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BACKGROUND: Over the past decades, positron emission tomography (PET) imaging has become an increasingly useful research modality in the field of multiple sclerosis (MS) research, as PET can visualise molecular processes, such as neuroinflammation, in vivo. The second generation PET radioligand [18F]DPA714 binds with high affinity to the 18-kDa translocator-protein (TSPO), which is mainly expressed on activated microglia. The aim of this proof of concept study was to evaluate this in vivo marker of neuroinflammation in primary and secondary progressive MS. METHODS: All subjects were genotyped for the rs6971 polymorphism within the TSPO gene, and low-affinity binders were excluded from participation in this study. Eight patients with progressive MS and seven age and genetic binding status matched healthy controls underwent a 60 min dynamic PET scan using [18F]DPA714, including both continuous on-line and manual arterial blood sampling to obtain metabolite-corrected arterial plasma input functions. RESULTS: The optimal model for quantification of [18F]DPA714 kinetics was a reversible two-tissue compartment model with additional blood volume parameter. For genetic high-affinity binders, a clear increase in binding potential was observed in patients with MS compared with age-matched controls. For both high and medium affinity binders, a further increase in binding potential was observed in T2 white matter lesions compared with non-lesional white matter. Volume of distribution, however, did not differentiate patients from healthy controls, as the large non-displaceable compartment of [18F]DPA714 masks its relatively small specific signal. CONCLUSION: The TSPO radioligand [18F]DPA714 can reliably identify increased focal and diffuse neuroinflammation in progressive MS when using plasma input-derived binding potential, but observed differences were predominantly visible in high-affinity binders.
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Encéfalo/diagnóstico por imagem , Encefalite/diagnóstico por imagem , Encefalite/etiologia , Esclerose Múltipla/complicações , Tomografia por Emissão de Pósitrons , Pirazóis/farmacocinética , Pirimidinas/farmacocinética , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Estudo de Prova de Conceito , Estatísticas não ParamétricasRESUMO
OBJECT: The current study assesses the multicenter feasibility of pharmacological arterial spin labeling (ASL) by comparing a caffeine-induced relative cerebral blood flow decrease (%CBF↓) measured with two pseudo-continuous ASL sequences as provided by two major vendors. MATERIALS AND METHODS: Twenty-two healthy volunteers were scanned twice with both a 3D spiral (GE) and a 2D EPI (Philips) sequence. The inter-session reproducibility was evaluated by comparisons of the mean and within-subject coefficient of variability (wsCV) of the %CBF↓, both for the total cerebral gray matter and on a voxel level. RESULTS: The %CBF↓ was larger when measured with the 3D spiral sequence (23.9 ± 5.9 %) than when measured with the 2D EPI sequence (19.2 ± 5.6 %) on a total gray matter level (p = 0.02), and on a voxel level in the posterior watershed area (p < 0.001). There was no difference between the gray matter wsCV of the 3D spiral (57.3 %) and 2D EPI sequence (66.7 %, p = 0.3), whereas on a voxel level, the wsCV was visibly different between the sequences. CONCLUSION: The observed differences between ASL sequences of both vendors can be explained by differences in the employed readout modules. These differences may seriously hamper multicenter pharmacological ASL, which strongly encourages standardization of ASL implementations.
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Encéfalo/fisiologia , Cafeína/administração & dosagem , Circulação Cerebrovascular/fisiologia , Imageamento Tridimensional/instrumentação , Imageamento Tridimensional/métodos , Angiografia por Ressonância Magnética/instrumentação , Encéfalo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação de Medicamentos/métodos , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Estudos Multicêntricos como Assunto/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de SpinRESUMO
OBJECT: While pseudo-continuous arterial spin labeling (pCASL) is a promising imaging technique to visualize cerebral blood flow, it is also (acoustically) very loud during labeling. In this paper, we reduced the labeling loudness on our scanner by increasing the interval between the RF pulses from the literature standard of 1.0 ms. We also propose recommendations to reduce the loudness on scanners of the same type at other sites. MATERIALS AND METHODS: First, the sound pressure level (SPL) was both simulated and measured as a function of the labeling interval (1.0-1.8 ms) and longitudinal position in the scanner (-10 to +10 cm, relative to isocenter). Subsequently, we selected the labeling interval with the lowest overall SPL for the "SPL-optimized" pCASL sequence. Nine volunteers were scanned to compare raw signal intensity, temporal signal-to-noise ratio (tSNR) and labeling efficiency between the SPL-optimized and the standard PCASL sequence. RESULTS: Sound pressure level measurements on our scanner showed that loudness was reduced by 6.5 dB at the approximate location of the ear by adjusting the labeling interval to 1.4 ms. Furthermore, image quality was not affected, since no significant differences in signal intensity, tSNR and labeling efficiency were observed. CONCLUSION: By increasing the pCASL labeling interval, acoustic noise in the pCASL sequence was reduced with 6.5 dB, while image quality was preserved.
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Encéfalo/fisiologia , Circulação Cerebrovascular/fisiologia , Aumento da Imagem/instrumentação , Aumento da Imagem/métodos , Angiografia por Ressonância Magnética/instrumentação , Angiografia por Ressonância Magnética/métodos , Ruído/prevenção & controle , Algoritmos , Velocidade do Fluxo Sanguíneo/fisiologia , Encéfalo/anatomia & histologia , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Imagens de Fantasmas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de SpinRESUMO
PURPOSE: To determine the clinical feasibility of arterial spin labeling (ASL) on a 1T open bore scanner. MATERIALS AND METHODS: First, the optimal postlabeling delay (PLD) at 1T was determined (n = 5), with and without vascular crushing. Second, the effect of different labeling approaches (pseudo-continuous ASL [pCASL] vs. pulsed ASL [PASL]), background suppression (BSup) and readout options (GRASE vs. EPI) was investigated (n = 9). Each effect was quantified by calculating the signal-to-noise ratio (SNR), convergence, and number of significant gray matter (GM) voxels in the ASL images. Finally, an example of an obese volunteer who could not have been scanned in a cylindrical scanner is presented. RESULTS: The optimal PLDs were found to be 1300 msec for pCASL with and without vascular crushing. pCASL labeling outperformed PASL labeling in terms of convergence, anatomical correspondence between GM and perfusion maps, and SNR (P < 0.05). BSup appeared to have no additional value on the convergence, anatomical GM correspondence, and SNR (P > 0.05). EPI readout yielded a slightly better convergence, while the SNR of the GRASE readout was higher (P < 0.05). CONCLUSION: ASL on 1T is clinically feasible using state-of-the-art sequences that were primarily developed for higher field strengths.
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Encéfalo/irrigação sanguínea , Aumento da Imagem/instrumentação , Interpretação de Imagem Assistida por Computador/instrumentação , Angiografia por Ressonância Magnética/instrumentação , Marcadores de Spin , Adulto , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Masculino , Valores de Referência , Fluxo Sanguíneo Regional/fisiologia , Adulto JovemRESUMO
PURPOSE: To design a time-efficient patient-friendly clinical diffusion tensor MRI protocol and postprocessing tool to study the complex muscle architecture of the human forearm. MATERIALS AND METHODS: The 15-minute examination was done using a 3 T system and consisted of: T(1) -weighted imaging, dual echo gradient echo imaging, single-shot spin-echo echo-planar imaging (EPI) diffusion tensor MRI. Postprocessing comprised of signal-to-noise improvement by a Rician noise suppression algorithm, image registration to correct for motion and eddy currents, and correction of susceptibility-induced deformations using magnetic field inhomogeneity maps. Per muscle one to five regions of interest were used for fiber tractography seeding. To validate our approach, the reconstructions of individual muscles from the in vivo scans were compared to photographs of those dissected from a human cadaver forearm. RESULTS: Postprocessing proved essential to allow muscle segmentation based on combined T(1) -weighted and diffusion tensor data. The protocol can be applied more generally to study human muscle architecture in other parts of the body. CONCLUSION: The proposed protocol was able to visualize the muscle architecture of the human forearm in great detail and showed excellent agreement with the dissected cadaver muscles.
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Imagem de Difusão por Ressonância Magnética/métodos , Antebraço/anatomia & histologia , Aumento da Imagem/métodos , Músculo Esquelético/anatomia & histologia , Posicionamento do Paciente/métodos , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
PURPOSE: To evaluate the applicability of arterial spin labeling (ASL) cerebral blood flow (CBF) measurements in children with sickle cell disease (SCD). MATERIALS AND METHODS: We included 12 patients and five controls. Conventional magnetic resonance imaging (MRI) (T2, fluid attenuated inversion recovery [FLAIR], and MR angiography) was performed to diagnose silent infarcts, vasculopathy, or leukoencephalopathy. Pseudo-continuous ASL was performed to measure CBF using two postlabeling delays to identify transit-time effects. Perfusion estimates were corrected for hematocrit and blood velocity in the labeling plane and compared to phase-contrast MR. CBF asymmetries between the flow maps of the left and right internal carotid arteries were tested for significance using paired t-tests. Significant asymmetries were expressed in terms of an asymmetry ratio (AR = absolute difference/mean). An AR >10% was considered clinically relevant. RESULTS: Mean CBF was higher in patients than in controls. Agreement between CBF and flow improved after applying hematocrit and velocity corrections. At a 2100 msec postlabeling delay one patient had a clinically relevant asymmetry. No association was observed between CBF asymmetries and silent infarcts. CONCLUSION: Care must be taken in the interpretation of ASL-CBF measurements in SCD patients. A long postlabeling delay with blood velocity correction anticipates overestimation of CBF asymmetries.
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Anemia Falciforme/patologia , Anemia Falciforme/fisiopatologia , Circulação Cerebrovascular , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/fisiopatologia , Angiografia por Ressonância Magnética/métodos , Adolescente , Anemia Falciforme/complicações , Velocidade do Fluxo Sanguíneo , Transtornos Cerebrovasculares/etiologia , Criança , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de Spin , Adulto JovemRESUMO
OBJECTIVES: This study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)-derived plaque volume and positron emission tomography (PET) determined ischemia. BACKGROUND: Inflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD). METHODS: A total of 539 patients who underwent CCTA and [15O]H2O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables. RESULTS: During a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm3, CPV >110 mm3, NCPV >85 mm3, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011). CONCLUSIONS: Parameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.
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Vasos Coronários , Infarto do Miocárdio , Tecido Adiposo/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Valor Preditivo dos Testes , Prognóstico , Tomografia Computadorizada por Raios XRESUMO
Quantification of regional cerebral blood flow (CBF) using [15O]H2O positron emission tomography (PET) requires the use of an arterial input function. Arterial sampling, however, is not always possible, for example in ill-conditioned or paediatric patients. Therefore, it is of interest to explore the use of non-invasive methods for the quantification of CBF. For validation of non-invasive methods, test-retest normal and hypercapnia data from 15 healthy volunteers were used. For each subject, the data consisted of up to five dynamic [15O]H2O brain PET studies of 10 min and including arterial sampling. A measure of CBF was estimated using several non-invasive methods earlier reported in literature. In addition, various parameters were derived from the time-activity curve (TAC). Performance of these methods was assessed by comparison with full kinetic analysis using correlation and agreement analysis. The analysis was repeated with normalization to the whole brain grey matter value, providing relative CBF distributions. A reliable, absolute quantitative estimate of CBF could not be obtained with the reported non-invasive methods. Relative (normalized) CBF was best estimated using the double integration method.
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Circulação Cerebrovascular/fisiologia , Radioisótopos de Oxigênio , Compostos Radiofarmacêuticos , Algoritmos , Artérias Cerebrais/diagnóstico por imagem , Criança , Simulação por Computador , Feminino , Substância Cinzenta/irrigação sanguínea , Substância Cinzenta/diagnóstico por imagem , Humanos , Cinética , Imageamento por Ressonância Magnética , Masculino , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/fisiopatologia , Tomografia por Emissão de Pósitrons , Reprodutibilidade dos Testes , ÁguaRESUMO
OBJECTIVES: Whole body [18F]-fluorodihydrotestosterone positron emission tomography ([18F]FDHT PET) imaging directly targets the androgen receptor and is a promising prognostic and predictive biomarker in metastatic castration-resistant cancer (mCRPC). To optimize [18F]FDHT PET-CT for diagnostic and response assessment purposes, we assessed how count statistics and reconstruction protocol affect its accuracy, repeatability, and lesion detectability. METHODS: Whole body [18F]FDHT PET-CT scans were acquired on an analogue PET-CT on two consecutive days in 14 mCRPC patients harbouring a total of 336 FDHT-avid lesions. Images were acquired at 45 min post-injection of 200 MBq [18F]FDHT at 3 min per bed position. List-mode PET data were split on a count-wise basis, yielding two statistically independent scans with each 50% of counts. Images were reconstructed according to current EANM Research Ltd. (EARL1, 4 mm voxel) and novel EARL2 guidelines (4 mm voxel + PSF). Per lesion, we measured SUVpeak, SUVmax, SUVmean, and contrast-to-noise ratio (CNR). SUV was normalized to dose per bodyweight as well as to the parent plasma input curve integral. Variability was assessed with repeatability coefficients (RCs). RESULTS: Count reduction increased liver coefficient of variation from 9.0 to 12.5% and from 10.8 to 13.2% for EARL1 and EARL2, respectively. SUVs of EARL2 images were 12.0-21.7% higher than EARL1. SUVs of 100% and 50% count data were highly correlated (R2 > 0.98; slope = 0.97-1.01; ICC = 0.99-1.00). Intrascan variability was volume-dependent, and count reduction resulted in higher intrascan variability for EARL2 than EARL1 images. Intrascan RCs were lowest for SUVmean (8.5-10.6%), intermediate for SUVpeak (12.0-16.0%), and highest for SUVmax (17.8-22.2%). Count reduction increased test-retest variance non-significantly (p > 0.05) for all SUV types and normalizations. For SUVpeak at 50% of counts, RCs remained < 30% when small lesions were excluded. Splitting data reduced CNR by median 4.6% (interquartile range 1.2-8.7%) and 4.6% (interquartile range 1.2-8.7%) for EARL1 and EARL2 images, respectively. CONCLUSIONS: Reducing [18F]FDHT PET acquisition time from 3 min to 1.5 per bed position resulted in a repeatability of SUVpeak (bodyweight) remaining ≤ 30%, which is generally acceptable for response monitoring purposes. However, EARL2 reconstruction was more affected, especially for SUVmax whose repeatability tended to exceed 30%. Lesion detectability was only slightly impaired by reducing acquisition time, which might not be clinically relevant in mCRPC.
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PURPOSE: Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images. PROCEDURES: Data were acquired from three previously reported clinical studies with [89Zr]antiCD20 (74 MBq, n = 7), [89Zr]antiEGFR (37 MBq, n = 7), and [89Zr]antiCD44 (37 MBq, n = 13), with imaging obtained 1 to 6 days post injection (D0-D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50 % of the original injected dose (e.g., 37 MBq74inj). Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images. RESULTS: The RC for the combined manually delineated organs for [89Zr] antiCD20 (37 MBq74inj) increased from D0 to D6 and was less than 6 % at all time points. Blood pool and bone marrow had higher RC, up to 43 % for 37 MBq74inj at D6. For tumor, the RC was up to 42 % for [89Zr]antiCD20 (37 MBq74inj). For [89Zr]antiCD20, (18 MBq74inj), [89Zr]antiEGFR (18 MBq37inj), and [89Zr]antiCD44 (18 MBq37inj), measurement variability was independent of the investigated antibody. CONCLUSIONS: Based on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37 MBq) around 6 % for manually delineated organs combined, increasing up to 43 % at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42 %.
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Anticorpos Monoclonais/imunologia , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/química , Zircônio/química , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Reprodutibilidade dos TestesRESUMO
PURPOSE: In longitudinal oncological and brain PET/CT studies, it is important to understand the repeatability of quantitative PET metrics in order to assess change in tracer uptake. The present studies were performed in order to assess precision as function of PET/CT system, reconstruction protocol, analysis method, scan duration (or image noise), and repositioning in the field of view. METHODS: Multiple (repeated) scans have been performed using a NEMA image quality (IQ) phantom and a 3D Hoffman brain phantom filled with 18 F solutions on two systems. Studies were performed with and without randomly (< 2 cm) repositioning the phantom and all scans (12 replicates for IQ phantom and 10 replicates for Hoffman brain phantom) were performed at equal count statistics. For the NEMA IQ phantom, we studied the recovery coefficients (RC) of the maximum (SUVmax ), peak (SUVpeak ), and mean (SUVmean ) uptake in each sphere as a function of experimental conditions (noise level, reconstruction settings, and phantom repositioning). For the 3D Hoffman phantom, the mean activity concentration was determined within several volumes of interest and activity recovery and its precision was studied as function of experimental conditions. RESULTS: The impact of phantom repositioning on RC precision was mainly seen on the Philips Ingenuity PET/CT, especially in the case of smaller spheres (< 17 mm diameter, P < 0.05). This effect was much smaller for the Siemens Biograph system. When exploring SUVmax , SUVpeak , or SUVmean of the spheres in the NEMA IQ phantom, it was observed that precision depended on phantom repositioning, reconstruction algorithm, and scan duration, with SUVmax being most and SUVpeak least sensitive to phantom repositioning. For the brain phantom, regional averaged SUVs were only minimally affected by phantom repositioning (< 2 cm). CONCLUSION: The precision of quantitative PET metrics depends on the combination of reconstruction protocol, data analysis methods and scan duration (scan statistics). Moreover, precision was also affected by phantom repositioning but its impact depended on the data analysis method in combination with the reconstructed voxel size (tissue fraction effect). This study suggests that for oncological PET studies the use of SUVpeak may be preferred over SUVmax because SUVpeak is less sensitive to patient repositioning/tumor sampling.
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Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/instrumentação , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Imagens de FantasmasRESUMO
The objective of this study was to validate several parametric methods for quantification of 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET in advanced-stage non-small cell lung carcinoma (NSCLC) patients with an activating epidermal growth factor receptor mutation who were treated with gefitinib or erlotinib. Furthermore, we evaluated the impact of noise on accuracy and precision of the parametric analyses of dynamic 18F-FLT PET/CT to assess the robustness of these methods. Methods: Ten NSCLC patients underwent dynamic 18F-FLT PET/CT at baseline and 7 and 28 d after the start of treatment. Parametric images were generated using plasma input Logan graphic analysis and 2 basis functions-based methods: a 2-tissue-compartment basis function model (BFM) and spectral analysis (SA). Whole-tumor-averaged parametric pharmacokinetic parameters were compared with those obtained by nonlinear regression of the tumor time-activity curve using a reversible 2-tissue-compartment model with blood volume fraction. In addition, 2 statistically equivalent datasets were generated by countwise splitting the original list-mode data, each containing 50% of the total counts. Both new datasets were reconstructed, and parametric pharmacokinetic parameters were compared between the 2 replicates and the original data. Results: After the settings of each parametric method were optimized, distribution volumes (VT) obtained with Logan graphic analysis, BFM, and SA all correlated well with those derived using nonlinear regression at baseline and during therapy (R2 ≥ 0.94; intraclass correlation coefficient > 0.97). SA-based VT images were most robust to increased noise on a voxel-level (repeatability coefficient, 16% vs. >26%). Yet BFM generated the most accurate K1 values (R2 = 0.94; intraclass correlation coefficient, 0.96). Parametric K1 data showed a larger variability in general; however, no differences were found in robustness between methods (repeatability coefficient, 80%-84%). Conclusion: Both BFM and SA can generate quantitatively accurate parametric 18F-FLT VT images in NSCLC patients before and during therapy. SA was more robust to noise, yet BFM provided more accurate parametric K1 data. We therefore recommend BFM as the preferred parametric method for analysis of dynamic 18F-FLT PET/CT studies; however, SA can also be used.
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Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Didesoxinucleosídeos/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Idoso , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/terapia , Simulação por Computador , Fator de Crescimento Epidérmico/genética , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Mutação/genética , Prognóstico , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Dexamphetamine (dAMPH) is a stimulant drug that is widely used recreationally as well as for the treatment of attention-deficit hyperactivity disorder (ADHD). Although animal studies have shown neurotoxic effects of dAMPH on the dopaminergic system, little is known about such effects on the human brain. Here, we studied the dopaminergic system at multiple physiological levels in recreational dAMPH users and age, gender, and IQ-matched dAMPH-naïve healthy controls. We assessed baseline D2/3 receptor availability, in addition to changes in dopamine (DA) release using single-photon emission computed tomography and DA functionality using pharmacological magnetic resonance imaging, following a dAMPH challenge. Also, the subjective responses to the challenge were determined. dAMPH users displayed significantly lower striatal DA D2/3 receptor binding compared with healthy controls. In dAMPH users, we further observed a blunted DA release and DA functionality to an acute dAMPH challenge, as well as a blunted subjective response. Finally, the lower D2/3 availability, the more pleasant the dAMPH administration was experienced by control subjects, but not by dAMPH users. Thus, in agreement with preclinical studies, we show that the recreational use of dAMPH in human subjects is associated with dopaminergic system dysfunction. These findings warrant further (longitudinal) investigations and call for caution when using this drug recreationally and for ADHD.
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Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Dextroanfetamina/farmacologia , Dopamina/metabolismo , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Humanos , Drogas Ilícitas/farmacologia , Imageamento por Ressonância Magnética , Masculino , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
In the last decade spatially nonselective arterial spin labeling (SNS-ASL) methods such as velocity-selective ASL (VS-ASL) and acceleration-selective ASL have been introduced, which label spins based on their flow velocity or acceleration rather than spatial localization. Since labeling also occurs within the imaging plane, these methods suffer less from transit delay effects than traditional ASL methods. However, there is a need for validation of these techniques. In this study, a comparison was made between these SNS-ASL techniques with [(15)O]H2O positron emission tomography (PET), which is regarded as gold standard to measure quantitatively cerebral blood flow (CBF) in humans. In addition, the question of whether these techniques suffered from sensitivity to arterial cerebral blood volume (aCBV), as opposed to producing pure CBF contrast, was investigated. The results show high voxelwise intracranial correlation (0.72 to 0.89) between the spatial distribution of the perfusion signal from the SNS-ASL methods and the PET CBF maps. A similar gray matter (GM) CBF was measured by dual VS-ASL compared with PET (46.7 ± 4.1 versus 47.1 ± 6.5 mL/100 g/min, respectively). Finally, only minor contribution of aCBV patterns in GM to all SNS-ASL methods was found compared with pseudo-continuous ASL. In conclusion, VS-ASL provides a similar quantitative CBF, and all SNS-ASL methods provide qualitatively similar CBF maps as [(15)O]H2O PET.
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Angiografia Cerebral/métodos , Artérias Cerebrais/diagnóstico por imagem , Circulação Cerebrovascular , Tomografia por Emissão de Pósitrons/métodos , Marcadores de Spin , Velocidade do Fluxo Sanguíneo , Artérias Cerebrais/fisiopatologia , Isótopos de Oxigênio/administração & dosagemRESUMO
IMPORTANCE: An increased risk for psychosis is observed in people with hearing impairment. According to the social defeat hypothesis, the long-term experience of exclusion leads to enhanced baseline activity and/or sensitization of the dopamine system and puts the individual at increased risk for psychosis. OBJECTIVE: To investigate whether young adults with severe hearing impairment (SHI) experience more feelings of social defeat, show greater dopamine release in response to dexamphetamine, and report a stronger subjective reaction to this substance than normal-hearing young adults and to examine whether dopamine release is associated with both self-reported social exclusion and dexamphetamine-induced psychotic experiences. DESIGN, SETTING, AND PARTICIPANTS: A sample of 19 participants with SHI and 19 smoking-, age-, and sex-matched healthy controls underwent single-photon emission computed tomography with iodine 123-labeled iodobenzamide as a radiotracer before and after an amphetamine challenge at an academic hospital. EXPOSURES: Dexamphetamine sulfate (0.3 mg/kg) administered intravenously. MAIN OUTCOMES AND MEASURES: Baseline D2/3 receptor binding and endogenous dopamine release. RESULTS: The participants with SHI reported experiencing more feelings of social defeat (U=109, z=-2.09, P=.04) and loneliness (U=87.5, z=-2.72, P=<.001) than did healthy controls, but they did not differ from healthy controls with regard to baseline psychotic symptoms (U=156.5, z=-0.70, P=.48). There were no significant group differences in baseline D2/3 receptor binding. However, repeated-measures multivariate analysis of covariance with age (in months) and tobacco smoking (in pack-years) as covariates showed that there was a greater amphetamine-induced striatal dopamine release among the participants with SHI than among the healthy controls (F1,34=4.55, P=.04). After amphetamine administration, the participants with SHI reported more changes in affect than the healthy controls, but not a greater increase in psychotic symptoms. Likewise, reports of social exclusion and an increase in psychotic symptoms were not associated with dopamine release. CONCLUSIONS AND RELEVANCE: Our study presents preliminary evidence of dopamine sensitization in a socially excluded group of people with hearing impairment. If replicated by future studies in other excluded groups, this finding may have major implications for our understanding of the underlying mechanism and for prevention of psychotic disorders.
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Sensibilização do Sistema Nervoso Central , Corpo Estriado/metabolismo , Dopamina/metabolismo , Perda Auditiva/metabolismo , Distância Psicológica , Esquizofrenia/metabolismo , Psicologia do Esquizofrênico , Adulto , Anfetamina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Feminino , Neuroimagem Funcional , Perda Auditiva/complicações , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidrocortisona/metabolismo , Iodobenzenos , Masculino , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Saliva/metabolismo , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Avaliação de Sintomas , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
INTRODUCTION: White matter (WM) perfusion measurements with arterial spin labeling can be severely contaminated by gray matter (GM) perfusion signal, especially in the elderly. The current study investigates the spatial extent of GM contamination by comparing perfusion signal measured in the WM with signal measured outside the brain. MATERIAL AND METHODS: Four minute 3T pseudo-continuous arterial spin labeling scans were performed in 41 elderly subjects with cognitive impairment. Outward and inward geodesic distance maps were created, based on dilations and erosions of GM and WM masks. For all outward and inward geodesic distances, the mean CBF was calculated and compared. RESULTS: GM contamination was mainly found in the first 3 subcortical WM voxels and had only minor influence on the deep WM signal (distances 4 to 7 voxels). Perfusion signal in the WM was significantly higher than perfusion signal outside the brain, indicating the presence of WM signal. CONCLUSION: These findings indicate that WM perfusion signal can be measured unaffected by GM contamination in elderly patients with cognitive impairment. GM contamination can be avoided by the erosion of WM masks, removing subcortical WM voxels from the analysis. These results should be taken into account when exploring the use of WM perfusion as micro-vascular biomarker.
Assuntos
Circulação Cerebrovascular/fisiologia , Demência/diagnóstico , Substância Cinzenta/irrigação sanguínea , Marcadores de Spin , Substância Branca/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Feminino , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Entrevista Psiquiátrica Padronizada , Fluxo Pulsátil/fisiologia , Substância Branca/patologiaRESUMO
PURPOSE: Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. MATERIAL AND METHODS: 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. RESULTS: Whereas the mean GM CBF of both vendors was almost equal (pâ=â1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (pâ=â0.3 and pâ=â0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. CONCLUSION: These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors.