Asymptomatic carotid artery stenosis is associated with cerebral hypoperfusion.

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.

Quantitative assessment of carotid plaque morphology (geometry and tissue composition) using computed tomography angiography.

OBJECTIVE: Quantification of carotid plaque morphology (geometry and tissue composition) may help stratify risk for future stroke and assess plaque progression or regression in response to medical risk factor modification. We assessed the feasibility and reliability of morphologic measurements of carotid plaques using computed tomography angiography (CTA) and determined the minimum detectable change in plaque features by this approach. METHODS: CTA images of both carotid arteries in 50 patients were analyzed by two observers using a semiautomatic image analysis program, yielding 93 observations per user (seven arteries were excluded because of prior stenting). One observer repeated the analyses 4 weeks later. Measurements included total plaque volume; percentage stenosis (by diameter and area); and tissue composition for calcium, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH). Reliability of measurements was assessed by intraclass and interclass correlation and Bland-Altman plots. Dice similarity coefficient (DSC) and modified Hausdorff distance (MHD) assessed reliability of geometric shape measurements. We additionally computed the minimum amount of change in these features detectable by our approach. RESULTS: The cohort was 51% male (mean age, 70.1 years), and 56% had a prior stroke. The mean (± standard deviation) plaque volume was 837.3 ± 431.3 mm3, stenosis diameter was 44.5% ± 25.6%, and stenosis area was 58.1% ± 29.0%. These measurements showed high reliability. Intraclass correlation coefficients for plaque volume, percentage stenosis by diameter, and percentage stenosis by area were 0.96, 0.87, and 0.83, respectively; interclass correlation coefficients were 0.88, 0.84, and 0.78. Intraclass correlations for tissue composition were 0.99, 0.96, and 0.86 (calcium, LRNC, and IPH, respectively), and interclass correlations were 0.99, 0.92, and 0.92. Shape measurements showed high intraobserver (DSC, 0.95 ± 0.04; MHD, 0.16 ± 0.10 mm) and interobserver (DSC, 0.94 ± 0.05; MHD, 0.19 ± 0.12 mm) luminal agreement. This approach can detect a change of at least 3.9% in total plaque volume, 1.2 mm3 in calcium, 4.3 mm3 in LRNC, and 8.6 mm3 in IPH with the same observer repeating measurements and 9.9% in plaque volume, 1.9 mm3 in calcium, 7.9 mm3 in LRNC, and 6.8 mm3 in IPH for two different observers. CONCLUSIONS: Carotid plaque geometry (total volume, diameter stenosis, and area stenosis) and tissue composition (calcium, LRNC, and IPH) are measured reliably from clinical CTA images using a semiautomatic image analysis program. The minimum change in plaque volume detectable is ∼4% if the same observer makes both measurements and ∼10% for different observers. Small changes in plaque composition can also be detected reliably. This approach can facilitate longitudinal studies for identifying high-risk plaque features and for quantifying plaque progression or regression after treatment.

Semiautomatic quantification of carotid plaque volume with three-dimensional ultrasound imaging.

OBJECTIVE: Vessel wall volume (VWV) assessed by three-dimensional duplex ultrasound (3DUS) imaging provides a more comprehensive measure of plaque burden than conventional two-dimensional measures of diameter stenosis. We previously demonstrated that manual outlining of the arterial lumen-intima boundary and outer wall boundary can be performed reliably on images obtained with a commercially available 3D-DUS transducer. Manual segmentation, however, is time consuming (∼45 minutes), limiting its clinical translation. We have developed a semiautomatic algorithm (manual selection of the carotid bifurcation image with subsequent automatic plaque outlining) to outline carotid plaques on 3DUS data sets. In this study, we investigated the accuracy, reproducibility, reliability, and time taken by this algorithm. METHODS: 3DUS data sets from 30 patients with asymptomatic ≥50% carotid stenosis underwent manual outlining of lumen-intima boundary and outer wall boundary to measure VWV. Two observers implemented a semiautomatic segmentation algorithm. The algorithm's accuracy was compared with manual outlining using the Pearson correlation coefficient. The Dice similarity coefficient (DSC) and modified-Hausdorff distance (MHD) were used to quantify the geometric similarity of the outlines. We also compared results after an intermediate stage of the algorithm vs the complete algorithm. Reproducibility and the least amount of detectable change in plaque volume were computed for each method. Intraobserver and interobserver metrics for each method were computed using the intraclass correlation coefficient (ICC), coefficient of variability (CV), minimum detectable change (MDC), and standard error of measurement (SEM) of the VWV. RESULTS: Plaque volume estimates obtained from the semiautomatic algorithm were accurate compared with manual outlining. The Pearson correlation coefficient was 0.76 (P < .001), and measurements were geometrically similar (DSC, 0.85; MHD, 0.48 mm). The algorithm was more reproducible and reliable and could detect smaller changes in plaque volume on repeat imaging (low interobserver variability: ICC, 0.9; CV, 8.22%; MDC, 5.57%; SEM, 1.45%; DSC, 0.88; MHD, 0.43 mm). Intraobserver variability was even lower (ICC, 0.9; CV, 8%; MDC, 3.62%; SEM, 1.31%; DSC, 0.89; MHD, 0.37 mm). Plaque volume estimates at the intermediate stage of the algorithm matched results from the full algorithm (Pearson correlation coefficient, 0.76; DSC, 0.84; MHD, 0.52 mm). The intermediate approach, however, was less reliable than the full algorithm (interobserver: ICC, 0.81; CV, 11.7%; MDC, 9.58%; SEM, 3.46%; DSC, 0.88; MHD, 0.42 mm; intraobserver: ICC, 0.87; CV, 8.6%; MDC, 4.55%; SEM, 1.64%; DSC, 0.89; MHD, 0.38 mm). The full algorithm required ∼14 minutes to implement. However, a quick (7 minutes) and accurate assessment of VWV can be obtained by running only the intermediate stage of the algorithm, although with a loss in repeatability and reliability. CONCLUSIONS: We present a unique algorithm to perform semiautomatic quantification of carotid plaque volume using 3DUS imaging. It is quick (mean time, 14 minutes), accurate, repeatable, and implementable in a clinical environment and in longitudinal studies tracking plaque progression. It reliably detects plaque volume changes as low as 4% to 6% with 95% confidence.

Asymptomatic carotid stenosis is associated with cognitive impairment.

BACKGROUND: Cerebrovascular risk factors (eg, hypertension, coronary artery disease) and stroke can lead to vascular cognitive impairment. The Asymptomatic Carotid Stenosis and Cognitive Function study evaluated the isolated impact of asymptomatic carotid stenosis (no prior ipsilateral or contralateral stroke or transient ischemic attack) on cognitive function. Cerebrovascular hemodynamic and carotid plaque characteristics were analyzed to elucidate potential mechanisms affecting cognition. METHODS: There were 82 patients with ≥50% asymptomatic carotid stenosis and 62 controls without stenosis but matched for vascular comorbidities who underwent neurologic, National Institutes of Health Stroke Scale, and comprehensive neuropsychological examination. Overall cognitive function and five domain-specific scores were computed. Duplex ultrasound with Doppler waveform and B-mode imaging defined the degree of stenosis, least luminal diameter, plaque area, and plaque gray-scale median. Breath-holding index (BHI) and microembolization were measured using transcranial Doppler. We assessed cognitive differences between stenosis patients and control patients and of stenosis patients with low vs high BHI and correlated cognitive function with microembolic counts and plaque characteristics. RESULTS: Stenosis and control patients did not differ in vascular risk factors, education, estimated intelligence, or depressive symptoms. Stenosis patients had worse composite cognitive scores (P = .02; Cohen's d = 0.43) and domain-specific scores for learning/memory (P = .02; d = 0.42) and motor/processing speed (P = .01; d = 0.65), whereas scores for executive function were numerically lower (P = .08). Approximately 49.4% of all stenosis patients were impaired in at least two cognitive domains. Precisely 50% of stenosis patients demonstrated a reduced BHI. Stenosis patients with reduced BHI performed worse on the overall composite cognitive score (t = -2.1; P = .02; d = 0.53) and tests for learning/memory (t = -2.7; P = .01; d = 0.66). Cognitive function did not correlate with measures of plaque burden (degree of stenosis, least luminal diameter, and plaque area) or with plaque gray-scale median. CONCLUSIONS: Asymptomatic carotid stenosis is associated with cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. Approximately 49.4% of these patients demonstrate impairment in at least two neuropsychological domains. The deficit is driven primarily by reduced motor/processing speed and learning/memory and is mild to moderate in severity. The mechanism for impairment is likely to be hemodynamic as evidenced by reduced cerebrovascular reserve and the likely result of hypoperfusion from a pressure drop across the stenosis in the presence of inadequate collateralization.

Infrapopliteal Arterial Pseudoaneurysm Development Secondary to Blunt Trauma: Case Series and Literature Review.

OBJECTIVES: Infrapopliteal arterial pseudoaneurysms (IAP) following blunt trauma with associated orthopedic injuries are uncommon, often present in a delayed fashion, and encompass a diagnostic and therapeutic dilemma. Herein, we present a series of IAPs that were diagnosed following blunt trauma and their management. METHODS: Case series consisting of 3 patients and a review of the international literature. RESULTS: Our case series included 3 patients presenting with IAPs following blunt trauma with associated orthopedic injuries. They were all identified in a delayed manner (>3 weeks) after the orthopedic injuries were treated. All patients presented with pain and a pulsatile mass while one concurrently had neurologic deficits. The pseudoaneurysms were diagnosed by duplex ultrasound and confirmed by angiography to be originating from the tibioperoneal trunk, anterior tibial, and posterior tibial arteries respectively. Two patients were treated with surgical excision. Of these, one required an arterial bypass procedure while the other underwent direct ligation only. The third patient was treated by endovascular coiling. A literature review from 1950 to the present found 51 reported cases of IAP resulting from blunt trauma. Ninety percent of trauma-related infrapopliteal injuries occurred in men with a mean delay in diagnosis of 5.6 months (median 1.8 months) after injury. Since 1950, management has shifted from primarily ligation to incorporating minimally invasive endovascular techniques when appropriate. CONCLUSIONS: Infrapopliteal artery pseudoaneurysms are rare following blunt skeletal trauma. A delay in diagnosis often occurs and can result in major morbidity and extensive surgical intervention. We recommend a high index of suspicion and a thorough vascular examination in patients with lower extremity skeletal trauma to help identify and treat these injuries early and effectively.

High prevalence of chronic venous disease among health care workers in the United States.

BACKGROUND: Health care workers spend extended times standing and walking short distances and are at risk for development of chronic venous insufficiency (CVI). We conducted a hospital-wide venous screening program designed to measure the prevalence of and risk factors for clinical manifestations of CVI and ultrasound evidence of venous reflux or obstruction in health care workers. We also determined their risk for deep venous thrombosis (DVT). METHODS: Free venous screening and education were offered to all hospital employees; the program started in April 2016, and results are presented from the first year. Demographics, medical history, and use of compression stockings were recorded. A physical examination determined the clinical class of the Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification for clinical disease, and an ultrasound test evaluated for reflux or obstruction in the common femoral vein, popliteal vein, and saphenofemoral junction. The Caprini score was recorded to evaluate risk of DVT. Descriptive statistics were reported, and logistic regression was used for multivariate analysis of risk factors. RESULTS: We enrolled 636 participants (1272 legs); 93.0% were women. The median age was 42 years (interquartile range, 31-52 years), mean body mass index was 29.2 ± 6.6 kg/m2, and most participants were white (49.1%) or African American (39.5%); 18% reported having hypertension, 7.1% had diabetes, and 6.1% were current smokers. The majority reported occasional leg pain (72.7%) and evening leg swelling (42.3%). Only 2.7% used daily compression stockings. Clinical evidence of CVI was present in at least one leg in 69.1% (C1, 49.0%; C2, 17.7%; C3, 1.9%; C4, 0.2%; C5, 0.2%). Venous reflux was present in at least one leg in 82.1%; obstruction was rare (0.2%). Reflux in either the superficial (saphenofemoral junction) or the deep (femoral or popliteal) venous system was present in the majority (71.0%) of patients with CVI (clinical class ≥C1). Reflux and white race were risk factors for clinical disease; clinical disease, age, female sex, and white race were risk factors for reflux. On the basis of the Caprini score, 14.1% of participants were in the highest risk category for DVT when experiencing a high-risk situation (including 2.2% with history of DVT). CONCLUSIONS: Prevalence of clinical CVI and venous reflux is high among health care workers despite a low frequency of cardiovascular comorbidities. Increased awareness about CVI and DVT and preventive strategies for venous disease must be instituted in this high-risk cohort.