Accession Number:

ADA591326

Title:

Noninvasive Detection and Differentiation of Axonal Injury/Loss, Demyelination, and Inflammation

Descriptive Note:

Annual rept. 30 Sep 2012-29 Sep 2013

Corporate Author:

WASHINGTON UNIV ST LOUIS MO

Report Date:

2013-10-01

Pagination or Media Count:

7.0

Abstract:

In the current proposal, in vivo diffusion basis spectrum imaging DBSI was employed to simultaneously quantify CNS white matter pathologies of axonal injury, demyelination, and inflammation, correlating with postmortem immunohistochemical staining, in experimental autoimmune encephalomyelitis EAE and cuprizone treated mice. During the first year of this study, we struggled with the lengthy data acquisition 5 hours in previously published paper. Despite the previous success, it proved to be very difficult to maintain consistent data quality using the old protocol. We thus developed a revised protocol taking the advantage of simple structure of optic nerve and corpus callosum to reduce the diffusion weighting scheme to 25 directions, shortened the acquisition time by 50. Our preliminary data from the cuprizone treated mice suggested that reduction in acquisition time indeed had significant impact in data quality for imaging corpus callosum since the RF coil could not be improved at the present time. However, preliminary results also support that the new scheme is sufficient to reflect the known pathologies in corpus callosum under the influence of cuprizone treatment. We have observed through the in vivo DBSI results axon and myelin pathologies seen by histology and EM that wer not reported by other MRI approaches. With the improved RF coil and the reduced diffusion weighting scheme, we found that the new protocol worked perfectly for mouse optic nerve DBSI measurements as outline in the proposal. We have identified various vendors of the FDA approved anti-inflammatory drug treating relapse-remitting MS, Gilenya finfolimod, or FTY720, for animal studies. Thus, we would like to request the pre-approval to replace our initially proposed use of dexamethasone with Gilenya to increase the clinical relevance of the current proposal.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE