Appropriate selection of background for 99Tcm-DTPA renography

Since 99Tcm-DTPA is diffusible and not significantly protein bound in plasma, it rapidly enters the extravascular space following injection. Therefore, during the first few minutes of the DTPA renogram, the period on which the measurements of individual kidney glomerular filtration rate and differential function are based, background activity comprises a rising extravascular signal and a falling intravascular signal. The aim of this study was to measure the ratio of these two signals in background present within the renal region of interest (ROI) and compare it with the ratio in a background ROI. An appropriate background ROI is one in which the ratio is equal to that in background in the renal ROI. To pursue this aim, we quantified the rates of change of the intravascular and extravascular activities in background and, by comparing them with the rate of increase of filtered activity, expressed them as GFR equivalents (the intravascular being negative). It is impossible, from a single renogram, to separate the rising extravascular signal from the signal due to filtered activity, and therefore impossible to quantify the extravascular GFR equivalent present in background within the renal ROI. We therefore studied six patients undergoing bone marrow transplantation before and after cyclosporin treatment. By comparing the dynamic renographic data between the two sequential studies, the substantial fall in GFR (from 107 +/- 12 S.D. to 49 +/- 7 ml min-1) permitted separate quantification of the extravascular GFR equivalent in the renal ROI in both studies. Three of the patients were studied on a third occasion after cyclosporin. In two, GFR remained low and these studies were paired with corresponding baseline studies, while in the other it increased and this was compared with the nephrotoxic study, giving a total of nine paired studies between which GFR changed. The ratio of intravascular to extravascular GFR equivalents in a background ROI placed above the kidney was considerably greater, and in a background ROI below the kidney considerably less, than that in the renal ROI. A background ROI which was the difference between the renal ROI and a perirenal ROI, 2 pixels outside the renal ROI along the horizontal and 1 pixel outside along the vertical, gave a ratio almost identical to that of the background within the renal ROI (renal ROI ratio:background ROI ratio = 1.09 +/- 0.17 S.D., n = 18).(ABSTRACT TRUNCATED AT 400 WORDS)     

Extravascular chest wall technetium 99m diethylene triamine penta-acetic acid: implications for the measurement of renal function during renography

Measurement of individual kidney glomerular filtration rate (IKGFR) from the gamma-camera technetium 99m diethylene triamine penta-acetic acid (99mTc-DTPA) renogram requires a continuous measurement of arterial activity. This is usually based on a region of interest (ROI) placed over the cardiac blood pool on the posterior view, with the assumption of negligible contamination from activity in the extravascular space of the chest wall. By injecting a small dose of technetium 99m human serum albumin (HSA) before the 99mTc-DTPA in 12 patients undergoing routine renography, the contribution of extravascular activity to the total signal recorded over the cardiac blood pool was calculated to be 11.0% (SE 2.1%) 1.5 min after DTPA injection, rising to 35.1% (SE 2.5%) at 15 min. Subtraction of the time-activity curve recorded from a ROI of the same size over the right lung generated a "pure" blood signal as shown by almost identical HSA/DTPA signal ratios recorded in blood samples taken 5 min after HSA and 15 min after DTPA and from the gamma-camera at the corresponding times. The effect of using a cardiac blood pool time-activity curve uncorrected for extravascular activity was to overestimate IKGFR by an average factor of 1.17 (SE 0.03).     

Extravascular chest wall technetium 99m diethylene triamine penta-acetic acid: implications for the measurement of renal function during renography

Measurement of individual kidney glomerular filtration rate (IKGFR) from the gamma-camera technetium 99m diethylene triamine penta-acetic acid (^99mTc-DTPA) renogram requires a continuous measurement of arterial activity. This is usually based on a region of interest (ROI) placed over the cardiac blood pool on the posterior view, with the assumption of negligible contamination from activity in the extravascular space of the chest wall. By injecting a small dose of technetium 99m human serum albumin (HSA) before the^99mTc-DTPA in 12 patients undergoing routine renography, the contribution of extravascular activity to the total signal recorded over the cardiac blood pool was calculated to be 11.0% (SE 2.1%) 1.5 min after DTPA injection, rising to 35.1% (SE 2.5%) at 15 min. Subtraction of the time-activity curve recorded from a ROI of the same size over the right lung generated a pure blood signal as shown by almost identical HSA/DTPA signal ratios recorded in blood samples taken 5 min after HSA and 15 min after DTPA and from the gamma-camera at the corresponding times. The effect of using a cardiac blood pool time-activity curve uncorrected for extravascular activity was to overestimate IKGFR by an average factor of 1.17 (SE 0.03). Offprint requests to: A.M. Peters     

Individual kidney glomerular filtration rate in the interpretation of non-diagnostic curves on captopril renography

Captopril renography is known to have low sensitivity in the detection of renovascular disease in patients with bilateral renovascular disease and in patients with unilateral renovascular disease with a small kidney. In these groups of patients, we have tried to make the standard captopril renogram more objective by simultaneously estimating the individual kidney glomerular filtration rate (IKGFR). Twenty-five patients (10 bilateral, 15 unilateral) with angiographically proven renal artery stenosis (RAS) were studied. Ten renal units in five hypertensive patients with normal renal arteries were used as controls. A fall of more than 10% in IKGFR post-captopril was considered a positive result. The sensitivities of renogram and IKGFR in patients with bilateral RAS were 52.9% and 88.2% respectively. In patients with unilateral RAS, the sensitivities of renogram and IKGFR were 30% and 80% respectively. A significant fall in IKGFR was noted in eight of the 15 'normal' renal units of the unilateral RAS group. In conclusion, individual kidney GFR estimation in combination with captopril renography improved significantly the sensitivity in patients with symmetrical bilateral RAS and unilateral RAS with a small, poorly functioning kidney. A fall in GFR in the normal counterpart of a unilateral RAS kidney may be indicative of ongoing damage in the non-involved kidney.     

Filtration fraction and its implications for radionuclide renography using diethylenetriaminepentaacetic acid and mercaptoacetyltriglycine

PURPOSE: Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined in 92 patients to calculate filtration fraction (GFR/EFPR) and evaluate its change in renal diseases. This information was used as the rationale for a renogram protocol using DTPA (to estimate GFR) and MAG3 (to produce images and curves). METHODS: Individual kidney GFR and ERPF were determined by gamma camera techniques using Tc-99m DTPA and I-131 OIH. Two hundred sixty-one determinations were performed in 92 patients who in turn were grouped into 4 categories: normal, obstruction, renal vascular disease, and chronic insufficiency. RESULTS: Mean filtration fractions in normal patients and those with obstruction were similar (0.16 and 0.15, respectively), whereas they were lower in renal vascular disease (0.11) and chronic renal insufficiency (0.08). Low filtration fraction indicates disproportionate loss of GFR compared with ERPF and was the pattern observed with advancing renal disease in most patients. The exception was ATN or contrast nephropathy when filtration fraction was increased (0.22) as a result of disproportionate loss of ERPF compared with GFR. CONCLUSIONS: OIH is no longer available in the United States, and MAG3 is now used as the renal tubular agent in renography. Clearance of MAG3 does not directly measure ERPF, but this might not be a significant loss in clinical practice if GFR is measured during renography because it is more adversely affected by renal disease than ERPF (with the exception of ATN and contrast nephropathy). Accordingly, a renogram protocol is presented for the combined use of DTPA and MAG3 resulting in GFR estimation (from DTPA) while yielding superior renal images and renogram curves from MAG3.     

Measurement of the ratio of glomerular filtration rate to plasma volume from the technetium-99m diethylene triamine pentaacetic acid renogram: comparison with glomerular filtration rate in relation to extracellular fluid volume

Individual kidney glomerular filtration rate (IKGFR) can be measured from the renogram from the rate of uptake of technetium-99m diethylene triamine penta-acetic acid (^99mTc-DTPA). A blood sample is required to derive IKGFR in millilitres per minute, which is then usually normalised to body surface area. We describe a technique which does not require a blood sample, is already normalised for plasma volume and uses the robust Patlak plot for measuring renal uptake. The rate of kidney uptake, dR(t)ldt, at time = 0, as a fraction of the injected dose, is equal to the fraction of the plasma volume (PV) filtered per minute, i.e. IKGFR/PV. The gradient dR(0)/dt cannot be accurately measured directly but is equal to [ · LV(0)], where is the renal uptake constant (proportional to IKGFR) and LV is the count rate over a left ventricular ROI. LV(0) was obtained by extrapolation of LV(t), while a is the slope of the Patlak plot up to 3 min. GFR/PV (i.e. right plus left kidneys) in patients with normal renal function was about 0.04 min^–1, as would be expected from normal values of GFR (120 ml/min) and plasma volume (3 l). GFR/PV correlated significantly with the ratio of GFR to extracellular fluid volume (ECV), measured from the terminal exponential of the plasma clearance curve (GFR/PV = 3.2.GFR/ECV + 5.3 ml/min/1 [r = 0.82,n = 82]). GFR/PV (r = 0.74) and GFR/ECV (r = 0.82) both correlated inversely and non-linearly with plasma creatinine in 43 studies where the measurement was made within 1 week of the^99mTcDTPA study. They also correlated significantly with the plasma cyclosporin trough level in 14 patients with dermatomyositis on the 30 occasions when this measurement was made within 1 week of the renogram (r = –0.38,P < 0.05 for GFR/PV andr = –0.77,P < 0.001 for GFR/ECV). The ratio of GFR/PV to GFR/ECV is the ratio of extracellular fluid volume to plasma volume, and this was 4.0 (SD 0.99). We conclude that both GFR/PV and GFR/ECV can be easily measured with^99mTc-DTPA and are physiologically valid expressions of GFR. Although GFR/PV and GFR/ECV correlate with each other, the question is raised as to which of the two fluid volumes is the most appropriate for normalising GFR. Correspondence to: A.M. Peters     

In vivo glomerular filtration rate measurement based solely on image processing

A simple and reliable technique was developed to measure split renal glomerular filtration (GFR) based solely on image processing of the standard 20-minute Tc-99m DTPA renogram. It requires neither syringe counting nor blood or urine sampling. Using three sequential blood samples in 36 patients, GFR values correlated well (r = 0.92) with in vitro GFR measurements.     

Techniques for the quantitative measurement of individual kidney function in the pig

A prerequisite for elucidating the effect of radiation on porcine renal function is the development of non-invasive methods for accurate quantification of unilateral glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The techniques presented here are (a) measurement of unilateral kidney filtration fraction (FF) determined by analysis of the early rise of the kidney's time-activity curves following the injection of tubular ([131I]hippuran) and glomerular ([99mTc]DTPA) tracers, and (b) deconvolution of the respective renogram. Unilateral FF values are obtained by calculating the ratio of glomerular to tubular clearances. Results for 23 female large white pigs indicate a highly significant correlation (r = 0.91, P less than 0.001) between computed FF values and those obtained from the plasma disappearance curves of [99mTc]DTPA and [131I]hippuran. Deconvolution of the renogram allows estimation of the mean transit time (MTT) for [99mTc]DTPA and [131I]hippuran, these are 6.94 +/- 1.87 and 6.86 +/- 1.44 min respectively. In addition, FF values calculated from the H0 values are significantly correlated (r = 0.7, P less than 0.05) with estimates from plasma disappearance curves of the tracers. Therefore these techniques appear to provide accurate non-invasive methods for determining individual porcine kidney function.     

99mTc-DTPA gamma-camera renography: normal values and rapid determination of single-kidney glomerular filtration rate

A method for 99mTc-diethylenetriaminepentaacetate (DTPA) gamma-camera renography is presented. From each renogram, an uptake index (UI) proportional to the single-kidney glomerular filtration rate (SKGFR) is defined. If the proportionality factor between UI and SKGFR is the same in all patients, UI can be used as an accurate measure of SKGFR. In order to test this, 99mTc-DTPA renography was performed in 101 patients with glomerular filtration rates (GFR) varying between 4 and 172 ml/min. The sum of the right- and left-kidney UIs correlated well with the total GFR calculated from the simultaneously measured plasma clearance of 99mTc-DTPA after a single injection. The correlation coefficient was 0.97. The method was tested in a prospective study of 57 patients. The total GFR estimated from the renograms was not significantly different from the GFR calculated from the plasma clearance of 99mTc-DTPA. The coefficient of variation--a combination of inaccuracy and imprecision in the estimates as well as in the reference values-was 11.8% at a GFR of 100 ml/min. It is concluded that, in adults, the SKGFR can be calculated as part of the clinical routine from 99mTc-DTPA gamma-camera renography without determining the injected dose or collecting urine or blood samples. Normal values for some parameters of the renogram obtained in 25 normal subjects are given.     

Calculation of relative glomerular filtration rate and correlation with delayed technetium-99m DMSA imaging

The relative renal uptake of Tc-99m DMSA was compared with the relative glomerular filtration rate (GFR) in ten patients with serum creatinines ranging from 0.3 to 2.5 mg/dl. Relative GFR was based on the renal uptake of Tc-99m DTPA determined by two methods: 1) integrating the counts from 1 to 3 minutes postinjection and correcting for background. 2) Totalizing the individual renal counts in a single 15-second frame from 2:45 minutes to 3:00 minutes postinjection and correcting for background. The two methods of determining relative DTPA uptake showed excellent correlation, r = 0.98. Relative DMSA uptake determined at 24 hours post-injection using computer-assisted regions of interest showed excellent correlation with the relative GFR determined by either the integral or single-frame method, r = 0.98. The addition of background subtraction for the DMSA images at 24 hours did not improve the correlation.     

Effect of food and activity on the reproducibility of isotopic GFR estimation

The reproducibility of the plasma clearance of 99Tcm DTPA was studied in 26 patients under standardized conditions with the subject fasting and at rest. The coefficient of variation of duplicate measurements in patients with glomerular filtration rates (GRF's) ranging from 11-103 ml min-1 was 8%. Mean GFR following a breakfast containing 670 kcal and 31 g protein was increased significantly from 40.7 +/- 28.1 ml min-1 to 43.6 +/- 30.8 ml min-1. When fasted but permitted free exercise there was no consistent trend in GFR but the coefficient of variation of duplicate estimates increased significantly to 12.1%. It is recommended that routine GFR measurement should be carried out fasting or following a light diet with restricted activity.     

99mTc-DTPA gamma-camera renography: Normal values and rapid determination of single-kidney glomerular filtration rate

A method for ^99mTc-diethylenetriaminepentaacetate (DTPA) gamma-camera renography is presented. From each renogram, an uptake index (UI) proportional to the single-kidney glomerular filtration rate (SKGFR) is defined. If the proportionality factor between UI and SKGFR is the same in all patients, UI can be used as an accurate measure of SKGFR. In order to test this, ^99mTc-DTPA renography was performed in 101 patients with glomerular filtration rates (GFR) varying between 4 and 172 ml/min. The sum of the right-and left-kidney UIs correlated well with the total GFR calculated from the simultaneously measured plasma clearance of ^99mTc-DTPA after a single injection. The correlation coefficient was 0.97. The method was tested in a prospective study of 57 patients. The total GFR estimated from the renograms was not significantly different from the GFR calculated from the plasma clearance of ^99mTc-DTPA. The coefficient of variation—a combination of inaccuracy and imprecision in the estimates as well as in the reference values — was 11.8% at a GFR of 100 ml/min. It is concluded that, in adults, the SKGFR can be calculated as part of the clinical routine from ^99mTc-DTPA gamma-camera renography without determining the injected dose or collecting urine or blood samples. Normal values for some parameters of the renogram obtained in 25 normal subjects are given.     

Radionuclide measurement of differential glomerular filtration rate in urinary tract obstruction

In a previous study using dogs whose renal function was rendered asymmetric by unilateral infarction, the efficacy of technetium-99m (99mTc) DTPA and DMSA in measuring differential glomerular filtration rate (GFR) was demonstrated. The present study was undertaken to determine whether the same techniques were applicable to unilateral ureteral obstruction. Five normal dogs and nine dogs with partial unilateral ureteral obstruction had determination of glomerular filtration rate by standard techniques using constant infusions of iothalamate and creatinine after ureteral catheterization. These results were compared with total GFR as measured by single injection of 99mTc DTPA and analysis of the plasma disappearance curve. Calculated differential GFR was obtained by multiplying total GFR from double exponential analysis of this curve (DTPA2) by each of three measures of differential function. These included the percent differential uptake of 99mTc DTPA and 99mTC DMSA in the posterior projection as well as the geometric mean of 99mTc DMSA uptake. There were good correlations between differential GFR determined by iothalamate clearances at ureteral catheterization and all noninvasive methods involving radionuclides and DTPA2 ( r = 0.93-0.99). Single exponential analysis of the 99mTc DTPA plasma disappearance curve was less satisfactory than double exponential analysis. These results and those reported previously support the use of radionuclides in the determination of differential GFR in a variety of clinical situations.     

Determination of glomerular filtration rate using a dual-detector gamma camera and the geometric mean of renal activity: correlation with the Tc-99m DTPA plasma clearance method

PURPOSE: In this study, the authors studied the use of a dual-detector gamma camera to measure the glomerular filtration rate (GFR). METHODS: Thirty-three patients with a wide range of renal function participated in this study. The GFR was measured using a dual-detector gamma camera by calculating the geometric mean of activity from each kidney and using an outline background. These results were compared with the GFR estimates obtained from Tc-99m DTPA plasma clearance using a multiple blood sample method. RESULTS: Correlation was excellent between GFR estimated using the dual-detector gamma camera and GFR measured using the plasma clearance of Tc-99m DTPA with multiple blood samples (r = 0.89). The correlation was especially strong in children younger than 13 years (r = 0.94). CONCLUSION: Measuring the GFR using a dual-detector gamma camera and calculating the geometric mean of renal activity yields relatively accurate results.     

Three-hour volume of distribution method: an accurate simplified method of glomerular filtration rate measurement

Eight hundred studies of glomerular filtration rate (GFR) measurements were performed by the standard slope-intercept method using [99mTc]DTPA and results were compared with a simultaneous measurement of the 3-hr tracer volume of distribution. A wide range of human renal function was studied and a nonlinear relationship between GFR and the volume of distribution resulted with an excellent correlation (r = 0.989). Agreement between the two measured parameters was not constant for all levels of renal function with the greatest accuracy being found for GFR = 60 to 100 ml/min.     

99Tcm-MAG3 for quantitation of differential renal function

We studied two different methods for the evaluation of differential renal function in a group of 100 patients with various kidney disorders whose effective renal plasma flow (ERPF) had been calculated previously by single 125I-orthoiodohippurate (OIH) injection and multiple blood sampling. Patients were divided into three groups according to their ERPF:ERPF is greater than or equal to 250 ml min-1; ERPF less than or equal to 100 ml min-1; and ERPF greater than 100 ml min-1 and less than 250 ml min-1. The two methods used to assess differential renal function were: first, relative 99Tcm-dimercaptosuccinic acid (DMSA) uptake calculated by normalized background and attenuation corrected cumulative counts in each kidney 24 h p.i.; and second, relative 99Tcm-mercaptoacetyl-triglycine (MAG3) uptake within 1 and 2 min p.i. calculated by normalized background and attenuation corrected counts on each renal area. The results obtained with each method correlated strongly with high significance (p less than 0.0001). In the right kidney, mean values obtained with 99Tcm-MAG3 tend to be higher than mean values obtained with 99Tcm-DMSA.     

Comparison of 99Tcm-mercaptoacetyltriglycine and 131I-orthoiodohippurate in determination of effective renal plasma flow (ERPF)

Recent studies have suggested that 99Tcm-labelled mercaptoacetyltriglycine (99Tcm-MAG3) is a potential replacement for 131I-orthoiodohippurate (131I-OIH). The two radiopharmaceuticals were studied in 19 patients with varying degrees of renal impairment, for comparison of effective renal plasma flow (ERPF). All patients were injected i.v. with 2-3 mCi 99Tcm-MAG3 and 250-300 microCi of 131I-OIH simultaneously in separate arms to avoid any chemical incompatibility. Serial digital images were acquired simultaneously for 99Tcm-MAG3 and 131I-OIH at 15 s per frame for 30 min. The renogram curve was generated and ERPF value was calculated for each kidney using both radiopharmaceuticals and applying the same computer program (Schlegel's program). In all cases, the 99Tcm-MAG3 and 131I-OIH renogram curves were quite similar. The values of ERPF of 99Tcm-MAG3 were not significantly different from those of 131I-OIH studies (paired t test, p less than 0.01). The correlation coefficient between the two methods was 0.95 (p less than 0.001) with a linear regression equation Y = -12.96 + 0.995X, where Y = ERPF determined by 131I-OIH and X = ERPF determined by 99Tcm-MAG3. This study indicates that 99Tcm-MAG3 is a useful 99Tcm replacement for 131I-OIH in the determination of ERPF and generation of renogram curves.     

Aluminemic disturbance of technetium-99m DTPA renal function measurement

During follow-up study of a patient with surgically corrected unilateral renal ischemia, using computer image generated [99mTc]diethylenethiaminepentaacetic acid (DTPA) glomerular filtration rate (GFR) and [131I]orthoiodohippurate estimated renal plasma flow (ERPF), we observed prominent gastric and intestinal uptake of 99mTc. Profound alteration in the GFR results, but not the ERPF results, was also observed. Radiopharmaceutical breakdown was suspected and shown to be endogenous and due to hyperaluminemia at 28 ng/ml. These case findings add DTPA to the list of 99mTc radiopharmaceuticals that have previously been reported to have altered biodistribution when hyperaluminemia is present. The case findings also reaffirm the benefits of obtaining images to corroborate the validity of quantitative data and demonstrate that quantitative radionuclide renal function data are not independent of renal chemical handling.     

Clinical approach to renal study incidental to99mTc-MDP bone scintigraphy

In order to investigate the feasibility of the assessment of renal function with 99mTc-MDP, we compared renographical images, renogram patterns and the glomerular filtration rate (GFR) obtained by means of a modified Gates' method and 200 MBq of 99mTc-MDP with those obtained by means of 99mTc-DTPA. Because 19 of 20 patients had malignant tumors in the genitourinary tract, there was no difference between the two tracers in identifying a parenchymal defect corresponding to renal cancer. Of eight patients with hydronephrosis, four had a defect or decreased uptake with a dilated pelvis, whereas the other four had marked radioisotope retention in the renal pelvis or the whole kidney on serial images. There was also no difference between the two tracers in identifying hydronephrosis. Of 38 paired renograms 35 showed the same renogram patterns with both tracers. Of three patients with different renogram patterns, two had hydronephrosis. In 20 patients including three patients with bone metastasis, total GFR and split GFR obtained with both tracers correlated with a correlation coefficient of r = 0.920 (p < 0.001) and r = 0.944 (p < 0.001), respectively. Excluding bone metastasis from the analysis, a linear-regression analysis showed excellent agreement between the two measurements with a correlation coefficient of r = 0.960 (p < 0.001) and r = 0.963 (p < 0.001), respectively. The linear regression equations were Y = 1.009X - 0.111 and Y = 1.034X - 0.714, respectively. In conclusion, 99mTc-MDP can be used as a supplement to evaluate renal function incidental to the survey of bone metastases in patients with malignant tumor.     

Estimation of glomerular filtration rate in the miniature pig by kidney uptake on the gamma camera

Measurement of glomerular filtration rate (GFR) by the renal uptake of 99Tcm-diethylene triamine penta-acetic acid (99Tcm-DTPA) in the miniature pig was compared to that by plasma disappearance of 99Tcm-DTPA using multiple blood samples. Nineteen animals were examined under identical conditions. There was a highly significant relationship between the two tests, r = 0.88, P less than 0.001, although the uptake method gave consistently higher results than those obtained from plasma disappearance. Reproducibility of the uptake method was also assessed in this group of animals by performing two consecutive renograms. Confidence limits of 95% were +/- 7.5% or 0.7 ml min-1 kg-1. The test is useful for the serial examination of single kidney GFR on follow-up renography but is unlikely to replace disappearance techniques as a more accurate means of GFR estimation.