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Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images
Published on: November 20, 2015
Histological correlates of postmortem ultra-high-resolution single-section MRI in cortical cerebral microinfarcts
Deniz Yilmazer-Hanke1, Theresa Mayer2, Hans-Peter Müller3
1Clinical Neuroanatomy, Department of Neurology, Institute for Biomedical Research, Ulm University, Helmholtzstr. 8/1, 89081, Ulm, Germany. deniz.yilmazer-hanke@uni-ulm.de.
Abstract:
The identification of cerebral microinfarctions with magnetic resonance imaging (MRI) and histological methods remains challenging in aging and dementia. Here, we matched pathological changes in the microvasculature of cortical cerebral microinfarcts to MRI signals using single 100 μm-thick histological sections scanned with ultra-high-resolution 11.7 T MRI. Histologically, microinfarcts were located in superficial or deep cortical layers or transcortically, compatible with the pattern of layer-specific arteriolar blood supply of the cerebral cortex. Contrary to acute microinfarcts, at chronic stages the core region of microinfarcts showed pallor with extracellular accumulation of lipofuscin and depletion of neurons, a dense meshwork of collagen 4-positive microvessels with numerous string vessels, CD68-positive macrophages and glial fibrillary acidic protein (GFAP)-positive astrocytes. In MRI scans, cortical microinfarcts at chronic stages, called chronic cortical microinfarcts here, gave hypointense signals in T1-weighted and hyperintense signals in T2-weighted images when thinning of the tissue and cavitation and/or prominent iron accumulation were present. Iron accumulation in chronic microinfarcts, histologically verified with Prussian blue staining, also produced strong hypointense T2*-weighted signals. In summary, the microinfarct core was occupied by a dense microvascular meshwork with string vessels, which was invaded by macrophages and astroglia and contained various degrees of iron accumulation. While postmortem ultra-high-resolution single-section imaging improved MRI-histological matching and the structural characterization of chronic cortical cerebral microinfarcts, miniscule microinfarcts without thinning or iron accumulation could not be detected with certainty in the MRI scans. Moreover, string vessels at the infarct margin indicate disturbances in the microcirculation in and around microinfarcts, which might be exploitable in the diagnostics of cortical cerebral microinfarcts with MRI in vivo.
Insights
Identifying chronic cerebral microinfarcts using MRI is difficult. This study links histological features like microvascular changes and iron accumulation to MRI signals, improving detection but noting limitations for small lesions.
Area of Science:
- Neuroimaging
- Neuropathology
- Cerebrovascular Diseases
Background:
- Accurate identification of cerebral microinfarcts using magnetic resonance imaging (MRI) and histology is challenging, particularly in aging and dementia.
- Understanding the histological characteristics of chronic microinfarcts is crucial for improving in vivo MRI diagnostics.
Purpose of the Study:
- To correlate pathological changes in microvasculature of cortical cerebral microinfarcts with MRI signals.
- To characterize chronic cortical microinfarcts using ultra-high-resolution MRI and histology.
Main Methods:
- Matching pathological changes in 100 μm-thick histological sections with ultra-high-resolution 11.7T MRI scans.
- Histological analysis including Prussian blue staining for iron and immunohistochemistry for CD68 and GFAP.
- Correlation of histological findings with T1-weighted, T2-weighted, and T2*-weighted MRI signals.
Main Results:
- Chronic microinfarcts showed specific histological features including extracellular lipofuscin, neuronal depletion, dense microvessel networks with string vessels, macrophages (CD68+), and astrocytes (GFAP+).
- MRI signals for chronic microinfarcts included hypointense T1 and hyperintense T2 signals, particularly with tissue thinning, cavitation, or iron accumulation.
- Iron accumulation correlated with strong hypointense T2* signals, aiding detection.
- Ultra-high-resolution imaging enhanced MRI-histological matching, but small microinfarcts lacking cavitation or iron were not reliably detected.
Conclusions:
- The microinfarct core contains a dense microvascular meshwork with string vessels, infiltrated by immune cells and potentially iron.
- While advanced MRI-histology correlation improves characterization, detecting all chronic microinfarcts in vivo remains challenging, especially smaller ones.
- Microcirculatory disturbances, indicated by string vessels, may offer future diagnostic targets for in vivo MRI.
