Abstract Details

Title Co-Registration of DTI and MTR MRI Data to Quantitative Immunohistochemistry in a Novel Mouse Model of Inflammatory Cerebral Demyelination

Topic MS and Related Diseases

Presentation(s) P06 - (-)

Poster/Presentation
Number 124

Objective

Background BACKGROUND: Conventional MRI is routinely utilized to evaluate the efficacy of therapeutic agents in MS clinical studies. However, the relationship between non-conventional, in vivo imaging measures and underlying pathophysiological processes remains poorly understood. In order to maximize the information gleaned from MRI data and appropriately steer clinical development of novel therapeutics, we have performed a rigorous correlation analysis between in vivo 3D MRI measures and gold-standard, post-mortem quantitative immunohistochemistry (qIHC) measures in mice with focal inflammatory/demyelinating cerebral lesions.

Design/Methods DESIGN/METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in C57Bl/6 mice (n=12) using MOG35-55 peptide emulsified in CFA containing Mycobacterium tuberculosis. One week post-EAE induction, mice underwent unilateral stereotaxic injections of TNF-? and IFN-? into the corpus callosum. Two weeks post-EAE induction, 3D DTI and MTI images were acquired using 7T MRI. MR images were processed using a fully-automated pipeline to generate DTI fractional anisotropy/diffusivity and MTR maps. Following euthanasia, formalin-fixed, paraffin-embedded, whole brains were serially-sectioned. The sections underwent IHC staining to assess myelin density and inflammation. The IHC sections were digitized, reconstructed into 3D qIHC volumes, and spatially normalized to the MRI data (PERMITSTM, Biospective Inc.). Lesion-based correlation analyses were performed between MRI and qIHC measures.

Results RESULTS: All mice developed MRI-visible, focal inflammatory/demyelinating lesions in the vicinity of the corpus callosum. Details of the correlation analysis between in vivo MRI (FA, mean/axial/radial diffusivity, MTR) and post-mortem qIHC (myelin, edema) measures will be presented.

Conclusions CONCLUSIONS: Accurate co-registration of MRI and qIHC volumes from relevant mouse models is a powerful approach to interrogate the biological underpinnings of non-invasive, non-conventional imaging data and potentially guide the rational use of novel imaging biomarkers in MS clinical development.

Authors/Disclosures
Simone P. Zehntner PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Diego Cadavid, MD, FAAN (Verge Genomics)	Dr. Cadavid has received personal compensation for serving as an employee of Verge Genomics. Dr. Cadavid has received personal compensation for serving as an employee of Vertex Pharmaceuticals. Dr. Cadavid has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. Dr. Cadavid has or had stock in Verge Genomics.Dr. Cadavid has or had stock in Vertex Pharmaceuticals.
Edward A. Neuwelt, MD (Oregon Health Science Univ)	No disclosure on file

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