Regional apparent diffusion coefficient measurements in children with migraine: a case–control diffusion-weighted MRI study

Abstract Purpose Pediatric migraine is a common neurological disorder, but evidence regarding potential brain microstructural alterations remains limited. This study aimed to compare apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) between children with migraine and non-migraine clinical controls across seven prespecified brain regions. Methods In this prospective case–control study, 48 children with migraine diagnosed according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), and 48 non-migraine clinical controls with comparable age and sex distributions were recruited from a tertiary pediatric neurology center. DWI was performed using a 1.5-Tesla MRI scanner with b -values of 0, 500, and 1000 s/mm 2 and three orthogonal diffusion-encoding directions. ADC values were measured bilaterally in seven prespecified brain regions using standardized manually placed regions of interest by two blinded radiologists. Between-group comparisons were performed using two-sided Mann–Whitney U tests, with Bonferroni correction across the seven prespecified regional comparisons. Effect sizes were expressed as Cohen’s d with 95% confidence intervals. An age- and sex-adjusted linear mixed-effects model was additionally performed as a sensitivity analysis. Results In the unadjusted analysis, mean thalamic ADC was higher in children with migraine than in controls (835.92 ± 23.50 vs. 823.40 ± 34.20 × 10 −6 mm 2 /s; mean difference, 12.52 × 10 −6 mm 2 /s; 95% CI 0.61–24.43; p = 0.020; Cohen’s d = 0.43). This difference did not remain statistically significant after Bonferroni correction (adjusted p = 0.140), and no other regional comparison met the corrected significance threshold. In the age- and sex-adjusted sensitivity analysis, the thalamus again showed a higher ADC in the migraine group (adjusted mean difference, 13.68 × 10 −6 mm 2 /s; 95% CI 3.10–24.25; p = 0.011), but this association also did not remain significant after correction (adjusted p = 0.067). The overall group effect and group-by-region interaction were not statistically significant. Conclusion No regional ADC difference remained statistically significant after correction for multiple comparisons. Although the thalamus showed the largest and directionally consistent between-group difference in both unadjusted and age- and sex-adjusted analyses, this finding should be considered exploratory rather than evidence of a definitive migraine-related microstructural abnormality. Regional ADC assessment therefore cannot currently be established as a diagnostic biomarker for pediatric migraine. Larger, adequately powered multicenter studies with detailed clinical phenotyping and standardized imaging and analysis protocols are warranted to determine whether subtle regional diffusion patterns are reproducible and clinically meaningful.