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Biomedical subjects

J F Mangin

Publications and source records attributed to J F Mangin.

At least 19 recordsLinked to original sources

Role of the supplementary motor area in motor deficit following medial frontal lobe surgery.

OBJECTIVE: Patients undergoing surgical resection of medial frontal lesions may present a transient postoperative deficit that remains largely unpredictable. The authors studied the role of the supplementary motor area (SMA) in the occurrence of this deficit using fMRI. METHODS: Twenty-three patients underwent a preoperative fMRI before resection of medial frontal lesions. Tasks included self-paced flexion/extension of the left and right hand, successively. Preoperative fMRI data were compared with postoperative MRI data and with neurologic outcome. RESULTS: Following surgery, 11 patients had a motor deficit from which all patients recovered within a few weeks or months. The deficit was similar across patients, consisting of a global reduction in spontaneous movements contralateral to the operated side with variable severity. SMA activation was observed in all patients. The deficit was observed when the area activated in the posterior part of the SMA (SMA proper) was resected. CONCLUSIONS: fMRI is able to identify the area at risk in the SMA proper whose resection is highly related to the occurrence of the motor deficit. The clinical characteristics of this deficit support the role of the SMA proper in the initiation and execution of the movement.

Adult↗

Detection of fMRI activation using cortical surface mapping.

A methodology for fMRI data analysis confined to the cortex, Cortical Surface Mapping (CSM), is presented. CSM retains the flexibility of the General Linear Model based estimation, but the procedures involved are adapted to operate on the cortical surface, while avoiding to resort to explicit flattening. The methodology is tested by means of simulations and application to a real fMRI protocol. The results are compared with those obtained with a standard, volume-oriented approach (SPM), and it is shown that CSM leads to local differences in sensitivity, with generally higher sensitivity for CSM in two of the three subjects studied. The discussion provided is focused on the benefits of the introduction of anatomical information in fMRI data analysis, and the relevance of CSM as a step toward this goal.

Brain Mapping↗

Diffusion tensor imaging: concepts and applications.

The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three-dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications.

Brain Diseases↗

Motion correction algorithms may create spurious brain activations in the absence of subject motion.

This paper describes several experiments that prove that standard motion correction methods may induce spurious activations in some motion-free fMRI studies. This artifact stems from the fact that activated areas behave like biasing outliers for the difference of square-based measures usually driving such registration methods. This effect is demonstrated first using a motion-free simulated time series including artificial activation-like signal changes. Several additional simulations explore the influence of activation amplitude and extent. The effect is finally highlighted on an actual time series obtained from a 3-T magnet. All the experiments are performed using four different realignment methods, which allows us to show that the problem may be overcome by methods based on a robust similarity measure like mutual information.

Algorithms↗

Cerebral mechanisms of word masking and unconscious repetition priming.

We used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) to visualize the cerebral processing of unseen masked words. Within the areas associated with conscious reading, masked words activated left extrastriate, fusiform and precentral areas. Furthermore, masked words reduced the amount of activation evoked by a subsequent conscious presentation of the same word. In the left fusiform gyrus, this repetition suppression phenomenon was independent of whether the prime and target shared the same case, indicating that case-independent information about letter strings was extracted unconsciously. In comparison to an unmasked situation, however, the activation evoked by masked words was drastically reduced and was undetectable in prefrontal and parietal areas, correlating with participants' inability to report the masked words.

Adult↗

Evaluation of inverse methods and head models for EEG source localization using a human skull phantom.

We used a real-skull phantom head to investigate the performances of representative methods for EEG source localization when considering various head models. We describe several experiments using a montage with current sources located at multiple positions and orientations inside a human skull filled with a conductive medium. The robustness of selected methods based on distributed source models is evaluated as various solutions to the forward problem (from the sphere to the finite element method) are considered. Experimental results indicate that inverse methods using appropriate cortex-based source models are almost always able to locate the active source with excellent precision, with little or no spurious activity in close or distant regions, even when two sources are simultaneously active. Superior regularization schemes for solving the inverse problem can dramatically help the estimation of sparse and focal active zones, despite significant approximation of the head geometry and the conductivity properties of the head tissues. Realistic head models are necessary, though, to fit the data with a reasonable level of residual variance.

Electroencephalography↗

A multiresolution framework to MEG/EEG source imaging.

A new method based on a multiresolution approach for solving the ill-posed problem of brain electrical activity reconstruction from electroencephaloram (EEG)/magnetoencephalogram (MEG) signals is proposed in a distributed source model. At each step of the algorithm, a regularized solution to the inverse problem is used to constrain the source space on the cortical surface to be scanned at higher spatial resolution. We present the iterative procedure together with an extension of the ST-maximum a posteriori method [1] that integrates spatial and temporal a priori information in an estimator of the brain electrical activity. Results from EEG in a phantom head experiment with a real human skull and from real MEG data on a healthy human subject are presented. The performances of the multiresolution method combined with a nonquadratic estimator are compared with commonly used dipolar methods, and to minimum-norm method with and without multiresolution. In all cases, the proposed approach proved to be more efficient both in terms of computational load and result quality, for the identification of sparse focal patterns of cortical current density, than the fixed scale imaging approach.

Algorithms↗

Diffusion tensor imaging study of subcortical gray matter in cadasil.

BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), water diffusion changes suggestive of microstructural tissue alterations have been recently reported in abnormal- and normal-appearing white matter as seen on T2-weighted images. In the subcortical gray matter, typical lacunar infarcts are repeatedly observed. Whether microstructural tissue changes are also present outside these lesions within the putamen or thalamus remains unknown. METHODS: We used diffusion tensor imaging, an MRI method highly sensitive to cerebral microstructure, in 20 CADASIL patients and 12 controls. Both the trace of the diffusion tensor [Tr(D)] and an anisotropic diffusion index (volume ratio) of diffusion were measured within the putamen and thalamus outside typical lacunar infarcts as detected on both T1- and T2-weighted images. RESULTS: A significant increase in Tr(D) and a decrease in anisotropy were observed in the putamen and thalamus in patients. The right/left indices of Tr(D) in the thalamus, but not in the putamen, were strongly correlated with the corresponding indices calculated in the white matter of the centrum semiovale. In addition, the diffusion increase in the thalamus was positively correlated with Tr(D) and with the load of small deep infarcts within the white matter and negatively correlated with the Mini-Mental State Examination score. CONCLUSIONS: Our results suggest that microstructural tissue alterations are present in the putamen and thalamus, outside the typical lacunar infarcts in CADASIL. In the thalamus, these microstructural changes appear constant and are even observed in asymptomatic subjects. Some of these thalamic changes appear to result from degeneration of thalamocortical pathways secondary to ischemic white matter damage. The importance of this degenerative phenomenon in the pathophysiology of CADASIL requires further investigation.

Analysis of Variance↗

Structural group analysis of functional activation maps.

We present here a new method for cerebral activation detection over a group of subjects. This method is performed using individual activation maps of any sort. It aims at processing a group analysis while preserving individual information and at overcoming as far as possible limitations of the spatial normalization used to compare different subjects. We designed it such that it provides the individual occurrence of the activations detected at a group level. The localization can then be performed on the individual anatomy of each subject. The analysis starts with a hierarchical multiscale object-based description of each individual map. These descriptions are then compared, rather than comparing the images directly. The analysis is thus performed at an object level instead of voxel by voxel. It is made using a comparison graph, on which a labeling process is performed. The label field on the graph is modeled by a Markov random field, which allows us to introduce high-level rules of interrogation of the data. The process has been evaluated on simulated data and real data from a PET protocol.

Brain↗

Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography.

OBJECTIVE: The nature of the underlying brain dysfunction of childhood autism, a life-long severe developmental disorder, is not well understood. Although researchers using functional brain imaging have attempted to contribute to this debate, previous studies have failed to report consistent localized neocortical brain dysfunction. The authors reasoned that early methods may have been insensitive to such dysfunction, which may now be detectable with improved technology. METHOD: To test this hypothesis, regional cerebral blood flow was measured with positron emission tomography (PET) in 21 children with primary autism and in 10 nonautistic children with idiopathic mental retardation. Autistic and comparison groups were similar in average age and developmental quotients. The authors first searched for focal brain dysfunction in the autistic group by using a voxel-based whole brain analysis and then assessed the sensitivity of the method to detect the abnormality in individual children. An extension study was then performed in an additional group of 12 autistic children. RESULTS: The first autistic group had a highly significant hypoperfusion in both temporal lobes centered in associative auditory and adjacent multimodal cortex, which was detected in 76% of autistic children. Virtually identical results were found in the second autistic group in the extension study. CONCLUSIONS: PET and voxel-based image analysis revealed a localized dysfunction of the temporal lobes in school-aged children with idiopathic autism. Further studies will clarify the relationships between these temporal abnormalities and the perceptive, cognitive, and emotional developmental abnormalities characteristic of this disorder.

Adolescent↗

Effect of selenium on rat thioredoxin reductase activity: increase by supranutritional selenium and decrease by selenium deficiency.

Thioredoxin reductase is a newly identified selenocysteine-containing enzyme that catalyzes the NADPH-dependent reduction of the redox protein thioredoxin. Thioredoxin stimulates cell growth, is found in dividing normal cells, and is over-expressed in a number of human cancers. Redox activity is essential for the growth effects of thioredoxin; thus, thioredoxin reductase could be involved in regulating cell growth through its reduction of thioredoxin. In rats fed a selenium-deficient diet (<0.01 ppm) for up to 98 days, thioredoxin reductase activity was decreased, compared with that of rats fed a normal selenium diet (0.1 ppm), in lung, liver, and kidney, while thioredoxin reductase activity in the spleen and prostate was unaltered. Rats fed a high selenium diet (1.0 ppm) exhibited a 1.5-fold increase in kidney and a 2.0-fold increase in lung thioredoxin reductase activity that began to return to control values after 20 and 69 days, respectively. Liver showed a 2.1-fold increase in thioredoxin reductase activity at 20 days only. Thioredoxin reductase protein levels measured by western blotting using an antibody to human thioredoxin reductase were decreased in rats fed the selenium-deficient diet and did not increase in rats fed the high selenium diet. Rat thioredoxin reductase was shown to incorporate 75Selenium. Thus, in some tissues at least, the increase in thioredoxin reductase activity of rats fed a high selenium diet appears to be due to an increase in the specific activity of the enzyme, possibly caused by increased selenocysteine incorporation without an increase in thioredoxin reductase protein synthesis.

Animals↗

Clinical severity in CADASIL related to ultrastructural damage in white matter: in vivo study with diffusion tensor MRI.

BACKGROUND AND PURPOSE: CADASIL is a newly recognized cause of subcortical ischemic strokes that progressively leads to dementia associated with pseudobulbar palsy and severe motor disability. This deleterious progression and the severity of clinical presentation are widely variable among affected subjects. The exact role played by MRI white-matter abnormalities, a hallmark of the disease, in the severity of the clinical phenotype remains poorly understood. METHODS: To address this issue, we used diffusion tensor imaging (DTI), a new MRI technique highly sensitive to white-matter microstructural changes, in 16 symptomatic patients and 10 age-matched controls. Mean diffusivity and anisotropy of diffusion were measured within hyperintensities identified on T2-weighted images (T2WI) and outside these lesions on 4 slices at the level of centrum semiovale. RESULTS: We found a 60% increase of water mean diffusivity and a parallel loss of diffusion anisotropy in hyperintensities identified on T2WI. The same pattern of diffusion changes, but of lesser intensity, was found in the normal-appearing white matter on T2WI. Mean diffusivity in regions with increased signal on T2WI was higher in patients with severe clinical disability compared with those with no or mild deficit (1.33+/-0.11 versus 1.13+/-0.11 10(-3) mm(2)/s, P<0.01). Furthermore, diffusion measured within T2 hyperintensities correlated with both the Mini-Mental State Examination and Rankin scale scores. In patients with a severe clinical status, the increase of water diffusion in these regions exceeded 70% in comparison with values obtained in the normal white matter in control subjects. CONCLUSIONS: These results indicate that DTI is able to detect important ultrastructural changes in regions with increased signal on T2WI and within the normal-appearing white matter in CADASIL. The diffusion changes might be related to both neuronal loss and demyelination. The degree of the underlying ultrastructural alterations is related to the severity of the clinical status with a possible threshold level of white-matter damage above which severe neurological impairment may occur in this disease. DTI appears to be a promising technique for monitoring disease progression in CADASIL.

Adult↗

Use of subtraction ictal SPECT co-registered to MRI for optimizing the localization of seizure foci in children.

UNLABELLED: Ictal SPECT studies are increasingly used to localize seizure foci in children with refractory epilepsy, but few studies have reported on ictal-interictal subtraction images co-registered to MRI at this age. METHODS: Twenty-seven children with partial epilepsy (aged 3 mo-18 y) underwent ictal ethyl cysteinate dimer (ECD) SPECT (20 mCi/1.73 m2) combined with video-electroencephalography (EEG) and interictal ECD SPECT followed 2 d later by three-dimensional MRI. Ictal-interictal and interictal-ictal subtraction images were computed by registering and normalizing the ictal to the interictal SPECT scans for each child. The ictal, interictal SPECT and subtraction images were registered to each child's MRI. Difference images (ictal-interictal) were then superimposed on MRI for anatomic localization of the perfusion changes. Intra- and interobserver reproducibility and "facility of interpretation" of overlay images were compared with standard analysis of the non-coregistered ictal and interictal scans. RESULTS: Overlay images allowed the detection of at least one hyperperfused focus in 93% of the children, compared with 74% using ictal and interictal scans separately. Seizure onset was suspected clinically, on EEG or on MRI in 20 children. Overlay images were concordant (n = 11) or larger (n = 7) than the suspected focus in 18 of 20 (90%), whereas these images failed to show any abnormality in 1 child and were discordant with MRI in another patient. In the remaining 7, images showed cortical localization in 6 patients. Among the 5 patients who underwent electrocorticography, overlay images were concordant in 3, larger in 1 and absent in 1. The intra- and interobserver reproducibility and facility of interpretation were significantly higher using overlay images than standard analysis, even when ictal and interictal SPECT were co-registered. CONCLUSION: The co-registration of ictal-interictal subtraction SPECT images to MRI seems to be a helpful technique in localizing the onset of seizure and guiding the intracranial recording in childhood epilepsy. Moreover, this method improves sensitivity, enhances intra- and interobserver reproducibility and makes interpretation easier.

Adolescent↗

In vivo imaging of human cerebral acetylcholinesterase.

We report here the first positron emission tomography (PET) images showing the in vivo regional distribution of acetylcholinesterase (AChE) in human brain. The study was carried out in eight healthy human volunteers using as a tracer [11C]-physostigmine ([11C]PHY), an inhibitor of AChE. After intravenous injection of [11C]PHY, radioactivity was rapidly taken up in brain tissue and reached maximal uptake within a few minutes, following a regional pattern mostly related to cerebral perfusion. After the peak, the cerebral radioactivity gradually decreased with a half-life varying from 20 to 35 min, depending on the brain structure. [11C] PHY retention was higher in regions rich in AChE, such as the striatum (half-life, 35 min), than in regions poor in AChE, such as the cerebral cortex (half-life, 20 min). At later times (25-35 min postinjection), the cerebral distribution of [11C]PHY was typical of AChE activity: putamen-caudate > cerebellum > brainstem > thalamus > cerebral cortex, with a striatal to cortex ratio of 2. These results suggest that PET studies with [11C]PHY can provide in vivo brain mapping of human AChE and are promising for the study of changes in AChE levels associated with neurodegenerative diseases.

Acetylcholinesterase↗

Clinical correlates of [18F]fluorodopa uptake in five grafted parkinsonian patients.

To assess the efficacy of fetal mesencephalic grafts in Parkinson's disease, it is important to know if the grafted cells survive and are functional. Positron emission tomography (PET) and [18F]fluorodopa ([18F]dopa) have been used to demonstrate the survival of the grafted cells, but the relationship of [18F]dopa uptake changes in the grafted striatum to motor function remains unclear. We investigated this question with 16 serial PET scans in 5 severe parkinsonian patients unilaterally grafted in whom we found a significant and progressive increase of the [18F]dopa uptake in the grafted putamen. The number of patients was too small to assess the sensitivity of [18F]dopa PET scans in individual patients. Yet, by analyzing the 16 serial PET scans we found a correlation between the [18F]dopa uptake (Ki) in the grafted putamen and the percentage of daily time spent "on," suggesting that Ki changes have a functional meaning. In addition, the Ki values were correlated with the contralateral finger dexterity to the same extent in both the grafted and nongrafted putamen. These results indicate that [18F]dopa uptake reflects the motor function of the opposite side of the body, similarly in the grafted and ungrafted putamen, at least in terms of these tasks. Finally, extrapolating from these correlations offers the suggestion that clinical optimal results of the graft could be achieved if the graft brings the Ki values in the putamen to about two standard deviations of mean control values.

Brain↗

Is interictal temporal hypometabolism related to mesial temporal sclerosis? A positron emission tomography/magnetic resonance imaging confrontation.

The mechanism of interictal glucose hypometabolism remains unclear, but this abnormality occurs more frequently in temporal lobe epilepsy (TLE) than in other types of partial epilepsy. Therefore temporal hypometabolism has been suggested to reflect mesial temporal sclerosis (MTS). To investigate this, we selected 22 patients with refractory partial epilepsy of mesial temporal lobe origin (MTLE) who had hippocampal atrophy based on magnetic resonance imaging (MRI) volumetric analysis. We then analyzed the metabolic correlates of unilateral hippocampal atrophy. Thirteen temporal regions of interest (ROI) were defined on MRI scans for each individual and then applied to high-resolution FDG-positron emission tomography (PET) images obtained parallel to the long axis of the hippocampus. The most hypometabolic regions were the temporal pole and the hippocampal region. When we analyzed ensembles of temporal regions grouped into related networks, the temporolimbic network, which included the hippocampal region and the temporal pole, was abnormal in 95% of the patients at a 3-SD threshold. PET hypometabolism was highly correlated with the degree of hippocampal atrophy in this network, but not in other parts of the temporal lobe, which were less frequently hypometabolic. These data indicate that hypometabolism is a consequence of MTS in the temporolimbic region but not necessarily in the other parts of the temporal lobe. Our results also suggest that the combination of PET and MRI may facilitate the noninvasive diagnosis of MTLE.

Adult↗

Generic model for the localization of the cerebral cortex and preoperative multimodal integration in epilepsy surgery.

In cerebral cortex neurosurgery and particularly in epilepsy surgery, the recognition of individual cortical anatomic landmarks is necessary for presurgical evaluation and planning. To overcome the classical great variability in the superficial aspect of the human cerebral cortex, we have developed an original generic description of the cerebral cortex in a three-dimensional structure. The result is a generic model matching the cortical topography of each brain regardless of inter- and intra-individual variability. In this model, sulcal roots (fundi) are separated by more or less superficial annectent gyrus, and buried by operculization during the gyrification. This original generic model of the cerebral cortex enabled us to develop a mathematical methodology for the construction of a structural representation of the cortical topography from a T1-weighted three-dimensional MR image. This program can provide automatic detection and recognition of the main cortical sulci.

Algorithms↗

Fast nonsupervised 3D registration of PET and MR images of the brain.

We propose a fully nonsupervised methodology dedicated to the fast registration of positron emission tomography (PET) and magnetic resonance images of the brain. First, discrete representations of the surfaces of interest (head or brain surface) are automatically extracted from both images. Then, a shape-independent surface-matching algorithm gives a rigid body transformation, which allows the transfer of information between both modalities. A three-dimensional (3D) extension of the chamfer-matching principle makes up the core of this surface-matching algorithm. The optimal transformation is inferred from the minimization of a quadratic generalized distance between discrete surfaces, taking into account between-modality differences in the localization of the segmented surfaces. The minimization process is efficiently performed via the precomputation of a 3D distance map. Validation studies using a dedicated brain-shaped phantom have shown that the maximum registration error was of the order of the PET pixel size (2 mm) for the wide variety of tested configurations. The software is routinely used today in a clinical context by the physicians of the Service Hospitalier Frédéric Joliot (> 150 registrations performed). The entire registration process requires approximately 5 min on a conventional workstation.

Algorithms↗