Evaluation of developing lesions with a combined approach of Magnetic Resonance Imaging, Magnetic Resonance Elastography and histopathology in an animal model of multiple sclerosis.

• Applicant: Dr. Katharina Schregel
• Subject Area: Medical Physics, Biomedical Technology
• Term: from 2016 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 317305913

Multiple Sclerosis (MS) is the most common neuroinflammatory disease. It leads to demyelination, axonal and neuronal damage in the central nervous system resulting in considerable impairment of those affected. MS is an immune-mediated disorder in genetically susceptible individuals. However, cause and pathogenesis are still unknown. Magnetic Resonance Imaging (MRI) has emerged as most important paraclinical tool to diagnose and monitor MS. However, conventional MRI-parameters lack specificity and correlate only poorly with the clinical course. Additionally, they hardly allow conclusions to be drawn with regard to the underlying pathology and the prognostic value is limited. Hence, novel in vivo parameters are needed to improve this situation.The proposed project focuses on the detection of inflammatory foci in the brain of MS patients in a very early stage. The experimental autoimmune encephalitis (EAE) mouse model will be used to test whether early neuroinflammatory changes can be depicted. Conventional MRI will be combined with a special arterial spin labeling (ASL) technique allowing for the quantification of vessel permeability and with Magnetic Resonance Elastography (MRE). MRE provides quantitative information on the biomechanical properties of a tissue non-invasively and in vivo. These properties are acquired by analyzing the propagation of low-frequency shear waves, which are mechanically elicited in the organ of interest. Finally, imaging parameters will be correlated to histopathological analyses focusing on inflammation, myelin and the extracellular matrix.Lesion development in MS and EAE respectively comprises the influx of autoreactive T-cells in the brain, recruitment and activation of further immune cells leading to demyelination and damage of axons and neurons. These processes interfere with the normal geometrical network of the brain parenchyma, which renders them mechanically detectable with MRE.During acute inflammation, some mediators are released leading to a disruption of the blood brain barrier (BBB). This can be investigated with a novel ASL method. It renders information on the capillary transfer time, a parameter reflecting changes in the integrity of the BBB as it is linked to capillary function.In order to facilitate influx of immune cells and to make the site of lesion development predictable, the BBB will be gradually opened in a predefined area using focused ultrasound. In summary, the project combines the evaluation of BBB integrity and the assessment of biomechanical properties in the EAE-model of MS to potentially find a biomarker able to predict the development of lesions. Such a biomarker has the potential to significantly improve the management of MS-patients. The non-invasive identification of early inflammatory activity could firstly facilitate the diagnosis of MS, secondly improve decision-making when a treatment should be initiated or modified and thirdly could help to predict the disease course.

• DFG Programme: Research Fellowships
• International Connection: USA
• Participating Institution: Brigham and Women's Hospital
• Host: Professor Dr. Charles R.G. Guttmann