Cerebral microbleeds in community-dwelling older people imaged both in-vivo and ex-vivo MRI
Poster No:
923
Submission Type:
Abstract Submission
Authors:
Md Tahmid Yasar1, Grant Nikseresht1, Abdur Raquib Ridwan2, Shengwei Zhang2, David Bennett2, Julie Schneider2, Konstantinos Arfanakis2
Institutions:
1Illinois Institute of Technology, Chicago, IL, 2Rush University Medical Center, Chicago, IL
First Author:
Co-Author(s):
Introduction:
Cerebral microbleeds (CMBs), visible as small hypointense spots on T2*-weighted MRI, represent small brain hemorrhages with hemosiderin deposits causing faster signal dephasing [1]. CMBs are common in older adults and are associated with cognitive decline, brain atrophy, and increased risk of intracerebral hemorrhage, stroke, and mortality [2]. CMBs have also been identified as a risk factor for amyloid-related imaging abnormalities (ARIA) in Alzheimer's treatments involving monoclonal antibodies [3]. In-vivo studies link lobar CMBs, particularly in the occipital lobe, to cerebral amyloid angiopathy (CAA) and subcortical CMBs to hypertensive arteriopathy [4]. Ex-vivo and autopsy studies further associate frontal lobe CMBs with CAA and arteriolosclerosis [5]. However, systematic comparisons of CMBs in in-vivo and ex-vivo MRI are lacking. This study aimed to investigate CMBs appearing in both scans and their association with clinical evaluations and neuropathologies.
Methods:
The longitudinal study included 37 community-based older adults who participated in four aging studies: Rush Memory and Aging Project, Religious Orders Study, Minority Aging Research Study, and Clinical Core of the Rush Alzheimer's Disease Research Center [6,7]. All participants underwent cognitive function testing and brain MRI imaging annually (Figure 1). Whole brain 3D T1w MPRAGE (1mm×1mm×1mm), and multi echo gradient echo (ME-GRE) (0.7mm×0.7mm×1.3mm, TE1 = 4.6ms, and ΔTE = 4.5ms) MRI data were acquired in-vivo using 3T clinical scanners [8]. After death and autopsy, one cerebral hemisphere 3D multi-echo spin echo (ME-SE) (0.6mm×0.6mm×1.5mm) and ME-GRE (1mm×1mm×1mm, TE1 = 5ms, and ΔTE = 5ms) of each participant was imaged ex-vivo at room temperature, at approximately 30 days postmortem using 3T scanners [5]. Following ex-vivo MRI, all hemispheres underwent detailed neuropathologic assessment including cerebrovascular pathologies like cerebral amyloid angiopathy (CAA), arteriolosclerosis, atherosclerosis, and gross and microscopic infarcts [9].
CMBs were annotated on the last acquired in-vivo before death and ex-vivo ME-GRE blinded to all pathologic and clinical data [5]. The ex-vivo CMB mask was first transformed to ME-SE space using FSL, then registered to the MIITRA template with ANTs [10]. The in-vivo CMB mask for the corresponding ex-vivo hemisphere was initially registered to N4-corrected MPRAGE and subsequently aligned with the MIITRA template using ANTs. The two CMB masks for each participant were then superimposed in MIITRA space to assess chronological changes in CMB characteristics among older individuals. In-vivo and ex-vivo CMBs that overlapped exactly were considered to be the same CMBs and denoted as matched CMBs (Figure 1). A participant was denoted matched if all ex-vivo CMBs had spatially matched with in-vivo CMBs.
CMBs were annotated on the last acquired in-vivo before death and ex-vivo ME-GRE blinded to all pathologic and clinical data [5]. The ex-vivo CMB mask was first transformed to ME-SE space using FSL, then registered to the MIITRA template with ANTs [10]. The in-vivo CMB mask for the corresponding ex-vivo hemisphere was initially registered to N4-corrected MPRAGE and subsequently aligned with the MIITRA template using ANTs. The two CMB masks for each participant were then superimposed in MIITRA space to assess chronological changes in CMB characteristics among older individuals. In-vivo and ex-vivo CMBs that overlapped exactly were considered to be the same CMBs and denoted as matched CMBs (Figure 1). A participant was denoted matched if all ex-vivo CMBs had spatially matched with in-vivo CMBs.
Results:
Of the 37 participants, 22 (59%) had at least one CMB in ex-vivo data. The maximum number of matched in-vivo and ex-vivo CMBs in a single participant was 12. Among these participant, 24 (65%) showed exact matches between in-vivo and ex-vivo CMBs (Figure 2a, 2b). All mismatched cases, ex-vivo CMB counts were higher than in-vivo. The ex-vivo CMB counts were higher in participants with higher antemortem intervals (Figure 2c). Further investigation revealed, participants with no cognitive impairment (NCI) were more likely to have matched in-vivo and ex-vivo CMBs (Figure 2d). Additionally, participants with pathology confirmed CAA had a higher likelihood of having more ex-vivo CMBs than in-vivo (odds ratio = 3.33, p < 0.1). Two participants had five in-vivo CMBs that were not identifiable in ex-vivo imaging (Figure 2d).
Conclusions:
This study combined in-vivo and ex-vivo MRI in community-dwelling older adults, showing that CMBs observed in life persist and remain detectable on ex-vivo MRI postmortem. Furthermore, additional CMBs develop over time, especially in those with cognitive impairment and CAA.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Lifespan Development:
Aging 1
Keywords:
Aging
Cerebrovascular Disease
Cognition
Other - Cerebral microbleeds; Cerebral amyloid angiopathy; Ex-vivo applications; In-vivo applications
1|2Indicates the priority used for review
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Provide references using APA citation style.
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