Citations

BACKGROUND: This study aimed to develop and validate a computed tomography angiography based machine learning model that uses plaque composition data and degree of carotid stenosis to detect symptomatic carotid plaques in patients with carotid atherosclerosis. METHODS: The machine learning based model was trained using degree of stenosis and the volumes of 13 computed tomography angiography derived intracarotid plaque subcomponents (eg, lipid, intraplaque hemorrhage, calcium) to identify plaques associated with cerebrovascular events. The model was internally validated through repeated 10-fold cross-validation and tested on a dedicated testing cohort according to discrimination and calibration. RESULTS: This retrospective, single-center study evaluated computed tomography angiography scans of 268 patients with both symptomatic and asymptomatic carotid atherosclerosis (163 for the derivation set and 106 for the testing set) performed between March 2013 and October 2019. The area-under-receiver-operating characteristics curve by machine learning on the testing cohort (0.89) was significantly higher than the areas under the curve of traditional logit analysis based on the degree of stenosis (0.51, P <0.001), presence of intraplaque hemorrhage (0.69, P <0.001), and plaque composition (0.78, P <0.001), respectively. Comparable performance was obtained on internal validation. The identified plaque components and associated cutoff values that were significantly associated with a higher likelihood of symptomatic status after adjustment were the ratio of intraplaque hemorrhage to lipid volume (≥50%, 38.5 [10.1–205.1]; odds ratio, 95% CI) and percentage of intraplaque hemorrhage volume (≥10%, 18.5 [5.7–69.4]; odds ratio, 95% CI). CONCLUSIONS: This study presented an interpretable machine learning model that accurately identifies symptomatic carotid plaques using computed tomography angiography derived plaque composition features, aiding clinical decision-making.

Introduction In the current paper, the “carotid artery calcium score” method is presented with the target to offer a metric method to quantify the amount of calcification in the carotid artery. Model and Definition The Volume of Interest (VOI) should be extracted and those voxels, with a Hounsfield Unit (HU) value ≥130, should be considered. The total weight value is determined by calculating the sum of the HU attenuation values of all voxels with values ≥130 HU. This value should be multiplied by the conversion factor (“or voxel size”) and divided by a weighting factor, the attenuation threshold to consider a voxel as calcified (and therefore 130 HU): this equation determines the Carotid Artery Calcium Score (CACS). Results In order to provide the demonstration of the potential feasibility of the model, the CACS was calculated in 131 subjects (94 males; mean age 72.7 years) for 235 carotid arteries (in 27 subjects, unilateral plaque was present) considered. The CACS value ranged from 0.67 to 11716. A statistically significant correlation was found (rho value = 0.663, p value = .0001) between the CACS in the right and left carotid plaques. Moreover, a statistically significant correlation between the age and the total CACS was present (rho value = 0.244, p value = .005), whereas no statistically significant difference was found in the distribution of CACS by gender ( p = .148). The CACS was also tested at baseline and after contrast and no statistically significant difference was found. Conclusion In conclusion, this method is of easy application, and it weights at the same time the volume and the degree of calcification in a unique parameter. This method needs to be tested to verify its potential utility, similar to the coronary artery calcium score, for the risk stratification of the occurrence of cerebrovascular events of the anterior circulation. Further studies using this new diagnostic tool to determine the prognostic value of carotid calcium quantification are needed.

Introduction: Diabetes mellitus and insulin resistance are associated with accelerated vascular injury and progression of coronary atherosclerosis. CD34 + progenitor cells are mobilized and recruited to repair the endothelial and vascular damage. Hypothesis: We hypothesized that the interaction of insulin levels and retention of CD34+ progenitors in the coronary arteries will be different between patients with and without insulin resistance. Methods: In patients with no obstructive coronary artery disease (NOCAD: <40% angiographic stenosis), blood samples were collected concurrently from the proximal aorta and the coronary sinus, and CD34+ cells counted using flow cytometry. CD34+ cells gradient was calculated by subtracting aortic from coronary sinus cell counts, with a higher gradient reflecting lower retention. Patients on antidiabetic medications were excluded. Insulin resistance (IR) was estimated as HOMA-IR index ([insulin]*[glucose]/405)) ≥2. Results: Of 128 patients (mean age 51±11 years, 77% females), 60 (47%) had IR (mean age 51±10 years, 73% females) and 68 (53%) did not (mean age 50±13 years, 79% females). The groups did not differ in age, sex or LDL cholesterol. The IR group had higher BMI and triglyceride levels and lower HDL cholesterol. CD34 + cell gradient correlated directly significantly with insulin levels in patients without IR (r=0.25, p=0.04) (Fig1A) , but inversely in those with IR (r=-0.39, p=0.01) (Fig1B) . Both associations remained significant after adjustment for age, sex, and BMI (IR: r=-0.39, p=0.02; no IR: r=29, p=0.04). Conclusions: In NOCAD patients with IR, higher levels of serum insulin were associated with increased retention of CD34 + cells in the coronary arteries. The current study supports a potential role for CD34 + cells for vascular repair in patients with IR.

Coronary artery calcification (CAC) accompanies the development of advanced atherosclerosis. Its role in atherosclerosis holds great interest because the presence and burden of coronary calcification provide direct evidence of the presence and extent of coronary artery disease; furthermore, CAC predicts future events independently of concomitant conventional cardiovascular risk factors and to a greater extent than any other noninvasive biomarker of this disease. Nevertheless, the relationship between CAC and the susceptibility of a plaque to provoke a thrombotic event remains incompletely understood. This review summarizes the current understanding and literature on CAC. It outlines the pathophysiology of CAC and reviews laboratory, histopathological, and genetic studies, as well as imaging findings, to characterize different types of calcification and to elucidate their implications. Some patterns of calcification such as microcalcification portend increased risk of rupture and cardiovascular events and may improve prognosis assessment noninvasively. However, contemporary computed tomography cannot assess early microcalcification. Limited spatial resolution and blooming artifacts may hinder estimation of degree of coronary artery stenosis. Technical advances such as photon counting detectors and combination with nuclear approaches (eg, NaF imaging) promise to improve the performance of cardiac computed tomography. These innovations may speed achieving the ultimate goal of providing noninvasively specific and clinically actionable information.

Carotid artery stenosis is a major cause of morbidity and mortality. The journey to understanding carotid disease has developed over time and radiology has a pivotal role in diagnosis, risk stratification and therapeutic management. This paper reviews the history of diagnostic imaging in carotid disease, its evolution towards its current applications in the clinical and research fields, and the potential of new technologies to aid clinicians in identifying the disease and tailoring medical and surgical treatment.

Introduction: The carotid artery rim sign on CTA is characterized by soft-plaque components surrounded by a rind of thin, adventitial calcification and its role in plaque instability is not established yet. Intraplaque hemorrhage (IPH) and the inflammatory microenvironment in carotid atheroma are considered features of atherosclerotic plaque vulnerability leading to cerebrovascular events. Hypothesis: The association between rim sign on CTA and carotid IPH and inflammation remains scantly investigated. In this study, we aimed to determine whether rim sign is associated with IPH on MRA and with the extent of IPH and inflammation on histology. We hypothesized that rim sign may be a radiological predictor of carotid IPH and inflammation. Methods: We retrospectively enrolled 100 consecutive patients who underwent carotid endarterectomy (CEA) and neck CTA before CEA. On CTA, the ipsilateral rim sign was defined as the presence of adventitial calcifications with internal soft-tissue plaque of ≥2 mm in maximum thickness. Of the included patients, 25 had MRA with 3D magnetization-prepared rapid acquisition with gradient echo (MPRAGE) sequence. Carotid plaque specimens were collected and stained with H&E to quantify IPH (%). Histologically, we defined IPH as an area of carotid plaque with blood elements, and inflammatory microenvironment as the presence of lymphocytes and plasma cells (chronic inflammation) and foam cells. Results: The rim sign on CTA was present in 56 (56%) of patients. IPH on MRA was present in 11 (44%) patients. The rim sign was significantly associated with the presence of IPH on MRA [9 (81.8%) vs 2 (14.3%); p=0.003]. On histology, the rim sign was associated with a higher extent of IPH [5.0 % (IQR 2.0-25.0) vs 5.0% (IQR 0.0-10.0); p=0.017], with chronic inflammation [44 (78.6%) vs 12 (21.4%); p=0.003], and foam cells [51 (91.1%) vs 5 (8.9%); p<0.001]. Conclusions: These findings suggest that rim sign on CTA may be proposed as a potential imaging marker of IPH as well as a histologic predictor of IPH extent and carotid plaque inflammatory microenvironment.

Abstract Background Carotid intraplaque hemorrhage (IPH) is considered a strong marker of histologically defined plaque vulnerability leading to cerebrovascular ischemic events. Cerebral microbleeds (CMBs) represent hemorrhage-prone small vessel disease and they are a common finding on brain MRI in patients with cerebrovascular disease. However, the potential mechanism and the risk for CMBs are not clear. The characteristics of carotid lesions have been considered relevant in the relationship between carotid artery atherosclerosis and the presence of CMBs. The potential association between carotid IPH histologically defined and CMBs has not been investigated yet. Purpose We have previously reported the prevalence of IPH in patients with non-obstructive carotid disease in patients who underwent carotid endarterectomy (CEA). In this study, we aimed to investigate whether the presence and the extent of carotid IPH are related to the existence of CMBs. We hypothesized that patients with carotid IPH would have a higher risk of CMBs. Methods This retrospective study enrolled 101 consecutive patients undergoing CEA with symptomatic (including ischemic stroke, TIA, and amaurosis fugax) or asymptomatic ipsilateral carotid artery disease. Carotid plaque specimens were collected at CEA from all the patients and stained with Movat Pentachrome to identify the presence and the extent (%) of IPH. Neck CTA was obtained to measure the degree of carotid stenosis. Brain MRI was pre-surgically performed and CMBs were studied using T2*-weighted gradient-recalled echo (GRE) or susceptibility-weighted imaging (SWI) sequence. The CMBs were counted and localized. Clinical and biochemical data, comorbidities, and medications were recorded. The association between carotid IPH and CMBs was examined adjusted for other risk factors. Results The presence of carotid IPH was in 57 (56.4%) patients. CMBs were more observed in patients with carotid IPH compared to those without IPH [19 (33.3%) vs 5 (11.4%); p=0.010]. Logistic regression analysis demonstrated an association between the extent of IPH in the carotid atheroma and the presence of CMBs [OR 1.051 (95% CI 1.012–1.090); p=0.009]. Moreover, the carotid IPH extent was associated with the number of CMBs (p=0.004). In patients with CMBs, the median degree of ipsilateral carotid stenosis was 40% (35–65%) and it was 70% (50–80%) in those without CMBs, with a significant difference between the two groups (p=0.049). Conclusions In patients undergoing CEA, the histologically defined presence of carotid IPH and its extent are associated with CMBs on brain MR imaging. CMBs may be a potential mechanism for cerebrovascular events in patients with carotid atherosclerotic IPH and they may be an imaging marker that can distinguish the severity of the carotid artery disease. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Mayo Clinic Foundation