Characterization of Brain Abnormalities in Lactational Neurodevelopmental Poly I:C Rat Model of Schizophrenia and Depression Using Machine-Learning and Quantitative MRI.
Rona Haker, Coral Helft, Emilya Natali Shamir, Moni Shahar, Hadas Solomon, Noam Omer, Tamar Blumenfeld-Katzir, Sharon Zlotzover, Yael Piontkewitz, Ina Weiner, Noam Ben-Eliezer
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Abstract
Background: A recent neurodevelopmental rat model, utilizing lactational exposure to polyriboinosinic-polyribocytidilic acid (Poly I:C) leads to mimics of behavioral phenotypes resembling schizophrenia-like symptoms in male offspring and depression-like symptoms in female offspring.
Purpose: To identify mechanisms of neuronal abnormalities in lactational Poly I:C offspring using quantitative MRI (qMRI) tools.
Study type: Prospective.
Animal model: Twenty Poly I:C rats and 20 healthy control rats, age 130 postnatal day.
Field strength/sequence: 7 T. Multiflip-angle FLASH protocol for T1 mapping; multi-echo spin-echo T2-mapping protocol; echo planar imaging protocol for diffusion tensor imaging.
Assessment: Nursing dams were injected with the viral mimic Poly I:C or saline (control group). In adulthood, quantitative maps of T1, T2, proton density, and five diffusion metrics were generated for the offsprings. Seven regions of interest (ROIs) were segmented, followed by extracting 10 quantitative features for each ROI.
Statistical tests: Random forest machine learning (ML) tool was employed to identify MRI markers of disease and classify Poly I:C rats from healthy controls based on quantitative features.
Results: Poly I:C rats were identified from controls with an accuracy of 82.5 ± 25.9% for females and 85.0 ± 24.0% for males. Poly I:C females exhibited differences mainly in diffusion-derived parameters in the thalamus and the medial prefrontal cortex (MPFC), while males displayed changes primarily in diffusion-derived parameters in the corpus callosum and MPFC.
Data conclusion: qMRI shows potential for identifying sex-specific brain abnormalities in the Poly I:C model of neurodevelopmental disorders.
Level of evidence: NA TECHNICAL EFFICACY: Stage 2.
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