Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) is a sensitive method for imaging cardiac transthyretin (ATTR) amyloid. We report utility and limitations of ...(99m)Tc-DPD scintigraphy in 321 patients with suspected cardiac amyloidosis.
The cohort included wild-type ATTR (ATTRwt) amyloidosis in 94 (29%), ATTR-Val122Ile amyloidosis in 38 (12%), hereditary ATTR (ATTRmt) amyloidosis in 46 (14%), primary light-chain (AL) amyloidosis in 44 (14%), secondary (AA) amyloidosis in three (1%), other hereditary amyloidosis types in nine (3%), undetermined types in two (0.5%), and 85 (26.5%) patients in whom systemic amyloidosis was ultimately excluded. All 158 patients with ATTR amyloidosis with clinical cardiac involvement had cardiac (99m)Tc-DPD uptake, with median Grade 2 intensity. Thirteen further ATTR amyloidosis patients without clinical evidence of cardiac involvement also demonstrated (99m)Tc-DPD cardiac uptake. Eighteen of 35 (51%) AL patients with cardiac involvement had (99m)Tc-DPD cardiac uptake (median Grade 1 intensity). SPECT imaging indicates that the apparent reciprocal reduction in bone uptake is due to masking of bone uptake by extensive soft-tissue uptake in ATTR amyloidosis, especially ATTRwt, and ATTR-Val122Ile types.
(99m)Tc-DPD scintigraphy is a highly sensitive technique for imaging cardiac ATTR amyloidosis and is an important investigation in the diagnostic pathway of patients with cardiac amyloidosis. It is not specific for ATTR in isolation but must be interpreted in a broad clinical context to avoid dangerous diagnostic errors. Diffuse skeletal muscle uptake identifies muscle as a hitherto unrecognized site that merits investigation as a target organ in ATTR amyloidosis.
The aim of this study was to conduct a nationwide survey of computed tomography (CT) doses for a wide range of PET-CT and single photon emission computed tomography-computed tomography (SPECT-CT) ...imaging procedures, with the aim of generating proposed UK national diagnostic reference levels (NDRLs).
CT protocol and dosimetry data for three PET-CT and seven SPECT-CT examinations were gathered from centres across the UK. Data were divided according to CT purpose (attenuation correction, localization or diagnostic) and third quartile values of scanner average dose metrics were used to generate suggested NDRLs for a range of examination and CT purpose combinations. Achievable doses were also established from the median of the dose distributions.
Data were obtained from 47 centres, allowing suggested NDRLs to be produced for fluorine-18-fluorodeoxyglucose half-body PET-CT, and parathyroid, post-thyroid ablation, meta-iodobenzylguanidine/octreotide, cardiac and bone SPECT-CT examinations.Variations in dose of up to a factor of 35 were observed for a given examination/CT purpose combination. For fluorine-18-fluorodeoxyglucose half-body PET-CT examination dose levels for the three CT purposes overlapped, which highlights the variability in the way in which CT purposes are interpreted across the UK. This lack of standardization is believed to be the largest contributor to the dose variations that were observed. The survey highlighted the need for targeted optimization work in many centres.
Suggested UK NDRLs and achievable doses for six common PET-CT and SPECT-CT examinations have been established as a result of this study.
Background
The 2018 BNMS Glomerular Filtration Rate (GFR) guidelines recommend a single-sample technique with the sampling time dictated by the expected renal function, but this is not known with any ...accuracy before the test. We aimed to assess whether the sampling regime suggested in the guidelines is optimal and determine the error in GFR result if the sample time is chosen incorrectly. We can then infer the degree of flexibility in the sampling regime.
Methods
Data from 6328 patients referred for GFR assessment at 6 different hospitals for a variety of indications were reviewed. The difference between the single-sample (Fleming) GFR result at each sample time and the slope–intercept GFR result at each hospital was calculated. A second dataset of 777 studies from one hospital with nine samples collected from 5 min to 8 h post-injection was analysed to provide a reference GFR to which the single-sample results were compared.
Results
Recommended single-sample times have been revised: for an expected GFR above 90 ml/min/1.73m
2
a 2-h sample is recommended; between 50 and 90 ml/min/1.73m
2
a 3-h sample is recommended; and between 30 and 50 ml/min/1.73m
2
a 4-h sample is recommended. Root mean square error in single-sample GFR result compared with slope–intercept can be kept less than or equal to 3.30 ml/min/1.73m
2
by following these recommendations.
Conclusion
The results of this multisite study demonstrate a reassuringly wide range of sample times for an acceptably accurate single-sample GFR result. Modified recommended single-sample times have been proposed in line with the results, and a lookup table has been produced of rms errors across the full range of GFR results for the three sample times which can be used for error reporting of a mistimed sample.
The 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.
...Thirteen 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.
The 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%.
This 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.
Glomerular filtration rate (GFR) is frequently assessed using the slope-intercept method by fitting a single exponential to plasma samples obtained 2-5 h after injection. The body surface area ...(BSA)-corrected one-pool clearance (CO,BSA) overestimates true GFR (CT,BSA) because it fails to sample the full plasma curve, and values of CT,BSA are usually estimated from CO,BSA using the Brøchner-Mortensen (BM) equation. An improved equation, CT,BSA=CO,BSA/(1+fBSA×CO,BSA), with fBSA a fixed constant, was proposed by Fleming, but subsequently Jødal and Brøchner-Mortensen (JBM) reported that fBSA varies with BSA. We report data for a large group of individuals who underwent GFR investigations with sampling of the full plasma curve. The aims were to validate the JBM equation with independent data and assess whether replacing the BM equation with a BSA-dependent correction based on Fleming's equation can increase the accuracy of the slope-intercept method.
Plasma data were analysed for 142 children and adults aged 0.6-56 years who underwent technetium-99m-diethylenetriaminepentaacetic acid GFR investigations with blood samples taken between 5 min and 8 h after injection. Values of CO,BSA were calculated using the 2, 3 and 4 h data. Values of CT,BSA were calculated by integrating the plasma curve between 5 min and 4 h and extrapolating the terminal exponential. Individual values of fBSA were calculated using the relationship fBSA=1/CT,BSA-1/CO,BSA. Nonlinear regression was used to fit the function fBSA=f1×BSA and find the best-fit values for f1 and n. Scatter and Bland-Altman plots were drawn comparing the various formulae for correcting slope-intercept GFR.
The trend for fBSA to decrease with increasing BSA was highly significant (Spearman's test: RS=-0.31; P=0.0002). When the data were fitted by nonlinear regression, the best-fit values (95% confidence interval) of the model parameters were n=-0.13 (from -0.21 to -0.04) and f1=0.00191 (from 0.00183 to 0.00200).
The results confirm that fBSA varies with BSA and provide independent values of the parameters f1 and n. Differences from GFRs calculated using the original JBM equation were small and not clinically significant. The BM equation also performed well for CT,BSA less than 125 ml/min/1.73 m. However, there was a small number of children with CT,BSA greater than 150 ml/min/1.73 m for whom the JBM formula provided more accurate estimates of true GFR than did the BM equation.
Previously we have proposed a technique for the measurement of plasma clearance in patients with ascites. The impact of using the technique was assessed and the results compared with those from a ...reference technique in 111 patients having glomerular filtration rate measurements as part of their workup for liver transplantation.
Results of calculations using the new technique were compared with plasma clearance measurements obtained using a conventional slope-intercept technique and with clearance measurements based on urine collection. Discrepancies between the results of plasma clearance and urinary clearance assessments were investigated by using an uncollimated gamma camera to measure the total retention of the tracer.
Conventional slope-intercept calculations overestimated clearance compared with the new technique by more than 20% in 21% of the patients. Significant differences between the results of the two methods were more likely in patients with more severe ascites. Results of urine collection-based measurements of Cr-51 EDTA clearance were frequently significantly lower than measurements using the new technique, whereas measurements of urinary clearance of creatinine were higher. Gamma camera measurements suggest that discrepancies between total and urinary clearance of Cr-51 EDTA are due to incomplete urine collection.
The new technique is a practical method for assessment of kidney function and should be used in patients with liver disease who have or may have ascites.
Glomerular 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.
We 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 Tc-DTPA studies in 142 patients, mostly paediatric patients, with suspected fluid disturbances.
CL (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.
Compared 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.
The study objective was to establish the diagnostic efficacy of cystatin C in the assessment of glomerular filtration rate (GFR) in paediatric oncology patients by investigating the relationships ...between serum cystatin C, serum creatinine and isotope clearance and determining whether these relationships are different from those seen in a group of patients of similar age with renal disease. This was a cohort study in which patients were divided into two groups: group A comprised renal patients and group B comprised oncology patients. All patients were referred for isotopic GFR assessment as part of routine clinical management and concurrently also had assessments made of their serum creatinine and cystatin C levels, together with height and weight measurements. Reciprocals of cystatin C correlate well with isotopic GFR; correlation coefficients from linear regression were 0.83 and 0.66 for the renal and oncology groups, respectively. However, when GFR was assessed from serum creatinine and cystatin C, levels of agreement were still very high (95% levels of agreement: -33 and 31 ml/min/1.73 m for cystatin C and -46 and 30 ml/min/1.73 m for the Counahan serum creatinine estimate). Receiver-operator characteristic curve analysis demonstrated that cystatin C has improved diagnostic utility for identifying patients with GFRs both below normal (90 ml/min/1.73 m) and below the point at which chemotherapy dose reduction may be considered (60 ml/min/1.73 m). Levels of intrapatient variability were similar for both tracers. Cystatin C was shown to be a better indicator of renal function compared with serum creatinine in oncology patients as demonstrated by receiver-operator characteristic curve and Bland-Altman analyses; however, sensitivity of the tracer to mild reductions in GFR is still low.
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).
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.
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%).
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.
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