The Use of Single Photon Emission Computed Tomography in Aerosol Medicine.

Imaging of radiolabeled aerosols provides useful in vivo data on both the initial site of deposition and its subsequent transport by mucociliary clearance and epithelial permeability. Single Photon Emission Computed Tomography (SPECT) uses a gamma camera with multiple rotating heads to produce three-dimensional (3D) images of inhaled radioaerosol labeled with technetium-99m. This enables total lung deposition and its 3D regional distribution to be quantified. Aligned 3D images of lung structure allow deposition data to be related to lung anatomy. Mucociliary clearance or epithelial permeability can be assessed from a time series of SPECT aerosol images. SPECT is slightly superior to planar imaging for measuring total lung deposition. However, it is more complex to use, and for studies where total lung deposition is the endpoint, planar imaging is recommended. However, SPECT has been shown to be clearly superior to planar imaging for assessing regional distribution of aerosol and is the method of choice for this purpose. It therefore has applications in studying the influence of regional deposition on clinical effectiveness and also in validating computer models of deposition. The inability to directly radiolabel drug molecules with 99mTc is a clear disadvantage of SPECT and limits its potential use for pharmacokinetic studies. SPECT provides a wealth of data on aerosol deposition, which has been relatively underused at present. Optimal methods of analyzing and interpreting the data need to be developed. SPECT can also, in principle, provide detailed information of mucociliary clearance and has the potential to significantly improve knowledge of this process and hence clarify the role of clearance as a biomarker.

Quantitative Assessment of Regional Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging.

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study investigates the value of regional clearance measurements in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (i) healthy nonsmoking controls (NSCs) (n = 9), (ii) smoking controls (SCs) who were current smokers with normal lung function (n = 10), and (iii) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volumes at 1 second (FEV1) for the three groups were 109 (± 18), 94 (± 5), and 78 (± 12), respectively. After inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Both lung clearance and tracheobronchial clearance (TBC) (normalized to 24 hours clearance) were calculated for inner and outer lung zones. Inner zone clearance was corrected for input from the outer zone. A novel parameter, the bronchial airways clearance index (BACI), which combined clearance data from both zones, was also evaluated. Regional results were compared with whole lung clearance in the same subjects. Results: Corrected inner zone clearance at 3 hours was not reduced compared with NSC in either SCs or COPD. Outer zone clearance was higher in COPD than in the other groups. Corrected inner zone TBC showed significant reductions in SC and COPD compared with NSC. BACI was significantly reduced in COPD compared with NSC and also correlated with FEV1. The mean BACI for SC was also reduced compared with NSC, but the distribution of results was bimodal, with a significant proportion of subjects having values in the NSC range. Conclusions: Regional MCC demonstrated differences between NSCs, SCs, and subjects with mild-to-moderate COPD, which were not apparent with whole lung measurements.

Propagation of measurement errors in glomerular filtration rate determination: a comparison of slope-intercept, single-sample and slope-only methods.

BACKGROUND: Measurement errors occurring during glomerular filtration rate (GFR) studies propagate to an error in the calculated GFR. Previous work has modelled measurement errors for slope-intercept (SI-GFR), single-sample (SS-GFR) and slope-only (SO-GFR) methods. In this study, we have extended these models. The primary aims were to (i) compare measurement errors in two-sample SI-GFR, three-sample SI-GFR, SS-GFR and SO-GFR, and (ii) determine the sensitivity of GFR to errors arising from different measurements. PATIENTS AND METHODS: This study expanded on previous models of GFR measurement error incorporating biological data from 786 patients and realistic measurement errors. GFR median absolute error and the coefficient of variation (CV) were calculated for each method. A sensitivity analysis was carried out for individual measurement errors. RESULTS: The median absolute error ranged between 1.2 and 2.3 ml/min/1.73 m, lowest for SS-GFR (4 h) and highest for SO-GFR. At higher rates of clearance, CV was less than 5% for all methods. CV increased rapidly when GFR decreased below a threshold ranging between 34 and 56 ml/min/1.73 m, lowest for three-point SI-GFR and highest for SO-GFR. SI-GFR and SS-GFR are most sensitive to injected activity quantification, but less sensitive to other measurement errors. CONCLUSION: Measurement errors are probably insignificant relative to biological variation for GFR of more than 60 ml/min/1.73 m, but become significant irrespective of biological variation at lower GFR, particularly in serial studies when GFR less than 25 ml/min/1.73 m. Limits of precision recommended in the 2018 British Nuclear Medicine Society guideline are appropriate for once-off GFR measurement, whereas slightly more stringent limits are proposed for serial studies.

Quantitative Assessment of Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging Using the Change in Penetration Index.

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study compared the use of change in penetration index (PI) with conventional whole lung clearance in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (1) healthy nonsmoking controls (n = 9), (2) smoking controls who were current smokers with normal lung function (n = 10), and (3) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volume at 1 second (FEV1) for the three groups was 109 (±18), 94 (±5), and 78 (±12), respectively. Following inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Total lung clearance and tracheobronchial clearance (TBC; normalized to 24-hour clearance) were calculated. A novel parameter, the normalized change in PI (NOCHIP), was also evaluated. PI is the ratio of counts between outer and inner lung zones normalized to lung volume. Results: More aerosol was deposited in central airways in COPD compared to nonsmoking controls, using 24-hour clearance measurements (p < 0.001). Smoking controls had intermediate values. The optimal endpoint for MCC assessment was chosen to be 3 hours, when intersubject variability was minimal, while preserving a measure of early clearance. There was no statistical difference between the three groups in mean total lung clearance, or TBC, at 3 hours. NOCHIP at 3 hours was reduced significantly, compared to nonsmoking controls, in both smoking controls (p = 0.007) and COPD (p < 0.0001). It also correlated with FEV1 (p = 0.003). A higher proportion of smoking control subjects had NOCHIP values in the nonsmoking control range than in the COPD group. Conclusions: NOCHIP was a more sensitive measure of MCC than whole lung clearance and TBC in mild-to-moderate COPD.

Probable range for whole kidney mean transit time values determined by reexamination of UK audit studies.

OBJECTIVES: Inconsistency in the intercentre measurement of whole kidney mean transit time (MTT) has been reported in a previously published UK audit. The main objectives of this study were to identify a probable value of MTT for each kidney in the UK audit data and to find likely reasons for the reported variations. METHODS: Datasets of MTT values were obtained by an independent review of the audit data by four experienced practitioners of deconvolution techniques. The deconvolution techniques used included the matrix method, a constrained least squares method as well as a residence time technique. The datasets were compared using t-test, linear regression, and mean difference analysis. RESULTS: Twelve of a total of 13 datasets showed nonsignificant differences using a paired t-test (P>0.05). For each kidney (x), a collective mean and standard deviation, Mx and SDx, respectively, were calculated from these 12 datasets and a probable range was defined as Mx+/-3SDx. Average SDx/Mx was 3.6% (range 1.5-7.7%). For five kidneys, Mx exceeded the median of the audit results by 3.5-15.3 SDx (P<0.001). CONCLUSION: Probable ranges for whole kidney MTT have been estimated with good precision. Underestimation of the area under the plateau of the renal retention function as well as overestimation of the plateau height might have contributed to an underestimation of MTT apparent in some audit results. Visual display of both the renal retention function and the reconvolution curve are suggested as simple quality control measures for analysis software.

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.

An improved equation for correcting slope-intercept measurements of glomerular filtration rate for the single exponential approximation.

OBJECTIVES: Glomerular filtration rate (GFR) is commonly assessed by plasma sampling using the slope-intercept technique. This method assumes a single exponential approximation to the plasma curve. To obtain an accurate estimate of GFR it is necessary to correct the slope-intercept value for the approximation. This is commonly done using the Brochner-Mortensen equation. This has been validated for normal and abnormally low GFRs, but there has been some suggestion that it may underestimate supra-normal GFR. This paper investigates this suggestion and aims to produce a new equation based on compartmental analysis, which should extrapolate the correction to higher values of GFR. METHODS: Compartmental analysis was used to produce the complete expression of the relationship between true GFR and slope-intercept GFR. A simplified analytical equation was then derived. The performance of the new equation was compared to the Brochner-Mortensen and Chantler equations using the true GFR as reference. RESULTS: The new analytical equation had minimal systematic error compared to true GFR up to 250 ml x min(-1) per 1.73 m(2). The Brochner-Mortensen equation was shown to underestimate high values of GFR. The error increased with GFR with a 10% underestimation at 180 ml x min(-1) per 1.73 m(2). The Chantler equation gave a systematic overestimate of GFR. The error increased with GFR with a 30% overestimate at 180 ml x min(-1) per 1.73 m(2). CONCLUSIONS: The new equation described in this paper gave considerably improved correction for the single exponential approximation at high GFR compared to previously described equations.

A technique for the simulation of planar radionuclide images of the kidney.

BACKGROUND: Although Tc-dimercaptosuccinic acid (DMSA) scans are routinely used to quantify relative renal function, no quantification method is universally adopted. Audits using real patient data indicate reasonable consistency but, as the true relative function is unknown, accuracy cannot be assessed. The aim was to simulate realistic DMSA images that can be used to assess accuracy. METHODS: Anatomical models were created from computed tomography (CT) scans of a patient who had also undergone DMSA imaging. Organs that take up DMSA were outlined on CT and each assigned an activity concentration (with renal cortex and medulla modelled separately). The simulated images were visually compared to the patient's clinical images and subtracted to identify differences. Iteration was used on the posterior image to find the organ activities that produced the most realistic simulated image. The optimal activity distribution was then used to also simulate an anterior image. To assess the simulations, the percentage difference was calculated between the counts in each kidney on the real and simulated images. RESULTS: Visually, the clinical and simulated images appear similar and the subtracted images indicate only small differences. The percentage difference in kidney counts between the images was less than 1% for both kidneys on the posterior image and less than 5% on the anterior image. The cortex and medulla activity concentrations were approximately equal. CONCLUSION: A technique for realistic simulation of DMSA images has been devised and should prove useful for evaluating image analysis software.

Limitations of the HMPAO SPECT appearances of occipital lobe perfusion in the differential diagnosis of dementia with Lewy bodies.

OBJECTIVE: To assess the utility of the appearances of occipital lobe perfusion on HMPAO SPECT in the diagnosis of dementia with Lewy bodies (DLB) using the 123I-FP-CIT findings as the diagnostic 'gold standard'. METHODS: Eighty-four consecutive patients underwent both HMPAO SPECT and 123I-FP-CIT as part of their routine investigations for suspected DLB. RESULTS: Thirty-nine of the 84 FP-CIT scans were abnormal indicating a prevalence of 44% of patients with DLB in this series. In those patients classified as DLB, 28% of HMPAO SPECT scans demonstrated occipital hypoperfusion. In those patients with a dementia other than DLB 31% of patients demonstrated occipital hypoperfusion (P=0.8). CONCLUSION: Occipital lobe hypoperfusion as demonstrated by HMPAO SPECT in patients with suspected Lewy body dementia does not appear to be able to either rule in, or rule out, the diagnosis of DLB.

An analytical technique to recover the third dimension in planar imaging of inhaled aerosols--2 estimation of the deposition per airway generation.

An analytical algorithm has been recently described for converting planar scintigraphic images of aerosol distributions in the lungs to an equivalent three-dimensional (3D) representation. The recovery of the volumetric information has opened up to planar imaging the possibility of measuring aerosol deposition per airway generation. This paper investigates the accuracy and precision of the generation analysis achievable with planar imaging using simulation. Typical generation parameters--such as the bronchial and conducting airway deposition fractions (BADF and CADF)--have been derived. The accuracy of the technique has been measured by the coefficient of variation (COV) of the estimates from the known values used in the simulation. The results have also been compared to those obtained from 3D imaging (single photon emission computed tomography or SPECT). Finally, the technique has been applied to two aerosol studies conducted on a healthy volunteer, to demonstrate its implementation on clinical data. The accuracy of the BADF and CADF estimates from planar imaging were 42% and 41%, respectively; the corresponding values from SPECT were 32% and 22%. In conclusion, approximate estimates of airway distribution parameters can be derived from planar imaging. However, the errors are significantly higher than with SPECT.

Quantification of [123I]FP-CIT SPECT brain images: an accurate technique for measurement of the specific binding ratio.

PURPOSE: A technique is described for accurate quantification of the specific binding ratio (SBR) in [(123)I]FP-CIT SPECT brain images. METHODS: Using a region of interest (ROI) approach, the SBR is derived from a measure of total striatal counts that takes into account the partial volume effect. Operator intervention is limited to the placement of the striatal ROIs, a task facilitated by the use of geometrical template regions. The definition of the image for the analysis is automated and includes transaxial slices within a "slab" approximately 44 mm thick centred on the highest striatal signal. The reference region is automatically defined from the non-specific uptake in the whole brain enclosed in the slab, with exclusion of the striatal region. A retrospective study consisting of 25 normal and 30 abnormal scans-classified by the clinical diagnosis reached with the scan support-was carried out to assess intra- and inter-operator variability of the technique and its clinical usefulness. Three operators repeated the quantification twice and the variability was measured by the coefficient of variation (COV). RESULTS: The COVs for intra- and inter-operator variability were 3% and 4% respectively. A cutoff approximately 4.5 was identified that separated normal and abnormal groups with a sensitivity, specificity and diagnostic concordance of 97%, 92% and 95% respectively. CONCLUSION: The proposed technique provides a reproducible and sensitive index. It is hoped that its independence from the partial volume effect will improve consistency in quantitative measurements between centres with different imaging devices and analysis software.

Defining the lung outline from a gamma camera transmission attenuation map.

Segmentation of the lung outline from gamma camera transmission images of the thorax is useful in attenuation correction and quantitative image analysis. This paper describes and compares two threshold-based methods of segmentation. Simulated gamma camera transmission images of test objects were used to produce a knowledge base of the variation of threshold defining the lung outline with image resolution and chest wall thickness. Two segmentation techniques based on global (GT) and context-sensitive (CST) thresholds were developed and evaluated in simulated transmission images of realistic thoraces. The segmented lung volumes were compared to the true values used in the simulation. The mean distances between segmented and true lung surface were calculated. The techniques were also applied to three real human subject transmission images. The lung volumes were estimated and the segmentations were compared visually. The CST segmentation produced significantly superior segmentations than the GT technique in the simulated data. In human subjects, the GT technique underestimated volumes by 13% compared to the CST technique. It missed areas that clearly belonged to the lungs. In conclusion, both techniques segmented the lungs with reasonable accuracy and precision. The CST approach was superior, particularly in real human subject images.

A technique for analysis of geometric mean renography.

BACKGROUND AND OBJECTIVES: Renography is used routinely to assess relative right to left renal function. Quantification is usually carried out using posterior images. Errors in relative renal function may occur if the kidneys are at different depths. Geometric mean images from combined anterior and posterior views are much less affected by kidney depth and offer the opportunity of more accurate and precise quantification. Background subtraction is a key part of the analysis process and validated protocols for geometric mean imaging have not been devised. This study aims to derive a suitable background subtraction protocol for geometric mean imaging. METHODS: Simultaneous anterior and posterior renography using Tc mercaptoacetyltriglycine (MAG3) was performed on 16 adults. Analysis was carried out using both geometric mean and posterior images. The geometric mean background subtraction protocol was modified to give the same results as a posterior method, which had previously been validated by correlation with measurements of glomerular filtration rate. Absolute and relative uptakes were then obtained from both geometric mean and posterior analyses. For each analysis values were obtained both with and without depth correction. RESULTS: A revised background subtraction protocol for geometric mean renography was devised which operated successfully on all studies. Both absolute renal uptake and relative function values obtained from geometric mean analysis were not systematically different from those obtained using posterior analysis with depth correction. Values of the relative renal function from posterior analysis after depth correction were closer to the geometric mean values than estimates obtained before correction. CONCLUSION: A technique for analysing geometric mean renography data has been developed which gives results consistent with a previously validated posterior-only method.

Comparison of SPECT aerosol deposition data with a human respiratory tract model.

Three-dimensional (3D) radionuclide imaging provides detailed information on the distribution of inhaled aerosol material within the body. Analysis of the data can provide estimates of the deposition per airway generation. In this study, two different nebulizers have been used to deliver radiolabeled aerosols of different particle size to 12 human subjects. Medical imaging has been used to assess the deposition in the body. The deposition pattern has also been estimated using the International Commission on Radiological Protection (ICRP) empirical model and compared to values obtained by experiment. The results showed generally good agreement between model and experiment for both aerosols for the deposition in the extrathoracic and conducting airways. However, there were significant differences in the fate of the remainder of the aerosol between the amount deposited in the alveolar region and that exhaled. The inter-subject variability of deposition predicted by the model was significantly less than that measured, for all regions of the body. The model predicted quite well the differences in deposition distribution pattern between the two aerosols. In conclusion, this study has shown that the ICPR model of inhaled aerosol deposition shows areas of good agreement with results from experiment. However, there are also areas of disagreement, which may be explained by hygroscopic particle growth and individual variation in airway anatomy.

Analytical technique to recover the third dimension in planar imaging of inhaled aerosols: (1) impact on spatial quantification.

An analytical algorithm is described for converting planar scintigraphic images of aerosol distributions in the lungs to an equivalent three-dimensional (3D) representation. The recovery of volumetric information should benefit regional quantification. The technique has been validated using simulated planar images of eleven known aerosol distributions in ten realistic lungs. Global and regional 3D parameters, such as the total activity deposition (A), the penetration index (PI) and the relative penetration index (rPI), were quantified on the planar images and on their 3D representation. Random and systematic errors of the estimation were measured. Finally, the performance of planar imaging was compared with that of single-photon emission computed tomography (SPECT). SPECT images were simulated for the same aerosol distributions in the same subjects and quantified for A, PI, and rPI. The systematic errors in A, PI and rPI obtained from planar imaging were 8.9%, 64.8%, and 54.1%, respectively, using the two-dimensional (2D) analysis; they improved significantly to 4.4%, 19.0%, and 25.5% with the 3D analysis (p < 0.01). The corresponding values for SPECT were 5.2%, 9.8%, and 15.7%, significantly better for PI and rPI (p < 0.01). The random errors of A were similar for all techniques being about 5%; those of PI and rPI measurements were significantly higher for planar imaging (

Comparison of SPECT aerosol deposition data with twenty-four-hour clearance measurements.

Three-dimensional (3D) radionuclide imaging provides detailed information on the distribution of inhaled aerosol material within the body. Analysis of the data can provide estimates of the deposition per airway generation. Information on regional distribution of deposited aerosol can also be obtained from 24-hour clearance measurements. In this study, a nebulizer was used to deliver a radiolabeled aerosol to nine human subjects. Single photon emission computed tomography (SPECT) has been used to assess the distribution of aerosol deposition per airway generation. The deposition pattern was also estimated using measurements of the aerosol remaining in the lung 24 h after inhalation. The error in the SPECT value was assessed by simulation and that in the 24-h clearance value by repeat analysis. The mean fraction of lung deposition in the conducting airway (CADF) from SPECT was 0.21. The corresponding 24-h clearance value was 0.23. These values were not significantly different. There was a weak but non-significant correlation between the SPECT and 24-h measurements (r = 0.49). The standard error of the difference was 0.11. The corresponding errors on the SPECT and 24-h clearance measurements were 0.04 and 0.05, respectively. There was no systematic difference between the values of conducting airways deposition obtained from 24-h measurements and SPECT. However, there were random differences on individual subjects, which were larger than the estimated measurement errors.

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung.

Development of a new drug for the treatment of lung disease is a complex and time consuming process involving numerous disciplines of basic and applied sciences. During the 2015 Congress of the International Society for Aerosols in Medicine, a group of experts including aerosol scientists, physiologists, modelers, imagers, and clinicians participated in a workshop aiming at bridging the gap between basic research and clinical efficacy of inhaled drugs. This publication summarizes the current consensus on the topic. It begins with a short description of basic concepts of aerosol transport and a discussion on targeting strategies of inhaled aerosols to the lungs. It is followed by a description of both computational and biological lung models, and the use of imaging techniques to determine aerosol deposition distribution (ADD) in the lung. Finally, the importance of ADD to clinical efficacy is discussed. Several gaps were identified between basic science and clinical efficacy. One gap between scientific research aimed at predicting, controlling, and measuring ADD and the clinical use of inhaled aerosols is the considerable challenge of obtaining, in a single study, accurate information describing the optimal lung regions to be targeted, the effectiveness of targeting determined from ADD, and some measure of the drug's effectiveness. Other identified gaps were the language and methodology barriers that exist among disciplines, along with the significant regulatory hurdles that need to be overcome for novel drugs and/or therapies to reach the marketplace and benefit the patient. Despite these gaps, much progress has been made in recent years to improve clinical efficacy of inhaled drugs. Also, the recent efforts by many funding agencies and industry to support multidisciplinary networks including basic science researchers, R&D scientists, and clinicians will go a long way to further reduce the gap between science and clinical efficacy.

Quality control of slope-intercept measurements of glomerular filtration rate using single-sample estimates.

OBJECTIVES: Measurement of glomerular filtration rate (GFR) using the slope-intercept technique determines the plasma clearance curve by fitting a straight line to the logarithm of sample count rate. When two samples are used there is no check on the validity of curve fitting. GFR may also be estimated from single-sample concentrations. This study describes a method of quality control for the two-sample technique using the agreement between the one-sample and two-sample estimates. METHODS: GFR measurements using Tc-DTPA were performed on 225 adults and 100 children using two samples taken between 2 h and 4 h post-injection. The two-sample values obtained using the British Nuclear Medicine Guidelines slope-intercept technique were compared to one-sample estimates obtained using a new general equation. Equations describing the variation of GFR error with GFR value were defined. These were used to determine action levels giving the limits of expected agreement between slope-intercept and single-sample values. The use of these action levels for quality control was demonstrated in a further 120 GFR measurements. RESULTS: The variation of single-sample error estimate with GFR depended both on the time of sample and body surface area. For specific sample groups, the error variation with GFR could be approximated using a truncated quadratic equation. Four studies were identified as failing quality control in the dataset used to define the error equations. Two studies failed in the test dataset. CONCLUSIONS: One-sample equations give reliable estimates of GFR, which may be used for quality control of slope-intercept GFR assessment.

A general equation for estimating glomerular filtration rate from a single plasma sample.

OBJECTIVES: Glomerular filtration rate (GFR) may be estimated from a single plasma sample measurement using empirical equations. This method forms the basis of international guidelines on GFR measurement. New guidelines have recently been recommended by the British Nuclear Medicine Society (BNMS). These use the slope-intercept technique in which several samples are obtained. Quality control of measurement may be achieved by comparison with the individual single-sample values. This paper compares international guideline single-sample estimates of GFR with the new BNMS method and derives an improved general single-sample equation. METHODS: GFR measurements using Tc-DTPA were performed on 180 adults and 100 children using samples at approximately 2 h and 3 h and a further 45 adults with samples at 2, 3 and 4 h. The two-sample values obtained using the BNMS guideline method were compared to one-sample estimates obtained using (1) international guidelines and (2) a new equation derived from the data. The new equation was evaluated in a further 145 subjects. RESULTS: The international guidelines technique had systematic differences between the one-sample and two-sample estimates of GFR. The new equation had minimal systematic error and reduced random error (standard error of the estimate 4.5 ml . min per 1.73 m). CONCLUSIONS: There were significant differences between GFR values obtained using the international guidelines single-sample method and the slope-intercept method described in the BNMS guidelines. The new equation described in this paper gave considerably improved agreement and is recommended if single-sample estimates are to be used as quality control for BNMS guideline measurements.