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Abstract #3239

In vivo MRI characterization of a mouse model of vanishing white matter disease

Xiaomeng Zhang1, Bradley A Hooker 1, Arthur Nikkel1, Holly M Robb1, Ana M Basso1, Ann E. Tovcimak1, Carmela Sidrauski2, Gerard B. Fox1, Kathleen Martin2, Michael J. Dart1, and Yanping Luo1

1Discovery, Global Pharmaceutical Research and Development, Abbvie, North Chicago, IL, United States, 2Calico Life Sciences LLC, South San Francisco, CA, United States

Vanishing White Matter Disease (VWMD) is a rare genetic disorder characterized by white matter degeneration. Here we employed MRI to longitudinally characterize pathological changes in white matter with contrasts sensitive to pathology (T2W) and myelin integrity (MTR, DTI). Statistically significant difference were detected in T2W and MTR comparing wild-type and homozygous mice starting at 14 and 22 weeks of age, respectively. These differences between the wild-type and homozygous mice were observed before symptomatic behavioral changes, and became more prominent over the time. Correlations with immunohistochemistry markers provided underlying pathology corresponding to the observed imaging changes.

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