Exploratory MIA Study: Multimodal Magnetic Resonance Imaging Characteristics of Rat Offspring Induced by Maternal Poly(I:C) Exposure During Pregnancy

Bin Wu¹Zhang Yijie^1*Liu Yunxia²Zhiwei Feng¹Sun Wenjun^3*

• ¹Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
• ²Miyun District Hospital of Traditional Chinese Medicine, Beijing, China
• ³Department of Encephalopathy, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China

ABSTRACT Background: Maternal infection or inflammatory stimulation during pregnancy can disrupt fetal brain development through immune activation, increasing the risk of psychiatric disorders in offspring, including schizophrenia. Using a maternal immune activation (MIA) model induced by polyinosinic–polycytidylic acid (Poly(I:C)) during pregnancy, this study employed multimodal magnetic resonance imaging (MRI)—including T2 structural imaging, diffusion tensor imaging (DTI), arterial spin labeling (ASL), and magnetic resonance spectroscopy (MRS)—to comprehensively assess offspring brain alterations across structure, white matter integrity, cerebral perfusion, and metabolite levels. Methods: Pregnant Wistar rats were randomly assigned to a Poly(I:C) model group or a saline control group. Adult male offspring underwent T2 structural imaging, DTI, ASL, and MRS. Voxel-based morphometry of T2 images evaluated structural changes; DTI quantified fractional anisotropy (FA) and diffusivity indices (mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]); ASL measured cerebral blood flow (CBF) in the prefrontal cortex and striatum; and MRS assessed metabolite levels in the prefrontal cortex. Group differences were analyzed (p<0.05). Results: Poly(I:C) offspring exhibited significant gray matter density reductions in the prefrontal cortex, hippocampus, striatum, cingulate cortex, and sensorimotor cortex, whereas the right posterior parietal cortex showed increased density and the left third ventricle was enlarged. DTI revealed elevated MD and RD in the hippocampal dentate gyrus, along with increased RD in the genu of the corpus callosum, indicating white matter microstructural damage and abnormalities in myelination. ASL demonstrated significantly increased CBF in the prefrontal cortex and striatum, reflecting abnormal regional perfusion. MRS showed a significant reduction in NAA/Cr in the prefrontal cortex, suggesting impaired neuronal function. Bin Wu et al. MRI Features in Poly(I:C)-Induced Rats Conclusion: Offspring rats exposed to maternal Poly(I:C) during pregnancy exhibited abnormalities across multiple domains, including brain structure, white matter microstructure, cerebral perfusion, and metabolism. This study provides additional evidence that maternal inflammation during pregnancy can interfere with offspring brain development and impair neurological function.