Christopher Zoppo ¹ Josephine Kolstad ¹ Jean Johnston ² Precilla D. Souza ² Anna L. Kühn ¹ Zeynep Vardar ¹ Ahmet Peker ³ Clifford Lindsay ¹ Zubir S. Rentiya ⁴ Robert King ¹ Heather Gray-Edwards ¹ Behroze Vachha ¹ Maria T. Acosta ² Cynthia Tifft ² Mohammed Salman Shazeeb ^1*

• ¹ University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States
• ² National Institutes of Health (NIH), Bethesda, Maryland, United States
• ³ Koç University Hospital, Istanbul, Türkiye
• ⁴ University of Virginia, Charlottesville, Virginia, United States

GM1-gangliosidosis (GM1) leads to extensive neurodegenerative changes and atrophy that precludes the use of automated MRI segmentation techniques for generating brain volumetrics. We developed a standardized segmentation protocol for brain MRIs of patients with type II GM1 and then assessed the inter-and intra-rater reliability of this methodology. The volumetric data may be used as a biomarker of disease burden and progression, and standardized methodology may support research into the natural history of the disease which is currently lacking in the literature. Approach Twenty-five brain MRIs were included in this study from 22 type II GM1 patients of which 8 were late-infantile subtype and 14 were juvenile subtype. The following structures were segmented by two rating teams on a slice-by-slice basis: whole brain, ventricles, cerebellum, lentiform nucleus, thalamus, corpus callosum, and caudate nucleus. The inter-and intra-rater reliability of the segmentation method was assessed with an intraclass correlation coefficient as well as Sorensen-Dice and Jaccard coefficients.Based on the Sorensen-Dice and Jaccard coefficients, the inter-and intra-rater reliability of the segmentation method was significantly better for the juvenile patients compared to late-infantile (p < 0.01). In addition, the agreement between the two rater teams and within themselves can be considered good with all p-values < 0.05.The standardized segmentation approach described here has good inter-and intra-rater reliability and may provide greater accuracy and reproducibility for neuromorphological studies in this group of patients and help to further expand our understanding of the natural history of this disease.