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.

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.

Characterisation of MRI Indeterminate Breast Lesions Using Dedicated Breast PET and Prone FDG PET-CT in Patients with Breast Cancer-A Proof-of-Concept Study.

Magnetic resonance imaging (MRI) in patients with breast cancer to assess extent of disease or multifocal disease can demonstrate indeterminate lesions requiring second-look ultrasound and ultrasound or MRI-guided biopsies. Prone positron emission tomography-computed tomography (PET-CT) is a dedicated acquisition performed with a breast-supporting device on a standard PET-CT scanner. The MAMmography with Molecular Imaging (MAMMI, Oncovision, Valencia, Spain) PET system (PET-MAMMI) is a true tomographic ring scanner for the breast. We investigated if PET-MAMMI and prone PET-CT were able to characterise these MRI- indeterminate lesions further. A total of 10 patients with breast cancer and indeterminate lesions on breast MRI were included. Patients underwent prone PET-MAMMI and prone PET-CT after injection of FDG subsequently on the same day. Patients then resumed their normal pathway, with the clinicians blinded to the results of the PET-MAMMI and prone PET-CT. Of the MRI-indeterminate lesions, eight were histopathologically proven to be malignant and two were benign. PET-MAMMI and prone PET-CT only were able to demonstrate increased FDG uptake in 1/8 and 0/8 of the MRI-indeterminate malignant lesions, respectively. Of the MRI-indeterminate benign lesions, both PET-MAMMI and prone PET-CT demonstrated avidity in 1/2 of these lesions. Our findings do not support the use of PET-MAMMI to characterise indeterminate breast MRI lesions requiring a second look ultrasound.

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.

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.

Sentinel node detection in early breast cancer with intraoperative portable gamma camera: UK experience.

PURPOSE: Access to nuclear medicine department for sentinel node imaging remains an issue in number of hospitals in the UK and many parts of the world. Sentinella® is a portable imaging camera used intra-operatively to produce real time visual localisation of sentinel lymph nodes. METHODS: Sentinella® was tested in a controlled laboratory environment at our centre and we report our experience on the first use of this technology from UK. Moreover, preoperative scintigrams of the axilla were obtained in 144 patients undergoing sentinel node biopsy using conventional gamma camera. Sentinella® scans were done intra-operatively to correlate with the pre-operative scintigram and to determine presence of any residual hot node after the axilla was deemed to be clear based on the silence of the hand held gamma probe. RESULTS: Sentinella® detected significantly more nodes compared with CGC (p < 0.0001). Sentinella® picked up extra nodes in 5/144 cases after the axilla was found silent using hand held gamma probe. In 2/144 cases, extra nodes detected by Sentinella® confirmed presence of tumour cells that led to a complete axillary clearance. CONCLUSIONS: Sentinella® is a reliable technique for intra-operative localisation of radioactive nodes. It provides increased nodal visualisation rates compared to static scintigram imaging and proves to be an important tool for harvesting all hot sentinel nodes. This portable gamma camera can definitely replace the use of conventional lymphoscintigrams saving time and money both for patients and the health system.

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).

Radiation dose of 18F-FDG to lactating breasts, its effect on the effective dose and a more accurate effective dose from 18F-FDG.

INTRODUCTION: Lactating breasts have greater uptake of fluorine-18 fluorodeoxyglucose (F-FDG) than nonlactating breasts; however, there are no published data on the radiation dose from F-FDG to lactating breasts or this effect on the effective dose (ED). In addition, the International Commission on Radiological Protection's (ICRP) most recently published ED of 1.9×10 mSv/MBq from F-FDG was calculated using weighting factors that have since been superseded. We therefore calculated the F-FDG radiation dose to the lactating breast, its effect on the ED and calculated more up-to-date EDs from F-FDG for nonlactating patients. METHODS: Breast uptake of F-FDG and volume were determined from PET/CT images of a lactating patient. These data, together with previously published biokinetic data on F-FDG, were used to calculate a radiation dose to the lactating breasts and its effect on the ED. In addition, tissue weighting factors and organ doses from the ICRP publications 103 and 106 were used to calculate more up-to-date EDs from F-FDG in nonlactating patients. RESULTS: The absorbed dose to the lactating breast from F-FDG is 1.75×10 mGy/MBq, which results in an increase in the ED of 6%. In nonlactating patients, a more up-to-date ED from F-FDG is 1.77×10 mSv/MBq for women and 1.64×10 mSv/MBq for men. CONCLUSION: This is the first reported dosimetry of F-FDG in lactating breasts, data that are required when justifying the radiation dose from an F-FDG PET scan in lactating patients. In addition, we calculated more up-to-date EDs from F-FDG that are lower than the current widely reported ED and should be used in future publications on F-FDG.

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.

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.

Validation and impact of a new technique for assessment of glomerular filtration rate in patients with liver disease.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Evaluation of image enhancement software as a method of performing half-count bone scans.

Reducing the radiation dose and scanning time of diagnostic tests is often desirable. One method uses image enhancement software such as Pixon, which processes lower-count scans and aims to produce high-quality images. However, it is essential that diagnostic accuracy is not compromised. We compared the level of agreement between clinicians using standard scans, with half-count and Pixon-enhanced half-count scans. Bone scans from 150 patients referred to diagnose metastatic disease were degraded by a process of Poisson-preserving binomial resampling to generate equivalent half-count scans and then processed by Pixon software to recreate 'original' high-quality scans. Two experienced clinicians reported the scans in a randomized, blinded manner for metastatic disease (yes/no) and assigned a confidence level to this diagnosis. Levels of agreement between clinicians were calculated for the full-count, half-count, and Pixon-enhanced half-count scans and between scanning methods for each clinician. Agreement between clinicians for standard full-count scans was 92% (±4%, κ=0.80), compared with 92% (±4%, κ=0.79) for half-count scans and 87% (±5%, κ=0.70) for Pixon-processed half-count scans. Agreement for a single clinician viewing full-count versus half-count scans was 95% (±2%, κ=0.88), similar to the agreement for a single clinician viewing full-count versus Pixon-processed half-count scans (95%, ±2%, κ=0.88). With respect to confidence in diagnosis, 127 full-count scans were scored in the highest category, compared with 98 half-count and 88 Pixon-processed half-count scans. Switching to half-count scanning does not introduce more diagnostic disagreement than is already present between clinicians. However, clinicians feel less confident reporting half-count scans. The Pixon enhancement step improved neither objective diagnostic agreement nor clinician confidence.