Intracranial volume normalization methods: considerations when investigating gender differences in regional brain
Richard Nordenskjöld1, Filip Malmberg2, Elna-Marie Larsson1
1Department of Radiology, Uppsala University, MRT, Entrance 24, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
Psychiatry Research
|February 11, 2015
Summary
Choosing the right intracranial volume (ICV) normalization method is crucial for studying brain volume differences between genders. Different methods reveal varying gender dimorphisms, impacting aging brain research.
Area of Science:
- Neuroimaging
- Gerontology
- Biostatistics
Background:
- Intracranial volume (ICV) normalization is standard for analyzing regional brain volumes (v) in aging brain studies.
- Existing normalization methods vary, necessitating an evaluation of their appropriateness, especially in gender dimorphism research.
- Understanding how normalization choices affect observed volume differences is critical for accurate interpretation.
Purpose of the Study:
- To assess the suitability of different ICV normalization methods for gender dimorphism studies in the aging brain.
- To investigate the impact of various normalization techniques on the detection of regional brain volume differences between genders.
- To introduce and evaluate a novel weighted ICV matching method for improved visualization of gender-related volume relations.
Main Methods:
- Theoretical analysis and simulated experiments were conducted to model the effects of normalization.
- Real-world data from 400 elderly subjects (age 75) with gold-standard ICV segmentation were used for evaluation.
- A new weighted ICV matching technique was developed and compared against existing methods.
Main Results:
- The choice of ICV normalization method significantly influenced the detected gender dimorphism in regional brain volumes.
- Both simulated and real data demonstrated method-dependent differences in findings.
- Method performance was found to be contingent on the linear relationship parameters (slope B, intercept m) between regional volume and ICV, and cohort gender distribution.
Conclusions:
- The study highlights the critical influence of ICV normalization method selection on gender dimorphism findings in brain volumetric research.
- A novel weighted ICV matching method offers enhanced visualization of gender-related volume differences.
- A practical workflow is proposed to guide the selection of appropriate ICV normalization methods for studies investigating sex-based differences in regional brain volumes.


