Carotid stenosis is responsible for up to 20% of strokes in the adult population.¹ Carotid interventions such as carotid endarterectomy (CEA) and carotid artery stenting (CAS) have been shown to decrease this risk but can be associated with post-operative cognitive impairment that is not clearly linked to cardiovascular risk factors, age or perioperative complications.² We hypothesized that patterns of cerebral blood flow (CBF) changes over the post-surgical course may identify patients at increased risk of developing cognitive impairment after carotid intervention. While some post-operative MRI based perfusion studies have suggested variations in CBF are associated with cognitive impairment,³ no studies evaluating longitudinal CBF changes and cognitive impairment using arterial spin labelled MRI (ASL) have been performed.

Patient enrollment: Under institutional guidelines, 55 male veterans scheduled to undergo carotid intervention for a single carotid vessel (CAS or CEA) were enrolled. 7 of these subjects were re-enrolled in the study when undergoing surgery on the contralateral carotid vessel, for a total of 62 subjects.

Imaging: Patients were imaged as part of a clinical acquisition using the product GE 3D PC-ASL imaging sequence (PLD=2.5 ms, 6-8 arms, 4-5mm slice thickness, 3-4 NEX) using a 3T MRI (Discovery MR 750 Software Rev. 23, GE Medical Systems, Milwaukee, WI, USA). Imaging was performed within a month prior to surgery (PRE), within 24 hours after surgery (POST), and again 6 months after surgery (6MO).

Neuropsychological Testing: All subjects underwent cognitive testing prior to and 1 month after surgery that included the Rey Auditory Verbal Learning Test (RAVLT),⁴ which is a measure of episodic memory recall for verbal information that tests encoding, consolidating, storing and retrieval of verbal information.

Image Analysis: CBF maps were generated from product ASL images. CBF maps were then normalized using the method outlined by Dai et al.⁵ All images were flipped so the side of surgery was on the left, and then an 8 mm smoothing kernel was applied. Next GLMs were computed using SPM 8.

ASL imaging was obtained on all subjects, however, ASL imaging was not able to be obtained at all 3 time points for all subjects. 20 subjects underwent ASL imaging at all 3 sessions(10 CEA, 10 CAS), 37 subjects obtained PRE and POST ASL imaging only (16 CAS and 21 CEA), 24 Subjects obtained PRE and 6MO imaging only (12 CEA and 12 CAS), and 28 subjects received POST and 6MO imaging only (13 CEA, 15 CAS). A total of 131 ASL MRI scans were included for analysis.

All results are after multiple comparison correction.

PRE to POST: the cerebral hemisphere ipsilateral to the side of vessel repair experiences significant increased CBF, but less than the opposite hemisphere (p=0.001). CEA subjects also demonstrated significantly increased CBF on the hemisphere of vessel surgery compared to CAS (p=0.05) on PRE vs POST imaging. Lower increases in CBF from PRE to POST were also associated with greater decline at 1 month of RAVLT short delay. Lower increases from PRE to POST in CBF demonstrated a trend for decline at 1 month on RAVLT sum of trials (p=0.093).

POST to 6MO: There was a significant decrease in CBF (p=0.05). PRE to 6MO: There was no significant difference in CBF (p=0.05). Demonstrating greater CBF increase from PRE to 6MO was associated with greater decline at 1 month on the RAVLT long delay (p=0.05). Additionally, greater increase in CBF from

PRE to 6MO were associated with cognitive decline on the RAVLT long delay at 1 month (p=0.05).

Our findings demonstrate significant CBF increases at 24 hours after surgery, decreases between 24 hours and 6 months after surgery, and no significant CBF change from preoperative baseline to 6 months after surgery. This finding is consistent with the concept of cerebral autoregulation maintaining a constant CBF⁶, and suggests that shortly after carotid revascularization surgery significant, but transient CBF increases take place (Figure 1). We also found that patients with lower increases in CBF from baseline to 24 hours after surgery had greater decline in verbal learning and memory as reflected by the RAVLT short delay portion and a trend towards decreased performance on the RAVLT sum of trials portion (Figure 2). Our finding that subjects with greater increase in CBF from baseline to 6 months after surgery is associated with greater decline on the 1 month RAVLT long delay exam portion suggests that patients who do not normalize CBF back to presurgical levels may have impaired dynamic cerebral autoregulation, as has been shown in some carotid stenosis studies.^{7, 8}