MRI-HISTOPATHOLOGY ASSOCIATIONS OF MICROBLEEDS AND MICROINFARCTS IN INTACT EX VIVO HEMISPHERES OF PATIENTS WITH CEREBRAL AMYLOID ANGIOPATHY

Abstract

Microbleeds and microinfarcts are widespread lesions in cerebral amyloid angiopathy (CAA), at least partially detectable during life. We studied the prevalence and topographical distribution of microbleeds and microinfarcts on ex vivo MRI in CAA cases. Moreover, we determined number of microbleeds and microinfarcts on microscopy of standard samples to compare to the numbers detected by MRI. We specifically sought to compare MRI's methodologic advantage of providing full brain coverage to microscopy's advantage of greater sensitivity for detection of these two lesion types. We included four patients with a diagnosis of CAA during life who donated their brains to CAA research (mean age at death 73.4±6.7 years). One control case was included from our neuropathology database, a 90-year old individual without cognitive impairment. At autopsy, the brains were removed and formalin-fixed. The hemisphere without macrohemorrhage was packed in a bag with periodate-lysine-paraformaldehyde and scanned overnight at 3T MRI. The protocol included a flash (resolution 500x500x500μm3) and a T2-weighted sequence (resolution 500x500x500μm3). On the acquired scans, cortical microbleeds and microinfarcts were assessed. In parallel, the hemisphere was cut in 10mm-thick coronal slabs. Subsequently, four pre-defined standard areas were sampled, blinded to MRI (one area from the frontal, parietal, temporal, and occipital cortex), embedded in paraffin, and cut in 6μm-thick sections. One section was stained with H&E, and screened microscopically for microbleeds and microinfarcts. The adjacent section underwent Aβ immunohistochemistry to determine CAA severity. On ex vivo MRI 426 microbleeds [range 39–261] and 313 microinfarcts [range 21–144] were identified in the four CAA cases. Microbleeds and microinfarcts did not spatially overlap on MRI, but showed distinct topographical patterns. Microscopy revealed 3 microbleeds [range 0–2 per case] and 25 microinfarcts [range 0–15 per case] in the 16 examined sections. All cases showed CAA, ranging from mild-to-severe. The control case had 3 microinfarcts and 0 microbleeds on MRI, and microscopy revealed no lesions of either type and absence of CAA. In CAA, superior brain coverage provided by MRI resulted in more sensitive microbleed detection. In contrast, MRI appears to substantially undercount microinfarcts, which are often better detectable by the more sensitive method of histopathology.