Asymptomatic carotid artery stenosis is associated with cerebral hypoperfusion

Abstract

Objective: We have shown that almost 50% of patients with asymptomatic carotid stenosis (ACS) will demonstrate cognitive impairment. Recent evidence has suggested that cerebral hypoperfusion is an important cause of cognitive impairment. Carotid stenosis can restrict blood flow to the brain, with consequent cerebral hypoperfusion. In contrast, cross-hemispheric collateral compensation through the Circle of Willis, and cerebrovascular vasodilation can also mitigate the effects of flow restriction. It is, therefore, critical to develop a clinically relevant measure of net brain perfusion in patients with ACS that could help in risk stratification and in determining the appropriate treatment. To determine whether ACS results in cerebral hypoperfusion, we developed a novel approach to quantify interhemispheric cerebral perfusion differences, measured as the time to peak (TTP) and mean transit time (MTT) delays using perfusion-weighted magnetic resonance imaging (PWI) of the whole brain. To evaluate the utility of using clinical duplex ultrasonography (DUS) to infer brain perfusion, we also assessed the relationship between the PWI findings and ultrasound-based peak systolic velocity (PSV).

Methods: Structural and PWI of the brain and magnetic resonance angiography of the carotid arteries were performed in 20 patients with ≥70% ACS. DUS provided the PSV, and magnetic resonance angiography provided plaque geometric measures at the stenosis. Volumetric perfusion maps of the entire brain from PWI were analyzed to obtain the mean interhemispheric differences for the TTP and MTT delays. In addition, the proportion of brain volume that demonstrated a delay in TTP and MTT was also measured. These proportions were measured for increasing severity of perfusion delays (0.5, 1.0, and 2.0 seconds). Finally, perfusion asymmetries on PWI were correlated with the PSV and stenosis features on DUS using Pearson's correlation coefficients.

Results: Of the 20 patients, 18 had unilateral stenosis (8 right and 10 left) and 2 had bilateral stenoses. The interhemispheric (left-right) TTP delays measured for the whole brain volume identified impaired perfusion in the hemisphere ipsilateral to the stenosis in 16 of the 18 patients. More than 45% of the patients had had ischemia in at least one half of their brain volume, with a TTP delay >0.5 second. The TTP and MTT delays showed strong correlations with PSV. In contrast, the correlations with the percentage of stenosis were weaker. The correlations for the PSV were strongest with the perfusion deficits (TTP and MTT delays) measured for the whole brain using our proposed algorithm (r = 0.80 and r = 0.74, respectively) rather than when measured on a single magnetic resonance angiography slice as performed in current clinical protocols (r = 0.31 and r = 0.58, respectively).

Conclusions: Interhemispheric TTP and MTT delay measured for the whole brain using PWI has provided a new tool for assessing cerebral perfusion deficits in patients with ACS. Carotid stenosis was associated with a detectable reduction in ipsilateral brain perfusion compared with the opposite hemisphere in >80% of patients. The PSV measured at the carotid stenosis using ultrasonography correlated with TTP and MTT delays and might serve as a clinically useful surrogate to brain hypoperfusion in these patients.

Keywords: Atherosclerosis; Carotid; Cerebral hemodynamics; Perfusion imaging; Stenosis.

Fig 1.

Raw perfusion maps at the level of basal ganglia for a sample patient with a right-sided stenosis: time to peak (TTP; A), mean transit time (MTT; B), relative cerebral blood volume (rCBV; C), and relative cerebral blood flow (rCBF; D). Interhemispheric perfusion differences are visible, especially for TTP (arrow in A) and MTT maps. No difference was found in perfusion between hemispheres when the color in any given part of the brain was the same in the two hemispheres. Blue and red represent the lowest and highest values in each scan, respectively. The ventricles in each hemisphere were excluded from the analysis. A.U., Arbitrary units.

Fig 2.

Interhemispheric (left–right) differences in perfusion parameters at the level of the basal ganglia and whole brain: time to peak (TTP; A), mean transit time (MTT; B), relative cerebral blood flow (rCBF; C), and relative cerebral blood volume (rCBV; D). Negative values indicate increased perfusion deficits in the right hemisphere because the differences were computed by subtracting the right hemisphere values from those of the left. Laterality is indicated by the sign of the parameter, and the magnitude quantifies the extent of interhemispheric dissimilarity. The patients were arranged by stenosis laterality (left, bilateral, right) and decreasing whole brain TTP differences for all four parameters.

Fig 3.

Proportion of ipsilateral brain volume with hypoperfusion, when the hypoperfusion threshold was set at a delay of >0.5 second, >1 second, and >2 seconds relative to the contralateral hemisphere using voxel-level analysis for time to peak (TTP; A) and mean transit time (MTT; B). The threshold of >0.5, 1, and 2-second counted all voxels at which the TTP or MTT was greater than 0.5, 1, or 2 seconds, with the proportion determined by the corresponding hemispheric brain volume. The mean percentage for the three thresholds (gray bars) and standard deviation (error bars) are also presented for each patient. Patients were presented in decreasing order of the mean percentages.

Fig 4.

Interhemispheric perfusion differences (absolute values) as a function of collateralization through the Circle of Willis (CoW) for whole brain (WB) and single slice (SS) analysis. Time to peak (TTP; A), mean transit time (MTT; B), relative cerebral blood flow (rCBF; C), and relative cerebral blood volume (rCBV; D). *P < .05; **P < .005.

Fig 5.

The in vivo peak systolic velocity (PSV) measured at stenosis using Doppler ultrasonography as a function of the magnitude of interhemispheric differences in perfusion parameters. A.U., Arbitrary units; MTT, mean transit time; rCBF, relative cerebral blood flow; rCBV, relative cerebral blood volume; SS-BG, single-slice at basal ganglia; TTP, time to peak; WB, whole brain.