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INTRODUCTION: Studies of cognitive functioning in patients with attention-deficit/hyperactivity disorder (ADHD) have often used healthy comparison groups. The present study examines cognitive profiles, including general intellectual and executive functions, in a young adult psychiatric outpatient clientele with ADHD and evaluates whether their cognitive profiles can help differentiate them from patients with non-ADHD-associated psychiatric disorders. METHODS: The study group comprised 141 young adult psychiatric patients (age range 18-25 years) of whom 78 had ADHD. Comprehensive neuropsychological assessment included the Wechsler Adult Intelligence Scale, 4th version and subtests from Delis-Kaplan Executive Function System. Clinical psychiatric assessments and diagnostic evaluation were performed. RESULTS: The ADHD group (including all subtypes) had significantly lower verbal comprehension and full-scale intelligence quotient than the non-ADHD group. Tests measuring working memory or executive function did not separate those with and without ADHD. CONCLUSION: The results of our study suggest that, except for the need to establish overall cognitive performance level, the clinical implication of testing is small if the purpose is to "rule out" an ADHD diagnosis.
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Transtorno do Deficit de Atenção com Hiperatividade , Função Executiva , Testes Neuropsicológicos , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Masculino , Feminino , Adulto , Adolescente , Adulto Jovem , Função Executiva/fisiologia , Cognição/fisiologia , Memória de Curto Prazo/fisiologia , Inteligência/fisiologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/diagnósticoRESUMO
PURPOSE: T 2 $$ {}_2 $$ -weighted turbo-spin-echo (TSE) sequences are a fundamental technique in brain imaging but suffer from field inhomogeneities at ultra-high fields. Several methods have been proposed to mitigate the problem, but were limited so far to nonselective three-dimensional (3D) measurements, making short acquisitions difficult to achieve when targeting very high resolution images, or needed additional calibration procedures, thus complicating their application. METHODS: Slab-selective excitation pulses were designed for flexible placement utilizing the concept of k T $$ {}_T $$ -spokes. Phase-coherent refocusing universal pulses were subsequently optimized with the Gradient Ascent Pulse Engineering algorithm and tested in vivo for improved signal homogeneity. RESULTS: Implemented within a 3D variable flip angle TSE sequence, these pulses led to a signal-to-noise ratio (SNR) improvement ranging from 10% to 30% compared to a two-dimensional (2D) T2w TSE sequence employing B 1 + $$ {\mathrm{B}}_1^{+} $$ -shimmed pulses. B 1 + $$ {\mathrm{B}}_1^{+} $$ field inhomogeneities could be mitigated and artifacts from B 0 $$ {\mathrm{B}}_0 $$ deviations reduced. The concept of universal pulses was successfully applied. CONCLUSION: We present a pulse design method which provides a set of calibration-free universal pulses (UPs) for slab-selective excitation and phase-coherent refocusing in slab-selective TSE sequences.
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Algoritmos , Encéfalo , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Razão Sinal-Ruído , Humanos , Encéfalo/diagnóstico por imagem , Calibragem , Imagens de Fantasmas , Ondas de Rádio , Processamento de Imagem Assistida por Computador/métodosRESUMO
PURPOSE: We present a time-efficient water-selective, parallel transmit RF excitation pulse design for ultra-high field applications. METHODS: The proposed pulse design method achieves flip angle homogenization at ultra-high fields by employing spatially nonselective k T $$ {\mathrm{k}}_T $$ -points pulses. In order to introduce water-selection, the concept of binomial pulses is applied. Due to the composite nature of k T $$ {\mathrm{k}}_T $$ -points, the pulse can be split into multiple binomial subpulse blocks shorter than half the precession period of fat, that are played out successively. Additional fat precession turns, that would otherwise impair the spectral response, can thus be avoided. Bloch simulations of the proposed interleaved binomial k T $$ {\mathrm{k}}_T $$ -points pulses were carried out and compared in terms of duration, homogeneity, fat suppression and pulse energy. For validation, in vivo MP-RAGE and 3D-EPI data were acquired. RESULTS: Simulation results show that interleaved binomial k T $$ {\mathrm{k}}_T $$ -points pulses achieve shorter total pulse durations, improved flip angle homogeneity and more robust fat suppression compared to available methods. Interleaved binomial k T $$ {\mathrm{k}}_T $$ -points can be customized by changing the number of k T $$ {\mathrm{k}}_T $$ -points, the subpulse duration and the order of the binomial pulse. Using shorter subpulses, the number of k T $$ {\mathrm{k}}_T $$ -points can be increased and hence better homogeneity is achieved, while still maintaining short total pulse durations. Flip angle homogenization and fat suppression of interleaved binomial k T $$ {\mathrm{k}}_T $$ -points pulses is demonstrated in vivo at 7T, confirming Bloch simulation results. CONCLUSION: In this work, we present a time efficient and robust parallel transmission technique for nonselective water excitation with simultaneous flip angle homogenization at ultra-high field.
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Processamento de Imagem Assistida por Computador , Água , Algoritmos , Encéfalo , Simulação por Computador , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Imagens de FantasmasRESUMO
OBJECTIVES: GABA is the most important inhibitory neurotransmitter. Thus, variation in its concentration is connected to a wide variety of diseases. However, the low concentration and the overlap of more prominent resonances hamper GABA quantification using MR spectroscopy. The hippocampus plays a pivotal role in neurodegeneration. Susceptibility discontinuities in the vicinity of the hippocampus cause strong B0 inhomogeneities, impeding GABA spectroscopy. The aim of this work is to improve the reproducibility of hippocampal GABA+ MRS. METHODS: The GABA+/total creatine ratio in the hippocampus was measured using a MEGA-sLASER sequence at 7 Tesla. 10 young healthy volunteers participated in the study. A dedicated pre-processing approach was established. Spectral quantification was performed with Tarquin. The quantification parameters were carefully adjusted to ensure optimal quantification. RESULTS: An inter-subject coefficient of variation of the GABA+/total creatine of below 15% was achieved. Additional to spectral registration, which is essential to obtain reproducible GABA measures, eddy current compensation and additional difference artifact suppression improved the reproducibility. The mean FWHM was 23.1 Hz (0.078 ppm). CONCLUSION: The increased spectral dispersion of ultra-high-field spectroscopy allows for reproducible spectral quantification, despite a very broad line width. The achieved reproducibility enables the routine use of hippocampal GABA spectroscopy at 7 Tesla.
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Hipocampo , Adulto , Encéfalo , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Reprodutibilidade dos Testes , Adulto Jovem , Ácido gama-AminobutíricoRESUMO
INTRODUCTION: During descent in freediving there is exposure to rapidly increasing pressure. Inability to quickly equalise middle ear pressure may cause trauma to the ear. This study aimed to evaluate the occurrence of pressure-related damage to the middle ear and the Eustachian tube during freediving and to identify possible risk factors. METHODS: Sixteen free divers performed diving sessions in an indoor pool 20 metres' freshwater (mfw) deep. During each session, each diver performed four own free dives and up to four safety dives. Naso- and oto-endoscopy and Eustachian tube function tests were performed on the right and left ears before diving, between each session and after the last session. The otoscopic findings were classified according to the Teed classification (0 = normal tympanic membrane to 4 = perforation). Additionally, ENT-related complaints were assessed using a questionnaire. RESULTS: Participants performed 317 dives (on average 20 dives per diver, six per session). The average depth was 13.3 mfw. Pressure-related changes (Teed 1 and 2) were detected in 48 % of ears. Teed level increased significantly with an increasing number of completed sessions (P < 0.0001). Higher pressure-related damage (Teed 2) occurred in less experienced divers, was associated with significantly lower peak pressures in the middle ear and led to more ear-related symptoms. A preference for the Frenzel technique for middle ear pressure equalisation during freediving was shown. CONCLUSIONS: Pressure exposure during freediving had a cumulative effect on the middle ear. Factors such as diving depth, diving experience and number of diving sessions correlated with the occurrence of higher Teed levels.
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Barotrauma , Mergulho , Tuba Auditiva , Barotrauma/etiologia , Orelha Média , Humanos , OtoscopiaRESUMO
PURPOSE: Demonstration of a 3D version of the DREAM sequence (3DREAM) for rapid 3D flip angle and B1+ mapping of the human brain. METHODS: A rectangular non-selective STE preparation is followed by a 3D readout with a Cartesian center-out spiral phase encoding order. This enables parallel imaging acceleration in both phase encoding dimensions as well as early capture of the prepared magnetization. RESULTS: B1+ mapping of the whole human head is demonstrated on a 7T system at a nominal resolution of 5 mm with and without parallel imaging acceleration. Artifacts caused by the different signal decay of the FID and STE signal during the long imaging train is suppressed by appropriate filtering of the FID image. Remaining blurring can be controlled by adjusting the echo train length and readout flip angle. CONCLUSIONS: 3DREAM provides a whole-brain flip angle map in a few seconds or individual maps for an 8-channel array in about a minute.
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Encéfalo/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Artefatos , Cabeça/diagnóstico por imagem , Humanos , Imagens de FantasmasRESUMO
PURPOSE: The fluid attenuated inversion recovery sequence is a pillar technique to detect brain lesions in MRI. At ultrahigh field, the lengthening of T1 often advocates a T2 -weighting preparation module to regain signal and contrast between tissues, which can be affected by transmit RF field inhomogeneity. In this note, we report an extension of a previous fluid attenuated inversion recovery study that now incorporates the T2 preparation with parallel transmission calibration-free universal pulses to mitigate the problem. METHODS: The preparation consisted of a 90°-τ-180° -τ-90° module to implement an effective inversion in the CSF and a saturation in the brain tissues. Care was taken for the pulses to have the desired phase relationship in every voxel by appropriate pulse design. The RF pulse design made use of the kT -point parametrization and was based on a database of 20 B1+ and ΔB0 maps previously acquired on different subjects at 7 T. Simulations and experiments on 5 volunteers, not contained in the database, were performed for validation. RESULTS: Simulations reported very good inversion efficiency for the preparation module with 8% variation, with respectively 4 and 6 times less power and specific absorption rate than for the adiabatic version. Experiments revealed fluid attenuated inversion recovery images free of B1+ artifacts. CONCLUSION: This work contributes further to the panel of 3D sequences validated and now available with universal pulses at 7 T. The drop in power and specific absorption rate demand compared with adiabatic pulses in the T2 preparation leads to more freedom for the design of the readout train.
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Encefalopatias/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Esclerose Múltipla/diagnóstico por imagem , Algoritmos , Artefatos , Calibragem , Líquido Cefalorraquidiano , Simulação por Computador , Voluntários Saudáveis , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Esclerose Múltipla/líquido cefalorraquidiano , Imagens de Fantasmas , Razão Sinal-RuídoRESUMO
PURPOSE: To investigate the impact of accelerated, single-shot 3D-GRASE acquisition on quantitative arterial spin labeling (ASL) with multiple and single post-labeling delay (PLD) in terms of perfusion-weighted SNR per unit scan time (TSNRPW ) and quantification accuracy. METHODS: Five subjects were scanned on a 3T MRI scanner using the pseudo-continuous arterial spin labeling (PCASL) technique with a 3D-GRASE imaging sequence capable of parallel imaging acceleration. A 3-inversion pulse background suppression was simulated and implemented in the sequence. Three time-matched single PLD measurements, a segmented one without acceleration, 1 with conventional GRAPPA, and 1 with CAIPIRINHA sampling, were used to compare TSNRPW . Three time-matched multiple PLD measurements with the identical imaging parameters were additionally evaluated (no acceleration vs. CAIPIRINHA sampling vs. CAIPIRINHA sampling with doubled number of PLDs). Cerebral blood flow and arterial transit time fit uncertainties were compared and used as a quality measure. RESULTS: The single PLD measurements show an 11% TSNRPW increase using CAIPIRINHA sampling instead of GRAPPA sampling, while the non-accelerated scan exhibits 35% higher TSNRPW compared to the GRAPPA scan. However, taking advantage of the increased number of averages for multiple PLD acquisitions, a 14%/16% (gray matter) and 34%/36% (white matter) reduction of CBF fit uncertainty is observed with CAIPIRINHA sampling (6 PLDs/12 PLDs) compared to no acceleration. CONCLUSION: Accelerated single-shot 3D-GRASE with PCASL allows for smaller quantification uncertainties than time-matched segmented acquisitions. Corresponding single-shot acquisitions with acceptable blurring and no intra-volume motion render state-of-the-art ASL methods in a clinically feasible time possible.
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Artérias/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Marcadores de Spin , Adulto , Teorema de Bayes , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Calibragem , Circulação Cerebrovascular , Simulação por Computador , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Movimento (Física) , Perfusão , Reprodutibilidade dos Testes , Razão Sinal-RuídoRESUMO
PURPOSE: The aim of this project was to develop a GRAPPA-based reconstruction for wave-CAIPI data. Wave-CAIPI fully exploits the 3D coil sensitivity variations by combining corkscrew k-space trajectories with CAIPIRINHA sampling. It reduces artifacts and limits reconstruction induced spatially varying noise enhancement. The GRAPPA-based wave-CAIPI method is robust and does not depend on the accuracy of coil sensitivity estimations. METHODS: We developed a GRAPPA-based, noniterative wave-CAIPI reconstruction algorithm utilizing multiple GRAPPA kernels. For data acquisition, we implemented a fast 3D magnetization-prepared rapid gradient-echo wave-CAIPI sequence tailored for ultra-high field application. The imaging results were evaluated by comparing the g-factor and the root mean square error to Cartesian CAIPIRINHA acquisitions. Additionally, to assess the performance of subcortical segmentations (calculated by FreeSurfer), the data were analyzed across five subjects. RESULTS: Sixteen-fold accelerated whole brain magnetization-prepared rapid gradient-echo data (1 mm isotropic resolution) were acquired in 40 seconds at 7T. A clear improvement in image quality compared to Cartesian CAIPIRINHA sampling was observed. For the chosen imaging protocol, the results of 16-fold accelerated wave-CAIPI acquisitions were comparable to results of 12-fold accelerated Cartesian CAIPIRINHA. In comparison to the originally proposed SENSitivity Encoding reconstruction of Wave-CAIPI data, the GRAPPA approach provided similar image quality. CONCLUSION: High-quality, wave-CAIPI magnetization-prepared rapid gradient-echo images can be reconstructed by means of a GRAPPA-based reconstruction algorithm. Even for high acceleration factors, the noniterative reconstruction is robust and does not require coil sensitivity estimations. By altering the aliasing pattern, ultra-fast whole-brain structural imaging becomes feasible.
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Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Neuroimagem/métodos , Algoritmos , Artefatos , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , SoftwareRESUMO
PURPOSE: The aim of this project was to implement an ultra-high field (UHF) optimized double inversion recovery (DIR) sequence for gray matter (GM) imaging, enabling whole brain coverage in short acquisition times ( ≈5 min, image resolution 1 mm3 ). METHODS: A 3D variable flip angle DIR turbo spin echo (TSE) sequence was optimized for UHF application. We implemented an improved, fast, and specific absorption rate (SAR) efficient TSE imaging module, utilizing improved reordering. The DIR preparation was tailored to UHF application. Additionally, fat artifacts were minimized by employing water excitation instead of fat saturation. RESULTS: GM images, covering the whole brain, were acquired in 7 min scan time at 1 mm isotropic resolution. SAR issues were overcome by using a dedicated flip angle calculation considering SAR and SNR efficiency. Furthermore, UHF related artifacts were minimized. CONCLUSION: The suggested sequence is suitable to generate GM images with whole-brain coverage at UHF. Due to the short total acquisition times and overall robustness, this approach can potentially enable DIR application in a routine setting and enhance lesion detection in neurological diseases. Magn Reson Med 79:2620-2628, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
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Encéfalo/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Artefatos , Humanos , Interpretação de Imagem Assistida por Computador/métodosRESUMO
INTRODUCTION: We investigated the effect of repetitive pressure exposure during freshwater dives on Eustachian tube function and the middle ear, assessed by the Eustachian tube function test (ETFT). METHODS: This prospective observational cohort study included 23 divers over three consecutive days of diving in freshwater lakes in Nordhausen, Germany. Participants underwent otoscopy and ETFT before the first dive, between each dive and after the last dive. ETFT included regular tympanometry (R-tymp), tympanometry after Valsalva (V-tymp) and after swallowing (S-tymp). The peak pressure difference between the R-tymp and the V-tymp (R-VdP) defined effectiveness of pressure equalization after Valsalva manoeuvres. We evaluated the change in compliance and peak pressure and correlated the results to the otoscopic findings and diving experience. RESULTS: Twenty-three divers performed 144 dives. Middle ear barotrauma was assessed using the Edmonds modification of the TEED scoring system. In the ETFT, the R-tymp peak pressure displayed a negative shift from day one to three (P = 0.001) and differed significantly between the experience groups (P = 0.01). R-VdP did not change significantly on any of the three days of diving (all P > 0.05). Participants without MEBt showed significantly lower R-tymp values than did those with barotrauma (P = 0.019). CONCLUSION: Repetitive pressure exposure during three consecutive days of freshwater diving led to a negative shift of the peak pressure in the middle ear. Less experienced divers showed significantly higher middle ear peak pressure and higher pressure differences after equalization manoeuvres. Higher middle ear peak pressure was also associated with a higher prevalence of barotrauma.
Assuntos
Testes de Impedância Acústica/métodos , Mergulho/fisiologia , Tuba Auditiva/fisiologia , Água Doce , Adulto , Complacência (Medida de Distensibilidade) , Mergulho/estatística & dados numéricos , Orelha Média/fisiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Otoscopia , Pressão , Estudos Prospectivos , Recreação , Fatores de Tempo , Manobra de Valsalva/fisiologiaRESUMO
INTRODUCTION: We investigated in a prospective, observational trial the feasibility of using the Eustachian tube function test (ETFT) to measure the effect of repetitive pressure exposure during open seawater dives on Eustachian tube function. METHODS: The study included 28 adult divers during six consecutive days of diving in the Red Sea. Participants underwent otoscopy and ETFT before the first dive, between each dive and after the last dive. ETFT included regular tympanometry (R-tymp), tympanometry after Valsalva (V-tymp) and after swallowing (S-tymp). The R-tymp was obtained as 'baseline' peak pressure. After a Valsalva, the peak pressure should shift (positively), revealing a positive shift of the tympanic membrane. This pressure shift is defined here as R-VdP. The changes in compliance and peak pressure were recorded and correlated with otoscopic findings and diving experience. Middle ear barotrauma was scored using the Edmonds modified TEED scale. RESULTS: The 28 participants performed 437 dives. Positive shift of pressure in the middle ear was evident with significant changes from day one to day three (P < 0.0001). Divers with barotrauma showed significantly lower values of R-tymp peak pressure and significantly higher negative R-VdP, compared to divers with normal otoscopic findings (P < 0.05). Diving experience significantly correlated with R-tymp peak pressure and prevalence of middle ear barotrauma. CONCLUSION: Significant changes in middle ear pressure and pressure equalization from repeated pressure exposure in saltwater were seen using ETFT. Repetitive, multi-day diving led to significantly decreased compliance and increased R-tymp peak pressure (overpressure) in the middle ear. Most profound changes were observed in less and intermediate experienced divers.
Assuntos
Testes de Impedância Acústica/métodos , Mergulho/fisiologia , Tuba Auditiva/fisiologia , Água do Mar , Adulto , Barotrauma/fisiopatologia , Deglutição , Mergulho/estatística & dados numéricos , Orelha Média/fisiologia , Estudos de Viabilidade , Feminino , Humanos , Oceano Índico , Masculino , Otoscopia , Pressão , Estudos Prospectivos , Recreação , Fatores de Tempo , Manobra de Valsalva/fisiologiaRESUMO
While widely in use in automated segmentation approaches for the detection of group differences or of changes associated with continuous predictors in gray matter volume, T1-weighted images are known to represent dura and cortical vessels with signal intensities similar to those of gray matter. By considering multiple signal sources at once, multimodal segmentation approaches may be able to resolve these different tissue classes and address this potential confound. We explored here the simultaneous use of FLAIR and apparent transverse relaxation rates (a signal related to [Formula: see text] relaxation maps and having similar contrast) with T1-weighted images. Relative to T1-weighted images alone, multimodal segmentation had marked positive effects on 1. the separation of gray matter from dura, 2. the exclusion of vessels from the gray matter compartment, and 3. the contrast with extracerebral connective tissue. While obtainable together with the T1-weighted images without increasing scanning times, apparent transverse relaxation rates were less effective than added FLAIR images in providing the above mentioned advantages. FLAIR images also improved the detection of cortical matter in areas prone to susceptibility artifacts in standard MPRAGE T1-weighted images, while the addition of transverse relaxation maps exacerbated the effect of these artifacts on segmentation. Our results confirm that standard MPRAGE segmentation may overestimate gray matter volume by wrongly assigning vessels and dura to this compartment and show that multimodal approaches may greatly improve the specificity of cortical segmentation. Since multimodal segmentation is easily implemented, these benefits are immediately available to studies focusing on translational applications of structural imaging.
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The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.
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Atlas como Assunto , Neoplasias/sangue , Bases de Dados Factuais , HumanosRESUMO
OBJECT: Implementation of an accelerated Magnetization Prepared RApid Gradient Echo (MP-RAGE) sequence for T1 weighted neuroimaging; exploiting modern MRI technologies to minimize scan time while preserving the image quality. MATERIALS AND METHODS: A custom MP-RAGE sequence was implemented on a state-of-the-art 3T MR scanner equipped with a 32-channel receiver array head coil. The sequence utilized a shifted CAIPIRINHA k y -k z under-sampling pattern combined with elliptical scanning and a two-dimensional view ordering scheme to achieve high parallel imaging acceleration factors at maintained image contrast. RESULTS: It could be shown that MP-RAGE accelerated in two k-space directions outperforms single direction acceleration, which is the common practice with standard view ordering. Applying the CAIPIRINHA technique in conjunction with elliptical scanning further increased this benefit. CONCLUSION: By combining MP-RAGE with CAIPIRINHA sampling and elliptical scanning, the scan time can be reduced from 4-5 min to 2-3 min with insignificant reduction in image quality.
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Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Artefatos , Humanos , Imageamento por Ressonância Magnética/instrumentação , Razão Sinal-Ruído , Fatores de TempoRESUMO
In vivo (19)F MRI allows quantitative cell tracking without the use of ionizing radiation. It is a noninvasive technique that can be applied to humans. Here, we describe a general protocol for cell labeling, imaging, and image processing. The technique is applicable to various cell types and animal models, although here we focus on a typical mouse model for tracking murine immune cells. The most important issues for cell labeling are described, as these are relevant to all models. Similarly, key imaging parameters are listed, although the details will vary depending on the MRI system and the individual setup. Finally, we include an image processing protocol for quantification. Variations for this, and other parts of the protocol, are assessed in the Discussion section. Based on the detailed procedure described here, the user will need to adapt the protocol for each specific cell type, cell label, animal model, and imaging setup. Note that the protocol can also be adapted for human use, as long as clinical restrictions are met.
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Rastreamento de Células/métodos , Imageamento por Ressonância Magnética/métodos , Animais , Flúor/química , Processamento de Imagem Assistida por Computador/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , CamundongosRESUMO
The pharmacological induction of apoptosis in neoplastic B cells presents a promising therapeutic avenue for the treatment of chronic lymphocytic leukemia (CLL). We profiled a panel of clinical multi-kinase inhibitors for their ability to induce apoptosis in primary CLL cells. Whereas inhibitors targeting a large number of receptor and intracellular tyrosine kinases including c-KIT, FLT3, BTK and SYK were comparatively inactive, the CDK inhibitors BMS-387032 and flavopiridol showed marked efficacy similar to staurosporine. Using the kinobeads proteomics method, kinase expression profiles and binding profiles of the inhibitors to target protein complexes were quantitatively monitored in CLL cells. The targets most potently affected were CDK9, cyclin T1, AFF3/4 and MLLT1, which may represent four subunits of a deregulated positive transcriptional elongation factor (p-TEFb) complex. Albeit with lower potency, both drugs also bound the basal transcription factor BTF2/TFIIH containing CDK7. Staurosporine and geldanamycin do not affect these targets and thus seem to exhibit a different mechanism of action. The data support a critical role of p-TEFb inhibitors in CLL that supports their future clinical development.
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Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteômica , Apoptose/efeitos dos fármacos , Flavonoides/uso terapêutico , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Oxazóis/uso terapêutico , Piperidinas/uso terapêutico , Fator B de Elongação Transcricional Positiva/antagonistas & inibidores , Tiazóis/uso terapêuticoRESUMO
There is a need for predictive biomarkers that identify non-small-cell lung cancer (NSCLC) patients most likely to respond to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. There are numerous potential candidates, although none has been proven in prospective clinical trials. The EGFR gene copy number evaluated by fluorescence in situ hybridisation (FISH) has been highlighted as one of the most effective markers for sensitivity to EGFR TKIs in large phase III, randomised placebo-controlled trials and has been used in clinical settings to assist physicians in defining the therapeutic regimen. The EGFR FISH assay has technical challenges and it is critical that detailed guidelines are provided to help clinical laboratories in performing and interpreting the test. Excellent assay reproducibility and portability rates among laboratories are crucial to guarantee that accurate clinical decisions can be made for patients with NSCLC. This article discusses the consensus outcomes of a global workshop convened to discuss key technical issues and standardise reading strategies for the EGFR FISH assay of NSCLC tumour tissue.
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Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Receptores ErbB/metabolismo , Neoplasias Pulmonares/diagnóstico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Receptores ErbB/antagonistas & inibidores , Humanos , Hibridização in Situ Fluorescente/métodos , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Neoplasias/metabolismo , Guias de Prática Clínica como Assunto , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Respiratory motion and pulsatile blood flow can generate artifacts in morphological and functional lung imaging. Total acquisition time, and thus the achievable signal to noise ratio, is limited when performing breath-hold and/or electrocardiogram-triggered imaging. To overcome these limitations, imaging during free respiration can be performed using respiratory gating/triggering devices or navigator echoes. However, these techniques provide only poor gating resolution and can induce saturation bands and signal fluctuations into the lung volume. In this work, acquisition schemes for nonphase encoded navigator echoes were implemented into different sequences for morphological and functional lung imaging at 1.5 Tesla (T) and 0.2T. The navigator echoes allow monitoring of respiratory motion and provide an ECG-trigger signal for correction of the heart cycle without influencing the imaged slices. Artifact free images acquired during free respiration using a 3D GE, 2D multislice TSE or multi-Gradient Echo sequence for oxygen-enhanced T(2)(*) quantification are presented.
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Artefatos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Pulmão/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Mecânica Respiratória , Técnicas de Imagem de Sincronização Respiratória/métodos , Algoritmos , Humanos , Imageamento Tridimensional/métodos , Movimento (Física) , Reconhecimento Automatizado de Padrão/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To develop a magnetization transfer (MT) module in conjunction with a single-shot MRI readout technique and to investigate the MT phenomenon in non-small-cell lung cancer (NSCLC) as an adjunct for radiation therapy planning. MATERIALS AND METHODS: A total of 10 patients with inoperable NSCLC were investigated using a 1.5T MR scanner. MT ratio (MTR) maps of several slices throughout the tumor were assessed. Each MTR-map was acquired within a short breathhold. Fluorodeoxyglucose positron emission tomography (FDG-PET) investigations were performed in addition to the MRI protocol. A total of 60 structures appearing conspicuous in FDG-PET were compared with structures appearing conspicuous in corresponding MTR maps. Quantification of similarity between both modalities was performed using similarity index calculation. RESULTS: MTR-maps showed different contrast than FDG-PET images. However, structures that appeared conspicuous in FDG-PET images, either by a marked signal enhancement or signal decrease, were found to be similarly present in MTR maps. A mean similarity index of 0.65 was calculated. MTR values of suspected atelectasis were on average lower than MTR values of tumor tissue. CONCLUSION: The proposed MT-MRI technique provides a high MT efficiency, while being robust and fast enough for breathhold acquisition. The results obtained encourage for further exploration of MT-MRI as an adjunct for radiotherapy planning in NSCLC.