Measurement of cortical thickness asymmetry in carotid occlusive disease

Abstract

Despite being considered an important anatomical parameter directly related to neuronal density, cortical thickness is not routinely assessed in studies of the human brain in vivo. This paucity has been largely due to the size and convoluted shape of the human cortex, which has made it difficult to develop automated algorithms that can measure cortical thickness efficiently and reliably. Since the development of such an algorithm by Fischl and Dale in 2000, the number of studies investigating the relationship between cortical thickness and other physiological parameters in the brain has been on the rise. There have been no studies however that have validated cortical asymmetry against known vascular anatomy. To this aim, using high-resolution MRI, we measured cortical thickness and volume in the primary motor (M1) and primary visual (V1) cortex in patients with unilateral, high-grade carotid occlusive disease (n = 29, age = 74 ± 10 years). These regions were selected based on the hypothesis that there will be thinning of the cortical thickness of M1 in the territory supplied by the occluded carotid artery, whereas V1 will show no asymmetry since its blood supply is provided by unaffected posterior arteries. To test for an effect of handedness, cortical thickness and volume were also measured in healthy volunteers (n = 8, age = 37 ± 13 years). In patients, we found thinner cortex in M1 on the occluded side (mean = 2.07 ± 0.19 mm vs 2.15 ± 0.20 mm, p = 0.0008) but no hemispheric difference in V1 (1.80 ± 0.17 mm in occluded vs 1.78 ± 0.16 mm in unoccluded, p = 0.31). Although the mean cortical volume of M1 in the occluded hemisphere was also lower, the difference did not reach statistical significance (p = 0.09). Similarly, in healthy controls, the results showed no hemispheric asymmetry in either cortical thickness or volume in either region (p > 0.1). To test for an orientation bias in the method, the analysis was repeated with images flipped from neurological to radiological orientation. While the algorithm did not yield identical results for the two orientations, the effect did not alter the findings of the study. These results provide a method for within-subject validation of a pathophysiological effect of carotid occlusive disease on the human cortex and warrant further investigation for underlying mechanisms.

Altered cerebral hemodyamics and cortical thinning in asymptomatic carotid artery stenosis

“…[ 29 ] No patients in our cohort had frank stroke, and WMH volumes and silent subcortical infarcts did not correlate with cortical thinning. Taken together, our results extend our prior findings that cortical thickness differed by side of occlusion,[ 15 ] and suggest that there is a differential susceptibility to cortical thinning in the anterior circulation that was not present in the posterior circulation. Moreover, this susceptibility had both a generalized effect across both hemispheres in the carotid territories, as well as a hemispheral effect, based on presence of the unilateral high grade obstruction that produced hemispheral hypoperfusion.…”

“…In the multiple linear regression analysis, regional blood flow predicted cortical thickness in M1 on both sides, age remained a predictor on the unoccluded side in M1, and there were no predictors of cortical thickness for V1 ( Table 2 ). As reported previously[ 15 ], cortical thickness was significantly lower in the primary motor cortex on the side of carotid occlusion compared with the unoccluded side (2.07mm vs. 2.15mm, paired t-test, P<0.001), and no significant hemispheral asymmetry was present in the visual cortex (1.78mm on ipsilateral side vs. 1.80mm on contralateral side, paired t-test P>0.2).…”

“…The following sequences were obtained on each participant: 1) A high-resolution 3D T1-weighted magnetization-prepared rapid gradient echo (MPRAGE) image was acquired with the following parameters: TE/TR = 3ms/6.7ms, voxel size = 0.9 x 0.9 x 0.9 mm 3 , 120 axial slices. This image was used to compute both the regional cortical thickness (rCT)[ 15 ] and to extract tissue volume data for partial volume effect correction (PVEc) of the arterial spin labeling (ASL) images. [[ 16 , 17 ]] 2) Fluid-attenuated inversion recovery (FLAIR) images were acquired in the Multi-Slice Turbo Spin Echo (MS-TSE) mode with FOV = 250 mm, acquisition matrix of 192x133 resampled to 256x256 in reconstruction, slice thickness = 3 mm, TE/TR = 144 ms/5500 ms, inversion recovery delay = 1900 ms, and flip angle = 90 deg.…”

“…Cortical Thickness measurement was performed on the Freesurfer platform[ 25 ], using volumetric tissue segmentation and inference of cortical structure from each patient’s MPRAGE image as described in our previous work. [ 15 ] Skull stripping was performed using the in-house thresholding method described above.…”

“…We recently reported asymmetry in cortical thickness between the cortex supplied by a unilaterally occluded carotid artery and the cortex in the opposite hemisphere. [ 15 ] This finding prompted us to examine blood flow differences as a potential causal factor in cortical thinning. In the present study, using the same cohort, we investigated the relationship between cortical thinning and regional cortical blood flow (rCBF).…”