A control systems approach for the simulation of renal dynamic software phantoms for nuclear medicine.

For renal dynamic studies, the COST B2 hybrid phantom is an example of an artificially created software phantom. Although this phantom is useful, it is not possible to implement the phantom in a self-consistent fashion to produce, for example, a collection of tracer in the bladder which is related to the flow from the kidneys. In this study control systems are used to provide a self-consistent model. A feed-forward control system was designed for the transport of DTPA in the human body using SIMULINK. The system is based on a three-compartment model described by a set of differential equations with flow rates which may be set by the operator. The differential uptake in the kidneys may also be specified, while the flow of tracer through the renal parenchyma and collecting system of each kidney is determined using two-parameter retention functions. Curves corresponding to normal or pathological conditions may be simulated for plasma, parenchyma, collecting system and bladder by appropriate selection of parameters. The system is user-friendly and can be used to simulate almost all conditions seen in patient studies. The next stage of using this information to design dynamic image simulations is in progress.

Intra- and interoperator variations in region-of-interest drawing and their effect on the measurement of glomerular filtration rates.

PURPOSE: Quantitative results are often obtained from images after drawing regions of interest (ROIs) about the organ or area being evaluated. The accuracy and reproducibility of ROIs is an important aspect of quality-control protocols. Attempts to increase ROI accuracy and precision by generating them automatically must be compared with manually processed images to evaluate the success of the automatic methods. Operators' abilities to reproduce ROIs and the effect this has on the reproducibility of estimating glomerular filtration rate from renograms were assessed. METHODS: Estimation of the glomerular filtration rate using Sampson's method requires a) exclusion ROIs around both kidneys for background subtraction, b) whole-kidney ROIs, and c) exclusion ROIs for the collecting system. Two nuclear medicine professionals were asked to produce glomerular filtration rate estimates for 20 patients with diverse renal function. This was repeated 1 month later. The intra- and interoperator variations were calculated for the glomerular filtration rate results and on a pixel basis for the ROIs. RESULTS: THE percentage of common pixels, on average, for a) intraoperator repeats and b) interoperator comparisons were a) 95%, 94%, 85%, and b) 94%, 93%, and 81% for region types 1, 2, and, 3, respectively. Analysis of variance for the glomerular filtration rate estimates showed significant variations in estimates for left kidneys (P < 0.025) but none (P > 0.1) for right kidneys. CONCLUSION: Spatial reproducibility in ROI drawing does not necessarily relate directly to the associated quantitative reproducibility.

An assessment of two methods for generating automatic regions of interest.

Two fully automatic methods for generating regions of interest (ROIs) for nuclear medicine images are described and assessed. One of these, involving registration of a previously defined ROI onto a new image, uses spatial information and is appropriate for two- and three-dimensional images which may be static or dynamic. The other method is based on artificial neural networks and uses temporal information. It is appropriate for dynamic images only. The registration method has been tested using 10 pairs of stress and redistribution images obtained from cardiac perfusion SPET. Regions of interest of the left ventricular muscle, defined on the stress images, were registered onto the redistribution images, where they were compared with reproducibility of manually drawn ROIs. Both methods were tested on 17 99Tcm-MAG3 kidney dynamic studies, where the original ROIs corresponding to both kidneys and the bladder were defined using the COST B2 hybrid phantom. Our results indicate that neither method is as reliable as having ROIs redrawn by the operator, although there are indications that an artificial neural network which combines the use of the spatial and temporal information could prove useful for dynamic studies.

A quantitative comparison of some FADS methods in renal dynamic studies using simulated and phantom data.

Simulated and phantom data were used to determine if factor analysis of dynamic structures (FADS) methods can be used quantitatively. FADS methods tested included variants of apex seeking, the intersection method, cluster analysis and spatial constraints. These were compared with a region-of-interest (ROI) approach. Simulated renal studies were prepared using from three to six homogeneous structures. These corresponded to two blood background structures; two structures (one pathological) for parenchyma; and two structures (one pathological) for the collecting system. Time-activity curves for background, parenchyma and collecting system were obtained for each method and compared with the true curve. A kidney phantom was modelled using a tunnelled vessel filled with chelating material A variable flow was controlled by a peristaltic pump representing the renal filtration of fluid. The glomerular filtration rate (GFR) was estimated using FADS and ROI-based methods and compared with the values measured experimentally. Most FADS methods perform well in the absence of pathology, but less well than the ROI-based method when pathology is present. Some FADS methods perform better than the ROI-based method when background estimation is a problem as in the GFR experiment. For quantitative analysis, the success of FADS depends on the validity of the underlying assumptions and on the appropriate nature of the constraints.

Comparison of two interpolative background subtraction methods using phantom and clinical data.

Two interpolative background subtraction methods used in scintigraphy are tested using both phantom and clinical data. Cauchy integral subtraction was found to be relatively free of artefacts but required more computing time than bilinear interpolation. Both methods may be used with reasonable confidence for the quantification of relative measurements such as left ventricular ejection fraction and myocardial perfusion index but should be avoided if at all possible in the quantification of absolute measurements such as glomerular filtration rate.

Technetium-99m DTPA uptake and transit in bone: effect on blood clearance in rabbits.

The purpose of this study is to explain the initial "plateau" distribution of [99mTc]DTPA in the forearm found when using serial external counting for kidney clearance measurements. A study by a MIRD task group, McAfee et al. 1979 (1), measured the biologic distribution of [99mTc]DTPA(Sn) in most body tissues but omitted bone, which we believe is a major contributor to this initial "plateau". Using MIRD criteria, measurements were carried out on rabbit humeri and these were compared with results obtained from human subjects. It would appear that initial accumulation of the compound by interstitial bone is the reason for the "plateau" and explains why blood sampling for GFR studies should not be undertaken over the first 2 hr. In addition, the results of this study provide valuable information relevant to bone perfusion studies and the biologic distribution and concentration of i.v. administered drugs during the first 2 hr postinjection.

The influence of renal prostaglandins on urinary calcium excretion in idiopathic urolithiasis.

Hypercalciuria is well recognized as an important factor in the cause of idiopathic calcium stone disease. Identification of the exact mechanism for the renal tubular handling of calcium has proved elusive, hence, treatment methods to alter the concentration of urine calcium in hypercalciuric stone formers have hitherto been non-specific. It is now well established that renal prostaglandins influence intrarenal hemodynamics and tubular electrolyte excretion. As the renal handling of sodium and calcium is intimately related, the possibility that the mechanism underlying hypercalciuria may be prostaglandin mediated was considered. Experiments were performed in conscious Sprague-Dawley rats (n = 10) to determine the changes in calcium excretion following prostaglandin synthetase inhibition with indomethacin. Calcium excretion was significantly reduced (p less than 0.01), compared with control animals (n = 10). Further experiments were performed in anesthetized monkeys (Macaca fascicularis) to see if the inhibitory effect of indomethacin was reversible. Exogenous prostaglandin (PGE2) infusion resulted in a marked calciuretic response without producing changes in glomerular filtration rate or blood pressure. Forty-three hypercalciuric patients were treated with a prostaglandin inhibitor for periods ranging from 2 to 4 weeks, and all showed a significant fall in urinary calcium excretion to within the normal range. This clinical and experimental study suggests that prostaglandin (PGE2) is a hormone which determines the renal handling of calcium by influencing renal tubular function.

The influence of renal prostaglandins on glomerular filtration rate (GFR) and calcium excretion in urolithiasis.

In a clinical study of 275 idiopathic stone formers the GFR was significantly raised in hypercalciuric patients compared with normal controls P less than 0.001). The possibility that the mechanism underlying hypercalciuria and raised GFR may be prostaglandin-mediated was considered because it is now well established that prostaglandins regulate intra-renal haemodynamics and influence tubular electrolyte excretion. Experiments were performed in conscious Sprague Dawley rats to determine the changes in calcium and sodium excretion following prostaglandin synthetase inhibition with indomethacin. Both calcium and sodium excretion together with urine flow were significantly reduced (P less than 0.002). Further experiments were performed in anaesthetised monkeys (Macacca fascicularis) to see if the inhibitory effect of indomethacin was reversible. Exogenous prostaglandin (PGE2) infusion resulted in a marked calciuretic response without producing changes in GFR or blood pressure. Selected hypercalciuric patients were treated with indomethacin, which resulted in a significant fall in urinary calcium excretion (P less than 0.001). This clinical and experimental study suggests that PGE2 is the hormone which determines the renal handling of calcium by controlling renal tubular function.

External monitoring of kidney transplant function using Tc-99m(Sn)DTPA.

The purpose of this study was to evaluate the use of an external counting technique to provide daily monitoring of kidney transplant function by measuring the renal clearance of Tc-99m(Sn)DTPA. During the first few weeks following transplant, 15 patients had their renal clearance of Tc-99m DTPA measured daily over periods of 5-24 hr. Clearance rates were compared with daily plasma creatinine levels, and the effects of diurnal variation, drug treatment, and physical activity noted. The results show that any significant fall in clearance rate of chelate, indicating a rejection episode, preceded a rise in plasma creatinine levels by at least 24 hr. One episode of transplant failure presented as a sudden deterioration in clearance rate of chelate; in the others the change was more gradual but was still apparent within hours. It is considered that this noninvasive, low-dose, easy-to-perform technique is of considerable value in extended daily monitoring of renal function and is superior to standard daily or twice-weekly renography for the early detection of transplant rejection.

Principal components analysis as an aid to classification of renal dynamic studies.

Four hundred renal dynamic studies obtained using 99mTc-(Sn) DTPA were classified clinically into four classes (normal, pre-renal lesion, intrarenal lesion and urinary tract obstruction). Principal components analysis was then applied to the kidney activity/time curves and yielded good class separation using only three components. The separation of normal and obstructed or damaged kidneys using only the first component was better than that obtained using the calculated mean transit time.

Urinary clearance of 113m In-DTPA and 99mTc-(Sn)DTPA measured by external arm counting.

Single shot glomerular filtration rate measurements involving chelates (113mIn-DTPA, 99mTc-DTPA etc) assume direct loss from the plasma to urine via glomerular filtration and excretion. Inherent errors, due to considerable uptake of activity in tissue and uncertainty of complete bladder emptying are ignored and taking of half-hourly blood and urine samples involves patient discomfort. This paper describes a simple method of measuring urinary clearance of chelates using serial external arm counting which entails only an initial injection and takes into account tissue loss from plasma. The resultant plotted curve exhibits three phases, the first two depicting input and equilibration between plasma and tissue and the third and exponential part, which is a measure of the biological half-life of the chelate, being representative of the efficiency of renal glomerular filtration, the parameter to be measured. Results obtained, compared with single shot glomerular filtration rate measurements performed simultaneously, gave better correlation with clinical data including renography.