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IRONMAP: Iron Network Mapping and Analysis Protocol for Detecting Over-Time Brain Iron Abnormalities in Neurological
Abstract:
Pathologically altered iron levels, detected using iron-sensitive MRI techniques such as quantitative susceptibility mapping (QSM), are observed in neurological disorders such as multiple sclerosis (MS) and may play a crucial role in disease pathophysiology. However, brain iron changes occur slowly, even in neurological diseases, and can be influenced by physiological factors such as diet. Therefore, novel analysis methods are needed to improve sensitivity to disease-related iron changes as compared to conventional region-based analysis methods. This study introduces IRONMAP, Iron Network Mapping and Analysis Protocol, which is a novel network-based analysis method to evaluate over-time changes in magnetic susceptibility. With this novel methodology, we analyzed short-term (<1 year) longitudinal QSM data from a cohort of individuals with MS (pwMS) and healthy controls (HCs) and assessed disease-related network patterns, comparing the new approach to a conventional per-region rate-of-change method. IRONMAP analysis was able to detect over-time, MS-related brain iron abnormalities that were undetectable using the rate-of-change approach. IRONMAP was applicable on the per-subject level, improving binary classification of pwMS vs HCs compared to rate-of-change data alone (areas under the curve: 0.773 vs 0.636, p = 0.024). Further analysis revealed that the observed IRONMAP-derived HC network structure closely aligned with simulated networks based on healthy aging-related susceptibility data, suggesting that disruptions in normal aging-related iron changes may contribute to the network differences seen in pwMS. IRONMAP is generalizable to any neurological disease, including Alzheimer's disease and Parkinson's disease, and may allow for study of brain iron abnormalities over shorter timeframes than previously possible.
Insights
A new method called IRONMAP detects subtle, over-time brain iron changes in multiple sclerosis (MS) that conventional analysis misses. This network-based approach improves classification of MS patients versus healthy controls, offering potential for earlier disease detection.
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.
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