Contact

Dr. phil. Gisela Hagberg

Adresse: Spemannstr. 41
72076 Tübingen
Raum Nummer: 3.B.09
Tel.: 07071 601 1648
Fax: 07071 601 652
E-Mail: gisela.hagberg

 

Bild von Hagberg, Gisela, Dr. phil.

Gisela Hagberg

Position: Gastwissenschaftler  Abteilung: Scheffler

Anwendungen der Hoch-Feld MRT in klinisch-wissenschaftlichen Studien zur Mikrostruktur des menschlichen Gehirns

Ultra-hohe Magnetfelder erlauben sehr detaillierte, nicht-invasive, strukturelle und funktionelle Untersuchungen des menschlichen Gehirns.

 

MR-basierte Signale entstehen wiederum auf einer noch mehr detaillierteren Ebene, auf Grund kleiner Bewegungen der Wasser Moleküle durch die anatomische Vielfalt des Gehirns.  Die Gewebsstruktur und ihre Zusammensetzung erzeugen lokale magnetische Effekte auf das Wasser, die mit der Gehirn-Funktion oder Pathologische Prozesse sich stets in Wandel befinden.

Der  Schwerpunkt meiner Forschung liegt im Bereich der Untersuchung solche pathophysiologische Prozesse mit MR Methoden. Hierbei möchte ich herausfinden wie im MR Bild Kontraste erzeugt und quantifiziert werden können die der mikrostrukturellen  Einflüsse entsprechen.  Das Ziel ist es Methoden bei Ultrahohe Magnetfeldern zu erarbeiten, die quantitative anatomische und  MR Studien erlauben und neue medizinische Nutzfelder ermöglichen.

A core of quantitative MRI tools

for clinical and neuroscientific in vivo research at 9.4T has been established. Besides mapping of the transmit field, necessary to correct for the strong inhomogeneity, they consist of MP2RAGE-based mapping of the longitudinal relaxation (T1; R1) with isotropic voxel-sizes of 800µm down to 300µm; a multi echo 3D GRE sequence; with voxel-sizes of 375x375x800µm down to an isotropic voxel size of 400µm mainly for mapping the effective transverse relaxation (T2*; R2*), but that can also be used for quantitative susceptibility mapping (QSM); and a high-resolution acquisition weighted, single-echo 3D GRE sequence; with voxel-sizes down to 113x118x600µm used for QSM.

The whole protocol has a total duration of 45min and is therefore suited for clinical examinations of patients using a multi-modal imaging approach but without too harsh constraints on patient compliance. For validation purposes, this core of sequences has been complemented with single slice inversion-recovery mapping of T1 using EPI, and CPMG based mapping of T2, with an echo train consisting of 32 echoes and a minimum inter-echo time of 9ms, without exceeding SAR limits.

These protocols have been used to elucidate amongst other age-depndent variation in healthy subjects, the anatomical detail of the superior colliculus, beta-amyloid plaques in Alzheimer's and in post-mortem tissue.

The severe inhomogeneity of the transmit field poses a limit for quantitative studies at 9.4T. We found that this factor not only affects the MR signal excitation, but also impacts inversion efficiency, despite the use of adiabatic pulses. Such pulses are generally assumed to be immune to variations in B1, but through Bloch simulations and experiments we could confirm studies from the early ’90 demonstrating the vulnerability of that assumption (Hagberg et al., 2017). These findings further led us to propose an efficient correction for T1 (R1) mapping at 9.4T that tackles this issue and yields a high in vivo test-retest variability (< 1%) and low coefficient-of-variation (CoV<3% across 25 subjects at the level of extended regions-of-interest). Consistent with previous studies, we found that the primary sensory and motor areas had the greatest quantitative R1 values, in line with their greater myelin content with respect to other brain areas, and observed that the quantitative MRI parameters measured at 9.4T have a greater dynamic range than at 3T (Fig. 1). Nevertheless we could observe that the voxel wise CoV reached levels beyond 15% in grey matter regions, being several fold higher than in white matter voxels. This is interesting in view of the difficulty to detect myelin-related signals outside the white matter at 3T (Groeschel et al., 2016). Upon closer scrutiny we found that this effect derives from age-related variation in R1. The observed dynamics of MR-parameters across the human life-span could be explained in a model that takes into account decreasing grey matter volume fractions, increased iron levels and increased myelination of the cortical fibers with age (Fig. 2 and Hagberg et al., 2017b).

With further advancing age, several changes of the brain microstructure occur that may impact quantitative MRI measures. With age, the likelihood of presenting β-amyloid deposits increases, with prevalence peaking at age 70, even in a cognitively healthy population (Jack et al., 2017). In patient populations showing mild cognitive impairment, early identification of the presence of such deposits is essential since patients without them have a different clinical course towards non-Alzheimer dementia. Recently we found that QSM of post mortem samples can detect single β-amyloid plaques in Alzheimer’s at 14.1T, but only when voxel-sizes (37-50µm) on the order of the size of single plaques were employed (Fig. 3 and Tuzzi et al., 2016; 2017). This finding poses important questions regarding the best imaging protocols to use for in vivo MRI and the resolution necessary to answer clinical questions at UHF, since pathology–related effects of β-amyloid can be detected at high field but with coarser sampling (van Rooden et al., 2016).

A particularly challenging area for MRI research are the function and the anatomy of the deep brain nuclei located in the midbrain, characterized by a limited available signal-to-noise-ratio and a strong variation in background magnetic susceptibility. The superior colliculus (SC) is one of these brain nuclei and is a layered structure which serves as a gateway for several sensory modalities. Up-to-date, the layering pattern could only be identified in histology, or in vivo by functional challenge. We recently showed that layer specific fMRI activations of the superior colliculus (SC) can be detected at 9.4T (Loureiro 2017a). More recently (Loureiro 2016; 2017b) we found that the combined use of several quantitative MRI parameters provides a mean to study layer specific anatomy of the SC in vivo with features that are sensitive to the local microstructure that are reproducible across subjects. Moreover we observed that the combined use of several MRI parameters enabled identification of several anatomical structures within the midbrain areas (Fig. 4). Along with these measurements we employed MRI of post mortem samples at 14.1T and polarized light microscopy imaging to validate our observations regarding detectability of white matter fascicles in the brain stem. We are currently pursuing research activities in this direction with the aim to pin-point the source behind the obtained quantitative MRI measures and have extended our focus to include signal variations within and beyond the cortical rim in the occipital cortex (Fig. 5).

 

Wissenschaftlicher Werdegang
Seit 06/2012    Projektleiterin, Hochfeld Magnetresonanz, Max-Planck-Institut für Biologische Kybernetik  und Abt. Biomedizinische Magnetresonanz, Universitätsklinikum Tübingen, Deutschland
09/10-05/12    Wissenschaftliche Mitarbeiterin, Max-Planck-Institut für Biologische Kybernetik, Abt. Physiologie kognitiver Prozesse, Tübingen, Deutschland
06/06-08/10    Gruppenleiterin MR Physik, Fondazione Santa Lucia IRCCS, Rom, Italien;
12/2007    Medizin Physik Expertin (MPE), Università Sapienza, Rom, Italien
04/99-06/06    Wissensch. Mitarbeiterin, Fondazione Santa Lucia IRCCS, Rom, Italien
03/99-03/03    Wissensch. Mitarbeiterin, 10% PET centre, Uppsala Universität, Schweden
06/96-02/99        Wissensch. Mitarbeiterin (100%) Positron EmissionTomography (PET) Centre, Uppsala Universität, Schweden
12/94-12/95    Post-Doktorandin, Dep. Pharmacokinetics, Pharmacia&Upjohn, Milano, Italien
07/93-06/94    Post-Doktorandin, Abt. Biophysikalische Chemie, Universität Basel, Schweiz
06/1993    Doktor der Philosophie, verliehen durch die Universität Basel, Schweiz
Thema: Metabolism of the Human Brain Investigated by 1H-MRS
06/90-06/93    Doktorandin, Abt. Biophysikalische Chemie, Universität Basel, Schweiz
10/90        Diplom-Ingenieur Physik, Lunds Tekniska Högskola (LTH) Schweden
01/90        Diplom-Ingenieur Physik Ecole Polytechnique Fédérale de Lausanne, Schweiz
04/88-01/90    Hauptstudium der Physik an der Ecole Polytechnique Fédérale de Lausanne, Schweiz, im Rahmen eines europäischen Doppeldiplomprogramms mit den Schwerpunkten Physik und allgemeine Ingenieurwissenschaften
09/85-03/88    Grundstudium der Physik an Lunds Tekniska Högskola (LTH) Schweden

Publikationen

Anzahl insgesamt: 62 peer-reviewed; 5 Buchkapiteln, 3 Patente, h-index 26/31; i10: 52 (siehe: http://www.researcherid.com/rid/A-2134-2010 sowie Google Scholar)

Mitgliedschaft
•    Society for Magnetic Resonance in Medicine, ISMRM
•    Italienische Gesellschaft für Medizinische Physik, AIFM
•    Italienischer Verband für Strahlungs Forschung, FIRR
•    European Society for Molecular Imaging

Eingeworbene Drittmittel
05/13 – 04/15 Functional neuroimaging of the human brainstem at 9.4T Werner Reichardt Centre for Integrative Neurosciences    
04/06 - 03/08 Cognitive control during aging: physiology of decline and preclinical evaluation Italian Ministry of Health
04/01 – 03/03 Prognosis for functional motor recovery post-stroke: a study of anatomically correlated neurophysiology Italian Ministry of Health
04/01 – 03/03 Neuropsychological, genetic and neurobiological basis of cerebellar injury Italian Ministry of Health     

Gremienarbeit
Gremiums-Mitglied der Italienischer Verband für Strahlungs Forschung, FIRR, 2008-2012
Scientific Committe:
•    Tagungen der AIFM: 2011 und 2013
•    EFOMP/ESMRMB/AIFM Kurs, Udine 22-15.10.2010
Advances in High Field Magnetic Resonance Imaging
•    Workshop, FIRR, Rom 14.5.2009
Radiation: Biology, Clinic, Environment, und Protection

Lehre
Lehrveranstaltungen: Universität Tübingen (Anwendungen der MRI in klinische und neurowissenschaftliche Forschung; MRI Kontrast im Rahmen der Medizintechnik); Universität Tor Vergata, Rom (Angewandte Physik); Fondazione Santa Lucia (Brain Imaging)
Betreuung von Studenten und Doktoranden: Phd (3); MSc (3); Spezialisierung der Medizinphysik (1)
Eingeladen Vorträge: Karolinska Institutet - Stockholm, CNR - Genova, International School on Magnetic Resonance and Brain Function – Erice, Strasbourg, France, Radboud University, Nijmegen, The Netherlands; Workshops und Kongresse: AIFM und ISMRM

Präferenzen: 
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Vorträge (19):

Hagberg GE, Bause J, Ethofer T, Ehses P, Dresler T, Shajan G, Pohmann R, Herbert C, Fallgatter A, Laske C, Pavlova M und Scheffler K (Mai-9-2016) Abstract Talk: Consistent detection of age-dependent variations of the longitudinal relaxation time in cortical brain regions investigated by MP2RAGE at 9.4T: influence of correcting for a non-uniform transmit field, 24th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2016), Singapore(0059).
Hagberg A (November-5-2015) Invited Lecture: Il controllo di qualità nell’imaging funzionale, I Controlli di Qualitá nelle Procedure RM Avanzate, Brescia, Italy.
Hagberg G (Oktober-15-2015) Invited Lecture: Clinical MRI at 9.4T: initial results, University of Glasgow: Seminar Series in Psychology, Glasgow, UK.
Loureiro JA, Hagberg GE, Ethofer T, Erb M und Scheffler K (Oktober-2015) Abstract Talk: Depth-Dependence of Visual Signals in the Human Superior Colliculus at 9.4T, 32nd Annual Scientific Meeting ESMRMB 2015, Edinburgh, UK, Magnetic Resonance Materials in Physics, Biology and Medicine, 28(1 Supplement) S246-S247.
Hagberg GE, Bause J, Ethofer T, Dresler T, Herbert C, Pohmann R, Shajan G, Fallgatter A und Scheffler K (Oktober-2015) Abstract Talk: T1 relaxometry and tissue segmentation of the human brain at 9.4T and 3T using MP2RAGE, 32nd Annual Scientific Meeting ESMRMB 2015, Edinburgh, UK, Magnetic Resonance Materials in Physics, Biology and Medicine, 28(1 Supplement) S234-S235.
Chadzynski GK, Hagberg G, Bause J, Shajan G, Bisdas S, Pohmann R und Scheffler K (Juni-5-2015) Abstract Talk: In-vivo proton MR spectroscopic imaging of the human brain gliomas at 9.4 Tesla: evaluation of metabolite coordinates, 23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015), Toronto, Canada(0763).
Hagberg G (Oktober-24-2013) Invited Lecture: First clinical studies at 9.4T: hurdles and opportunities, 4th Annual Meeting by the Italian Chapter of the ISMRM: Risonanza Magnetica in Medicina 2013:, Perugia, Italy.
Keliris A, Hagberg GE, Engelmann J und Scheffler K (Mai-26-2013) Abstract Talk: Dual modality approach for detection of enzyme activity by means of 1H/19F MRI, 8th European Molecular Imaging Meeting (EMIM 2013), Torino, Italy(298).
Balla DZ, Sanchez Panchuelo RM, Wharton SJ, Hagberg GE, Scheffler K, Francis ST und Bowtell RW (April-23-2013) Abstract Talk: Experimental investigation of the relation between gradient echo BOLD fMRI contrast and underlying susceptibility changes at 7T, 21st Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2013), Salt Lake City, UT, USA 910.
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Mamedov I, Engelmann J, Hagberg GE, Logothetis NK, Gambino G, Tei L und Botta M (November-2012) Abstract Talk: Development of multimodal imaging probes for neuroanatomical connectivity studies in vivo, Fifth Annual World Molecular Imaging Congress (WMIC 2012), Dublin, Ireland, Molecular Imaging and Biology, 14(Supplement 2) S1901.
Hagberg G (Oktober-25-2012) Invited Lecture: 19F-Lanthanide complexes: T1 and T2-dependent signal gain using gradient echoes, Nijmegen Center for Molecular Life Sciences: Radboud University, Nijmegen, The Netherlands.
Balla DZ, Sanchez-Panchuelo RM, Wharton S, Hagberg GE, Scheffler K, Francis ST und Bowtell RW (Mai-8-2012) Abstract Talk: Functional Quantitative Susceptibility Mapping (fQSM), 20th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2012), Melbourne, Australia(325).
Hagberg G (September-22-2010) Invited Lecture: Basic hardware: magnet, gradients and RF coils, IVth European Conference of Medical Physics on Advances in High Field Magnetic Resonance Imaging 2010, Udine, Italy 72-73.
Hagberg GI (Mai-2005) Invited Lecture: Feasibility of direct detection of neuronal currents using MRI, 3rd Course: Brain Function Research by Magnetic Resonance, Electrophysiology and Molecular Probes, Erice, Italy.
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Last updated: Montag, 22.05.2017