartments (whole blood and liver). k1 and k2 were parameters which represented transfer rate constant from blood to liver, and from liver to blood, respectively. Two differential equations based on 2C2P model were integrated, so that k1, k2, k1/k2 and VLmg were estimated from the time-activity curves of the heart and liver. VLmg was computed as maximum amount of 99mTc-GSA binding to liver. The results were compared with the liver function tests and the conventional 99mTc-GSA indices: HH15, LHL15, and LU15. k1/k2 and VLmg values had positive correlation with the result of the serum liver function tests, Plt., T.Bil., ChE, GOT, LDH, ALP and gamma GTP. It is concluded that this new method using 2C2P model is not invasive and simplest in the 99mTc-GSA liver scintigraphies, and may be useful in evaluating liver function.     

Clinical evaluation of hepatic scintigraphy using 99mTc-GSA]

Functional hepatic imaging was performed using 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a radiolabeled ligand that reacts specifically to the asialoglycoprotein receptor that resides at the plasma membrane of hepatocytes, in 21 patients: five with chronic active hepatitis (CAH), 14 with compensative liver cirrhosis (LC), one with chronic inactive hepatitis and one with acute hepatitis. The former two diseases were mainly investigated. Serial liver images were acquired at the rates of 10 sec/frame for 0-5 min and 2 min/frame for 6-30 min after the injection of 99mTc-GSA, and the images were compared with 99mTc-phytate images in 2 patients with CAH and 11 with LC, and those with portal scintigrams using 123I-iodoamphetamine (IMP) in 3 patients with LC. The images using 99mTc-GSA were in better agreement with hepatic function than those using 99mTc-phytate, and with the findings of portal scintigraphy using 123I-IMP. LHL15 (liver/liver and heart radioactivities at 15 min after the injection of 99mTc-GSA) correlated with the hepaplastin test (r = 0.978 in CAH, and r = 0.544 in LC), indicators of hepatic reserve. These results suggest that liver scintigraphy using 99mTc-GSA might be a useful method for evaluating liver function.     

Preoperative assessment of residual hepatic functional reserve using 99mTc-DTPA-galactosyl-human serum albumin dynamic SPECT.

Preoperative assessment of residual hepatic functional reserve offers important strategic information for hepatic resection. To predict the postoperative residual liver function, we assessed the value of hepatic 99mTc-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) clearance estimated by dynamic SPECT analysis. METHODS: We investigated 114 consecutive patients with liver disease, including 55 hepatectomy cases. One minute after injection of 185 MBq 99mTc-GSA, 15 serial dynamic SPECT images were obtained every minute. The initial five sets of SPECT images were analyzed by Patlak plot to estimate the sequential initial hepatic 99mTc-GSA clearance (mL/min) as an index of hepatic function. The sum of hepatic 99mTc-GSA clearance of the segments immune from resection was categorized as predicted residual 99mTC-GSA clearance. In the hepatectomy cases, scintigraphy was performed before and 37 +/- 10 d after the operation. RESULTS: Good correlation was observed between the total hepatic 99mTc-GSA clearance and conventional hepatic function tests: plasma retention rate of iodocyanine green (ICG) at 15 min (ICG R15), r = -0.600, P < 0.0001, n = 94; plasma disappearance rate of ICG (K ICG), r = 0.670, P < 0.0001, n = 83; cholinesterase, r = 0.539, P < 0.0001, n = 121; serum albumin, r = 0.421, P = 0.0001, n = 123; and hepaplastin test, r = 0.456, P < 0.0001, n = 120. There was good correlation between the predicted residual 99mTc-GSA clearance and the postoperative total hepatic 99mTc-GSA clearance in patients who underwent segmentectomy or lobectomy (r = 0.84, P < 0.0001, n = 28) and between the pre- and postoperative total hepatic 99mTc-GSA clearance in patients who underwent subsegmentectomy (r = 0.91, P < 0.0001, n = 25). Five patients who had postoperative complications due to hepatic insufficiency (2 patients died of postoperative hepatic failure within 2 mo after operation) showed significantly lower predicted residual 99mTc-GSA clearance compared with the patients without complications (90.3 +/- 37.2 versus 320.9 +/- 158.8 mL/min; P < 0.005). CONCLUSION: The total hepatic 99mTC-GSA clearance reflected hepatic function. In addition, preoperative predicted residual hepatic 99mTc-GSA clearance was a good indicator of postoperative hepatic function and early prognosis. 99mTc-GSA dynamic SPECT is assumed to be a useful method for determining the surgical strategy in patients with hepatic tumor and especially in patients with hepatic dysfunction.     

Assessment of hepatic blood flow by PET with 15O water: correlation between per-rectal portal scintigraphy with 99Tc(m)-pertechnetate and scintigraphy with 99Tc(m)-GSA

We performed positron emission tomography with 15O water (H2(15)O) to measure hepatic arterial and portal blood flow. In addition, portal haemodynamics and hepatic functional reserve were measured by per-rectal portal scintigraphy and scintigraphy with galactosyl human serum albumin, respectively. We studied 15 patients who had cirrhosis of the liver with underlying viral infection. After the intravenous injection of H2(15)O, positron emission tomography was performed. Blood samples were obtained after beginning the emission scan. The blood samples and positron emission tomographic images were analysed to calculate the radioactivity in the blood and liver. One-compartment model analysis was used to estimate hepatic arterial and portal blood flow. Computer acquisition of gamma-camera data was started just before the injection of 99Tc(m)-galactosyl human serum albumin. A receptor index and an index of blood clearance were calculated on the basis of the radioactivity of the liver and heart. A 99Tc(m)-pertechnetate solution was instilled into the rectum; serial scintigrams were performed and radioactivity curves for the liver and heart were recorded sequentially. A per-rectal portal shunt index was calculated from the curves. Median portal blood flow was 80 ml x 100 g(-1) x min(-1), median hepatic arterial blood flow was 56 ml x 100 g(-1) x min(-1), and median total hepatic blood flow was 138 ml x 100 g(-1) x min(-1) in patients with cirrhosis. The correlations between portal blood flow and the Child-Turcotte classification score, portal shunt index and receptor index were all significant. Our results show that hepatic arterial and portal blood flow can be measured by positron emission tomography with H2(15)O non-invasively and physiologically. This technique may be useful in pathophysiological studies of liver disease.     

Phase III multi-center clinical study on 99mTc-GSA, a new agent for functional imaging of the liver]

A multi-center clinical study was performed in patients with hepatic disorders to evaluate the clinical usefulness of 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA), a new radiopharmaceutical which binds to asialoglycoprotein receptors on hepatocytes. The blood clearance and hepatic accumulation were evaluated on the basis of the dynamic data and serial hepatic images obtained for 20 min after 99mTc-GSA injection. The blood clearance and hepatic accumulation indices of 99mTc-GSA demonstrated the followings. 1) In acute liver diseases, these indices reflected the clinical features of the disease and correlated with the laboratory test indices for the blood coagulation system. 2) In chronic liver diseases, these indices changed in direct proportion to the progression of the hepatic disorder and correlated well with the conventional laboratory test results. 3) In obstructive jaundice, these indices aided evaluation of the liver function despite the high serum bilirubin level. 4) The indices reflected the change in the number of hepatocytes before and after hepatectomy. The scintigraphic findings with 99mTc-GSA permitted both functional and morphological evaluations of the liver and provide additional information compared with conventional liver scintigraphy. These results suggest that 99mTc-GSA scintigraphy may be useful for evaluating both the function and morphology of the liver from a new viewpoint of receptor-mediated accumulation.     

Quantitative evaluation of liver function using 99mTc-GSA in rats with liver injury induced by ischemia-reperfusion]

We evaluated quantitatively the liver injury of rats induced by ischemia-reperfusion, using 99mTc-DTPA-Galactosyl-Human-Serum-Albumin (99mTc-GSA). The vessels of the left lobe were clamped for 5, 10, or 45 minutes followed by 15 minutes reperfusion. Then, 99mTc-GSA was intravenously administered (170 micrograms/kg body weight) to rats. Two compartment analysis was made on measurement curves in the heart and liver to obtain clearance parameters. Significant difference was observed between the ischemic group (clamped for 10 and for 45 minutes) and the control. These results suggest that 99mTc-GSA is useful in the estimation of liver injury produced by ischemia-reperfusion.     

Correlation of 99mTc-GSA hepatic scintigraphy with liver biopsies in patients with chronic active hepatitis type C.

99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA) liver scintigraphy was performed in 230 patients with chronic active hepatitis type C, and its quantitative indices were compared with histological findings. 99mTc-GSA findings correlated well with four indices of the histology activity index (HAI), especially with the fibrosis score. Ninety patients were given interferon treatments, and 99mTc-GSA findings were compared with the results of the treatments. We classified the effects of interferon treatment into three groups according to clinical outcome: group 1: good effect (HCV-RNA negative, n = 34), group 2: moderate effect (HCV-RNA positive, but the value of GPT was normal for six months after the end of treatment, n = 19) and group 3: no effect (n = 37). Quantitative indices of 99mTc-GSA showed significant differences between groups. Follow-up study with 99mTc-GSA scintigrams was obtained in eight patients. The results of 99mTc-GSA improved in three patients in group 1 and deteriorated in five patients in group 3. There is a possibility that 99mTc-GSA scintigraphy can be used to predict the clinical outcome of chronic active hepatitis type C after interferon treatment.     

Dynamic liver scanning in cirrhosis

Dynamic hepatic scintigraphy was performed in 49 patients with established cirrhosis, using intravenous 99Tcm-pertechnetate and 99Tcm-sulphur colloid in a prospective study of its predictive value. There was a close correlation between the hepatic perfusion index (reflecting the ratio of arterial to total hepatic blood flow) obtained with pertechnetate (HPI-P) and with sulphur colloid (HPI-C) (r = 0.775; p less than 0.0001), and both indices correlated with disease severity (HPI-P p less than 0.0001; HPI-C p less than 0.01). HPI-P was significantly increased in patients who died, in patients with varices and in those with hepatic encephalopathy. HPI-C was significantly increased in patients with varices, in patients with hepatic encephalopathy and in those who had bled from varices. Neither HPI-P nor HPI-C was able accurately to predict the development of complications during the follow-up period. The trapping index (TI), reflecting a combination of hepatic extraction efficiency, degree of intrahepatic shunting and extrahepatic extraction of colloid, was significantly impaired in patients who died and in those with ascites, varices and/or variceal bleeding, but not in patients with hepatic encephalopathy. The trapping index correlated with disease severity, as did the computer-derived spleen-liver ratio (S-L ratio). Neither TI nor S-L ratio was able to predict the development of complications. The clearance rate constant of colloid from peripheral blood, the uptake rate constants for liver and spleen, and splenic volume were all found to be unhelpful as indicators of disease severity or as predictors of complications. While perfusion indices derived by dynamic hepatic scintigraphy reflect the severity of the underlying liver disease, their determination on a single occasion appears to offer no benefit in predicting the likelihood of major complications.     

Simple scintigraphic parameters with Tc-99m galactosyl human serum albumin for clinical staging of chronic hepatocellular dysfunction

Technetium-99m labeled diethylenetriaminepentaacetic acid (DTPA)-galactosyl human serum albumin (GSA) has been used for hepatocellular functional evaluation. This study proposed new and simple parameters to overcome the limitations of conventional parameters, and they were applied to the clinical staging of chronic liver dysfunction. The study group consisted of 93 patients including 81 with liver dysfunction and 12 control patients. In addition to the two conventional parameters, namely, receptor index (LHL15 = liver count divided by the sum of liver and heart counts at 15 minutes) and clearance index (HH15 = heart count at 15 minutes divided by the heart count at 3 minutes), 6 new parameters for Tc-99m GSA uptake and clearance were generated. The conventional receptor index of LHL15 showed a large variation depending on the size of region of interest (ROI) over the heart. The LHL15 normalized by the ROI size (nLHL15) showed more stable data and a better separation of mild liver dysfunction. A hyperbolic relationship between the LHL15 and HH 15 changed to a linear relationship by using the nLHL15 index. The combination of the liver to heart average count ratio at 15 minutes (LH 15) and T-half (minute) of the heart count also could differentiate each stage well. In conclusion, the use of the ROI-area normalized nLHL is recommended instead of the conventional LHL15. The indices of LH15 and T-half could be alternatively used as practical parameters for clinical staging in liver function.     

Comparisons of the time-activity curves of the cardiac blood pool and liver uptake by99mTc-GSA dynamic SPECT and measured99mTc-GSA blood concentrations

OBJECTIVES: The aim of this study was to determine the time-activity curve in the cardiac and hepatic region by 99mTc-GSA dynamic SPECT which is clinically used in liver scintigraphy and evaluate the temporal changes in the consistency and errors at the absolute scale using the regression equation of changes in the blood concentration of 99mTc-GSA. METHODS: In 11 patients who underwent 99mTc-GSA dynamic SPECT over the 30 min period after IV injection, the percentages of activity in the collected blood and in the blood pool estimated by dynamic SPECT were determined as the plasma clearance by blood collection and as the blood clearance by cardiac pooling. Extrahepatic uptake, expressesd as 100--(% uptake in the liver by dynamic SPECT (%)) was calculated as the blood clearance by the liver. The regression equation (Y = Y0 + Ae(-alphat)) was determined from the changes in the counts, expressed as a percent. Percent errors and the differences in the Y-intercept (Y0), coefficient (A) and slope (alpha) on the regression curve were compared. RESULTS: Blood pool clearance gradually exceeded the measured plasma clearance. The clearance by the liver started from a very low initial value and gradually became equal to that of plasma clearance over the first 15 minutes and exceeded it over the second 15 minutes. The Y-intercept was significantly higher in the blood pool clearance than that in the measured plasma clearance (p < 0.001), and the coefficient was significantly lower in the former than the latter (p < 0.001). The coefficient and slope were significantly lower in the hepatic clearance than the plasma clearance (p < 0.001, p < 0.005). Conclusion: The time-activity curve of the blood pool showed a tendency towards overestimation in the second half of the examination, probably due to scatter effect from the liver. The time-activity curve of liver uptake showed a tendency towards overestimation in the first half of the examination, probably due to the high concentration in the hepatic blood pool, and underestimation in the second half.     

A method for improving the accuracy in measurement of 99mTc-GSA liver uptake]

In order to improve the accuracy in the measurement of liver uptake rate of radioactivity at 15 minutes after injection of 99mTc-GSA, the corrected liver uptake rate (LU15VW) for tissue attenuation of gamma ray was measured. On the basis of the results of phantom studies, LU15VW was obtained as a ratio of the liver counts to the calculated counts of the injected dose supposed to homogeneously distribute in the liver of each patient and to decrease in count rate by the tissue attenuation of gamma ray, which was caused by the liver itself and body wall. The values of LU15VW were compared with those of the other 99mTc-GSA indices (LU15, LHL15, and HH15) and of the laboratory tests of liver function in 5 patients with chronic persistent hepatitis (CPH), 25 patients with chronic active hepatitis (CAH) 2A, 8 with CAH 2B, 8 with liver cirrhosis (LC), and 20 with hepatocellular carcinoma. LU15VW showed a good correlation with LU15, LHL15, and HH15 (r = 0.912, 0.864, and -0.869). The relationships between the results of LU15VW and the laboratory tests of liver function such as ICGR15, serum albumin, platelets counts, and hepaplastin test (r = -0.800, 0.684, 0.599, and 0.465) were more excellent as compared with those between the results of the other 99mTc-GSA indices and the laboratory tests. LU15VW was distinctly different in the mean values among the three groups of patients with CAH 2A, CAH 2B, and LC. These results indicated that LU15VW was an useful method for improvement of the accuracy in the measurement of liver uptake rate of 99mTc-GSA.     

<Superscript>99m</Superscript>Tc-GSA liver dynamic SPECT for the preoperative assessment of hepatectomy

OBJECTIVE: The purpose of the present study was to devise a predictive index to predict residual liver function before hepatic resection, using technetium-99m diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (99mTc-GSA) liver dynamic single photon emission computed tomography (SPECT). METHODS: Fifty-seven patients with liver disease underwent liver dynamic SPECT with 99mTc-GSA. Dynamic SPECT was performed to obtain the k-value according to the accumulation curve after injection of 99mTc-GSA. The k-value is a mathematical reflection of the rate of disappearance of the circulating radiotracer as it is accumulated into the hepatocytes. We devised an original predictive residual index (PRI) by combining k-value with liver volume (V) and functional liver volume (FV). Correlation between these parameters and results of liver function tests and the grade of liver disease severity was analyzed. We investigated retrospectively the correlation between PRI and post-operative patient prognosis. RESULTS: The k-value slightly correlated with indocyanine green clearance test at 15 mins, bilirubin level and hepaplastin test. FV and V did not correlate with liver function tests. Post-operative complications were observed in 5 patients. The PRI of these patients was below 0.37. When PRI was above 0.38, no patient had hepatic failure. CONCLUSIONS: When PRI is above 0.38, there is a low probability of hepatic failure after hepatectomy. The PRI is useful in preoperative prediction of post-hepatectomy residual liver function in patients with liver disease.