A single sample method for evaluating 51chromium-ethylene diaminic tetraacetic acid clearance in normal and hyperthyroid cats.

BACKGROUND: Chronic kidney failure is frequently seen in middle-aged and elderly cats. 51Chromium-ethylene diaminic tetraacetic acid (51Cr-EDTA) clearance and single blood sample (SBS) method are used in several species to estimate the glomerular filtration rate (GFR). HYPOTHESIS: The hypothesis of this study was that 51Cr-EDTA clearance could be determined using an SBS method in normal and hyperthyroid cats. ANIMALS: Forty-six cats were included in this study, with an average age of 9.5 years. Of these cats, 27 had hyperthyroidism; 19 were healthy. METHODS: After IV injection of 51Cr-EDTA (average dose: 4.25 MBq), 7 blood samples were obtained between 5 and 240 minutes. Reference clearance was calculated in mL/min and mL/min/kg body weight, using a 2-compartment model. Optimal time for clearance measurement with SBS was then determined by systematically comparing each individual plasma concentration to the reference multisample clearance. RESULTS: The average reference plasma clearance of 51Cr-EDTA for all cats was 14.9 mL/min (3.7 mL/min/kg). The clearance in hyperthyroid cats averaged 16.4 mL/min (4.3 mL/min/kg) and in normal cats averaged 10.3 mL/min (2.4 mL/min/kg). The optimal time for the SBS was 48 minutes after injection of tracer 51Cr-EDTA (R2= 0.9414), giving the following converting equation: clearance = (0.0066 x DV48 minutes) - 0.9277 (in mL/min). CONCLUSIONS AND CLINICAL IMPORTANCE: In this study, the single sample 51Cr-EDTA clearance method was used to estimate the global GFR in cats. The method identified differences in clearance between normal and hyperthyroid cats. The optimal time for an SBS was 48 minutes.

Interobserver reproducibility in reporting on 99mTc-DMSA scintigraphy for detection of late renal sequelae.

UNLABELLED: This study was designed to evaluate the interobserver variability in reporting on 99mTc-dimercaptosuccinic acid (DMSA) scanning performed 6 mo after an acute episode of pyelonephritis for the detection of late renal sequelae. METHODS: Forty-six children were selected, who had early and late DMSA studies for evaluation of acute pyelonephritic lesions as well as sequelae. Three observers reported independently and separately on the early and late DMSA scans and, in a second step, on the late scan in the presence of the early scan. Interobserver reproducibility was evaluated for the early DMSA scan, the late DMSA scan alone, and the late DMSA scan with the early scan for comparison. RESULTS: Complete agreement between the three observers was reached in 75%, 78%, and 77% for the early DMSA scan, the late DMSA scan alone, and the late DMSA scan with the early scan for comparison, respectively. CONCLUSION: Interobserver reproducibility was high and was comparable for both early and late DMSA scintigraphy.

Influence of errors in sampling time and in activity measurement on the single sample clearance determination.

INTRODUCTION: Plasma clearance rate of 51Cr-EDTA estimated by using one blood sample is commonly used for the calculation of glomerular filtration rate. AIM: To estimate the error on single-sample clearance determination induced by errors in sampling time and activity measurement, and to compare it with the error observed on the clearance determination obtained using the slope-intercept method. METHODS: Forty-five adult patients were chosen from a data base of 51Cr-EDTA plasma clearance values determined by using two blood samples taken around 2 and 4 h. Patients were selected in such a way as to include clearances from 30 ml.min-1 to 155 ml.min-1, with steps of 3 ml.min-1. Based on the slope and the intercept of the slope with the y-axis, the plasma concentration at exactly 2 and 4 h was determined. Normally distributed random errors were then introduced in the sampling time (SD of 0, 1 and 2 min) as well as in the activity measurement (SD of 0, 1, 2 and 5%). Then, clearance was calculated using two single-sample methods (i.e. the algorithms of Groth and Tauxe), and the slope-intercept method, which requires two blood samples. For each setting, the simulation was repeated 200 times. The effects on clearance of a random error on the time sampling and/or the activity measurement were then evaluated. RESULTS: The error on single-sample clearance induced by a 2 min error in sampling time associated with a 5% error in activity measurement was negligible. For all clearance levels, the SD of the error on the calculated clearance was less than 3.8 ml.min-1. Whatever algorithm was chosen, the errors on the single-sample clearance were systematically lower than those observed with the slope-intercept method, for the whole clearance range. CONCLUSION: Errors in sampling time and in activity measurement induced only a very small error on the single-sample EDTA clearance, which is systematically lower compared to that observed on the slope-intercept method using two blood samples.

Influence of time interval and number of blood samples on the error in renal clearance determination using a mono-exponential model: a Monte Carlo simulation.

Mono-compartmental analysis based on 2- and 4-h blood samples (BS) of 51Cr-EDTA (EDTA, ethylenediaminetetraacetic acid) is commonly used for the calculation of the glomerular filtration rate (GFR). The purposes of this study were to estimate the magnitude of error in clearance induced by errors in the time of sampling and activity measurement; to estimate the impact of changing the interval between the BS; and to assess the influence of a higher number of BS in reducing the error. A model of mono-exponential curves based on a finite number of BS was created. Normally distributed random errors were introduced in the time of sampling and activity measurement. In a first step, three different time intervals were used; in a second step, seven different numbers of BS were used, all taken between 120 and 240 min. For each setting, the random errors were successively introduced 200 times and the coefficients of variation (CV) of the calculated clearances were determined. Variable errors in clearance were induced by errors in the time of sampling and activity measurement. In general, the observed errors were higher for high and low clearance, with lower errors for moderately reduced clearances. The errors in indicating the time of sampling played an important role for high clearance, whereas the errors in activity measurements led to important errors for low clearance. Prolonging the interval from 1 to 2 h resulted generally in an important decrease in error, except in the range 60-100 ml x min(-1). Prolonging the interval from 2 to 3 h resulted in only a small additional decrease in error, except for very low clearance. Errors in indicating the time of sampling and in activity measurements induce errors in clearance determination. These errors cannot be significantly reduced by simply increasing the number of BS or by prolonging the interval between the samples. It is probably better, in most cases, to keep using the 2-4-h method and to take extreme care when indicating the time of sampling and when measuring the activity, instead of increasing the number of samples or lengthening the procedure.

Atlas on acute pyelonephritis in children.

The authors describe various patterns of Tc-99m DMSA images that correspond to a diagnosis of acute pyelonephritis. Only those children with complete scintigraphic healing or considerable improvement after 6 months have been considered.

Inter-observer reproducibility of relative 99Tcm-DMSA uptake.

99Tcm-DMSA planar images of 49 randomly selected patients (10 adults, 39 children) were sent to 15 physicians at various centres in Belgium. They were asked to calculate, using their own routine program, the relative uptake (expressed as a percentage) of each kidney. The data were sent on disks formatted so that they could be read by all participants, using their own computer systems. For each scan, the inter-observer variability was expressed using the maximum difference and the standard deviation of left renal uptake. Left renal uptake measured by the 15 observers in the 49 patients was 29.0-72.0% (mean +/- s = 49.8 +/- 6.4%). The maximum differences in left renal uptake ranged between 1.7% and 12.0% (4.5 +/- 2.6%); however, the maximum difference did not exceed 8% in about 90% of the patients. The standard deviations of the individual left renal uptake were between 0.6 and 3.9 (1.3 +/- 0.8). The standard deviations were significantly higher in adults (mean standard deviation = 2.05) than in children (mean standard deviation = 1.12) (P < 0.001); this was probably related to the high background observed in three adults with severe renal impairment. Indeed there was a significant correlation (P < 0.001) between the standard deviation and both the signal-to-noise ratio and the degree of asymmetry between the right and left kidneys. The differences between right and left kidney uptake were systematically lower for some observers, suggesting an influence of the calculation programs.

How good is the slope on the second exponential for estimating 51Cr-EDTA renal clearance? A Monte Carlo simulation.

It has been suggested that the slope of the second exponential of the plasma disappearance curve may be used to monitor changes in renal function instead of plasma clearance calculated using the slope-intercept method. The purpose of this study was to evaluate the magnitude of error in the slope induced by errors in sampling time and in activity measurement, and to compare it with the error observed in clearance. A model of mono-exponential curves based on two blood samples, taken at 120 and 240 min, was created. Normally distributed random errors were introduced into the sampling times and activity measurements. For each setting, the random errors were successively introduced 200 times and the coefficients of variation of the calculated slopes and clearances were determined. Variable errors in slope and clearance were induced by errors in sampling time and activity measurement. In general, the observed errors in the slope were high in the case of low slope values, decreasing progressively for increasing slope values. The errors in clearance followed a different pattern: highest errors were observed in the case of very low clearance, decreasing progressively for higher clearance values and attaining the minimal value at a lambda around 0.006 min-1, which corresponds to clearance of about 90 ml.min-1. The magnitude of the errors then started to increase again for higher clearance. For a large range of clearance values, the errors in the slope were higher than the errors in clearance. The only exceptions were cases with very high clearance rates. In conclusion, clearance calculation using the slope-intercept method should be preferred to that using the slope alone for monitoring changes in renal function.

Simplified algorithms for the estimation of 99Tcm-MAG3 clearance.

The aim of this study was to evaluate two formulae allowing the determination of MAG3 clearance by means of a single blood sample, namely Bubeck's formula and Russell's formula. As a first step, a simulation study was performed with the two single-sample algorithms to predict MAG3 clearance as a function of plasma concentration, using various times for blood sampling and various body surface areas. As a second step, a validation study on 47 adult patients with varying renal function allowed a clinical comparison between the reference technique, namely the multiple blood sample technique, and the two simplified techniques. The simplified algorithms were calculated using the fitted value at 44 min. In the simulation study, whatever the time of blood sampling or the level of correction introduced for body surface area, the results obtained by means of Bubeck's algorithm diverged significantly from those of Russell's algorithm, for low clearance values as well as for high clearance values. The curve of the differences between the two methods had a typical boomerang shape. In the clinical study, the difference between Russell's algorithm and the reference method was generally within 20 ml.min-1, with no systematic bias; with Bubeck's algorithm there was a marked underestimation, both in the low and high clearance ranges. We suggest Russell's single-sample method is the method of choice.

A multicenter trial on interobserver reproducibility in reporting on 99mTc-DMSA planar scintigraphy: a Belgian survey.

UNLABELLED: Conflicting opinions have been expressed regarding reproducibility in 99mTc-dimercaptosuccinic acid (DMSA) planar renal image interpretation. The purpose of this investigation was to determine the level of interobserver variability among a large group of Belgian nuclear medicine physicians who evaluated a randomly selected series of DMSA planar scintigraphic examinations performed on children and adults. METHODS: All Belgian nuclear medicine centers (n = 82) were invited to participate in a reproducibility study on 99mTc-DMSA scintigraphy. 99mTc-DMSA scans obtained on 10 adults and 40 children were randomly selected from the databases of 2 hospitals. Those participating in this investigation (65 centers = 79%) received a series of computer disks containing 50 99mTc-DMSA studies. To avoid potential problems related to unfamiliar display, the disks were formatted to be interpretable using the participants' own computer systems. Each participant was then free to use his or her usual display (hard copies, contrast enhancement, color scale, gray scale, and so forth). For each kidney, the observers had to choose between the following answers: normal, abnormal, equivocal, and lack of quality. RESULTS: Forty-two responses were obtained from a wide variety of institutions and from observers with different levels of experience in interpreting 99mTc-DMSA scintigraphy. Altogether, the following data were obtained: 60.8% normal, 25.2% abnormal, 7.0% equivocal, and 3.2% lack of quality. The median percentage of agreement (overall reproducibility) for the 42 observers was 92%. When the results of all 42 observers were compared, the median agreements on normality and abnormality were 93.5% and 90.5%, respectively. In a small number (n = 4) of kidneys, reproducibility was poor and ranged from 51% to 70%. Except for 2 outliers, all observers had almost the same level of performance. CONCLUSION: A large number of Belgian nuclear medicine physicians participated in evaluating a large randomly selected sample of 99mTc-DMSA studies, and excellent interobserver agreement was found.

The use of cerebral blood flow as an index of neuronal activity in functional neuroimaging: experimental and pathophysiological considerations.

Over recent years, activation studies that have been undertaken using brain imaging techniques, such as functional magnetic resonance imaging, positron emission tomography or near infrared spectroscopy, have greatly improved our knowledge of the functional anatomy of the brain. Nevertheless, activation studies do not directly quantify the variations of synaptic transmission (neuronal activity) but detect it indirectly either through the visualisation of changes in cerebral blood flow, oxidative or glycolytic metabolism (for positron emission tomography), or through the measurement of a global index that is dependent on both cerebral blood flow and oxidative metabolism (for functional magnetic resonance imaging and near infrared spectroscopy). Such approaches are based on the concept of a tight parallelism--termed coupling--between variations in neuronal activity, metabolism and cerebral blood flow. However, several "uncoupled" situations between these parameters have been reported over the last decade through experimental, pharmacological and pathophysiological studies. The aim of this review is to focus on these data that have to be taken into account for the interpretation of the results obtained in activation paradigms.

Quantification of 99Tcm-HMPAO brain SPET in two series of healthy volunteers using different triple-headed SPET configurations: normal databases and methodological considerations.

We evaluated the methodological issues underlying the assessment of normal confidence intervals, as used in clinically based region-of-interest (ROI) semi-quantification of 99Tcm-HMPAO brain SPET. At two different centres equipped with high-resolution, triple-headed gamma cameras, HMPAO SPET scans were performed on two groups of 24 and 15 healthy volunteers respectively. Together with an operator-defined analysis (ODA), a semi-automated analysis (SAA) was conducted on the normal datasets in one centre. Tests of intra- and inter-observer variability were performed. Repeat scans were performed within 72 h after the first to analyse short-term regional inter-study variations. The overall regional uptake showed significant differences in most regions between both normal datasets. Intra-observer and inter-observer reproducibility were on average within 4% for the ODA, while for the SAA it was less than 1%. Inter-study variations were excellent for both centres, ranging from -4% to +3% for most regions studied. The variability in clinical brain perfusion studies largely depends on the reproducibility of the data analysis technique. A semi-automated approach shows clear advantages over an entirely operator-defined approach. Intra-subject repeat studies show enough stability for use as reliable baseline measurements in the construction of a normal database or to allow activation studies with high sensitivity.

Estimation of risk based on biological dosimetry for patients treated with radioiodine.

A multicentre study was undertaken to assess the cytogenetic damage to peripheral blood lymphocytes in 31 patients treated with 131I for thyrotoxicosis using the cytokinesis-blocked micronucleus assay. The results were compared to those for eight thyroid carcinoma patients using the same method. For each patient, blood samples were taken immediately before and 1 week after iodine administration. The first blood sample was divided into three fractions and each fraction was subsequently irradiated in vitro with 0, 0.5 and 1 Gy 60Co gamma rays, respectively. After blood culture for 70 h, cells were harvested, stained with Romanowsky-Giemsa and the micronuclei scored in 1000 binucleated cells. For both patient groups, a linear-quadratic dose-response curve was fitted through the data set of the first blood sample by a least squares analysis. The mean increase in micronuclei after 131I therapy (second blood sample) was fitted to this curve and the mean equivalent total body dose (ETBD) calculated. Surprisingly, in view of the large difference in administered activity between thyroid carcinoma patients and thyrotoxicosis patients, the increase in micronuclei after therapy (mean +/- S.D.: 32 +/- 30 and 32 +/- 23, respectively) and the equivalent total body dose (0.34 and 0.32 Gy, respectively) were not significantly different (P > 0.1). The small number of micronuclei induced by 131I therapy (32 +/- 29), compared with external beam radiotherapy for Hodgkin's disease (640 +/- 381) or cervix carcinoma (298 +/- 76) [1], gave a cancer mortality estimate of less than 1%. This also explains why late detrimental effects in patients after 131I treatment have not been reported in the literature.

The contribution of bone scintigraphy in occupational health or medical insurance claims: a retrospective study.

Patients with a suspicion of bone damage following an industrial or traffic accident are often referred for bone scintigraphy as part of an occupational health or medical insurance investigation. The aim of this study was to assess the contribution and the potential role of bone scintigraphy compared with X-ray investigations in the aforementioned situation. To this end we evaluated 70 consecutive patients referred for bone scintigraphy during 1996 and 1997 by occupational health or medical insurance physicians. The most common reasons for referral were the exclusion of occult fractures of hands and feet, whiplash injuries, reflex sympathetic dystrophy or avascular necrosis, or the differentiation between an old and a recent vertebral fracture. X-rays were only available for comparative review of 53 patients, so only those were analysed. The results of bone scintigraphy were compared with X-rays, and their contribution and potential role in occupational health or medical insurance investigations assessed. In 31 out of the 53 patients investigated, bone scintigraphy findings concurred with X-rays as to the number and location of abnormalities. For 19 of the 53 patients, bone scintigraphy showed clinically relevant additional foci when compared with X-rays, predominantly involving lesions to hands/wrists and feet/ankles. Among these 19 patients, scintigraphic diagnoses were subsequently confirmed in ten cases by means of X-ray or computed tomography. In four patients, supplementary radiological investigations revealed no abnormalities, and in five patients no further investigations were undertaken. Finally, in three of the 53 patients, X-rays revealed bone damage (burst fractures) whilst the corresponding bone scintigraphy was negative, thus excluding recent injury. In conclusion, in 22 patients, representing 42% of the cases analysed, bone scintigraphy was conclusive compared with X-ray imaging in the final diagnosis and in this way in detecting occult or excluding active bone damage after a traffic or industrial accident. This makes bone scintigraphy a useful investigation in situations where a full or partial disablement claim has to be confirmed, extended or terminated.

Technetium-99m-MDP scintigraphy and long-term follow-up of treated primary malignant bone tumors.

UNLABELLED: Local malignant bone tumor excision followed by high-dose extracorporeal irradiation (300 Gy) and subsequent reimplantation is a unique technique for treatment of primary bone and cartilage tumors. The long-term scintigraphic findings of irradiated bone autografts in relation to clinical patient data were reviewed retrospectively. METHODS: Thirty-seven patients (12 women, 25 men; age range 13.0-66.7 yr; average age 29.1 yr) were studied. Postsurgical anatomopathological diagnoses included osteosarcoma, 20 patients; chondrosarcoma, 7 patients; and other less-frequent primary osteogenic tumors, 10 patients. Three hundred ninety 99mTc-methylene diphosphonate (MDP) whole-body scans performed between 3 mo and 18.3 yr (mean 6.5 yr) after treatment were reviewed. RESULTS: The 10-yr actuarial survival rate was 78%. After a mean period of 19.4 mo, 6 patients developed a local recurrence, and MDP scintigraphy detected the recurrence in 4. Distant metastases developed in 11 patients (30%), of which 10 were nonosseous. Initially, all autografts appeared as photon-deficient areas. Diffusely increased bone uptake was present at osteotomy sites and at articulating surfaces contiguous with autografts within the first few months after surgery. Of all 25 patients with adequate follow-up, 7 showed persistent decreased uptake up to 129 mo after surgery. The other patients developed partial tracer uptake after 19.6 mo, on average. In 6 patients, scintigraphic images consistent with complete revascularisation were noted later (mean 31.5 mo). Local, sometimes multiple, complications were noted in 22 patients, mainly mechanical graft-related (15) or infections (11). Scintigraphic sensitivity for mechanical complications was 100%. Significantly more fractures and collapses were seen when partial tracer uptake suggestive of revascularisation occurred. Altered bone stress gave rise to focal and diffuse scintigraphic abnormalities, often in the spine and lower extremities. In recent literature, similar clinical complication patterns are found for massive allografts. CONCLUSION: Skeletal scintigraphy is a sensitive technique for evaluating long-term follow-up of massive grafts to treat primary malignant bone tumors. Revascularisation and partial bone ingrowth are not sufficient conditions for a lower complication rate.

Optimizing background correction when calculating differential renal function in the presence of hydroureteronephrosis using 99Tc(m)-DTPA.

We performed a prospective study to establish the optimal background correction algorithm for the determination of differential renal function (DRF), using 99Tc(m)-diethylenetriamine pentaacetate (99Tc(m)-DTPA) in the presence of unilateral hydronephrosis, with 24 h 99Tc(m)-dimercaptosuccinic acid (99Tc(m)-DMSA) uptake as the 'gold standard'. From September 1996 to June 1997, 12 males and 4 females (mean age 10 years, range 1 month to 72 years), presenting with unilateral hydronephrosis, were studied. All patients underwent both DTPA renography and quantitative DMSA scintigraphy within 24 h. In all patients, using a surface method, the DRF of the obstructed kidney was determined using infrarenal, suprarenal and perirenal background correction, time intervals of 60-180 s (t1), 120-180 s (t2) and 80-140 s (t3), and the application or non-application of a Rutland-Patlak correction (RPC). In the absence of RPC, for all three types of background correction, no difference in DTPA DRF for any of the three time intervals was noted; higher DTPA DRF values were found (mean +/- S.D.: overestimates of 7.8+/-24.4%, 6.5+/-9.5% and 3.3+/-14.9% for suprarenal, infrarenal and perirenal background correction, respectively). Application of RPC resulted in an overall decrease in both the mean and standard deviation values, which was most pronounced with infrarenal background correction: -0.38+/-6.5% for t1, 0.31+/-6.3% for t2 and -1.3 +/-6.9% for t3 (t1 vs t2, P = 0.06; t3 vs t1 or t2, P = 0.04). Our results suggest that infrarenal background correction using t1 or t2 and RPC is the best algorithm for DRF estimation using 99Tc(m)-DTPA renography.

Dipyridamole-induced angina pectoris during sestamibi stress test in patients with significant coronary artery disease: clinical, angiographic, and nuclear determinants.

Intravenous dipyridamole induces angina pectoris (AP) in some patients with significant coronary artery disease (CAD). The aim of this prospective study was to identify the angiographic, nuclear, and clinical determinants. The authors examined 50 patients consecutively with significant CAD on coronary angiography. All antiischemic medications were stopped twenty-four hours (nitrates only 6 hours) before injection of dipyridamole (0.84 mg/kg). ECGs were taken before, during, and after this injection. The regional myocardial activity of Tc-99m-Sestamibi at rest and after dipyridamole injection was measured with single-photon emission computed tomography (SPECT). During dipyridamole injection 20 patients had AP, of whom 15 had ST segment depression on ECG (P < 0.001). The only significant difference on coronary angiography between patients with dipyridamole-induced AP and those without AP was the presence of collaterals (P < 0.05). In patients with AP and collaterals, ECG and SPECT changes were always noted in the collateralized territory. Subgroup analysis showed that patients without previous myocardial infarction (MI, n = 17, P < 0.05) or nontransmural MI (n = 17, P < 0.05) had a good correlation between collaterals and AP, whereas patients with a history of transmural MI (n = 16) did not. No further significant variables could be found as a predictor of AP after dipyridamole injection. These findings suggest that AP during dipyridamole stress test is due to ischemia, which is not related to the severity of CAD. Ischemia is probably due to coronary steal to the collateralized territory in patients without transmural MI. Dipyridamole-induced angina pectoris is predictive for collaterals and may indicate viability in patients with MI.

Renal technetium-99m-DMSA SPECT in normal volunteers.

UNLABELLED: Dimercaptosuccinic acid (DMSA) renal scintigraphy today is considered a sensitive and useful technique for the detection of cortical abnormalities. Recent studies have suggested that lesion detection can be improved by SPECT imaging. This study investigated normal kidneys using different SPECT modalities. METHODS: Ten young, healthy volunteers with normal clinical history and normal renal ultrasound underwent planar and SPECT DMSA imaging 2 to 4 hr after intravenous injection of 99mTc-DMSA (185 MBq). Analysis of SPECT data was focused on the homogeneity of cortical uptake (comparison of upper and lower pole activity) as well as on the presence or absence of focal cortical defects. RESULTS: No abnormality could be observed on the planar images. SPECT revealed, in seven kidneys (five left and two right), the presence of a hypoactive upper pole. This was visually observed on the coronal slices with up to 35% difference between upper and lower pole. Moreover, three focal cortical defects were visualized on the coronal slices as well as on three-dimensional surface shade displays. CONCLUSION: These normal patterns should be recognized when evaluating a patient with possible renal involvement.