Thomas Grüning

Extracellular fluid volume and glomerular filtration rate in 1878 healthy potential renal transplant donors: effects of age, gender, obesity and scaling

UNLABELLED Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects. METHODS This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV. RESULTS ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (<30 years) had higher GFR than young men but the reverse was recorded in the elderly (>65 years). There was no difference in GFR between obese (BMI>30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable. CONCLUSION There are several significant differences in GFR and ECV between healthy men and women.

Three-year clinical experience with VQ SPECT for diagnosing pulmonary embolism: diagnostic performance.

Ventilation-perfusion (VQ) single-photon emission computed tomography (SPECT) comprised the administration of SmartVent (n=386) or Technegas (n=1564) and 200 MBq (99m)Tc-MAA. 1406 scans were normal, 462 showed PE, 61 showed a singular subsegmental mismatched defect, 21 scans were non-diagnostic. 26% of scans performed with Technegas showed PE, compared to 15% with SmartVent. VQ SPECT had a sensitivity of 95.7%, specificity 98.6%, positive predictive value 95.7%, negative predictive value 98.6%. A normal VQ SPECT scan implied a more than ten-fold lower cause-specific mortality (1 in 1406) than a scan showing PE (1 in 116). NPV of a negative D-dimer was 94.3%.

The reliability of glomerular filtration rate measured from plasma clearance: a multi-centre study of 1,878 healthy potential renal transplant donors

PurposeThe objective of the study was to undertake a clinical audit of departmental performance in the measurement of glomerular filtration rate (GFR) using the coefficient of variation (CV) of extracellular fluid volume (ECFV) as the benchmark. ECFV is held within narrow limits in healthy subjects, narrower than GFR, and should therefore have a low CV.MethodsFifteen departments participated in this retrospective study of healthy renal transplant donors. Data were analysed separately for men (n ranged from 28 to 115 per centre; total = 819) and women (n = 28–146; 1,059). All centres used the slope-intercept method with blood sample numbers ranging from two to five. Subjects did not fast prior to GFR measurement. GFR was scaled to body surface area (BSA) and corrected for the single compartment assumption. GFR scaled to ECFV was calculated as the terminal slope rate constant and corrected for the single compartment assumption. ECFV/BSA was calculated as the ratio of GFR/BSA to GFR/ECFV.ResultsThe departmental CVs of ECFV/BSA and GFR/BSA ranged from 8.3 to 25.8% and 12.8 to 21.9%, respectively, in men, and from 9.6 to 21.1% and 14.8 to 23.7%, respectively, in women. Both CVs correlated strongly between men and women from the same centre, suggesting department-specific systematic errors. GFR/BSA was higher in men in 14 of 15 centres, whereas GFR/ECFV was higher in women in 14 of 15 centres. Both correlated strongly between men and women, suggesting regional variation in GFR.ConclusionThe CV of ECFV/BSA in normal subjects is a useful indicator of the technical robustness with which GFR is measured and, in this study, indicated a wide variation in departmental performance.

Diagnosing venous thromboembolism in pregnancy

OBJECTIVE We report the imaging outcomes of all pregnant patients referred for suspected thromboembolism over a 43-month period. METHODS We identified 168 patients who underwent ventilation/perfusion (VQ) single-photon emission CT (SPECT), CT pulmonary angiography (CTPA) or a Doppler ultrasound scan of the lower legs, as well as a control group of 89 non-pregnant age- and sex-matched patients who underwent VQ SPECT during the same period. Imaging outcomes were recorded, and radiation doses were calculated for individual patients. RESULTS VQ SPECT and CTPA were equally likely to diagnose pulmonary embolism (PE) in about one patient out of every seven patients investigated. One in three CTPA scans was of suboptimal quality. A Doppler ultrasound examination of the legs will find deep venous thrombosis much less often, in about 1 patient out of every 15 patients investigated. The prevalence of PE in pregnant patients (as diagnosed by VQ SPECT) was similar to that in the non-pregnant, age- and sex-matched control group. The effective dose and the absorbed radiation dose to the maternal breast were lower with VQ SPECT. The foetal dose is comparable for both VQ SPECT and CTPA. CONCLUSION VQ SPECT and CTPA provide a similar diagnostic yield for diagnosing PE during pregnancy, but VQ SPECT does so with a lower radiation dose to the mother (effective dose and breast dose). ADVANCES IN KNOWLEDGE Ours is the first report of the diagnostic performance of VQ SPECT, rather than planar VQ scans, in pregnancy in a routine clinical setting.

Can administration of metoclopramide reduce artefacts related to abdominal activity in myocardial perfusion SPECT

Objectives Myocardial perfusion SPECT is frequently affected by artefacts related to abdominal activity. Metoclopramide has been suggested to relieve this, but two previous studies have shown conflicting results. Methods Ninety-five patients received 10 mg metoclopramide orally after injection of 99mTc-tetrofosmin for the stress scan and 86 patients had metoclopramide after their rest injection. A control group of 82 patients did not receive metoclopramide. Scans were evaluated visually by three readers. Results Metoclopramide given before the stress scan led to abdominal activity being visually better in 16 scans, worse in 10, and unchanged in 67 scans, compared to the same patients rest scan without metoclopramide administration. Metoclopramide administered before the rest scan resulted in abdominal activity in 11 scans being visually better, in 19 worse, and 53 scans were deemed unchanged. These differences were not significant. The number of repeat stress or rest scans was not significantly different between patients who had received metoclopramide and those who had not. The administration of metoclopramide, irrespective of whether it was given before the stress or rest scan, made no significant difference to inferior wall-to-abdomen count ratio. Conclusion Neither qualitative nor quantitative analysis showed an effect of metoclopramide on abdominal activity in myocardial perfusion SPECT.

Comment on “State-of-the-Art Imaging in Pulmonary Embolism : Ventilation/Perfusion Single-Photon Emission Computed Tomography versus Computed Tomography Angiography—Controversies, Results, and Recommendations from a Systematic Review”

Hess et al1 believe that ventilation/perfusion scintigraphy with single-photon emission computed tomographyand lowdose X-ray computed tomography (V/Q SPECT/CT) should be considered the first-line imaging modality for diagnosing pulmonary embolism (PE) in most clinical settings, based on overall better diagnostic performance.We believe that this conclusion is not substantiated by the data presented in their meta-analysis: First, therewas no significant difference in the diagnostic performance of V/Q SPECT and V/Q SPECT/CT in the studies included (although there was only a single study included for V/Q SPECT/CT, and another study included from the same group dealing with planar and V/Q SPECT). Second, the authors did not include several studies that met their inclusion criteria. In a study on V/Q SPECT based on 1,785 patients with suspected PE who underwent clinical follow-up, PE was reported in 607 patients (34%).2 In 608 patients with a final diagnosis of PE, 601 patients had positive V/Q SPECT (99%). In 1,177 patients without a final diagnosis of PE, 1,153 patients had negative V/Q SPECT (98%). The report was nondiagnostic in 19 patients (1%). Six cases were classified as false negative for PE, because PEwas diagnosed at follow-up andwas fatal in one case. Six cases were classified as false-positive for PE because the clinician decided not to treat. In addition, in this study, 152 patients had both CTA and V/Q SPECT, due to continuing clinical suspicion of PE after the first test. In this subgroup, CTA showed a sensitivity of 43% and specificity of 73%, measured against a decision to treat, while V/Q SPECT had a sensitivity of 97% and specificity of 89%. CTA applied as second procedure had a low diagnostic impact in this and a previous study.3 The authors1 also did not include, in their meta-analysis, another study that involved almost 2,000 patients, andwhich showed that sensitivity, specificity, and positive and negative predictive values of V/Q SPECT against a composite reference standard were all greater than 95%.4 The authors1 also cite data from 81 patients simultaneously imaged with V/Q SPECT and V/Q SPECT/CT, 38% of which had PE.5 They showed 97% sensitivity and 88% specificity when only V/Q SPECTwas used. However, when adding lowdose CT, the sensitivity was unchanged, but specificity increased to 100%. Interestingly, 18% of patients had a falsepositive diagnosis of PE when V/Q SPECT alone was interpreted. A reason for this may be that every mismatch was interpreted as PE rather than only mismatches that conform to segmental lung anatomy, as recommended by European guidelines.6,7 In our opinion, the recommendation to use a hybrid system for PE diagnosis is premature. Coco and O’Gurek8 showed that CT utilization has increased dramatically in the evaluation of patients with suspected PE, without improving the rate of PE or other clinically significant diagnoses. Moreover, patients are exposed to ever greater radiation doses from imaging.9 Therefore, it is important to properly validate V/Q SPECT/CT and not adopt it too quickly, without fully assessing the benefits and risks.

Higher extracellular fluid volume in women is concealed by scaling to body surface area

Abstract Objective. The objective was to assess body surface area (BSA) for scaling extracellular fluid volume (ECV) in comparison with estimated lean body mass (LBM) and total body water (TBW) across a range of body mass indices (BMI). Methods. This was a multi-centre study from 15 centres that submitted raw data from routine measurement of GFR in potential kidney transplant donors. There were 819 men and 1059 women in total. ECV was calculated from slope-intercept and slope-only measurements of GFR. ECV was scaled using two methods: Firstly, division of ECV by the scaling variable (ratio method), and secondly the regression method of Turner and Reilly. Subjects were placed into five BMI groups: < 20, 20–24.9, 25–29.9, 30–34.9, and 35 + kg/m2. LBM and TBW were estimated from previously published, gender-specific prediction equations. Results. Ratio and regression scaling gave almost identical results. ECV scaled to BSA by either method was higher in men in all BMI groups but ECV scaled to LBM and TBW was higher in women. There was, however, little difference between men and women in respect to ECV per unit weight in any BMI group, even though women have 10% more adipose tissue. The relations between TBW and BSA and between LBM and BSA, but not between LBM and TBW, were different between men and women. Conclusion. Lean tissue in women contains more extracellular water than in men, a difference that is obscured by scaling to BSA. The likely problem with BSA is its insensitivity to body composition.

Can plasma D-dimer predict the result of a ventilation-perfusion scan?

The use of plasma D-dimer assay has been advocated for the exclusion of pulmonary embolism. We retrospectively looked at 840 patients in whom both ventilation-perfusion scan and D-dimer assay were performed within 48 h. The negative predictive value of a negative D-dimer assay was 96% for emergency admissions and 98% for inpatients. We present the cases of two patients with negative D-dimer assay results who had a high-probability lung scan, and we have found a further three patients with negative D-dimer assay results who had an intermediate-probability lung scan.

Efficacy of various SPECT reconstruction algorithms in differentiating bowel uptake from inferior wall uptake in myocardial perfusion scans.

ObjectiveBowel uptake is a frequent artefact in myocardial perfusion scans (MPS) that can impede the assessment of the inferior wall, necessitating repeat acquisitions. This study is a retrospective analysis of MPS reconstructed with different algorithms to see whether corrections for scatter or depth-dependent loss of resolution may help differentiate apparently joined uptake in the inferior wall of the left ventricle from that in the bowel. MethodsA total of 79 sequential stress MPS acquired 1 h after injection of 600 MBq 99mTc-tetrofosmin on a Siemens Symbia T were reconstructed using filtered back projection (FBP), iteratively with ordered subset expectation maximization (OSEM) and iteratively with three-dimensional collimator beam modelling (Siemens Flash3D), Flash3D with scatter correction (SC) and/or attenuation correction (AC). Single-photon emission computed tomography studies were classified by a nonblinded observer as follows: I, no artefact; II, abdominal activity just touching the inferior wall (not interfering with interpretation); III, abdominal activity covering some myocardium (interpretation still meaningful); and IV, nondiagnostic scan for large parts of the myocardium. ResultsThe following numbers of scans were placed in categories I/II/III/IV for each algorithm: FBP 58/15/2/4; OSEM 54/16/5/4; Flash3D 54/20/5/0; Flash3D+SC 61/17/1/0; Flash3D+AC 21/36/17/5; and Flash3D+SC+AC 29/39/9/2. These differences were significant (Friedman test, P<0.0001). ConclusionWe conclude that the use of Flash3D+SC produces the least number of nondiagnostic or difficult-to-interpret scans.

Resolution recovery in planar bone scans: diagnostic value in metastatic disease.

Recovery of spatial resolution lost through increasing lesion-to-detector distance can improve the spatial resolution of planar images. We compare two commercial solutions, HiScan (http://www.scivis.de) and Xact.bone (http://www.ultraspect.com), with unprocessed planar whole-body bone scans. Thirty-five patients with suspected bone metastases were scanned 3 h after injection of 600 MBq 99mTc-HMDP at 12 cm/min. Two patients with more than 20 lesions were used for reporter training and were excluded from the analysis. Two blinded reporters categorized each scan as benign, indeterminate or malignant and assigned individual lesions to those same categories. Image quality was first graded on a 1 (worst) to 10 (best) scale for each individual scan, and then all three scans of each patient were ranked according to image quality. Reporter A detected 65, 90 and 83 malignant lesions with the unprocessed scan, HiScan and Xact.bone and 23, 24 and 17 indeterminate lesions, respectively. Reporter B detected 60, 80 and 75 malignant lesions with the unprocessed scan, HiScan and Xact.bone and 17, 16 and 14 indeterminate lesions, respectively. To summarize, reporters A/B detected 38/33% and 28/25% more malignant lesions with HiScan and Xact.bone than with the unprocessed scan, respectively (Friedman’s test, P<0.05). The number of indeterminate lesions did not increase, but the percentage of unclear lesions decreased. Mean image quality for the unprocessed scan, HiScan and Xact.bone was 6.5, 9.1 and 7.9 for reporter A and 5.6, 7.5 and 6.7 for reporter B, respectively (P<0.0001). HiScan was ranked best for image quality in 82% of patients and Xact.bone in 18%. Resolution recovery in planar whole-body bone scans significantly increases the absolute number of detectable malignant lesions, decreases the percentage of indeterminate lesions, significantly increases image quality and is an easy-to-implement addition to routine clinical practice.