Noninvasive Assessment of Neurodevelopmental Disorders after In Utero Irradiation in Mice: An In Vivo Anatomical and Diffusion MRI Study.

In utero exposure to ionizing radiation can lead to cerebral alterations during adulthood. Using anatomical magnetic resonance imaging (MRI), it is possible to assess radiation-induced structural brain damage noninvasively. However, little is currently known about microstructure alterations in brain tissue. Therefore, the goal of this study was to establish, based on an original and robust pipeline of MRI image analysis, whether the long-term effects of in utero radiation exposure on brain tissue microstructure could be detected noninvasively. Pregnant C57BL/6N mice received a single dose of 1 Gy on gestation day 14.5, which led to behavioral impairments in adults. At 3 months old, in vivo MRI data were acquired from in utero irradiated and nonirradiated male mice. An MRI protocol was designed to assess the effects of radiation on the parameters of brain volume, non-Gaussian diffusion (ADC0, kurtosis and signature index) and anisotropic diffusion (fractional anisotropy and mean, axial, radial diffusivities and anisotropic signature index) in 10 key cerebral structures defined using an in-house atlas of the mouse brain. Based on the relative amplitude of these anatomical and microstructural changes, maps of the radiosensitivity of the brain to in utero irradiation were created. We observed microcephaly in irradiated mice with noticeably larger volume changes in the cortex and the corpus callosum. We also observed significantly lower ADC0, anisotropy fraction (sFA), radial diffusivity (sRD), as well as signature index (S-index and SI3) values, which are original markers sensitive to tissue microstructure alterations. All these changes together are in favor of a decreased cellular "imprint" and in some regions a reduced density in myelinated axons. A reduction in the number and complexity of myelinated axons was further revealed by myelin basic protein immunostaining. Combining anatomical and diffusion MRI is a promising approach to noninvasively investigate the radiosensitivity of local brain areas in adult mice after in utero irradiation in terms of microstructure.

Resultados imediatos e a curto prazo do tratamento percutâneo do vazamento para protético / Immediate and short-term results of percutaneous leak treatment for prosthetic

INTRODUÇÃO: A regurgitação paraprotética (RPP) é um defeito que ocorre entre o local de sutura e o anel protético. A correção por transcateter tem surgido como uma opção à cirurgia para pacientes (pts) de alto risco. OBJETIVO: Avaliar os resultados imediatos e a curto prazo da oclusão da RPP por meio de cateter. MÉTODOS: Trata-se de um estudo prospectivo, de portadores de RPP, sintomáticos, submetidos a oclusão percutânea. O diagnóstico da RPP foi feito por meio da Doppler ecocardiografia TT e TE 3-D. O Critério de sucesso era: regurgitação residual discreta, melhora da classe funcional, regressão da hemólise e ausência de complicações fatais em até 30 dias. O critério de insucesso foi: complicações relacionadas ao procedimento, persistência de reflux moderado ou grave, hemólise, insuficiência cardíaca (IC) ou necessidade de cirurgia de urgência. RESULTADOS: Foram incluídos 20pts (24 próteses) com RPP, com média das idades de 61,5 anos, 11 pts femininos (55%). O número de cirurgias prévias variou de 1 a 4. A maioria (14) tinha 1 RPP, 5 tinham 2 e 1 tinha 4 orifícios regurgitantes. Cinco pts tinham prótese biológica (3 mitrais e 2 aórticas) e 15 próteses mecânicas (8 mitrais, 3 aórticas e 4 mitroaórticas). A indicação da intervenção foi a presença de IC com ou sem hemólise na maioria. A RPP foi grave em 16 pacientes, moderado em 3 e discreto em 1. A via de acesso percutâneo foi femoral em 17 pts. O dispositivo utilizado foi Amplatzer Vascular Plug, O número de plugs variou de 1a 4. Os pts foram distribuídos em 2 grupos: G1 (sucesso) e G2 (insucesso) segundo a definição acima. G1: o sucesso ocorreu em 13 dos 20pts (65%), 5 prótese biológica aórtica (100%) e 8 tinham prótese mecânica (53%) (5 mitrais e 3 aórticas). G2: insucesso ocorreu em 7 dos 20pts (35%), todos com prótese mecânica. Dois pts morreram antes da alta hospitalar (10%). Destes, um foi submetido a cirurgia de urgência por mal posicionamento do plug e o outro complicou com PCR e óbito. Cinco pts receberam alta hospitalar. Em uma evolução média de 14 meses, dos 13pts do G1, 3 morreram (1 acidente vascular cerebral hemorrágico, 1 infarto agudo do miocárdio e 1 IC descompensada); 10 estão evoluindo bem. Dentre os 5 pts do G2, 3 morreram, um continua em tratamento clínico e um foi operado. CONCLUSÃO: Em uma população de alto risco cirúrgico, a mortalidade relacionada a oclusão transcateter da RPP foi 10%. A resolução da RPP foi 65% e foi melhor nas próteses biológicas (100%) que nas mecânicas (53%).

Cost-effectiveness analysis of 3D versus 2D transesophageal echocardiography for the evaluation of patients with primary mitral regurgitation with indication of surgical treatment

OBJECTIVES: To perform the cost-effectiveness analysis of three-dimensional transesophageal echocardiography (3DTEE) in comparison to two-dimensional transesophageal echocardiography (2DTEE) for the anatomic-functional evaluation and surgical planning of severe primary mitral regurgitation. METHODS: a complete economic study was based on a systematic review of 3DTEE and 2DTEE accuracy and private health system costs of two different surgical interventions: mitral valve plasty and mitral valve replacement. The prevalence of common postoperative complications was also predicted for elective procedures: atrial fibrillation (8.6%); acute myocardial infarction (1.4%); thrombosis (3.5%); bleeding (1.5%); endocarditis (6.3%). The decision tree method was adopted as a data analysis model. The Bayes" theorem was used based on sensitivity and specificity measurements. The costs, considering literature and professional tables, were: 3DTEE = US$ 349; 2DTEE = US$ 204; diagnostic evaluation = US$ 597; surgical procedure = US$ 3,643; surgical treatment = US$ 374. RESULTS: The deterministic analysis of the diagnostic test shows that 3DTEE (non-dominated) is superior to 2DTEE (absolutely dominated). The 3DTEE presents a cost reduction of US$ 1,147 and incremental effectiveness (true identification) of 22% when compared to 2DTEE. The multivariate probabilistic sensitivity analysis showed that after 100,000 iterations, the diagnosis based on the 3DTEE becomes the first choice regardless of the willingness to pay threshold. CONCLUSIONS: 3DTEE was cost-effective compared to 2DTEE. Thus, 3DTEE is a potential device to promote health compared to 2DTEE for surgical planning of severe primary mitral regurgitation. (AU)

Long-term analysis of pulmonary hypertension and tricuspid regurgitation after transcatheter aortic valve replacement

INTRODUCTION: transcatheter aortic valve replacement (TAVR) is increasingly utilized in treatment of aortic stenosis (AS). AS is commonly associated to pulmonary hypertension (PH) and tricuspid regurgitation (TR). We aimed to evaluate the long-term post-TAVR course of PH and TR. METHODS: Patients undergoing TAVR were screened for 24-month echocardiographic data on PH and TR. All echocardiograms were performed by a sing le team. Patients were divided in groups according to TR and PH (pulmonary systolic pressure ≥ or < 45 mmHg) grading at 24 months with follow-up of up to 96 months. Standardized clinical outcomes and survival were compared. RESULTS: 156 and 151 patients were se le cted for PH and TR follow-up, respectively. Mean follow-up was 42.23±17.53 months and 42.60±17.67 months for PH and TR groups. Maximum follow-up was 96 months. PH was reduced post-TAVR (32.7% pre-TAVR vs. 20.5% post-TAVR, p<0.001), but no significant difference in TR was found (11.9% pre-TAVR vs. 10.6% post-TAVR). Increased le ft atrial (LA) diameter (p = 0.002) was associated to maintenance PH. Moreover, increased LA diameter (p=0.015) and increased EuroSCORE II (p=0.041) were correlated to new onset PH. On a multivariab le Cox regression model, new onset PH (HR 6.17, 95% CI 1.71­22.29, p=0.005), diastolic dysfunction type II or III (HR 1.06, 95% CI 1.06-1.11, p=0.036) and LA diameter (HR 1.11, 95% CI 1.02­1.21, p=0.02) were independent predictors of long-term mortality. CONCLUSIONS: TAVR was ab le to reduce the severity of PH, but not TR, in this cohort. Additionally, long-term survival was affected by PH, diastolic dysfunction and LA sizing.

Preditores de degeneração hemodinâmica protética após implante de prótese aórtica transcateter / Predictors of prosthetic hemodynamic degeneration after transcatheter aortic prosthesis implantation

INTRODUÇÃO: O implante valvar aórtico percutâneo (TAVI - transcatheter aortic valve implantation) se estabeleceu como tratamento para pacientes com estenose aórtica severa sintomática de alto ou proibitivo risco cirúrgico. Estudos recentes demonstraram não-inferioridade ou superioridade para TAVI em relação à cirurgia em pacientes de risco intermediário. A degeneração hemodinâmica e consequente disfunção protética em pacientes submetidos a TAVI passa a ser uma preocupação evolutiva, pelo que sua durabilidade tem sido questionada. Com isso, o objetivo do trabalho é escrever a evolução do perfil hemodinâmico e durabilidade da bioprótese nos pacientes submetidos a TAVI na experiência de dois centros nacionais. MÉTODOS: Pesquisa observacional, longitudinal, com coleta de dados prospectiva de pacientes com diagnóstico de estenose grave sintomática submetidos à TAVI. O acompanhamento foi feito de julho de 2009 até julho de 2016 em dois centros nacionais. Usamos as definições estandardizadas para deterioração estrutural (SVD ­ structural valve deterioration) e falência de prótese (BVF ­ bioprosthetic valve failure) publicadas pelo consenso da European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Society of Cardiology (ESC) e European Association for Cardio-Thoracic Surgery (EACTS), publicadas em 2017 no European Heart Journal. Foram incluídos para análise de degeneração hemodinâmica da prótese os pacientes com avaliação ecocardiográfica no pós procedimento e com pelo menos uma avaliação de seguimento em pelo menos seis meses após o implante. RESULTADOS: Obtivemos dados de 339 pacientes, com média de idade de 81,6 anos, sendo 45,86% (n=156) homens e 54,14% (n=183) mulheres. A mortalidade por todas as causas até o último seguimento foi de 20,1% (n=68). A média do Euroscore foi de 7,5+6,01 e o STS de 6,56+5,96. Pacientes tratados com prótese balão expansível foram 38% (n=130), enquanto 62% (n=208) com auto expansível. Após seguimento médio de 42 meses, foi observado 28 (8,25%) pacientes com SVD e 2 (0,6%) pacientes apresentaram BVF. O gradiente sistólico médio no baseline foi de 20,06+ 8,49mmHg e a área valvar de 1,9+ 0,3mmHg, e mantiveram-se com comportamento estável no seguimento. CONCLUSÕES: O seguimento após TAVI mostrou favorável performance hemodinâmica e boa durabilidade da bioprótese em nossa experiência de dois centros nacionais. (AU)

Anesthetic management during endocardial radiofrequency ablation of septal hypertrophy ­ a case report

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disorder present in up to 1/500 individuals, about 20­30% of them presenting with hypertrophic obstructive cardiomyopathy (HOCM) due to left ventricle outflow tract obstruction. This is an important cause of sudden cardiac death. Endocardial radiofrequency ablation of septal hypertrophy (ERASH) might be an attractive treatment for HOCM, particularly in patients who do not respond to trans coronary alcohol septal ablation (TASA). Aim: To describe technical aspects related to the procedure and anesthetic management of an ERASH case. Case REPORT: A 64-year-old woman with HOCM was scheduled for ERASH. She had worsening of dyspnea on exertion and generalized fatigue for the previous weeks after previous surgical myomectomy about 6 months ago. The anatomy was unfavorable for TASA and the patient was not willing to undergo another surgery. Preoperative transthoracic echocardiography (TTE) showed asymmetric mid-septal hypertrophy, systolic anterior motion with septal contact and left ventricular outflow tract maximum gradient of 68 mmHg at rest and 105 mmHg after the Valsalva maneuver. General anesthesia was performed. Pulse pressure variation, echocardiography parameters and passive leg raising test where used to guide fluid therapy. At the end of the procedure, analgesia was provided together with prophylaxis of nausea and vomiting. Extubation was uneventful and the patient was transported to the intensive care unit eupneic and hemodynamically stable. On the fourth postoperative day, TTE showed septal hypocontractility and maximum gradient reduction of 33% at rest (68 mmHg to 45 mmHg) and 31% after the Valsalva maneuver (105 mmHg to 73 mmHg). The patient was discharged from hospital at the sixth postoperative day. One month later, she reported progressive improvement of symptoms and expressed satisfaction with the results. CONCLUSION: Better understanding of the pathophysiology and natural history of HCM has enabled earlier diagnosis, as well as a more adequate therapeutic approach. Anesthesiologists should be aware of the pathophysiology of HOCM and must be prepared to anticipate the hemodynamic changes and cardiovascular instability that such patients may show perioperatively. ERASH is a promising therapeutic modality increasingly used for HOCM and anesthesiologists should become more familiar with it.

Signal-domain optimization metrics for MPRAGE RF pulse design in parallel transmission at 7 tesla.

PURPOSE: Standard radiofrequency pulse design strategies focus on minimizing the deviation of the flip angle from a target value, which is sufficient but not necessary for signal homogeneity. An alternative approach, based directly on the signal, here is proposed for the MPRAGE sequence, and is developed in the parallel transmission framework with the use of the kT -points parametrization. METHODS: The flip angle-homogenizing and the proposed methods were investigated numerically under explicit power and specific absorption rate constraints and tested experimentally in vivo on a 7 T parallel transmission system enabling real time local specific absorption rate monitoring. Radiofrequency pulse performance was assessed by a careful analysis of the signal and contrast between white and gray matter. RESULTS: Despite a slight reduction of the flip angle uniformity, an improved signal and contrast homogeneity with a significant reduction of the specific absorption rate was achieved with the proposed metric in comparison with standard pulse designs. CONCLUSION: The proposed joint optimization of the inversion and excitation pulses enables significant reduction of the specific absorption rate in the MPRAGE sequence while preserving image quality. The work reported thus unveils a possible direction to increase the potential of ultra-high field MRI and parallel transmission. Magn Reson Med 76:1431-1442, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

Serviços de ecocardiografia no Brasil: uma visão geral / General profile of echocardiography services in Brazil

Introdução: Devido a um crescimento cada vez maior do número de ecocardiografistas no Brasil, assim como dos serviços de ecocardiografia, tornou-se importante compreender o status quo dessa área de atuação em nosso país.Objetivo: Visualizar um perfil acurado dos serviços ecocardiográficos oferecidos no Brasil.Métodos: Realizou-se por meio da internet uma pesquisa com os sócios ecocardiografistas do Departamento de Imagem Cardiovascular (DIC), respondendo questões específicas sobre infraestrutura, serviços disponibilizados, número de exames, treinamento e formação profissional.Resultados: Dentre os 429 centros participantes, foram computados apenas aqueles que responderam completamente ao questionário (n = 157). Desses, 55 são centros formadores em ecocardiografia e a maioria está localizada na Região Sudeste. Observou-se que 146 serviços (93%) possuem ao menos um profissional habilitado em ecocardiografia pelo Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia.Conclusão: A maioria dos centros de ecocardiografia do Brasil possui profissionais qualificados e habilitados para realização do método.

Toward global tractography.

Diffusion-based tractography is an ill-posed problem, because the step-by-step reconstruction of a fibre bundle trajectory cannot afford any serious mistake in the evaluation of the local fibre orientations. Such evaluation is difficult, however, because the myriad fibres passing through a single voxel follow different directions. Modelling tractography as a global inverse problem is a simple framework which addresses the ill-posed nature of the problem. The key idea is that the results of tractography in the neighbourhood of an ambiguous local diffusion profile can help to infer the local fibre directions. This paper provides an overview of past achievements of global tractography and proposes guidelines for a future research programme in the hope that the potential of the technique will increase the interest of the community.

Hindered diffusion of MRI contrast agents in rat brain extracellular micro-environment assessed by acquisition of dynamic T1 and T2 maps.

The knowledge of brain tissues characteristics (such as extracellular space and tortuosity) represents valuable information for the design of optimal MR probes for specific biomarkers targeting. This work proposes a methodology based on dynamic acquisition of relaxation time maps to quantify in vivo MRI contrast agent concentration after intra-cerebral injection in rat brain. It was applied to estimate the hindered diffusion in brain tissues of five contrast agents with different hydrodynamic diameters (Dotarem(®) ≈ 1 nm, P846 ≈ 4 nm, P792 ≈ 7 nm, P904 ≈ 22 nm and Gd-based emulsion ≈ 170 nm). In vivo apparent diffusion coefficients were compared with those estimated in an obstacle-free medium to determine brain extracellular space and tortuosity. At a 2 h imaging timescale, all contrast agents except the Gd-based emulsion exhibited significant diffusion through brain tissues, with characteristic times compatible with MR molecular imaging (<70 min to diffuse between two capillaries). In conclusion, our experiments indicate that MRI contrast agents with sizes up to 22 nm can be used to perform molecular imaging on intra-cerebral biomarkers. Our quantification methodology allows a precise estimation of apparent diffusion coefficients, which is helpful to calibrate optimal timing between contrast agent injection and MRI observation for molecular imaging studies.

Parallel-transmission-enabled magnetization-prepared rapid gradient-echo T1-weighted imaging of the human brain at 7 T.

One of the promises of Ultra High Field (UHF) MRI scanners is to bring finer spatial resolution in the human brain images due to an increased signal to noise ratio. However, at such field strengths, the spatial non-uniformity of the Radio Frequency (RF) transmit profiles challenges the applicability of most MRI sequences, where the signal and contrast levels strongly depend on the flip angle (FA) homogeneity. In particular, the MP-RAGE sequence, one of the most commonly employed 3D sequences to obtain T1-weighted anatomical images of the brain, is highly sensitive to these spatial variations. These cause deterioration in image quality and complicate subsequent image post-processing such as automated tissue segmentation at UHF. In this work, we evaluate the potential of parallel-transmission (pTx) to obtain high-quality MP-RAGE images of the human brain at 7 T. To this end, non-selective transmit-SENSE pulses were individually tailored for each of 8 subjects under study, and applied to an 8-channel transmit-array. Such RF pulses were designed both for the low-FA excitation train and the 180° inversion preparation involved in the sequence, both utilizing the recently introduced k(T)-point trajectory. The resulting images were compared with those obtained from the conventional method and from subject-specific RF-shimmed excitations. In addition, four of the volunteers were scanned at 3 T for benchmarking purposes (clinical setup without pTx). Subsequently, automated tissue classification was performed to provide a more quantitative measure of the final image quality. Results indicated that pTx could already significantly improve image quality at 7 T by adopting a suitable RF-Shim. Exploiting the full potential of the pTx-setup, the proposed k(T)-point method provided excellent inversion fidelity, comparable to what is commonly only achievable at 3 T with energy intensive adiabatic pulses. Furthermore, the cumulative energy deposition was simultaneously reduced by over 40% compared to the conventional adiabatic inversions. Regarding the low-FA k(T)-point based excitations, the FA uniformity achieved at 7 T surpassed what is typically obtained at 3 T. Subsequently, automated white and gray matter segmentation not only confirmed the expected improvements in image quality, but also suggests that care should be taken to properly account for the strong local susceptibility effects near cranial cavities. Overall, these findings indicate that the k(T)-point-based pTx solution is an excellent candidate for UHF 3D imaging, where patient safety is a major concern due to the increase of specific absorption rates.

Brain tissue water comes in two pools: evidence from diffusion and R2' measurements with USPIOs in non human primates.

Diffusion-weighted MRI of non-human primates revealed that USPIO Bulk Magnetic Susceptibility (BMS) T2' effects of Ultrasmall Superparamagnetic Particles with Iron Oxide (USPIO) in the brain cannot be explained by a single compartment model, as diffusion and T2' effects appear coupled: Apparent Diffusion Coefficient (ADC) values depend on USPIO concentration and relaxivity effects of USPIO decrease with the b value. On the other hand, USPIO and diffusion effects could be well uncoupled using a model consisting in a fast and a slow diffusion pool with different relaxivities. Diffusion-weighting acts as a filter which emphasizes the contribution of the slow pool when increasing b values (apparent decrease in ADC and R2'). Those results have implications for human studies using BMS contrast agents, as well as BOLD and diffusion fMRI.

Automatic fiber bundle segmentation in massive tractography datasets using a multi-subject bundle atlas.

This paper presents a method for automatic segmentation of white matter fiber bundles from massive dMRI tractography datasets. The method is based on a multi-subject bundle atlas derived from a two-level intra-subject and inter-subject clustering strategy. This atlas is a model of the brain white matter organization, computed for a group of subjects, made up of a set of generic fiber bundles that can be detected in most of the population. Each atlas bundle corresponds to several inter-subject clusters manually labeled to account for subdivisions of the underlying pathways often presenting large variability across subjects. An atlas bundle is represented by the multi-subject list of the centroids of all intra-subject clusters in order to get a good sampling of the shape and localization variability. The atlas, composed of 36 known deep white matter bundles and 47 superficial white matter bundles in each hemisphere, was inferred from a first database of 12 brains. It was successfully used to segment the deep white matter bundles in a second database of 20 brains and most of the superficial white matter bundles in 10 subjects of the same database.

Reduced-distortion diffusion MRI of the craniovertebral junction.

BACKGROUND AND PURPOSE: CVJ lesion suffers from a high sensitivity to susceptibility and distortion artifacts, which sometimes makes diffusion image difficult to interpret. Our purpose was to evaluate the potential for diffusion MR imaging using RS-EPI compared with SS-EPI in the assessment of the CVJ. MATERIALS AND METHODS: RS-EPI and SS-EPI DTI images were acquired from 10 healthy volunteers using 3T MRI with a 32-channel head coil. For both sequences, the following parameters were used: 1-mm(2) in-plane resolution; 3-mm section thickness; TR = 5200 ms; 1 acquisition at b = 0 and 12 different encoding directions at b = 1000 seconds/mm(2). The RS-EPI sequence scan time was 9.44 minutes (1 average). The SS-EPI sequence was 9.37 minutes (8 averages). Diffusion tensor calculation and image analysis were performed using DTIStudio software. Diffusion trace images and color-coded fiber orientation maps were evaluated by 2 independent readers for distortion and delineation of fine structure using a semiquantitative scale in selected landmark locations. The absolute distances between the temporal base and the cerebellar contour between the T2-weighted images and the diffusion trace images obtained with RS-EPI and SS-EPI were also compared. RESULTS: The contours of the temporal lobe and cerebellum were better delineated and distortion artifacts were clearly reduced with the RS-EPI sequence. More fine structures were also visible in the brain stem and cerebellum with the RS-EPI sequence. The amount of distortion was significantly reduced with RS-EPI compared with SS-EPI (P < .01). CONCLUSIONS: The RS-EPI DTI sequence was less prone to geometric distortion than the SS-EPI sequence and allowed a better delineation of CVJ internal structure. Although the acquisition time is still relatively long, the RS-EPI appears as a promising approach to perform DTI studies in CVJ lesions, such as brain stem ischemia, neurodegenerative diseases, brain and skull base tumors, or inflammation.

kT -points: short three-dimensional tailored RF pulses for flip-angle homogenization over an extended volume.

With Transmit SENSE, we demonstrate the feasibility of uniformly exciting a volume such as the human brain at 7T through the use of an original minimalist transmit k-space coverage, referred to as "k(T) -points." Radio-frequency energy is deposited only at a limited number of k-space locations in the vicinity of the center to counteract transmit sensitivity inhomogeneities. The resulting nonselective pulses are short and need little energy compared to adiabatic or other B 1+-robust pulses available in the literature, making them good candidates for short-repetition time 3D sequences at high field. Experimental verification was performed on three human volunteers at 7T by means of an 8-channel transmit array system. On average, whereas the standard circularly polarized excitation resulted in a 33%-flip angle spread (standard deviation over mean) throughout the brain, and a static radio-frequency shim showed flip angle variations of 17% and up, application of k(T) -point-based excitations demonstrated excellent flip angle uniformity (8%) for a small target flip angle and with sub-millisecond durations.

[Brain development of infant and MRI by diffusion tensor imaging]. / Neurophysiologie clinique : développement cérébral du nourrisson et imagerie par résonance magnétique.

Studying how the brain develops and becomes functional is important to understand how the man has been able to develop specific cognitive abilities, and to comprehend the complexity of some developmental pathologies. Thanks to magnetic resonance imaging (MRI), it is now possible to image the baby's immature brain and to consider subtle correlations between the brain anatomical development and the early acquisition of cognitive functions. Dedicated methodologies for image acquisition and post-treatment must then be used because the size of cerebral structures and the image contrast are very different in comparison with the adult brain, and because the examination length is a major constraint. Two recent studies have evaluated the developing brain under an original perspective. The first one has focused on cortical folding in preterm newborns, from 6 to 8 months of gestational age, assessed with T2-weighted conventional MRI. The second study has mapped the organization and maturation of white matter fiber bundles in 1- to 4-month-old healthy infants with diffusion tensor imaging (DTI). Both studies have enabled to highlight spatio-temporal differences in the brain regions' maturation, as well as early anatomical asymmetries between cerebral hemispheres. These studies emphasize the potential of MRI to evaluate brain development compared with the infant's psychomotor acquisitions after birth.

Brain activation by short-term nicotine exposure in anesthetized wild-type and beta2-nicotinic receptors knockout mice: a BOLD fMRI study.

RATIONALE: The behavioral effects of nicotine and the role of the beta2-containing nicotinic receptors in these behaviors are well documented. However, the behaviors altered by nicotine rely on the functioning on multiple brain circuits where the high-affinity beta2-containing nicotinic receptors (beta2*nAChRs) are located. OBJECTIVES: We intend to see which brain circuits are activated when nicotine is given in animals naïve for nicotine and whether the beta2*nAChRs are needed for its activation of the blood oxygen level dependent (BOLD) signal in all brain areas. MATERIALS AND METHODS: We used functional magnetic resonance imaging (fMRI) to measure the brain activation evoked by nicotine (1 mg/kg delivered at a slow rate for 45 min) in anesthetized C57BL/6J mice and beta2 knockout (KO) mice. RESULTS: Acute nicotine injection results in a significant increased activation in anterior frontal, motor, and somatosensory cortices and in the ventral tegmental area and the substantia nigra. Anesthetized mice receiving no nicotine injection exhibited a major decreased activation in all cortical and subcortical structures, likely due to prolonged anesthesia. At a global level, beta2 KO mice were not rescued from the globally declining BOLD signal. However, nicotine still activated regions of a meso-cortico-limbic circuit likely via alpha7 nicotinic receptors. CONCLUSIONS: Acute nicotine exposure compensates for the drop in brain activation due to anesthesia through the meso-cortico-limbic network via the action of nicotine on beta2*nAChRs. The developed fMRI method is suitable for comparing responses in wild-type and mutant mice.

Structural asymmetries in the infant language and sensori-motor networks.

Both language capacity and strongly lateralized hand preference are among the most intriguing particularities of the human species. They are associated in the adult brain with functional and anatomical hemispheric asymmetries in the speech perception-production network and in the sensori-motor system. Only studies in early life can help us to understand how such asymmetries arise during brain development, and to which point structural left-right differences are the source or the consequence of functional lateralization. In this study, we aimed to provide new in vivo structural markers of hemispheric asymmetries in infants from 1 to 4 months of age, with diffusion tensor imaging. We used 3 complementary analysis methods based on local diffusion indices and spatial localizations of tracts. After a prospective approach over the whole brain, we demonstrated early leftward asymmetries in the arcuate fasciculus and in the cortico-spinal tract. These results suggest that the early macroscopic geometry, microscopic organization, and maturation of these white matter bundles are related to the development of later functional lateralization.

[See the thinking brain: a story about water]. / Voir le cerveau penser: une histoire d'eau.

Among the astonishing Einstein's papers from 1905, there is one which unexpectedly gave birth to a powerful method to explore the brain. Molecular diffusion was explained by Einstein on the basis of the random translational motion of molecules which results from their thermal energy. In the mid 1980s it was shown that water diffusion in the brain could be imaged using MRI. During their random displacements water molecules probe tissue structure at a microscopic scale, interacting with cell membranes and, thus, providing unique information on the functional architecture of tissues. A dramatic application of diffusion MRI has been brain ischemia, following the discovery that water diffusion drops immediately after the onset of an ischemic event, when brain cells undergo swelling through cytotoxic edema. On the other hand, water diffusion is anisotropic in white matter, because axon membranes limit molecular movement perpendicularly to the fibers. This feature can be exploited to map out the orientation in space of the white matter tracks and image brain connections. More recently, it has been shown that diffusion MRI could accurately detect cortical activation. As the diffusion response precedes by several seconds the hemodynamic response captured by BOLD fMRI, it has been suggested that water diffusion could reflect early neuronal events, such as the transient swelling of activated cortical cells. If confirmed, this discovery will represent a significant breakthrough, allowing non invasive access to a direct physiological marker of brain activation. This approach will bridge the gap between invasive optical imaging techniques in neuronal cell cultures, and current functional neuroimaging approaches in humans, which are based on indirect and remote blood flow changes.