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Objective: Qualitative positron emission tomography (PET) myocardial perfusion imaging (MPI) scans are reconstructed with a delay after an injection of rubidium-82 (Rb) to ensure blood pool clearance and sufficient left ventricle to myocardium contrast. Our aim was to derive the minimal starting time of data reconstruction (STDR) after an injection of Rb for which the diagnostic value and image quality remained unaffected., Materials and Methods: We retrospectively included 23 patients who underwent rest-stress Rb PET MPI using 740 MBq. Patients fulfilling one of the two criteria indicating a slow blood pool clearance (ejection fraction <50% and/or cardiac output <3 l/min) were included in a consecutive manner. PET images using five different STDRs (1:15-2:15 min) were reconstructed and compared with reference images (STDR of 2:30 min). Differences in the summed rest score greater than or equal to 3 and total perfusion deficit greater than 3% were considered to significantly influence the diagnostic value. In addition, image quality was scored by two experts as not interpretable, inferior, adequate, or excellent., Results: The summed rest score differed greater than or equal to 3 from the reference in seven or more patients (≥30%) using STDR less than or equal to 2:00 min (P<0.02). STDR less than or equal to 1:30 min resulted in six or more patients (≥26%) with a total perfusion deficit difference greater than 3% (P<0.03).In addition, STDR less than or equal to 2:00 min resulted in a lower image quality (P<0.002) and STDR less than or equal to 2:15 min resulted in greater than or equal to two scans with noninterpretable image quality., Conclusion: STDR less than or equal to 2:15 min resulted in lower diagnostic value or insufficient image quality for qualitative PET MPI using 740 MBq Rb. An STDR of 2:30 min can be considered for clinical adoption.

Objectives: Recommended rubidium-82 activities for relative myocardial perfusion imaging (MPI) using present-generation PET scanners may be unnecessarily high. Our aim was to derive the minimum activity for a reliable relative PET MPI assessment., Materials and Methods: We analyzed 140 scans from 28 consecutive patients who underwent rest-stress MPI-PET (Ingenuity TF). Scans of 852, 682, 511, and 341 MBq were simulated from list-mode data and compared with a reference scan using 1023 MBq. Differences in the summed rest score, total perfusion deficit, and image quality were obtained between the reference and each of the simulated rest scans. Combined stress-rest scans obtained at a selected activity of 682 MBq were diagnostically interpreted by experts and outcome was compared with the reference scan interpretation., Results: Differences in summed rest score more than or equal to 3 were found using 682, 511, and 341 MBq in two (7%), four (14%), and five (18%) patients, respectively. Differences in total perfusion deficit more than 7% were only found at 341 MBq in one patient. Image quality deteriorated significantly only for the 341 MBq scans (P<0.001). Interpretation of stress-rest scans did not differ between 682 and 1023 MBq scans., Conclusion: A significant reduction in administered Rb-82 activity is feasible in relative MPI. An activity of 682 MBq resulted in reliable diagnostic outcomes and image quality, and can therefore be considered for clinical adoption.

Objective: The presence of extensive coronary artery calcifications (CAC) influences treatment decisions, particularly for revascularization. However, important CAC might be missed with invasive coronary angiography (ICA). Our aim was to determine the accuracy of ICA in the identification of CAC using computed tomography (CT) as reference standard., Patients and Methods: Overall, 349 consecutive patients who underwent both CT-based CAC-scoring and invasive coronary angiography within 60 days were retrospectively included. Two experienced operators classified CAC on ICA, without knowledge of CT-based CAC scoring, for each of the four main vessels as (0) absent, (1) mild, (2) moderate, or (3) dense calcifications. These scores were correlated with the CT-based Agatston CAC-scores, the noninvasive reference standard. The sensitivity, specificity, and accuracy of identified CAC using ICA were derived. Calcifications identified as moderate or dense on ICA or with a vessel-based Agatston score of more than 100 were considered important., Results: CT classified 671 (48%) of the 1396 vessels as having moderately or densely calcified vessels (Agatston score >100), whereas this was 137 (9.8%) using ICA (P<0.001). A significant correlation was found between the CT-based and ICA-based CAC-scores for all vessels (P<0.001). The sensitivity in detecting any CAC by means of ICA was 43% with a specificity of 92% and an accuracy of 55%. The sensitivity of important CAC identification by ICA was 19%, the specificity 99%, and the accuracy 61%., Conclusion: The accuracy of ICA for the identification of calcifications is very low as only 19% of the relevant calcifications was identified. Preprocedural assessment of CAC with CT could be considered to improve the treatment approach.

Objectives: Three commonly used techniques for localization of nonpalpable breast cancer are radioactive seed localization (RSL), wire-guided localization (WGL) and radioguided occult lesion localization (ROLL). In this study, we analysed the surgical margins of these three techniques., Methods: Women diagnosed with nonpalpable breast cancer undergoing breast-conserving surgery with one of the above-mentioned techniques were retrospectively included. The primary outcome parameter was tumour-free margin rate. Secondary outcomes were re-excision rate, recurrence of disease and volume of removed tissue., Results: In total, 272 women were included in whom RSL (n=69), WGL (n=76) or ROLL (n=137) was performed. RSL showed a higher tumour-free margin rate [64 (92.8%)] compared with WGL [51 (67.1%)] and ROLL [113 (82.5%)] (P=0.001). In our multivariable analysis, RSL showed a higher tumour-free margin rate as well compared with WGL (P=0.036) and ROLL (P=0.049). Also, fewer re-excisions were encountered using RSL [5 (7.2%)] compared with WGL [13 (17.1%)] and ROLL [15 (10.9%)] (P=0.171). In 11 patients (WGL n=2, ROLL n=9), recurrence of disease occurred, despite a radical excision. The mean resection volumes were comparable within the three groups., Conclusion: RSL results in a higher tumour-free margin rate in nonpalpable breast tumours compared with WGL and ROLL. Therefore, we prefer using RSL in nonpalpable breast tumours.

Background: The prognostic value of coronary artery calcium (CAC) scoring on top of myocardial perfusion imaging with single-photon emission computed tomography (SPECT) in patients suspected for coronary artery disease is not well established., Methods and Results: Four thousand eight hundred ninety-seven symptomatic patients without a history of coronary artery disease referred for SPECT and CAC scoring were included. Major adverse cardiac events (MACEs) were defined as late revascularization (>90 days after scanning), nonfatal myocardial infarction, and all-cause mortality. The frequency of abnormal SPECT increased with higher CAC scores, from 12% in patients with CAC scores of 0 to 19%, 32%, 37%, and 50% among those with CAC scores 1 to 99, 100 to 399, 400 to 999, and ≥1000, respectively (P<0.001). During a median follow-up of 940 days (25th to 75th percentile, 581-1377), a total of 278 MACEs were observed. Overall incidence of MACE was 2.3% per year. A stepwise increase of MACE was present with increasing CAC scores, both in patients with normal SPECT (annual event rate CAC score 0: 0.6%; CAC score ≥1000: 5.5%) and abnormal SPECT (annual event rate CAC score 0: 0.4%; CAC score ≥1000: 7.6%). After multivariate analysis, both SPECT and CAC score were independent predictors of MACE (CAC score ≥1000: hazard ratio, 7.7; P<0.001 and large perfusion defect on SPECT: hazard ratio, 3.7; P<0.001)., Conclusions: CAC score and SPECT are independent predictors of MACE in patients suspected for coronary artery disease. Our findings strongly support performing a CAC score in addition to SPECT in symptomatic patients to better define the risk of events during follow-up., (© 2016 American Heart Association, Inc.)

Background: Proton-pump inhibitors (PPIs) induce potentially interfering stomach wall activity in single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) with technetium-99m ((99m)Tc)-sestamibi. However, no data are available for (99m)Tc-tetrofosmin. We assessed the influence of prolonged (>2 weeks) PPI use on the stomach wall uptake of (99m)Tc-tetrofosmin in patients referred for stress MPI with a cadmium-zinc-telluride-based SPECT camera and its relation with dyspepsia symptoms., Methods and Results: Consecutive patients (n=127) underwent a 1-day adenosine stress-first SPECT-MPI with (99m)Tc-tetrofosmin, of whom 54 (43%) patients had been on PPIs for more than 2 weeks. Stomach wall activity was identified on stress SPECT using computed tomographic attenuation maps and was scored using a four-point grading scale into clinically relevant (scores 2 or 3) or nonrelevant (scores 0 or 1).Patients on PPIs had stomach wall uptake more frequently as compared with patients not using PPIs (22 vs. 7%, P=0.017). Dyspepsia was similar in both groups., Conclusion: Prolonged use of PPIs is associated with stomach wall uptake of (99m)Tc-tetrofosmin in stress cadmium-zinc-telluride-SPECT images. Gastric symptoms were not associated with stomach wall uptake.

Background: The new multipinhole cardiac single photon emission computed tomography/computed tomography (SPECT/CT) cameras with cadmium-zinc-telluride (CZT) detectors are highly sensitive and produce images of high quality but rely on complex dedicated reconstruction algorithms. The aim of this study was to determine the impact of various processing steps on image formation and in the detection of ischaemia in CZT-SPECT/CT both with and without attenuation correction (AC)., Materials and Methods: Data on 20 consecutive patients who underwent a 1-day protocol stress-rest SPECT/CT using 99mTc-tetrofosmin were processed twice by three experienced operators, yielding 120 AC and 120 noncorrected (NC) data sets. Processing steps included selection and determination of myocardial axes, manual SPECT/CT coregistration for AC and myocardial masking. Using the 17-segment cardiac model, differences between stress and rest segmental uptake (%) were calculated for NC and AC image sets. Both interoperator and intraoperator variations were considered significant for the diagnosis of ischaemia when greater than 5%., Results: The mean interoperator variations were 2.4±1.4% (NC) and 3.8±1.9% (AC) (P<0.01). In 6% (NC) and 23% (AC) of the 120 processed cases, operator variation was larger than 5% and therefore potentially clinically interfering with the diagnosis of ischaemia. Differences between interoperator and intraoperator variations were nonsignificant., Conclusion: Operator variations in the processing of myocardial perfusion image data using CZT-SPECT/CT are significant and may influence the diagnosis of ischaemia, especially when AC is applied. Clearer guidelines for image processing are necessary to improve the reproducibility of the studies and to obtain a more reliable diagnosis of ischaemia.

Aim: In Canada, staging of carcinoid tumors is largely based on computed tomography (CT) imaging sometimes complemented with somatostatin receptor scintigraphy (SRS). This study assessed the diagnostic accuracy of 6-[¹⁸F]fluoro-3,4-dihydroxyphenylalanine (¹⁸F-FDOPA) PET/CT in neuroendocrine tumors., Methods: We prospectively included 27 patients with either suspected carcinoid (n=6, with all prior tests negative) or with an established diagnosis of intestinal carcinoid tumor (n=21) from two Canadian treatment centers. Findings of ¹⁸F-FDOPA PET/CT were compared with SRS, CT, and combined SRS/CT using a composite reference standard comprising all available imaging, biochemistry, surgery, and follow-up data. Sensitivity was calculated per patient, per body region, and per lesion. The contribution to patient management was estimated from the feedback of attending physicians., Results: In documented carcinoid patients, ¹⁸F-FDOPA PET/CT identified disease in 20 of 21 patients (patient-based sensitivity 95%). In 56 positive regions, ¹⁸F-FDOPA PET/CT detected 53, CT detected 34, SRS detected 34, and CT+SRS detected 39 regions, leading to region-based sensitivities of 95, 61, 62, and 71%, respectively. Lesion-based sensitivities were 96, 69, 50, and 72%, respectively. In the six patients with suspected disease only, one CT scan was positive, but ¹⁸F-FDOPA PET/CT was negative for all. ¹⁸F-FDOPA PET contributed to patient management in 12/21 patients (57%)., Conclusion: ¹⁸F-FDOPA PET/CT proved to be an excellent modality for staging of carcinoid tumor patients, with superior performance compared with currently applied methods in Canada. In patients with suspected disease with negative prior imaging investigations, ¹⁸F-FDOPA was not helpful.

Melanoma patients with lymph node metastases have to deal with diagnostic tests to exclude the presence of distant metastases; results of the tests could have major implications for their prognosis and treatment. There are, however, few studies concerning the patients' psychological issues and perception of diagnostic tests. The aim of this study was to describe the burden of diagnostic tests [radiograph, computed tomography (CT) and positron emission tomography (PET)] experienced by melanoma patients with lymph node metastases. Patients were asked to complete a questionnaire concerning satisfaction and burden experienced during the diagnostic tests. The levels of embarrassment, discomfort and anxiety for the different tests, as well as total scores for each burden were calculated. Logistic regression was used to examine factors associated with the degree of experienced burden. Fifty-nine of the 68 patients completed the questionnaire and the response rate was 87%. The overall mean scores on satisfaction and quality of life were high. More than half of the patients experienced no burden during PET, 65% no burden during computed tomography and 80% no burden during chest radiograph. Patients experienced significantly more discomfort during the PET scan than during the CT (P=0.003). Less burden was experienced (in univariate analysis) by patients who were more satisfied. The overall experienced burden by patients is low and should therefore not interfere with primary choice for a diagnostic test based on accuracy, costs and percentage of patients upstaged. Attention should be paid in explaining the procedure and answering questions of the patients to reduce burden.

Background: The purpose of this prospective study is to evaluate the possibility of 11C-methionine (Met) PET compared with 18F-fluorodeoxyglucose (FDG) PET for the detection of recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC)., Materials and Methods: Twenty patients with clinical suspicion of recurrent DTC but negative posttreatment 131I-whole body scans were included in the study. Both 11C-Met PET and 18F-FDG PET were performed within 1 week. PET images were analyzed by two independent and blinded physicians using visual and standardized uptake value analysis. PET results were also correlated with radiologic and/or cytological investigations., Results: Thirteen patients showed concordant findings on both PET scans: six patients showed uptake and in seven no uptake was observed. In six of the seven patients without Met and FDG uptake, additional MRI and ultrasound-guided fine needle aspiration cytology of the lymph nodes revealed inconclusive or negative results. Six patients showed discordant findings on the PET scans: in three patients uptake was only observed on the Met PET, confirmed by MRI in one. In three patients lesions were seen on the FDG PET, confirmed by computed tomography or ultrasound-guided fine needle aspiration cytology. However, those lesions were not compatible with the lesions seen on the Met PET. In general, FDG uptake appeared to be higher than Met uptake, but was not significant (P=0.075)., Conclusion: This study shows that imaging using radiolabeled amino acids is feasible in DTC. For now, 11C-Met PET has not proven to be superior to 18F-FDG PET in the detection of recurrent disease in DTC. Complementary uptake of Met and FDG has, however, been observed, which has to be further clarified and long-term follow-up is needed to define the true clinical value of the 11C-Met PET, and possible other amino acids tracers.

Background: Similar to the situation in other tumour types, it is currently unclear whether fluorodeoxyglucose (FDG) positron emission tomography (PET) is adequate in the detection of bone metastases of thyroid cancer. The purpose of this retrospective study was to evaluate the performance of bone scans in comparison with FDG PET in the detection of bone metastases in patients with differentiated thyroid cancer (DTC)., Materials and Methods: Twenty-four patients had undergone both FDG PET and bone scans within 6 months because of suspected bone metastases. All scans were re-evaluated using all available additional imaging and clinical data for verification. Scan findings were scored as positive, negative or doubtful., Results: Bone metastases were present in eight of 24 (33%) patients. Only bone scintigraphy but not FDG PET suggested the presence of bone metastases in three patients, all confirmed with magnetic resonance imaging (MRI)/X-ray. Five patients were identified with bone metastases on both bone scan and FDG PET, which was confirmed by computed tomography (CT)/MRI/X-ray in four. Five patients had doubtful findings on bone scans whereas FDG PET scans were negative. MRI showed degenerative disorders in two of five and was normal in two. Eleven patients had both a negative bone scan and FDG PET scan., Conclusion: In three of eight (38%) thyroid cancer patients bone metastases were only identified on bone scans. Therefore, bone scans are still valuable in detecting bone metastases in patients with DTC and can not be replaced by FDG PET.

Background: The combination of angina pectoris, angiographically normal coronary arteries, and a positive exercise stress test (EST) is referred to as cardiac syndrome X. However, a large group of patients suspected of syndrome X reveals a normal exercise stress test and weakens the diagnosis of syndrome X. Previous studies demonstrated an impaired coronary flow reserve on ammonia positron emission tomography (PET) in patients with syndrome X., Aim: To evaluate the coronary flow reserve in patients suspected of syndrome X with positive and negative EST findings, using [(13)N]ammonia PET as the diagnostic aid., Methods: Forty-two patients with chest pain and a normal coronary angiography, were analysed by exercise stress testing (EST) and the dypyridamole stress test (DST) on [(13)N]ammonia PET. Two subgroups were predefined, based on outcome of EST: an EST positive and negative group. A normal control group was used as the reference method., Results: A total of 24 (57%) out of 42 patients had significant ST-T changes (EST positive). [(13)N]ammonia PET showed a significantly lower rest flow in the EST positive and EST negative group compared to controls (P<0.001 and P=0.0028, respectively). DST [(13)N]ammonia PET perfusion was significantly reduced in flow in both the EST positive and EST negative groups (P<0.001 both), as was the DST/rest [(13)N]ammonia perfusion reserve (P<0.001 for both), compared to normal controls., Conclusion: PET demonstrates a reduced coronary flow reserve in patients suspected of syndrome X, irrespective of the EST findings.

Background: The new anti-cancer drug imatinib mesylate inhibits the tyrosine kinase growth factor receptor, c-KIT, and has shown spectacular activity in patients with gastrointestinal stromal tumours (GISTs)., Objective: To assess whether fluorodeoxyglucose positron emission tomography (FDG PET) is suitable for response evaluation of this new type of tumour treatment., Methods: Sixteen consecutive patients with irresectable or metastasized GIST or another c-KIT (CD117) positive mesenchymal tumour underwent FDG PET before and 1 week after the start of treatment with imatinib mesylate (Glivec). Visual findings and standard uptake values (SUVs) were compared with the overall response to treatment, based on clinical and radiological response., Results: PET visualized all known and some unknown tumour locations. The separation by PET after 1 week of treatment in "PET responders" (11/16 patients, mean SUV reduction 65%) versus "PET non-responders" (5/16 patients, mean SUV increase 16%) appeared to match almost perfectly with overall treatment response and proved correct in 14/15 patients (prediction sensitivity 93%). FDG uptake changes after 1 week of treatment were of greater magnitude than tumour volume changes on computed tomography at 8 weeks. Progression-free survival was significantly better in patients with a PET response (P=0.002). PET response predicted treatment outcome better than the radiological response. Finally, PET was helpful during follow-up, in discriminating side effects from tumour progression., Conclusion: FDG PET is a valuable tool in patients with gastrointestinal stromal tumours treated with imatinib mesylate. It improves staging, accurately separates responders from non-responders in an early phase, and is helpful during follow-up.

Planar gated blood-pool imaging (GBPI) is a standard method for non-invasive assessment of left ventricular (LV) function. Gated blood-pool single photon emission computed tomographic (GBPS) data acquisition can be accomplished in the same time as GBPI, with the benefit of enabling visualization of all cardiac chambers simultaneously. The purpose of this investigation was to evaluate the degree to which automated and manual LVEF calculations agree with one another and with conventional GBPI LVEF measurements. GBPI studies were performed in 22 consecutive, unselected patients, followed by GBPS data acquisition. GBPS left ventricular ejection fraction (LVEF) calculations were performed by available software (NuSMUGA, Northwestern University, Chicago, IL) automatically and manually, using all LV gated short axis slices. Automatic LVEF assessed by GBPS correlated well with conventional planar GBPI (r = 0.88, P < 0.001). Mean planar GBPI LVEF was 50% +/- 12%, and mean GBPS automatic LVEF was significantly lower at 45% + 14% (P = 0.001), with a mean difference of 6% +/- 5%. Manual GBPS LVEF also correlated well with conventional planar GBPI (r = 0.90, P < 0.0001). Mean LVEF measurement by manual GBPS versus GBPI was significantly higher at 59% +/- 13%, with a mean difference of 10% +/- 6% (P < 0.001). Manual GBPS LVEF values were also significantly higher than automatically determined GBPS LVEF values (P < 0.001). It is concluded that LVEF values assessed by NuSMUGA GBPS software were reproducible, and automatic and manual values correlated well with conventional GBPI values. However, both automatic and manual GBPS calculations were significantly different from one another and from GBPI values, so that GBPI and NuSMUGA calculations cannot be considered to be equivalent.

Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-sestamibi ( Tc-MIBI) and metabolism using F-fluorodeoxyglucose ( F-FDG) in a single study. The prerequisite is that the Tc-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered Tc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-MIBI and 185 MBq of F-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-FDG and Tc-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r =0.93, P<0.0001) between the Tc-MIBI uptake detected in the single and dual isotope acquisition. The average difference between the dual and single isotope Tc-MIBI uptake was -1.2% (not significantly different from zero) and the coefficient of variation of the difference was 8.7%. Of the 79 regions with irreversible perfusion defects on previous rest-stress Tc-MIBI, six regions in five patients showed a perfusion-metabolism mismatch pattern. We conclude that DISA does not affect the quality of the Tc-MIBI images. Furthermore, F-FDG- Tc-MIBI DISA may show viability in a small but significant (7.6%, P<0.0034) number of regions with irreversible perfusion defects on rest-stress Tc-MIBI.

The radiolabelled amino acid analogue L-3-[125I]iodo-alpha-methyl-tyrosine (IMT) is under evaluation in brain tumours, where it reflects amino acid transport activity, but is also taken up in many other tumour types. This study investigated the uptake mechanism of IMT in tumour cells not derived from brain tumours, in comparison with the native amino acid 14C-tyrosine (Tyr) from which IMT is derived. Human GLC4 small-cell lung cancer cells in log-phase were incubated with IMT and Tyr. Tracer uptake was determined in various buffers, incubation periods, concentrations of specific amino acid transport blockers, pH and temperature. IMT uptake was very fast, reaching a plateau within 5 min, while Tyr kept on accumulating for > 60 min. Based on steady-state experiments, > 90% of IMT uptake could be attributed to amino acid transport activity. The L transport system was the most important, both for IMT and Tyr. IMT uptake into GLC4 tumour cells is almost completely the result of amino acid transport activity (especially the L system) and is very similar to Tyr uptake. Therefore, also outside the brain, IMT is a metabolic tracer that may reflect the increased amino acid transport that is characteristic for malignant tumours.