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Simple diameters, accurate stages:a practical approach to HD-ISS staging
Beatrice Heim1, Florian Krismer1, Greta Hemicker1
1Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Insights
A new simplified linear measurement, the bifrontal-to-bicaudate ratio (FCR), accurately estimates brain volumes for Huntington's disease staging. This method offers a practical alternative to complex volumetric analysis, improving accessibility for clinical practice and research.
Area of Science:
- Neuroimaging
- Neurology
- Biomarkers
Background:
- Huntington's disease (HD) is a neurodegenerative disorder linked to CAG repeat expansions.
- The Huntington's Disease Integrated Staging System (HD-ISS) uses clinical, biological, and imaging data, with caudate and putamen volumes as key early biomarkers.
- Conventional automated volumetric methods for assessing these biomarkers are complex and require specialized expertise, limiting their widespread use.
Purpose of the Study:
- To evaluate simple linear measurements, specifically the bifrontal-to-bicaudate ratio (FCR), as a practical alternative for assessing striatal atrophy in HD.
- To determine if FCR can reliably predict caudate and putamen volumes for HD-ISS staging.
- To assess the feasibility of using FCR in clinical practice and non-specialist research settings.
Main Methods:
- Caudate and putamen volumes were initially measured using automated segmentation (FreeSurfer).
- Linear measurements, including frontal horn width and intercaudate distance, were used to calculate FCR in a training cohort (n=44).
- Regression models predicting volumes from FCR were developed and validated in an independent test cohort (n=11); interrater reliability was assessed.
Main Results:
- FCR demonstrated a strong correlation with both caudate (r=0.866) and putamen volumes (r=0.897).
- Predictive equations based on FCR accurately estimated caudate and putamen volumes.
- HD-ISS staging classifications derived from FCR-based estimations were identical to those from conventional volumetric measurements for all participants in the test cohort.
Conclusions:
- FCR-based linear estimation provides an accurate and reliable method for assessing caudate and putamen volumes for HD-ISS staging.
- This simplified approach is a practical, time-efficient alternative to traditional volumetric analysis.
- The FCR method has the potential to increase the accessibility and application of HD-ISS staging in diverse clinical and research environments.
Background:
Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat expansions. The Huntington's Disease Integrated Staging System (HD-ISS) classifies disease stages (0-3) using clinical, biological, and imaging assessments, with caudate and putamen volumes serving as key early biomarkers. Conventional automated volumetric methods typically require specialized software and experienced operators, limiting broader accessibility. Simple linear measurements, such as the bicaudate ratio (BCR) and bifrontal-to-bicaudate ratio (FCR), may provide a practical alternative for assessing striatal atrophy.
Methods:
Reference caudate and putamen volumes were measured using automated segmentation (FreeSurfer). Linear measurements (frontal horn width, intercaudate distance, inner table width) were used to calculate BCR and FCR in a training cohort of 44 HD mutation carriers. Regression models predicting caudate and putamen volumes based on FCR were developed and validated in an independent test cohort of 11 HD mutation carriers. Interrater reliability was assessed via intraclass correlation coefficients (ICC).
Results:
Interrater reliability was excellent. Among linear measurements, FCR had the strongest correlation with caudate (r = 0.866; R2 = 0.749) and putamen volumes (r = 0.897; R2 = 0.805). Predictive equations derived from FCR-based regression models accurately estimated volumes, resulting in identical HD-ISS staging classifications compared to actual volumetric measurements for all test cohort participants.
Conclusion:
FCR-based linear estimation of caudate and putamen volumes provides accurate and reliable HD-ISS staging. This simplified method offers a practical and time-efficient alternative to conventional volumetry, potentially facilitating wider application of HD-ISS staging in clinical practice and non-specialist research settings.
