Correlates of markers of dyssynchrony in patients with STEMI and multivessel disease: an analysis from the IAEA SPECT STEMI trial.

BACKGROUND: In this substudy of the Value of Gated-SPECT MPI for Ischemia- Guided PCI of non-culprit vessels in STEMI Patients with Multi vessel Disease after primary PCI trial after primary PCI we aim to assess if infarct size affects conventional measures of dyssynchrony at rest. Additionally, we explore if there is an independent correlation of stress-inducible ischemia with dyssynchrony at rest. METHODS: The 48 patients with imaging at randomization were analyzed. Gated-single-photon emission computed tomography (SPECT) MPI with vasodilator stress and technetium-99m-labeled tracers was performed. The phase histogram bandwidth (HBW), phase SD, and entropy were obtained with the QGS software. Correlation between dyssynchrony at rest and infarct size and inducible ischemia was performed using the Spearman test. RESULTS: According to normal database limits dyssynchrony parameters at rest were abnormal for men. In women only HBW was abnormal. Correlation between the summed rest score with dyssynchrony was significant only for entropy ( P  = 0.035). No correlation was observed for dyssynchrony and stress-induced ischemia. CONCLUSION: Entropy, as a measure of dyssynchrony, has potential in the assessment of patients with STEMI and multivessel disease after primary PCI. Smaller residual myocardial scars in PCI-reperfused patients with STEMI may contribute to the lack of correlation between dyssynchrony at rest and infarct size and stress-induced ischemia, respectively.

Ischemia-guided vs routine non-culprit vessel angioplasty for patients with ST segment elevation myocardial infarction and multi-vessel disease: the IAEA SPECT STEMI trial.

BACKGROUND: In patients with multi-vessel disease presenting with ST elevation myocardial infarction (STEMI), the efficacy and safety of ischemia-guided, vs routine non-culprit vessel angioplasty has not been adequately studied. METHODS: We conducted an international, randomized, non-inferiority trial comparing ischemia-guided non-culprit vessel angioplasty to routine non-culprit vessel angioplasty, following primary PCI for STEMI. The primary outcome was the between-group difference in percent ischemic myocardium at follow-up stress MPI. All MPI images were processed and analyzed at a central core lab, blinded to treatment allocation. RESULTS: In all, 109 patients were enrolled from nine countries. In the ischemia-guided arm, 25/48 (47%) patients underwent non-culprit vessel PCI following stress MPI. In the routine non-culprit PCI arm, 43/56 (77%) patients underwent angioplasty (86% within 6 weeks of randomization). The median percentage of ischemic myocardium on follow-up imaging (mean 16.5 months) was low, and identical (2.9%) in both arms (difference 0.13%, 95%CI - 1.3%-1.6%, P < .0001; non-inferiority margin 5%). CONCLUSION: A strategy of ischemia-guided non-culprit PCI resulted in low ischemia burden, and was non-inferior to a strategy of routine non-culprit vessel PCI in reducing ischemia burden. Selective non-culprit PCI following STEMI offers the potential for cost-savings, and may be particularly relevant to low-resource settings. (CTRI/2018/08/015384).

Correlation between brain glucose metabolism (18F-FDG) and cerebral blood flow with amyloid tracers (18F-Florbetapir) in clinical routine: Preliminary evidences.

OBJECTIVE: This study compared the performance of 18F-Florbetapir PET/CT early acquisitions to 18F-FDG PET/CT. METHODS: We included 12 patients who underwent 18F-FDG PET/CT and a dual-time 18F-Florbetapir PET/CT (1-6 min early-scan and 50 min late-scan). PET/CT were analyzed visually by three nuclear medicine physicians with different experience using a four-point scale (0 = no reduction, 1 = slight, 2 = moderate, 3 = severe reduction) for 18F-Florbetapir early-phase and 18F-FDG images in 10 cortical regions (bilateral frontal, temporal, parietal, occipital, posterior cingulate/precuneus), and 18F-Florbetapir late-phase in the same cortical regions using a three-point scale (0 = normal, 1 = abnormal with minor plaques, 2 = abnormal with major plaques). We used SPM12 for semiquantitative analysis applying a ROI-based correlation analysis (considering precuneus as target region and normalized for the mean global binding), a covariance-analysis taking precuneus as target and a comparison of global DMN (default mode network). RESULTS: Inter-reader agreement was high (Cohen's kappa 0.762 for 18F-FDG, 0.775 for 18F-Florbetapir early-phase and 0.794 for late-phase). Regional visual scores of early-phase and 18F-FDG were significantly correlated (ρ = 0.867). Also ROI-based analysis, global brain visual analysis and DMN comparison revealed concordant results, especially at parietal and precuneus (p < 0.001). CONCLUSIONS: 18F-Florbetapir early-phase scans significantly correlate on quantitative and visual images with 18F-FDG-PET/CT scans, suggesting that amyloid tracer could be instead of 18F-FDG.

Prognostic Role of 2-[18F]FDG PET/CT Metabolic Volume Parameters in Patients Affected by Differentiated Thyroid Carcinoma with High Thyroglobulin Level, Negative 131I WBS and Positive 2-[18F]-FDG PET/CT.

The clinical and prognostic role of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in the study of patients affected by differentiated thyroid carcinoma (DTC) with positive serum thyroglobulin (Tg) level and negative [131I] whole-body scan ([131I]WBS) has already been demonstrated. However, the potential prognostic role of semi-quantitative PET metabolic volume features, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), has not yet been clearly investigated. The aim of this retrospective study was to investigate whether the main metabolic PET/CT parameters may predict the prognosis. We retrospectively included 122 patients with a positive 2-[18F]FDG PET/CT for DTC disease after a negative [131I]WBS with Tg > 10 ng/mL. The maximum and mean standardized uptake value (SUVmax and SUVmean), MTV and TLG of the hypermetabolic lesion, total MTV (tMTV) and total TLG (tTLG) were measured for each scan. Progression-free survival (PFS) and overall survival (OS) curves were plotted according to the Kaplan-Meier analysis. After a median follow up of 53 months, relapse/progression of disease occurred in 87 patients and death in 42. The median PFS and OS were 19 months (range 1-132 months) and 46 months (range 1-145 months). tMTV and tTLG were the only independent prognostic factors for OS. No variables were significantly correlated with PFS. The best thresholds derived in our sample were 6.6 cm3 for MTV and 119.4 for TLG. In patients with negative WBS and Tg > 10 ng/mL, 2-[18F]FDG PET/CT metabolic volume parameters (tMTV and tTLG) may help to predict OS.

Role of 18F-FDG PET/CT Radiomics Features in the Differential Diagnosis of Solitary Pulmonary Nodules: Diagnostic Accuracy and Comparison between Two Different PET/CT Scanners.

The aim of this retrospective study was to investigate the ability of 18 fluorine-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) metrics and radiomics features (RFs) in predicting the final diagnosis of solitary pulmonary nodules (SPN). We retrospectively recruited 202 patients who underwent a 18F-FDG-PET/CT before any treatment in two PET scanners. After volumetric segmentation of each lung nodule, 8 PET metrics and 42 RFs were extracted. All the features were tested for significant differences between the two PET scanners. The performances of all features in predicting the nature of SPN were analyzed by testing three classes of final logistic regression predictive models: two were built/trained through exploiting the separate data from the two scanners, and the other joined the data together. One hundred and twenty-seven patients had a final diagnosis of malignancy, while 64 were of a benign nature. Comparing the two PET scanners, we found that all metabolic features and most of RFs were significantly different, despite the cross correlation being quite similar. For scanner 1, a combination between grey level co-occurrence matrix (GLCM), histogram, and grey-level zone length matrix (GLZLM) related features presented the best performances to predict the diagnosis; for scanner 2, it was GLCM and histogram-related features and metabolic tumour volume (MTV); and for scanner 1 + 2, it was histogram features, standardized uptake value (SUV) metrics, and MTV. RFs had a significant role in predicting the diagnosis of SPN, but their accuracies were directly related to the scanner.

2-[18F]-FDG PET/CT Role in Detecting Richter Transformation of Chronic Lymphocytic Leukemia and Predicting Overall Survival.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is an indolent, low-grade B-cell lymphoproliferative disorder, which may evolve into aggressive lymphoma, a phenomenon called Richter syndrome (RS). Our aim was to study the accuracy of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]-FDG PET/CT) and its semiquantitative parameters for the detection of RS and the impact on overall survival (OS). MATERIALS AND METHODS: Eighty patients with histologically proven CLL were retrospectively included. PET/CT images were qualitatively and semiquantitatively examined by estimating the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-blood-pool SUV ratio (L-BP SUV R), lesion-to-liver SUV ratio (L-L SUV R), total lesion glycolysis (TLG), and metabolic tumor volume (MTV) and comparing them with the main clinical-histologic variables. OS curves were plotted according to the Kaplan-Meier method. RESULTS: Seventy-eight patients had positive 2-[18F]-FDG PET/CT, whereas the remaining 2 were not FDG-avid. All PET/CT metabolic parameters were significantly higher in the RS group compared with the no-RS group, except for MTV and TLG. The best thresholds identified were 9 for SUVbw, 5.3 for SUVlbm, 1.7 for SUVbsa, 2 for L-L SUV R, and 4.8 for L-BP SUV R. After a median follow-up of 32 months, 24 patients died; OS was significantly shorter in patients with RS than patients without RS (16.5 vs. 27.8 months; P = .001). Binet-stage, B symptoms, SUVbw, SUVlbm, SUVbsa, L-L SUV R, and L-BP SUV R were shown to be independent prognostic features. CONCLUSIONS: Semiquantitative PET/CT parameters that are SUV-related may be useful in discriminating patients with a high risk of developing RS and also for predicting OS.

Comparison between N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT in the evaluation of absolute myocardial blood flow and flow reserve.

BACKGROUND: PET/CT is the standard for quantitative assessments of myocardial blood flow (MBF), but it requires short-lived-tracers, costly, and not widely available. SPECT with Cadmium Zinc Telluride (CZT) detectors allows dynamic acquisition and quantitation of MBF. The study aims were to compare MBF measurements by 99mTc-tetrofosmin-CZT to N13NH3 PET/CT after regadenoson-induced coronary hyperemia and to evaluate the effect of attenuation correction (AC). METHODS: 54 patients were evaluated at rest and during vasodilation by 99mTc-tetrofosmin-CZT and N13NH3 PET/CT within 2 weeks. MBF and MBF reserve (MFR) were measured by CZT with or without AC (NAC). RESULTS: The global rest MBF was 0.76 ± 0.19 mL/min/gr by PET and 0.76 ± 0.24 by AC-CZT (P = NS) and 1.14 ± 0.4 by NAC-CZT (P < 0.001 vs PET and AC-CZT). Stress MBF was higher when measured by PET than AC-CZT (1.87 ± 0.45 vs 1.62 ± 0.68 mL/min/gr, P < 0.0008), but lower than NAC-CZT (2.36 ± 1.1, P < 0.0003). The MBF reserve ratio (MFR) was higher by PET than AC-CZT (2.52 ± 0.56 vs 2.22 ± 1 (P < 0.009) and NAC-CZT (2.18 ± 1.0, P < 0.004). Linear regression was better between PET (MFR and stress MBF) and AC-CZT than between PET and NAC-CZT. ROC curve analysis showed the significant ability of AC-CZT to predict MFR < 2 and stress MBF < 1.7 (AUC = 0.75 and 0.82 respectively) and to differentiate between normal and CAD patients (AUC = 0.747 and 0.892 for MFR and stress MBF, respectively). CONCLUSIONS: Our data show a reasonable correlation between MBF and MFR measured by N13NH3-PET and 99mTc-Tetrofosmin-CZT SPECT. NAC-CZT overestimates MBF. AC is recommended when using CZT for measuring MBF.

Inter-reader variability of SPECT MPI readings in low- and middle-income countries: Results from the IAEA-MPI Audit Project (I-MAP).

BACKGROUND: Consistency of results between different readers is an important issue in medical imaging, as it affects portability of results between institutions and may affect patient care. The International Atomic Energy Agency (IAEA) in pursuing its mission of fostering peaceful applications of nuclear technologies has supported several training activities in the field of nuclear cardiology (NC) and SPECT myocardial perfusion imaging (MPI) in particular. The aim of this study was to verify the outcome of those activities through an international clinical audit on MPI where participants were requested to report on studies distributed from a core lab. METHODS: The study was run in two phases: in phase 1, SPECT MPI studies were distributed as raw data and full processing was requested as per local practice. In phase 2, images from studies pre-processed at the core lab were distributed. Data to be reported included summed stress score (SSS); summed rest score (SRS); summed difference score (SDS); left ventricular (LV) ejection fraction (EF) and end- diastolic volume (EDV). Qualitative appraisals included the assessment of perfusion and presence of ischemia, scar or mixed patterns, presence of transient ischemic dilation (TID), and risk for cardiac events (CE). Twenty-four previous trainees from low- and middle-income countries participated (core participants group) and their results were assessed for inter-observer variability in each of the two phases, and for changes between phases. The same evaluations were performed for a group of eleven international experts (experts group). Results were also compared between the groups. RESULTS: Expert readers showed an excellent level of agreement for all parameters in both phase 1 and 2. For core participants, the concordance of all parameters in phase 1 was rated as good to excellent. Two parameters which were re-evaluated in phase 2, namely SSS and SRS, showed an increased level of concordance, up to excellent in both cases. Reporting of categorical variables by expert readers remained almost unchanged between the two phases, while core participants showed an increase in phase 2. Finally, pooled LVEF values did not show a significant difference between core participants and experts. However, significant differences were found between LVEF values obtained using different software packages for cardiac analysis. CONCLUSIONS: In this study, inter-observer agreement was moderate-to-good for core group readers and good-to-excellent for expert readers. The quality of reporting is affected by the quality of processing. These results confirm the important role of the IAEA training activities in improving imaging in low- and middle-income countries.

Comparison of visual criteria for amyloid-PET reading: could criteria merging reduce inter-rater variability?

BACKGROUND: Three different amyloid tracers labeled with 18-flourine have been introduced into clinical use. The leaflets of tracers indicate different visual criteria for PET reporting. In clinical practice, it is not yet ascertained whether these criteria are equivalent in terms of diagnostic accuracy or if anyone is better than another. We aimed to evaluate the inter and intra-rater variability of visual assessment of 18F-Florbetapir PET/CT images among six independent readers with different clinical experience. METHODS: We analyzed 252 PET/CT scans, visually assessed by each reader three times, applying independently the three different reading criteria proposed. Each reader evaluated the regional uptake specifying for each cortical region a numeric value of grading of positivity in order to assign a final score. At the end of each reading a level of confidence was determined by assigning a score from 0 (negative) to 4 (positive). After first reading, those cases in which the evaluations by two experienced readers did not match (discordant cases) were independently reevaluated merging all the three different visual interpretation criteria. RESULTS: Good agreement was observed for visual interpretation among the six readers' confidence-level using independently the three visual reading criteria: ICC=0.83 (0.80-0.86) for 18F-florbetapir, ICC=0.84 (0.81-0.87) for 18F-florbetaben, and ICC=0.86 (0.83-0.88) for 18F-flutemetamol reading. A good inter-rater agreement was observed for final-score too: ICC=0.74 (0.70-0.78) for 18F-florbetapir; ICC=0.82 (0.79-0.85) for 18F-florbetaben; ICC=0.84 (0.81-0.87) for 18F-flutemetamol. Intra-rater agreement was good for final-score (from 0.76 to 0.90; P<0.001) and confidence-level (Spearman's rho from 0.89 to 1.00; P<0.001). Disagreement between the two experienced readers was observed in 22 of 252 cases (9%). The agreement converged over a second round of independent reading in 12 of 22 cases (54%), by merging all the criteria. CONCLUSIONS: All the criteria proposed are useful to determine the grading of positivity or negativity of amyloid deposition and their merging improves the diagnostic confidence and provides a better agreement.

Radioguided lung lesion localization: introducing a fluoroscopy system in a SPECT/CT scan.

PURPOSE: The purpose was to report our experience in the use of radiotracer localization and resection of small, indistinct, or nonpalpable pulmonary lesions. We developed an innovative technique implementing a fluoroscopy system on a single-photon emission computed tomography/computed tomography (SPECT/CT) scan that allowed to perform CT-guided injection of radiotracer directly on SPECT/CT. PATIENTS AND METHODS: Patients were selected for the radiotracer procedure in presence of difficulties in locating nodules with video-assisted thoracoscopic surgery (VATS). Overall, 0.2 ml of technetium-99m macroaggregated albumin and 0.3 ml of nonionic iodinated contrast were injected under CT guidance. During the VATS procedure, an endoscopic gamma detecting probe was introduced to scan the lung surface. The area of major radioactivity, which matched with the area of the nodule, was resected. RESULTS: Between January 2016 and October 2018, 37 patients underwent CT-guided radiotracer injection. The mean nodule size was 11 mm. CT nodule morphology characteristics were as follows: 15 nodules were ground glass, 12 were solid, and 10 were partly solid. No significant adverse events occurred. In one patient, the surgeons decided for an open thoracotomy after unsuccessfully VATS. Overall, lobectomy was performed in two patients, segmentectomy in one, and wedge resection in 33 patients. No mortality occurred. The pathological diagnosis was 15 (42%) primary lung cancer, eight (22%) metastases, and 13 (36%) benign lesions. CONCLUSION: Radioguided pulmonary nodule localization is a reliable procedure with a high rate of success, minimal complications, and lower risk of failures, with no associated mortality or significant morbidity. Our SPECT/CT system is the first to benefit from the technological improvement with successfully implementation and application of fluoroscopy to SPECT/CT.

Clinical and prognostic role of detection timing of distant metastases in patients with differentiated thyroid cancer.

PURPOSE: Distant metastases (DM) from DTC occur in 5-25% of cases and are correlated to lower survival; the prognostic significance of the temporal onset of DM is unclear. Our aim was to retrospectively analyze the prevalence of DM and to assess the prognostic role of the timing of manifestation of DM regarding the outcome. MATERIALS AND METHODS: We included 174 patients (mean age 64 years). According to the time of manifestation, DM were divided in two groups: synchronous DM (SDM, n = 108) defined as metastases present at initial diagnosis and metachronous DM (MDM, n = 66) as diagnosed during follow-up. SDM were further sub grouped in pre-RAIT when diagnosed during pre-surgery work-up (n = 35) and baseline-RAIT when detected by first whole body scan after RAIT (n = 73). Disease-specific survival (DSS) was analyzed using the Kaplan-Meier method. RESULTS: Total RAI activities and number of treatments were significantly higher in MDM, also loss of RAI avidity was more frequent in MDM. Forty-four patients died during follow-up, of which 41 were DTC-related deaths, 5-year and 10-year DSS were 80% and 56%. On univariate analysis MDM had significantly shorter DSS; also histotype and RAI avidity were significant risk factors of impaired survival. On multivariate analysis, only loss of RAI avidity remained as independent negative predictor (p = 0.043). Considering SDM, DSS was significantly shorter in pre-RAIT group than baseline-RAIT (p = 0.004). Instead there was no significant difference between pre-RAIT-SDM and MDM in survival outcome (p = 0.875). CONCLUSIONS: In DTC with DM, loss of RAI uptake has an important role in survival. No significant difference in survival outcome was discovered between SDM and MDM; but, among SDM, pre-RAIT had significant shorter DSS than baseline-RAIT.

Prognostic role of pretreatment 18F-FDG PET/CT in primary brain lymphoma.

OBJECTIVE: Primary brain lymphoma is an aggressive extranodal non-Hodgkin lymphoma with poor prognosis. Many possible prognostic factors are investigated with controversial results, but possible prognostic role of 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) features remains unclear. Our aim was to study the metabolic behavior of brain lymphoma at 18F-FDG PET/CT and the prognostic impact of qualitative and semiquantitative PET/CT parameters. METHODS: Between 2006 and 2018, 52 patients (26 females and 26 males; mean age: 61 years) with histologically confirmed diagnosis of brain lymphoma who underwent 18F-FDG PET/CT for staging before any treatment were included. PET images were qualitatively and semiquantitatively analyzed by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS) times. Cox regression models were performed to determinate the relation between qualitative and semiquantitative PET/CT features and OS and PFS. RESULTS: Thirty-nine patients had positive 18F-FDG PET/CT showing 18F-FDG uptake (mean SUVbw of 18.2; SUVlbm of 13.9; SUVbsa of 5; MTV of 14.8; TLG of 153) at the corresponding cerebral lesion; the remaining 13 were not 18F-FDG avid. Relapse or progression of disease occurred in 22 patients with an average time of 9.7 months; death occurred in 18 patients with an average of 7.9 months. There was no difference in PFS and OS between baseline PET/CT positive and negative groups or considering SUVbw, SUVlbm, and SUVbsa. PFS and OS was significantly shorter in patients with MTV ≥ 9.8 cm3 (p = 0.037 and p = 0.022, respectively) and TLG ≥ 94 (p = 0.045 and p = 0.0430, respectively). CONCLUSIONS: 18F-FDG avidity was noted in 75% of cases. Only metabolic tumor parameters (MTV and TLG) were independently correlated with PFS and OS.

Comparison between the summed difference score and myocardial blood flow measured by 13N-ammonia.

BACKGROUND: Both the myocardial perfusion pattern and myocardial blood flow (MBF) are used to assess patients with suspected coronary artery disease (CAD). The aim of this study was to compare the perfusion pattern (using the summed difference score [SDS]) to MBF in a consecutive group of patients undergoing PET/CT with 13 N-ammonia (13NH3). METHODS: 47 consecutive patients, aged 65 ± 12 years (42 men) with known or suspected CAD, underwent vasodilator stress/rest PET/CT with 13NH3 for clinical indications. The SDS was determined by a commercially available software based on a 17-segment model. MBF was measured at rest and during hyperemia by dynamic acquisition and single-compartment model analysis. From the rest and stress MBF, the absolute difference (stress-rest) in myocardial blood flow defined as difference in myocardial blood flow (DMBF) was derived. RESULTS: There were no significant differences between patients with no ischemia (SDS ≤ 1) and those with ischemia (SDS > 1) in CFR (2.84 ± 0.73 vs 2.63 ± 0.89, P = NS) and DMBF (1.34 ± 0.45 vs 1.24 ± 0.53 mL·minute-1·g-1, P = NS). There were however significant regional differences (141 different vascular territories in 47 patients) between these two groups (CFR: 2.84 ± 0.95 vs 2.16 ± 0.57, P < .001 and DMBF: 1.39 ± 0.6 vs 0.87 ± 0.39, P < .0001). The correlation between regional CFR and regional DMBF with SDS was significant (y = 2.7145e-0.059x R = 0.358 and y = 1.2769e-0.119x R = 0.44) CONCLUSION: The SDS is the difference between two measurements (stress-rest) and it correlates better with regional DMBF, which is another measurement that reflects the difference between stress and rest. The correlation is better on regional than global basis.

Comparative analysis of iterative reconstruction algorithms with resolution recovery and time of flight modeling for 18F-FDG cardiac PET: A multi-center phantom study.

BACKGROUND: The purpose of this study was to evaluate the image quality in cardiac 18F-FDG PET using the time of flight (TOF) and/or point spread function (PSF) modeling in the iterative reconstruction (IR). METHODS: Three scanners and an anthropomorphic cardiac phantom with an insert simulating a transmural defect (TD) were used. Two sets of scans (with/without TD) were acquired, and four reconstruction schemes were considered: (1) IR; (2) IR + PSF, (3) IR + TOF, and (4) IR + TOF + PSF. LV wall thickness (FWHM), contrast between LV wall and inner chamber (C IC), and TD contrast in LV wall (C TD) were evaluated. RESULTS: Tests of the reconstruction protocols showed a decrease in FWHM from IR (13 mm) to IR + PSF (11 mm); an increase in the C IC from IR (65%) to IR + PSF (71%) and from IR + TOF (72%) to IR + TOF + PSF (77%); and an increase in the C TD from IR + PSF (72%) to IR + TOF (75%) and to IR + TOF + PSF (77%). Tests of the scanner/software combinations showed a decrease in FWHM from Gemini_TF (13 mm) to Biograph_mCT (12 mm) and to Discovery_690 (11 mm); an increase in the C IC from Gemini_TF (65%) to Biograph_mCT (73%) and to Discovery_690 (75%); and an increase in the C TD from Gemini_TF/Biograph_mCT (72%) to Discovery_690 (77%). CONCLUSION: The introduction of TOF and PSF increases image quality in cardiac 18F-FDG PET. The scanner/software combinations exhibit different performances, which should be taken into consideration when making cross comparisons.

Differentiated thyroid carcinoma: Incremental diagnostic value of 131I SPECT/CT over planar whole body scan after radioiodine therapy.

The purpose of this prospective study was to determine the incremental diagnostic value of single photon emission computed tomography/computed tomography with iodine-131 over planar whole body scan in the staging of patients with differentiated thyroid carcinoma. A total of 365 patients (270 female, 95 male) with differentiated thyroid carcinoma were treated with radioiodine therapy for thyroid remnant ablation with radical intent after thyroidectomy between January 2013 and November 2014. In addition to planar whole body scan, single photon emission computed tomography/computed tomography of neck and chest were performed. Each radioactive focus at whole body scan was classified as positive or equivocal with respect of specific territories: thyroid bed, cervical lymph nodes and distant metastases.Whole-body scan detected focal uptake in 353 patients and no uptake in 12. The location was considered equivocal in 100. Single photon emission computed tomography/computed tomography detected focal uptake in 356 patients and no uptake in nine. In three patients with negative wholebody scan, single photon emission computed tomography/computed tomography provided information about residual activity in the thyroid bed. By single photon emission computed tomography/computed tomography the location was equivocal in 18 patients only. Single photon emission computed tomography/computed tomography was helpful in 82 out of 100 patients with equivocal findings by whole body scan allowing a correct identification of the uptake sites. In a great number of equivocal whole body scan, due to high remnant activity, single photon emission computed tomography/computed tomography was able to differentiate between thyroid remnant and lymph nodes uptake. In 22 out of 100 patients with doubtful whole body scan, single photon emission computed tomography/computed tomography correctly identified nodal or distant metastases, and in 2/100 patients, focal uptake classified as metastatic by whole body scan was reclassified as para-physiological by single photon emission computed tomography/computed tomography. The TNM classification changed in 13 out of 22 patients. Single photon emission computed tomography/computed tomography improves detection and localization of the iodine-131 uptake after thyroidectomy in patients with differentiated thyroid carcinoma and it is more accurate than whole body scan to evaluate lymph nodes and to identify and characterize distant metastases. Single photon emission computed tomography/computed tomography aids assessment of lower/upper stage in a significant number of patients with differentiated thyroid carcinoma and it can affect therapy decision-making and patient management.

The strange case of the [13N]NH3: validation of the production process for human use.

OBJECTIVE: PET radiopharmaceuticals are often injected in patients before all quality controls are performed and before sterility results are available. We propose a process validation to produce very safe and pure [N]NH3 for human use. METHODS: [N]NH3 was produced in the cyclotron target. Online purification was performed by anionic exchange resin. All the production steps were subjected to a sterility test. Some additional controls were added to those required by the monograph. RESULTS: The radiochemical yield of the syntheses was 26.3 and 61.5% corrected for decay, with a radiochemical purity of 100%. In addition to quality controls requested by the European Pharmacopeia monograph, we carefully analyzed the product for the presence of possible contaminants. Some elements, mainly metals, were found in very low amounts at concentrations in the range of ppb. The radionuclidic purity was verified. The achievement of the parameters of osmolality, by addition of saline solution to the preparation, made the analysis of chemical purity difficult and worsened the measurement of radiochemical purity by high performance liquid chromatography. Only pH control is necessary before administration to patients and therefore a safe production process was set up to prevent microbiological contamination. All phases were carefully standardized, starting from in-target production of [N]NH3, to final splitting in the syringes. Sterility tests showed no bacterial growth, indicating the safety of the production process. CONCLUSION: All our syntheses followed the monograph indications and were optimal to obtain PET imaging of a patient's myocardium.

1-23I-MIBG thyroid uptake: Implications for MIBG imaging of the heart.

BACKGROUND: 123I-MIBG has been widely used in patients with heart failure and neurological disorders. The patients are pre-treated with Lugol's oral solution or potassium perchlorate to prevent thyroid uptake of unlabeled 123I to limit the thyroid radiation exposure. However, despite the inhibition of the iodide pump, the thyroid is frequently visualized. The aim of this study was to study the pattern of thyroid uptake. METHODS: We reviewed the 123I-MIBG images of 57 patients studied in three different centers in Italy for cardiac (n = 42) or neurological (n = 15) indications. They were imaged at 15 minutes and 4 hours after injection and in all patients, the thyroid was included in the imaging field of view. In 2 of the 3 centers, the patients were pre-treated with Lugol's oral solution and/or potassium perchlorate (group 1) but in the third center, they were not (group 2). The following imaging parameters were evaluated: heart-to-mediastinum ratio (H/M), thyroid-to-mediastinum ratio (T/M) at 4 hours, and tracer wash out from the heart (HWO) and from the thyroid (TWO). RESULTS: In the cardiac patients, the HWO was 22.98 ± 7.16% and TWO was 11.4 ± 11.86% (P < .0001). The TWO was 12.2 ± 13.1% in group 1 and 10.05 ± 8.97% in group 2 (P = NS). In the neurological patients the HWO was 26 ± 8.1% and the TWO was 20.32 ± 6.41 (P < .05). The difference in TWO was statistically significant (P < .01) between cardiac and neurological patients, whereas the HWO was not. The 4-hour H/M was 1.49 ± 0.23 in cardiac patients vs 1.4 ± 0.39 in neurological patients (P = NS). The 4-hour T/M was 1.33 ± 0.3 in cardiac patients vs 1.15 ± 0.13 in neurological patients (P < 0.05). CONCLUSION: The thyroid visualization in MIBG imaging is likely an expression of thyroid sympathetic innervation. The differences in TWO and T/M ratio in cardiac and neurological patients probably express differences in thyroid dopaminergic receptors. Thus, pre-treatment with potassium perchlorate or Lugol's solution may not be justified in patients undergoing 123I-MIBG imaging in whom the risk of side effects due to pre-treatment could be higher than the risk due to thyroid radiation exposure.

Detection of post-exercise stunning by early gated SPECT myocardial perfusion imaging: results from the IAEA multi-center study.

BACKGROUND: Transient post-ischemic LV dysfunction due to myocardial stunning in patients with coronary artery disease can be missed by conventional gated SPECT (GSPECT) acquisitions. The aim of this IAEA-sponsored multi-center study was to determine whether early post-exercise imaging is more likely to detect stunning than conventional without adversely affecting image quality or perfusion information. METHODS AND RESULTS: Patients undergoing exercise/rest GSPECT were enrolled in this international multicenter study. Post-exercise studies were acquired at 15 ± 5 minutes after radiotracer injection (Stress-1) and repeated at 60 ± 15 minutes (Stress-2). Rest studies (R) were acquired at 60 minutes post injection. A core laboratory quantitatively assessed perfusion pattern and LV blinded to the acquisition time. Ischemia was defined as summed stress score (SDS) ≥4, and stunning was defined as the difference between rest and post-stress LVEF (Δ-LVEF). In the 229 patients enrolled into the study, both image quality and perfusion information were similar between Stress-1 and Stress-2. Post-stress LVEF was associated with both ischemia and time of acquisition, with a significant correlation between SDS and Δ-LVEF, which was stronger at Stress-1 than Stress-2 in the ischemic compared to the non-ischemic population (r = 0.23 vs 0.08, P = 0.10). CONCLUSIONS: Early post-exercise imaging is feasible, and can potentially improve the detection of post-ischemic stunning without compromising image quality and perfusion data.