Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The royal free hospital cirrhosis glomerular filtration rate.

Current expressions based on serum creatinine concentration overestimate kidney function in cirrhosis, leading to significant differences between "true" and calculated glomerular filtration rate (GFR). We compared the performance of the four-variable and six-variable Modification of Diet in Renal Disease and chronic kidney disease epidemiology with "true," or measured, GFR (mGFR) and the impact of this difference on Model for End-Stage Liver Disease (MELD) calculation. We subsequently developed and validated a GFR equation specifically for cirrhosis and compared the performance of the new derived formula with existing GFR formulae. We included 469 consecutive patients who had a transplant assessment between 2011 and 2014. mGFR was measured using plasma isotope clearance according to a technique validated in patients with ascites. A corrected creatinine was derived from the mGFR after application of the Modification of Diet in Renal Disease formula. Subsequently, a corrected MELD was calculated and compared with the conventionally calculated MELD. Stepwise multiple linear regression was used to derive a GFR equation. This was compared with the mGFR in independent external and internal validation sets of 82 and 174 patients with cirrhosis, respectively. A difference >20 mL/minute/1.73 m2 between existing formulae and mGFR was observed in 226 (48.2%) patients. The corrected MELD score was ≥3 points higher in 177 (37.7%) patients. The predicted equation (r2 = 74.6%) was GFR = 45.9 × (creatinine-0·836 ) × (urea-0·229 ) × (international normalized ratio-0·113 ) × (age-0.129 [Corrected November 29, 2016: originally written as "age-129."]) × (sodium0·972 ) × 0.809 (if female) × 0.92 (if moderate/severe ascites). An online calculator is available at http://rfh-cirrhosis-gfr.ucl.ac.uk. The model was a good fit and showed the greatest accuracy compared to that of existing formulae. CONCLUSION: We developed and validated a new accurate model for GFR assessment in cirrhosis, the Royal Free Hospital cirrhosis GFR, using readily available variables; this remains to be tested and incorporated in prognostic scores in patients with cirrhosis. (Hepatology 2017;65:582-591).

Quantitative lymphoscintigraphy of the lower limbs for the diagnosis of phlebolymphoedema.

INTRODUCTION: Phlebolymphoedema is caused by the interaction of the venous and lymphatic systems in a state of chronic venous insufficiency in which increased microvascular filtration causes an increased rate of lymph production. Lymphatic drainage rate increases in response, but this is unsustainable and can cause lymphatic failure and oedema. We hypothesise that in phlebolymphoedema we could measure unusually high lymphatic drainage while the lymph system is still fully functional. METHOD: Patients referred for lymphoscintigraphic investigation of swollen legs between April 2021 and December 2022 were reviewed. Quantitative lymphoscintigraphy was performed following the technique of Keramida et al . (2017) and ilio-inguinal nodal uptake (IIQ%) was calculated. The presence of scintigraphic features of increased lymph production was noted for each limb. RESULTS: A total of 39 patients were reviewed (78 limbs, 29F, 10M). Seven limbs were identified with supranormal lymphatic function (IIQ > 30%) plus three borderline. Of these 10 limbs, all had at least two scintigraphic features of increased lymph production. CONCLUSION: Quantitative lymphoscintigraphy, although developed for diagnosing abnormally low lymphatic function, may also have utility at the upper end of the spectrum for identifying chronic venous insufficiency. An IIQ% upper normal limit of 30% could be used to diagnose venous insufficiency as the cause for limb swelling. This is of note for patients of large body habitus in whom venous ultrasound is difficult.

The role of serial 99mTc-DPD scintigraphy in monitoring cardiac transthyretin amyloidosis.

PURPOSE: Cardiac transthyretin amyloidosis is a usually fatal form of restrictive cardiomyopathy for which clinical trials of treatments are ongoing. It is anticipated that quantitative nuclear medicine scintigraphy, which is experiencing growing interest, will soon be used to evaluate treatment efficacy. We investigated its utility for monitoring changes in disease load over a significant time period. METHODS: Sixty-two treatment-naive patients underwent 99mTc-labelled 3,3-diphosphono-1,2propanodicarboxylic acid (99mTc-DPD) scintigraphy two to four times each over a five-year period. Quantitation of cardiac 99mTc-DPD retention was performed according to two established methods: measurement of heart-to-contralateral ratio (H/CL) in the anterior view (planar) and percentage of administered activity in the myocardium (SPECT). RESULTS: In total 170 datasets were analysed. Increased myocardial retention of 99mTc-DPD was demonstrable as early as 12 months from baseline. Year-on-year progression across the cohort was observed using SPECT-based quantitation, though on 30 occasions (27.8%) the change in our estimate was negative. CONCLUSIONS: The spread of our results was notably high compared to the year-on-year increases. If left unaccounted for, variance may draw fallacious conclusions about changes in disease load. We therefore urge caution in drawing conclusions solely from nuclear medicine scintigraphy on a patient-by-patient basis, particularly across a short time period.

Tailoring the sampling time of single-sample GFR measurement according to expected renal function: a multisite audit.

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/1.73m2 a 2-h sample is recommended; between 50 and 90 ml/min/1.73m2 a 3-h sample is recommended; and between 30 and 50 ml/min/1.73m2 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/1.73m2 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.

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

PURPOSE: The 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. METHODS: Ten (51)Cr-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. RESULTS: The 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). CONCLUSION: CL(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.

Accuracy of next-day single-sample measurement for low glomerular filtration rate and comparison with same-day slope-intercept glomerular filtration rate.

AIM: We aimed to investigate the accuracy of a single-sample glomerular filtration rate (SS-GFR) technique with a sample taken at 24 h post-injection for patients with GFR lower than 25 mL/min/1.73 m2. A comparison with the results from same-day slope-intercept GFR (SI-GFR) was also performed. METHODS: Data from patients referred for GFR assessment to inform the management of chronic kidney disease at the Royal Free Hospital were reviewed. Four-sample SI-GFR calculation with samples at 2-, 4-, 6-, and 24-h post-injection was taken as the reference measurement to which the Gref and Karp SS-GFR (24-h sample) and same-day SI-GFR (2- and 4-h samples) were compared. The effect of protein binding on GFR accuracy was modelled. RESULTS: A total of 43 GFR examinations with reference GFR less than 25 mL/min/1.73 m2 were included in the analysis. Bland-Altman analysis gave mean differences of 0.4 mL/min/1.73 m2 (95% confidence interval: 0-0.7) for SS-GFR (24 h) and 3.0 mL/min/1.73 m2 (95% confidence interval: 1.9-4.2) for same-day SI-GFR. 95% limits of agreement were -2.0 to 2.8 mL/min/1.73 m2 for SS-GFR (24 h) and -4.0 to 10.1 mL/min/1.73 m2 for same-day SI-GFR. CONCLUSIONS: SS-GFR with a 24-h sample is more accurate than same-day SI-GFR in patients with GFR less than 25 mL/min/1.73 m2. Using SS-GFR with a 24-h sample in routine clinical practice will result in clinically insignificant differences in GFR result compared with the reference technique, whereas a same-day SI-GFR measurement could cause large inaccuracies.

Correction of slope-intercept glomerular filtration rate measurement without scaling for body size.

AIM: The aim of this study was to evaluate a slope-intercept glomerular filtration rate (GFR) one-compartment correction method based exclusively on the rate constant (α2) of the exponential between 2 and 4 h post-injection that requires no scaling for BSA. METHODS: The correction factor is 1/([C.α2]+1). C depends on the difference between one-compartment-corrected and uncorrected GFR, so varies with different correction procedures. Patients were in four groups: group 1 (Cr-EDTA; n = 141) and group 2 (Tc-DTPA; n = 47) had sampling at 2, 3 and 4 h. Groups 3A (Tc-DTPA; n = 168) and 3B (Tc-DTPA; n = 361) gave nine samples up to 480 min. C was calculated from GFR corrected using Brochner-Mortensen (BM) without prior BSA-scaling (CBM; GFRBM), after BSA-scaling then reverse-scaling as per British Nuclear Medicine Society (BNMS) guidelines (CBNMS; GFRBNMS), and after correction using the equations containing 'f' described by Fleming (CFlem; GFRFlem) and Jodal and Brochner-Mortensen (CJBM; GFRJBM). In group 3A, C (C9) was determined from GFR measured from all nine samples (GFR9) and from seven samples (C7) up to 240 min. In 3B, GFRC, corrected using 1/([C9.α2]+1), was compared with GFRBM, GFRBNMS, GFRFlem and GFRJBM against GFR9 (gold-standard). RESULTS: C derived from these one-compartment correction formulae ranged from 25 to 32 min. In group 3, C7 and C9 were 28 ± 11 and 38 ± 14 min (P < 0.0001). Biases of GFRBM, GFRBNMS, GFRJBM, GFRFlem and GFRC against GFR9 were 2.7, 1.5, 4.2, 3.4 and 0.4 ml/min. Corresponding precisions were 9.3, 7.3, 7.0, 6.7 and 7.6 ml/min. CONCLUSION: Correction using α2 avoids BSA scaling, has a low bias against gold-standard GFR and does not over-correct at high GFR.

DPD Quantification in Cardiac Amyloidosis: A Novel Imaging Biomarker.

OBJECTIVES: To assess whether single-photon emission computed tomography (SPECT/CT) quantification of bone scintigraphy would improve diagnostic accuracy and offer a means of quantifying amyloid burden. BACKGROUND: Transthyretin-related cardiac amyloidosis is common and can be diagnosed noninvasively using bone scintigraphy; interpretation, however, relies on planar images. SPECT/CT imaging offers 3-dimensional visualization. METHODS: This was a single-center, retrospective analysis of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scans reported using the Perugini grading system (0 = negative; 1 to 3 = increasingly positive). Conventional planar quantification techniques (heart/contralateral lung, and heart/whole-body retention ratios) were performed. Heart, adjacent vertebra, paraspinal muscle and liver peak standardized uptake values (SUVpeak) were recorded from SPECT/CT acquisitions. An SUV retention index was also calculated: (cardiac SUVpeak/vertebral SUVpeak) × paraspinal muscle SUVpeak. In a subgroup of patients, SPECT/CT quantification was compared with myocardial extracellular volume quantification by CT imaging (ECVCT). RESULTS: A total of 100 DPD scans were analyzed (patient age 84 ± 9 years; 52% male): 40 were Perugini grade 0, 12 were grade 1, 41 were grade 2, and 7 were grade 3. Cardiac SUVpeak increased from grade 0 to grade 2; however, it plateaued between grades 2 and 3 (p < 0.001). Paraspinal muscle SUVpeak increased with grade (p < 0.001), whereas vertebral SUVpeak decreased (p < 0.001). The composite parameter of SUV retention index overcame the plateauing of the cardiac SUVpeak and increased across all grades (p < 0.001). Cardiac SUVpeak correlated well (r2 = 0.73; p < 0.001) with ECVCT. Both the cardiac SUVpeak and SUV retention index had excellent diagnostic accuracy (area under the curve [AUC]: 0.999). The heart to contralateral lung ratio performed the best of the planar quantification techniques (AUC: 0.987). CONCLUSIONS: SPECT/CT quantification in DPD scintigraphy is possible and outperforms planar quantification techniques. Differentiation of Perugini grade 2 or 3 is confounded by soft tissue uptake, which can be overcome by a composite SUV retention index. This index can help in the diagnosis of cardiac amyloidosis and may offer a means of monitoring response to therapy.

Renal function evaluated by measured GFR during follow-up in pediatric liver transplant recipients.

Calcineurin inhibitors form the mainstay of immunosuppression in pediatric liver transplantation, but may cause significant nephrotoxicity. We evaluated renal function in liver transplant recipients treated with a tacrolimus-based immunosuppressive regimen. GFR was measured using 99 mTc-DTPA in patients pretransplant and annually thereafter. GFR calculated by Schwartz formula was compared with the measured values. Sixty patients who underwent 69 transplants were followed for at least one yr post-transplant (median three yr). In children over two yr of age at transplant GFR fell significantly from pretransplant (140 mL/min/1.73 m(2)) to one yr post-transplant (112 mL/min/1.73 m(2)) (p = 0.01) but thereafter there was no significant decline. In younger children the picture was confounded by maturation of renal function, but again there was no significant fall to five yr post-transplant. Although 13 (22%) patients developed renal dysfunction post-transplant, none required renal replacement therapy. cGFR correlated poorly with measured values (r = 0.21). Use of a tacrolimus-based immunosuppressive regimen is associated with an initial decline in GFR, though this picture is confounded in younger children by normal maturation of renal function. There is no further significant fall in GFR in the medium-term. The Schwartz formula is inaccurate in determining GFR in this patient group.

99mTc DTPA vs. 51Cr EDTA for glomerular filtration rate measurement: is there a systematic difference?

AIM: The study aimed to investigate whether a systematic difference exists between Cr EDTA and Tc DTPA for measurement of glomerular filtration rate (GFR). METHODS: The distribution of GFR results from candidates attending the Royal Free Hospital for assessment of suitability for kidney donation was compared before and after the change from Cr EDTA to Tc DTPA using three-sample slope-intercept GFR calculation with samples at 2, 3, and 4 hours. A second cohort of oncology patients attending Leeds Teaching Hospitals NHS Trust underwent simultaneous GFR measurement with both tracers by full characterisation of the plasma clearance curve with nine samples between 5 minutes and 8 hours post-injection. Three-sample slope-intercept GFR was also calculated for comparison with cohort 1. RESULTS: From the first cohort, a statistically significant (P = 0.008) systematic difference of 5.8% (95% confidence interval: 1.5%-10.1%) was found in the three-sample slope-intercept GFR, with Tc DTPA giving the higher result. From the second cohort, a statistically significant (P = 0.00001) systematic difference of 2.9% (95% confidence interval: 1.8%-3.9%) was found in three-sample slope-intercept GFR, with Tc DTPA giving the higher result. There was no statistically significant difference between the tracers when GFR was calculated by full characterisation of the plasma clearance curve. CONCLUSION: There is a small systematic difference between GFR measured with Tc DTPA and Cr EDTA using abbreviated techniques, which is removed when GFR is calculated by full characterisation of the plasma clearance curve. The difference is not clinically significant in the context of intra-patient variability of GFR measurement.

UK audit of glomerular filtration rate measurement in 2001.

OBJECTIVE: To investigate the consistency of glomerular filtration rate (GFR) calculation from plasma sampling in the UK. METHODS: Ten patients' data sets from plasma sampling measurements of GFR were distributed throughout the UK. The data included count rates from four samples taken between 2 and 4 h after injection, a diluted sample of injected dose for standardisation, the patient's height, weight, age and sex. Participants were asked to use the routine method to calculate GFR and express the results in absolute terms (i.e. in millilitres/minute) and normalized for body surface area (ml/min/1.73 m2). Supplementary data were also requested relating to workload, method used and normal range. Intercentre variability was assessed by calculating the root median square (RMedS) deviation of each GFR from the median for that data set. Centres using a particular analysis method were grouped together and the RMedS deviation of each result from the median for that group and that data set was calculated. The influence of using normalized data and number of samples was also studied. RESULTS: Seventy-nine returns were received. For the normalized data, the overall RMedS variability was 5.8 ml/min/1.73 m2. This decreased significantly to 0.6 ml/min/1.73 m2 when results were grouped by analysis method. Results were similar for non-normalized data. A small but significant decrease in error with the number of samples was observed. CONCLUSION: Considerable variability in GFR values obtained at different centres in the UK for a given set of data was observed. Nearly all this variability was due to different methods of analysis. If methodology were standardized then intercentre variability in GFR analysis could be reduced dramatically. Radionuclide techniques are confirmed as being the method of choice if an accurate value of GFR is required.

Quantitation of 99mTc-DPD uptake in patients with transthyretin-related cardiac amyloidosis.

PURPOSE: Transthyretin (ATTR) amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), initially developed as a bone-seeking radiotracer, is remarkably sensitive for imaging cardiac ATTR amyloid deposits. Our aim was to investigate the feasibility and utility of estimating 99mTc-DPD uptake in myocardial tissue; this has the potential to yield reliable quantitative information on cardiac amyloid burden, which is urgently required to monitor disease progression and response to novel treatments. METHODS: Three methods of quantitation were developed and tested on 74 patients with proven cardiac ATTR amyloidosis who had recently undergone 99mTc-DPD planar whole-body imaging and SPECT-CT. Quantitative results were compared to measurements of extracellular volume fraction (ECV) by cardiac magnetic resonance imaging, a validated technique for measuring amyloid burden. RESULTS: An experienced clinician graded uptake using a widely-used visual scoring system as 1 (n = 15), 2 (n = 39) or 3 (n = 20). Linear correlations between the SPECT and ECV data (p < .001) were demonstrated. None of the methods showed that 99mTc-DPD uptake in the heart was significantly greater in patients with grade-3 uptake than in those with grade-2 uptake. CONCLUSIONS: Quantitation of 99mTc-DPD uptake in cardiac transthyretin amyloid deposits is complex and is hindered by competition for radiotracer with amyloid in skeletal muscle. The latter underlies differences in uptake between grade-2 and grade-3 patients, not cardiac uptake.

A pilot study demonstrating cardiac uptake with 18F-florbetapir PET in AL amyloidosis patients with cardiac involvement.

18F-florbetapir is a promising tracer in amyloidosis. This study evaluates its use in patients with systemic AL amyloidosis (AL) before and after treatment as well as its serial utility in monitoring. Fifteen AL patients with cardiac involvement underwent 18F-florbetapir PET imaging and three patients underwent repeat imaging after chemotherapy. All patients had demonstrable cardiac uptake with 18F-florbetapir. Cardiac uptake appeared greater in chemotherapy-naïve vs. chemotherapy-established AL patients median (left ventricular retention index 0.21 vs. 0.14 min-1, respectively) and greater in patients that had not achieved at least a partial haematological response (left ventricular retention index 0.2 vs. 0.14 min-1, respectively). There was no interval difference in cardiac uptake and no correlation in cardiac uptake with cardiac biomarkers or serum free light chains. This is the largest study of 18F-florbetapir in patients with AL amyloidosis. It is the first study to include patients prior to starting chemotherapy and uniquely includes patients who underwent repeat imaging after chemotherapy. All patients had cardiac uptake with 18F-florbetapir, regardless of haematological or NT-proBNP response to chemotherapy. There was a suggestion that treatment-naïve patients may have higher cardiac uptake. Larger studies are required to establish the role of this tracer in screening patients with amyloidosis for cardiac involvement, discriminating between ATTR and AL amyloidosis, and in disease monitoring.

Can oncology patients' central venous catheters be used for isotope assessment of glomerular filtration rate? An in-vitro study.

BACKGROUND: Isotope assessment of glomerular filtration rate (GFR) is frequently performed in patients with central venous catheters (CVCs). Use of the CVCs for administration of tracer and subsequent blood sampling would be less distressing for patients (particularly paediatric) and would reduce the frequency of failed samples due to poor venous access. However, the GFR test is quantitative and could be affected by incomplete tracer delivery due to adhesion to the CVC and also by contamination of blood samples due to adhered tracer leaching back into the sampled blood as it passes through the CVC. AIM: This in vitro study aimed to quantify the effects on GFR assessment of tracer adhesion and leaching, in single-lumen and dual-lumen CVCs. METHOD: New and clinically used single-lumen CVCs were injected with tracer (99mTc-DTPA and 51Cr-EDTA) and then flushed repeatedly with saline. The outflows were assayed in a gamma counter and, where possible, the CVCs were imaged on a gamma camera to take snap shots of tracer movement throughout a GFR assessment. In a separate experiment, a phantom patient was used to compare blood sampling through a dual lumen CVC with peripheral sampling. RESULT AND CONCLUSION: A CVC successfully delivers >99% of tracer. Subsequent blood samples can be taken through the other lumen of a dual-lumen CVC but not through a single-lumen as this significantly alters the GFR result due to contamination.

A national survey of computed tomography doses in hybrid PET-CT and SPECT-CT examinations in the UK.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Suggested UK NDRLs and achievable doses for six common PET-CT and SPECT-CT examinations have been established as a result of this study.

Patient-specific optimisation of administered activity and acquisition times for 18F-FDG PET imaging.

BACKGROUND: The purpose of this study is to identify a method for optimising the administered activity and acquisition time for 18F-FDG PET imaging, yielding images of consistent quality for patients with varying body sizes and compositions, while limiting radiation doses to patients and staff. Patients referred for FDG scans had bioimpedance measurements. They were injected with 3 MBq/kg of 18F up to 370 MBq and scanned on a Siemens Biograph mCT at 3 or 4 min per bed position. Data were rebinned to simulate 2- and 1-min acquisitions. Subjective assessments of image quality made by an experienced physician were compared with objective measurements based on signal-to-noise ratio and noise equivalent counts (NEC). A target objective measure of image quality was identified. The activity and acquisition time required to achieve this were calculated for each subject. Multiple regression analysis was used to identify expressions for the activity and acquisition time required in terms of easily measurable patient characteristics. RESULTS: One hundred and eleven patients were recruited, and subjective and objective assessments of image quality were compared for 321 full and reduced time scans. NEC-per-metre was identified as the objective measure which best correlated with the subjective assessment (Spearman rank correlation coefficient 0.77) and the best discriminator for images with a subjective assessment of "definitely adequate" (area under the ROC curve 0.94). A target of 37 Mcount/m was identified. Expressions were identified in terms of patient sex, height and weight for the activity and acquisition time required to achieve this target. Including measurements of body composition in these expressions was not useful. Using these expressions would reduce the mean activity administered to this patient group by 66 MBq compared to the current protocol. CONCLUSIONS: Expressions have been identified for the activity and acquisition times required to achieve consistent image quality in FDG imaging with reduced patient and staff doses. These expressions might need to be adapted for other systems and reconstruction protocols.

Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) amyloidosis and its relationship with skeletal muscle and soft tissue amyloid.

AIMS: High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99mTechnetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99mTc-DPD scintigraphy has prognostic significance in ATTR amyloidosis. METHODS AND RESULTS: Patient survival from time of 99mTc-DPD scintigraphy was determined in 602 patients with ATTR amyloidosis, including 377 with wild-type ATTR (ATTRwt) and 225 with mutant ATTR (ATTRm) amyloidosis. Patients were stratified according to Perugini grade (0-3) on 99mTc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99mTc-DPD scan (n = 28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n = 28), 2 (n = 436) or 3 (n = 110) 99mTc-DPD scan (P < 0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99mTc-DPD scan in ATTRwt (n = 369), V122I-associated ATTRm (n = 92) or T60A-associated ATTRm (n = 59) amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99mTc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (P < 0.001). CONCLUSION: 99mTc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.

A systematic review of single-sample glomerular filtration rate measurement techniques and demonstration of equal accuracy to slope-intercept methods.

PURPOSE: We aimed to identify the most accurate single-sample glomerular filtration rate (SS-GFR) technique for all patient ages. MATERIALS AND METHODS: We performed a systematic review of all published SS-GFR measurement techniques and compared the results from each test with a gold-standard nine-point 'area-under-curve' measurement of GFR as well as slope-intercept (SI-GFR) methods for 412 GFR tests. RESULTS: We have shown that for patients of all ages the SS-GFR technique developed by Fleming and colleagues delivers the best accuracy and precision, with results equivalent to those calculated by SI-GFR. The median percentage difference from the gold-standard GFR for the Fleming technique is 4.8% (95% confidence interval 3.9-5.7%) and that for the three-point SI-GFR is 5.6% (95% confidence interval 4.9-6.3%). The interquartile range of the distribution of percentage difference from the gold standard is -0.23 to 11% for the Fleming method and 1.6-11% for the three-point SI-GFR. CONCLUSION: The Fleming technique outperforms the method currently recommended by the international guidelines, and is simpler as only one equation is required for all patients instead of separate equations for adults and children. We propose that the SS-GFR technique of Fleming replace the methods currently recommended by the international and BNMS guidelines for routine measurement of GFR for expected results greater than 30 ml/min/1.73 m. A thorough system of measurement checks should be implemented for all methods of GFR assessment; the perceived lack of opportunity for quality control checks to be performed on the result of a single-sample measurement is addressed in the companion paper of this study.

Effectiveness of quality control methods for glomerular filtration rate calculation.

PURPOSE: In this work, we aimed to identify the types of errors encountered in glomerular filtration rate (GFR) measurement and test the effectiveness of all published quality control (QC) methods for detection of clinically significant errors. METHODS: A total of 412 GFR tests were carried out on adults and children. The three-point slope-intercept glomerular filtration rate (SI-GFR) was compared with the nine-point 'area under curve' calculation as a gold standard to determine the error in SI-GFR. The Durbin-Watson test was used to characterize the nature of the errors. The sensitivity, specificity and positive predictive value (PPV) of QC methods for detecting clinically significant errors were calculated and receiver operating characteristic curves were constructed. The QC methods were also applied to a dataset of 100 four-point GFR tests from different institutions. RESULTS: Model failure is the dominant cause of clinically significant error in this dataset, with individual point measurement errors only giving rise to clinically significant errors in a small number of cases. No QC test had an acceptable combination of sensitivity, PPV and specificity. The correlation coefficient QC test had the largest area under the receiver operating characteristic curve (0.73). No other QC test had an area greater than 0.57. CONCLUSION: All the QC methods have poor sensitivity and PPV for detecting clinically significant errors and so cannot be relied on to ensure a robust measurement of GFR, underlining the need for careful working practices and a thorough system of measurement checks. We found no evidence for the value of multiple sampling with respect to QC; until such evidence is published, their clinical utility is unproven.

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

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.