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Evaluation of Brain Microstructural Alterations in Preschool Autism Spectrum Disorder: A Voxel‐Wise Multimodal MRI Study

Year: 2026

Type: article

Abstract: BACKGROUND: Autism Spectrum Disorder (ASD) presents with early neurodevelopmental alterations in preschool children, yet comprehensive characterization using multimodal quantitative MRI remains limited in this age group. PURPOSE: To investigate voxel-wise brain microstructural differences in preschool ASD through integrated analysis of cerebral perfusion, multiparametric relaxometry, and magnetic susceptibility. STUDY TYPE: Prospective case-control. POPULATION: Twenty nine-children with ASD (age 2-6 years; 23 males/6 females) and 25 age-/sex-matched healthy controls (HC). FIELD STRENGTH/SEQUENCE: 3.0 T MRI; high-resolution 3D-T1WI, quantitative susceptibility mapping (QSM), synthetic MRI (SyMRI), 3D pseudo-continuous arterial spin labeling (3D-pCASL). ASSESSMENT: Clinical assessments included the Gesell Developmental Schedules (GDS) and Childhood Autism Rating Scale (CARS). Imaging analysis consisted of voxel-wise whole-brain assessment of QSM, T1/T2/PD, and cerebral blood flow (CBF) maps. STATISTICAL TESTS: General linear models with cluster-based thresholding were applied for group comparison; Spearman's rank correlation with Bonferroni correction was used for clinical associations; and receiver operating characteristic (ROC) analysis with Delong's test was performed to compare diagnostic performance based on the areas under the curve (AUCs). RESULTS: Compared to HC, children with ASD showed decreased QSM values in the left superior/middle frontal gyri (SFG/MFG; cluster = 212 voxels, peak T = 5.55, p < 0.001). They also had reduced T1 relaxation times in bilateral SFG/MFG/precentral/postcentral gyri (four clusters: 315-750 voxels, peak T = 5.11-5.88, all p < 0.001). QSM values in the left SFG/MFG correlated positively with fine motor scores (r = 0.630, p < 0.001), while T1 values in the bilateral precentral/postcentral gyri correlated with gross motor scores (right: r = 0.548, p = 0.002; left: r = 0.461, p = 0.012). ROC analysis showed high diagnostic accuracy for both QSM (left SFG/MFG AUC = 0.858) and T1 values (left SFG/MFG AUC = 0.905; bilateral precentral/postcentral gyri AUC = 0.892-0.908). DATA CONCLUSION: Preschool ASD demonstrates prefrontal iron deficiency (reduced QSM) and sensorimotor myelination alterations (decreased T1), which correlate with motor deficits and show high diagnostic efficacy. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Source: Journal of Magnetic Resonance Imaging

DOI: 10.1002/jmri.70185