Carotid Artery Wall Thickness and Leukoaraiosis: Preliminary Results Using Multidetector Row CT Angiography

Patient Population

We created a data base from retrospective case material from our institution and then searched the data base prospectively as a hypothesis-driven scientific study. Inclusion criteria were ≥60 years of age and previous MDCT imaging of the brain and carotid arteries performed at the same sitting, whereas exclusion criteria were other possible causes of white matter hypoattenuation, such as multiple sclerosis, vasculitis, acute disseminated encephalomyelitis, or connective tissue diseases.²³

From August 2009 to March 2010, 98 patients (65 men, 33 women; mean age, 72 years; age range, 60–82 years) met the above-mentioned criteria in our university hospital and were selected for the study.

Each patient underwent MDCTA for suspected carotid artery pathology. The inclusion criteria for performing MDCTA in our institution have previously been published^11,14,21,22 and are as follows: the presence of an US examination that showed a pathologic stenosis and/or a plaque alteration, or US being unable to provide sufficient information about the degree of stenosis and plaque type—for example, in the presence of large calcified plaques with acoustic shadowing, high carotid bifurcation, or a thick neck (edema, patients with obesity). With US, plaque alteration was considered as the presence of a heterogeneous plaque, an irregular surface, intraplaque hemorrhage, and/or ulceration in the plaque. Exclusion criteria for the MDCTA examination were a known allergy to iodinated contrast material or elevated renal function tests.

Demographic details, including age, sex, and risk factors (hypertension, diabetes, coronary artery disease, dyslipidemia, and tobacco use) were recorded.

This retrospective review evaluated existing clinical data and records. No additional procedures were performed. The review was conducted in accordance with the guidelines of the research committee of our institution.

Classification of Cerebrovascular Symptoms

Patients were classified as symptomatic or asymptomatic according to the neurologic assessment documented in the clinical chart review. A patient with a TIA or stroke was considered as “symptomatic.” TIA was regarded as an episode of neurologic dysfunction, such as hemiparesis, hemiparesthesia, dysarthria, dysphasia, or monocular blindness for <24 hours. If the episode of neurologic dysfunction exceeded 24 hours, it was classified as a stroke. The time window for inclusion in the symptomatic group was 6 months; when a patient underwent an MDCTA examination >6 months after the TIA/stroke event, he or she was excluded from the symptomatic group and included in the asymptomatic group. A patient who had no current history of symptoms or who had a remote (>6-month) history of symptoms at the time of examination was considered “asymptomatic.” In our institution, the carotid arteries of asymptomatic patients are studied if the patient has diabetes and is >50 years of age and if the patient has undergone a cardiac intervention for coronary artery disease, an aortic intervention, or lower leg artery surgery.

Cardiovascular Risk Factors

Cardiovascular risk factors and coexisting comorbidities and treatment known before stroke or TIA are systematically recorded in our institution as described previously.^11,14,21,22 In this study, we considered the following parameters: CAD, high blood pressure, dyslipidemia, diabetes, and cigarette smoking status. Diabetes was indicated by an abnormal fasting plasma glucose level (>7.9 mmol/L) or the current use of insulin or an oral hypoglycemic agent. Cigarette smoking status was categorized as never or current (if the patient had stopped in the last 24 months, he or she was considered a current smoker). “Dyslipidemia” was defined as abnormal fasting plasma cholesterol (low-attenuation lipoprotein cholesterol) levels (fasting cholesterol >5.0 mmol/L) or the current use of lipid-lowering agents. CAD was diagnosed in the presence of the following: 1) visible luminal narrowing of coronary arteries documented by coronary angiography or MDCTA, 2) a previous history of myocardial infarction, or 3) previous coronary interventional/surgical procedures. “Essential hypertension” was defined as a systolic blood pressure of >140 mm Hg and/or a diastolic blood pressure of >90 mm Hg or the current use of blood pressure−lowering drugs.

MDCTA Technique

All patients underwent MDCTA of the supra-aortic vessels by using a 16-detector multidetector-row CT system (Brilliance; Philips Healthcare, Best, the Netherlands). A basal scan was obtained and was followed by the angiographic phase in which 80 mL of contrast medium (iomeprol, Iomeron 400; Bracco, Milan, Italy) was injected into a cubital vein, by using a power injector at a flow rate of 5 mL/s and an 18-ga intravenous catheter. A bolus-tracking technique was used to calculate the correct timing of the scan. Dynamic monitoring scanning began 6 seconds after the beginning of the intravenous injection of contrast material. The trigger threshold inside the region of interest was set at +80 HU above the baseline. The delay between the acquisition of each monitoring scan was 1 second. When the threshold was reached, the patient was instructed not to breathe, and after an interval of 4 seconds, the scan was started in the caudocranial direction. CT technical parameters included the following: matrix 512 × 512; FOV, 14–19 cm; mAs, 180–200; kV, 120–140; section thickness, 1 mm; increment, 0.5 mm. The window level was preset according to Saba and Mallarini.^24,25 Angiographic acquisition included the carotid siphon. None of the patients included in the study had a medical history of cardiac output failure or any contraindications to iodinated contrast media.

MDCTA of the Brain

CT brain studies were performed with the same scanner used for carotid analyses (Philips Brilliance). Acquisitions were performed before and after injection of contrast material from the base of the skull to the vertex. CT technical parameters included the following: matrix, 512 × 512; FOV, 25 cm; mAs, 320–340; 120–140 kV; section thickness, 2 mm; increment, 1 mm.

Analysis of Carotid Artery and CAWT

The degree of stenosis of each carotid artery was measured by using the North American Symptomatic Carotid Endarterectomy Trial criteria.^26–28 The degree of stenosis was calculated by selecting a reformat plane perpendicular to the lumen centerline. Particular attention was paid to avoid the key calculation pitfalls of percentage stenosis: The first step was to recognize near-occlusion (in this case, attempts to calculate a percentage may be fallacious), which was identified by 2 criteria: 1) evidence of narrowed poststenotic ICA, and 2) a poststenotic ICA that was similar to or smaller than the ipsilateral external carotid artery. Second, we measured the diameter of the normal ICA wall beyond the bulb where the walls were parallel,^26–28 4–6 cm distal to the plaque. Each carotid stenosis received the following grades: I, normal; II (1%–39%), mildly stenosed; III (40%–69%), moderately stenosed; IV (70%–99%), severely stenosed; and V, occluded.

CAWT, as indicated by Saba et al,²² and Fanning et al²³ was measured at its thickest point on the distal (far) wall of the common carotid artery, where there was no evidence of plaque,²⁹ 2 cm proximal to the bulb. This distance was necessary because if the wall is measured close to a plaque, it should be thicker. Three measurements were performed at the 6, 9, and 12 o'clock positions for each carotid artery (Fig 1). We measured CAWT between the leading edge of the opacified lumen vessel and the external visible limit of the artery wall, where it was surrounded by adjacent adipose tissue. The individual subject's mean common carotid CAWT values were then obtained by averaging the values obtained for each carotid artery.

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Fig 1.

Examples of LA. A, Grade 0. B, Grade 1. C, Grade 2. D, Grade 4.

To perform logistic regression analyses, we also analyzed the type of plaque. For the measurement of Hounsfield unit attenuation, a circular or elliptic region-of-interest cursor was used in the predominant plaque area; those areas showing contamination by contrast material or beam hardening were carefully avoided. We used the classification proposed by de Weert et al^30–32: “fatty” (soft) plaque was a plaque with an attenuation <60 HU; “mixed (intermediate) plaque” was a plaque with an attenuation between 60 and 129 HU; and “calcified plaque” was a plaque with a attenuation of >130 HU.

Analysis of Brain MDCT

MDCT images of the brain were analyzed by reviewers who were blinded to the patient's demographic details, and 2 experienced radiologists quantified the white matter scores and resolved any differences by consensus. In this study, the hemispheric white matter score and corresponding ipsilateral carotid characteristics—degree of stenosis and type of plaque—were considered as a single unit of analysis.^11,23 Therefore 196 carotid-hemisphere units were analyzed.

For white matter assessment, we used a visual scale for the severity of white matter change based on the European Task Force on Age-Related White Matter Changes.³³ We used a 4-point grading scale as follows: 0, no lesions; 1, focal lesions >5 mm; 2, early confluent lesions; and 3, diffuse involvement of an entire brain region. For all patients, the highest score for each hemisphere was used in the analysis (Fig 2).

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Fig 2.

MDCTA axial image of a 79-year-old man. A, The white arrow indicates the right common carotid artery. B, A 200% magnification is shown, and the 3 measurements at 6, 9, and 12 o‘ clock positions are visible.

Statistical Analysis

Continuous data were described as the mean value ± SD. The normality of data distribution was assessed by using the Kolmogorov-Smirnov test. Age was boxplotted against LA severity and CAWT. The correlation coefficient between CAWT and LA severity was calculated by using a Spearman correlation (ρ). Logistic regression analysis was also performed to examine the relationship between the dichotomous variable LA and independent variables such as CAWT, age, class of carotid artery stenosis, sex, tobacco use, hypertension, dyslipidemia, and diabetes mellitus. The Cohen κ test³⁴ was applied to assess the interobserver agreement for white matter scores. A value of <0.20 implied poor agreement; 0.21–0.40, fair agreement; 0.41–0.60, moderate agreement; 0.61–0.80, substantial agreement; and 0.81–1.0, almost perfect agreement. The Bland-Altman analysis was performed to analyze the interobserver agreement in the CAWT quantification. R software (www.r-project.org) was used for these analyses. A P value < .05 was considered to indicate statistical significance.