Prognostic value of early MR imaging in term infants with severe perinatal asphyxia.

The prognostic significance of magnetic resonance imaging (MRI) in the neonatal period was studied prospectively in 43 term infants with perinatal asphyxia. MRI was performed between 1 and 14 days after birth with a high field system (2.35 Tesla). Neurodevelopmental outcome was assessed by a standardized neurological examination and the Griffiths developmental test at a mean age of 18.9 months. The predictive value of the various MRI patterns was as follows: Severe diffuse brain injury (pattern AII+III; n = 7) and lesions of thalamus and basal ganglia (pattern C; n = 5) were strongly associated with poor outcome and greatly reduced head growth. Mild diffuse brain injury (pattern AI; n = 7), parasagittal lesions (B; n = 7), periventricular hyperintensity (D; n = 2), focal brain necrosis and hemorrhage (E; n = 3) and periventricular hypointense stripes (on T2-weighted images; F; n = 3) led in one third of the infants to minor neurological disturbances and mild developmental delay. Infants with normal MRI findings (G; n = 9) developed normally with the exception of one infant who was mildly delayed at 18 months. The results indicate that MRI examination during the first two weeks of life is of prognostic significance in term infants suffering from perinatal asphyxia. Severe hypoxic-ischemic brain lesions were associated highly significantly with poor neuro-developmental outcome, whereas infants with inconspicuous MRI developed normally.

Temporal evolution of MR perfusion in neonatal hypoxic-ischemic encephalopathy

PURPOSE: To illustrate the evolution of brain perfusion-weighted magnetic resonance imaging (PWI-MRI) in severe neonatal hypoxic-ischemic (HI) encephalopathy, and its possible relation to further neurodevelopmental outcome. MATERIALS AND METHODS: Two term neonates with HI encephalopathy underwent an early and a late MRI, including PWI. They were followed until eight months of age. A total of three "normal controls" were also included. Perfusion maps were obtained, and relative cerebral blood flow (rCBF) and cerebral blood volume (rCBV) values were measured. RESULTS: Compared to normal neonates, a hyperperfusion (increased rCBF and rCBV) was present on early scans in the whole brain. On late scans, hyperperfusion persisted in cortical gray matter (normalization of rCBF and rCBV ratios in white matter and basal ganglia, but not in cortical gray matter). Diffusion-weighted imaging (DWI) was normalized, and extensive lesions became visible on T2-weighted images. Both patients displayed very abnormal outcome: Patient 2 with the more abnormal early and late hyperperfusion being the worst. CONCLUSION: PWI in HI encephalopathy did not have the same temporal evolution as DWI, and remained abnormal for more than one week after injury. This could be a marker of an ongoing mechanism underlying severe neonatal HI encephalopathy. Evolution of PWI might help to predict further neurodevelopmental outcome.

Blockade of the renin-angiotensin system and renal tissue oxygenation as measured with BOLD-MRI in patients with type 2 diabetes.

AIM: To assess whether blockade of the renin-angiotensin system (RAS), a recognized strategy to prevent the progression of diabetic nephropathy, affects renal tissue oxygenation in type 2 diabetes mellitus (T2DM) patients. METHODS: Prospective randomized 2-way cross over study; T2DM patients with (micro)albuminuria and/or hypertension underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) at baseline, after one month of enalapril (20mgqd), and after one month of candesartan (16mgqd). Each BOLD-MRI was performed before and after the administration of furosemide. The mean R2* (=1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. RESULTS: Twelve patients (mean age: 60±11 years, eGFR: 62±22ml/min/1.73m(2)) completed the study. Neither chronic enalapril nor candesartan intake modified renal cortical or medullary R2* levels. Furosemide significantly decreased cortical and medullary R2* levels suggesting a transient increase in renal oxygenation. Medullary R2* levels correlated positively with urinary sodium excretion and systemic blood pressure, suggesting lower renal oxygenation at higher dietary sodium intake and blood pressure; cortical R2* levels correlated positively with glycemia and HbA1c. CONCLUSION: RAS blockade does not seem to increase renal tissue oxygenation in T2DM hypertensive patients. The response to furosemide and the association with 24h urinary sodium excretion emphasize the crucial role of renal sodium handling as one of the main determinants of renal tissue oxygenation.

Extensor carpi ulnaris accessory tendinous slips (ECUATS): MRI features at 3.0T and correlation with tendinosis : 49

Purpose: To assess the visibility and the features of ECUATS on 3.0-T MRI studies, and evaluate their correlation with tendinosis. Methods and materials: Our retrospective study was approved by IRB, with waiver of informed consent. Fifty wrist MRI and 48 MR arthrographies from 98 patients (55 males, 43 females, mean age 42.3 years) performed between January and November 2009 on 3.0-T units were reviewed. Images (transverse T1, T2, FS Gd T1 and VIBE) were independently analyzed by two radiologists, and a consensus reached with a third reader in case of disagreement. The visibility of ECUATS was assessed on each available transverse sequence. When present, ECUATS' origins, diameters and insertions were noted. ECU tendinosis was also evaluated. Inter-rater agreement was assessed using Cohen's Kappa coefficient. Results: ECUATS observed prevalence was 23.5% (23/98). ECUATS were more frequently noted on the VIBE sequence, with a good inter-rater agreement (Kappa = 0.72). Origins were noted in 95.7% of cases: 3 were at the level of, and 20 distal to ECU subsheath. Insertions were seen in 43.5%: 2 were on 5th metacarpal bone, 8 on extensor apparatus of 5th finger. ECUATS mean shortest and longest diameters were 0.54 and 0.85 mm respectively. ECU tendinosis was statistically more frequently noted in patients with ECUATS (p <0.05). Conclusion: ECUATS are readily visible on 3.0-T MRI studies, especially on transverse GRE VIBE images. ECU tendinosis is more frequently noted in patients bearing ECUATS.

Comparison and validation of tissue modelization and statistical classification methods in T1-weighted MR brain images.

This paper presents a validation study on statistical nonsupervised brain tissue classification techniques in magnetic resonance (MR) images. Several image models assuming different hypotheses regarding the intensity distribution model, the spatial model and the number of classes are assessed. The methods are tested on simulated data for which the classification ground truth is known. Different noise and intensity nonuniformities are added to simulate real imaging conditions. No enhancement of the image quality is considered either before or during the classification process. This way, the accuracy of the methods and their robustness against image artifacts are tested. Classification is also performed on real data where a quantitative validation compares the methods' results with an estimated ground truth from manual segmentations by experts. Validity of the various classification methods in the labeling of the image as well as in the tissue volume is estimated with different local and global measures. Results demonstrate that methods relying on both intensity and spatial information are more robust to noise and field inhomogeneities. We also demonstrate that partial volume is not perfectly modeled, even though methods that account for mixture classes outperform methods that only consider pure Gaussian classes. Finally, we show that simulated data results can also be extended to real data.

Long-term monitoring of post-stroke plasticity after transient cerebral ischemia in mice using in vivo and ex vivo diffusion tensor MRI.

WE USED A MURINE MODEL OF TRANSIENT FOCAL CEREBRAL ISCHEMIA TO STUDY: 1) in vivo DTI long-term temporal evolution of the apparent diffusion coefficient (ADC) and diffusion fractional anisotropy (FA) at days 4, 10, 15 and 21 after stroke 2) ex vivo distribution of a plasticity-related protein (GAP-43) and its relationship with the ex vivo DTI characteristics of the striato-thalamic pathway (21 days). All animals recovered motor function. In vivo ADC within the infarct was significantly increased after stroke. In the stroke group, GAP-43 expression and FA values were significantly higher in the ipsilateral (IL) striatum and contralateral (CL) hippocampus compared to the shams. DTI tractography showed fiber trajectories connecting the CL striatum to the stroke region, where increased GAP43 and FA were observed and fiber tracts from the CL striatum terminating in the IL hippocampus.Our data demonstrate that DTI changes parallel histological remodeling and recovery of function.

A new early and automated MRI-based predictor of motor improvement after stroke.

OBJECTIVES: In this study, we investigated the structural plasticity of the contralesional motor network in ischemic stroke patients using diffusion magnetic resonance imaging (MRI) and explored a model that combines a MRI-based metric of contralesional network integrity and clinical data to predict functional outcome at 6 months after stroke. METHODS: MRI and clinical examinations were performed in 12 patients in the acute phase, at 1 and 6 months after stroke. Twelve age- and gender-matched controls underwent 2 MRIs 1 month apart. Structural remodeling after stroke was assessed using diffusion MRI with an automated measurement of generalized fractional anisotropy (GFA), which was calculated along connections between contralesional cortical motor areas. The predictive model of poststroke functional outcome was computed using a linear regression of acute GFA measures and the clinical assessment. RESULTS: GFA changes in the contralesional motor tracts were found in all patients and differed significantly from controls (0.001 ≤ p < 0.05). GFA changes in intrahemispheric and interhemispheric motor tracts correlated with age (p ≤ 0.01); those in intrahemispheric motor tracts correlated strongly with clinical scores and stroke sizes (p ≤ 0.001). GFA measured in the acute phase together with a routine motor score and age were a strong predictor of motor outcome at 6 months (r(2) = 0.96, p = 0.0002). CONCLUSION: These findings represent a proof of principle that contralesional diffusion MRI measures may provide reliable information for personalized rehabilitation planning after ischemic motor stroke. Neurology® 2012;79:39-46.

ADC mapping of chronic cerebral hypoperfusion induced by carotid artery stenosis.

BACKGROUND: Carotid artery stenosis is associated with the occurrence of acute and chronic ischemic lesions that increase with age in the elderly population. Diffusion Imaging and ADC mapping may be an appropriate method to investigate patients with chronic hypoperfusion consecutive to carotid stenosis. This non-invasive technique allows to investigate brain integrity and structure, in particular hypoperfusion induced by carotid stenosis diseases. The aim of this study was to evaluate the impact of a carotid stenosis on the parenchyma using ADC mapping. METHODS: Fifty-nine patients with symptomatic (33) and asymptomatic (26) carotid stenosis were recruited from our multidisciplinary consultation. Both groups demonstrated a similar degree of stenosis. All patients underwent MRI of the brain including diffusion-weighted MR imaging with ADC mapping. Regions of interest were defined in the anterior and posterior paraventricular regions both ipsilateral and contralateral to the stenosis (anterior circulation). The same analysis was performed for the thalamic and occipital regions (posterior circulation). RESULTS: ADC values of the affected vascular territory were significantly higher on the side of the stenosis in the periventricular anterior (P<0.001) and posterior (P<0.01) area. There was no difference between ipsilateral and contralateral ADC values in the thalamic and occipital regions. CONCLUSIONS: We have shown that carotid stenosis is associated with significantly higher ADC values in the anterior circulation, probably reflecting an impact of chronic hypoperfusion on the brain parenchyma in symptomatic and asymptomatic patients. This is consistent with previous data in the literature.

Mechanisms underlying functional recovery after in vivo focal cerebral ischemia : from preconditioning to diffusion MRI

Version abregée L'ischémie cérébrale est la troisième cause de mort dans les pays développés, et la maladie responsable des plus sérieux handicaps neurologiques. La compréhension des bases moléculaires et anatomiques de la récupération fonctionnelle après l'ischémie cérébrale est donc extrêmement importante et représente un domaine d'intérêt crucial pour la recherche fondamentale et clinique. Durant les deux dernières décennies, les chercheurs ont tenté de combattre les effets nocifs de l'ischémie cérébrale à l'aide de substances exogènes qui, bien que testées avec succès dans le domaine expérimental, ont montré un effet contradictoire dans l'application clinique. Une approche différente mais complémentaire est de stimuler des mécanismes intrinsèques de neuroprotection en utilisant le «modèle de préconditionnement» : une brève insulte protège contre des épisodes d'ischémie plus sévères à travers la stimulation de voies de signalisation endogènes qui augmentent la résistance à l'ischémie. Cette approche peut offrir des éléments importants pour clarifier les mécanismes endogènes de neuroprotection et fournir de nouvelles stratégies pour rendre les neurones et la glie plus résistants à l'attaque ischémique cérébrale. Dans un premier temps, nous avons donc étudié les mécanismes de neuroprotection intrinsèques stimulés par la thrombine, un neuroprotecteur «préconditionnant» dont on a montré, à l'aide de modèles expérimentaux in vitro et in vivo, qu'il réduit la mort neuronale. En appliquant une technique de microchirurgie pour induire une ischémie cérébrale transitoire chez la souris, nous avons montré que la thrombine peut stimuler les voies de signalisation intracellulaire médiées par MAPK et JNK par une approche moléculaire et l'analyse in vivo d'un inhibiteur spécifique de JNK (L JNK) .Nous avons également étudié l'impact de la thrombine sur la récupération fonctionnelle après une attaque et avons pu démontrer que ces mécanismes moléculaires peuvent améliorer la récupération motrice. La deuxième partie de cette étude des mécanismes de récupération après ischémie cérébrale est basée sur l'investigation des bases anatomiques de la plasticité des connections cérébrales, soit dans le modèle animal d'ischémie transitoire, soit chez l'homme. Selon des résultats précédemment publiés par divers groupes ,nous savons que des mécanismes de plasticité aboutissant à des degrés divers de récupération fonctionnelle sont mis enjeu après une lésion ischémique. Le résultat de cette réorganisation est une nouvelle architecture fonctionnelle et structurelle, qui varie individuellement selon l'anatomie de la lésion, l'âge du sujet et la chronicité de la lésion. Le succès de toute intervention thérapeutique dépendra donc de son interaction avec la nouvelle architecture anatomique. Pour cette raison, nous avons appliqué deux techniques de diffusion en résonance magnétique qui permettent de détecter les changements de microstructure cérébrale et de connexions anatomiques suite à une attaque : IRM par tenseur de diffusion (DT-IR1V) et IRM par spectre de diffusion (DSIRM). Grâce à la DT-IRM hautement sophistiquée, nous avons pu effectuer une étude de follow-up à long terme chez des souris ayant subi une ischémie cérébrale transitoire, qui a mis en évidence que les changements microstructurels dans l'infarctus ainsi que la modification des voies anatomiques sont corrélés à la récupération fonctionnelle. De plus, nous avons observé une réorganisation axonale dans des aires où l'on détecte une augmentation d'expression d'une protéine de plasticité exprimée dans le cône de croissance des axones (GAP-43). En appliquant la même technique, nous avons également effectué deux études, rétrospective et prospective, qui ont montré comment des paramètres obtenus avec DT-IRM peuvent monitorer la rapidité de récupération et mettre en évidence un changement structurel dans les voies impliquées dans les manifestations cliniques. Dans la dernière partie de ce travail, nous avons décrit la manière dont la DS-IRM peut être appliquée dans le domaine expérimental et clinique pour étudier la plasticité cérébrale après ischémie. Abstract Ischemic stroke is the third leading cause of death in developed countries and the disease responsible for the most serious long-term neurological disability. Understanding molecular and anatomical basis of stroke recovery is, therefore, extremely important and represents a major field of interest for basic and clinical research. Over the past 2 decades, much attention has focused on counteracting noxious effect of the ischemic insult with exogenous substances (oxygen radical scavengers, AMPA and NMDA receptor antagonists, MMP inhibitors etc) which were successfully tested in the experimental field -but which turned out to have controversial effects in clinical trials. A different but complementary approach to address ischemia pathophysiology and treatment options is to stimulate and investigate intrinsic mechanisms of neuroprotection using the "preconditioning effect": applying a brief insult protects against subsequent prolonged and detrimental ischemic episodes, by up-regulating powerful endogenous pathways that increase resistance to injury. We believe that this approach might offer an important insight into the molecular mechanisms responsible for endogenous neuroprotection. In addition, results from preconditioning model experiment may provide new strategies for making brain cells "naturally" more resistant to ischemic injury and accelerate their rate of functional recovery. In the first part of this work, we investigated down-stream mechanisms of neuroprotection induced by thrombin, a well known neuroprotectant which has been demonstrated to reduce stroke-induced cell death in vitro and in vivo experimental models. Using microsurgery to induce transient brain ischemia in mice, we showed that thrombin can stimulate both MAPK and JNK intracellular pathways through a molecular biology approach and an in vivo analysis of a specific kinase inhibitor (L JNK1). We also studied thrombin's impact on functional recovery demonstrating that these molecular mechanisms could enhance post-stroke motor outcome. The second part of this study is based on investigating the anatomical basis underlying connectivity remodeling, leading to functional improvement after stroke. To do this, we used both a mouse model of experimental ischemia and human subjects with stroke. It is known from previous data published in literature, that the brain adapts to damage in a way that attempts to preserve motor function. The result of this reorganization is a new functional and structural architecture, which will vary from patient to patient depending on the anatomy of the damage, the biological age of the patient and the chronicity of the lesion. The success of any given therapeutic intervention will depend on how well it interacts with this new architecture. For this reason, we applied diffusion magnetic resonance techniques able to detect micro-structural and connectivity changes following an ischemic lesion: diffusion tensor MRI (DT-MRI) and diffusion spectrum MRI (DS-MRI). Using DT-MRI, we performed along-term follow up study of stroke mice which showed how diffusion changes in the stroke region and fiber tract remodeling is correlating with stroke recovery. In addition, axonal reorganization is shown in areas of increased plasticity related protein expression (GAP 43, growth axonal cone related protein). Applying the same technique, we then performed a retrospective and a prospective study in humans demonstrating how specific DTI parameters could help to monitor the speed of recovery and show longitudinal changes in damaged tracts involved in clinical symptoms. Finally, in the last part of this study we showed how DS-MRI could be applied both to experimental and human stroke and which perspectives it can open to further investigate post stroke plasticity.

Generative FDG-PET and MRI model of aging and disease progression in Alzheimer's disease.

The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer's Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.

Impulse response recovery of linear systems through weighted cumulant slice

Identifiability of the so-called ω-slice algorithm is proven for ARMA linear systems. Although proofs were developed in the past for the simpler cases of MA and AR models, they were not extendible to general exponential linear systems. The results presented in this paper demonstrate a unique feature of the ω-slice method, which is unbiasedness and consistency when order is overdetermined, regardless of the IIR or FIR nature of the underlying system, and numerical robustness.

Delayed contrast-enhanced MRI of the coronary artery wall in takayasu arteritis.

BACKGROUND: Takayasu arteritis (TA) is a rare form of chronic inflammatory granulomatous arteritis of the aorta and its major branches. Late gadolinium enhancement (LGE) with magnetic resonance imaging (MRI) has demonstrated its value for the detection of vessel wall alterations in TA. The aim of this study was to assess LGE of the coronary artery wall in patients with TA compared to patients with stable CAD. METHODS: We enrolled 9 patients (8 female, average age 46±13 years) with proven TA. In the CAD group 9 patients participated (8 male, average age 65±10 years). Studies were performed on a commercial 3T whole-body MR imaging system (Achieva; Philips, Best, The Netherlands) using a 3D inversion prepared navigator gated spoiled gradient-echo sequence, which was repeated 34-45 minutes after low-dose gadolinium administration. RESULTS: No coronary vessel wall enhancement was observed prior to contrast in either group. Post contrast, coronary LGE on IR scans was detected in 28 of 50 segments (56%) seen on T2-Prep scans in TA and in 25 of 57 segments (44%) in CAD patients. LGE quantitative assessment of coronary artery vessel wall CNR post contrast revealed no significant differences between the two groups (CNR in TA: 6.0±2.4 and 7.3±2.5 in CAD; p = 0.474). CONCLUSION: Our findings suggest that LGE of the coronary artery wall seems to be common in patients with TA and similarly pronounced as in CAD patients. The observed coronary LGE seems to be rather unspecific, and differentiation between coronary vessel wall fibrosis and inflammation still remains unclear.

Electrical source imaging for presurgical focus localization in epilepsy patients with normal MRI.

PURPOSE: Patients with magnetic resonance (MR)-negative focal epilepsy (MRN-E) have less favorable surgical outcomes (between 40% and 70%) compared to those in whom an MRI lesion guides the site of surgical intervention (60-90%). Patients with extratemporal MRN-E have the worst outcome (around 50% chance of seizure freedom). We studied whether electroencephalography (EEG) source imaging (ESI) of interictal epileptic activity can contribute to the identification of the epileptic focus in patients with normal MRI. METHODS: We carried out ESI in 10 operated patients with nonlesional MRI and a postsurgical follow-up of at least 1 year. Five of the 10 patients had extratemporal lobe epilepsy. Evaluation comprised surface and intracranial EEG monitoring of ictal and interictal events, structural MRI, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), ictal and interictal perfusion single photon emission computed tomography (SPECT) scans. Eight of the 10 patients also underwent intracranial monitoring. RESULTS: ESI correctly localized the epileptic focus within the resection margins in 8 of 10 patients, 9 of whom experienced favorable postsurgical outcomes. DISCUSSION: The results highlight the diagnostic value of ESI and encourage broadening its application to patients with MRN-E. If the surface EEG contains fairly localized spikes, ESI contributes to the presurgical decision process.