Publications by authors named "Jean-Paul Armspach"

39 Publications

Brain network remodelling reflects tau-related pathology prior to memory deficits in Thy-Tau22 mice.

Brain 2020 12;143(12):3748-3762

Laboratory of Engineering, Informatics and Imaging (ICube), Integrative multimodal imaging in healthcare (IMIS), UMR 7357, University of Strasbourg, 67000 Strasbourg, France.

In Alzheimer's disease, the tauopathy is known as a major mechanism responsible for the development of cognitive deficits. Early biomarkers of such affectations for diagnosis/stratification are crucial in Alzheimer's disease research, and brain connectome studies increasingly show their potential establishing pathology fingerprints at the network level. In this context, we conducted an in vivo multimodal MRI study on young Thy-Tau22 transgenic mice expressing tauopathy, performing resting state functional MRI and structural brain imaging to identify early connectome signatures of the pathology, relating with histological and behavioural investigations. In the prodromal phase of tauopathy, before the emergence of cognitive impairments, Thy-Tau22 mice displayed selective modifications of brain functional connectivity involving three main centres: hippocampus (HIP), amygdala (AMG) and the isocortical areas, notably the somatosensory (SS) cortex. Each of these regions showed differential histopathological profiles. Disrupted ventral HIP-AMG functional pathway and altered dynamic functional connectivity were consistent with high pathological tau deposition and astrogliosis in both hippocampus and amygdala, and significant microglial reactivity in amygdalar nuclei. These patterns were concurrent with widespread functional hyperconnectivity of memory-related circuits of dorsal hippocampus-encompassing dorsal HIP-SS communication-in the absence of significant cortical histopathological markers. These findings suggest the coexistence of two intermingled mechanisms of response at the functional connectome level in the early phases of pathology: a maladaptive and a likely compensatory response. Captured in the connectivity patterns, such first responses to pathology could further be used in translational investigations as a lead towards an early biomarker of tauopathy as well as new targets for future treatments.
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http://dx.doi.org/10.1093/brain/awaa312DOI Listing
December 2020

A mouse model of MSU-induced acute inflammation suggests imiquimod-dependent targeting of as relevant therapy for gout patients.

Theranostics 2020 12;10(5):2158-2171. Epub 2020 Jan 12.

Université de Strasbourg, INSERM, ImmunoRhumatologie Moléculaire UMR_S 1109, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, F-67000 Strasbourg, France.

: The role of Monosodium Urate (MSU) crystals in gout pathophysiology is well described, as is the major impact of IL-1β in the inflammatory reaction that constitutes the hallmark of the disease. However, despite the discovery of the NLRP3 inflammasome and its role as a Pattern Recognition Receptor linking the detection of a danger signal (MSU) to IL-1β secretion , the precise mechanisms leading to joint inflammation in gout patients are still poorly understood. : Acute urate crystal inflammation was obtained by subcutaneous injections of MSU crystals in mice. Symptoms were followed by scoring, cytokine quantification by ELISA and western blot, gene expression by RT-qPCR and RNAseq; Magnetic Resonance Imaging was also used to assess inflammation. : We provide an extensive clinical, biological and molecular characterization of an acute uratic inflammation mouse model which accurately mimics human gout. We report the efficacy of topical imiquimod treatment and its impact on Interferon-dependent down modulation of gene expression in this experimental model. : Our work reveals several key features of MSU-dependent inflammation and identifies novel therapeutic opportunities for gout patients.
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http://dx.doi.org/10.7150/thno.40650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019178PMC
January 2020

Correlations of quantitative MRI metrics with myelin basic protein (MBP) staining in a murine model of demyelination.

NMR Biomed 2019 09 21;32(9):e4116. Epub 2019 Jun 21.

Université de Strasbourg, CNRS, ICube, FMTS, Strasbourg, France.

Myelin imaging in the central nervous system is essential for monitoring pathologies involving white matter alterations. Various quantitative MRI protocols relying on the modeling of the interactions of water protons with myelinated tissues have shown sensitivities in case of myelin disruption. Some extracted model parameters are more sensitive to demyelination, such as the bound pool fraction (f) in quantitative magnetization transfer imaging (qMTI), the radial diffusivity in diffusion tensor imaging (DTI), and the myelin water fraction (MWF) in myelin water imaging (MWI). A 3D ultrashort echo time (UTE) sequence within an appropriate water suppression condition (Diff-UTE) is also considered for the direct visualization of the myelin semi-solid matrix (Diff-UTE normalized signal; rSPF). In this paper, we aimed at assessing the sensitivities and correlations of the parameters mentioned above to an immuno-histological study of the myelin basic protein (MBP) in a murine model of demyelination at 7 T. We demonstrated a high sensitivity of the MRI metrics to demyelination, and strong Spearman correlations in the corpus callosum between histology, macromolecular proton fraction (ρ>0.87) and Diff-UTE signal (ρ>0.76), but moderate ones with radial diffusivity and MWF (|ρ|<0.70).
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http://dx.doi.org/10.1002/nbm.4116DOI Listing
September 2019

Functional Disconnectivity during Inter-Task Resting State in Dementia with Lewy Bodies.

Dement Geriatr Cogn Disord 2018 3;45(1-2):105-120. Epub 2018 May 3.

IMIS/Neurocrypto, French National Centre for Scientific Research (CNRS), ICube Laboratory and Fédération de Médecine Translationnelle de Strasbourg (FMTS), University of Strasbourg, Strasbourg, France.

Aims: Limited research has been done on the functional connectivity in visuoperceptual regions in dementia with Lewy bodies (DLB) patients. This study aimed to investigate the functional connectivity differences between a task condition and an inter-task resting state condition within a visuoperceptual paradigm, in DLB patients compared with Alzheimer disease (AD) patients and healthy elderly control subjects.

Methods: Twenty-six DLB, 29 AD, and 22 healthy subjects underwent a detailed clinical and neuropsychological examination along with a functional MRI during the different conditions of a visuoperceptual paradigm. Functional images were analyzed using group-level spatial independent component analysis and seed-based connectivity analyses.

Results: While the DLB patients scored well and did not differ from the control and AD groups in terms of functional activity and connectivity during the task conditions, they showed decreased functional connectivity in visuoperceptual regions during the resting state condition, along with a temporal impairment of the default-mode network activity. Functional connectivity disturbances were also found within two attentional-executive networks and between these networks and visuoperceptual regions.

Conclusion: We found a specific functional profile in the switching between task and resting state conditions in DLB patients. This result could help better characterize functional impairments in DLB and their contribution to several core symptoms of this pathology such as visual hallucinations and cognitive fluctuations.
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http://dx.doi.org/10.1159/000486780DOI Listing
October 2018

A diffusion-based method for long-T suppression in steady state sequences: Validation and application for 3D-UTE imaging.

Magn Reson Med 2018 08 19;80(2):548-559. Epub 2017 Dec 19.

Université de Strasbourg, CNRS, ICube, FMTS, Strasbourg, France.

Purpose: To introduce a novel method for long-T signal physical suppression in steady-state based on configuration states combination and modulation using diffusion weighting. Its efficiency in yielding a high contrast in short-T structures using an ultrashort echo time acquisition module (Diff-UTE) is compared to the adiabatically prepared Inversion-Recovery-UTE sequence (IR-UTE).

Theory And Methods: Using a rectangular-pulse prepared 3D-UTE sequence, the possibility of long-T component signal cancellation through diffusion effects is addressed, and the condition met for sets of sequence parameters. Simultaneously, the short-T component signal is maximized using a Bloch equation-based optimization process. The method is evaluated from simulations, and experiments are conducted on a phantom composed of short and long-T components, as well as on an ex vivo mouse head.

Results: Within equal scan times, the proposed method allowed for an efficient long-T signal suppression, and expectedly yielded a higher signal to noise ratio in short-T structures compared to the IR-UTE technique, although an intrinsic short-T signal loss is expected through the preparation module.

Conclusion: The Diff-UTE method represents an interesting alternative to the IR-UTE technique. Diffusion weighting allowing for a long-T suppression results in a less penalizing method to generate a high and selective contrast in short-T components. Magn Reson Med 80:548-559, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.27057DOI Listing
August 2018

Cockayne syndrome: a diffusion tensor imaging and volumetric study.

Br J Radiol 2016 Nov 19;89(1067):20151033. Epub 2016 Sep 19.

2 Laboratoire ICube, UMR 7357/FMTS/Université de Strasbourg-CNRS, Strasbourg, France.

Objective: Cockayne syndrome (CS) is a rare disorder characterized by severe brain atrophy, white matter (WM) hypomyelination and basal ganglia calcifications. This study aimed to quantify atrophy and WM abnormalities using diffusion tensor imaging (DTI) and volumetric analysis, to evaluate possible differences between CS subtypes and to determine whether DTI findings may correspond to a hypomyelinating disorder.

Methods: 14 patients with CS and 14 controls underwent brain MRI including DTI and a volumetric three-dimensional T weighted sequence. DTI analysis was made through regions of interest within the whole brain to obtain fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values and in the left centrum semiovale to obtain DTI eigenvalues. The Student's t-test was used to compare patients and controls, and CS subtypes. Given the small number of patients with CS, they were pooled into two groups: moderate (CS1/CS3) and severe (CS2/cerebro-oculo-facio-skeletal syndrome).

Results: Total brain volume in CS was reduced by 57%, predominantly in the infratentorial area (68%) (p < 0.001). Total brain volume reduction was greater in the severe group, but there was no difference in the degree of infratentorial atrophy in the two groups (p = 0.7). Mean FA values were lower, whereas ADC was higher in most of the WM in patients with CS (p < 0.05). ADC in the splenium of the corpus callosum and the posterior limb of the internal capsule and FA in the cerebral peduncles were significantly different between the two groups (p < 0.05). Mean ADC values corresponded to a hypomyelinating disorder. All DTI eigenvalues were higher in patients with CS, mainly for transverse diffusivity (+51%) (p < 0.001).

Conclusion: DTI and volumetric analysis provide quantitative information for the characterization of CS and may be particularly useful for evaluating therapeutic intervention. Advances in knowledge: DTI combined with volumetric analysis provides additional information useful for not only the characterization of CS and distinction of clinical subtypes but also monitoring of therapeutic interventions.
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http://dx.doi.org/10.1259/bjr.20151033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124826PMC
November 2016

Identifying Dynamic Functional Connectivity Changes in Dementia with Lewy Bodies Based on Product Hidden Markov Models.

Front Comput Neurosci 2016 23;10:60. Epub 2016 Jun 23.

Centre National de la Recherche Scientifique, FMTS, University of Strasbourg, ICube-UMR 7357Strasbourg, France; CMRR (Memory Resources and Research Center), University Hospital of Strasbourg, Geriatrics and Neurology ServicesStrasbourg, France.

Exploring time-varying connectivity networks in neurodegenerative disorders is a recent field of research in functional MRI. Dementia with Lewy bodies (DLB) represents 20% of the neurodegenerative forms of dementia. Fluctuations of cognition and vigilance are the key symptoms of DLB. To date, no dynamic functional connectivity (DFC) investigations of this disorder have been performed. In this paper, we refer to the concept of connectivity state as a piecewise stationary configuration of functional connectivity between brain networks. From this concept, we propose a new method for group-level as well as for subject-level studies to compare and characterize connectivity state changes between a set of resting-state networks (RSNs). Dynamic Bayesian networks, statistical and graph theory-based models, enable one to learn dependencies between interacting state-based processes. Product hidden Markov models (PHMM), an instance of dynamic Bayesian networks, are introduced here to capture both statistical and temporal aspects of DFC of a set of RSNs. This analysis was based on sliding-window cross-correlations between seven RSNs extracted from a group independent component analysis performed on 20 healthy elderly subjects and 16 patients with DLB. Statistical models of DFC differed in patients compared to healthy subjects for the occipito-parieto-frontal network, the medial occipital network and the right fronto-parietal network. In addition, pairwise comparisons of DFC of RSNs revealed a decrease of dependency between these two visual networks (occipito-parieto-frontal and medial occipital networks) and the right fronto-parietal control network. The analysis of DFC state changes thus pointed out networks related to the cognitive functions that are known to be impaired in DLB: visual processing as well as attentional and executive functions. Besides this context, product HMM applied to RSNs cross-correlations offers a promising new approach to investigate structural and temporal aspects of brain DFC.
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http://dx.doi.org/10.3389/fncom.2016.00060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918689PMC
July 2016

Brain perfusion in dementia with Lewy bodies and Alzheimer's disease: an arterial spin labeling MRI study on prodromal and mild dementia stages.

Alzheimers Res Ther 2016 07 12;8:29. Epub 2016 Jul 12.

ICube laboratory, University of Strasbourg, CNRS, FMTS(Fédération de Médecine Translationnelle de Strasbourg), ICube - IPB, Faculté de Médecine, 4 rue Kirschleger, Strasbourg, 67085, France.

Background: We aimed to describe specific changes in brain perfusion in patients with dementia with Lewy bodies (DLB) at both the prodromal (also called mild cognitive impairment) and mild dementia stages, relative to patients with Alzheimer's disease (AD) and controls.

Methods: Altogether, 96 participants in five groups (prodromal DLB, prodromal AD, DLB with mild dementia, AD with mild dementia, and healthy elderly controls) took part in an arterial spin labeling MRI study. Three analyses were performed: a global perfusion value comparison, a voxel-wise analysis of both absolute and relative perfusion, and a linear discriminant analysis. These were used to assess the global decrease in perfusion, regional changes, and the sensitivity and specificity of these changes.

Results: Patterns of perfusion in DLB differed from AD and controls in both the prodromal stage and dementia, DLB having more deficits in frontal, insular, and temporal cortices whereas AD showed reduced perfusion in parietal and parietotemporal cortices. Decreases but also increases of perfusion in DLB relative to controls were observed in both absolute and relative measurements. All these regional changes of perfusion classified DLB patients with respect to either healthy controls or AD with sensitivity from 87 to 100 % and specificity from 90 to 96 % depending on the stage of the disease.

Conclusions: Our results are consistent with previous studies. We extend the scope of those studies by integrating prodromal DLB patients and by describing both hypo- and hyperperfusion in DLB. While decreases in perfusion may relate to functional impairments, increases might suggest a functional compensation of some brain areas.
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http://dx.doi.org/10.1186/s13195-016-0196-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940880PMC
July 2016

Which is the most appropriate strategy for conducting multivariate voxel-based group studies on diffusion tensors?

Neuroimage 2016 Nov 27;142:99-112. Epub 2016 May 27.

ICube, University of Strasbourg, CNRS, Fédération de Médecine Translationnelle de Strasbourg (FMTS), France.

There is a real need in the neuroscience community for efficient tools to compare Diffusion Tensor Magnetic Resonance Imaging across cohorts of subjects. Most studies focus on the comparison of scalar images such as fractional anisotropy or mean diffusivity. Although different statistical frameworks have been proposed to compare the whole diffusion tensor information, they are still seldom used in neuroimaging studies. In this paper, we investigate on both simulated and real data whether there is a real added value of considering the whole tensor information for conducting voxel-based group studies. Then, we compare two statistical tests dedicated to tensor, namely the Cramér test and a tensor-based extension of the General Linear Model (GLM), the latter presenting the advantage to account for covariates. We also evaluate the impact of different metrics (Euclidean, Log-Euclidean and affine-invariant Riemannian metrics) for estimating the GLM parameters. Finally, we address the problem of interpreting the change detection maps obtained by tensor-based methods by proposing a way to characterize each of the detected clusters according to several scalar indices. Our study suggests that if there is no prior assumption about the nature of the expected changes, it is really preferable to use tensor-based rather than scalar-based statistical analysis. The Cramér test can advantageously be used when no confounding variable hampers the group comparison, otherwise the GLM should be considered. Finally, the different metrics show similar performance in the real scenario, with a significant computational overhead for the Riemannian framework.
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http://dx.doi.org/10.1016/j.neuroimage.2016.05.040DOI Listing
November 2016

Cognitive and affective theory of mind in dementia with Lewy bodies and Alzheimer's disease.

Alzheimers Res Ther 2016 Mar 16;8(1):10. Epub 2016 Mar 16.

Neuropsychology Unit, Memory Resource and Research Centre (CMRR), Department of Neurology, University Hospital of Strasbourg, Strasbourg, France.

Background: Theory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have been published. The aim of our study was to assess ToM in patients with DLB and to search for neural correlates of potential deficits.

Methods: Thirty-three patients with DLB (DLB group) and 15 patients with Alzheimer's disease (AD group), all in the early stage of the disease, as well as 16 healthy elderly control subjects (HC group), were included in the study. After a global cognitive assessment, we used the Faux Pas Recognition (FPR) test, the Reading the Mind in the Eyes (RME) test and Ekman's Facial Emotion Recognition test to assess cognitive and affective components of ToM. Patients underwent cerebral 3-T magnetic resonance imaging, and atrophy of grey matter was analysed using voxel-based morphometry. We performed a one-sample t test to investigate the correlation between each ToM score and grey matter volume and a two-sample t test to compare patients with DLB impaired with those non-impaired for each test.

Results: The DLB group performed significantly worse than the HC group on the FPR test (P = 0.033) and the RME test (P = 0.015). There was no significant difference between the AD group and the HC group or between the DLB group and the AD group. Some brain regions were associated with ToM impairments. The prefrontal cortex, with the inferior frontal cortex and the orbitofrontal cortex, was the main region, but we also found correlations with the temporoparietal junction, the precuneus, the fusiform gyrus and the insula.

Conclusions: This study is the first one to show early impairments of ToM in DLB. The two cognitive and affective components both appear to be affected in this disease. Among patients with ToM difficulties, we found atrophy in brain regions classically involved in ToM, which reinforces the neuronal network of ToM. Further studies are now needed to better understand the neural basis of such impairment.
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http://dx.doi.org/10.1186/s13195-016-0179-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793654PMC
March 2016

Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages.

PLoS One 2015 10;10(6):e0127396. Epub 2015 Jun 10.

Institute of Neuroscience, Campus for Aging and Vitality, Newcastle University, Newcastle upon Tyne, United Kingdom.

Objectives: To assess and compare cortical thickness (CTh) of patients with prodromal Dementia with Lewy bodies (pro-DLB), prodromal Alzheimer's disease (pro-AD), DLB dementia (DLB-d), AD dementia (AD-d) and normal ageing.

Methods: Study participants(28 pro-DLB, 27 pro-AD, 31 DLB-d, 54 AD-d and 33 elderly controls) underwent 3Tesla T1 3D MRI and detailed clinical and cognitive assessments. We used FreeSurfer analysis package to measure CTh and investigate patterns of cortical thinning across groups.

Results: Comparison of CTh between pro-DLB and pro-AD (p<0.05, FDR corrected) showed more right anterior insula thinning in pro-DLB, and more bilateral parietal lobe and left parahippocampal gyri thinning in pro-AD. Comparison of prodromal patients to healthy elderly controls showed the involvement of the same regions. In DLB-d (p<0.05, FDR corrected) cortical thinning was found predominantly in the right temporo-parietal junction, and insula, cingulate, orbitofrontal and lateral occipital cortices. In AD-d(p<0.05, FDR corrected),the most significant areas affected included the entorhinal cortices, parahippocampal gyri and parietal lobes. The comparison of AD-d and DLB-d demonstrated more CTh in AD-d in the left entorhinal cortex (p<0.05, FDR corrected).

Conclusion: Cortical thickness is a sensitive measure for characterising patterns of grey matter atrophy in early stages of DLB distinct from AD. Right anterior insula involvement may be a key region at the prodromal stage of DLB and needs further investigation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0127396PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489516PMC
March 2016

Neural correlates of visual hallucinations in dementia with Lewy bodies.

Alzheimers Res Ther 2015 17;7(1). Epub 2015 Feb 17.

Neuropsychology Unit, Neurology Department, University Hospital of Strasbourg, 1, avenue Molière, 67098 Strasbourg, France ; CMRR (Memory Resource and Research Center), University Hospital of Strasbourg, 1, avenue Molière, 67098 Strasbourg, France ; University of Strasbourg and CNRS, ICube Laboratory UMR 7357, IMIS team and FMTS (Strasbourg Federation of Translational Medicine), 1, place de l'Hôpital, 67000 Strasbourg, France.

Introduction: The aim of this study was to investigate the association between visual hallucinations in dementia with Lewy bodies (DLB) and brain perfusion using single-photon emission computed tomography.

Methods: We retrospectively included 66 patients with DLB, 36 of whom were having visual hallucinations (DLB-hallu) and 30 of whom were not (DLB-c). We assessed visual hallucination severity on a 3-point scale of increasing severity: illusions, simple visual hallucinations and complex visual hallucinations. We performed voxel-level comparisons between the two groups and assessed correlations between perfusion and visual hallucinations severity.

Results: We found a significant decrease in perfusion in the left anterior cingulate cortex, the left orbitofrontal cortex and the left cuneus in the DLB-hallu group compared with the DLB-c group. We also found a significant correlation between decreased bilateral anterior cingulate cortex, left orbitofrontal cortex, right parahippocampal gyrus, right inferior temporal cortex and left cuneus perfusion with the severity of hallucinations.

Conclusions: Visual hallucinations seem to be associated with the impairment of anterior and posterior regions (secondary visual areas, orbitofrontal cortex and anterior cingulate cortex) involved in a top-down and bottom-up mechanism, respectively. Furthermore, involvement of the bilateral anterior cingulate cortex and right parahippocampal gyrus seems to lead to more complex hallucinations.
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http://dx.doi.org/10.1186/s13195-014-0091-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339752PMC
February 2015

3D+t brain MRI segmentation using robust 4D Hidden Markov Chain.

Annu Int Conf IEEE Eng Med Biol Soc 2014 ;2014:4715-8

In recent years many automatic methods have been developed to help physicians diagnose brain disorders, but the problem remains complex. In this paper we propose a method to segment brain structures on two 3D multi-modal MR images taken at different times (longitudinal acquisition). A bias field correction is performed with an adaptation of the Hidden Markov Chain (HMC) allowing us to take into account the temporal correlation in addition to spatial neighbourhood information. To improve the robustness of the segmentation of the principal brain structures and to detect Multiple Sclerosis Lesions as outliers the Trimmed Likelihood Estimator (TLE) is used during the process. The method is validated on 3D+t brain MR images.
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http://dx.doi.org/10.1109/EMBC.2014.6944677DOI Listing
October 2015

Ischaemic strokes with reversible vasoconstriction and without thunderclap headache: a variant of the reversible cerebral vasoconstriction syndrome?

Cerebrovasc Dis 2015 24;39(1):31-8. Epub 2014 Dec 24.

Unité Neuro-Vasculaire, Service de Neurologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Reversible vasoconstriction (RV) may cause ischaemic stroke (IS) in the absence of any other defined stroke aetiology. The three objectives of our study were to evaluate the frequency of RV in a prospective series of young IS patients, to describe the detailed clinical-radiological features in the patients with RV and IS, and to compare these characteristics with those of reversible cerebral vasoconstriction syndrome (RCVS).

Methods: We identified between October 2005 and December 2010, 159 consecutive young patients (<45 years) hospitalized for an acute IS confirmed by cerebral magnetic resonance imaging. An extensive diagnostic work-up was performed including toxicological urinary screening for cannabis, cocaine and amphetamines, and the usual biological, cardiac and vascular investigations for an IS in the young. We specifically studied patients with IS and RV, which was defined as multifocal intracranial arterial stenoses confirmed by intracranial arterial imaging that resolved within 3-6 months.

Results: Out of 159 patients with IS, 21 (13%, 12 males, 9 females; mean age 32 years) had multifocal cerebral arterial stenoses that were fully reversible at 3-6 months, and no other cause for stroke. IS were located on posterior territory in 71% of cases, and vasoconstriction predominated on posterior cerebral and superior cerebellar arteries. Precipitating factors of IS and RV were the use of cannabis resin (n = 14), nasal decongestants (n = 2) and triptan (n = 1). Most cases (74%) had unusual severe headache, but none had thunderclap headache. None of 21 cases had reversible posterior leukoencephalopathy, cortical subarachnoid or intracerebral haemorrhage.

Conclusion: RV was the sole identified cause of IS in 13% of our cohort. These young patients with IS and RV may have a variant of RCVS, related to an increased susceptibility to vasoactive agents in some individuals. RV in our patients differs from the classical characteristics of RCVS by the absence of thunderclap headache, reversible brain oedema and subarachnoid or intracranial haemorrhage. Intracranial arteries should be looked for, by appropriate vascular imaging, in young patients with IS at the acute stage and during the follow-up period.
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http://dx.doi.org/10.1159/000369776DOI Listing
October 2015

Right anterior insula: core region of hallucinations in cognitive neurodegenerative diseases.

PLoS One 2014 5;9(12):e114774. Epub 2014 Dec 5.

University of Strasbourg and CNRS, ICube laboratory UMR 7357, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Strasbourg, France.

Objectives: We investigated the neural basis of hallucinations Alzheimer's disease (AD) by applying voxel-based morphometry (VBM) to anatomical and functional data from the AD Neuroimaging Initiative.

Methods: AD patients with hallucinations, based on the Neuropsychiatric Inventory (NPI-Q) (AD-hallu group; n = 39), were compared to AD patients without hallucinations matched for age, sex, educational level, handedness and MMSE (AD-c group; n = 39). Focal brain volume on MRI was analyzed and compared between the two groups according to the VBM method. We also performed voxel-level correlations between brain volume and hallucinations intensity. A similar paradigm was used for the PET analysis. "Core regions" (i.e. regions identified in both MRI and PET analyses, simply done by retaining the clusters obtained from the two analyses that are overlapping) were then determined.

Results: Regions with relative atrophy in association with hallucinations were: anterior part of the right insula, left superior frontal gyrus and lingual gyri. Regions with relative hypometabolism in association with hallucinations were a large right ventral and dorsolateral prefrontal area. "Core region" in association with hallucinations was the right anterior part of the insula. Correlations between intensity of hallucinations and brain volume were found in the right anterior insula, precentral gyrus, superior temporal gyrus, and left precuneus. Correlations between intensity of hallucinations and brain hypometabolism were found in the left midcingulate gyrus. We checked the neuropathological status and we found that the 4 patients autopsied in the AD-hallu group had the mixed pathology AD and Dementia with Lewy bodies (DLB).

Conclusion: Neural basis of hallucinations in cognitive neurodegenerative diseases (AD or AD and DLB) include a right predominant anterior-posterior network, and the anterior insula as the core region. This study is coherent with the top-down/bottom-up hypotheses on hallucinations but also hypotheses of the key involvement of the anterior insula in hallucinations in cognitive neurodegenerative diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0114774PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257732PMC
April 2016

High frequency of intracranial arterial stenosis and cannabis use in ischaemic stroke in the young.

Cerebrovasc Dis 2014 23;37(6):438-43. Epub 2014 Jul 23.

Unité Neuro-Vasculaire, Hôpitaux Universitaires de Strasbourg (HUS), Strasbourg, France.

Background: Leading aetiologies of ischaemic stroke in young adults are cervico-cerebral arterial dissections and cardio-embolism, but the causes remain undetermined in a considerable proportion of cases. In a few reports, intracranial arterial stenosis has been suggested to be a potential cause of ischaemic stroke in young adults. The aim of our work was to evaluate the frequency, characteristics and risk factors of intracranial arterial stenosis in a prospective series of young ischaemic stroke patients.

Methods: The study was based on a prospective consecutive hospital-based series of 159 patients aged 18-45 years who were admitted to our unit for an acute ischaemic stroke from October 2005 to December 2010. A structured questionnaire was used in order to assess common vascular risk factors such as hypertension, diabetes, hypercholesterolemia, use of tobacco, alcohol and illicit drugs, migraine, and, in women, oral contraceptive use. A systematic screening was performed, including the following: brain magnetic resonance imaging or, if not feasible, brain computed tomography scan, carotid and vertebral Duplex scanning and trans-cranial Doppler sonography, 3D time-of-flight magnetic resonance cerebral angiography or cerebral computed tomography angiography. Long-duration electrocardiography, trans-thoracic and trans-oesophageal echocardiography were performed and laboratory blood investigations were extensive. Urine samples were screened for cannabinoids, cocaine, amphetamine and methylene-dioxy-methamphetamine. When this initial work-up was inconclusive, trans-femoral intra-arterial selective digital subtraction angiography with reconstructed 3D images was performed.

Results: In this series, 49 patients (31%) had intracranial arterial stenosis. Other defined causes were found in 91 patients (57%), including cardio-embolism in 32 (20%), cervical dissection in 23 (14%), extracranial atherosclerosis in 7 (4%), haematological disorders in 7 (4%), small vessel disease in 1, and isolated patent foramen ovale in 21 (13%); in 19 patients (12%), ischaemic stroke was related to an undetermined aetiology. Comparing risk factors between patients with intracranial arterial stenosis and those with other definite causes showed that there were only two significant differences: a lower age and a higher frequency of vasoactive substances (especially cannabis) in patients with intracranial arterial stenosis. All intracranial arterial stenosis in patients who used vasoactive substances were located in several intracranial vessels.

Conclusions: Intracranial arterial stenosis may be an important mechanism of stroke in young patients and it should be systematically investigated using vascular imaging. Strong questioning about illicit drug consumption (including cannabis) or vasoactive medication use should also be performed. It should be emphasized for health prevention in young adults that cannabis use might be associated with critical consequences such as stroke.
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http://dx.doi.org/10.1159/000363618DOI Listing
June 2015

On the estimation and correction of bias in local atrophy estimations using example atrophy simulations.

Comput Med Imaging Graph 2013 Oct-Dec;37(7-8):538-51. Epub 2013 Aug 12.

DeVry University, Chicago Campus, 3300 North Campbell Avenue, Chicago 60618, USA. Electronic address:

Brain atrophy is considered an important marker of disease progression in many chronic neuro-degenerative diseases such as multiple sclerosis (MS). A great deal of attention is being paid toward developing tools that manipulate magnetic resonance (MR) images for obtaining an accurate estimate of atrophy. Nevertheless, artifacts in MR images, inaccuracies of intermediate steps and inadequacies of the mathematical model representing the physical brain volume change, make it rather difficult to obtain a precise and unbiased estimate. This work revolves around the nature and magnitude of bias in atrophy estimations as well as a potential way of correcting them. First, we demonstrate that for different atrophy estimation methods, bias estimates exhibit varying relations to the expected atrophy and these bias estimates are of the order of the expected atrophies for standard algorithms, stressing the need for bias correction procedures. Next, a framework for estimating uncertainty in longitudinal brain atrophy by means of constructing confidence intervals is developed. Errors arising from MRI artifacts and bias in estimations are learned from example atrophy simulations and anatomies. Results are discussed for three popular non-rigid registration approaches with the help of simulated localized brain atrophy in real MR images.
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http://dx.doi.org/10.1016/j.compmedimag.2013.07.002DOI Listing
July 2014

Evaluation of an albumin-binding gadolinium contrast agent in multiple sclerosis.

Neurology 2013 Jul 12;81(3):206-10. Epub 2013 Jun 12.

Service de Radiologie, Hôpital de Hautepierre, CHU de Strasbourg, Strasbourg, France.

Objective: The first goal of this study is to compare gadofosveset trisodium--a gadolinium agent that reversibly binds to albumin--to an extracellular contrast agent (Gd-DOTA) for the detection of multiple sclerosis lesions. The second goal is to determine the best postinjection time for the detection of contrast-enhanced lesions.

Methods: Nine patients underwent 2 MRI examinations, respectively, after Gd-DOTA (0.1 mmol/kg) and gadofosveset trisodium (0.03 mmol/kg) administration. Axial T1 spin-echo-weighted images were acquired at several time points after injection (4 minutes for Gd-DOTA, and 4, 8, 12, 16, 20 minutes, 1 hour, and 4 hours for gadofosveset trisodium). Images were analyzed by 4 neuroradiologists who marked the contrast-enhanced lesions and, for each marked lesion, chose the acquisition they preferred and segmented the lesion on their preferred acquisition.

Results: The 4-hour gadofosveset trisodium acquisition was ranked best for the 3 tasks: contrast-enhanced lesions were seen by more readers, they preferred this acquisition, and improvements of the signal enhancement (125%) and of the contrast-to-noise ratio (73%) vs Gd-DOTA at 4 minutes were observed (p < 0.05).

Conclusion: Gadofosveset trisodium after 4 hours significantly improves the number of detected contrast-enhanced multiple sclerosis lesions as compared to Gd-DOTA after 4 minutes, even though the injected dose of gadolinium was two-thirds lower.
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http://dx.doi.org/10.1212/WNL.0b013e31829bfdb9DOI Listing
July 2013

Longitudinal change detection: inference on the diffusion tensor along white matter pathways.

Med Image Anal 2013 Apr 9;17(3):375-86. Epub 2013 Feb 9.

University of Strasbourg, CNRS, ICube, FMTS Strasbourg, France.

Diffusion weighted magnetic resonance imaging (DW-MRI) makes it possible to probe brain connections in vivo. This paper presents a change detection framework that relies on white matter pathways with application to neuromyelitis optica (NMO). The objective is to detect local or global fiber diffusion property modifications between two longitudinal DW-MRI acquisitions of a patient. To this end, we develop two frameworks based on statistical tests on tensor eigenvalues to detect local or global changes along the white matter pathways: a pointwise test that compares tensor populations extracted in bundles cross sections and a fiberwise test that compares paired tensors along all the fiber bundles. Experiments on both synthetic and real data highlight the benefit of considering fiber based statistical tests compared to standard voxelwise strategies.
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http://dx.doi.org/10.1016/j.media.2013.01.004DOI Listing
April 2013

Cannabis-related stroke: myth or reality?

Stroke 2013 Feb 27;44(2):558-63. Epub 2012 Dec 27.

Unité Neuro-Vasculaire, Hôpitaux Universitaires de Strasbourg, 67085 Strasbourg Cedex, France.

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http://dx.doi.org/10.1161/STROKEAHA.112.671347DOI Listing
February 2013

White matter atrophy and cognitive dysfunctions in neuromyelitis optica.

PLoS One 2012 3;7(4):e33878. Epub 2012 Apr 3.

Neuropsychology Service, Department of Neurology, University Hospital of Strasbourg, Strasbourg, France.

Neuromyelitis optica (NMO) is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N) to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain) and VBM for focal brain volume (GM and WM), NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54%) had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM) was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in NMO patients, particularly in the WM.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0033878PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317931PMC
August 2012

Longitudinal change detection in diffusion MRI using multivariate statistical testing on tensors.

Neuroimage 2012 May 25;60(4):2206-21. Epub 2012 Feb 25.

University of Strasbourg, CNRS, UMR 7005, LSIIT, France.

This paper presents a longitudinal change detection framework for detecting relevant modifications in diffusion MRI, with application to neuromyelitis optica (NMO) and multiple sclerosis (MS). The core problem is to identify image regions that are significantly different between two scans. The proposed method is based on multivariate statistical testing which was initially introduced for tensor population comparison. We use this method in the context of longitudinal change detection by considering several strategies to build sets of tensors characterizing the variability of each voxel. These strategies make use of the variability existing in the diffusion weighted images (thanks to a bootstrap procedure), or in the spatial neighborhood of the considered voxel, or a combination of both. Results on synthetic evolutions and on real data are presented. Interestingly, experiments on NMO patients highlight the ability of the proposed approach to detect changes in the normal-appearing white matter (according to conventional MRI) that are related with physical status outcome. Experiments on MS patients highlight the ability of the proposed approach to detect changes in evolving and non-evolving lesions (according to conventional MRI). These findings might open promising prospects for the follow-up of NMO and MS pathologies.
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http://dx.doi.org/10.1016/j.neuroimage.2012.02.049DOI Listing
May 2012

Computation of axonal elongation in head trauma finite element simulation.

J Mech Behav Biomed Mater 2011 Nov 23;4(8):1905-19. Epub 2011 Jun 23.

University of Strasbourg, IMFS-CNRS, 2 rue Boussingault, 67000 Strasbourg, France.

In the case of head trauma, elongation of axons is thought to result in brain damage and to lead to Diffuse Axonal Injuries (DAI). Mechanical parameters have been previously proposed as DAI metric. Typically, brain injury parameters are expressed in terms of pressure, shearing stresses or invariants of the strain tensor. Addressing axonal deformation within the brain during head impact can improve our understanding of DAI mechanisms. A new technique based on directional measurements of water diffusion in soft tissue using Magnetic Resonance Imaging (MRI), called Diffusion Tensor Imaging (DTI), provides information on axonal orientation within the brain. The present study aims at coupling axonal orientation from a 12-patient-based DTI 3D picture, called "DTI atlas", with the Strasbourg University Finite Element Head Model (SUFEHM). This information is then integrated in head trauma simulation by computing axonal elongation for each finite element of the brain model in a post-processing of classical simulation results. Axonal elongation was selected as computation endpoint for its strong potential as a parameter for DAI prediction and location. After detailing the coupling technique between DTI atlas and the head FE model, two head trauma cases presenting different DAI injury levels are reconstructed and analyzed with the developed methodology as an illustration of axonal elongation computation. Results show that anisotropic brain structures can be realistically implemented into an existing finite element model of the brain. The feasibility of integrating axon fiber direction information within a dedicated post-processor is also established in the context of the computation of axonal elongation. The accuracy obtained when estimating level and location of the computed axonal elongation indicates that coupling classical isotropic finite element simulation with axonal structural anisotropy is an efficient strategy. Using this method, tensile elongation of the axons can be directly invoked as a mechanism for Diffuse Axonal Injury.
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http://dx.doi.org/10.1016/j.jmbbm.2011.06.007DOI Listing
November 2011

Longitudinal change detection: inference on the diffusion tensor along white-matter pathways.

Med Image Comput Comput Assist Interv 2011 ;14(Pt 2):1-8

University of Strasbourg, LSIIT, UMR 7005, CNRS, France.

Diffusion tensor magnetic resonance imaging (DT-MRI) tractography allows to probe brain connections in vivo. This paper presents a change detection framework that relies on white-matter pathways with application to neuromyelitis optica (NMO). The objective is to detect global or local fiber diffusion property modifications between two longitudinal DT-MRI acquisitions of a patient. To this end, estimation and testing tools on tensors along the white-matter pathways are considered. Two tests are implemented: a pointwise test that compares at each sampling point of the fiber bundle the tensor populations of the two exams in the cross section of the bundle and a fiberwise test that compares paired tensors along all the fiber bundle. Experiments on both synthetic and real data highlight the benefit of considering fiber based statistical tests compared to the standard voxelwise strategy.
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http://dx.doi.org/10.1007/978-3-642-23629-7_1DOI Listing
November 2011

Generalized likelihood ratio tests for change detection in diffusion tensor images: application to multiple sclerosis.

Med Image Anal 2012 Jan 8;16(1):325-38. Epub 2011 Sep 8.

University of Strasbourg, CNRS, Laboratoire des Sciences de l'Image, de l'Informatique et de la Télédétection, UMR 7005, Bd Sébastien Brant, 67412 Illkirch Cedex, France.

The automatic analysis of subtle changes between MRI scans is an important tool for monitoring disease evolution. Several methods have been proposed to detect changes in serial conventional MRI but few works have considered Diffusion Tensor Imaging (DTI), which is a promising modality for monitoring neurodegenerative disease and particularly Multiple Sclerosis (MS). In this paper, we introduce a comprehensive framework for detecting changes between two DTI acquisitions by considering different levels of representation of diffusion imaging, namely the Apparent Diffusion Coefficient (ADC) images, the diffusion tensor fields, and scalar images characterizing diffusion properties such as the fractional anisotropy and the mean diffusivity. The proposed statistical method for change detection is based on the Generalized Likelihood Ratio Test (GLRT) that has been derived for the different diffusion imaging representations, based on the core assumption of a Gaussian diffusion model and of an additive Gaussian noise on the ADCs. Results on synthetic and real images demonstrate the ability of the different tests to bring useful and complementary information in the context of the follow-up of MS patients.
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http://dx.doi.org/10.1016/j.media.2011.08.007DOI Listing
January 2012

Change detection in diffusion MRI using multivariate statistical testing on tensors.

Med Image Comput Comput Assist Interv 2010 ;13(Pt 2):117-24

University of Strasbourg, CNRS, UMR 7005, LSIIT, France.

This paper presents a longitudinal change detection framework for detecting relevant modifications in diffusion MRI, with application to Multiple Sclerosis (MS). The proposed method is based on multivariate statistical testings which were initially introduced for tensor population comparison. We use these methods in the context of longitudinal change detection by considering several strategies to build sets of tensors characterizing the variability of each voxel. These testing tools have been considered either for the comparison of tensor eigenvalues or eigenvectors, thus enabling to differentiate orientation and diffusivity changes. Results on simulated MS lesion evolutions and on real data are presented. Interestingly, experiments on an MS patient highlight the ability of the proposed approach to detect changes in non evolving lesions (according to conventional MRI) and around lesions (in the normal appearing white matter), which might open promising perspectives for the follow-up of the MS pathology.
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http://dx.doi.org/10.1007/978-3-642-15745-5_15DOI Listing
November 2010

SPECT assessment of brain activation induced by caffeine: no effect on areas involved in dependence.

Dialogues Clin Neurosci 2010 ;12(2):255-63

INSERM U666, Strasbourg, France.

Caffeine is not considered addictive, and in animals it does not trigger metabolic increases or dopamine release in brain areas involved in reinforcement and reward. Our objective was to measure caffeine effects on cerebral perfusion in humans using single photon emission computed tomography with a specific focus on areas of reinforcement and reward. Two groups of nonsmoking subjects were studied, one with a low (8 subjects) and one with a high (6 subjects) daily coffee consumption. The subjects ingested 3 mg/kg caffeine or placebo in a raspberry-tasting drink, and scans were performed 45 min after ingestion. A control group of 12 healthy volunteers receiving no drink was also studied. Caffeine consumption led to a generalized, statistically nonsignificant perfusion decrease of 6% to 8%, comparable in low and high consumers. Compared with controls, low consumers displayed neuronal activation bilaterally in inferior frontal gyrus-anterior insular cortex and uncus, left internal parietal cortex, right lingual gyrus, and cerebellum. In high consumers, brain activation occurred bilaterally only in hypothalamus. Thus, on a background of widespread low-amplitude perfusion decrease, caffeine activates a few regions mainly involved in the control of vigilance, anxiety, and cardiovascular regulation, but does not affect areas involved in reinforcing and reward.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181952PMC
August 2010

Use of simulated atrophy for performance analysis of brain atrophy estimation approaches.

Med Image Comput Comput Assist Interv 2009 ;12(Pt 2):566-74

LINC-IPB (UMR CNRS-UDS 7191), Strasbourg, France.

In this paper, we study the performance of popular brain atrophy estimation algorithms using a simulated gold standard. The availability of a gold standard facilitates a sound evaluation of the measures of atrophy estimation, which is otherwise complicated. Firstly, we propose an approach for the construction of a gold standard. It involves the simulation of a realistic brain tissue loss based on the estimation of a topology preserving B-spline based deformation fields. Using this gold standard, we present an evaluation of three standard brain atrophy estimation methods (SIENA, SIENAX and BSI) in the presence of bias field inhomogeneity and noise. The effect of brain lesion load on the measured atrophy is also evaluated. Our experiments demonstrate that SIENA, SIENAX and BSI show a deterioration in their performance in the presence of bias field inhomogeneity and noise. The observed mean absolute errors in the measured Percentage of Brain Volume Change (PBVC) are 0.35% +/- 0.38, 2.03% +/- 1.46 and 0.91% +/- 0.80 for SIENA, SIENAX and BSI, respectively, for simulated whole brain atrophies in the range 0-1%.
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http://dx.doi.org/10.1007/978-3-642-04271-3_69DOI Listing
June 2010

Statistical detection of longitudinal changes between apparent diffusion coefficient images: application to multiple sclerosis.

Med Image Comput Comput Assist Interv 2009 ;12(Pt 1):959-66

Université de Strasbourg, CNRS, UMR 7005, LSIIT, France.

The automatic analysis of longitudinal changes between Diffusion Tensor Imaging (DTI) acquisitions is a promising tool for monitoring disease evolution. However, few works address this issue and existing methods are generally limited to the detection of changes between scalar images characterizing diffusion properties, such as Fractional Anisotropy or Mean Diffusivity, while richer information can be exploited from the whole set of Apparent Diffusion Coefficient (ADC) images that can be derived from a DTI acquisition. In this paper, we present a general framework for detecting changes between two sets of ADC images and we investigate the performance of four statistical tests. Results are presented on both simulated and real data in the context of the follow-up of multiple sclerosis lesion evolution.
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http://dx.doi.org/10.1007/978-3-642-04268-3_118DOI Listing
June 2010

Symmetric nonrigid image registration: application to average brain templates construction.

Med Image Comput Comput Assist Interv 2008 ;11(Pt 2):897-904

Laboratoire des Sciences de l'Image, de l'Informatique et de la Télédétection, LSIIT, UMR CNRS-ULP 7005, Bd Sébastien Brant, 67412 Illkirch, France.

Image registration aims at estimating a consistent mapping between two images. Common techniques consist in choosing arbitrarily one image as a reference image and the other one as a floating image, thus leading to the estimation of inconsistent mappings. We present a symmetric formulation of the registration problem that maps the two images in a common coordinate system halfway between them. This framework has been considered to devise an efficient strategy for mapping a large set of images in a common coordinate system. Some results are presented in the context of 3-D nonrigid brain MR image registration for the construction of average brain templates.
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http://dx.doi.org/10.1007/978-3-540-85990-1_108DOI Listing
December 2008