IRONMAP: Iron Network Mapping and Analysis Protocol for Detecting Over-Time Brain Iron Abnormalities in Neurological...

Area of Science:

• Neuroimaging
• Neurology
• Biophysics

Background:

• Altered brain iron levels are implicated in neurological disorders like multiple sclerosis (MS).
• Conventional analysis of iron changes using quantitative susceptibility mapping (QSM) lacks sensitivity for early detection due to slow changes and physiological influences.
• Novel analytical methods are required to enhance the detection of subtle, disease-related iron alterations over time.

Purpose of the Study:

• To introduce and validate IRONMAP (Iron Network Mapping and Analysis Protocol), a novel network-based analysis method for evaluating longitudinal changes in magnetic susceptibility.
• To compare the sensitivity of IRONMAP against conventional per-region rate-of-change methods for detecting MS-related brain iron abnormalities.
• To assess the utility of IRONMAP for subject-level classification and its generalizability to other neurological diseases.

Main Methods:

• Longitudinal quantitative susceptibility mapping (QSM) data (<1 year) from individuals with MS (pwMS) and healthy controls (HCs) were analyzed using IRONMAP.
• IRONMAP, a network-based approach, was developed to evaluate over-time changes in magnetic susceptibility.
• The performance of IRONMAP was compared to a conventional per-region rate-of-change method for detecting MS-related abnormalities and for binary classification (pwMS vs. HCs).

Main Results:

• IRONMAP successfully detected over-time, MS-related brain iron abnormalities that were undetectable using the conventional rate-of-change method.
• IRONMAP demonstrated improved binary classification of pwMS versus HCs (AUC: 0.773) compared to the rate-of-change approach (AUC: 0.636, p = 0.024).
• The IRONMAP-derived healthy control network structure aligned with healthy aging-related susceptibility data, suggesting age-related iron changes contribute to network differences in MS.

Conclusions:

• IRONMAP is a sensitive, network-based method capable of detecting subtle, short-term, MS-related brain iron changes.
• This novel protocol enhances subject-level classification accuracy for MS and is applicable to other neurological conditions like Alzheimer's and Parkinson's disease.
• IRONMAP offers a potential advancement for studying brain iron abnormalities over shorter timeframes than previously feasible.