EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond.

These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/PSPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/PSPECT an essential method for the diagnosis of PE. When V/PSPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/PSPECT interpretation are discussed. In conclusion, V/PSPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.

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

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/m(2). 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.

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

PURPOSE: The 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. METHODS: Fifteen 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. RESULTS: The 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. CONCLUSION: The 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.

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.

On specificity of 2nd generation TSH receptor autoantibody measurements.

BACKGROUND: TSH receptor (TSHR) antibodies (TRAb) are the hallmark in the serological diagnosis of Graves' disease (autoimmune hyperthyroidism). Irrespective of receptor origin second generation TRAb assays have been shown to be more sensitive than original first generation assays. The specificity of both assay generations is claimed to be close to 100% for discriminating healthy individuals from Graves' disease patients. However, there are a small number of Hashimoto's thyroiditis (autoimmune hypothyroidism) patients demonstrating detectable TRAb. MATERIALS AND METHODS: One hundred and sixty-six Hashimoto's thyroiditis patients and 72 with Graves' disease were tested in second generation assays employing porcine and recombinant human TSHR. Receiver operating characteristics (ROC) were calculated for comparison. RESULTS: Using a threshold of 1.5 IU/L for both assays, 7 out of 166 Hashimoto's patients demonstrated positive TRAb in the human TSHR assay whereas only 1 patient was measured positive in the porcine TSHR assay (specificity: 95.8% and 99.4%, respectively). Seventy-one out of 72 Graves' disease patients were positive in the human TSHR assay whereas 70 showed positive results in the porcine TSHR assay (sensitivity: 98.6% and 97.2%, respectively; ROC p = 0.16). CONCLUSION: In this study, two commercial second generation TRAb assays with differing TSHR have been compared regarding the specificity in Hashimoto's thyroiditis patients. The slightly higher sensitivity of the human TSHR assay is obtained at the expense of a lower specificity. The impact of the different specificities should be considered due to the differing type of therapy for both patient groups.

Influence of female sex hormones on thyroid parameters determined in a thyroid screening.

This is a cross-sectional study with a non-randomly selected population to ascertain the influence of female sex hormones on thyroid function. TSH, TT4, FT4, TT3 and FT3 were determined in 251 women using either oral hormonal contraceptives or hormone replacement treatment, 255 women not taking either, and a control group of 900 men. Women with normal thyroid morphology using oral hormonal contraceptives in the pre-menopausal group had a significantly higher TT4 and TT3, and lower FT3, respectively, than both non-users and men. FT4 and TSH remained unchanged. In the peri-/post-menopausal group, thyroid function of women using hormone replacement treatment was not significantly different from non-users, but either women still had a significantly lower FT3 than men. We conclude that oral hormonal contraceptives and hormone replacement treatment increase TT4 and TT3 and do not influence FT4 and TSH. They decrease FT3 which is in contrast to what would be expected theoretically and what has been observed in earlier studies.

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 patient's 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.

X-ray-based attenuation correction of myocardial perfusion scans: practical feasibility and diagnostic impact.

OBJECTIVES: This study describes the practical implementation of X-ray-based attenuation correction (AC) of myocardial perfusion scans in a large teaching hospital, characterizes the impact of AC on the diagnostic confidence of the interpreter and tries to predict which patients are likely to benefit from the technique. METHODS: One hundred and seven consecutive patients underwent a 2 day (99m)Tc-tetrofosmin protocol with adenosine stress using GE Millennium VG with AC and ECG-gated acquisition (ECG-g). The diagnostic impact of AC/ECG-g was judged by a panel of three observers. RESULTS: AC was not achieved in 46 patients. Individual observers rated AC 'essential' in 37 scans and 'helpful' in 68 scans. For ECG-g, this applied to 12 and 78 scans, respectively. The rating for AC was better than that for ECG-g in 57 scans, and vice versa in 31 scans. Equal ratings were recorded in 41 scans, and neither technique was needed in 54 scans. Diagnostic interpretation of abnormal scans was significantly more likely to benefit from either AC or ECG-g than interpretation of normal scans. Patients in whom AC was considered useful had a significantly higher body mass and chest circumference, but the overlap was large. CONCLUSIONS: In practice, AC was not feasible in a significant proportion of our patients. AC received better ratings from observers more often than ECG-g. Interpreter confidence with AC was significantly greater in scans with perfusion defects than in normal scans. Body mass and chest circumference cannot be used to predict which patients will benefit from AC.

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.

18F-FDG PET for detecting myocardial viability: validation of 3D data acquisition.

UNLABELLED: (18)F-FDG PET is an important diagnostic tool for detecting myocardial viability in patients with coronary artery disease. In combination with perfusion scanning, (18)F-FDG PET allows differentiation between reversibly and irreversibly damaged myocardium and selection of patients likely to benefit from revascularization. Viability PET is usually performed in two-dimensional (2D) mode. Taking into account the rising number of three-dimensional (3D)-only scanners, a validation of 3D acquisition is required. METHODS: Twenty-one patients with coronary artery disease referred for (18)F-FDG PET underwent an imaging protocol of nongated 2D (2D-NG) and gated 2D (2D-G) acquisitions for 15 min each, followed by 3D gated acquisitions for 10 min (3D-10) and 5 min (3D-5), using an ECAT Exact HR+ scanner. Results were analyzed using a 20-segment polar map in terms of activity concentration (Bq/mL), viability (50% uptake threshold), regional activity distribution, visual assessment of viability based on a 3-point rating scale, and left ventricular ejection fraction. RESULTS: Activity concentration measured in each segment with 2D-G, 3D-10, and 3D-5 showed a good linear correlation with 2D-NG. Quantitative viability assessment with 3D-5 gave a sensitivity of 84% and a specificity of 98%, compared with 2D-NG. No differences in regional activity distribution and visual viability assessment were found between the various protocols. Left ventricular ejection fractions obtained with 3D-10 and 3D-5 showed a good linear correlation with those measured with 2D-G. CONCLUSION: An ECG-gated 3D imaging protocol gave results comparable to those of 2D acquisition with regard to absolute and regional myocardial activity distribution, left ventricular function, and visual viability assessment. Sensitivity for viability assessment with a 50% uptake threshold was significantly less with 3D, but specificity was maintained. This protocol delivers a clinical performance nearly equivalent to that of 2D acquisition.

Retinoic acid for redifferentiation of thyroid cancer--does it hold its promise?

OBJECTIVES: To evaluate the effectiveness of isotretinoin for improving (131)I uptake in recurrent/metastasized thyroid cancer with no/insufficient (131)I uptake. DESIGN: Retrospective analysis of 25 patients treated between June 1999 and May 2001. METHODS: 15 female and 10 male patients were given isotretinoin at 1 mg/kg for 3 months, followed by (131)I treatment. All patients received a (131)I scan 72 h after administration, thyroglobulin measurement, chest X-ray and ultrasound of the neck, and some patients underwent a (18)F-fluorodeoxyglucose (FDG) positron emission tomography (n=14) and computed tomography scan of the chest (n=11). RESULTS: In two out of 14 patients with raised thyroglobulin but no (131)I uptake, a slightly improved (131)I uptake was seen. In a further 11 patients an improvement of (131)I uptake of known lesions was desired or further non-(131)I-accumulating lesions were known. A dosimetrically relevant improvement of uptake was seen in three of these patients. (18)F-FDG uptake and thyroglobulin did not correlate with the success/failure of the isotretinoin treatment. Side effects including a strong "sunburn", cheilitis, mucositis, conjunctivitis and raised transaminases occurred in two-thirds of patients. They were of an overall tolerable level and were reversible after isotretinoin had been stopped. CONCLUSION: From our clinical experience over a period of 2 years we conclude that the therapeutic effect of isotretinoin in thyroid cancer is certainly less than previously reported. An indiscriminate use of isotretinoin in all patients with otherwise untreatable thyroid cancer cannot be recommended.

99mTc labelled model drug carriers - labeling, stability and organ distribution in rats.

The surface characteristics of intravenously administered particulate drug carriers decisively influence the protein adsorption that is regarded as a key factor for the in vivo fate of the carriers. We labeled surface-modified polymer particles with the gamma-emitting radioisotope 99mTc in order to test their properties in blood and follow their in vivo fate. The biodistribution was different in various types of polymer particles. As expected, labeled particles were found in the mononuclear phagocyte system in a large scale but markedly different biodistribution for some particles were also shown.

Autoantibodies to thyroperoxidase (TPOAb) in a large population of euthyroid subjects: implications for the definition of TPOAb reference intervals.

OBJECTIVE: Measurement of autoantibodies against thyroperoxidase (TPOAb) plays an important role in the diagnosis of autoimmune thyroid disease. The assessment of reference intervals for TPOAb, however, is a controversial issue since elevated TPOAb values are sometimes found in subjects without other evidence of thyroid disease. METHODS: TPOAb were measured in 1,295 euthyroid individuals using a highly sensitive, fully automated chemiluminescence assay (Advantage A-TPO, Nichols Institute Diagnostics, CA, USA). The study subjects participated in a population study on the prevalence of thyroid disorders in the German federal state of Saxony, an area of mild iodine deficiency. RESULTS: TPOAb above the detection limit of 0.45 IU/ml were found in 1,277/1,295 euthyroid individuals. TPOAb values in the low measurable range below 1.1 IU/ml followed a normal distribution, and this was independent of age and sex. When using a cut-off value of 1.1 IU/ml, which corresponds to a sensitivity of 79% and a specificity of 95% resulting from the receiver-operator characteristic plot for discrimination between a main type and other types with a higher mean value of TPOAb, elevated TPOAb were found in 14.4% of euthyroid men and in 25.8% of euthyroid women. CONCLUSIONS: The results demonstrate for the first time that TPOAb are detectable in nearly all euthyroid individuals and that TPOAb values in the low measurable range are normally distributed. The distribution of TPOAb values in the low range is independent of age and sex. Based on these data, reference intervals for TPOAb can be defined that are independent of the population investigated. The clinical significance of slightly elevated TPOAb, however, has still to be defined by prospective studies.

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%.

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

OBJECTIVE: Bowel 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. METHODS: A total of 79 sequential stress MPS acquired 1 h after injection of 600 MBq Tc-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. RESULTS: The 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). CONCLUSION: We 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 (99m)Tc-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.

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.