Neuroimaging in Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative disease causing widespread tissue damage in the brain and spinal cord. This disease is the leading cause of non-traumatic neurological disability among young adults. MRI plays a key role in the diagnosis, management and research of MS.

The Neuroimaging in Multiple Sclerosis Group

Headed by Professor Hartwig Siebner, the aim of the Neuroimaging in Multiple Sclerosis group (NiMS) is to push the frontiers of MRI to capture MS-related tissue damage and uncover the underlying pathophysiological mechanisms. The group uses a wide range of MR-based techniques such as functional MRI, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), but also electrophysiological methods such as electroencephalography (EEG) and transcranial magnetic stimulation (TMS). The current focus is on exploiting the potential of MRI at ultra-high field strength (7 tesla) to detect neocortical involvement and characterize microstructural changes in cerebral white matter.

An image based on diffusion weighted imaging demonstrating fibre directionality in the coronal representation of corpus callosum. Estimating voxelwise fibre directions is the first stage in the process of mapping structural brain connectivity in patients with multiple sclerosis.

Neuroimaging research in the field of MS has a long tradition at DRCMR and greatly benefits from a long-standing and inspiring collaboration with the Danish Multiple Sclerosis Centre, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Denmark. In recent years, the NiMS group pursued several lines of neuroimaging research, including studies of the blood-brain barrier dysfunction in normal appearing white matter (PhD project by Henrik Lund) and the atrophy pattern of the upper cervical spinal cord (Ellen Grade and Henrik Lundell). Together with the DRCMR Reader Centre, the NIMS group participates in the analysis of the MRI data that are acquired at DRCMR as part of investigator-driven as well as company initiated clinical trials.

An overarching theme of our research is to examine how MS alters functional and structural brain connectivity and how such MS-related connectivity changes contribute to clinical disability (Kasper W. Andersen, Kristoffer H. Madsen). Using rs-fMRI, the NiMS group was able to identify distinct changes in functional connectivity in the motor resting-state network in a group of patients with relapsing-remitting or secondary progressive MS (PhD project by Anne-Marie Dogonowski). We found that MS impairs regional functional connectivity in the cerebellum. At the brain network level, patients with MS showed a more widespread coupling of the basal ganglia with the motor resting-state network, indicating an impaired “funneling” function of the basal ganglia in MS. Moreover, resting-state connectivity of pre-motor cortex reflected the degree of disability on the Expanded Disability Status Scale (EDSS).

Key projects

What causes fatigue in patients with multiple sclerosis? – A network perspective

We are currently conducting a comprehensive multi-modal brain mapping study, in which we aim at delineating abnormalities in brain function and structure that lead to fatigue in patients with MS. Fatigue is one of the most common symptoms in Multiple Sclerosis (MS). It has been suggested that fatigue is a consequence of disease-related microstructural alterations in specific white matter (WM) tracts. By applying anatomical connectivity mapping (ACM), we wish to probe whether fatigued MS patients have different levels of anatomical connectedness compared to non-fatigued MS patients. (PhD projects by Olivia Svolgaard and Christian Bauer).

Cortical lesion in primary sensorymotor hand area and their impact on dexterity in multiple sclerosis: a 7T MRI study

In this project, we wish to clarify the impact of regional cortical lesions within the sensorymotor hand area (SM1-HAND) on cortical function and manual dexterity. Exploiting the increased sensitivity of ultra-high field 7 Tesla MRI to detect cortical lesions, we will assess the number, size and regional distribution of cortical lesions in SM1-HAND, and relate regional lesion load in SM1-HAND to MRI-based, electrophysiological, and behavioural correlates of hand function (PhD project by Mads Alexander Just Madsen). Diffusion weighted magnetic resonance spectroscopy at ultra-high field:

Unravelling microstructural changes in cerebral white matter in patients with multiple sclerosis

We are currently pursuing the first clinical ultra-high field (7T) MR study in Denmark. In this project, we will combine magnetic resonance spectroscopy with diffusion MRI to shed new light into the microstructural alterations in major motor white-matter tract caused by MS. The project is conducted by Senior Researcher Henrik Lundell who received a “Sapere Aude” award by the Danish Council for Independent Research.

Group Leader

Hartwig R. Siebner

hartwig@drcmr.dk
+45 3862 6541

Group Members

Henrik Lundell

lundell@drcmr.dk
+45 3862 0633

Vanessa Wiggermann

vanessaw@drcmr.dk

Tim Dyrby

timd@drcmr.dk
+45 3862 6542

Sascha Gude

saschag@drcmr.dk
+45 3862 6118

Sussi Larsen

sussil@drcmr.dk
+45 3862 0422

Jesús Díaz Pereira

jesusdp@drcmr.dk

Chiara Cabras

chiarac@drcmr.dk

Ana Lucia Neves

lucian@drcmr.dk

Collaborators

Anne Mette Leffers, MD

Radiology Department
Hvidovre Hospital

Camilla Gøbel Madsen

Centre for Functional and Diagnostic Imaging
Hvidovre Hospital

Prof. Per Soelberg Sørensen

Danish Multiple Sclerosis Centre
Copenhagen University Hospital Rigshospitalet

Prof. Finn Sellebjerg

Danish Multiple Sclerosis Centre
Copenhagen University Hospital Rigshospitalet

Senior Consultant, Neurologist, PhD Morten Blinkenberg

Danish Multiple Sclerosis Centre
Copenhagen University Hospital Rigshospitalet

Assoc. Professor Kathrine S. Madsen

Faculty of Health and Technology, Metrolitan University College

Associate Prof. Morten Mørup

Section for Cognitive Systems
Technical University of Denmark

MSc., PhD Jesper Bencke

Human Movement Analysis Laboratory
Hvidovre Hospital

Associate Prof. Itamar Ronen

Department of Radiology
Leiden University Medical Center

Prof. Christian Dettmers

Kliniken Schmieder Heidelberg

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