Modification of a two blood sample method used for measurement of GFR with 99mTc-DTPA.

BACKGROUND: Measurements of GFR may be performed with a slope/intercept method (S/I), using only two blood samples taken in strictly defined time points. The aim of the study was to modify this method in order to extend time intervals suitable for blood sampling. Modification was based on a variation of a Russel et al. model parameter, selection of time intervals suitable for blood sampling and assessment of uncertainty of calculated results. MATERIAL AND METHODS: Archived values of GFR measurements of 169 patients with different renal function, from 5.5 to 179 mL/min, calculated with a multiple blood sample method were used. Concentrations of a radiopharmaceutical in consecutive minutes, from 60th to 190th after injection, were calculated theoretically, using archived parameters of biexponential functions describing a decrease in 99mTc-DTPA concentration in blood plasma with time. These values, together with injected activities, were treated as measurements and used for S/I clearance calculations. Next, values of S/I clearance were compared with the multiple blood sample method in order to calculate suitable values of exponent present in a Russel's model, for every combination of two blood sampling time points. A model was considered accurately fitted to measured values when SEE ≤ 3.6 mL/min. Assessments of uncertainty of obtained results were based on law of error superposition, taking into account mean square prediction error and also errors introduced by pipetting, time measurement and stochastic radioactive decay. RESULTS: The accepted criteria resulted in extension of time intervals suitable for blood sampling to: between 60 and 90 minutes after injection for the first sample and between 150 and 180 minutes for the second sample. Uncertainty of results was assessed as between 4 mL/min for GFR = 5-10 mL/min and 8 mL/min for GFR = 180 mL/min. CONCLUSIONS: Time intervals accepted for blood sampling fully satisfy nuclear medicine staff and ensure proper determination of GFR. Uncertainty of results is entirely acceptable and for high GFR values even comparable with uncertainty of multi-sample measurements.

Assessment of accuracy and precision of (99m)Tc-HEPIDA clearances determined by means of a simplified method.

BACKGROUND: The aim of the present study was the assessment of the accuracy and precision of our own simplified method for the determination of (99m)Tc-HEPIDA liver clearance. MATERIAL AND METHODS: It has been assumed that archived results of plasma clearance (Cl(Pl)) and hepatic (Cl(Hp)), determined by means of multisample methods, could be legitimately used as a reference standard. The accuracy and precision of the simplified method was assessed by means of a Monte Carlo method alternatively utilizing three blood sampling times (T) of 68, 75 and 83 minutes post i.v. administration of (99m)Tc-HEPIDA. The corresponding alternative three urine voiding times (Y) were: 75, 80, and 95 min p.i. The analysed model was created accepting values of Cl(Pl) and Cl(Hp), of administered activity A(p) and parameters of biexponential function, describing the concentration C(t) decrease of the radiopharmaceutical (RF) in plasma during time as real values. Using the function C(t) for each individual, the plasma concentrations of RF at three sampling times, urinary clearance (Cl(Pl) - Cl(Hp)), and voided activity (A(Ur)(Y)) were calculated. Simulated random errors were added to the assumed blood sampling times T and to voiding time Y. To the activity A(p) and A(Ur)(Y), and RF plasma concentrations random errors were added, assuming normal distribution with relative SD from 0 to 5% and then clearance values were computed. For each process there were 5000 repeated simulated determinations. The accuracy of the simplified methods was assessed by comparing mean values of simulated clearance computations with the reference. Comparison of standard deviations with mean uncertainties enabled us to gain insight into the degree of agreement of the estimator of relative uncertainty with the coefficient of variation as a measure of precision. RESULTS: There were strong correlations between the reference clearance values and the mean values of determinations by means of the simplified procedure (r > 0.93). The correlations were practically insensitive to the uncertainty of pipetting. The lines of regression differed slightly from the lines of identity, giving an indication that there was a systematic error involved; it amounted to +4 ml/min at Cl(Pl) = 60 ml/min and to -7 ml/min for Cl(Pl) of 370 ml/min. For Cl(Pl) a bias of +6 ml/min was found for a clearance value of 16 ml/min and -13 ml/min at Cl(Pl) > 300 ml/min. At uncertainty of pipetting of 2%, a precision of 6-7% was found for Cl(Pl) of 300 ml/min. For Cl(Pl) of 200 and 150 ml/min the corresponding precisions were 7-8% and 10%, respectively. For Cl(Pl) of 200, 150 and 100 ml/min the corresponding precisions were 10, 12 and 17%, respectively. These precisions are 5 percent worse than those that were obtained from determinations by means of multisampling procedures.

Comparison of (99m)Tc-HEPIDA and (99m)Tc-MBrIDA from the standpoint of hepatic clearance determination-- preliminary communication.

BACKGROUND. In order to evaluate the functional capacity of the liver by means of clearance determination, the derivative of iminodiacetic acid ((99m)Tc-HEPIDA) has been used in recent decades. Because of recent problems with manufacturing and delivery of (99m)Tc-HEPIDA, an investigation was undertaken with the aim of testing whether a more widely available (99m)Tc-MBrIDA could be used for clearance determination and whether hepatic clearance measured with the use of this compound provides a similarly useful test of hepatic function. MATERIAL AND METHODS. Comparative investigations were performed in 73 patients of both sexes. The state of the efficiency of liver parenchyma was determined based on seven widely used biochemical tests, i.e. levels of: bilirubin, albumin, and gamma globulin; activity of AST, ALT, GGTP, and prothrombin index. The clearances of both radiopharmaceuticals, (99m)Tc-HEPIDA and (99m)Tc-MBrIDA, were determined by means of multisample technique. The results of determination were correlated among themselves and with the results of biochemical tests. The set of results of all estimations allowed a factorial analysis to be performed to find a common factor and to compute the values of factor loadings in particular tests. RESULTS. Obvious correlation between plasma and hepatic clearances of both radiopharmaceuticals was obtained and between plasma clearance of (99m)Tc-MBrIDA and hepatic clearance of (99m)Tc-HEPIDA. Correlation coefficients of (99m)Tc-MBrIDA clearance and the biochemical test results attained somewhat lower values than for (99m)Tc-HEPIDA clearance. Similarly, values of chi(2) test of independence of (99m)Tc-MBrIDA clearances and test results were also less close than for (99m)Tc-HEPIDA clearances. Factorial analysis showed that common factor loading is greatest for hepatic clearance of (99m)Tc-HEPIDA; the values of two loadings of (99m)Tc-MBrIDA clearances are very close, but somewhat lower than those for (99m)Tc-HEPIDA. CONCLUSIONS. From the performed investigations it is possible to conclude that (99m)Tc-MBrIDA clearances may be used for the evaluation of liver parenchyma performance, even if the results may not be as certain as those obtained using (99m)Tc-HEPIDA.

Conventional and parametric kidney scintigrams - reproducibility of semiquantitative image evaluation.

BACKGROUND: Parametric kidney scintigraphy gives the possibility of regional function distribution assessment of these organs; the clinical application of the method has thus far been limited. The usefulness of the method for the assessment of postinflammatory scars and diabetic nephropathy has been demonstrated. Preliminary data also indicate that this type of imaging allows the assessment of kidney function after extracorporeal shock wave lithotripsy. The aim of this study was the evaluation of the reproducibility of semiquantitative parametric kidney image evaluation. MATERIAL AND METHODS: The results of 98 dynamic kidney scintigraphic series were evaluated, obtained from examination of 44 patients (20 males, 24 females) with nephrolithiasis, who had been treated by means of lithotripsy. The semiquantitative assessment involved conventional renoscintigraphic images obtained from summation of scintigraphic serial records in the secretory phase, and parametric clearance images. A 5-level score was applied for assessment of both types of images, based upon numbers of detected defects of the regional function (0 - no defects; 1, 2, 3 - for 1, 2 or 3 defects, and 4 for higher numbers). Altogether, 196 kidney images were evaluated. The assessment was performed independently by 2 observers: A - an experienced specialist in nuclear medicine, who evaluated the images twice, and B - a resident physician with limited experience in the field. RESULTS: The agreement between the two evaluations by the specialist (intra-observer test) reached a level of 96% for conventional images and 90% for the parametric ones. In the inter-observer test, full agreement reached the levels of 84% and 71% for conventional and parametric images, respectively. If +/- 1 degree of the image score was taken as factual agreement, the intra-observer concordance reached 100%, and for inter-observer comparison, the agreement reached 99% and 97% for conventional and parametric images, respectively. CONCLUSIONS: The concordance of image assessment for conventional and parametric images is very good. In observations by two physicians, a somewhat closer agreement was reached for conventional than for parametric images; the difference between the two series of image assessments was small.

Parametric clearance kidney scintigrams; diagnostic potential in diabetes.

BACKGROUND: The diagnostic usefulness of parametric clearance kidney images was studied in the early diagnosis of diabetic nephropathy, juxtaposed with conventional dynamic urinary investigation (renoscintigraphy) combined with deconvolution procedure of renal and blood time activity curves and determination of plasma clearance of (99m)Tc-ethylenedicysteine ((99m)Tc-EC). MATERIAL AND METHODS: The investigation was performed on a group of 70 individuals (41 males, 29 females) in whom diabetes type 1 was diagnosed (age 10 to 30 y.; mean 19 y.) and on a control group of 35 healthy individuals (15 males, 20 females) in the age-bracket of 18-25 years (mean 19 y.). In all subjects studied, renoscintigraphy was performed after administration of (99m)Tc-EC (activity 40-120 MBq) combined with determination of urinary clearance (ERPF) of the radiopharmaceutical. The renographic curves were evaluated taking into account their shape and individual share of each kidney, and the clearance function was calculated (RClr). From analysis of the time-activity, kidney curves T(max) and T(1/2) were assessed. In addition, the mean (99m)Tc-EC transport time through the complete kidney (MTT) and organ's parenchyma (PTT) were calculated from results of deconvolution of the curve. From the dynamic urinary system study, conventional images of radiopharmaceutical distribution in the kidneys in the secretion phase were obtained. The parametric clearance images were also computed on the basis of relative clearance values in all the pixels of both kidney regions of interest. The disturbances in kidney function were assessed separately by means of conventional scintigram analysis and of corresponding parametric images. A three-stage classification was used in both cases for the evaluation of abnormal findings in the kidneys RESULTS AND CONCLUSIONS: In all studied individuals, the (99m)Tc-EC (ERPF) clearance values were within the normal range. When renographic time activity curves were considered the flattening of the curves (III phase) was more frequent in diabetic individuals than in the controls (39.3% vs. 15.7%; p = 0.001). The shape of the curves in phases I and II were normal in all studied individuals of both groups. There were no differences observed between mean values of T(max), T(1/2) and PTT in diabetics and controls. However, mean MTT values were significantly higher in diabetics than in controls (p = 0.02). In conventional summation images (phase II of the renograms), there were no significant differences in frequency of defects in kidney parenchyma diabetics and controls (4.3% vs. 2.9%). In contrast, analysis of parametric kidney clearance images revealed that parenchyma defects were found with significantly greater frequency in diabetic individuals (35.7%) than in control subjects (8.6%; p < 0.001). Summarizing the findings, it appears that parametric clearance kidney images reveal local deviations of renal uptake and secretory function while conventional indicators of renal function are still in the normal range. This observation points to the fact that clearance parametric images may have potential value in the early diagnosis of diabetic nephropathy, and perhaps in other types of renal damage. Incorporation of parametric images into the dynamic study of the urinary system may be promising when early detection of kidney damage seems vital.

Specific 99mTC-HEPIDA hepatic clearance--essential value ranges from a clinical stand-point.

BACKGROUND: Determinations of plasma 99mTc-HEPIDA clearance (ClPl) have been performed in some centres for 30 years to assess liver parenchyma damage, mostly for monitoring of organ performance in the course of various diseases. The main disadvantage of such a procedure rests with the fact that elimination of the compound from the system occurs not only via the liver and gall ducts, but also via the urinary route; the contribution of the latter compound being quite variable. This circumstance may lead to false assessment of liver parenchyma performance. A method has been developed therefore for assessment of specific hepatic clearance of 99mTc-HEPIDA (Cl(Hp)). Using this method it was demonstrated that results of Cl(Hp) correlated better with independently assessed degrees of liver impairment than did the values of ClPl. MATERIAL AND METHODS: To delineate ranges of Cl(Hp) that would provide valuable clinical information 134 individuals were studied, of whom 48 served as healthy controls and 86 had varying degrees of livers function impairment, resulting from various chronic diseases affecting the organs functional capacity. The latter was assessed on the basis of a series of commonly used biochemical indicators. RESULTS AND CONCLUSIONS: For delineation of meaningful ranges of 99mTc-HEPIDA specific hepatic clearance ROC curve method was used. The following results were obtained: Cl(Hp) >or= 150 ml min(-1) 1.72 m(-2)--excludes with high probability presence of substantial liver parenchyma damage; Cl(Hp)

(99m)Tc-HEPIDA hepatic clearance as a diagnostic tool: usefulness of a single sample plasma and hepatic clearance of (99m)Tc-HEPIDA for assessment of hepatic parenchyma performance.

BACKGROUND: A simplified method of (99m)Tc-HEPIDA clearance determination, both plasma and hepatic, depends upon measuring the radiopharmaceutical concentration in plasma of a blood sample taken once in the time range from 68-83 min after injection of compound, and measurement of activity voided (excreted) with urine about five minutes after blood sampling. The aim of the present study was to analyze the clinical usefulness of both clearances, as determined by the simplified method in view of the diagnostic usefulness of both clearances (particularly of hepatic clearance) as determined by the respective multisampling method. MATERIAL AND METHODS: For the analysis, archived data of studies in 134 individuals (48 healthy individuals and 86 patients with chronic liver parenchyma damage) were used, in which plasma clearance (Cl(Pl)) and hepatic clearance (Cl(Hp)) (99m)Tc -HEPIDA were determined by the standard multisample method--the values of such determined clearances constituted clearance referential values for further comparative analyses. The clearances Cl(Pl) and Cl(Hp) were determined by the simplified method separately for three blood sampling times of: 60, 75 and 90 min, using the same archived data for calculation of corresponding concentrations of (99m)Tc-HEPIDA in plasma. For urinary clearances--which were necessary for calculation of Cl(Hp)--archived data were utilized on activity contained in voided urine (at about 95 min.). The clinical reference system used here was the semi-quantitative assessment of liver function, performed on the basis of commonly used basic biochemical indices (AST, ALT, GGTP, bilirubin, albumin and gammaglobulin in serum, proteinogram and prothrombin index). For each test there were 4 categories of results (sub-ranges) selected, which were ranked from 0 to 3. For each patient the ranks for the results of each test were summed, giving a total sum (called SP). These latter sums of ranks served as a reference system, characterizing liver condition (performance) in each individual. RESULTS: Clearance, Cl(Pl) and Cl(Hp), values, obtained by a simplified method, were correlated with respective values determined by the multisampling method, and with ranks (SP) representing classification of degree of hepatic parenchyma damage--SP. On the basis of the attribute independence Chi(2) test, the coherence of clearances (simplified determination) with SP was assessed. Also, analysis of variance of SP-values and clearance was performed using Spearman's theory for testing the correlation of non-continuous variables. By factorial analysis a factor responsible for changes in individual quantities (results of biochemical tests and (99m)Tc-HEPIDA clearances) was computed. Its loading was determined for each individual quantity. During analysis for each moment of blood sampling tight correlations of clearance values, obtained by the simplified method, were determined with referential values. The closest correlation was obtained for blood sampling at 75 min. It was found that there are negative correlations between values of hepatic and plasmatic clearances and SP. The values of r obtained for Cl(Hp) are close to those obtained for analogical correlations by multisampling methods. However, the values of correlation coefficient obtained for Cl(Pl) by single sample method are greater than those for Cl(Pl) determined by multisampling method. CONCLUSIONS: Factor loading, known as "liver incapacity", is greater for Cl(Hp) determined by single sample method, but lower than comparable hepatic clearance loading determined by the multi-sample procedure. Values of incapacity factor for Cl(Pl) are lower than for Cl(Hp), but the lowest value was obtained for Cl(Pl) determined by the multisampling method. Obtained values Chi(2), r and loading of incapacity factor speak in favour of the correlations between the degree of hepatic parenchyma performance and the values of clearances determined by the simplified method. However, this correlation is closer for Cl(Hp) than for Cl(Pl). In view of such a distinct correlation, there is good justification for the implementation of the simplified method for the determination of hepatic clearances used in diagnostic analysis of hepatic performance.

Uncertainty analysis of (99m)Tc-HEPIDA liver clearance determination.

BACKGROUND: The aim of the study was to obtain information on the accuracy and precision of (99m)Tc-HEPIDA hepatic (Cl(Hp)) and plasma (Cl(Pl)) clearances and selection of an appropriate estimator of the measurement uncertainty of a single determination of these quantities. MATERIAL AND METHODS: In a simulation (Monte Carlo) experiment, it was assumed that the recorded results of plasma and hepatic clearances, as obtained from 185 patients, provided authentic information about (99m)Tc-HEPIDA behaviour in the body over a wide range of the clearances studied. The time course (99m)Tc-HEPIDA concentration in blood plasma has been described by means of biexponential function with parameter values derived for each patient. For each patient, using these data and urinary excretion data, there had been 5000 simulations performed; in each of the latter, the directly measured numbers have been substituted by simulated ones, obtained by means of varying the real ones, using random generated values. These reflected errors of plasma and radioactive standard pipetting (from 1 to 5%) and stochasticity of counting radioactive decay (1%). The time of blood sampling and urine voiding was also varied, assuming realistic uncertainty. The varied values were then used for computation of the simulated clearances. From the 5,000 calculated clearances for each patient, mean-values were calculated, as well as mean standard errors, standard deviations and mean uncertainty of measurements using a widely accepted rule of partial error propagation, and, in addition, a modified rule of the latter. Accuracy of clearance (Cl(Pl), Cl(Hp), Cl(Ur)) determination was assessed on the basis of comparison of mean values from simulations with those from directly recorded values. Precision was identified with standard deviation of each of the 5000 simulations. The uncertainty thus obtained was compared with results of calculated traditional and modified uncertainty. There was good agreement between standard deviation of the simulations with results of the modified calculation of total differential. Therefore, a coefficient of variation from simulation computations and a modified means of calculation of the propagated errors was accepted as a measure of uncertainty of a single determination. RESULTS/CONCLUSIONS: There was a very high correlation between the mean values from simulations and those from direct determinations (r > 0.98 in each case). The regression lines practically corresponded to the lines of identity. These correlations were not affected by the assumed range of pipetting uncertainty. In conclusion, the methods of (99m)Tc-HEPIDA clearance determination are satisfactory. Precision of clearance measurements depends substantially upon uncertainty of pipetting. For plasma clearance, the coefficients of variations at Cl(Pl) > 350 ml/min and at ab.80 ml/min amounted to 2 and 11% respectively, at pipetting uncertainty of 2%. Similarly, for hepatic clearances of (99m)Tc-HEPIDA of 300 ml/min and 30 ml/min, CV was 2.5 and 25%, respectively (at the same uncertainty of pipetting).

99mTc-HEPIDA hepatic clearance as a diagnostic tool: usefulness of plasma and hepatic clearance for assessment of hepatic parenchyma performance.

Plasma clearance of (99m)Tc-HEPIDA (Cl(Pl)) has been used for two decades for assessment of liver function in patients with diseases of this organ. A specific determination of (99m)Tc-HEPIDA liver clearance (Cl(Hp)) has been developed that provides more direct possibility to evaluate performance of liver parenchyma. Both tests have been studied in healthy volunteers of varying age (48 individuals) and in 83 patients with varying degree of liver damage. The liver damage has been evaluated on the basis of 5 biochemical tests (AspAT, ALAT, GGTP, bilirubine serum concentration, proteinogram) and a score system used for total impairment, which was calculated for each patient. Normal range of Cl(Pl) and Cl(Hp) was determined from a study on healthy individuals (volunteers). The results seem independent of age, but show sex differences. The following values (mean +/- SD) of Cl(Hp) were found in males and females of: (181 +/- 31) ml//min/1.73 m(2) and (158 +/- 22) ml/min/1.73m(2), and of Cl(Pl) were (224 +/- 33) ml/min/1.73 m(2) and (202 +/- 25) ml/min/1.73 m(2) respectively. Accepted lower boundaries of both quantities (mean -2SD) are 115 ml/min/1.73 m(2) and 150 ml/min/1.73 m(2) correspondingly. Negative correlation of individual values of both clearances in all patients with individual score of liver damage were highly significant and correlation coefficients obtained were higher for Cl(Hp) (r = -0.63) than those for Cl(Pl) (r= -0.56). Factorial analysis was performed with the intention of seeing which of the studied factors had the highest factor loading for parenchyma performance that was assumed as the common factor responsible for correlations. The highest value was obtained for hepatic clearance (Cl(Hp)) of (99m)Tc-HEPIDA. In conclusion this quantity seems highly promising as a clinically useful test for assessment of liver performance, both in screening for liver damage and for monitoring of organ conditions during therapy and follow-up of patients.

Hepatic plasma clearance of 99mTc-HEPIDA as a diagnostic tool: experimentally derived equations for a simplified determination.

Determination of the plasma (Cl(Pl)) and specific hepatic clearance (Cl(Hp)) of (99m)Tc-HEPIDA is gaining acceptance as one of the best tests for the assessment of liver parenchyma functional capacity. A standard method utilises numerous blood samples, collected after injection of the radiopharmaceutical, plus collection of the urine if specific hepatic clearance is required. It is not always necessary to obtain values of the clearances by means of the laborious multi-sample procedure. In the paper there are presented formulas, based on experimental data, that form the basis of a simplified method for determination of Cl(Pl) and Cl(Hp) using single administration of (99m)Tc-HEPIDA. To arrive at the value of Cl(Pl) it is sufficient to withdraw 1 blood sample in the time range of 60 to 83 min post administration of the radio-pharmaceutical. If Cl(Hp) is required, additional collection of urine over the time from 0 to 88-100 min post injection is necessary. The values of Cl(Pl) and Cl(Hp) obtained by the simplified procedure are in full accordance with those obtained by the reference method utilising a series of blood samples, collected from 5 to 90 min post injection. The simplified method is sufficient as a procedure for screening of patients for liver parenchymal damage.