The influence of number of counts in the myocardium in the determination of reproducible functional parameters in gated-SPECT studies simulated with GATE

Myocardial perfusion gated-single photon emission computed tomography (gated-SPECT) imaging is used for the combined evaluation of myocardial perfusion and left ventricular (LV) function. The aim of this study is to analyze the influence of counts/pixel and concomitantly the total counts in the myocardium for the calculation of myocardial functional parameters. Material and methods: Gated-SPECT studies were performed using a Monte Carlo GATE simulation package and the NCAT phantom. The simulations of these studies use the radiopharmaceutical 99mTc-labeled tracers (250, 350, 450 and 680MBq) for standard patient types, effectively corresponding to the following activities of myocardium: 3, 4.2, 5.4-8.2MBq. All studies were simulated using 15 and 30s/projection. The simulated data were reconstructed and processed by quantitative-gated-SPECT software, and the analysis of functional parameters in gated-SPECT images was done by using Bland-Altman test and Mann-Whitney-Wilcoxon test. Results: In studies simulated using different times (15 and 30s/projection), it was noted that for the activities for full body: 250 and 350MBq, there were statistically significant differences in parameters Motility and Thickness. For the left ventricular ejection fraction (LVEF), end-systolic volume (ESV) it was only for 250MBq, and 350MBq in the end-diastolic volume (EDV), while the simulated studies with 450 and 680MBq showed no statistically significant differences for global functional parameters: LVEF, EDV and ESV. Conclusion: The number of counts/pixel and, concomitantly, the total counts per simulation do not significantly interfere with the determination of gated-SPECT functional parameters, when using the administered average activity of 450MBq, corresponding to the 5.4MBq of the myocardium, for standard patient types.

Imaging in neurological and vascular brain diseases (SPECT and SPECT/CT)

Since the first in vivo studies of cerebral function with radionuclides by Ingvar and Lassen, nuclear medicine (NM) brain applications have evolved dramatically, with marked improvements in both methods and tracers. Consequently it is now possible to assess not only cerebral blood flow and energy metabolism but also neurotransmission. Planar functional imaging was soon substituted by single-photon emission computed tomography (SPECT) and positron emission tomography (PET); it now has limited application in brain imaging, being reserved for the assessment of brain death.

Influence of reconstruction parameters for FBP in semiquantification of brain studies with 123I-FPCIT

Brain dopamine transporters imaging by Single Photon Emission Tomography (SPECT) with 123I-FP-CIT has become an important tool in the diagnosis and evaluation of parkinsonian syndromes, since this radiopharmaceutical exhibits high affinity for membrane transporters responsible for cellular reabsorption of dopamine on the striatum. However, Ordered Subset Expectation Maximization (OSEM) is the method recommended in the literature for imaging reconstruction. Filtered Back Projection (FBP) is still used due to its fast processing, even if it presents some disadvantages. The aim of this work is to investigate the influence of reconstruction parameters for FBP in semiquantification of Brain Studies with 123I-FPCIT compared with those obtained with OSEM recommended reconstruction.

Radiopharmaceuticals for myocardial perfusion imaging: SPECT & PET

Myocardial perfusion imaging (MPI) is used on a daily basis to access coronary blood flow in patients that are suspected or have known Coronary Artery Disease (CAD). A Single Photon Emission Computed Tomography (SPECT) or and Positron Emission Tomography (PET) scan are used to access regional blood flow quantification either at rest or stress, the imaging acquisition is connected to an Electrocardiogram (ECG) and it is able to determine and quantify other myocardial parameters like myocardial wall thickness and wall motion. PET is not used so broadly due to its high procedure cost, the proximity with cyclotron, where are produced the majority of radiopharmaceuticals used in PET, due to their shor thalf-life. This work is intended to carry out a review of the tests relating to radiopharmaceuticals that are used in clinical practice in SPECT or PET for assessment of myocardial perfusion, also focusing very promising radiopharmaceuticals that are under investigation or in clinical trials with great potential for conventional nuclear medicine or PET, proceeding to a comparative analysis of both techniques and respective radiopharmaceuticals used.

Autism Spectrum Disorder Secondary to Enterovirus Encephalitis

Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Nevertheless, these viruses are also associated with severe and life-threatening infections, such as meningitis and encephalitis. We describe a 32-month-old patient with enteroviral encephalitis confirmed by polymerase chain reaction in cerebrospinal fluid, with unfavorable clinical course with marked developmental regression, autistic features, persistent stereotypes and aphasia. She experienced slow clinical improvement, with mild residual neurologic and developmental deficits at follow-up. Viral central nervous system infections in early childhood have been associated with autism spectrum disorders but the underlying mechanisms are still poorly understood. This case report is significant in presenting a case of developmental regression with autistic features and loss of language improving on follow-up. To our knowledge, this is the first published report of enterovirus encephalitis leading to an autism spectrum disorder.

Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review

Objectives: The therapeutic effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BMs) as an outcome. Therefore, our aim was to review noninvasive brain stimulation trials in depression using BMs. Methods: The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and transcranial direct current stimulation as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. Results: Of 1234 potential articles, 52 articles were included. Only studies using TMS were found. Biological markers included immune and endocrine serum markers, neuroimaging techniques, and electrophysiological outcomes. In 12 articles (21.4%), end point BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. Biological marker outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. Conclusions: Functional magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, cortical excitability, and brain-derived neurotrophic factor consistently showed positive results. Brain-derived neurotrophic factor was the best predictor of patients’ likeliness to respond. These initial results are promising; however, all studies investigating BMs are small, used heterogeneous samples, and did not take into account confounders such as age, sex, or family history. Based on our findings, we recommend further studies to validate BMs in noninvasive brain stimulation trials in MDD.

Procesos fotofísicos y fotoquímicos en sistemas organizados

Se estudiará el comportamiento de moléculas sonda aromáticas flourescentes en micelas inversas de AOT y BHDC y en soluciones de polielectrolitos y mezclas de polielectrolitos y detergentes. Se espera obtener información sobre la estructura de los sistemas microheterogéneos y cómo esta estructura afecta la formación de iones radicales obtenidos a partir de reacciones entre moléculas sonda y moléculas donoras o aceptoras de electrones. Las técnicas a emplear incluyen espectroscopía de absorción y emisión, láser flash fotólisis, flourescencia pulsada por láseres y time correlated single photon counting. Objetivos generales y específicos: 1. Fotofísica y fotoquímica en micelas inversas. 1.1. Exciplejos en micelas inversas. 1.2. Rendimientos de estados electrónicos triplete en micelas inversas. 1.3. Comportamiento de ftalocianinas y porfirinas en micelas inversas. 2. Soluciones de polielectrolitos y mezclas de polielectrolitos con detergentes. 2.1. Reacciones fotoinducidas. 2.2. Comportamiento de derivados de porfirinas y ftalocianinas. 3. Montaje de la técnica de Time Correlated Single Photn Counting. 4. Montaje de un equipo adicional de laser flash fotólisis. 5. Síntesis de derivados solubles en agua de porfirinas y ftalocianinas.

Insights into molecular mechanisms regulating the activity of multidomain proteins in living cells using FRET-FLIM

FRET-FLIM, ENERGY TRANSFER, LIFETIME, DECAY ASSOCIATED SPECTRUM, DAS, KINASE, MAGUKS, SINGLE PHOTON COUNTING, PICOSECOND-TIME RESOLVED FLUORESCENCE SPECTROSCOPY, GFP, CFP, YFP, TOPAZ, NANOMETER, MICROSCOPY, LYMPHOCYTES, LCK, SAP97

The Benefits of Prone SPECT Myocardial Perfusion Imaging in Reducing Both Artifact Defects and Patient Radiation Exposure

AbstractBackground:Prone imaging has been demonstrated to minimize diaphragmatic and breast tissue attenuation.Objectives:To determine the role of prone imaging on the reduction of unnecessary rest perfusion studies and coronary angiographies performed, thus decreasing investigation time and radiation exposure.Methods:We examined 139 patients, 120 with an inferior wall and 19 with an anterior wall perfusion defect that might represented attenuation artifact. Post-stress images were acquired in both the supine and prone position. Coronary angiography was used as the “gold standard” for evaluating coronary artery patency. The study was terminated and rest imaging was obviated in the presence of complete improvement of the defect in the prone position. Quantitative interpretation was performed. Results were compared with clinical data and coronary angiographic findings.Results:Prone acquisition correctly revealed defect improvement in 89 patients (89/120) with inferior wall and 12 patients (12/19) with anterior wall attenuation artifact. Quantitative analysis demonstrated statistically significant difference in the mean summed stress scores (SSS) of supine and mean SSS of prone studies in patients with disappearing inferior wall defect in the prone position and patent right coronary artery (true negative results). The mean difference between SSS in supine and in prone position was higher with disappearing than with remaining defects.Conclusion:Technetium-99m (Tc-99m) tetrofosmin myocardial perfusion imaging with the patient in the prone position overcomes soft tissue attenuation; moreover it provides an inexpensive, accurate approach to limit the number of unnecessary rest perfusion studies and coronary angiographies performed.

Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block

Abstract Background: Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB). Objective: To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP) by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA) (stenosis ≥ 70%) as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA) and compare the results with those of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. Methods: Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution’s ethics committee. Results: The patients’ mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001). Conclusion: The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB.

Electroencephalographic source imaging: a prospective study of 152 operated epileptic patients.

Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission-computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (<32 channels) and a template head model. This study demonstrated the validity and clinical utility of electric source imaging in a large prospective study. Given the low cost and high flexibility of electroencephalographic systems even with high channel counts, we conclude that electric source imaging is a highly valuable tool in pre-surgical epilepsy evaluation.

Defectos paradójicos en regiones con necrosis miocárdica. análisis mediante gated-spect de perfusión miocárdica.

Objectius: Valorar el significat dels defectes paradoxals (DP) segmentaris (captació en esforç més gran que en repòs) a la gated-SPECT (Single Photon Emission Computer Tomography) de perfusió miocàrdica amb compostos tecneciats en regions amb necrosi miocàrdica. Material i mètodes: Es van revisar 1764 SPECT de perfusió miocàrdica estrès-repòs consecutives de pacients amb infart (IM) previ i es van identificar 117 pacients (6,6%) en els quals els DPs corresponien a una regió amb necrosi miocàrdica. Es van valorar els criteris gammagràfics de viabilitat (intensitat del defecte, valor d'aquesta intensitat ponderat pel nombre de segments compromesos-VIP-, la motilitat i l'engrossiment miocàrdic sistòlic) en els segments d'aquestes regions i les característiques de l'artèria responsable en els 96 pacients en els quals s'havia practicat una coronariografia. Resultats: Es van analitzar 160 necrosis, 125 (75%) paradoxals (67 (54%) en regió AnteroSeptoApical i 58 (46%) en regió InferoLateral) i 35 (25%) no paradoxals (19 (54%) ASA i 16 ( 46%) IL). Els valors de severitat de la necrosi i del VIP van ser inferiors en l'estudi d'estrès respecte al repòs i la diferència d'aquests va ser sempre negativa, evidenciant un comportament gammagràfic paradoxal. Per contra, aquests valors van ser inferiors al repòs respecte a l'estrès en les necrosi no paradoxals posant de manifest un comportament gammagràfic de mínima o nul reversibilitat. Així mateix, es van trobar alteracions lleus en la motilitat i engrossiment de les necrosi paradoxals i moderats en les necrosi no paradoxals. Es van trobar 102 necrosis amb DP i coronariografia dels quals, 84 (88%) tenien permeabilitat a l'artèria responsable de la necrosi i 12 pacients (12%) tenien circulació colateral per compensar l'oclusió de l'artèria responsable. Conclusions: Tots els segments amb DP en regions amb necrosi complien criteris gammagràfics de viabilitat en les imatges d'estrès, considerant aquestes imatges millors per a l'avaluació d'aquest tipus de lesions. El vas responsable de la regió amb DP es trobava permeable o bé presentava circulació colateral evident en els casos en què la coronària es trobava closa.

Chest pain and ST-segment elevation in a patient with Duchenne muscular dystrophy, what really happened?

Introduction: Myocardial infarction is rare in children, if it occurs, findings are almost similar to adults. In Ouchenne muscular dystrophy (OMO), ST segment displacement associated with typical chest pain can occur. We report the case of a young boy with OMO presenting symptoms suggestive of myocardial ischemia. Case report: 7 year old boy, diagnosed with OMO, eoming to the emergency department with complaints of acute chest pain, dyspnoea and anxiety the night before. Clinical examination was not remarkable, with exception of findings of the OMO. ECG showed important ST-segment elevation in right precordial leads. Major increase in troponin 1 42.33 mcg/(normal, <0.04 mcg/I) was found. Echocardiography revealed slight yskinesia of postero-septal wall without decrease in ventricular function. As acute pain had happened more han 12 hours before referral and as the child was asymptomatic, he received anti-platelets therapy. The serum level of troponin 1 declined and the ECG normalised in a few days. Cardiac catheterization did not show any coronary anomaly or eardiac dysfunction. Cardiac biopsy revealed myocardial cell damaged compatible with OMO cardiomyopathy. Tc99m myocardial single-photon emission computed tomography (SPECT) did not show any radionuclide uptake defect. Conclusions: ln this particular context of children with OMO, the classical signs of myocardial ischemia could be misleading, standard investigation failed to demonstrate the cause of chest pain and inerease of troponin l, there was also no evidence of myocarditis. Role of late enhancement (LE) signal in eontrast-enhanced MRI in the understanding of the occurring process has to be evaluated.

Phase-I/II radio-immunotherapy study with Iodine-131-labeled anti-CEA monoclonal antibody F6 F(ab')2 in patients with non-resectable liver metastases from colorectal cancer.

Experimental studies in nude mice with human colon-carcinoma grafts demonstrated the therapeutic efficiency of F(ab')2 fragments to carcinoembryonic antigen (CEA) labeled with a high dose of 131Iodine. A phase I/II study was designed to determine the maximum tolerated dose of 131I-labeled F(ab')2 fragments (131I-F(ab')2) from anti-CEA monoclonal antibody F6, its limiting organ toxicity and tumor uptake. Ten patients with non-resectable liver metastases from colorectal cancer (9 detected by CT scan and 1 by laparotomy) were treated with 131I-F(ab')2, doses ranging from 87 mCi to 300 mCi for the first 5 patients, with a constant 300-mCi dose for the last 5 patients. For all the patients, autologous bone marrow was harvested and stored before treatment. Circulating CEA ranged from 2 to 126 ng/ml. No severe adverse events were observed during or immediately following infusion of therapeutic doses. The 9 patients with radiologic evidence of liver metastases showed uptake of 131I-F(ab')2 in the metastases, as observed by single-photon-emission tomography. The only toxicity was hematologic, and no severe aplasia was observed when up to 250 mCi was infused. At the 300-mCi dose, 5 out of 6 patients presented grade-3 or -4 hematologic toxicity, with a nadir for neutrophils and thrombocytes ranging from 25 to 35 days after infusion. In these 5 cases, bone marrow was re-infused. No clinical complications were observed during aplasia. The tumor response could be evaluated in 9 out of 10 patients. One patient showed a partial response of one small liver metastasis (2 cm in diameter) and a stable evolution of the other metastases, 2 patients had stable disease, and 6 showed tumor progression at the time of evaluation (2 or 3 months after injection) by CT scan. This phase-I/II study demonstrated that a dose of 300 mCi of 131I-F(ab')2 from the anti-CEA Mab F6 is well tolerated with bone-marrow rescue, whereas a dose of 200 mCi can be infused without severe bone-marrow toxicity.

Insulinoma associated with a case of multiple endocrine neoplasia type I: Functional somatostatin receptors and abnormal glucose-induced insulin secretion.

A sporadic case of multiple endocrine neoplasia type I with coexisting insulinoma and hyperparathyroidism was investigated in vivo and in vitro. The insulinoma was localized by somatostatin receptor scintigraphy and these receptors were functionally active. Octreotide administration decreased the basal insulin and glucagon secretion by 90 and 46%, respectively. Immunocytochemistry of the insulinoma tissue was positive for insulin, chromogranin A and neuropeptide Y. The insulinoma cells were also isolated and cultured in vitro. Incubation experiments revealed that a low glucose concentration (1 mmol/l) was sufficient to increase cytosolic free calcium and to produce a maximal glucose-induced insulin release. Northern blot analysis of RNA obtained from the tumor showed a high abundance of the low Km glucose transporter GLUT1 but no transcript for the high Km glucose transporter GLUT2. The abnormal distribution of glucose transporters probably relates to the abnormal glucose sensing of insulinoma cells, and explains their sustained insulin secretion at low glucose concentrations. Whether these abnormalities share a pathogenetic link with the presence of functionally active somatostatin receptors remains to be elucidated.