Project

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Advanced techniques to investigate the physiopathology of multiple sclerosis using high and ultra-high field MRI

Applicant Granziera Cristina
Number 131914
Funding scheme Ambizione
Research institution Service de Neurologie Département des Neurosciences Cliniques CHUV
Institution of higher education University of Lausanne - LA
Main discipline Neurology, Psychiatry
Start/End 01.09.2011 - 31.08.2014
Approved amount 598'293.00
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All Disciplines (2)

Discipline
Neurology, Psychiatry
Molecular Biology

Keywords (5)

Multiple sclerosis; High field MRI-Cerebellum; Epstein Barr virus; Early markers of disease; Biologico-radiological scores

Lay Summary (English)

Lead
Lay summary
Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by a dynamic sequence of inflammatory, restorative and degenerative processes. Previous studies have shown the potential of magnetic resonance imaging (MRI) to better understand MS physiopathology and to perform diagnosis. More recent MRI studies aim at providing biomarkers of disease progression and response to therapy. However, the correlation between MRI findings and clinical deficits in MS patients remains insufficient, indicating that a more comprehensive understanding of the disease and its evolution is needed. Recent advances in MRI technology provide higher sensitivity and new contrasts. This opens further perspectives, especially to investigate (a) the early stages of MS and (b) disease-related alterations in complex brain structures like the cerebellum. Interestingly, cerebellar alterations have been poorly studied, despite they may strongly affect patients' outcome and could provide valuable markers of disease.

In the present project, we will investigate MS patients at very early stages of the disease and follow them over 2 years by using the following approaches:

1.) exploiting advanced MRI techniques to characterize the alterations of the cerebellum in MS. Using multi-contrast 3D high resolution whole brain MRI, we aim at obtaining higher sensitivity to lesion count and investigating lesion properties, to identify imaging markers that complement conventional MRI procedures in MS diagnosis and disease monitoring,

2.) merging MRI markers of cerebellar pathology with the alterations observed in the brain hemispheres in order to develop a global radiological score considering lesions count and tissue characteristics as well as clinical scores. Serial imaging and clinical data of a 2 year interval will be used to extend the model to predict disease evolution, and

3.) combining the global clinico-radiological score with a biological marker of MS, the Epstein Barr Virus (EBV). Numerous works have shown that EBV virus may play a triggering role in MS and we hypothesize that combining the global score and biological markers will further increase accuracy for monitoring the disease and improve the understanding of the physiopathology of cortical lesions.

In summary, our project will apply state of the art MRI resources to investigate unexplored aspects of MS physiopathology in early stages of the disease, evaluate these aspects as potential markers of disease and develop a combined score from MRI, biological tests and clinical analysis for disease classification, evolution and prognosis.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis.
Simioni Samanta, Amarù Fabio, Bonnier Guillaume, Kober Tobias, Rotzinger David, Du Pasquier Renaud, Schluep Myriam, Meuli Reto, Sbarbati Andrea, Thiran Jean-Philippe, Krueger Gunnar, Granziera Cristina (2014), MP2RAGE provides new clinically-compatible correlates of mild cognitive deficits in relapsing-remitting multiple sclerosis., in Journal of neurology, 0.
MP2RAGE Multiple Sclerosis Magnetic Resonance Imaging at 3 T
Kober T, Granziera C, Ribes D, Browaeys P, Schluep M, Meuli R, Frackowiak R, Gruetter R, Krueger G (2012), MP2RAGE Multiple Sclerosis Magnetic Resonance Imaging at 3 T, in INVESTIGATIVE RADIOLOGY, 47(6), 346-352.
The history and role of long duration stimulation in fMRI.
Krueger Gunnar, Granziera Cristina (2012), The history and role of long duration stimulation in fMRI., in NeuroImage, 62(2), 1051-5.
Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis
Guillaume Bonnier13 Alexis Roche1 David Romascano12 Samanta Simioni3 Djalel Meskaldji2 David, Advanced MRI unravels the nature of tissue alterations in early multiple sclerosis, in Annals of Clinical and Traslational Neurology, 000.
Brain inflammation, degeneration and plasticity in multiple sclerosis
Cristina Granziera, Till Sprenger, Brain inflammation, degeneration and plasticity in multiple sclerosis, in Arthur Toga (ed.), Elsevier, Oxford, 00.
Effects of MRI scan acceleration on brain volume measurement consistency.
Krueger Gunnar, Granziera Cristina, Jack Clifford R, Gunter Jeffrey L, Littmann Arne, Mortamet Bénédicte, Kannengiesser Stephan, Sorensen Alma Gregory, Ward Chadwick P, Reyes Denise A, Britson Paula J, Fischer Hubertus, Bernstein Matt A, Effects of MRI scan acceleration on brain volume measurement consistency., in Journal of magnetic resonance imaging : JMRI.
MRI in clinical management of multiple sclerosis
Cristina Granziera, Katrin Weier, Till Sprenger, MRI in clinical management of multiple sclerosis, in Arthur Toga (ed.), Elsevier, Oxford, 107.

Collaboration

Group / person Country
Types of collaboration
Pr D. Van De Ville and J.P. Thiran, EPFL, Lausanne and University of Geneva and Pr J-P-Thiran, EPFL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Pr G. Krueger, EPFL-Siemens (ACICT group) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
- Industry/business/other use-inspired collaboration
Pr C. Mainero, MGH and Harvard University, Boston, USA United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Pr Reichenbach J. (Jena University, Germany) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Pr T. Sprenger and Dr J. Khule, University Basel, CH Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Pr Frahm J. (Max-Planck_Institute Goettingen, Germany) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Pr R. Du Pasquier and PD Dr Schluep, Neuroimmunology unit-CHUV Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Dr Hadjidemetriou S. (University of Freiburg, Germany) Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
ACTRIMS/ECTRIMS Poster Multiple Sclerosis lesion fingerprint using multicontrast MRI 10.09.2014 Boston, United States of America Bonnier Guillaume; Granziera Cristina;
ISMRM Outreach Workshop Individual talk Neuroimaging: Overview of emerging techniques” and “Neuroimaging: new techniques and their impact in the clinic”. 02.05.2013 Sao Paulo, Brazil Granziera Cristina;
International Society of Magnetic Resonance in Medicine Individual talk Ultra-Fast T2 Mapping of Multiple Sclerosis Pathology in Early Disease 05.05.2012 Salt Lake City, United States of America Bonnier Guillaume; Granziera Cristina;


Associated projects

Number Title Start Funding scheme
154508 Advanced techniques to study the physiopathology of multiple cclerosis (MS) using high and ultra-high field MRI 01.09.2014 Ambizione
150828 Development of Advanced Translational High-Field MRI 12.05.2014 R'EQUIP

Abstract

Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by a dynamic sequence of inflammatory, restorative and degenerative processes. Previous studies have shown the potential of magnetic resonance imaging (MRI) to better understand MS physiopathology and to perform diagnosis. More recent MRI studies aim at providing biomarkers of disease progression and response to therapy. However, the correlation between MRI findings and clinical deficits in MS patients remains insufficient, indicating that a more comprehensive understanding of the disease and its evolution is needed.Recent advances in MRI technology provide higher sensitivity and new contrasts. This opens further perspectives, especially to investigate (a) the early stages of MS and (b) disease-related alterations in complex brain structures like the cerebellum. Interestingly, cerebellar alterations have been poorly studied, despite they may strongly affect patients’ outcome and could provide valuable markers of disease. In the present project, we will investigate MS patients at very early stages of the disease and follow them over 2 years by using the following approaches:1.) exploiting advanced MRI techniques to characterize the alterations of the cerebellum in MS. Using multi-contrast 3D high resolution whole brain MRI, we aim at obtaining higher sensitivity to lesion count and at investigating lesion properties, to identify imaging markers that complement conventional MRI procedures in MS diagnosis and disease monitoring, 2.) merging MRI markers of cerebellar pathology with the alterations observed in the brain hemispheres in order to develop a global radiological score considering lesions count and tissue characteristics as well as clinical scores. Serial imaging and clinical data of a 2 year interval will be used to extend the model to predict disease evolution, and3.) combining the global clinico-radiological score with a biological marker of MS, the Epstein Barr Virus (EBV). Numerous works have shown that EBV virus may play a triggering role in MS and we hypothesize that combining the global score and biological markers will further increase accuracy for monitoring the disease and improve the understanding of the physiopathology of cortical lesions. In summary, our project will apply state of the art MRI resources to investigate unexplored aspects of MS physiopathology in early stages of the disease, evaluate these aspects as potential markers of disease and develop a combined score from MRI, biological tests and clinical analysis for disease classification, evolution and prognosis.
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