http://repub.eur.nl/res/aut/41916/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37500/ 2012-10-11T00:00:00Z Intraplaque neovascularization is considered as an important indication for plaque vulnerability. We propose a semiautomatic algorithm for quantification of neovasculature, thus, enabling assessment of plaque vulnerability. The algorithm detects and tracks contrast spots using multidimensional dynamic programming. Classification of contrast tracks into blood vessels and artifacts was performed. The results were compared with manual tracking, visual classification and maximal intensity projection. In 28 plaques, 97% of the contrast spots were detected. In 89% of the objects, the automatic tracking determined the contrast motion with an average distance of less than 0.5 mm from the manual marking. Furthermore, 75% were correctly classified into artifacts and vessels. The automated neovascularization grading agreed within 1 grade with visual analysis in 91% of the cases, which was comparable to the interobserver variability of visual grading. These results show that the method can successfully quantify features that are linked to vulnerability of the carotid plaque. http://repub.eur.nl/res/pub/28712/ 2010-07-01T00:00:00Z Proliferation of the adventitial vasa vasorum (VV) is inherently linked with early atherosclerotic plaque development and vulnerability. Recently, direct visualization of arterial VV and intraplaque neovascularization has emerged as a new surrogate marker for the early detection of atherosclerotic disease. This clinical review focuses on contrast-enhanced ultrasound (CEUS) as a noninvasive application for identifying and quantifying carotid and coronary artery VV and intraplaque neovascularization. These novel approaches could potentially impact the clinician's ability to identify individuals with premature cardiovascular disease who are at high risk. Once clinically validated, the uses of CEUS may provide a method to noninvasively monitor therapeutic interventions. In the future, the therapeutic use of CEUS may include ultrasound-directed, site-specific therapies using microbubbles as vehicles for drug and gene delivery systems. The combined applications for diagnosis and therapy provide unique opportunities for clinicians to image and direct therapy for individuals with vulnerable lesions. http://repub.eur.nl/res/pub/32406/ 2008-06-01T00:00:00Z Rationale: In acute inflammatory lung disease in newborn infants, exogenous surfactant only transiently improves lung function. We hypothesized that the transient nature of this protection is in part explained by elevated acid sphingomyelinase (a-SMase) activity that may inactivate surfactant and promote proinflammatory responses. Objectives: We investigated the intermediate-term effects (>12 h) of a-SMase inhibition in a neonatal piglet model of repeated airway lavage by the intratracheal use of the a-SMase inhibitor imipramine, together with exogenous surfactant as a carrier substance. Methods: After surfactant washout and induction of pulmonary inflammation, lung function was monitored over 24 hours of mechanical ventilation and followed by ex vivo analyses. In addition, we studied the effect of lipopolysaccharide inhalation in a-SMase-deficient mice at 48 hours. Measurements and Main Results: Surfactant washout increased both pulmonary a-SMase activity and ceramide content; this was attenuated by surfactant and prevented in the surfactant plus imipramine group. Compared with surfactant alone, PaO2, dynamic compliance, and extravascular lung water were improved in the final 12 hours in the surfactant plus imipramine group. At 24 hours, lavage fluid leukocyte counts and IL-8 concentrations decreased, and physical surfactant film properties improved. In the mouse model at 48 hours, a-SMase-deficient mice showed reduced pulmonary ceramide levels and attenuated leukocyte influx into the alveolar space. Conclusions: We conclude that stabilization of exogenous surfactant by adding imipramine to create a "fortified surfactant preparation" improves lung function in a clinically relevant piglet model, and that this effect can be attributed to the inhibition of a-SMase as evidenced in the mouse model.