A software engine to justify the conclusions of an expert system for detecting renal obstruction on 99mTc-MAG3 scans.

The purposes of this study were to describe and evaluate a software engine to justify the conclusions reached by a renal expert system (RENEX) for assessing patients with suspected renal obstruction and to obtain from this evaluation new knowledge that can be incorporated into RENEX to attempt to improve diagnostic performance. METHODS: RENEX consists of 60 heuristic rules extracted from the rules used by a domain expert to generate the knowledge base and a forward-chaining inference engine to determine obstruction. The justification engine keeps track of the sequence of the rules that are instantiated to reach a conclusion. The interpreter can then request justification by clicking on the specific conclusion. The justification process then reports the English translation of all concatenated rules instantiated to reach that conclusion. The justification engine was evaluated with a prospective group of 60 patients (117 kidneys). After reviewing the standard renal mercaptoacetyltriglycine (MAG3) scans obtained before and after the administration of furosemide, a masked expert determined whether each kidney was obstructed, whether the results were equivocal, or whether the kidney was not obstructed and identified and ranked the main variables associated with each interpretation. Two parameters were then tabulated: the frequency with which the main variables associated with obstruction by the expert were also justified by RENEX and the frequency with which the justification rules provided by RENEX were deemed to be correct by the expert. Only when RENEX and the domain expert agreed on the diagnosis (87 kidneys) were the results used to test the justification. RESULTS: RENEX agreed with 91% (184/203) of the rules supplied by the expert for justifying the diagnosis. RENEX provided 103 additional rules justifying the diagnosis; the expert agreed that 102 (99%) were correct, although the rules were considered to be of secondary importance. CONCLUSION: We have described and evaluated a software engine to justify the conclusions of RENEX for detecting renal obstruction with MAG3 renal scans obtained before and after the administration of furosemide. This tool is expected to increase physician confidence in the interpretations provided by RENEX and to assist physicians and trainees in gaining a higher level of expertise.     

iRENEX: a clinically informed decision support system for the interpretation of 99mTc-MAG3 scans to detect renal obstruction

Purpose

Decision support systems for imaging analysis and interpretation are rapidly being developed and will have an increasing impact on the practice of medicine. RENEX is a renal expert system to assist physicians evaluate suspected obstruction in patients undergoing mercaptoacetyltriglycine (MAG3) renography. RENEX uses quantitative parameters extracted from the dynamic renal scan data using QuantEM?II and heuristic rules in the form of a knowledge base gleaned from experts to determine if a kidney is obstructed; however, RENEX does not have access to and could not consider the clinical information available to diagnosticians interpreting these studies. We designed and implemented a methodology to incorporate clinical information into RENEX, implemented motion detection and evaluated this new comprehensive system (iRENEX) in a pilot group of 51 renal patients.

Methods

To reach a conclusion as to whether a kidney is obstructed, 56 new clinical rules were added to the previously reported 60 rules used to interpret quantitative MAG3 parameters. All the clinical rules were implemented after iRENEX reached a conclusion on obstruction based on the quantitative MAG3 parameters, and the evidence of obstruction was then modified by the new clinical rules. iRENEX consisted of a library to translate parameter values to certainty factors, a knowledge base with 116 heuristic interpretation rules, a forward chaining inference engine to determine obstruction and a justification engine. A clinical database was developed containing patient histories and imaging report data obtained from the hospital information system associated with the pertinent MAG3 studies. The system was fine-tuned and tested using a pilot group of 51 patients (21 men, mean age 58.2?±?17.1?years, 100 kidneys) deemed by an expert panel to have 61 unobstructed and 39 obstructed kidneys.

Results

iRENEX, using only quantitative MAG3 data agreed with the expert panel in 87?% (34/39) of obstructed and 90?% (55/61) of unobstructed kidneys. iRENEX, using both quantitative and clinical data agreed with the expert panel in 95?% (37/39) of obstructed and 92?% (56/61) of unobstructed kidneys. The clinical information significantly (p?Conclusion Our renal expert system for detecting renal obstruction has been substantially expanded to incorporate the clinical information available to physicians as well as advanced quality control features and was shown to interpret renal studies in a pilot group at a standardized expert level. These encouraging results warrant a prospective study in a large population of patients with and without renal obstruction to establish the diagnostic performance of iRENEX.     

Diagnostic performance of an expert system for interpretation of 99mTc MAG3 scans in suspected renal obstruction.

The purpose of the study was to compare diuresis renography scan interpretation generated by a renal expert system with the consensus interpretation of 3 expert readers. METHODS: The expert system was evaluated in 95 randomly selected furosemide-augmented patient studies (185 kidneys) obtained for suspected obstruction; there were 55 males and 40 females with a mean age +/- SD of 58.6 +/- 16.5 y. Each subject had a baseline (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG3) scan followed by furosemide administration and a separate 20-min acquisition. Quantitative parameters were automatically extracted from baseline and furosemide acquisitions and forwarded to the expert system for analysis. Three experts, unaware of clinical information, independently graded each kidney as obstructed/probably obstructed, equivocal, and probably nonobstructed/nonobstructed; experts resolved differences by a consensus reading. These 3 expert categories were compared with the obstructed, equivocal, and nonobstructed interpretations provided by the expert system. Agreement was assessed using weighted kappa, and the predictive accuracy of the expert system compared with expert readers was assessed by the area under receiver-operating-characteristic (ROC curve) curves. RESULTS: The expert system agreed with the consensus reading in 84% (101/120) of nonobstructed kidneys, in 92% (33/36) of obstructed kidneys, and in 45% (13/29) of equivocal kidneys. The weighted kappa between the expert system and the consensus reading was 0.72 and was comparable with the weighted kappa between experts. There was no significant difference in the areas under the ROC curves when the expert system was compared with each expert using the other 2 experts as the gold standard. CONCLUSION: The renal expert system showed good agreement with the expert interpretation and could be a useful educational and decision support tool to assist physicians in the diagnosis of renal obstruction. To better mirror the clinical setting, algorithms to incorporate clinical data must be designed, implemented, and tested.     

F+0 diuresis renography in infants and children.

The purpose of this study was to evaluate the feasibility of modifying diuresis renography by the simultaneous administration of 99mTc-mercaptoacetyltriglycine (MAG3) and furosemide in the investigation of hydronephrosis and hydroureteronephrosis in infants and children. Two parameters were assessed: the diuretic response in normal kidneys and the ability of the F+0 study to differentiate between renal obstruction and nonobstruction and to identify the level of obstruction in cases of renal obstruction. METHODS: Seventy-two patients (48 males, 24 females; age 2 d to 7 y; median age 6 wk) with sonographic diagnoses of hydronephrosis or hydroureteronephrosis were reviewed prospectively over a 3-y period. All patients had prior sonographic studies and micturating cystourethrography. Bladder catheterization was not routinely performed and was undertaken only if the child had suspected vesicoureteric junction (VUJ) obstruction or grade II or more vesicoureteric reflux. A weight-adjusted dose of 99mTc-MAG3 (maximum 200 MBq, minimum 20 MBq) and 1 mg/kg of furosemide (maximum 40 mg) were administered intravenously at the same time. Posterior imaging of the kidneys and bladder was performed for 20 min and followed by gravity-assisted drainage or imaging after voiding. All patients were followed-up for 6-12 mo, and the final diagnoses were based on either surgery or conservative management with repeated sonography or follow-up 99mTc-MAG3 studies (or both). The results of the F+0 diuresis renography were then compared with the final diagnoses. RESULTS: A renal unit was defined as a kidney and its ureter. There were 151 renal units with 1 patient having bilateral duplex kidneys, 6 patients having unilateral duplex kidneys and 1 patient having a solitary kidney. Fifty-five normal renal units and 96 abnormal renal units on the basis of sonographic findings were assessed. The furosemide clearance half-time for the 55 normal renal units was 1.3-6.3 min (mean 3.8 min). Of the 96 abnormal renal units, 53 were classified as nonobstructed and 43 were classified as obstructed. Of the 53 renal units classified as nonobstructed, there were 48 true-negative studies and 5 false-negative studies; of the 43 renal units classified as obstructed, there were 40 true-positive studies and 3 false-positive studies. The sensitivity was 88.9%, specificity was 94.1% and accuracy was 91.7%. The level of obstruction, either pelviureteric junction or VUJ, was also correctly identified. CONCLUSION: F+0 diuresis renography shows excellent diuretic responses in normal kidneys and is a valid method for the investigation of hydronephrosis and hydroureteronephrosis in infants and children.     

Volume expanded diuretic renography in the postnatal assessment of suspected uretero-pelvic junction obstruction.

Controversy surrounds the role of 99mTc-diethylenetriamine pentaacetic acid renography in suspected uretero-pelvic junction obstruction in early life. Accordingly, we retrospectively reviewed 18 patients (28 hydronephrotic kidneys) with a mean age of 2 mo (range: 1 wk-6 mo) who underwent a total of 36 scans using intravenous volume expansion (10 ml/kg) and furosemide diuresis (1 mg/kg). Initial scans were classified as obstructed, not obstructed or indeterminate using differential renal function, furosemide washout T 1/2 and visual assessment of tracer clearance. Those initially classified as obstructed (n = 8) have been surgically confirmed. In the indeterminate (n = 6) and nonobstructed (n = 14) groups, three and two kidneys, respectively, developed obstruction on progress scans. Mean follow-up in the nonsurgical patients was approximately 9 mo (range: 4-17 mo). A total of 13 kidneys had developed obstruction by renographic criteria, and to date 12 have surgical confirmation. Our data indicate that: (1) scans classified as obstructed correlate well with surgery; (2) an initial classification of indeterminate or nonobstructed does not exclude later development of obstruction; and (3) serial scans correctly stratify children with possible uretero-pelvic junction obstruction.     

Unenhanced urinary CT: value of parenchymal attenuation measurements in differentiating acute vs. chronic renal obstruction

Objective

We aimed to search if the renal parenchymal attenuation measurements on unenhanced CT scans could be useful in differentiating acutely obstructed kidneys from chronic cases or unobstructed kidneys.

Material and methods

Unenhanced CT scans of 101 patients were retrospectively reviewed. Thirty-two patients with unilateral acute renal obstruction, 34 patients with unilateral chronic renal obstruction due to various reasons and 35 control subjects were included in the study. The parenchymal densities of both kidneys were measured, from the upper poles, middle portions, and lower poles of each kidney. The mean parenchymal densities of both kidneys were calculated in all three groups of subjects. Secondary signs of renal obstruction such as perinephric stranding, size of ureteral stone, degree of hydronephrosis were also noted for each kidney.

Results

The mean parenchymal attenuation value on the acutely obstructed side was lower than the unobstructed side, 24.21 ± 3.68 and 30.68 ± 4.75 respectively (p < 0.001). The mean parenchymal attenuation value on the acutely obstructed side (24.21 ± 3.68) was lower than both the chronically obstructed side (30.85 ± 4.53), and the control subjects (29.62 ± 3.03 on corresponding side). There was no statistically significant attenuation difference between right and left kidneys in the control group and chronic obstruction group.

Conclusion

Renal parenchymal attenuation measurements and attenuation differences of both kidney of same patient could be useful in differentiating acute unilateral obstruction from chronic cases.     

Decision support systems in diuresis renography

The volume of diagnostic imaging studies performed in the United States is rapidly increasing resulting from an increase in the number of patients as well as an increase in the volume of studies per patient. Concurrently, the number and complexity of images in each patient data set are also increasing. Nuclear medicine physicians and radiologists are required to master an ever-expanding knowledge base whereas the hours available to master this knowledge base and apply it to specific tasks are steadily shrinking. The convergence of an expanding knowledge base and escalating time constraints increases the likelihood of physician errors. The problem is particularly acute for low-volume studies such as MAG3 diuresis renography where many imagers may have had limited training or experience. To address this problem, renal decision support systems (DSS) are being developed to assist physicians evaluate suspected obstruction in patients referred for diuresis renography. Categories of DSS include neural networks, case-based reasoning, expert systems and statistical systems; RENEX and CART are examples of renal DSS currently in development. RENEX (renal expert) uses a set of rules obtained from human experts to analyze a knowledge base of expanded quantitative parameters obtained from diuresis MAG3 scintigraphy whereas CART (classification and regression tree analysis) is a statistical method that grows and prunes a decision tree based on an analysis of these quantitative parameters in a training data set. RENEX can be queried to provide the reasons for its conclusions. Initial data show that the interpretations provided by RENEX and CART are comparable to the interpretations of a panel of experts blinded to clinical information. This project should serve as a benchmark for the scientific comparison and collaboration of these 2 fields of medical decision-making. Moreover, we anticipate that these DSS will better define the essential interpretative criteria, foster standardized interpretation, teach trainees to better interpret renal scans, enhance diagnostic accuracy and provide a methodology applicable to other diagnostic problems in radiology and medicine.     

Kit preparation of technetium-99m-mercaptoacetyltriglycine: analysis, biodistribution and comparison with technetium-99m-DTPA in patients with impaired renal function

Technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) was prepared by a frozen solution method, enabling the preparation of kits yielding a product substantially free of lipophilic impurities (96% 99mTc-MAG3). However, biliary activity was not completely eliminated as HPLC-purified 99mTc-MAG3 was also excreted by that route. Sequential 99mTc-DTPA and 99mTc-MAG3 renal scans were performed in 15 patients with renal dysfunction, including renal transplant recipients. In all cases, the 99mTc-MAG3 kit preparation provided superior images to 99mTc-DTPA at all levels of renal function due to a higher target-to-background ratio and a plasma clearance twice as fast as 99mTc-DTPA. Interpretation of delayed 99mTc-MAG3 images, however, was complicated by biliary excretion which will limit quantitative estimates of renal clearance. A 99mTc-MAG3 kit is likely to be of value in renal transplant assessment and in cases of significant renal impairment but would not appear to offer major advantages over 99mTc-DTPA in routine renal imaging.     

Renal vein Doppler sonography of obstructive uropathy

OBJECTIVE: Obstructive uropathy in the early stages can be difficult to diagnose using either standard sonography or the arterial resistive index. We tested the hypothesis that acute obstruction of the renal collecting system reduces the intraparenchymal renal compliance, which affects the intraparenchymal venous blood flow to a greater degree than the arterial flow. SUBJECTS AND METHODS: Twelve patients with clinical evidence of acute obstructive uropathy were referred for helical CT to confirm the diagnosis and to provide a gold standard by which we could evaluate the sonographic findings in the 12 test patients. Twelve patients without renal disease served as a control group. Doppler sonography of the interlobar arteries and veins of both kidneys then was performed, with the sonographer unaware of which kidney had an obstruction. Peak venous flow measurements and arterial resistive and venous impedance indexes were obtained. The impedance indexes of the obstructed and unobstructed kidney were compared for each patient. RESULTS: The mean arterial resistive indexes of the obstructed kidneys were larger than those of the unobstructed kidneys, 0.67 +/- 0.08 and 0.62 +/- 0.05, respectively (p = 0.05). The venous impedance indexes comparing obstructed and unobstructed sides were 0.38 +/- 0.25 and 0.80 +/- 0.25, respectively, a statistically significant result (p = 0.0002). On average, the peak venous flow signal in the obstructed kidney was 69% higher than that of the unobstructed kidney (p = 0.04) and 86% higher than that of the peak venous flow signal in the control group (p = 0.005). CONCLUSION: Renal obstruction alters the venous flow to a greater extent than the arterial flow, and a comparison between the venous flow in the obstructed and unobstructed kidneys may improve diagnostic accuracy.     

MAG3-F0 scintigraphy in decision making for emergency intervention in renal colic after helical CT positive for a urolith.

Patients with renal colic are evaluated with clinical, laboratory, and imaging methods for stratification for emergency decompression, medical treatment, or discharge and follow up. The current standard practice is heavily based on unenhanced helical CT for detecting uroliths. However, the presence of a urolith does not necessarily mean that the kidney is obstructed and requires emergency decompression. In this study, technetium-mercaptoacetyltriglycine (MAG3) diuretic scintirenography was used to detect obstruction in patients with renal colic. The contribution of this test to patient management after positive findings from helical CT was also studied. METHODS: Diagnostic criteria were established on the basis of previous experience with 60 patients who had renal colic and had undergone radiography of the kidneys, ureters, and urinary bladder (KUB) and diuretic Tc-MAG3 scintirenography and were followed up to correlate scintigraphic findings with clinical outcome. Subsequently, 80 patients with renal colic underwent scintigraphy within 12 h of presentation in the emergency room, after abdominal helical CT showed findings positive for calculus and suggestive of obstruction. After therapeutic oral or intravenous hydration and analgesics, diuretic dynamic renal scintigraphy (flow, function, delayed imaging) was performed after intravenous injections of 10 mCi (370 MBq) 99mTc-MAG3 and 40 mg furosemide (at zero time, or F0). Results were available soon after completion of the study and were considered in patient management. Four characteristic patterns of scintirenography, essential in patient stratification and treatment, had been standardized and were used for interpretation of the studies: the unobstructed kidney; the partially obstructed kidney, proximally or distally obstructed, with mild to severe obstruction and impairment of function; the totally obstructed kidney, with arrested renal function; and the unobstructed but dysfunctioning kidney after decompression, or stunned kidney. RESULTS: Among the 80 patients with positive helical CT findings, 56.5% were found to have obstruction by scintigraphy (32.5% partially, 24% completely); the remaining 43.5% did not have obstruction (21% without an indication of recent obstruction and 22.5% with stunned kidneys after spontaneous decompression). Occasionally, findings of preexistent urine extravasation or infection were present. Patients who, by scintigraphy, never had obstruction or had experienced spontaneous decompression did not require admission or emergency intervention; those with complete or severe obstruction required admission and decompression for relief of pain or restoration of function, whereas those with mild obstruction were treated variably with forced fluids, analgesics, or, less frequently, elective surgery. Outcome information from clinical examination, imaging, and interventional findings indicated that this stratification was successful. The test caused no side effects. CONCLUSION: For renal colic, clinical selection, KUB radiography, and even positive helical CT findings were all found to have a low positive predictive value for obstruction (in this study, 35%, 32%, and 56% respectively). Anatomic studies, including helical CT, should be followed by diuretic MAG3-F0 scintirenography to diagnose and quantify or exclude obstruction, detect spontaneous decompression, and appropriately stratify patients for emergency intervention, observation and medical therapy, or further work-up and discharge with referral to the clinic.     

Differences of renal parenchymal attenuation for acutely obstructed and unobstructed kidneys on unenhanced helical CT: a useful secondary sign?

OBJECTIVE: The purpose of this study was to ascertain whether the difference in attenuation frequently noted on unenhanced helical CT scans between a patient's acutely obstructed kidney and the unobstructed kidney is a reliable secondary sign of acute renal obstruction. CONCLUSION: In 95% of patients with acute renal obstruction, the affected kidney was less dense than the unobstructed kidney. When visually detected by radiologists using CT, this difference in density was at least two standard deviations above normal, making it a reliable secondary sign for acute obstruction.     

Improved renal clearance and tumor targeting of 99mTc-labeled anti-Tac monoclonal antibody Fab by chemical modifications

This study was undertaken to improve the renal clearance and tumor targeting properties of 99mTc-labeled humanized anti-Tac (HuTac) monoclonal antibody Fab fragments using two chemical approaches: 1) labeling with a renal secretion agent 99mTc-mercaptoacetyltriglycine (MAG3) and 2) lowering its isoelectric point (pI) by acylation. HuTac Fab (3.3 mg/mL) was reacted with a trifluorophenyl ester (TFP) of 99mTc-MAG3 alone or was additionally reacted with TFP-glycolate to reduce the pI. In Balb/c mice, 99mTc-MAG3-Fab (pI > 9.3) rapidly accumulated in the kidneys (177% injected dose [ID]/g at 15 min) and then gradually cleared out of the kidneys. In contrast, the glycolation (pI 4.6 approximately 6.6) drastically reduced the renal uptake (31% ID/g) and also the whole-body retention (82% ID vs 101% for the nonglycolated) at 15 min, indicating that the glycolated 99mTc-MAG3-Fab (pI 4.6 approximately 6.6) was rapidly excreted. The glycolated remained in the blood longer than the nonglycolated (1.2% vs 0.3% ID/g at 360 min), but this effect was less drastic than the effect shown on the renal uptake. In nude mice bearing receptor-positive (ATAC4) tumors, the glycolated 99mTc-MAG3-Fab increased the peak tumor uptake to 14.8% ID/g from 8.3% ID/g for 99mTc-MAG3-Fab, whereas the glycolation resulted in a drastic reduction of the renal uptake at 15 min. We demonstrated that the renal clearance and the tumor targeting of Fab could be optimized by chemical modifications.     

Evaluation of renal function from 99mTc-MAG3 renography without blood sampling.

To develop a camera-based method for evaluating renal function with 99mTc-mercaptoacetyltriglycine (MAG3), we examined the relationship between various renogram parameters and 99mTc-MAG3 clearance. METHODS: Twenty-one patients underwent renal scintigraphy with 99mTc-MAG3. Eighty 3-s frames were obtained after the bolus injection of 250 MBq tracer, followed by the collection of 52 30-s frames. Regions of interest were drawn for the kidneys, perirenal background areas and subrenal background areas, and background-subtracted renograms were generated. Renal accumulation at 0.5-1.5, 0.5-2, 1-2, 1-2.5 and 1.5-2.5 min after tracer arrival in the kidney was calculated as area under the background-subtracted renogram, and percent renal uptake was obtained after correction for soft-tissue attenuation and injected dose. The slope of the renogram was determined for the same segments used in calculating area under the renogram, and slope index was computed as slope corrected for attenuation and injected dose. Percent renal uptakes and slope indices were correlated by linear regression analysis with 99mTc-MAG3 clearance measured using a single blood sampling method. RESULTS: Among the values of percent renal uptake, the value obtained at 1.5-2.5 min using the perirenal background correlated best with 99mTc-MAG3 clearance. The slope index at 0.5-1.5 or 0.5-2 min using the subrenal background provided better accuracy than percent renal uptake for predicting clearance. There were no substantial differences in the relative function of the right kidney between the methods using percent renal uptake and slope index. CONCLUSION: 99mTc-MAG3 clearance can be assessed with acceptable accuracy by a camera-based method. The method based on the slope of the renogram may replace the one based on the area under the renogram in evaluating renal function from 99mTc-MAG3 renograms.     

The absent kidney in 99Tcm-MAG3 renogram: a dramatic reversible consequence of contrast nephrotoxicity superimposed on renal obstruction

99Tcm-mercaptoacetyltriglycine (MAG3) renogram is a robust imaging technique used to delineate upper urinary tract obstruction. The changes observed on the renogram are often reversible on relief of obstruction. We present two cases illustrating the extreme consequence of contrast nephrotoxicity on pre-existing obstructed kidneys. In one case, this led to severe impairment of perfusion and uptake observed on 99Tcm-MAG3 renogram and in the second case virtual non-visualization of the obstructed kidney. Subsequent treatment of obstruction, led to dramatic improvement in renal function. It is important for clinicians, nuclear medicine physicians and radiologists to be aware of the potential of contrast nephrotoxicity in obstructed kidneys.     

Technetium-99m-L,L-ethylenedicysteine: a renal imaging agent. I. Labeling and evaluation in animals.

L,L-ethylenedicysteine (L,L-EC) can be labeled efficiently with 99mTc at pH 12 to obtain a highly pure and very stable tracer agent (99mTc-L,L-EC). The biological behavior of 99mTc-L,L-EC was studied in mice and a baboon. In mice, 99mTc-L,L-EC demonstrated a more rapid urinary excretion and less retention in the kidneys, the liver, the intestines, and the blood than did 99mTc-MAG3 at 10 and 60 min p.i. Urinary excretion decreased in probenecid pretreated mice, which indicates active tubular transport. In the baboon, the renograms for 99mTc-MAG3 and 99mTc-L,L-EC were comparable. Plasma-protein binding of 99mTc-L,L-EC was lower than that of 99mTc-MAG3 while its distribution volume and 1-hr plasma clearance were clearly higher. The promising results of the animal experiments suggest that 99mTc-L,L-ethylenedicysteine may be a useful alternative to 99mTc-MAG3 for renal function studies in humans.     

MRI in patients with chronic obstructive uropathy and compromised renal function: a sole method for morphological and functional assessment

The aim of this study was to assess the role of MRI as a single modality for anatomical and functional evaluation of obstructed kidneys in patients with compromised renal function. The study included 96 adults with unilateral or bilateral chronic obstructive hydronephrosis and compromised renal function (serum creatinine >or=1.8 mg dl(-1)). Patients were subjected to gadolinium-enhanced MRI (Gd-MRI), which determined the anatomy of both renoureteral units, as well as their function, through selective calculation of the glomerular filtration rate (GFR) of each kidney. All patients underwent a technetium-99m diethylenetriamine-pentaacetic acid renal scan. Moreover, a correlation was made between the GFR determined by Gd-MRI and the isotope GFR. The study comprised 59 males and 37 females. A comprehensive MRI study detected the cause of obstruction in all kidneys with non-calcular obstruction (sensitivity of 100%) and in 21 kidneys with calcular obstruction (sensitivity of 70%). The overall sensitivity of MRI combined with plain X-ray of the abdomen and ultrasound in the detection of various causes of obstruction was 97%. A comparison between the isotope GFR of the obstructed kidneys and the corresponding magnetic resonance urography (MRU) GFR showed perfect correlation. In conclusion, combined static and dynamic MRU is a promising technique that allows anatomical and functional evaluation of obstructed kidneys in patients with impaired renal function but, owing to the possible risk of nephrogenic systemic fibrosis in patients with a GFR <30 ml min(-1), the lowest possible dose of the most stable Gd-macrocyclic chelates should be used if a functional MRI study is required.     

Pharmacokinetics of technetium-99m-MAG3 in humans

Technetium-99m-mercaptoacetylglycylglycylglycine (99mTc-MAG3) is introduced to replace o-iodohippurate (OIH) for renal function studies. For interpretation of clinical findings, extensive pharmacokinetic studies were performed on patients. These showed that 99mTc-MAG3, compared with OIH, has a higher plasma-protein binding, an essentially higher intravascular concentration, a smaller volume of distribution and, with practically identical biologic half-lives, a correspondingly lower clearance. Simultaneous steady-state measurements resulted in a 1.5-fold higher clearance of OIH than of 99mTc-MAG3 (n = 124). Competitive inhibition of the tubular transport system by p-aminohippurate (PAH) (20 patients) revealed a distinctly higher suppression of the 99mTc-MAG3 clearance than of OIH which indicates a lower affinity of the 99mTc complex to the tubular cell. The plasma extraction efficiencies of both agents, measured during surgery (n = 5), did not indicate an extrarenal elimination of 99mTc-MAG3. This new radiopharmaceutical is a pragmatic alternative to OIH and offers advantages not only for scintigraphic imaging but is also suited for quantitative renal function studies.     

99Tcm-mercapto acetyl triglycine in paediatric renal tract disease.

The use of 99Tcm-mercapto acetyl triglycine (99Tcm-MAG3), a new hippuran substitute, has been reported widely in adults but not in children. Our experience of its use in 100 infants and children for renography and indirect micturating cystography (IMC) is reported. The average age was 5.6 years. 65 patients completed IMC studies and nine patients had 99Tcm-dimercaptosuccinic acid (99Tcm-DMSA) scans performed on the same day. The majority of patients were referred for the investigation of urinary tract infection. 32 kidneys were found to be scarred on 99Tcm-MAG3 scans, 17 kidneys and ureters refluxed on IMC and 14 kidneys were obstructed. The results of 99Tcm-MAG3 scans were compared with those of other urinary tract investigations including ultrasound, micturating cystography (MCUG), intravenous urography (IVU) and 99Tcm-DMSA scintigraphy. No kidney which was scarred had a normal 99Tcm-MAG3 scan. All significant degrees of dilatation or obstruction on IVU or ultrasound were also detected by 99Tcm-MAG3. 99Tcm-MAG3 gave more information than any other single imaging modality and we believe it represents an ideal initial screening test in the investigation of urinary tract infection in older toilet-trained children.     

Quantitative SPECT of 99mTc-DMSA uptake in kidneys of infants with unilateral ureteropelvic junction obstruction: assessment of structural and functional abnormalities.

We evaluated individual renal function using quantitative SPECT of dimercaptosuccinic acid (DMSA) uptake by the kidneys (QDMSA) in infants with unilateral ureteropelvic junction (UPJ) obstruction and compared our findings with infants without obstruction. METHODS: QDMSA was performed on 13 infants (mean age of 2.8 +/- 2.8 mo) with unilateral UPJ obstruction and on 15 age-matched controls without obstruction. RESULTS: Control kidneys (n = 30) had a volume of 43.5 +/- 8.8 mL, a percentage injected dose (%ID)/mL 0.62 +/- 0.12 and uptake of 26.1% +/- 3.9%. Kidneys with UPJ obstruction (n = 13) had a volume of 61.2 +/- 19.3 mL, a %ID/mL of 0.42 +/- 0.11 and uptake of 25.4% +/- 8.2%. Contralateral kidneys (n = 13) had a volume of 44.0 +/- 11.9 mL, a %ID/mL of 0.57 +/- 0.16 and uptake of 24.2% +/- 4.6%. The uptake in obstructed kidneys was similar to that observed in contralateral and control kidneys (t = -0.77, P = 0.45; t = -0.37, P = 0.71; respectively). UPJ kidneys had a statistically significant increased volume and decreased %ID/mL, compared with contralateral kidneys (t = 3.35, P < 0.006 and t = 3.75, P < 0.003, respectively) and control kidneys (t = -4.2, P < 0.001 and t = 4.7, P < 0.001, respectively). There was no significant difference between contralateral kidneys and control kidneys regarding volume (t = -0.16, P = 0.87), %ID/mL (t = 0.98, P = 0.33) and uptake (t = -1.41, P = 0.16). Of 13 infants, 11 (85%) showed large kidneys with thinning of the renal cortex. In 1 infant, there was no difference between the obstructed and contralateral kidneys regarding volume, %ID/mL and uptake, and 1 infant showed significant decreased uptake in the UPJ kidney compared with the contralateral kidney. CONCLUSION: Although the overall renal function of the obstructed kidneys remained unchanged, there was a statistically significant decrease in the %ID/mL of renal tissue in UPJ kidneys, which may represent renal dysfunction. Increased functional volume with a thin cortex may represent a compensatory mechanism of the obstructed kidney. Such changes may contribute to the understanding of pathophysiologic mechanisms and may be an early sign of obstruction in infants with hydronephrosis. Further longitudinal studies with an extended number of infants and serial measurements of kidney volumes and %ID/mL are warranted to assess the significance of QDMSA in the management of infants with asymptomatic unilateral renal pelvic dilatation.     

The evaluation of split renal function in the experimentally induced transient renal vein obstruction

The split renal function was measured in order to evaluate the alteration of renal function secondary from transient renal vein obstruction. Three microcuries of I-131 Hippuran and 7 microCi of Tc-99m DTPA were injected into the femoral vein of adult male rats 30 min, 3 hr, 6 hr, 2 days and 1 week after the renal vein obstruction for 30 min. Blood samples were taken from the tail vein 5, 10, 15, 20 and 30 min after injection. Immediately after taking blood sample at 30 min, both kidneys and urinary bladder with ureters were taken. The radioactivities of Tc-99m and I-131 of these samples were measured respectively using a well type scintillation counter at the energy ranges of 140 KeV +/- 25% and 360 KeV +/- 25%. In the obstructed side, the blood clearances of I-131 Hippuran (ERPF) and Tc-99m DTPA (GFR) were decreased at 30 min and 6 hr after the release of left renal vein obstruction. Therefore the filtration fraction was not significantly changed. In conclusion, the single study using either Tc-99m DTPA or I-131 Hippuran may be enough to evaluate the alteration of split renal function in a model of renal vein obstruction, although the combined study using both agents is more preferable.