By Melissa Silverberg
Children with migraine often undergo MRI scans that appear entirely normal — leaving families and clinicians scrambling for answers. New research presented in a Sunday session shows that morphometric similarity mapping (MSM)—an advanced analytic technique applied to standard MRI sequences—can unmask subtle but meaningful brain network changes in pediatric migraine patients despite normal scan reports.
“Migraine is the leading headache in childhood, and yet we still lack objective biomarkers that help us understand why some children develop disabling symptoms while their brain MRIs look entirely normal,” said Alessia Guarnera, MD, pediatric neuroradiologist at Saint Camillus International University of Health and Medical Sciences in Rome. “This situation can be particularly frustrating for patients, families and professionals.”
Dr. Guarnera’s group used MSM, integrating data from 3D T1 MPRAGE and diffusion-weighted imaging. Unlike functional MRI or tractography techniques, MSM uses standard structural MRI sequences, minimizing motion-artifact issues—a major advantage in pediatric imaging.
“MSM is cost-efficient, sustainable and requires a short acquisition time. It offers a glimpse into the brain’s hidden architecture and provides a more nuanced view of what a ‘normal’ MRI means.”
Alessia Guarnera, MD
In the study, the investigators retrospectively reviewed 498 children (ages 6-18) with migraine without aura and 100 healthy controls, all of whom met criteria of normal MRI and neurological exam. Eleven cortical parameters were extracted to construct morphometric similarity networks and assess regional brain organization.
The analysis revealed significant differences in three major pathways: the executive function network, the nociceptive pathway, and the default mode network. These networks respectively govern attention and pain regulation, sensory-pain processing, and internal cognitive/emotional activity.
“These findings reinforce that migraine symptoms arise from network dysfunction rather than isolated regions,” Dr. Guarnera said.
One of the most striking findings was how strongly biological sex predicted network organization differences—even more than attack frequency or symptom severity.
“We were particularly surprised by how strongly sex mattered,” Dr. Guarnera said. “Boys and girls appeared to recruit different networks in response to migraine.”
In the cohort, boys showed greater alterations in sensory–affective brain areas, while girls exhibited more involvement of cognitive–attentional regions.
“These patterns indicate that the same clinical syndrome may rely on partly different brain mechanisms in boys and girls,” Dr. Guarnera said. Recognizing this may help clinicians tailor management approaches and anticipate migraine trajectories through puberty.
Dr. Guarnera said MSM could become a powerful imaging tool for pediatric migraine if validated in larger cohorts and followed longitudinally.
“A normal MRI does not mean a normal brain in pediatric migraine. Thanks to MSM, we can detect subtle but meaningful alterations in the brain’s network architecture,” she said.
She said radiologists should consider MSM’s potential: when a standard MRI appears “clean” in a child with migraine, the story may not be over. Incorporating network-based imaging biomarkers could reshape how doctors assess and manage pediatric migraine.
“MSM uses standard MRI sequences and provides objective measures of how cortical regions relate to one another,” she said. “It may help identify vulnerable children earlier, monitor disease evolution and support individualized therapy.”
Access the presentation, “Morphometric Similarity Mapping in Pediatric Migraine without Aura: Unraveling the Role of Biological Sex,” (S4-SSNR01-6) on demand at RSNA.org/MeetingCentral
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The RSNA 2025 Daily Bulletin is the official publication of the 110th Scientific Assembly and Annual Meeting of the Radiological Society of North America. Published online Sunday, November 30 — Thursday, December 4.
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