Histopathology of Cerebral Microinfarcts and Microbleeds in Spontaneous Intracerebral Hemorrhage

Abstract

In patients with spontaneous intracerebral hemorrhage caused by different vasculopathies, cerebral microinfarcts have the same aspect on MRI and the same applies to cerebral microbleeds. It is unclear what pathological changes underlie these cerebral microinfarcts and cerebral microbleeds. In the current study, we explored the histopathological substrate of these lesions by investigating the brain tissue of 20 patients (median age at death 77 years) who died from ICH (9 lobar, 11 non-lobar) with a combination of post-mortem 7-T MRI and histopathological analysis. We identified 132 CMIs and 204 CMBs in 15 patients on MRI, with higher numbers of CMIs in lobar ICH patients and similar numbers of CMBs. On histopathology, CMIs and CMBs were in lobar ICH more often located in the superficial than in the deep layers of the cortex, and in non-lobar ICH more often in the deeper layers. We found a tendency towards more severe CAA scores in lobar ICH patients. Other histopathological characteristics were comparable between lobar and non-lobar ICH patients. Although CMIs and CMBs were found in different segments of the cortex in lobar ICH compared to non-lobar ICH patients, otherwise similar histopathological features of cortical CMIs and CMBs distant from the ICH suggest shared pathophysiological mechanisms in lobar and non-lobar ICH caused by different vasculopathies.

Keywords: Cerebral amyloid angiopathy; Histopathology; Spontaneous intracerebral hemorrhage; Ultra-high-field MRI.

Fig. 1

Flowchart of identified, retrieved, and evaluated lesions. CMB, cerebral microbleed; CMI, cerebral microinfarct; D-CAA, Dutch-type hereditary CAA

Fig. 2

Representative examples of the different cortical location of CMIs and CMBs on ex vivo 7-T MRI and the matched histopathological sections in lobar and non-lobar ICH patients. In this figure, we show representative examples of cerebral microinfarcts (A, B) and microbleeds (C, D) in patients with lobar ICH (A [case no. 1] and C [case no. 8]) and non-lobar ICH (B [case no. 17] and D [case no. 11]) indicated with the black and white arrows. From each lesion, we show how we matched the lesions found on ex vivo 7 T T₂ and T₂*-weighted images with the histological section on an overview of the H&E section and the identified lesion on H&E and iron staining. The insert in the overview of the H&E section shows in more detail the location of the CMIs and CMBs in the superficial layers of the cortex in lobar ICH (A, C) and in the deeper layers of the cortex in non-lobar ICH (B, D). Scale bars in the T₂ and T₂*-weighted images are 10 mm; in the overview of the H&E section, 5 mm; in the more detailed H&E and iron staining sections of panels A and C, 200 µm; and the H&E and iron staining sections of panels B and D, 400 µm