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.
Highlights
Cerebral microinfarcts are found in the brains of elderly, in cognitive impairment and dementia of vascular origin, and in patients with various neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease [2, 12, 52]
To overcome challenges that result from histological matching of microinfarcts to magnetic resonance imaging (MRI) scans [1], in a step we developed a new ultra-highresolution postmortem MRI technique by imaging single thick histological sections with proven microinfarcts with MRI at 11.7 T
The extracellular lipofuscin aggregates in microinfarcts could be clearly distinguished from intraneuronal lipofuscin granules (Fig. 2e2, see [44]) or the purplish, cytoplasmic aldehyde fuchsine staining seen in macrophages that clustered in the microinfarct core (Fig. 2a1, see [8])
Summary
Cerebral microinfarcts are found in the brains of elderly, in cognitive impairment and dementia of vascular origin, and in patients with various neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease [2, 12, 52]. Despite growing evidence for the contribution of cortical cerebral microinfarcts to the development of cognitive deficits and dementia, their identification in conventional magnetic resonance imaging (MRI) remains challenging [9, 21, 26, 29, 42]. Owing to their small size, cortical microinfarcts often remain below the detection limit of the image resolution in conventional MRI at 1.5 T and 3 T, the detection rate of microinfarcts was improved in vivo with 7 T MRI [28, 45, 48]. It is unknown whether these cortical cerebral microinfarcts escaped detection and produced false negative results in MRI scans due to problems associated with technical limitations in image resolution at 7 T or MRI-histological matching [1, 37], or whether there is a subset of microinfarcts that produces a different MRI signal pattern
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