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

Author

Julien Lamy, Frédéric Blanc, Jean-Paul Armspach, Marion Sourty, Meltem Karatas, Emilie Faivre, Vincent Noblet, Luc Buée, Laetitia Degiorgis, Anne-Laurence Boutillier, Thomas Bienert, Laura-Adela Harsan, David Blum, Dominik von Elverfeldt, Marco Reisert, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Imagerie Multimodale Intégrative en Santé [Strasbourg] (IMIS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), University of Freiburg [Freiburg], Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), The University of Sydney, Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CHU Strasbourg, Anne Laurence, Boutillier, Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC))

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Hippocampus, Mice, Transgenic, tau Proteins, Context (language use), Biology, Amygdala, Mice, 03 medical and health sciences, 0302 clinical medicine, Connectome, Image Processing, Computer-Assisted, medicine, Animals, Humans, Cognitive Dysfunction, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], tau, Gliosis, Dynamic functional connectivity, Memory Disorders, Resting state fMRI, medicine.diagnostic_test, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Brain, medicine.disease, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Tauopathies, Astrocytes, Disease Progression, functional MRI, resting state connectivity, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Tauopathy, Nerve Net, Functional magnetic resonance imaging, Alzheimer’s disease, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery, dementia
Abstract

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.

Published
2020

2. The TOTEM RRMS (Testosterone Treatment on neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis) trial: study protocol for a randomized, double-blind, placebo-controlled trial

Author

Ayikoe-Guy Mensah-Nyagan, Paulo Loureiro de Sousa, Laurent Kremer, Dominique Bagnard, Nicolas Meyer, Jérôme De Seze, Anne Kerbrat, Thibault Tricard, Eric Berger, Katline Metzger-Peter, Guillaume Mathey, Julien Lamy, Gilles Edan, Nicolas Collongues, Marc Debouverie, Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Oncology, Male, medicine.medical_specialty, medicine.medical_treatment, Placebo-controlled study, Medicine (miscellaneous), Placebo, law.invention, Multiple sclerosis, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Medicine, Humans, Multicenter Studies as Topic, Pharmacology (medical), Testosterone, Myelin Sheath, Randomized Controlled Trials as Topic, lcsh:R5-920, business.industry, medicine.disease, Magnetic Resonance Imaging, Neuroprotection, Clinical trial, Treatment Outcome, Remyelination, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], 030220 oncology & carcinogenesis, Disease Progression, Hormone therapy, business, lcsh:Medicine (General), 030217 neurology & neurosurgery, medicine.drug
Abstract

Background Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair. It is demonstrated that testosterone can act through neural androgen receptors and several clinical observations stimulated an interest in the potential protective effects of testosterone treatment for MS. Here, we sought to demonstrate the effects of a testosterone supplementation in testosterone-deficient men with relapsing-remitting MS. Methods/design This report presents the rationale and methodology of TOTEM RRMS, a French, phase 2, multicenter, randomized, placebo-controlled, and double-blind trial, which aims to prevent the progression of MS in men with low testosterone levels by administration of testosterone undecanoate, who were kept under natalizumab (Tysabri®) to overcome the anti-inflammatory effect of testosterone. Forty patients will be randomized into two groups receiving either a testosterone treatment (Nebido®) or a matching placebo. The intervention period for each group will last 66 weeks (treatment will be injected at baseline, week 6, and then every 12 weeks). The main objective is to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyses. As secondary objectives, impacts of the testosterone supplementation will be studied using other conventional and unconventional MRI parameters and with clinical outcomes. Discussion The action of testosterone is observed in different experimental autoimmune encephalomyelitis models and epidemiological studies in humans. However, despite several preclinical data and some small clinical trials in MS, clear evidence for a therapeutic effect of hormone therapy is still missing. Therefore, our goal is to demonstrate the effects of testosterone therapies in MS. As there is no effective treatment currently available on fatigue in MS, careful attention should also be paid to secondary endpoints: fatigue, cognitive functions, and other symptoms that may improve life quality. Assuming a positive outcome of the trial, this treatment could be considered as a new neuroprotective and remyelinating therapy in relapsing-remitting MS and could be applicable to other demyelinating diseases. Trial registration ClinicalTrials.gov NCT03910738. Registered on 10 April 2019.

Published
2020

3. A Motion Correction Strategy for Multi-Contrast based 3D parametric imaging: Application to Inhomogeneous Magnetization Transfer (ihMT)

Author

Jean-Philippe Ranjeva, Maxime Guye, Lucas Soustelle, Olivier M. Girard, Gopal Varma, Guillaume Duhamel, Jean Pelletier, Arnaud Le Troter, David C. Alsop, Andreea Hertanu, Julien Lamy, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS), ANR-17-CE18-0030,verISMO,IRM du transfert d'aimantation inhomogène : vers un nouveau biomarqueur in vivo spécifique et sensible de la myéline(2017), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Duhamel, Guillaume, IRM du transfert d'aimantation inhomogène : vers un nouveau biomarqueur in vivo spécifique et sensible de la myéline - - verISMO2017 - ANR-17-CE18-0030 - AAPG2017 - VALID, and Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM)

Subjects
Computer science, business.industry, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Image registration, Function (mathematics), Motion correction, 030218 nuclear medicine & medical imaging, Image (mathematics), 03 medical and health sciences, 0302 clinical medicine, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Multi contrast, Parametric imaging, Computer vision, Magnetization transfer, Artificial intelligence, business, 030217 neurology & neurosurgery
Abstract

PurposeTo propose an efficient retrospective image-based method for motion correction of multi-contrast acquisitions with a low number of available images (MC-MoCo) and evaluate its use in 3D inhomogeneous Magnetization Transfer (ihMT) experiments in the human brain.MethodsA framework for motion correction, including image pre-processing enhancement and rigid registration to an iteratively improved target image, was developed. The proposed method was compared to Motion Correction with FMRIB’s Linear Image Registration Tool (MCFLIRT) function in FSL over 13 subjects. Native (pre-correction) and residual (post-correction) motions were evaluated by means of markers positioned at well-defined anatomical regions over each image.ResultsBoth motion correction strategies significantly reduced inter-image misalignment, and the MC-MoCo method yielded significantly better results than MCFLIRT.ConclusionMC-MoCo is a high-performance method for motion correction of multi-contrast volumes as in 3D ihMT imaging.

Published
2021

4. Determination of optimal parameters for 3D single‐point macromolecular proton fraction mapping at 7T in healthy and demyelinated mouse brain

Author

Lucas Soustelle, Julien Lamy, Maria Cristina Antal, Laura-Adela Harsan, Paulo Loureiro de Sousa, ICube, CNRS, University of Strasbourg, France, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Physics, Brain Mapping, Proton, Pulse (signal processing), Macromolecular Substances, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Brain, Magnetic Resonance Imaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Mice, 0302 clinical medicine, Sampling (signal processing), Histogram, Mesothelin, Animals, Radiology, Nuclear Medicine and imaging, Fraction (mathematics), Magnetization transfer, Single point, Protons, Biological system, 030217 neurology & neurosurgery, Preclinical imaging, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; PurposeTo determine optimal constrained tissue parameters and off-resonance sequence parameters for single-point macromolecular proton fraction (SP-MPF) mapping based on a comprehensive quantitative magnetization transfer (qMT) protocol in healthy and demyelinated living mice at 7T.MethodsUsing 3D spoiled gradient echo-based sequences, a comprehensive qMT protocol is performed by sampling the Z-spectrum of mice brains, in vivo. Provided additional T1, urn:x-wiley:07403194:media:mrm28397:mrm28397-math-0001 and B0 maps allow for the estimation of qMT tissue parameters, among which three will be constrained, namely the longitudinal and transverse relaxation characteristics of the free pool (R1,fT2,f), the cross-relaxation rate (R) and the bound pool transverse relaxation time (T2,r). Different sets of constrained parameters are investigated to reduce the bias between the SP-MPF and its reference based on the comprehensive protocol.ResultsBased on a whole-brain histogram analysis about the constrained parameters, the optimal experimental parameters that minimize the global bias between reference and SP-MPF maps consist of a 600° and 6 kHz off-resonance irradiation pulse. Following a Bland-Altman analysis over regions of interest, optimal constrained parameters were R1,fT2,f = 0.0129, R = 26.5 s−1, and T2,r = 9.1 µs, yielding an overall MPF bias of 10−4 (limits of agreement [−0.0068;0.0070]) and a relative variation of 0.64% ± 5.95% between the reference and the optimal single-point method across all mice.ConclusionThe necessity of estimating animal model- and field-dependent constrained parameters was demonstrated. The single-point MPF method can be reliably applied at 7T, as part of routine preclinical in vivo imaging protocol in mice.

Published
2021

5. Biomarkers of treatment response in patients with progressive multiple sclerosis treated with high-dose pharmaceutical-grade biotin (MD1003)

Author

Thibault Moreau, Nicolas Meyer, Michael Amann, Christian Barro, Julien Lamy, Ludwig Kappos, Nicolas Collongues, Jens Kuhle, Jens Wuerfel, Katrin Parmar, Charidimos Tsagkas, Jérôme De Seze, CHU Strasbourg, University of Basel (Unibas), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Groupe Méthodes en Recherche Clinique [Strasbourg] (GMRC), Nouvel Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and univOAK, Archive ouverte

Subjects
medicine.medical_specialty, Biotin, brain volume, Logistic regression, multiple sclerosis, Gastroenterology, 050105 experimental psychology, lcsh:RC321-571, 03 medical and health sciences, Behavioral Neuroscience, chemistry.chemical_compound, Disability Evaluation, 0302 clinical medicine, MD1003, Internal medicine, progressive form, Medicine, Humans, 0501 psychology and cognitive sciences, In patient, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, Progressive multiple sclerosis, Expanded Disability Status Scale, business.industry, Multiple sclerosis, 05 social sciences, Bayes Theorem, medicine.disease, Spinal cord, Magnetic Resonance Imaging, spinal cord volume, medicine.anatomical_structure, neurofilament light chain, chemistry, Brain size, Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, 030217 neurology & neurosurgery, Biomarkers
Abstract

Background High‐dose pharmaceutical‐grade biotin (MD1003) has positive effects on disability in progressive multiple sclerosis (PMS), but its mechanism of action remains unclear. The objective of our study was to quantify the effect of MD1003 in patients with PMS, using clinical response, plasma neurofilament light chain (pNfL) levels, and brain (BV) or cervical spinal cord volume (CSCV). Materials and methods Forty‐eight patients with PMS newly treated with MD1003 were followed during one year. Patients were assessed clinically using the Expanded Disability Status Scale (EDSS), the nine‐hole peg test (9HPT), and the 25‐foot walk time (25FWT). CSCV was quantified using CORDIAL software and BV using SIENA or SIENAX. We measured pNfL level using SIMOA at several time points. Bayesian linear and logistic regressions were used to evaluate potential prognostic factors. Results Treatment response, defined as a significant decrease of EDSS, 25FWT, or 9HPT at 1 year, was observed in 13 patients (27%). A gain of volume was noted in 7/24 patients for brain and in 10/19 patients for cervical spinal cord. The strongest predictors of poor treatment response were a high pNfL level at MD1003 onset (OR 0.96; 95% CI [0.91; 1]), high age at MS onset (OR 0.95; 95% CI [0.89; 1.01]), and an increase in brain lesion load during MD1003 treatment (OR 0.81; 95% CI [0.55; 1.05]). Conclusions MD1003 treatment was associated with clinical, BV, and CSCV improvement at 1 year. The correlation between the levels of pNfL at baseline, the age at multiple sclerosis onset, and a treatment response at M12 is consistent with a better effect in less disabled patients., MD1003 treatment was associated with clinical, brain and cervical spinal cord volumes improvement at 1 year. The correlation between the levels of pNfL at baseline, the age at MS onset and a treatment response at M12 is consistent with a better effect in less disabled patients. Our study provides a set of objective assessments that, taken together, argue for a possible neuroprotective or remyelinating effect of MD1003 in progressive forms of MS.

Published
2020

6. Signal changes in enhanced T1-weighted images related to gadolinium retention: A three-time-point imaging study

Author

Anne-Lise Diepenbroek, Thibault Willaume, François Lersy, François Cotton, Guillaume Bierry, Stéphane Kremer, Julien Lamy, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), and Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Gadolinium, chemistry.chemical_element, Contrast Media, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, T1 weighted, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Longitudinal Studies, GADOBENATE DIMEGLUMINE, Retrospective Studies, Radiological and Ultrasound Technology, business.industry, Imaging study, 3. Good health, Dentate nucleus, Globus pallidus, chemistry, Cerebellar Nuclei, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Signal intensity, business, Nuclear medicine, 030217 neurology & neurosurgery, GADOTERATE MEGLUMINE
Abstract

Background and Purpose Concern has grown about the finding of gadolinium deposits in the brain after administering gadolinium-based contrast agents (GBCAs). The mechanism is unclear, and related questions remain unanswered, including the stability over time. Therefore, we conducted a three-time-point study to explore T1-weighted (W) signal changes in the dentate nucleus (DN) and globus pallidus (GP), after the first, fifth, and tenth injections of either a macrocyclic agent (gadoterate meglumine) or a linear agent (gadobenate dimeglumine). Materials and methods For this retrospective, multicenter, longitudinal study, two groups of 18 (gadoterate meglumine) and 19 (gadobenate dimeglumine) patients were identified. The evolution of the signal over time was analyzed using DN/pons (DN/P) and GP/thalamus (GP/T) ratios. Results DN/P and GP/T ratios tended to increase after the fifth administration of gadobenate dimeglumine, following by a downward trend. A trend in a decrease in DN/P and GP/T ratios were found after the fifth and tenth administrations of gadoterate meglumine. Conclusion After exposure to gadobenate dimeglumine, the signal intensity (SI) tended to increase after the fifth injection owing to gadolinium accumulation, however, a SI increase was not found after the tenth administration supporting the hypothesis of a slow elimination of the previously retained gadolinium (wash-out effect) from the brain or of a change in form (by dechelation), causing the signal to fade. No increasing SI was found in the DN and GP after exclusive exposure to gadoterate meglumine, thus confirming its stability. We found, instead, a trend for a significative gadolinium elimination over time.

Published
2020

7. A diffusion-based method for long-T2suppression in steady state sequences: Validation and application for 3D-UTE imaging

Author

Lucas Soustelle, Julien Lamy, Paulo Loureiro de Sousa, François Rousseau, and Jean-Paul Armspach

Subjects
Physics, Sequence, Steady state (electronics), Signal, Imaging phantom, 030218 nuclear medicine & medical imaging, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Signal-to-noise ratio, Bloch equations, Modulation, Radiology, Nuclear Medicine and imaging, Diffusion (business), Algorithm, 030217 neurology & neurosurgery
Abstract

Purpose To introduce a novel method for long-T2 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-T2 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-T2 component signal cancellation through diffusion effects is addressed, and the condition met for sets of sequence parameters. Simultaneously, the short-T2 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-T2 components, as well as on an ex vivo mouse head. Results Within equal scan times, the proposed method allowed for an efficient long-T2 signal suppression, and expectedly yielded a higher signal to noise ratio in short-T2 structures compared to the IR-UTE technique, although an intrinsic short-T2 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-T2 suppression results in a less penalizing method to generate a high and selective contrast in short-T2 components. Magn Reson Med 80:548-559, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Published
2017

8. Emotional disturbances in multiple sclerosis: A neuropsychological and fMRI study

Author

Line Pfaff, Julien Lamy, Jérôme De Seze, Daniel Gounot, Vincent Noblet, J.-B. Chanson, Frédéric Blanc, Biopathologie de la Myéline, Neuroprotection et Stratégies Thérapeutiques (BMNST), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), and Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, medicine.medical_specialty, Cognitive Neuroscience, Emotions, Experimental and Cognitive Psychology, Audiology, Neuropsychological Tests, 050105 experimental psychology, Arousal, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Sensation, medicine, Humans, 0501 psychology and cognitive sciences, Affective Symptoms, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Valence (psychology), Brain Mapping, Multiple sclerosis, Functional Neuroimaging, 05 social sciences, Neuropsychology, Emotional stimuli, Brain, Right fusiform gyrus, medicine.disease, Magnetic Resonance Imaging, Neuropsychology and Physiological Psychology, Orbitofrontal cortex, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, 030217 neurology & neurosurgery, Photic Stimulation
Abstract

Background Emotional disturbances in multiple sclerosis (MS) are often explored in terms of affect recognition, with controversial results that likely reflect the high lesional heterogeneity. Patients' emotional experience, however, has seldom been studied and has never been explored using fMRI. Objectives To explore the emotional experience in MS and compare these data with fMRI measurements using for the first time real-life emotional scenes differing in valence and arousal. Methods Twenty-five right-handed women with relapsing-remitting MS and 27 right-handed age-, sex-, and education-matched healthy controls visualized during an fMRI session, emotional scenes taken from the international affect picture system (IAPS) and differing in valence (positive, negative, neutral) and arousal (ranging from calm to excited). During a post-scanning debriefing, participants were asked to look again at each image and score it in terms of valence and arousal sensation on a scale of 1–9. Results Cognitively well-preserved MS subjects presented a significantly more scattered emotional experience compared to controls in response to positive and negative pictures. In fMRI, MS patients also presented a higher variability of response when compared to controls in left inferior orbitofrontal cortex for positive stimulations. For negative condition, no significant results were observed between the two groups. However, a trend was detected in left amygdala, right fusiform gyrus, right caudate nucleus and right pallidum for negative stimulations. Conclusion In response to emotional stimuli, MS subjects presented a scattered emotional experience subtended by a greater variability of brain response, highlighting an emotional pattern not previously reported in MS patients.

Published
2019

9. A Brain Imaging-Based Diagnostic Biomarker for Periodic Catatonia: Preliminary Evidence Using a Bayesian Approach

Author

Erik Sauleau, Benoit Schorr, Clément de Billy, Julien Lamy, Madalina Carmen Lupu, Olivier Mainberger, Lionel Landré, Vincent Noblet, Ludovic Christophe Jeanjean, Julie Clauss, Alexandre Obrecht, Jack R. Foucher, Fabrice Berna, Paulo Loureiro de Sousa, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg

Subjects
Adult, Male, medicine.medical_specialty, Elementary cognitive task, Context (language use), Proof of Concept Study, Sensitivity and Specificity, Premotor cortex, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neuroimaging, Internal medicine, medicine, Humans, Biological Psychiatry, Psychomotor learning, Core (anatomy), business.industry, Functional Neuroimaging, Bayes Theorem, Catatonia, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, medicine.anatomical_structure, Cerebral blood flow, Schizophrenia, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Cerebrovascular Circulation, Cardiology, Female, business, 030217 neurology & neurosurgery, Biomarkers
Abstract

Periodic catatonia (PC) is a psychomotor phenotype with a progressive-remitting course. While it can fit any disorder diagnosis of the schizoaffective spectrum, its core features consist of a mix of hypo- and hyperkinesias resulting in distortions of expressive movements such as grimacing and parakinesias. The replication of cerebral blood flow (CBF) increases in the left supplementary motor area (L-SMA) and lateral premotor cortex (L-LPM) in acute and remitting PC patients indicates that these increases could be used as diagnostic biomarkers. In this proof-of-concept study, 2 different MRI sequences were repeated on 3 separate days to get reliable measurement values of CBF in 9 PC and 26 non-PC patients during different cognitive tasks. Each patient was compared to 37 controls. In L-SMA [–9; +10; +60] and L-LPM [–46; –12; +43], a test was positive if the t value was >2.02 (α < 0.05; two tailed). The measurements had good analytical performance. Regarding the tests, their sensitivities and specificities were significantly different from the chance level on both measures, except for L-SMA sensitivities. When combining all the tests, among regions and methods, sensitivity was 98% (95% credible interval [CI] 76–100%) and specificity 88% (72–97%). Bayesian inferences of its negative predictive values for PC were >95% regardless of the context, while its positive predictive values reached 94% but only when used in combination with clinical criteria. The case-by-case analysis suggests that non-PC patients with neurological motor deficits are at risk to be false positive.

Published
2019

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

Author

François Rousseau, Lucas Soustelle, Julien Lamy, Jean-Paul Armspach, Paulo Loureiro de Sousa, Maria Cristina Antal, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département lmage et Traitement Information (IMT Atlantique - ITI), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Laboratoire de Traitement de l'Information Medicale (LaTIM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Rousseau, François, École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), IMT Atlantique (IMT Atlantique), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-IMT Atlantique (IMT Atlantique)

Subjects
quantitative magnetization transfer, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Central nervous system, Corpus callosum, Fluorescence, 030218 nuclear medicine & medical imaging, histology, 03 medical and health sciences, Myelin, Cuprizone, 0302 clinical medicine, Nuclear magnetic resonance, medicine, Animals, UTE imaging, Radiology, Nuclear Medicine and imaging, Spectroscopy, biology, Chemistry, Myelin Basic Protein, diffusion tensor imaging, Magnetic Resonance Imaging, Myelin basic protein, Staining, myelin water imaging, Mice, Inbred C57BL, Disease Models, Animal, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, medicine.anatomical_structure, nervous system, Murine model, biology.protein, Molecular Medicine, Ultrashort echo time, demyelination, 030217 neurology & neurosurgery, Diffusion MRI, Demyelinating Diseases
Abstract

International audience; 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).

Published
2018

11. Multi-parametric quantitative MRI reveals three different white matter subtypes

Author

Mathieu Santin, Olivier Mainberger, Julien Lamy, Paulo Loureiro de Sousa, Mathilde M Roser, Jack R. Foucher, Alexandre Vignaud, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research [ICM Paris] (CENIR), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut d'Imagerie BioMédicale (I2BM), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
Central Nervous System, Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, lcsh:Medicine, Biochemistry, Nervous System, 030218 nuclear medicine & medical imaging, Diagnostic Radiology, Corpus Callosum, Myelin, 0302 clinical medicine, Nuclear magnetic resonance, Nerve Fibers, Animal Cells, Cortex (anatomy), Medicine and Health Sciences, lcsh:Science, Neurons, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, Chemistry, Radiology and Imaging, Physics, Radial diffusivity, Magnetism, Brain, Middle Aged, Condensed Matter Physics, Lipids, Magnetic Resonance Imaging, White Matter, medicine.anatomical_structure, Cholesterol, Diffusion Tensor Imaging, Frontal lobe, Physical Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Anatomy, Protons, Cellular Types, Research Article, Adult, Imaging Techniques, Brain Morphometry, Neuroimaging, Research and Analysis Methods, White matter, 03 medical and health sciences, Diagnostic Medicine, medicine, Humans, Nuclear Physics, Nucleons, Multi parametric, lcsh:R, Biology and Life Sciences, Magnetic resonance imaging, Cell Biology, Axons, Magnetic Fields, Cellular Neuroscience, lcsh:Q, 030217 neurology & neurosurgery, Diffusion MRI, Neuroscience
Abstract

International audience; Introduction: Magnetic resonance imaging (MRI) shows slight spatial variations in brain white matter (WM). We used quantitative multi-parametric MRI to evaluate in what respect these inhomogeneities could correspond to WM subtypes with specific characteristics and spatial distribution.Materials and methods: Twenty-six controls (12 women, 38 ±9 Y) took part in a 60-min session on a 3T scanner measuring 7 parameters: R1 and R2, diffusion tensor imaging which allowed to measure Axial and Radial Diffusivity (AD, RD), magnetization transfer imaging which enabled to compute the Macromolecular Proton Fraction (MPF), and a susceptibility-weighted sequence which permitted to quantify R2* and magnetic susceptibility (χm). Spatial independent component analysis was used to identify WM subtypes with specific combination of quantitative parameters values.Results: Three subtypes could be identified. t-WM (track) mostly mapped on well-formed projection and commissural tracts and came with high AD values (all p < 10−18). The two other subtypes were located in subcortical WM and overlapped with association fibers: f-WM (frontal) was mostly anterior in the frontal lobe whereas c-WM (central) was underneath the central cortex. f-WM and c-WM had higher MPF values, indicating a higher myelin content (all p < 1.7 10−6). This was compatible with their larger χm and R2, as iron is essentially stored in oligodendrocytes (all p < 0.01). Although R1 essentially showed the same, its higher value in t-WM relative to c-WM might be related to its higher cholesterol concentration.Conclusions: Thus, f- and c-WMs were less structured, but more myelinated and probably more metabolically active regarding to their iron content than WM related to fasciculi (t-WM). As known WM bundles passed though different WM subtypes, myelination might not be uniform along the axons but rather follow a spatially consistent regional variability. Future studies might examine the reproducibility of this decomposition and how development and pathology differently affect each subtype.

Published
2018

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

Author

Vincent Noblet, Frédéric Blanc, Julien Lamy, Alix Bouchon, Fabrice Heitz, and Jean-Paul Armspach

Subjects
General linear model, Adult, Cognitive Neuroscience, Neuromyelitis Optica, Scalar (physics), Brain, computer.software_genre, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Diffusion Tensor Imaging, Neurology, Voxel, Data Interpretation, Statistical, Fractional anisotropy, Statistics, Covariate, Humans, Tensor, Algorithm, computer, 030217 neurology & neurosurgery, Mathematics, Statistical hypothesis testing, Diffusion MRI
Abstract

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 Cramer 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 Cramer 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.

Published
2015

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

Author

Xavier de Petigny, Benjamin Cretin, Alan J. Thomas, John T. O'Brien, Julien Lamy, John-Paul Taylor, Sean J. Colloby, Catherine Martin-Hunyadi, Fabrice Bing, Catherine Demuynck, Jean-Paul Armspach, Barbara Jung, Ian G. McKeith, Clélie Phillipps, Pierre Anthony, Nathalie Philippi, and Frédéric Blanc

Subjects
Male, medicine.medical_specialty, lcsh:Medicine, Prodromal Symptoms, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Alzheimer Disease, Internal medicine, mental disorders, medicine, Dementia, Humans, lcsh:Science, 030304 developmental biology, Aged, Cerebral Cortex, 0303 health sciences, Multidisciplinary, Dementia with Lewy bodies, business.industry, Prodromal Stage, lcsh:R, Parietal lobe, Middle Aged, medicine.disease, nervous system diseases, medicine.anatomical_structure, nervous system, Cerebral cortex, Cardiology, lcsh:Q, Female, Lewy Bodies, Alzheimer's disease, business, Insula, 030217 neurology & neurosurgery, Research Article
Abstract

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

Published
2015

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