Abstract
BACKGROUND AND PURPOSE: White matter lesions are 1 age-related manifestation of cerebrovascular disease, but subthreshold abnormalities have been identified in nonlesional WM. We hypothesized that structural and physiologic MR imaging findings of early cerebrovascular disease can be measured in middle-aged subjects in tissue adjacent to WM lesions, termed “penumbra.”
MATERIALS AND METHODS: WM lesions were defined using automated segmentation in 463 subjects, 43–56 years of age, from the Coronary Artery Risk Development in Young Adults (CARDIA) longitudinal observational cohort study. We described 0- to 2-mm and 2- to 4-mm-thick spatially defined penumbral WM tissue ROIs as rings surrounding WM lesions. The remaining WM was defined as distant normal-appearing WM. Mean signal intensities were measured for FLAIR, T1-, and T2-weighted images, and from fractional anisotropy, mean diffusivity, CBF, and vascular reactivity maps. Group comparisons were made using Kruskal-Wallis and pair-wise t tests.
RESULTS: Lesion volumes averaged 0.738 ± 0.842 cm3 (range, 0.005–7.27 cm3). Mean signal intensity for FLAIR, T2, and mean diffusivity was increased, while T1, fractional anisotropy, and CBF were decreased in white matter lesions versus distant normal-appearing WM, with penumbral tissues showing graded intermediate values (corrected P < .001 for all group/parameter comparisons). Vascular reactivity was significantly elevated in white matter lesions and penumbral tissue compared with distant normal-appearing white matter (corrected P ≤ .001).
CONCLUSIONS: Even in relatively healthy 43- to 56-year-old subjects with small white matter lesion burden, structural and functional MR imaging in penumbral tissue reveals significant signal abnormalities versus white matter lesions and other normal WM. Findings suggest that the onset of WM injury starts by middle age and involves substantially more tissue than evident from focal white matter lesions visualized on structural imaging.
ABBREVIATIONS:
- BMI
- body mass index
- BOLD
- blood oxygen level–dependent
- dNAWM
- distant normal-appearing white matter
- FA
- fractional anisotropy
- MD
- mean diffusivity
- NAWM
- normal-appearing white matter
- RFscore
- risk factor score
- VR
- vascular reactivity
- WML
- white matter lesion
Footnotes
Disclosures: Ilya M. Nasrallah—RELATED: Grant: National Institutes of Health*; Support for Travel to Meetings for the Study or Other Purposes: National Institutes of Health*; UNRELATED: Grants/Grants Pending: National Institutes of Health.* Guray Erus—RELATED: Grant: National Institutes of Health.* John A. Detre—RELATED: Grant: National Institutes of Health*; UNRELATED: Consultancy: Blackfynn, CHDI Foundation, Dana Foundation, National Institutes of Health, Comments: I have provided expert advice on neuroimaging to the University of Pennsylvania spinoff startup company Blackfynn. I have received stock options. I have provided consulting to the CHDI Foundation, a private foundation involved in Huntington disease research, but none in the last year. I am compensated as a grant reviewer for the Dana Foundation and the National Institutes of Health, total approximately $2000 per year; Grants/Grants Pending: National Institutes of Health*; Payment for Manuscript Preparation: Dana Foundation, Comments: I received $10,000 from the Dana Foundation for assisting with a Web article on neuroimaging; Patents (Planned, Pending or Issued): University of Pennsylvania, Comments: I am listed as a coinventor on 2 University of Pennsylvania patents for optical monitoring of cerebral blood flow. Neither has been licensed. Lenore J. Launer—UNRELATED: Employment: National Institutes of Health. Robert N. Bryan—RELATED: Grant: National Institutes of Health*; UNRELATED: Board Membership: Galileo CDS, Comments: no cash transaction or value; Grants/Grants Pending: National Institutes of Health; Patents (Planned, Pending or Issued): University of Pennsylvania patent license to Galileo CDS; Stock/Stock Options: Galileo CDS. *Money paid to the institution.
The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (HHSN268201800005I, HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and the Kaiser Foundation Research Institute (HHSN268201800004I). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging and an intra-agency agreement between National Institute on Aging and National Heart, Lung, and Blood Institute (AG0005). This article has been reviewed by CARDIA for scientific content. Data processing and analysis was supported by NIH grants S10OD023495, P41 EB015893, P30 AG010124, and R01 NS111115.
Paper previously presented, in part, at: American Society of Neuroradiology Annual Meeting and the Foundation of the ASNR Symposium, May 21–26, 2016; Washington DC.
- © 2019 by American Journal of Neuroradiology
Indicates open access to non-subscribers at www.ajnr.org
