Effect of background region of interest and time-interval selection on glomerular filtration ratio estimation by percentage dose uptake of (99m)Tc-DTPA in comparison with (51)Cr-EDTA clearance in healthy cats.

Evaluation of glomerular function is a useful part of the diagnostic approach in animals suspected of having renal disease. Time-interval and background region of interest (bg ROI) selection are determining factors when calculating the glomerular filtration ratio (GFR) based on percentage uptake of (99m)technetium-labelled diethylene triamine penta-acetic acid ((99m)Tc-DTPA). Therefore, three different time intervals (60-120 s, 120-180 s, 60-180 s) and three different bg ROIs (C-shape, caudolateral, cranial + caudal) were investigated. In addition, global GFRs based on percentage dose uptake of (99m)Tc-DTPA for the different time-intervals and bg ROIs were compared with the global GFR based on (51)chromium-ethylene diaminic tetra-acetic acid ((51)Cr-EDTA) plasma clearance in nine healthy European domestic shorthair cats. Paired Student's t-tests and linear regression analysis were used to analyse the data. Different time intervals seemed to cause significant variation (P <0.01) in absolute GFR values, regardless of the choice of bg ROI. Significant differences (P <0.01) between bg ROIs were only observed in the 120-180s time interval between the C-shape and cranial + caudal bg ROI, and between the caudolateral and cranial + caudal bg ROI. The caudolateral bg ROI in the 60-180 s time interval showed the highest correlation coefficient (r = 0.882) between (99m)Tc-DTPA and (51)Cr-EDTA, although a significant difference (P <0.05) was present between both techniques.

(99m)Tc-DMSA absolute and relative renal uptake in cats: procedure and normal values.

In this study we investigated the influence of technical factors (positioning, background (BG) correction and attenuation correction) on qualitative and quantitative (absolute (AU) and relative (RU) uptake) assessment of feline kidneys with (99m)technetium labelled dimercaptosuccinic acid ((99m)Tc-DMSA). Eleven healthy adult cats were included. Influence of BG and depth correction on quantitative assessment was evaluated. Depth correction was based on the geometric mean method (using dorsal and ventral images) and the use of two standards placed over each individual kidney. Visual evaluation showed superiority of dorsal and ventral over lateral positioning due to increased separation of the kidneys permitting region of interest (ROI) placement without overlap. No apparent influence of BG correction was found for RU. However, AU was systematically overestimated without BG correction. Depth correction did not seem to affect RU in most cases, however, in some cats the differences were not negligible. The values for AU without depth correction were lower compared to depth corrected values.

Interobserver reproducibility of the interpretation of I-123 FP-CIT single-photon emission computed tomography.

OBJECTIVES: I-123 ioflupane (FP-CIT) single-photon emission computed tomography is a recognized tool in the diagnosis of Parkinsonian syndromes. In practice, data interpretation relies on visual and semiquantitative analyses. Good interobserver reproducibility is a prerequisite before claiming the robustness of a technique. This study aimed at evaluating interobserver reproducibility of this approach. METHODS: Thirty nuclear medicine physicians participated in the study. Data included FP-CIT images and semiquantitative measurements of 12 cases, covering a wide spectrum of scintigraphic patterns and for which a 'true' clinical diagnosis based on long-term follow-up was available. Interobserver agreement was defined, for each case, as the highest percentage reached among the three proposed answers with complete agreement arbitrarily set at 80% or more. Variability in an individual observer's sensitivity to assess data as normal, equivocal or abnormal was scored using a three-point scale. RESULTS: Response rate was 99.7%. Among the three possible answers,'normal' accounted for 41.2% of the total, 'abnormal' for 49.8% and 'equivocal' for 8.1%. The mean interobserver agreement was 76% (range: 37-100%), with complete agreement being reached only in five cases. The interpretation proposed by most observers accorded to clinical diagnosis in 75% of the cases. Abnormalities of the central nervous system were encountered in all the cases with disagreement between the observer's interpretation and clinical diagnoses. An important variability in the observers' sensitivity was seen. CONCLUSION: In the particular setting of this preliminary study evaluating the reproducibility of FP-CIT single-photon emission computed tomography interpretation in a group of nuclear medicine physicians with various experiences, interobserver agreement was suboptimal. Collegial discussion and standardized interpretation criteria could contribute to an improved reproducibility.

Determination of optimal sampling times for a two blood sample clearance method using (51)Cr-EDTA in cats.

Estimation of the glomerular filtration rate (GFR) is a useful tool in the evaluation of kidney function in feline medicine. GFR can be determined by measuring the rate of tracer disappearance from the blood, and although these measurements are generally performed by multi-sampling techniques, simplified methods are more convenient in clinical practice. The optimal times for a simplified sampling strategy with two blood samples (2BS) for GFR measurement in cats using plasma (51)chromium ethylene diamine tetra-acetic acid ((51)Cr-EDTA) clearance were investigated. After intravenous administration of (51)Cr-EDTA, seven blood samples were obtained in 46 cats (19 euthyroid and 27 hyperthyroid cats, none with previously diagnosed chronic kidney disease (CKD)). The plasma clearance was then calculated from the seven point blood kinetics (7BS) and used for comparison to define the optimal sampling strategy by correlating different pairs of time points to the reference method. Mean GFR estimation for the reference method was 3.7+/-2.5 ml/min/kg (mean+/-standard deviation (SD)). Several pairs of sampling times were highly correlated with this reference method (r(2) > or = 0.980), with the best results when the first sample was taken 30 min after tracer injection and the second sample between 198 and 222 min after injection; or with the first sample at 36 min and the second at 234 or 240 min (r(2) for both combinations=0.984). Because of the similarity of GFR values obtained with the 2BS method in comparison to the values obtained with the 7BS reference method, the simplified method may offer an alternative for GFR estimation. Although a wide range of GFR values was found in the included group of cats, the applicability should be confirmed in cats suspected of renal disease and with confirmed CKD. Furthermore, although no indications of age-related effect were found in this study, a possible influence of age should be included in future studies.

Pixel-by-pixel mean transit time without deconvolution.

BACKGROUND: Mean transit time (MTT) within a kidney is given by the integral of the renal activity on a well-corrected renogram between time zero and time t divided by the integral of the plasma activity between zero and t, providing that t is close to infinity. However, as the data acquisition of a renogram is finite, the MTT calculated using this approach might result in the underestimation of the true MTT. To evaluate the degree of this underestimation we conducted a simulation study. METHODS: One thousand renograms were created by convoluting various plasma curves obtained from patients with different renal clearance levels with simulated retentions curves having different shapes and mean transit times. RESULTS: For a 20 min renogram, the calculated MTT started to underestimate the MTT when the MTT was higher than 6 min. The longer the MTT, the greater was the underestimation. Up to a MTT value of 6 min, the error on the MTT estimation is negligible. CONCLUSION: As normal cortical transit is less than 2 min, this approach is used for patients to calculate pixel-to-pixel cortical mean transit time and to create a MTT parametric image without deconvolution.

Checking the consistency of the two blood samples slope-intercept method for estimating GFR using the single blood sample formula in children.

BACKGROUND: The slope-intercept method is widely used for the determination of the plasma clearance of 51Cr-EDTA. When three or more plasma samples are used, the goodness-of-fit (r2) can be used as a measure of consistency of the samples. This parameter can not be used, however, if only two samples are available. PURPOSE: To evaluate whether the single-sample technique (SBS) can be used to check the consistency of the slope-intercept method using two blood samples (2BS) in children. METHODS: Simulated computer models of a mono-exponential curve were created in order to represent three children aged 3, 6 and 10 years, each with a large range of clearances values and three distribution volumes, respectively 20%, 25% and 30% of body weight. Errors were then introduced in the injected dose (errors from -50% to +50%) and on the 120 or 240 min blood sample (errors from -50% to +50%). The effects of these errors on the clearance measurement using 2BS and SBS methods were calculated and compared. RESULTS: The errors on the injected dose, the 120 min and 240 min plasma samples introduced errors in the same direction and with the same magnitude on both the SBS and 2BS clearance values. For that reason, the comparison between the SBS methods and the 2BS techniques has a low sensitivity in detecting an eventual error. Striking differences between the SBS method and the 2BS technique were only observed when considerable errors on the injected dose or plasma samples were introduced, particularly in case of a reduced clearance. The comparison between the SBS clearances calculated using the 120 min sample to that obtained using the 240 min samples is slightly more sensitive. However, this approach is also slightly less specific. A difference of more than 10 ml . min(-1). 1.73 m(-2) can be observed in the absence of an error. CONCLUSIONS: The use of the SBS for checking the consistency of the 2BS constitutes an insensitive approach to detect an eventual error in the injected dose or in the plasma samples. Obvious different results obtained by SBS and 2BS or between the SBS calculated using the 120 min and the 240 min samples suggest the presence of an error, but comparable results do not exclude erroneous measurement. Moreover, a difference of more than 10 ml . min(-1). 1.73 m(-2) can be observed in the absence of an error in the injected dose or in the plasma samples.

Correction factors after having neglected the first exponential in the estimation of chromium-51 EDTA clearance: a reappraisal.

The aim of the present work was to evaluate two classical formulae allowing the correction for having neglected the first exponential in the slope-intercept method used for the determination of EDTA clearance, namely the Chantler's linear correction formula (CH) and the Bröchner-Mortensen's quadratic correction formula (BM). First, a comparison study was performed with the two correction formulae, in order to predict the behavior of the calculated clearance, for various levels of renal function. Second, using data obtained from 47 adult patients with normal renal function, the results obtained with the two correction formulae have been compared to the reference technique, namely the biexponential fit. The results of the comparison study indicated that for clearance values lower than 120 ml/min, the results obtained using CH were systematically lower than those of BM, whereas for clearance values between 120 and 140 ml/min, the reverse was observed. The differences however, never exceeded 8 ml/min. The results were quite different when the clearance was higher than 140 ml/min, when the difference between CH and BM results increased rapidly, and the BM provided values systematically lower than CH. The clinical study showed that, in the range of normal clearance values, both CH and BM clearances were slightly lower than the results obtained by means of the reference technique. Based on these results, a new specifically designed validation study involving patients with high clearance values is mandatory to determine which of these two correction methods is more accurate, or to devise a better correction formula.

Post-test quality control for the single blood sample technique in glomerular filtration rate measurement in children.

BACKGROUND: While the value of the single blood sample (SBS) method for estimating 51Cr-EDTA plasma clearance has been repeatedly demonstrated, some nuclear medicine physicians are still reluctant to use it because of the lack of quality control parameters. PURPOSE: To present a post-test quality control procedure for the SBS technique in children. METHODS: In addition to the SBS clearance calculated using the specific paediatric SBS method, three artificial slope intercept (ASI) method clearances were calculated by assuming the distribution volume as, respectively, 20%, 25% and 30% of body weight. By dividing the injected activity by the distributional volume, the initial plasma concentrations (A0,30%, A0,25% and A0,20%) were calculated. Using these A0 values and the available single sample, ASI clearances were calculated by using the classical slope-intercept method. The working hypothesis of this approach was as follows. In the absence of significant errors, the three ASI clearance values should be close to that of the SBS method. This hypothesis has been tested using both simulated and patients' data. RESULTS: The results of the simulated study showed that an error in the injected dose produced variable differences between SBS and ASI clearances depending on the clearance values. The effect of an error on the plasma sample also varied as a function of the clearance values. The analysis of patient data revealed that the ASI approach allowed the identification of patients in whom the classical slope-intercept method suggested the presence of a possible error. CONCLUSION: A post-test quality control procedure for the SBS GFR measurement is presented. When the SBS clearance shows a difference with the ASI method (> 10 ml . min(-1) per 1.73 m2), the presence of an error is highly probable. A smaller difference, however, does not exclude erroneous data.

Pediatric applications of renal nuclear medicine.

This review should be regarded as an opinion based on personal experience, clinical and experimental studies, and many discussions with colleagues. It covers the main radionuclide procedures for nephro-urological diseases in children. Glomerular filtration rate can be accurately determined using simplified 2- or 1-blood sample plasma clearance methods. Minor controversies related to the technical aspects of these methods concern principally some correction factors, the quality control, and the normal values in children. However, the main problem is the reluctance of the clinician to apply these methods, despite the accuracy and precision that are higher than with the traditional chemical methods. Interesting indications are early detection of renal impairment, hyperfiltration status, and monitoring of nephrotoxic drugs. Cortical scintigraphy is accepted as a highly sensitive technique for the detection of regional lesions. It accurately reflects the histological changes, and the interobserver reproducibility in reporting is high. Potential technical pitfalls should be recognized, such as the normal variants and the difficulty in differentiating acute lesions from permanent ones or acquired lesions from congenital ones. Although dimercaptosuccinic acid scintigraphy seems to play a minor role in the traditional approach to urinary tract infection, recent studies suggest that this examination might influence the treatment of the acute phase, the indication for chemoprophylaxis and micturating cystography, and the duration of follow-up. New technical developments have been applied recently to the renogram: tracers more appropriate to the young child, early injection of furosemide, late postmicturition and gravity-assisted images and, finally, more objective parameters of renal drainage. Pitfalls mainly are related to the interpretation of drainage on images and curves. Dilated uropathies represent the main indication of the renogram, but the impact of this technique on the management of the child is, in a great number of cases, still a matter of intense controversy. Direct and indirect radionuclide cystography are interesting alternatives to the radiograph technique and should be integrated into the process of diagnosis and follow-up of vesicoureteral reflux.

The influence of renal function on normalized residual activity.

OBJECTIVE: To quantify the influence of overall renal function on normalized residual activity (NORA) and to evaluate the modifying factors. METHODS: A computer simulation model generated renograms by convolution of plasma disappearance curves with artificially created retention functions. From a database, 1099mTc-MAG3 plasma curves were selected, corresponding to renal clearances ranging from 33 to 405 ml x min(-1). The retention functions had three properties: (1) until the minimal transit time (MinTT), no output and a linear increase in transit time after MinTT; (2) a ratio of MinTT to mean transit time (MTT) equal to 0.3 or 0.8; and (3) a MTT between 3 and 60 min, increasing in steps of 1 min. The model generated 1160 renograms and for each of them the NORA was calculated at 20, 40 and 60 min. For each value of MTT, the coefficient of variation (CV) of the NORA was calculated at 20, 40 and 60 min. RESULTS: For the same retention function, different clearances resulted in different values of NORA. The degree of variability of NORA depended on several factors, including the time of measurement, the MTT and the MinTT to MTT ratio. For clearances between 100 and 400 ml x min(-1), the CV of the NORA ranged from 15% to 30%, whilst for clearances below 100 ml x min(-1), the CV of the NORA ranged from 22% to 67%. Little influence of the MinTT to MTT ratio was observed. CONCLUSION: NORA is influenced by overall renal function. The influence is limited for 99mTc mercaptoacetyltriglycine (99mTc-MAG3) renal clearances over 100 ml x min(-1), whilst for clearances less than 100 ml x min(-1), the NORA is influenced much more.

Which single blood sample method should be used to estimate 51Cr-EDTA clearance in adolescents?

Single blood sample methods are widely used for the estimation of the glomerular filtration rate, but the methods recommended for adults are not the same as those for children. The question arises, therefore, as to which method should be used in an adolescent or young adult. The aim of this study was to compare the performance of two methods, a specific paediatric converting equation and an adult algorithm, in a group of adolescent and young adult patients. From a large database of 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) renal clearance determinations using the two blood sample method, 598 patients, aged 1 week to 90 years, were selected. The results of the 51Cr-EDTA slope intercept clearance of the two blood sample method were used as reference. Using the paediatric algorithm, no bias was observed until the age of 40 years. Then, an increasing positive bias occurred. The standard deviation of the difference was generally less than 4 ml/min until the age of 25 years and increased gradually to reach 7 ml/min at the age of 80 years. Using the Christensen and Groth adult algorithm, the best results were observed in patients older than 50 years. With the exception of children aged less than 5 years, no systematic bias was observed. The standard deviation, however, increased gradually and reached a value of around 8 ml/min in young children. For individuals aged 15-25 years, the mean of the difference between the paediatric algorithm and the slope intercept method was -1.1 ml/min, with a standard deviation of the difference of 3.3 ml/min. For the adult algorithm, the mean of the difference was 0.3 ml/min, with a standard deviation of the difference of 7.7 ml/min. It can be concluded that, for individuals aged 15-25 years, both methods performed correctly. In this series, the paediatric method gave better results than the adult algorithm, and its use is therefore recommended.

Recovery of renal retention function by differentiating the Patlak-Rutland plot.

INTRODUCTION: It has been suggested that renal retention function can be estimated by differentiation of the Patlak-Rutland plot. AIM: To evaluate the error resulting from this method. METHODS: A total of 5800 renograms were generated by convolving real input functions with artificial retention functions. Ten bi-exponential plasma disappearance curves of Tc mercaptoacetyltriglycine (Tc-MAG3) with varying renal clearances served as input functions and 580 retention functions with mean transit time between 3 and 60 min, and variable ratios of minimal to mean transit time served as original retention functions. The retention function was estimated by differentiation of the Patlak-Rutland plot of each renogram. A variant of this retention function was calculated by setting negative values to zero. RESULTS: Minimal transit time was estimated correctly in all cases but the recovered retention function systematically underestimated the original, and negative values were observed. Mean transit time was underestimated with a difference ranging from -22.05 to -0.06 min. By setting the negative values to zero, a less important underestimation was observed which ranged from -13.37 to 0.00 min. Maximal transit time was underestimated systematically with a difference ranging from -22.05 to 0.00 min. All differences were influenced by mean transit time, renal clearance and ratio of minimal to mean transit time. CONCLUSION: Estimation of the renal retention function by differentiation of the Patlak-Rutland plot results in systematic and sometimes important underestimations. By setting the negative values of the recovered retention function equal to zero, important but still partial improvement can be obtained.

The estimation of renal transit using renography--our opinion.

Renal transit estimation using renography has been employed for decades. A variety of methods have been developed, ranging from simple quantitative to more sophisticated techniques. In this review, the methods are discussed in perspective of their advantages and drawbacks. Finally, the most robust methods for estimation of renal transit are proposed.

Utility of posterior oblique views in (99m)Tc-DMSA renal scintigraphy in children.

OBJECTIVE: Procedure guidelines suggest that optimal (99m)Tc-dimercaptosuccinic acid (DMSA) planar scintigraphy of the kidney should include right and left posterior oblique views in addition to the posterior projection. However, in a small number of restless children, it is sometimes difficult to get 3 good-quality images. The aim of this study was to evaluate the prevalence of cases in which posterior oblique views were useful for interpreting (99m)Tc-DMSA renal scintigraphy. METHODS: Three nuclear medicine specialists were asked to interpret 40 (99m)Tc-DMSA renal scans twice, first on the basis of the posterior projection only and then by using the posterior and the right and left posterior oblique views. RESULTS: The oblique posterior views were considered useful by observers 1 and 2 for 4 kidneys and by observer 3 for 5 kidneys and were considered somewhat useful for up to 7 kidneys. The addition of oblique posterior views changed the interpretation on 5 occasions for observer 1, on 9 occasions for the observer 3, and on no occasion for observer 2. On average, therefore, changes in interpretation occurred for fewer than 6% of the kidneys. Moreover, no relationship was observed between the opinion of the clinicians that oblique views were useful and changes in the scintigraphic interpretations. CONCLUSION: Oblique views were found useful in only a few cases and, even in these cases, did not significantly modify the interpretations. Therefore, when restless children are being imaged, the focus should be on obtaining a good posterior projection, even at the price of not having oblique posterior views.

Influence of renal function on renal output efficiency.

UNLABELLED: The purpose of this study was to quantify the influence of renal function on output efficiency (OE) and to evaluate factors that may modify this effect. METHODS: Renograms were generated in a computer simulation model by convolution of plasma disappearance curves with artificially created retention functions. Ten plasma curves were derived from a database corresponding to renal clearances ranging from 33 to 405 mL/min. The created retention functions had 3 characteristics: (a) no output until the minimal transit time (MinTT) followed by a linear increase in transit time; (b) ratio of MinTT to mean transit time (MTT) equal to 0.3 or 0.8; and (c) MTT between 3 and 60 min, increasing with 1-min steps. For each of the 1,160 renograms generated, output efficiency at time (t), OE(t), was calculated at 20, 40, and 60 min. Mean and SD of OE(t) for all clearances were calculated for MTT values between 5 and 60 min, increasing with 5-min steps. RESULTS: For the same retention function, different clearances resulted in different values of OE(t). The degree of variability of OE(t) depended on several factors, including the value of t, the value of MTT, and the shape of the retention function, expressed as the MinTT-to-MTT ratio. For OE(20), OE(40), and OE(60), the respective maximum SDs were 5.4%, 6.6%, and 7.1% for retention functions with a MinTT-to-MTT ratio equal to 0.3, and 6.2%, 8.4%, and 9.4% for retention functions with a MinTT-to-MTT ratio equal to 0.8. CONCLUSION: OE is influenced by renal function. Care should be taken in establishing the cutoff values for obstruction, non-obstruction, and the nondiagnostic zone, since a change in overall clearance can cause as much as a 20% variation in OE.

Optimal time window for measurement of renal output parameters.

Although normalised residual activity (NORA) and output efficiency (OE) are usually measured at a fixed time t, their dependency on t may affect the prediction of mean transit time (MTT). This study aimed to evaluate their degree of dependency on t and to determine an optimal time of measurement by assessment of their relationship with MTT for various times t. A simulation model generated 232 cortical renograms by convolving one plasma disappearance curve with 232 created cortical retention functions. The results show that considerable changes are observed for NORA and OE, depending on the time of measurement t. The choice of this time significantly influences the predictive value of these parameters for estimating MTT. The optimal time for measurement of NORA and OE should be close to the MTT, at the moment when emptying takes place. In the clinical practice, it should be adapted to the clinical problem under investigation.