BACKGROUND AND OBJECTIVES:In an effort to help identify factors that maintain heavy smoking, this study tested the association of pretreatment cigarette use (cigarettes per day) with striatal dopamine release during smoking-cessation treatment.METHODS:Thirteen regular smokers (≥10 cigarettes per day) were evaluated on parameters of smoking behavior, and they entered a smoking cessation treatment protocol, including bupropion administration and individual counseling for 2 months. On week 7 of treatment, 10 of the participants underwent brain scans using [(11) C]raclopride with positron emission tomography to assess smoking-induced dopamine release in the caudate nucleus and putamen, inferred from changes in dopamine D2 -type receptor availability.RESULTS:Receptor availability, measured as binding potential referred to non-displaceable uptake (BPND ) in both striatal regions re-demonstrated a significant decrease after smoking a cigarette; and pre-treatment cigarette use significantly negatively correlated with smoking-induced dopamine release in the caudate.CONCLUSIONS AND SIGNIFICANCE:The negative association of cigarette use with dopamine release suggests tolerance or down-regulation of the dopamine system by chronic smoking, or a pre-existing condition that promotes more frequent smoking. This association should be regarded as preliminary evidence that warrants verification. (Am J Addict 2016;25:486-492).

Gated blood pool SPECT (GBPS) requires further validation for the assessment of the right ventricle (RV). This study evaluated three algorithms: BP-SPECT, QBS, and TOMPOOL (results are referred using this order). We compared (1) their “quantitative-accuracy”: estimation of RV ejection fraction (EF), end-diastolic volume (EDV), and cardiac output (CO); (2) their “qualitative-accuracy”: threshold values allowing diagnosing an impairment of the RV function; (3) their reproducibility: inter-observer relative variability (IOV).

the diagnosis of infected protheses in patients with long standing fever is difficult, challenging and has major impact on the management. Since 18-Fluo Desoxyglucose positron emission tomography performed together with computerized tomography (FDG PET-CT) has a role in the diagnosis and localization of infection; we evaluated its value in the diagnosis of infected prostheses, correlating its results with medical workup, echo-cardiogram and dedicated CT. Patients: Fourteen patients (pts) with cardiovascular prostheses (seven with a pacemaker, four with vascular grafts, two with pulmonary stent and one with mitral valve prosthesis were hospitalized for prolonged fever. All pts received antibiotics and underwent repeated medical workup. Eight of the 14 pts had a proven bacteriemia. Transthoracic and transoesophagial echocardiogram was performed as well as CT, for most of them. FDG PET-CT was performed in all of them, following injection of 370 MBq of F-18 FDG. All patients were normoglycemic at the time of injection. Results of the FDG PET-CT were compared with other diagnostic modalities and clinical follow up. In the 7 pts with pacemaker, FDG PET-CT was positive in 4, echo in 2/4. IN 3/4 the device was removed. A new pacemaker was implanted for two patients after few weeks. FEG PET-CT was negative in 3/7 pts with 1 positive, 1 negative and 1 intermediate results. All patients with vascular graft had positive FDG PET-CT scan and only one had a positive echocardiogram. This patient had a surgical proven abscess. Two pts with pulmonary stent had a positive FDG PET-CT scan and 1 positive echo. In this patient the stent extracted was infected. FDG PET-CT and echo was negative in the patient with mitral prosthesis.Conventional CT was positive in only 1 patient. Twelve pts return to normal including all the patients after prostheses extraction except one who died during graft replacement. FDG PET -CT is a useful tool for the diagnosis of infected cardiovascular prosthesis and is more accurate than stand alone CT. Correlation of the clinical, echo and FDG PET CT findings is crucial for the therapeutic decision.

A meta-analysis was performed to assess the association of hepatic cytochrome P450 2A6 (CYP2A6) gene polymorphisms with cigarette consumption.A comprehensive search was conducted to identify the studies of the above-mentioned association. The fixed effect model (FEM) or random effect model (REM) was selected based on the homogeneity test among studies. Heterogeneity among studies was evaluated using the I2. Meta-regression and the “leave one out” sensitive analysis were utilized to explore potential sources of heterogeneity. Publication bias was estimated by Harbord test. The effect of CYP2A6 gene polymorphisms on cigarette consumption was presented as standardized mean difference (SMD) with 95% confidence intervals (CI).After excluding one article that was the key contributor to between-study heterogeneity, there was a significant difference of cigarettes per day in groups of normal vs. reduced metabolizers of CYP2A6 gene (FEM: SMD = 0.134, 95%CI: 0.049–0.219). There was also a significant difference of age of smoking initiation between normal and intermediate metabolizers of CYP2A6 gene (FEM: SMD = 0.216, 95%CI: 0.056–0.377). No significant difference of tobacco dependence between normal and reduced metabolizers of CYP2A6 gene was found (FEM: SMD = 0.185, 95%CI = −0.001 to 0.371).This meta-analysis suggests that CYP2A6 gene polymorphism is associated with daily cigarette consumption. Individuals with intermediate nicotine metabolism might also initiate smoking later than normal metabolism.

To investigate whether MRI (RECIST 1.1, WHO criteria and the volumetric approach) or 18F-FDG PET/CT (PERCIST 1.0) are able to predict long-term outcome in nonsurgical patients with giant cell tumour of the tendon sheath or of the diffuse type (GCT-TS/DT).

BACKGROUND:The assessment of right ventricular function is crucial for management of heart disease. TOMPOOL is a software that processes data acquired with Tomographic Equilibrium Radionuclide Ventriculography. In this report, TOMPOOL's diagnostic accuracy and inter-observer reproducibility were assessed in a cohort of patients with various etiologies of ventricular dysfunction.METHODS AND RESULTS:End-diastolic volume (EDV), ejection fraction (EF), and cardiac output (CO) were calculated for the right ventricle (RV) and the left ventricle (LV) using TOMPOOL in 99 consecutive patients. Thirty-five patients underwent cardiac magnetic resonance imaging (CMR) considered as the reference-standard to measure EDV and EF; the Spearman's rho correlation coefficients were r = 0.73/0.80 and 0.67/0.73 for right/left EF and EDV, respectively. Twenty-one patients had thermodilution measurements of right CO (reference-standard), the correlation was r = 0.57. The best cut-off points (sensitivity/specificity) in order to diagnose a ventricular dysfunction or enlargement were 46% for RVEF (67%/89%), 62% for LVEF (100%/90%), 94 mL for RVEDV (77%/73%), and 84 mL for LVEDV (100%/91%). The areas under the ROC curve were, respectively, 0.79, 0.91, 0.83, and 0.99. Inter-observer reproducibility was r = 0.81/0.94, 0.77/0.90, and 0.78/0.75 for Right/Left EF, EDV, and CO, respectively.CONCLUSION:TOMPOOL is accurate: measurements of EDV, EF, and CO are reproducible and correlate with CMR and thermodilution. However, thresholds must be adjusted.

L’étude de la fonction ventriculaire droite nécessite actuellement l’intégration de nombreux paramètres échographiques, aucun n’étant suffisant pour permettre de la caractériser à lui seul. Nous avons testé et comparé à l’IRM deux nouveaux outils, le 2D speckle imaging (2DSI) et l’échographie tridimensionnelle comme marqueurs de la fonction ventriculaire droite.Trente-deux patients (19 avec fraction d’éjection du ventricule droit [FEVD] ≤ 45 %) ont bénéficié, premièrement, d’une échographie cardiaque transthoracique complète, incluant les paramètres standard d’évaluation de la fonction ventriculaire droite (fraction de raccourcissement en surface du VD [FRSVD], index de performance myocardique [IPM], excursion systolique du plan de l’anneau tricuspide [TAPSE] et étude doppler tissulaire du déplacement systolique de l’anneau tricuspide), avec coupes centrées sur le VD et acquisition tridimensionnelle (3D) du VD, et deuxièmement, d’une IRM myocardique avec mesure des volumes et de la FEVD (FEVD IRM). Le 2DSI a été appliqué à la paroi libre du VD avec mesure du pic de strain systolique (%) dans ses différents segments (basal, médian et apical). Le strain mesuré par 2DSI, surtout dans sa portion médiane et apicale, est abaissé chez les patients présentant une FEVD inférieure ou égale à 45 % (strain médian : −16,39 ± 5,27 vs −24,74 ± 8,00 [p = 0,002] ; strain apical : −13,01 ± 6,84 vs −22,53 ± 11,32 [p = 0,03]) avec une très bonne corrélation avec la FEVD IRM (r = −0,717 p = 0,0001) mais aussi avec les paramètres échographiques usuels, (FRS VD [r = 0,019], IPM [r = 0,01], vitesse maximale de l’onde S [r = 0,002]). La FEVD (3D) est elle aussi corrélée, mais de manière nettement moins forte, aux données de l’IRM (r = 0,447 p = 0,017). Le mode 3D a sous-estimé de manière importante les volumes ventriculaires.En analyse multivariée, seuls le strain apical (p = 0,004) et la FRSVD (p = 0,029) sont significativement prédictifs de la FEVD.Le strain mesuré par 2DSI, surtout dans les portions apicale et médiane de la paroi libre du VD, semble un paramètre prometteur dans l’estimation de la FEVD.L’étude de la FEVD en mode 3D apparaît plus décevante, en raison d’une franche sous-estimation des volumes ventriculaires droits.The echocardiographic assessment of right ventricular (RV) function requires many different parameters. We studied and compared with magnetic resonance imaging (MRI) two markers of RV function derived from new imaging tools: 2D speckle imaging (2DSI) and three dimensional echography.Thirty-two patients (19 with RV ejection fraction [RVEF] ≤ 45%) underwent both complete echocardiography – including standard parameters of RV function (fractional area change [FAC], Tei index, systolic velocity of tricuspid annulus by DTI), 3D full-volume acquisition on RV – and MRI for the evaluation of RV volumes and RVEF. 2DSI was applied to high frame rate cine loops centred on the RV free wall with measurement of peak systolic strain (%) in the basal, median and apical segments of this wall. Strain, especially in RV median and apical segments, is reduced in patients with RVEF less or equal to 45% (median strain: −16,39 ± 5,27 vs. −24,74 ± 8,00 [p = 0,002]; apical strain −13,01 ± 6,84 vs. 22,53 ± 11,32 [p = 0,03]) with a very good correlation with RVEF (r = −0,717, p = 0,0001) but also with the usual echographic parameters of RV function, (FAC: r = 0,019; Tei: r = 0,01; peak systolic velocity: r = 0,002). The 3D RVEF is also but poorly correlated with MRI RVEF, (r = 0,447, p = 0,017). Furthermore, 3D significantly underestimated RV volumes. By multivariate analysis, apical strain (p = 0,004) and FAC (p = 0,029) were predictive of a decreased RVEF.Apical strain as measured from 2DSI seems a promising parameter in the estimation of RV function. 3D estimation of RVEF is more disappointing because of an important underestimation of RV volumes.

Une analyse post-hoc en sous-groupes a été réalisée à partir des données groupées des deux essais INPULSIS afin de savoir s'il y avait un impact de l'emphysème sur la réduction du déclin de la capacité vitale forcée (CVF) avec le nintédanib. Les patients étaient divisés en deux groupes en fonction de la présence ou non d'emphysème déterminée à l'inclusion par une lecture qualitative centralisée de la tomodensitométrie thoracique haute résolution. Au total, 420 patients présentaient de l'emphysème et 641 en étaient indemnes. Il n'y avait pas de différence significative d'efficacité du nintédanib sur la réduction du déclin de la CVF selon la présence ou non d'emphysème à l'inclusion : différence de 102 ml/an (IC 95 % : 43,2–160,9) pour les patients avec emphysème contre 115,4 ml/an (IC 95 % : 73,8–157,1) pour les patients sans emphysème (p = 0,5199). Le nintédanib ralentit la progression de la maladie en réduisant le déclin de la fonction respiratoire chez les patients présentant une fibrose pulmonaire idiopathique, indépendamment de la présence d'emphysème à l'inclusion.A post-hoc subgroup analysis was conducted on pooled data from the two INPULSIS trials to evaluate the impact of emphysema on the reduction by nintedanib of FVC decline over one year in patients with ideopathic pulmonary fibrosis. The patients were separated into two groups according to the presence or absence of emphysema, determined at enrolement by a centralized analysis of high-resolution computerised tomography of the chest. In total, 420 patients had some emphysema and 641 did not. There was no significant difference in the reduction of FVC decline with nintedanib according to the presence of emphysema at baseline: the difference was 102 ml/year (IC 95 % : 43.2–160.9) in patients with emphysema, vs 115.4 ml/year (IC 95 % : 73.8–157.1) in patients without emphysema (p = 0.5199). Nintedanib slows disease progression by reducing the decline in lung function in patients with idiopathic pulmonary fibrosis, independently of the presence of emphysema at baseline.

There is a need for effective "broad spectrum" therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of (188)Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM) patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10 mCi (188)Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of (188)Re-6D2 was escalated to 54 mCi. SPECT/CT revealed (188)Re-6D2 uptake in melanoma metastases. The mean effective half-life of (188)Re-6D2 was 12.4 h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that (188)Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma.

Head-and-neck squamous cell carcinoma (HNSCC) is a high-risk disease. Historically, treatment often involved mutilating surgery, with devastating implications for quality of life, particularly in patients with advanced-stage laryngeal squamous cell carcinoma (ALSCC). Treatment for ALSCC always included total laryngectomy. Nowadays, treatment with more effective chemoradiotherapy regimes in newly diagnosed patients may often avoid total laryngectomy; however recurrence rates are relatively high. Techniques for early identification of recurrence or residual disease have therefore become crucial. Clinical diagnosis by laryngoscopy is problematic; radiotherapy induced laryngeal edema, which may persist for years, can mask local disease, resulting in detection at a late stage when total laryngectomy is unavoidable. F18-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT has emerged as an excellent imaging tool in the diagnosis and follow-up of HNSCC patients. In this review, we discuss experience with FDG PET/CT for follow-up of ALSCC after radiotherapy. While there is a high negative predictive value for FDG PET/CT in this situation, as in other HNSCC cases, a high rate of false positive findings in the larynx is described. Increased FDG uptake may be due to ongoing inflammation in the region of persistent edema, and may result in repeated laryngeal biopsies, with potentially deleterious long-term consequences. FDG PET/CT is an efficient imaging modality for the diagnosis and follow-up of HNSCC patients, but has limitations in the follow-up of ALSCC post-radiotherapy—benefits and risks must be weighed with caution. Keywords: Advanced laryngeal carcinoma, FDG PET/CT, post-radiotherapy edema.

BACKGROUND:Respiratory gating and gate optimization strategies present solutions for overcoming image degradation caused by respiratory motion in PET and traditionally utilize hardware systems and/or employ complex processing algorithms. In this work, we aimed to advance recently emerging data-driven gating methods and introduce a new strategy for optimizing the four-dimensional data based on information contained in that data. These algorithms are combined to form an automated motion correction workflow.METHODS:Software-based gating methods were applied to a nonspecific population of 84 small-animal rat PET scans to create respiratory gated images. The gated PET images were then optimized using an algorithm we introduce as 'gating+' to reduce noise and optimize signal; the technique was also tested using simulations. Gating+ is based on a principle of only using gated information if and where it adds a net benefit, as evaluated in temporal frequency space. Motion-corrected images were assessed quantitatively and qualitatively.RESULTS:Of the small-animal PET scans, 71% exhibited quantifiable motion after software gating. The mean liver displacement was 3.25 mm for gated and 3.04 mm for gating+ images. The (relative) mean percent standard deviations measured in background ROIs were 1.53, 1.05, and 1.00 for the gated, gating+, and ungated values, respectively. Simulations confirmed that gating+ image voxels had a higher probability of being accurate relative to the corresponding ungated values under varying noise and motion scenarios. Additionally, we found motion mapping and phase decoupling models that readily extend from gating+ processing.CONCLUSIONS:Raw PET data contain information about motion that is not currently utilized. In our work, we showed that through automated processing of standard (ungated) PET acquisitions, (motion-) information-rich images can be constructed with minimal risk of noise introduction. Such methods have the potential for implementation with current PET technology in a robust and reproducible way.

OBJECTIVE:We present a first study of the use of 11C-acetate (ACET) positron emission tomography (PET)/computed tomography (CT) in bladder urothelial carcinoma (UC) and an intraindividual comparison with 11C-choline (CHOL) PET/CT.METHODS:Fourteen patients with biopsy-proven UC (11 T2, 3 T1 refractory to treatment) were prospectively evaluated before radical cystectomy and excision of pelvic lymph nodes (LNs), with ACET and CHOL PET/CT scans performed within 1 week. Image acquisition started 5 minutes after intravenous injection of 12 to 14 mCi for both tracers. Standardized uptake values (SUVs) and tumor-to-background ratios (TBR) were calculated for all tumor and nodal findings and correlated with histopathology and follow-up.RESULTS:ACET and CHOL were taken up in all UCs, involved LNs, and prostate pathology. SUVs were on average slightly, nonsignificantly higher for CHOL uptake (SUV) in UCs and significantly higher for ACET in LNs. TBR was nonsignificantly higher with CHOL for UC and significantly higher for LNs.CONCLUSIONS:In this preliminary series, 11C-ACET and 11C-CHOL PET/CT showed equivalent results in the preoperative evaluation of UC. Both tracers have the potential to contribute to selecting patients who would benefit from combined treatment--neoadjuvant chemotherapy and surgery--by identifying pathologic LNs or from surgery only, thanks to their high negative predictive value for LN involvement.

Patients with posttraumatic stress disorder (PTSD) experience psychological and physiological distress. However, imaging research has mostly focused on the psychological aspects of the disorder. Considered an expression of distress, heart rate (HR) in PTSD is often elevated. In the current study, we sought to identify brain regions associated with increased HR in PTSD. Nine patients with PTSD and six healthy trauma survivors were scanned while resting, clenching teeth, and listening to neutral and traumatic scripts. Brain function was evaluated using H2O15 positron emission tomography (PET). HR was monitored by electrocardiogram. Data were analyzed using statistical parametric mapping (SPM). Subjects with PTSD exhibited a significant increase in HR upon exposure to traumatic scripts, while trauma survivors did not. Correlations between regional cerebral blood flow and HR were found only in patients with PTSD, in orbitofrontal, precentral and occipital regions. Neither group showed correlation between rCBF and HR in the amygdala or hippocampus. These preliminary results indicate that "top down" central nervous system regulation of autonomic stress response in PTSD may involve associative, sensory and motor areas in addition to regions commonly implicated in fear conditioning.

Objective: Gallium-68 (Ga-68) DOTA-1-NaI3-octreotide (DOTA-NOC) positron emission tomography (PET)/computed tomography (CT) is increasingly used for neuroendocrine tumors (NETs), often found primarily in the pancreas. However, physiologic uptake of DOTA-NOC has been described in the uncinate process of the pancreas. We studied DOTA-NOC uptake in this organ. Materials and Methods: Ninety-six patients underwent 103 DOTA-NOC scans, with pathology-proven pancreatic NET (n = 40) and nonpancreatic NET or biochemical suspicion of NET (n = 63). Results: DOTA-NOC uptake was detected in 35 documented pancreatic tumor sites (SUV: 5.5–165; mean: 25.7 ± 28.8; median: 17.8). Among 63 cases without previous known pathology, uptake was suspicious for tumor in 24 sites (SUV: 4.7–35; mean 16.3 ± 8.0; median: 14.1), and in 38 sites, it was judged as physiological, generally lower relative to adjacent structures (SUV: 2.2–12.6; mean: 6.6 ± 2.2; median: 6.2). In 24 scans with suspected tumor and in 37 of 38 scans with physiological uptake, diagnostic computed tomography or magnetic resonance imaging or endoscopic ultrasonography failed to detect tumor. Conclusions: Pancreatic DOTA-NOC uptake must be interpreted with caution, and further studies are required.