Carl A. Wesolowski

Validation of Tikhonov adaptively regularized gamma variate fitting with 24-h plasma clearance in cirrhotic patients with ascites

PurposeThe aim was to compare late-time extrapolation of plasma clearance (CL) from Tikhonov adaptively regularized gamma variate fitting (Tk-GV) and from mono-exponential (E1) fitting.MethodsTen 51Cr-ethylenediaminetetraacetic acid bolus IV studies in adults—8 with ascites—assessed for liver transplantation, with 12–16 plasma samples drawn from 5-min to 24-h, were fit with Tk-GV and E1 models and CL results were compared using Passing-Bablok fitting.ResultsThe 24-h CL(Tk-GV) values ranged from 11.4 to 79.7 ml/min. Linear regression of 4- versus 24-h CL(Tk-GV) yielded no significant departure from a slope of 1, whereas the 4- versus 24-h CL(E1) slope, 1.56, was significantly increased. For CL(Tk-GV-24-h) versus CL(E1-24-h), there was a biased slope and intercept (0.85, 5.97 ml/min). Moreover, the quality of fitting of 24-h data was significantly better for Tk-GV than for E1, as follows. For 10 logarithm of concentration curves, higher r values were obtained for each Tk-GV fit (median 0.998) than for its corresponding E1 fit (median 0.965), with p < 0.0001 (paired t-test of z-statistics from Fisher r-z transformations). The E1 fit quality degraded with increasing V/W [volume of distribution (l) per kg body weight, p = 0.003]. However, Tk-GV fit quality versus V/W was uncorrelated (p = 0.8).ConclusionCL(E1) values were dependent on sample time and the quality of fit was poor and degraded with increasing ascites, consistent with current opinion that CL(E1) is contraindicated in ascitic patients. CL(Tk-GV) was relatively more accurate and the good quality of fit was unaffected by ascites. CL(Tk-GV) was the preferred method for the accurate calculation of CL and was useful despite liver failure and ascites.

Development of a modified sampling and calculation method for isotope plasma clearance assessment of the glomerular filtration rate in patients with cirrhosis and ascites.

AimThe aim of this study was to identify a practical sampling regimen and calculation method that could be used to measure the glomerular filtration rate in patients with ascites using plasma sampling. Patients and methodsThirteen potential liver transplant patients with cirrhosis and ascites were injected with Cr-51 ethylenediaminetetraacetic acid, and plasma samples were obtained at up to 16 time points for each patient. Reference clearance values were calculated using the area under the plasma clearance curve, which was calculated using all the available data points. Clearance calculations were then performed using three and four data points from each patient and three different calculation methods to identify a sampling regimen and calculation method that yielded good agreement with the reference values. ResultsThe reference clearances ranged from 6 to 80 ml/min. Sampling at 2, 4, 8 and 24 h and calculation of the area under the plasma clearance curve using a log–linear trapezoidal rule with extrapolation to zero and infinity yielded a relative root mean square difference from the reference of less than 7%. ConclusionThis method for measuring glomerular filtration rate in patients with cirrhosis and ascites was found to be more accurate than the slope–intercept technique and is a practical alternative to urine collection.

A direct modeling approach to the early renal vascular transit of 99mTc chelates.

Delay channel integral methods are developed and applied for analyzing human renal scintiangiographic data produced after peripheral venous injection of a 99mTc chelete. The results include information for two renal vascular compartments (C1, C2) and a residual compartment (Cr). Each vascular compartment is associated with a fraction of the total renal plasma flow (A1, A2) and a mean transit time (T1, T2). The residual compartment has the residual plasma flow fraction Ar. The results obtained in 40 normal kidneys are presented and compared theoretically to the results from other methods.

The early plasma concentration of 51Cr-EDTA in patients with cirrhosis and ascites: a comparison of three models.

Objectives The aim of the study was to determine which of three two-parameter fitting functions (exponential, linear-log, and negative-power function of time) most accurately models early chromium-51-EDTA (51Cr-EDTA) plasma concentration data prior to 120 min in patients with cirrhosis and ascites and understand how these fitting functions affect the calculation of the area under the plasma concentration curve (AUC). Methods A bolus, antecubital intravenous injection of 2.6 MBq of 51Cr-EDTA was given to 13 patients with cirrhosis and ascites. Up to 16 blood samples were drawn at time points ranging from 5 to 1440 min following injection. The concentration data prior to 120 min were used as reference data. Early time concentration values, estimated by fitting exponential, linear-log, and negative-power functions of time to the time samples at 120, 180, and 240 min, were then compared with reference data. The AUC was calculated for each patient using the exponential, Bröchner-Mortensen-corrected exponential, and linear-log functions, and these values were compared. Results The withheld, observed plasma concentrations were (a) most accurately estimated by linear-log functions (Wilcoxon P=0.4548), (b) significantly underestimated by exponential functions (Wilcoxon P=0.0002), and (c) significantly overestimated by negative-power functions (Wilcoxon P=0.0034). The relative errors when ranked from best to worst were those for the linear-log (12.0%, 9.0%), exponential (22.9%, 14.2%), and negative-power (31.9%, 48.4%) functions of time, respectively (median, interquartile range). For each patient, the values for AUC calculated by the exponential function differed significantly (range=3.4–15.3%, median=8.3%) from those calculated by the corrected Bröchner-Mortensen exponential, as to a lesser extent did those values calculated using linear-log functions (range=0.4–8.0%, median=3.0%). Conclusion In patients with cirrhosis, linear-log functions were significantly more accurate than exponential or power functions in estimating early time plasma concentrations (<120 min). However, the improved linear-log early time plasma concentration model does not provide as much correction to the total AUC as does the corrected Bröchner-Mortensen exponential method. This is likely because of the large contribution of late time data to the AUC, and future work is suggested to explore the late time fit problem.

Avoidance of errors related to renal depth during radionuclide evaluation of renal perfusion.

Quantitative renal imaging is subject to errors related to varying renal depth. Lateral projection images, ultrasound, and geometric mean calculations can be utilized to measure renal depth or to correct for variations in the attenuation of renal activity. However, each of these methods is time consuming and each has the potential for introducing additional errors. As an alternative, the authors propose the use of quantitative indices that are insensitive to the effects of attenuation. This report illustrates how transit-time-distribution (TTD) parameters can be used to assess renal perfusion independent of varying renal depth.

Accurate and precise plasma clearance measurement using four 99mTc-DTPA plasma samples over 4 h.

ObjectivesGlomerular filtration rate can be measured as the plasma clearance (CL) of a glomerular filtration rate marker despite body fluid disturbances using numerous, prolonged time samples. We desire a simplified technique without compromised accuracy and precision. Materials and methodsWe compared CL values derived from two plasma concentration curve area methods – (a) biexponential fitting [CL (E2)] and (b) Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)] – for 4 versus 8 h time samplings from 412 99mTc-DTPA studies in 142 patients, mostly paediatric patients, with suspected fluid disturbances. ResultsCL (Tk-GV) from four samples/4 h and from nine samples/8 h, both accurately and precisely agreed with the standard, which was taken to be nine samples/8 h CL from (noncompartmental) numerical integration [CL (NI)]. The E2 method, four samples/4 h, and nine samples/8 h median CL values significantly overestimated the CL (NI) values by 4.9 and 3.8%, respectively. ConclusionCompared with the standard, CL (E2) from four samples/4 h and from nine samples/8 h proved to be the most inaccurate and imprecise method examined, and can be replaced by better methods for calculating CL. The CL (Tk-GV) can be used to reduce sampling time in half from 8 to 4 h and from nine to four samples for a precise and accurate, yet more easily tolerated and simplified test.

An improved method for determining renal sufficiency using volume of distribution and weight from bolus 99mTc-DTPA, two blood sample, paediatric data

Objectives To find an improved method of determining renal sufficiency by exploring power functions for estimating normal value, E(arg), single compartment glomerular filtration rate (G1), rate constant (&ggr;) and renal sufficiency index, RSI=&ggr;/E(&ggr;)=G1/E(G1), using compartment volume (V), patient mass ( W), patient age (A), patient height (H), and sex (S). To present the best estimator of normal, E(G1)=f(V, W). Methods One hundred and thirty 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) combined imaging and G1 studies in 97 children were screened by findings and history to obtain 44 normal studies of patients 1.46–18.5 years of age with blood samples at 109 (90–214) and 152 (120–246) min. Normal studies were used to generate predictive formulae. Results For power functions, the statistically acceptable formulae in descending order of adjusted R2 were f(V, W), f(V,A), f(V,H), f(V), f(W,A,H), f( W), f(H) and f(A). Relationships of the body surface area type, f(W, H, S) and f(W, H), were statistically unwarranted. Kleibers law, E(G1)∝∝W3/4, with E(G1)=6.9190W0.7618 found here, allowed confirmation of GFRinulin≈0.87G1. The best estimator is f(V, W)=10.998V0.64717 W0.20185, and may relate to a volumetric measure of body habitus. To verify methods, Monte Carlo simulation of the glomerular filtration rate (GFR) and f(V, W) was performed and yielded less than 5% precision error, 98% of the time. Normal RSI from f(V, W) had the smallest standard deviation, 11.3%, no regression bias over a six-fold range on a Bland–Altman ratio plot, p=0.4, and good agreement with clinical classification at 95% specificity (RSI>0.8589, Cohens Kappa 0.70±0.062 (mean±bootstrap standard error). Conclusions The best RSI from f(V, W) is RSI=90.927&ggr;V0.35283W−0.20185 and should detect mildly (14.1%) reduced renal sufficiency.

A Power Law for Determining Renal Sufficiency Using Volume of Distribution and Weight from Bolus 99mTc-DTPA, Two Blood Sample, Pediatric Data

Objectives: (1) Explore power laws for estimating the one-compartment glomerular filtration rate (G₁), i.e., E(G₁), as functions of compartment volume (V), patient mass (W), age (A), height (H) and sex (S). (2) Propose a renal sufficiency index, RSI=G₁/E(G₁). (3) Present the best estimator, E(G₁) = f(V,W) = 10.988 V^0.64717W^0.20185. (4) Present the first clinical application of RSI, prediction of relative bone age (RBA = E(A)/A). Methods: 130 ^99mTc-DTPA imaging and G₁ studies were screened to find 44 normal studies in children 1.46 to 18.5 years old. Results: E(G₁) formulae of the body surface area type, i.e., f(W,H,S) and F(W,H), were found to be statistically unwarranted. Statistically acceptable formulae, in descending adjusted R², were f(V,W), f(V,A), f(V,H), f(V), f(W,A,H), f(W), f(H) and f(A). Kleibers law, E(G₁) prop W^frac34, seems to confirm the previously reported relationship GFR_inulin ap 0.87G₁. Our best G₁ estimator, f(V,W), may be related to a physiological volume. RSI as predicted by f(V,W) had the smallest relative standard deviation, 11.3%, no regression bias and good agreement with clinical classification at 95% specificity. RBA was found to be correlated with RSI, with a peak at 88% E(RSI), with RSI accounting for 25% of its variance. Conclusions: Our best RSI predictor, RSI = 90.927gammaV^0.35283W^-0.20185, should be capable of detecting mildly reduced (14.1%) renal sufficiency.

Comparison of Tl-201 renal uptake with Tc-99m DTPA angiorenography in patients with hypertension. Measures of renal asymmetry.

Renal uptake of TI-201 reflects renal perfusion and may have a role in defining renal asymmetry in patients with hypertension who are referred for myocardial scintigraphy. The authors compared two methods of quantitating differential renal uptake of TI-201, with similar data obtained from the angiographic and renal uptake (RU) phases of Tc-99m DTPA scintigraphy in 35 patients with hypertension. For TI-201, asymmetry in renal counts was quantitated based on a simple outline technique or on interpolative background subtraction of 5-minute posterior images. Inter-observer and intra-observer variability among duplicate measurements were lower for TI-201, particularly with interpolative background subtraction, than for Tc-99m DTPA. Renal/background ratios were similar for TI-201 and RU-phase Tc-99m DTPA images when considering liver, spleen, or inter-renal regions as background; however, paraspinal uptake was relatively higher with TI-201 (P < 0.01). Qualitatively, renal asymmetry scores with the two radiotracers agreed (r = 0.89, blinded readings by four observers), although asymmetry was more marked with TI-201 (P = 0.06). Measurements with TI-201 agreed with both phases of Tc-99m DTPA (r = 0.96 to 0.98), but interpolative background subtraction systematically yielded greater inter-renal asymmetry than RU (P < 0.01), reflecting the qualitative impression. Thus, ancillary TI-201 imaging reflects differences between the kidneys in a fashion similar but not identical to Tc-99m DTPA scintigraphy.