Alterações de fluxos sanguíneos cerebrais regionais (FSCr) avaliados através de SPECT (Single Photon Emission Computed Tomography) em pacientes com câncer de mama submetidas à quimioterapia adjuvante

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Registry for the Evaluation of the Prognostik value of a novel integrated imaging approach combining Single Photon Emission Computed Tomography with coronary calcification imaging (REPROSPECT)

AIMS: Although an added diagnostic and prognostic value of the global coronary artery calcification (CAC) score as an adjunct to single-photon emission computed tomography (SPECT)-myocardial perfusion image (MPI) has been repeatedly documented, none of the previous studies took advantage of the anatomic information provided by the unenhanced cardiac CT. Therefore, no co-registration has so far been used to match a myocardial perfusion defect with calcifications in the subtending coronary artery. To evaluate the prognostic value of integrating SPECT-MPI with CAC images were obtained from non-enhanced cardiac computed tomography (CT) for attenuation correction to predict major adverse cardiac events (MACE). METHODS AND RESULTS: Follow-up was obtained in 462 patients undergoing a 1-day stress/rest (99m)Tc-teterofosmin SPECT and non-enhanced cardiac CT for attenuation correction. Survival free of MACE was determined using the Kaplan-Meier method. After integrating MPI and CT findings, patients were divided into three groups (i) MPI defect matched by calcification (CAC ≥ 1) in the subtending coronary artery (ii) unmatched MPI and CT finding (iii) normal finding by MPI and CT. At a mean follow-up of 34.5 ± 13 months, a MACE was observed in 80 patients (33 death, 6 non-fatal myocardial infarction, 9 hospitalizations due to unstable angina, and 32 revascularizations). Survival analysis revealed the most unfavourable outcome (P < 0.001 log-rank test) for patients with a matched finding. CONCLUSION: In the present study, a novel approach using a combined integration of cardiac SPECT-CAC imaging allows for refined risk stratification, as a matched defect emerged as an independent predictor of MACE.

A CASE STUDY IN PHARMACOLOGIC IMAGING USING PRINCIPAL CURVES IN SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

In this manuscript we are concerned with functional imaging of the colon to assess the kinetics of a microbicide lubricant. The overarching goal is to understand the distribution of the lubricant in the colon. Such information is crucial for understanding the potential impact of the microbicide on HIV viral transmission. The experiment was conducted by imaging a radiolabeled lubricant distributed in the subject’s colon. The tracer imaging was conducted via single photon emission computed tomography (SPECT), a non-invasive, in-vivo functional imaging technique. We develop a novel principal curve algorithm to construct a three dimensional curve through the colon images. The developed algorithm is tested and debugged on several difficult two dimensional images of familiar curves where the original principal curve algorithm does not apply. The final curve fit to the colon data is compared with experimental sigmoidoscope collection.

Evaluation of a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated bombesin-based radioantagonist for the labeling with single-photon emission computed tomography, positron emission tomography, and therapeutic radionuclides

PURPOSE: G protein-coupled receptor agonists are being used as radiolabeled vectors for in vivo localization and therapy of tumors. Recently, somatostatin-based antagonists were shown to be superior to agonists. Here, we compare the new [111In/68Ga]-labeled bombesin-based antagonist RM1 with the agonist [111In]-AMBA for targeting the gastrin-releasing peptide receptor (GRPR). EXPERIMENTAL DESIGN: IC50, Kd values, and antagonist potency were determined using PC-3 and HEK-GRPR cells. Biodistribution and imaging studies were done in nude mice transplanted with the PC-3 tumor. The antagonist potency was assessed by evaluating the effects on calcium release and on receptor internalization monitored by immunofluorescence microscopy. RESULTS: The IC50 value of [(nat)In]-RM1 was 14 +/- 3.4 nmol/L. [(nat/111)In]-RM1 was found to bind to the GRPR with a Kd of 8.5 +/- 2.7 nmol/L compared with a Kd of 0.6 +/- 0.3 nmol/L of [111In]-AMBA. A higher maximum number of binding site value was observed for [111In]-RM1 (2.4 +/- 0.2 nmol/L) compared with [111In]-AMBA (0.7 +/- 0.1 nmol/L). [(nat)Lu]-AMBA is a potent agonist in the immunofluorescence-based internalization assay, whereas [(nat)In]-RM1 is inactive alone but efficiently antagonizes the bombesin effect. These data are confirmed by the calcium release assay. The pharmacokinetics showed a superiority of the radioantagonist with regard to the high tumor uptake (13.4 +/- 0.8% IA/g versus 3.69 +/- 0.75% IA/g at 4 hours after injection. as well as to all tumor-to-normal tissue ratios. CONCLUSION: Despite their relatively low GRPR affinity, the antagonists [111In/68Ga]-RM1 showed superior targeting properties compared with [111In]-AMBA. As found for somatostatin receptor-targeting radiopeptides, GRP-based radioantagonists seem to be superior to radioagonists for in vivo imaging and potentially also for targeted radiotherapy of GRPR-positive tumors.

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography - A comparison with contrast-enhanced magnetic resonance imaging

OBJECTIVES We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). BACKGROUND Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. METHODS Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, 75% of the wall thickness replaced by scar. RESULTS As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (50% were viable by SPECT. CONCLUSIONS Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar. (C) 2004 by the American College of Cardiology Foundation.

Comparison between real-time three-dimensional echocardiography, T1-201 single photon emission computed tomography and cardiac magnetic resonance imaging in the quantitative assessment of left ventricular volumes

Left ventricular (LV) volumes have important prognostic implications in patients with chronic ischemic heart disease. We sought to examine the accuracy and reproducibility of real-time 3D echo (RT-3DE) compared to TI-201 single photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (MRI). Thirty (n = 30) patients (age 62±9 years, 23 men) with chronic ischemic heart disease underwent LV volume assessment with RT-3DE, SPECT, and MRI. Ano vel semi-automated border detection algorithmwas used by RT-3DE. End diastolic volumes (EDV) and end systolic volumes (ESV) measured by RT3DE and SPECT were compared to MRI as the standard of reference. RT-3DE and SPECT volumes showed excellent correlation with MRI (Table). Both RT- 3DE and SPECT underestimated LV volumes compared to MRI (ESV, SPECT 74±58 ml versus RT-3DE 95±48 ml versus MRI 96±54 ml); (EDV, SPECT 121±61 ml versus RT-3DE 169±61 ml versus MRI 179±56 ml). The degree of ESV underestimation with RT-3DE was not significant.

Collimation of a D-D Neutron Generator for Clinical Implementation of Neutron Stimulated Emission Computed Tomography: a Monte Carlo Study

This work is an investigation into collimator designs for a deuterium-deuterium (DD) neutron generator for an inexpensive and compact neutron imaging system that can be implemented in a hospital. The envisioned application is for a spectroscopic imaging technique called neutron stimulated emission computed tomography (NSECT).

Previous NSECT studies have been performed using a Van-de-Graaff accelerator at the Triangle Universities Nuclear Laboratory (TUNL) in Duke University. This facility has provided invaluable research into the development of NSECT. To transition the current imaging method into a clinically feasible system, there is a need for a high-intensity fast neutron source that can produce collimated beams. The DD neutron generator from Adelphi Technologies Inc. is being explored as a possible candidate to provide the uncollimated neutrons. This DD generator is a compact source that produces 2.5 MeV fast neutrons with intensities of 1012 n/s (4π). The neutron energy is sufficient to excite most isotopes of interest in the body with the exception of carbon and oxygen. However, a special collimator is needed to collimate the 4π neutron emission into a narrow beam. This work describes the development and evaluation of a series of collimator designs to collimate the DD generator for narrow beams suitable for NSECT imaging.

A neutron collimator made of high-density polyethylene (HDPE) and lead was modeled and simulated using the GEANT4 toolkit. The collimator was designed as a 52 x 52 x 52 cm3 HDPE block coupled with 1 cm lead shielding. Non-tapering (cylindrical) and tapering (conical) opening designs were modeled into the collimator to permit passage of neutrons. The shape, size, and geometry of the aperture were varied to assess the effects on the collimated neutron beam. Parameters varied were: inlet diameter (1-5 cm), outlet diameter (1-5 cm), aperture diameter (0.5-1.5 cm), and aperture placement (13-39 cm). For each combination of collimator parameters, the spatial and energy distributions of neutrons and gammas were tracked and analyzed to determine three performance parameters: neutron beam-width, primary neutron flux, and the output quality. To evaluate these parameters, the simulated neutron beams are then regenerated for a NSECT breast scan. Scan involved a realistic breast lesion implanted into an anthropomorphic female phantom.

This work indicates potential for collimating and shielding a DD neutron generator for use in a clinical NSECT system. The proposed collimator designs produced a well-collimated neutron beam that can be used for NSECT breast imaging. The aperture diameter showed a strong correlation to the beam-width, where the collimated neutron beam-width was about 10% larger than the physical aperture diameter. In addition, a collimator opening consisting of a tapering inlet and cylindrical outlet allowed greater neutron throughput when compared to a simple cylindrical opening. The tapering inlet design can allow additional neutron throughput when the neck is placed farther from the source. On the other hand, the tapering designs also decrease output quality (i.e. increase in stray neutrons outside the primary collimated beam). All collimators are cataloged in measures of beam-width, neutron flux, and output quality. For a particular NSECT application, an optimal choice should be based on the collimator specifications listed in this work.

SPECT (Single photon emission tomography): Gama câmara, reconstrução tomográfica e características funcional

The SPECT (Single Photon Emission Computed Tomography) systems are part of a medical image acquisition technology which has been outstanding, because the resultant images are functional images complementary to those that give anatomic information, such as X-Ray CT, presenting a high diagnostic value. These equipments acquire, in a non-invasive way, images from the interior of the human body through tomographic mapping of radioactive material administered to the patient. The SPECT systems are based on the Gamma Camera detection system, and one of them being set on a rotational gantry is enough to obtain the necessary data for a tomographic image. The images obtained from the SPECT system consist in a group of flat images that describe the radioactive distribution on the patient. The trans-axial cuts are obtained from the tomographic reconstruction techniques. There are analytic and iterative methods to obtain the tomographic reconstruction. The analytic methods are based on the Fourier Cut Theorem (FCT), while the iterative methods search for numeric solutions to solve the equations from the projections. Within the analytic methods, the filtered backprojection (FBP) method maybe is the simplest of all the tomographic reconstruction techniques. This paper's goal is to present the operation of the SPECT system, the Gamma Camera detection system, some tomographic reconstruction techniques and the requisites for the implementation of this system in a Nuclear Medicine service

18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response

To determine whether [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (±6.3) to 8.1 (±2.9) after 1 week of chemoradiation (P = 0.070). In nonresponders (72%), the results were 9.7 (±5.4) and 7.1 (±3.8), respectively (P = 0.003). The MTV in responders fell from 36.6 (±22.7) to 22.3 (±10.4) cm3 (P = 0.180), while in nonresponders, this fell from 35.9 (±36.7) to 31.9 (±52.7) cm3 (P = 0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer. © 2006 Cancer Research UK.

Myoblast transplantation and adenoviral VEGF-C transfer in porcine model of coronary artery disease

Heart failure is a common and highly challenging medical disorder. The progressive increase of elderly population is expected to further reflect in heart failure incidence. Recent progress in cell transplantation therapy has provided a conceptual alternative for treatment of heart failure. Despite improved medical treatment and operative possibilities, end-stage coronary artery disease present a great medical challenge. It has been estimated that therapeutic angiogenesis would be the next major advance in the treatment of ischaemic heart disease. Gene transfer to augment neovascularization could be beneficial for such patients. We employed a porcine model to evaluate the angiogenic effect of vascular endothelial growth factor (VEGF)-C gene transfer. Ameroid-generated myocardial ischemia was produced and adenovirus encoding (ad)VEGF-C or β-galactosidase (LacZ) gene therapy was given intramyocardially during progressive coronary stenosis. Angiography, positron emission tomography (PET), single photon emission computed tomography (SPECT) and histology evidenced beneficial affects of the adVEGF-C gene transfer compared to adLacZ. The myocardial deterioration during progressive coronary stenosis seen in the control group was restrained in the treatment group. We observed an uneven occlusion rate of the coronary vessels with Ameroid constrictor. We developed a simple methodological improvement of Ameroid model by ligating of the Ameroid–stenosed coronary vessel. Improvement of the model was seen by a more reliable occlusion rate of the vessel concerned and a formation of a rather constant myocardial infarction. We assessed the spontaneous healing of the left ventricle (LV) in this new model by SPECT, PET, MRI, and angiography. Significant spontaneous improvement of myocardial perfusion and function was seen as well as diminishment of scar volume. Histologically more microvessels were seen in the border area of the lesion. Double staining of the myocytes in mitosis indicated more cardiomyocyte regeneration at the remote area of the lesion. The potential of autologous myoblast transplantation after ischaemia and infarction of porcine heart was evaluated. After ligation of stenosed coronary artery, autologous myoblast transplantation or control medium was directly injected into the myocardium at the lesion area. Assessed by MRI, improvement of diastolic function was seen in the myoblast-transplanted animals, but not in the control animals. Systolic function remained unchanged in both groups.

Selective Review of Proton Magnetic Resonance Spectroscopy in Schizophrenia

Magnetic Resonance Spectroscopy (MRS) offers a unique opportunity to measure brain metabolites in-vivo, and in doing so enables one to understand the brain function and cellular processes implicated in the pathophysiology of psychiatric disorders. MRS, in addition to being non-invasive, is devoid of radioactive tracers and ionizing radiation, a distinct advantage over other imaging modalities like positron emission tomography and single photon emission computed tomography. With advances in MRS technique it is now possible to quantify concentrations of relevant compounds like neurotransmitters, neuronal viability markers and pharmacological compounds. Majority of the MRS studies have examined the neurometabolites in schizophrenia, a common and debilitating psychiatric disorder. Abnormalities in N Acetyl aspartate and Glutamate are consistently reported while the reports regarding the myoinsoitol and choline are inconsistent. These abnormalities are not changed across the illness stages and despite treatment. However, multiple technical challenges have limited the widespread use of MRS in psychiatric disorders. Guidelines for uniform acquisition and preprocessing are need of the hour, which. would increase the replicability and validity of MRS measures in psychiatry. Finally long term, prospective, longitudinal studies are required in different psychiatric disorders for potential clinical applications.