Incidental Magnetic Resonance Diffusion-Weighted Imaging–Positive Lesions Are Rare in Neurologically Asymptomatic Community-Dwelling Adults
Background and Purpose—Incidental magnetic resonance diffusion-weighted imaging (DWI)–positive lesions, considered to represent small acute infarcts, have been detected in patients with cerebral small vessel diseases or cognitive impairment, but the prevalence in the community population is unknown.
Methods—DWI sequences collected in 793 participants in the Prospective Urban Rural Epidemiological (PURE) study were reviewed for DWI lesions consistent with small acute infarcts.
Results—No DWI-positive lesions were detected (0%, 95% confidence interval, 0–0.5).
Conclusions—DWI-positive lesions are rare in an asymptomatic community population. The prevalence of DWI-positive lesions in the community seems to be lower than in patients with cerebral amyloid angiopathy, intracerebral hemorrhage, or cognitive impairment.
Silent brain infarcts are a common finding in older persons. However, neuropathology studies show that microinfarcts—infarcts <2 mm in diameter, visible only on microscopic examination of brain tissue—are much more frequent than grossly visible infarcts.1 Microinfarcts are essentially invisible on conventional magnetic resonance imaging (MRI) at field strengths of 1.5 or 3 T.1 MRI diffusion-weighted imaging (DWI) has been proposed to be able to detect acute microinfarcts in evolution. Small DWI-positive lesions, consistent with recent acute infarction in the last 10 to 14 days, have been detected incidentally in patients with symptomatic small vessel diseases or cognitive impairment.2–5
Because some brains may harbor thousands of microinfarcts,6 we reasoned that acute microinfarction could be a frequent silent occurrence detectable on DWI done in asymptomatic community-dwelling persons. To test this hypothesis, we analyzed DWI data from the Prospective Urban Rural Epidemiological (PURE) Mind substudy.
The methods and objectives of the PURE study have been published.7 The Canadian participants were recruited by population-based sampling within 55 prespecified communities, defined geographically based on Canadian postal code sorting areas. From 2010 to 2012, we recruited 803 dementia- and stroke-free Canadian PURE participants aged 40 to 79 into a brain MRI substudy (PURE-MIND).
Participants underwent brain MRI at 1 of 4 study centers (Table I in the online-only Data Supplement). DWI, apparent diffusion coefficient, T2-weighted, proton density-weighted, and fluid-attenuated inversion recovery sequences were acquired at each of 4 scan sites (Table II in the online-only Data Supplement). A radiologist (S.B.) identified DWI-positive lesions using standard criteria for recent small infarcts.8 DWI lesions were classified as absent, possible (when DWI hyperintensity was not accompanied by clearly visible reduced apparent diffusion coefficient), or probable (when there was a clearly defined DWI hyperintensity accompanied by reduced apparent diffusion coefficient). Reliability was checked by a second reader (E.E.S., a neurologist) who reviewed 2 possible lesions identified by a radiologist as well as in a random sample of 50 scans; there was perfect agreement. White matter hyperintensity burden was determined by the Fazekas scale9 and was defined as high white matter hyperintensity if either the periventricular or subcortical score was ≥2.
There were 793 participants with DWI (Table): 260 (33%) were 60 to 69 years old and 74 (9%) ≥70 years old.
No probable DWI lesions were detected (0%; 95% confidence interval, 0–0.5). Faint DWI hyperintensities were seen in only 2 of 793 (0.3%; 95% confidence interval, 0–0.9); however, in both cases, the faint hyperintensity corresponded to a chronic-appearing T2-hyperintense lesion without apparent diffusion coefficient hypointensity—1 white matter T2-hyperintensity (Figure 1) and 1 chronic small cavitated infarct (Figure 2).
This study provides the first community-based assessment of incidental DWI-positive lesions in asymptomatic persons. Small DWI-positive lesions are consistent with tiny recent acute infarctions and may represent acutely evolving microinfarcts.1 Among 793 participants with MRI DWI sequences, there were no probable DWI lesions. There were only 2 possible DWI-positive lesions, both of which were judged by consensus to represent chronic T2 hyperintensity and not acute infarction. The prevalence of incidental DWI-positive lesions in this study—<0.5%—is consistent with the incidental DWI-positive rate of 0.37% reported by a previous hospital-based study of 16 206 patients undergoing MRI for miscellaneous clinical indications.10
In contrast to the low rate of incidental DWI-positive lesions in the community, studies of patients with cerebral small vessel diseases show much higher prevalence of clinically asymptomatic acute DWI-positive lesions. A study of 78 patients with cerebral amyloid angiopathy showed that 12 (15%) had asymptomatic small DWI-positive lesions consistent with recent acute infarcts.2 A study of patients with primary intracerebral hemorrhage showed that 30 of 113 (26.5%) patients scanned at 1 month had acute DWI-positive lesions appear and that 83% of these lesions were not seen on the baseline MRI and therefore must have occurred asymptomatically in the interval between MRIs.3
Autopsy studies show that microinfarcts are one of the strongest predictors of antemortem dementia.1 Two recent studies have identified a high prevalence of asymptomatic clinically unsuspected acute DWI-positive lesions in patients with cognitive impairment. In a study of 649 patients from a memory clinic, 6 (0.9%) had incidental DWI-positive lesions of whom 5 had cognitive impairment (1 was demented and 4 had cognitive impairment without dementia).5 In another study of 251 patients from a memory clinic—to date presented only in abstract form—the prevalence of asymptomatic clinically unsuspected DWI-positive lesions was 13 of 251 (5.2%).4 In both studies, the DWI-positive lesion prevalence (0.9% and 5.2%) was higher than the upper limit of the 95% confidence interval estimated from this study of cognitively normal asymptomatic community-dwelling persons (0.5%), suggesting that persons with cognitive impairment are at higher risk for asymptomatic small infarction. The reason for the much higher prevalence in one of the studies in cognitive impairment compared with the other (5.2% versus 0.9%) is unclear but could be related to differences in population characteristics, severity of cognitive impairment, or MRI protocols.
There are some limitations to this study. Because of the low prevalence of DWI-positive lesions, a much larger study would be needed to precisely determine the exact prevalence; however, we can say with 95% confidence that the true prevalence is <0.5%. Participants were predominantly 40 to 69 years old with only 74 participants in their 70s; more studies will be needed to determine the rate of incidental DWI-positive lesions in more elderly (>80 years old) persons. This study did not include scanning at high field strength (7 T), which has been used to detect the largest-sized chronic microinfarcts.11
This study provides the first ever evidence that clinically unrecognized DWI-positive lesions in the community are rare and contrasts with the higher prevalence seen in cerebral amyloid angiopathy, intracerebral hemorrhage, and cognitive impairment. Because incidental acute small infarcts are rare in the absence of predisposing conditions, their identification should prompt a thorough investigation for causes of infarction such as embolism or small vessel disease. Although MRI DWI may prove to be a useful research and clinical tool for assessing acute microinfarcts due to small vessel disease in those specific clinical scenarios, it is not useful in the asymptomatic population because of the low prevalence. Research on microinfarcts in the asymptomatic population should focus on developing new methods for visualizing chronic microinfarcts, which are likely more prevalent but cannot be detected on conventional MRI.
Sources of Funding
Funded by the Population Health Research Institute, Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Canadian Stroke Network, Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, and through unrestricted grants from AstraZeneca, Sanofi–Aventis, Boehringer Ingelheim, Servier, GlaxoSmithKline, Novartis, and King Pharma.
Published in abstract form at the Canadian Vascular Meeting, Montreal, Quebec, Canada, October 17–20, 2013, and in Stroke (Batool S, O'Donnell M, Teo K, Dagenais G, Poirier P, Lear S, et al. Incidental small acute brain infarcts are rare in neurologically asymptomatic community-dwelling older adults. Stroke. 2013;45:2115-2117).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.114.005782/-/DC1.
- Received April 10, 2014.
- Revision received April 10, 2014.
- Accepted April 30, 2014.
- © 2014 American Heart Association, Inc.
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