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Iron quantification of microbleeds in postmortem brain
Grant McAuley1, Matthew Schrag, Samuel Barnes
1Neurosurgery Center for Research, Training and Education, Loma Linda University, Loma Linda, California 92354, USA.
Abstract:
Brain microbleeds (BMB) are associated with chronic and acute cerebrovascular disease and present a source of pathologic iron to the brain proportional to extravasated blood. Therefore, BMB iron content is potentially a valuable biomarker. We tested noninvasive phase image methods to quantify iron content and estimate true source diameter (i.e., unobscured by the blooming effect) of BMB in postmortem human tissue. Tissue slices containing BMB were imaged using a susceptibility weighted imaging protocol at 11.7T. BMB lesions were assayed for iron content using atomic absorption spectrometry. Measurements of geometric features in phase images were related to lesion iron content and source diameter using a mathematical model. BMB diameter was estimated by image feature geometry alone without explicit relation to the magnetic susceptibility. A strong linear relationship (R(2) = 0.984, P < 0.001) predicted by theory was observed in the experimental data, presenting a tentative standardization curve where BMB iron content in similar tissues could be calculated. In addition, we report BMB iron mass measurements, as well as upper bound diameter and lower bound iron concentration estimates. Our methods potentially allows the calculation of brain iron load indices based on BMB iron content and classification of BMB by size unobscured by the blooming effect.
Insights
Noninvasive imaging methods can quantify iron in brain microbleeds (BMB), a biomarker for cerebrovascular disease. This technique accurately estimates BMB size and iron content, aiding in brain iron load assessment.
Area of Science:
- Neuroimaging
- Biomarkers
- Cerebrovascular Disease
Background:
- Brain microbleeds (BMB) are linked to cerebrovascular diseases.
- BMB contribute pathologic iron to the brain, making iron content a potential biomarker.
- Accurate quantification of BMB iron and size is crucial for clinical assessment.
Purpose of the Study:
- To test noninvasive phase imaging methods for quantifying iron content in BMB.
- To estimate the true source diameter of BMB, unaffected by imaging artifacts.
- To establish a method for calculating brain iron load indices based on BMB.
Main Methods:
- Postmortem human brain tissue slices with BMB were imaged using 11.7T susceptibility weighted imaging.
- BMB iron content was measured using atomic absorption spectrometry.
- A mathematical model related phase image geometric features to iron content and true source diameter.
Main Results:
- A strong linear relationship (R² = 0.984) was observed between phase image geometry and BMB iron content, supporting a standardization curve.
- The method allowed estimation of BMB diameter independent of magnetic susceptibility effects.
- Iron mass, upper bound diameter, and lower bound concentration estimates for BMB were reported.
Conclusions:
- Noninvasive phase imaging can accurately quantify BMB iron content and true size.
- This technique offers a potential method for calculating brain iron load and classifying BMB.
- The findings pave the way for improved diagnostic and prognostic tools in cerebrovascular disease.
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