Measurement of changes in perfusion after carotid endarterectomy by 3D pseudo-continuous arterial spin labeling

Background: Carotid endarterectomy (CEA) is an effective method for treating cerebral ischemia caused by carotid stenosis, but there may be a risk of perfusion pressure breakthrough during early perfusion recovery. As a non-invasive and contrast-free magnetic resonance examination method, arterial spin labeling can be used for continuous observation and measurement in the early postoperative period of carotid endarterectomy. Results: Nineteen patients with severe unilateral carotid stenosis were examined using 3D pseudo-continuous arterial spin labeling before and after CEA, and we found that the pattern of dynamic cerebral blood flow changes is not the same in different regions. Conclusions: 3D pseudo-continuous arterial spin labeling might be helpful for the improvement of postoperative treatment and care of severe unilateral carotid stenosis patients.


Background
Ischemic stroke is closely associated with carotid atherosclerotic stenosis. Approximately 20-30% of transient ischemic attacks or cerebral infarctions are caused by severe carotid stenosis or occlusion [1]. Severe carotid stenosis decreases the blood vessel cross-sectional area and increases the local blood flow velocity. However, the blood flow per unit time is reduced [2], which is reflected by lower cerebral blood flow (CBF) in the brain. Carotid endarterectomy (CEA) is an effective mode for treating carotid stenosis and it has been clinically proven to significantly improve the intracranial CBF and effectively resolve the patient's clinical symptoms. However, CEA can cause iatrogenic complications such as perioperative stroke [3]. In particular, postoperative hyperperfusion syndrome has attracted increasing attention from clinicians due to the difficulty in its prediction and its serious consequences [4,5]. Therefore, monitoring the time and severity of postoperative hyperperfusion is of significance for both objective analysis of surgical efficacy and to prevent postoperative hyperperfusion syndrome [6][7][8].
Conventional vascular imaging techniques such as computed tomography arthrography (CTA), magnetic resonance angiography, and digital subtraction angiography (DSA) often overestimate the degree of arterial stenosis due to the presence of vascular remodeling [5]. The use of CT perfusion imaging or single-photon emission computed tomography to measure intracranial blood perfusion is also limited in clinical practice due to the presence of radioactivity [9][10][11]. In recent years, magnetic resonance perfusion imaging techniques such as dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) have received much attention owing to their good tissue resolution and lack of radioactivity. With the continuous advancement and updates of ASL in recent years, the measurement of perfusion has evolved from qualitative to quantitative. Compared with DSC, which requires a bolus injection of paramagnetic contrast agents, ASL is non-invasive and does not need contrast agents and therefore has a broader target population and development prospect. The specificity and sensitivity of diagnosis by ASL meet clinical requirements, and its application in patients with carotid atherosclerosis is expanding [12,13]. Previous studies have pointed out that for the changes of overall perfusion after CEA [6]. After checking the perfusion of different parts, we found that some corrections were needed for the time of prediction. In this study, we used ASL to evaluate the continuous change in cerebral perfusion during the early post-CEA period.

Medical history
Medical history revealed that 11 patients had previous hypertension, 7 had previous diabetes, 16 had previous hyperlipidemia, and 12 were smokers. Preoperative symptoms included numbness of the limbs (17 patients), dizziness (11 patients), decreased visual acuity (4 patients), and amaurosis (6 patients). Details are shown in Table 1.

CBF values in different regions
The CBF values of the bilateral frontal lobe, temporal lobe, watershed area, and basal ganglia were increased after CEA (p < 0.01), which are shown in Table 2. There was a significant difference in CBF between the stenotic and contralateral frontal lobes before CEA (p = 0.012), but the difference in CBF between the stenotic and contralateral frontal lobes was not significant on days 1, 2, 3, and 4 and at 3 months post-CEA (p > 0.05). The CBF differed significantly between the stenotic and contralateral temporal lobes before CEA (p = 0.010) and at 3 months post-CEA (p < 0.05), but not on days 1, 2, 3,  CBF values of the contralateral side, showed a similar trend to the ipsilateral side, but the increase in CBF on the contralateral side was smaller than that on the ipsilateral side. The data are illustrated in

Discussion
Intracranial blood is supplied by bilateral arteries interlinked by communicating arteries. The areas supplied by the internal carotid artery include the frontotemporal cortex, basal ganglia, and watershed area. When internal carotid stenosis occurs, self-regulation of blood flow and dilation of blood vessels decrease the cerebral perfusion pressure. However, the CBF in the frontal and temporal lobes is maintained at a normal level during the early stage of stenosis due to the rich vascular network and collateral circulation between the anterior cerebral artery and the middle cerebral artery [14]. The CBF decreases only when the perfusion pressure in these areas drops below a certain threshold and is beyond the control of self-regulation. Although intracranial perfusion has already decreased markedly at this time, no obvious infarction can be detected by MRI. As intracranial perfusion continues to decrease, neuronal cells will undergo irreversible damage [15]. To avoid these serious consequences, early CBF monitoring should be performed on areas that are sensitive to ischemia and hypoxia.
When internal carotid plaque is removed, self-regulation of blood flow and dilation of blood vessels restore blood flow in the arterial lumen, recover intracranial blood supply and increase the cerebral perfusion pressure. Therefore, the efficacy of CEA should be evaluated on the basis of postoperative hemodynamics and cerebral perfusion recovery [16]. Our study confirmed that CEA significantly improved the severe preoperative reduction in intracranial perfusion. The CBF was increased to varying degrees after CEA on both the ipsilateral and contralateral sides, and the increase was greater on the ipsilateral sides of the watershed area and basal ganglia.
Although CEA is effective in treating carotid stenosis and can significantly improve CBF in patients, the possibility of a significant pathological increase in postoperative perfusion should not be overlooked. A previous study reported that patients who underwent CEA had a 16-30% chance of developing cerebral hyperperfusion syndrome (CHS) when the CBF increased by more than twofold [17]. Brain hemorrhage and swelling were more likely to occur during this time, and complications such as cerebral hemorrhage, epilepsy, delirium, coma, and headache can also develop when there is severe stenosis or poor collateral circulation [18]. In the past we focused on global intracranial perfusion, which is correct but can go further. According to the results, the CBF values of the frontal and temporal lobes peaked at 72 h, while those of the watershed area and the basal ganglia peaked at 48 h postoperatively; then all gradually decreased to a stable level. This may be because after completion of CEA and recanalization, although there is abundant blood flow in the brain, the distribution of blood circulation is uneven, and CEA impairs baroreflex and attenuates vascular self-regulation, leading to a failure of intracranial arterioles to adapt to hyperperfusion promptly [19][20][21]. This study has several limitations: (1) As this is a single-center study, it is prone to selection bias; (2) As the subjects were elderly patients with severe carotid stenosis and the CBF values measured by ASL decreases with age, these subjects do not fully represent the entire patient population; (3) Compared with 3D voxel analysis, subjective factors are inevitable when hand-drawing the ROI for the analysis of cerebral perfusion images; (4) only a single PLD of 2.0 s as recommended was used in this study, which might lead to inaccurate blood flow measurement.

Conclusion
The pattern of dynamic CBF changes is not the same in different regions, which may be helpful for the improvement of postoperative treatment and care.

Patient information
This study included 19 symptomatic patients with severe unilateral carotid stenosis who were admitted to the Department of Neurosurgery, Chinese PLA General Hospital from November 2015 to November 2016. There were 12 men and 7 women with a mean age of 63.57 ± 9.17 years (range, 46-weighted imaging (T1WI) and 3D-ASL (PLD = 2025 ms). All the patients underwent CEA and were examined by MRI and 3D-ASL again on days 1, 2, 3, and 4 and at 3 months after CEA.

Inclusion and exclusion criteria
The inclusion criteria were as follows: (1) The patient was diagnosed by DSA as having ≥ 70% unilateral carotid stenosis with a normal contralateral side; (2) Presence of neurological symptoms; (3) Absence of major organ dysfunction, tolerance to CEA, and no difficulty in exposing the stenotic segment; (4) The patient signed an informed consent form before the scans; and (5)   Image processing and determination of CBF Original images of the scan sequences were transferred to an MRI image-processing workstation.
Pseudocolor images of CBF were generated using the image-processing software GE Function Tool