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Postmortem MRI and histopathology of white matter changes in Alzheimer brains. A quantitative, comparative study
Lena Bronge1, Nenad Bogdanovic, Lars-Olof Wahlund
1Institutions of KARO, Department of Radiology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. lena.bronge@radiol.hs.sll.se
Abstract:
To evaluate whether magnetic resonance imaging (MRI) of white matter changes in Alzheimer's disease either under- or overestimates the findings on neuropathology. Postmortem MRI and neuropathological examination were performed on 6 brains from elderly individuals with a postmortem diagnosis of AD. Using a specially designed brain slicer, the brains were cut corresponding to the MRI images, and stained by Luxol Fast Blue. Quantitative analysis of white matter changes on MRI and neuropathology was performed using stereological principles. Measures from MRI and pathology were highly correlated (r(2) = 0.71). However, pathology showed significantly more extensive changes than did MRI in all cases, with a mean of 54% larger areas. The lesions not identified with MRI represented, however, only minor changes with lower intensity of myelin staining and with an accentuation of the distance between fibres but with preserved axonal network and glial cell density.
Insights
Magnetic resonance imaging (MRI) for Alzheimer's disease (AD) white matter changes correlates with neuropathology. However, MRI underestimates the extent of these changes compared to direct pathological examination.
Area of Science:
- Neurology
- Neuroimaging
- Pathology
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder characterized by white matter changes.
- Magnetic resonance imaging (MRI) is a key tool for in vivo assessment of these changes.
- The accuracy of MRI in quantifying white matter pathology in AD requires further validation against postmortem findings.
Purpose of the Study:
- To compare the sensitivity of postmortem MRI with neuropathology in detecting white matter changes in Alzheimer's disease.
- To determine if MRI over- or underestimates the extent of white matter abnormalities in AD compared to direct pathological examination.
Main Methods:
- Postmortem MRI and neuropathological examination of 6 brains from individuals with a confirmed AD diagnosis.
- Correlative analysis of brain slices, prepared using a custom slicer, stained with Luxol Fast Blue.
- Stereological principles applied for quantitative analysis of white matter changes on both MRI and neuropathology.
Main Results:
- A strong correlation (r(2) = 0.71) was observed between white matter changes detected by MRI and neuropathology.
- Neuropathology revealed significantly more extensive white matter changes than MRI in all cases (mean 54% larger areas).
- Undetected lesions on MRI were characterized by minor myelin staining reduction and preserved axonal integrity.
Conclusions:
- Postmortem MRI demonstrates a strong correlation with neuropathology for white matter changes in Alzheimer's disease.
- MRI tends to underestimate the full extent of white matter pathology in AD.
- Further refinement of MRI techniques may be necessary to improve detection of subtle white matter alterations in AD.