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Estimating Total Cerebral Microinfarct Burden From Diffusion-Weighted Imaging
Eitan Auriel1, M Brandon Westover1, Matt T Bianchi1
1From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
Background And Purpose:
Cerebral microinfarcts (CMI) are important contributors to vascular cognitive impairment. Magnetic resonance imaging diffusion-weighted imaging (DWI) hyperintensities have been suggested to represent acute CMI. We aim to describe a mathematical method for estimating total number of CMI based on the presence of incidental DWI lesions.
Methods:
We reviewed magnetic resonance imaging scans of subjects with cognitive decline, cognitively normal subjects and previously reported subjects with past intracerebral hemorrhage (ICH). Based on temporal and spatial characteristics of DWI lesions, we estimated the annual rate of CMI needed to explain the observed rate of DWI lesion detection in each group. To confirm our estimates, we performed extensive sampling for CMI in the brain of a deceased subject with past lobar ICH who found to have a DWI lesion during life.
Results:
Clinically silent DWI lesions were present in 13 of 343 (3.8%) cognitively impaired and 10 of 199 (5%) cognitively intact normal non-ICH patients, both lower than the incidence in the past ICH patients (23 of 178; 12.9%; P<0.0006). The predicted annual incidence of CMI ranges from 16 to 1566 for non-ICH and 50 to 5041 for ICH individuals. Histological sampling revealed a total of 60 lesions in 32 sections. Based on previously reported methods, this density of CMI yields an estimated total brain burden maximum likelihood estimate of 9321 CMIs (95% confidence interval, 7255-11 990).
Conclusions:
Detecting even a single DWI lesion suggests an annual incidence of hundreds of new CMI. The cumulative effects of these lesions may directly contribute to small-vessel-related vascular cognitive impairment.
Insights
Detecting even one diffusion-weighted imaging (DWI) lesion indicates hundreds of new cerebral microinfarcts (CMI) annually. These microinfarcts likely contribute to vascular cognitive impairment.
Area of Science:
- Neurology
- Neuroimaging
- Pathology
Background:
- Cerebral microinfarcts (CMI) are significant contributors to vascular cognitive impairment.
- Diffusion-weighted imaging (DWI) hyperintensities are proposed indicators of acute CMI.
Purpose of the Study:
- To develop a mathematical method for estimating the total number of CMIs.
- To correlate incidental DWI lesions with CMI burden.
Main Methods:
- Review of MRI scans from subjects with and without cognitive decline, including those with prior intracerebral hemorrhage (ICH).
- Estimation of annual CMI rates based on DWI lesion characteristics.
- Histological sampling of a deceased subject with prior ICH and a DWI lesion.
Main Results:
- DWI lesions were found in 3.8% of cognitively impaired, 5% of cognitively intact, and 12.9% of ICH patients.
- Predicted annual CMI incidence varied widely (16-1566 for non-ICH, 50-5041 for ICH).
- Histological analysis estimated a total brain burden of 9321 CMIs.
Conclusions:
- A single DWI lesion suggests hundreds of new CMIs per year.
- Cumulative CMI burden may directly cause small-vessel vascular cognitive impairment.
