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SEIN Julien

PhD PostDoc
tel : +33 4 91 38 84 66
Key Words
- Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)
- Functional MRI
- in vivo imaging

Current Research Interest and projects

After being trained as a spectroscopist in the CRMN in Lyon (France) working with NMR at very high fields (11.7T to 23.3T) on crystallized proteins , I spent four years at the CRMN in Minneapolis (USA), working on MRI at high field (3T, 7T) to improve anatomical images in different human brain pathologies. My current research project as a research engineer at CRMBM in Marseille is focused on the processing of MRI data of the PharmaCog project. The PharmaCog project is funded under a public-private partnership and aims at tackling bottlenecks in Alzheimer’s disease (AD) drug discovery. Artificial paradigms are used to induce cognitive impairments akin to those seen in AD in order to test the ability of different drugs to reverse those cognitive effects. My project involves the analysis of resting-state MRI and functional MRI linked to episodic memory, working memory and attention. I will also analyze Magnetic Resonance Spectroscopy (MRS) performed on those subjects.



Journal Article

  • Albi, A, Pasternak, O, Minati, L, Marizzoni, M, Bartres-Faz, D, Bargallo, N, Bosch, B, Rossini, PM, Marra, C, Mueller, B, Fiedler, U, Wiltfang, J, Roccatagliata, L, Picco, A, Nobili, FM, Blin, O, Sein, J, Ranjeva, J-P, Didic, M, Bombois, S, Lopes, R, Bordet, R, Gros-Dagnac, H, Payoux, P, Zoccatelli, G, Alessandrini, F, Beltramello, A, Ferretti, A, Caulo, M, Aiello, M, Cavaliere, C, Soricelli, A, Parnetti, L, Tarducci, R, Floridi, P, Tsolaki, M, Constantinidis, M, Drevelegas, A, Frisoni, G & Jovicich, J 2017, “Free water elimination improves test-retest reproducibility of diffusion tensor imaging indices in the brain: A longitudinal multisite study of healthy elderly subjects”, Human Brain Mapping, vol. 38, no. 1, p. 12-26.
    Résumé : Free water elimination (FWE) in brain diffusion MRI has been shown to improve tissue specificity in human white matter characterization both in health and in disease. Relative to the classical diffusion tensor imaging (DTI) model, FWE is also expected to increase sensitivity to microstructural changes in longitudinal studies. However, it is not clear if these two models differ in their test-retest reproducibility. This study compares a bi-tensor model for FWE with DTI by extending a previous longitudinal-reproducibility 3T multisite study (10 sites, 7 different scanner models) of 50 healthy elderly participants (55-80 years old) scanned in two sessions at least 1 week apart. We computed the reproducibility of commonly used DTI metrics (FA: fractional anisotropy, MD: mean diffusivity, RD: radial diffusivity, and AXD: axial diffusivity), derived either using a DTI model or a FWE model. The DTI metrics were evaluated over 48 white-matter regions of the JHU-ICBM-DTI-81 white-matter labels atlas, and reproducibility errors were assessed. We found that relative to the DTI model, FWE significantly reduced reproducibility errors in most areas tested. In particular, for the FA and MD metrics, there was an average reduction of approximately 1% in the reproducibility error. The reproducibility scores did not significantly differ across sites. This study shows that FWE improves sensitivity and is thus promising for clinical applications, with the potential to identify more subtle changes. The increased reproducibility allows for smaller sample size or shorter trials in studies evaluating biomarkers of disease progression or treatment effects. Hum Brain Mapp 38:12-26, 2017. (c) 2016 Wiley Periodicals, Inc.
    Mots-clés : alzheimers-disease, brain diffusion tensor imaging, cerebral white-matter, false discovery rate, free-water imaging, healthy elderly, longitudinal, MRI, multisite diffusion MRI, parkinsons-disease, reliability, Schizophrenia, snc, spatial statistics, substantia-nigra, test-retest reproducibility, tracking.


Journal Article

  • Marchitelli, R, Minati, L, Marizzoni, M, Bosch, B, Bartrés-Faz, D, Müller, BW, Wiltfang, J, Fiedler, U, Roccatagliata, L, Picco, A, Nobili, F, Blin, O, Bombois, S, Lopes, R, Bordet, R, Sein, J, Ranjeva, J-P, Didic, M, Gros-Dagnac, H, Payoux, P, Zoccatelli, G, Alessandrini, F, Beltramello, A, Bargalló, N, Ferretti, A, Caulo, M, Aiello, M, Cavaliere, C, Soricelli, A, Parnetti, L, Tarducci, R, Floridi, P, Tsolaki, M, Constantinidis, M, Drevelegas, A, Rossini, PM, Marra, C, Schönknecht, P, Hensch, T, Hoffmann, K-T, Kuijer, JP, Visser, PJ, Barkhof, F, Frisoni, GB & Jovicich, J 2016, “Test-retest reliability of the default mode network in a multi-centric fMRI study of healthy elderly: Effects of data-driven physiological noise correction techniques”, Human Brain Mapping, vol. 37, no. 6, p. 2114-2132.
    Résumé : Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc.
    Mots-clés : crmbm, default mode network, Independent component analysis, multisite, physiological noise correction, resting-state networks, snc, task-free fMRI, test-retest reliability.


Journal Article

  • Lewandowski, JR, Sein, J, Blackledge, M & Emsley, L 2010, “Anisotropic collective motion contributes to nuclear spin relaxation in crystalline proteins”, Journal of the American Chemical Society, vol. 132, no. 4, p. 1246-1248.
    Résumé : A model for calculating the influence of anisotropic collective motions on NMR relaxation rates in crystalline proteins is presented. We show that small-amplitude (<10 degrees ) fluctuations may lead to substantial contributions to the (15)N spin-lattice relaxation rates and propose that the effect of domain motions should be included in solid-state NMR analyses of protein dynamics.
    Mots-clés : Anisotropy, Crystallization, Models, Molecular, Motion, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation, Proteins.

  • Lewandowski, JR, Sein, J, Sass, HJ, Grzesiek, S, Blackledge, M & Emsley, L 2010, “Measurement of site-specific 13C spin-lattice relaxation in a crystalline protein”, Journal of the American Chemical Society, vol. 132, no. 24, p. 8252-8254.
    Résumé : We demonstrate that it is possible to record site-specific spin-lattice relaxation rates for the majority of (13)C sites in uniformly (13)C and (15)N labeled solid proteins as a result of the slowing down of proton-driven spin diffusion at sample spinning frequencies > or = 60 kHz, thus providing a series of new experimental probes for characterizing molecular dynamics in solid proteins.
    Mots-clés : Carbon Isotopes, diffusion, Magnetics, Models, Molecular, Nanoparticles, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation, Proteins, Time Factors.


Journal Article

  • Laage, S, Marchetti, A, Sein, J, Pierattelli, R, Sass, HJ, Grzesiek, S, Lesage, A, Pintacuda, G & Emsley, L 2008, “Band-selective 1H-13C cross-polarization in fast magic angle spinning solid-state NMR spectroscopy”, Journal of the American Chemical Society, vol. 130, no. 51, p. 17216-17217.
    Résumé : A magic angle spinning (MAS) NMR technique to transfer polarization from protons to a specific set of the (13)C spins is introduced for the study of biomolecular samples in the solid-state. Ultrafast (>60 kHz) MAS and low irradiation rf fields are used to achieve band-selective Hartmann-Hahn cross-polarization (CP) between the whole proton bath and carbons whose resonances are close to the (13)C-transmitter offset. When compared to conventional, broadband (1)H-(13)C CP, the band-selective experiment can be established without any loss of sensitivity when polarizing the aliphatic signals of a protein sample, and with a significant gain when polarizing carbonyls. This scheme can be used as a building block in 2D (13)C-(13)C homonuclear correlation experiments to obtain a faster and more sensitive characterization of biological solids.
    Mots-clés : Carbon, Carbon Isotopes, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Conformation, Molecular Structure, Protons, Temperature.


Journal Article

  • Cadars, S, Sein, J, Duma, L, Lesage, A, Pham, TN, Baltisberger, JH, Brown, SP & Emsley, L 2007, “The refocused INADEQUATE MAS NMR experiment in multiple spin-systems: interpreting observed correlation peaks and optimising lineshapes”, Journal of magnetic resonance (San Diego, Calif.: 1997), vol. 188, no. 1, p. 24-34.
    Résumé : The robustness of the refocused INADEQUATE MAS NMR pulse sequence for probing through-bond connectivities has been demonstrated in a large range of solid-state applications. This pulse sequence nevertheless suffers from artifacts when applied to multispin systems, e.g. uniformly labeled (13)C solids, which distort the lineshapes and can potentially result in misleading correlation peaks. In this paper, we present a detailed account that combines product-operator analysis, numerical simulations and experiments of the behavior of a three-spin system during the refocused INADEQUATE pulse sequence. The origin of undesired anti-phase contributions to the spectral lineshapes are described, and we show that they do not interfere with the observation of long-range correlations (e.g. two-bond (13)C-(13)C correlations). The suppression of undesired contributions to the refocused INADEQUATE spectra is shown to require the removal of zero-quantum coherences within a z-filter. A method is proposed to eliminate zero-quantum coherences through dephasing by heteronuclear dipolar couplings, which leads to pure in-phase spectra.

  • Sein, J, Giraud, N, Blackledge, M & Emsley, L 2007, “The role of (15)N CSA and CSA/dipole cross-correlation in (15)N relaxation in solid proteins”, Journal of magnetic resonance (San Diego, Calif.: 1997), vol. 186, no. 1, p. 26-33.
    Résumé : The influence of the (15)N CSA on (15)N longitudinal relaxation is investigated for an amide group in solid proteins in powder form under MAS. This contribution is determined to be typically 20-33% of the overall longitudinal relaxation rate, at 11.74 and 16.45 T, respectively. The improved treatment is used to analyze the internal dynamics in the protein Crh, in the frame of a motional model of diffusion in a cone, using the explicit average sum approach. Significant variations with respect to the determined dynamics parameters are observed when properly accounting for the contribution of (15)N CSA fluctuations. In general, the fit of experimental data including CSA led to the determination of diffusion times (tau(w)) which are longer than when considering only an (15)N-(1)H dipolar relaxation mechanism. CSA-Dipole cross-correlation is shown to play little or no role in protonated solids, in direct contrast to the liquid state case.
    Mots-clés : Algorithms, Isotope Labeling, Magnetic Resonance Spectroscopy, Models, Chemical, Models, Molecular, Nitrogen Isotopes, Proteins, Statistics as Topic.


Journal Article

  • Giraud, N, Sein, J, Pintacuda, G, Böckmann, A, Lesage, A, Blackledge, M & Emsley, L 2006, “Observation of heteronuclear overhauser effects confirms the 15N-1H dipolar relaxation mechanism in a crystalline protein”, Journal of the American Chemical Society, vol. 128, no. 38, p. 12398-12399.
    Résumé : The observation of proton to nitrogen-15 heteronuclear Overhauser effects in the microcrystalline protein Crh is used to confirm that the principal mechanism of relaxation of amide nitrogens is due to the fluctuation of the N-H dipolar couplings caused by N-H bond dynamics. Our observations reveal the central role of water as the main source of proton magnetization, and we provide an analysis of the different pathways that could lead to the observed results.
    Mots-clés : Bacterial Proteins, Nitrogen Isotopes, Nuclear Magnetic Resonance, Biomolecular, Phosphoproteins, Protons.
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