Echolucent Carotid Plaques Becomes More Echogenic over Time - A 3D Ultrasound Study.

BACKGROUND: Despite the presence of only a few established risk factors, some patients will experience atherosclerotic events. Therefore, methods for improved risk stratification for atherosclerotic events are wanted. We aimed to detect changes in carotid artery atherosclerotic plaque volume and echogenicity over time in patients with an acute thromboembolic event and in patients with chronic atherosclerotic disease, both treated with statin, using a novel 3D ultrasound system. METHODS: We included two cohorts of patients; 70 patients, naïve to statin treatment, admitted with acute, first-time myocardial infarction (aMI), and 69 patients who had been on statin treatment for a minimum of 6 months with chronic peripheral arterial disease (cPAD). 3D ultrasound examination was performed at baseline and after 3 and 12 months. Plaque volume was quantified in 3D ultrasound plaque acquisitions, and echogenicity was assessed using grayscale median (GSM) and normalized with adventitia as reference. RESULTS: The aMI group had darker plaques than the cPAD group at baseline (mean GSM: 60.98, standard deviation (SD): 24.09 vs. 71.75, SD: 21.55; P = 0.006), 3 months (63.64, SD: 20.47 vs. 73.44, SD: 20.46; P = 0.006) and at 12 months follow-up (59.25, SD: 18.07 vs. 71.02, SD: 22.31; P = 0.004). The differences were not significant after adjusting for traditional risk factors. Dividing both groups by the median GSM, the darkest half of the aMI group's had an increase in GSM mainly within the first 3 months (10.49, CI 95%: 2.45 to 18.53; P = 0.012) and hereafter remained unchanged at 12 months follow-up (-0.53, CI 95%: -7.28 to 6.22, P = 0.875). In the darkest cPAD group GSM also increased within 3 months (8.14, CI 95%: 1.85-14.32, P = 0.012) and hereafter stabilized till 12 months (-2.54, CI 95%: -9.62 to 4.53, P = 0.475). Plaque volume did not change in the aMI group from baseline (median: 55.41 mm3, interquartile range (IQR): 24.24-84.31) to 12 months (58.67 mm3, IQR: 31.81-93.51) (P = 0.220) whereas there was a small decrease in the cPAD group from baseline (71.63 mm3, IQR: 40.12-135.61) to 12 months (67.73 mm3, IQR: 31.00-122.38) (P = 0.026). CONCLUSIONS: Echolucent carotid plaque, assessed with the novel 3D matrix ultrasound system, had increasing GSM within 3 months period, indicating stabilization of the more vulnerable plaques in aMI and cPAD patients. Plaque volume decreased over 12 months follow-up in a long-term statin-treated patient with cPAD, but not during the first 12 months statin therapy in patients with aMI.

In vivo detection of urokinase-type plasminogen activator receptor (uPAR) expression in arterial atherogenesis using [64Cu]Cu-DOTA-AE105 positron emission tomography (PET).

BACKGROUND AND AIMS: Urokinase-type plasminogen activator receptor (uPAR) is associated with extracellular matrix (ECM) degradation and cancer aggressiveness. Its role in arterial atherogenesis as a molecular imaging target is not well-established. The aim of this study was to non-invasively visualize uPAR expression in atherosclerosis by a novel uPAR-targeting positron emission tomography (PET) tracer [64Cu]Cu-DOTA-AE105. METHODS: We used molecular biology to investigate uPAR expression by analyzing human atherosclerotic plaques and cultured cells. A retrospective analysis was performed on patients, who underwent combined PET/CT (n = 10) to measure [64Cu]Cu-DOTA-AE105 uptake in five large arteries, divided into a high and low-risk group based on coronary artery calcium score (CAC score). RESULTS: The in vitro assay for THP-1 monocytes displayed a significantly upregulated uPAR expression upon stimulation (5.2-fold upregulation, p < 0.0001 by a one-way ANOVA followed by Tukey's test) by single-cell flowcytometric analysis. Freshly excised human atherosclerotic plaques underwent flow cytometric and microarray analyses manifesting 73.9 ± 2.9% of mononuclear phagocyte system (MPS) cells expressing uPAR and had a greater than 7-fold higher gene expression of plasminogen activator urokinase receptor (PLAUR, p = 0.002), integrin subunit alpha X (ITGAX, p = 0.0008), and cluster of differentiation 163 (CD163, p < 0.0001). The tissue-to-background ratios (TBRmax) in five large arteries showed a higher [64Cu]Cu-DOTA-AE105 uptake in the group with high CAC score compared to the group with low CAC score (2.4 ± 0.1 vs 1.7 ± 0.1, p = 0.057), significantly higher in the ascending aorta (2.7 ± 0.1 vs 2.0 ± 0.1, p = 0.038) and the abdominal aorta (3.2 ± 0.2 vs 2.0 ± 0.2, p = 0.038) by a non-parametric Mann-Whitney test. CONCLUSIONS: uPAR is abundantly expressed by MPS cells in atherosclerotic plaques and can be visualized by the novel PET tracer [64Cu]Cu-DOTA-AE105 that may non-invasively detect extracellular matrix remodeling during atherogenesis.

Carotid plaque inflammatory activity assessed by 2-[18F]FDG-PET imaging decrease after a neurological thromboembolic event.

BACKGROUND: Atherosclerotic plaque vulnerability is comprised by plaque composition driven by inflammatory activity and these features can be depicted with 3D ultrasound and 2-[18F]FDG-PET, respectively. The study investigated timely changes in carotid artery plaque inflammation and morphology after a thromboembolic event with PET/CT and novel ultrasound volumetric grayscale median (GSM) readings. Patients with a single hemisphere-specific neurological symptom and the presence of an ipsilateral carotid artery atherosclerotic plaque were prospectively included to both 2-[18F]FDG PET/CT and 3D ultrasound scans of the plaque immediately after their event and again three months later. On PET/CT images the maximum standardized uptake value (SUVmax) was measured and the volumetric ultrasound acquisitions were analyzed using a semiautomated software measuring GSM values. RESULTS: Baseline scans were performed by a mean of 7 days (range 2-14) after the symptom and again after 98 days (range 91-176). For the entire group (n = 14), we found a decrease in average SUVmax from baseline to follow-up of - 0.18 (95% confidence interval: - 0.34 to - 0.02, P = 0.034). GSM did not increase significantly over time (mean change: + 2.21, 95% confidence interval: - 17.02 to 21.44, P = 0.808). CONCLUSION: A decrease in culprit lesion 2-[18F]FDG-uptake 3 months after an event indicates a decrease in inflammatory activity, suggesting that carotid plaque stabilization over time. 3D ultrasound morphological quantitative differences in GSM were not detectable after 3 months.

Patients with Unstable Atherosclerosis Have More Echolucent Carotid Plaques Compared with Stable Atherosclerotic Patients: A 3-D Ultrasound Study.

Using a novel 3-D ultrasound system, we aimed to determine differences in carotid plaque size and echogenicity in two atherosclerotic groups. Seventy patients admitted with acute myocardial infarction (aMI) and 69 patients known with chronic peripheral arterial disease (cPAD) were included. The cPAD group had larger plaque volumes (median: 70.24 mm3, interquartile range [40.12-135.61] vs. 55.41 mm3 [4.24-84.31], p = 0.004), thicker plaques (2.45 mm [1.85-3.25] vs. 1.99 mm [1.55 - 2.64], p = 0.005) and higher gray-scale medians (GSMs) (mean: 71.75, standard deviation: 21.55 vs. 60.99 [24.09], p = 0.006) than the aMI group. After adjustment for traditional risk factors, the difference persisted for thickness and volume. The difference in GSM persisted after adjustment for volume only. Patients with stable atherosclerotic disease had larger and brighter carotid plaques compared with unstable atherosclerotic patients. 3-D ultrasound may prove useful in identifying thromboembolic risk.

Catheter-Directed Thrombolysis in the Treatment of Acute Ischemia in Lower Extremities Is Safe and Effective, Especially with Concomitant Endovascular Treatment.

Objective: To evaluate the influence of pre-procedural characteristics on immediate and late results as well as the safety of catheter-directed thrombolysis (CDT) in acute ischemia of the lower extremity. Materials and Methods: A retrospective study comprising 249 patients treated by CDT from January 2006 to December 2012. Outcomes were primary patency, haemorrhagic complications, amputation and mortality. Results: Primary patency for CDT alone was 68%, for CDT plus endovascular treatment 87% and for successful CDT with supplementary surgery 62% giving an overall primary patency of 76%. Two (0.8%) patients suffered from cerebral haemorrhage during CDT. We found a significant correlation between 30 day amputation rate and no visual distal run-off at CDT start (OR 2.31; CI95% 1.09-4.91; p-value=0.02) and onset of symptoms to CDT start of 8-14 days (OR 4.09; CI95% 1.42-11.81; p-value=0.01). Lack of visualized distal run-off was also associated with a significant risk of 30 day mortality (OR 5.84; CI95% 1.26-27.00; p-value=0.02). Conclusion: Our results show that CDT is a feasible and safe treatment option especially when combined with angioplasty +/- stent. However, no distal run-off at primary angiography is associated with higher rates of amputation during follow-up and 30 day mortality.

Heat shock proteins in the human eye.

Heat shock proteins (Hsps) are believed to primarily protect and maintain cell viability under stressful conditions such as those occurring during thermal and oxidative challenges chiefly by refolding and stabilizing proteins. Hsps are found throughout the various tissues of the eye where they are thought to confer protection from disease states such as cataract, glaucoma, and cancer. This minireview summarizes the placement, properties, and roles of Hsps in the eye and aims to provide a better comprehension of their function and involvement in ocular disease pathogenesis.