Quantitative MRI Assessment of Olfactory System in Septo-Optic Dysplasia Spectrum and Related Midline Brain...

Although olfactory system abnormalities have been described in septo-optic dysplasia (SOD), prior studies have relied on qualitative or semiquantitative assessment, and the reproducibility of continuous MRI measurements remains unknown.We assessed the reproducibility of quantitative MRI measurements of the olfactory sulcus (OS) and olfactory bulb (OB) in patients with the SOD spectrum and related midline brain malformations, and examined their associations with consensus olfactory system abnormality scores.

In this IRB-approved, single-center, retrospective study, pediatric and adult patients were identified by searching radiology reports for "septo-optic dysplasia." The full cohort included patients with classic SOD, SOD-plus, partial/possible SOD-spectrum phenotypes, and related septal/callosal abnormalities. Those without adequate postnatal MRI for olfactory assessment or with septal abnormalities considered secondary to longstanding severe hydrocephalus were excluded. Three readers measured OS depth and OB width on coronal images or reformats and OS length on axial images or reformats. These measurements were normalized to biparietal diameter (BPD) to derive BPD-normalized olfactory metrics. Readers also assigned ordinal olfactory system abnormality scores (0-3) for the ipsilateral olfactory bulb and tract, with the median across readers serving as the consensus score. Measurement reproducibility was assessed by calculating intraclass correlation coefficients (ICCs). Associations with consensus scores were evaluated using rank-transformed linear mixed-effects models. Reproducibility and score associations were reassessed in a subgroup restricted to patients with classic SOD or SOD-plus phenotypes.

The study included 37 patients (mean age, 22.6 ± 20.5 years; range, 0-65 years; 19 women; 74 sides). BPD-normalized olfactory metrics showed moderate reproducibility, with ICCs of 0.58 for OS depth/BPD, 0.69 for OS length/BPD, and 0.69 for OB width/BPD, whereas the olfactory system abnormality score showed low inter-reader agreement. OS depth/BPD, OS length/BPD, and OB width/BPD were significantly associated with consensus score categories (all P range, < .001-.01). Findings were preserved in the 25-patient classic SOD/SOD-plus subgroup.

BPD-normalized olfactory metrics were reproducible and associated with consensus scores, suggesting that they may facilitate more consistent recognition and characterization of olfactory system involvement in the SOD spectrum and complement categorical visual assessment.