Can Doppler Flow Parameters of Carotid Stenosis Predict the Occurrence of New Ischemic Brain Lesions Detected by Diffusion-Weighted MR Imaging after Filter-Protected Internal Carotid Artery Stenting?

Study Population

From July 2010 to April 2013, 72 patients with sonographically significant lesions (diameter stenosis of ≥50%) underwent elective carotid angiography and stent placement in the ICA (40 right, 32 left), of which 52 consecutive patients were enrolled and 20 patients were excluded from this study.

The following conditions were exclusion criteria: patients who underwent an urgent carotid artery stent placement for severe neurologic symptoms; those with disabling stroke; lack of compliance; prior carotid intervention; contralateral ICA occlusion; history of heart failure and myocardial infarction 72 hours before CAS; significant thyroid, renal, or hepatic dysfunction; incomplete or poor-quality MR imaging data; and any contraindication for MR imaging examination (pacemaker, claustrophobia).

The carotid angiograms were reviewed by an experienced cardiologist, who determined the severity of each lesion according to the criteria of the North American Symptomatic Carotid Endarterectomy Trial.¹⁸ According to our research protocol, the carotid artery was stented in asymptomatic patients with ≥80% stenosis of the extracranial carotid artery and in symptomatic patients with ≥70% stenosis.

Neurologic examination was performed before and after CAS by an experienced neurologist who was not involved in the CAS procedure. Patients were considered symptomatic in case of a transient ischemic attack, a retinal ischemic event, or an ischemic stroke within the territory of the narrowed carotid artery.

In addition, baseline risk factors for atherosclerosis, age, sex, hypertension, hyperlipidemia, diabetes mellitus, history of ischemic heart disease, and smoking were investigated for each patient.

The study, which complied with the Declaration of Helsinki, was approved by the local ethics committee, and all patients enrolled in the study gave written informed consent.

Carotid Ultrasonography

Baseline carotid ultrasonography was performed between 1 and 30 days before carotid angiography. All participants were examined after a 10-minute rest period to minimize the changes in blood pressure and heart rate to avoid influencing the Doppler parameters. Atherosclerosis of the carotid arteries was assessed by a radiologist who was blinded to the clinical data by using the same Doppler ultrasound device (Aplio MX; Toshiba Medical Systems, Tokyo, Japan). All patients were evaluated initially preprocedurally and postprocedurally with duplex ultrasonography of the ipsi- and contralateral common carotid artery (CCA) and ICA.

ICA atherosclerosis was evaluated by the maximum percentage of diameter reduction recorded by B-mode sonography and by the peak systolic velocity (PSV), end-diastolic velocity (EDV), and ICA/CCA PSV ratio per Doppler ultrasound. Lesion severity was defined as the greatest stenosis observed on either the right or left ICA. Sonography and Doppler findings were classified into 2 categories¹⁹:

1. Clinically insignificant: ICA stenosis of <50% (normal and noncritical). PSV < 125 cm/s with no signs of the presence of a sonographic atherosclerotic lesion (no plaque or intimal thickening is visible sonographically), correlating to additional criteria, including ICA/CCA PSV ratio < 2.0 and ICA EDV < 40 cm/s.

2. Clinically significant: a) ICA stenosis of 50%–69% (PSV = 125–230 cm/s and the presence of a sonographic atherosclerotic lesion). Additional criteria include an ICA/CCA PSV ratio of 2.0–4.0 and ICA EDV of 40–100 cm/s. b) ICA stenosis of ≥70%, but less than near-occlusion (PSV is >230 cm/s and the presence of a sonographic atherosclerotic lesion). Additional criteria include an ICA/CCA PSV ratio > 4 and ICA EDV > 100 cm/s (Fig 1).

• Download figure
• Open in new tab
• Download powerpoint

Fig 1.

Patient 27, with ≥70% stenosis of the left ICA. Duplex ultrasound image of the ICA shows a high PSV (369 cm/s) and color flow turbulence immediately distal to the stenotic segment, broadening of the pulse wave Doppler spectrum, and a high end-diastolic velocity (141 cm/s).

Patients with total or near-occlusion (defined as 0 PSV and no visible flow total or near-occlusion) were excluded.

Fifty-two patients with 50%–69% (n = 20, group 1) and 70%–99% (n = 32, group 2) ICA stenosis were treated with protected CAS following a prospective protocol.

Carotid Angiography and Carotid Artery Stent Placement Protocol

All procedures were performed by the femoral approach by using the standard Judikins technique. At least 2 projections of the carotid artery stenosis were obtained for the calculations of vessel diameter and degree of stenosis.

CAS was performed by an experienced interventional cardiologist by using a 0.014-inch platform with a distal embolus protection device (Emboshield NAV6; Abbott Laboratories, Abbott Park, Illinois). The appropriate length and diameter of self-expandable carotid stents (Xact; Abbott Laboratories) were used throughout the study. All stents were implanted from the ICA to the CCA. In case of technical difficulties with primary stent placement, the lesion was predilated before stent placement. After deployment, all stents were dilated with a 5.0- or 6.0-mm balloon (Falcon Grande; Invatec, Roncadelle, Italy). The filter was retrieved through a 4.3F dedicated catheter. A completion angiogram was obtained after removing the protection device. Patients were monitored in the recovery room and, barring any complication, were discharged in 3 days. The procedure was performed by the same experienced operator by using the same stent and the same filter (Fig 2), to keep any potential bias as low as possible.

• Download figure
• Open in new tab
• Download powerpoint

Fig 2.

Patient 15. Angiographic sequence of carotid stent placement (a 65-year-old male patient who presented with right hemiplegia and hemiparesis). A, Baseline angiography (arrow indicates the ICA and CCA) shows 80% ICA stenosis. B, A filter was placed. The stent was then extended from the ICA into the CCA. C, Angiography after the procedure (arrows indicate ICA patency).

MR Imaging Protocol

MR imaging was performed 48 hours before and after stent placement and at any time in case of neurologic deterioration (1.5T whole-body scanner, with a dedicated head coil; Signa Horizon; GE Healthcare, Milwaukee, Wisconsin).

DWI scans and the apparent diffusion coefficient maps were used to detect new acute ischemic lesions. A new lesion after CAS was defined as a focal hyperintense area detected by the fluid-attenuated inversion recovery sequence, corresponding to a restricted diffusion signal in the DWI sequence and confirmed by apparent diffusion coefficient mapping to rule out shinethrough artifacts. The diffusion-weighted sequence was performed with 2 levels of diffusion sensitization: b = 0 and b = 1000 s/mm². The higher level of diffusion sensitization was replicated in each of the 3 principal gradient directions (x, y, and z planes). The diffusion-weighted images from each of the 3 diffusion-sensitized acquisitions were separately displayed for analysis. Besides DWI, other sequences, which comprised the axial spin-echo T1-weighted image, the fast spin-echo T1-weighted image, the fast spin-echo T2-weighted image, the FLAIR image, the perfusion image, and the contrast-enhanced spin-echo T1-weighted image, were included (Fig 3). On each scan, the number and distribution (cortical, subcortical, or deep white matter) of lesions were recorded. Lesions were classified into 3 groups according to size (<5 mm, 5–10 mm, >10 mm).

• Download figure
• Open in new tab
• Download powerpoint

Fig 3.

Patient 9, a 58-year-old woman with asymptomatic stenosis (≥80%) of the right ICA. DWI and ADC map images in the 2 days before and the second day after filter-protected stent placement. A and B, No visible lesion is seen on both images. C and D, Poststent images demonstrate a single new ischemic lesion in the contralateral temporoparietal cortex (the lesion was hyperintense on the DWI and hypointense on the corresponding ADC map, arrowhead).

Two radiologists counted and recorded the number of new high-signal intensities in the cerebral hemispheres by comparing the pre- and postprocedural DWIs for each CAS procedure without any knowledge of the clinical status.

Concomitant Medical Therapy

All patients were treated with aspirin, 100 mg/day, plus clopidogrel, 75 mg/day, for at least 7 days before CAS and 1 month afterward. During CAS, patients received intravenous heparin (5000–10,000 U) to maintain activated clotting time between 250 and 300 seconds. Just before the poststenting dilation phase, atropine (0.5–1 mg IV) was given to most patients to reduce bradycardia and hypotension potentially associated with carotid dilation.

Statistical Analysis

Statistical evaluation was performed by using the Statistical Package for the Social Sciences, Version 17.0, software package for Windows (IBM, Armonk, New York). Quantitative variables are given as mean ± SD, and qualitative variables are expressed as frequency and percentage. Groups were compared by using the Student t test for continuous variables and the χ² test for categoric variables. When >2 groups were compared for parameters, analysis of variance was used; post hoc analysis was performed by using the Tukey honest significant difference test. Logistic regression models were fitted for new brain lesions detected by DWI–MR frequency and extension as the dependent variable, with adjustment for Doppler parameters of ICA, age, sex, smoking status, hypertension, diabetes mellitus, and hyperlipidemia. For all analyses, a 2-tailed P ≤ .05 was considered statistically significant.