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Cortical microinfarcts on 7T MRI correlate with medial temporal lobe thinning in healthy aging
Shokufeh Sadaghiani1, M. Dylan Tisdall2, Sandhitsu R. Das1, David A. Wolk1, and John A. Detre1
1Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States, 2Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States

Synopsis

We investigated the correlation of CMIs with MTL subregional cortical thickness in 21 healthy elderly subjects. We also showed that only 26% of total CMIs visible on 7T MRI scans are also visible on 3T scans suggesting a better visualization of CMIs by 7T MRI compared to 3T MRI. Our findings support an interaction between cerebrovascular and neurodegenerative mechanisms in healthy aging.

Introduction

Cerebral microinfarcts (CMIs) are one of the pathological features of cerebral small vessel disease (CSVD).1,2 CMIs are generally defined as ischemic lesions with the size of less than 5 mm in greatest dimension.3 They have been reported to be found not only in patients with various types of dementia, but also in cognitively normal elderly subjects.4-6 CMIs are negatively correlated with cognitive function in both healthy subjects and Alzheimer disease (AD) patients.7,8 Implementation of high field structural magnetic resonance imaging (MRI) has made in vivo detection of the largest CMIs possible.9 Although the precise underlying pathophysiological mechanisms are not yet fully understood, both age-related and pathological cognitive decline are considered to result from interactions between cerebrovascular and neurodegenerative processes.10,11 Medial temporal lobe (MTL) cortex is usually the earliest brain region demonstrating neurofibrillary tangle involvement and atrophy during AD progression.12,13 In the current study we investigated the correlation of CMIs as a measure of CSVD with MTL subregional cortical thickness. We also evaluated the utility of 3T structural MRI for detecting CMI.

Methods

Neuroimaging data of 21 healthy older subjects between 58 and 83 years of age (mean: 68.43 ± 4.99) were obtained from the Penn Alzheimer’s Disease Core Center (ADCC). (table 1) The data consisted of 7T T1-weighted MultiEcho-MP2RAGE (15 subjects), T1-weighted MP2RAGE (6 subjects) and FLAIR; and 3T T1-weighted and FLAIR scans. Table 2 shows MRI sequences parameters. CMIs were scored by an expert rater on 7T MRI scans according to proposed detection criteria by van Veluw, et al.3 Automated segmentation and MTL cortical thickness measurements were performed using method described by Xie, et al.14 Spearman’s bivariate nonparametric correlation test was used in order to investigate the relationship between number of CMIs and MTL subregional cortical thickness. 3T T1-weighted and FLAIR images were then examined in order to assess the number of previously detected CMIs visible on 3T scans.

Results

A total of 35 CMIs were detected on 21 7T T1-weighted and FLAIR MRI scans (mean: 1.67 ± 1.62). Age, sex, and years of education were not significantly correlated with the number of CMIs detected. We observed significant negative correlation between the number of CMIs and mean parahippocampal cortical thickness (p=0.05). A similar negative correlation was also observed in Entorhinal and BA36 regions, although not significant. Only 9 (26%) of 35 CMIs were also visible on 3T T1-weighted and/or FLAIR MR images (mean: 0.43 ± 0.51) and 74% were not detectable. Figure 1 shows an example of a CMI only visible on 7T T1-weighted scans but not on 7T FLAIR and 3T T1-weighted and FLAIR scans.

Discussion

Our results demonstrated a negative correlation between CMI number and parahippocampal cortical thickness with similar, but non-significant, relationships in other MTL regions. Given that CMIs are ischemic lesions and MTL atrophy is associated with neurodegeneration, the association between CMI and MTL cortical thickness supports the notion that cerebrovascular and neurodegenerative processes interact in even healthy aging and may have synergistic roles in progression to Alzheimer’s Disease. We also observed that the majority of CMIs visible on 7T MRI scans were not visible on 3T, consistent with a prior report that 7T MRI provides higher signal intensity and contrast for detection of small lesions15 and a previous 7T MRI study which has reported 27% of CMIs were also visible on 3T scans.9 However, since 7T data were acquired at slightly higher voxel resolution than 3T data, some effect of image resolution cannot be excluded.

Conclusion

The number of CMIs is negatively correlated with parahippocampal cortical thickness which supports an interaction between cerebrovascular and neurodegenerative processes in healthy aging. Ultra high resolution MRI provides a better visualization of CMIs compared to 3T MRI.

Acknowledgements

Research reported in this abstract was supported by NIH under award number P30 AG010124. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References

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9. Van Veluw SJ, Zwanenburg JJ, Engelen-Lee J, et al. In vivo detection of cerebral cortical microinfarcts with high-resolution 7T MRI. Journal of Cerebral Blood Flow & Metabolism. 2013;33(3):322-329.

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15. Maruyama S, Fukunaga M, Fautz H-P, Heidemann R, Sadato N. Comparison of 3T and 7T MRI for the visualization of globus pallidus sub-segments. Scientific Reports. 2019;9(1):1-8.

Figures

Table 1. Subjects characteristics.

Table 2. 7T and 3T MRI sequences parameters.

Figure 1. A. A cortical microinfarct visible on 7T T1-weighted MP2RAGE MRI scan. The CMI is not visible on B. 7T FLAIR MRI scan, C. 3T T1-weighted MRI scan and D. 3T FLAIR MRI scan.

Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)
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