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    <title>Knaapen, M.W.</title>
    <link>http://repub.eur.nl/res/aut/15858/</link>
    <description>List of Publications</description>
    <language>en</language>
    <image>
      <url>http://repub.eur.nl/static-eur/img/logo.png</url>
      <title>RePub, Erasmus University Rotterdam</title>
      <link>http://repub.eur.nl</link>
    </image>
    <item>
      <title>Lumen enhancement influences absolute noncalcific plaque density on multislice computed tomography coronary angiography: Ex-vivo validation and in-vivo demonstration (Article)</title>
      <link>http://repub.eur.nl/res/pub/28531/</link>
      <pubDate>2010-05-01T00:00:00Z</pubDate>
      <description>Aim: The purpose of this study was to define the in-vitro and in-vivo effects of intracoronary enhancement on the absolute density values of coronary plaques during multislice computed tomography. Methods: We studied seven ex-vivo left coronary artery specimens surrounded by olive oil and filled with isotonic saline and four solutions with decreasing dilutions of contrast material: control (isotonic saline), 1/200, 1/80, 1/50, and 1/20. The multislice computed tomography protocol was: slice/collimation 32 × 2 × 0.6 mm and rotation time 330 ms. The attenuation (Hounsfield units) value of atherosclerotic plaques was measured for each dilution in lumen, plaque (noncalcified coronary wall thickening), calcium, and surrounding oil. In-vivo assessment was performed in 12 patients (nine men; mean age 58.7 ± 9.9 years) who underwent two subsequent multislice computed tomography scans (arterial and delayed) after intravenous administration of a single bolus of contrast material. The attenuation values of lumen and plaques during arterial and delayed computed tomography were compared. The results were compared with one-way analysis of variance and correlated with Pearson's test. Results: Mean lumen (45 ± 38-669 ± 151 HU) and plaque (11 ± 35-101 ± 72 HU) attenuation differed significantly (P &lt; 0.001) among the different dilutions. The attenuation of lumen and plaque of coronary plaques showed moderate correlation (r = 0.54, P &lt; 0.001). The mean attenuation value in vivo for the arterial and delayed phase scans differed significantly (P &lt; 0.001) for lumen (325 ± 70 and 174 ± 46 HU, respectively) and plaque (138 ± 71 and 100 ± 52 HU, respectively). Conclusion: Coronary plaque attenuation values are significantly modified by differences in lumen contrast densities both ex vivo and in vivo. This should be taken into account when considering the distinction between lipid and fibrous plaques. </description>
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      <title>A histological "Fly-Through" of a diseased coronary artery (Article)</title>
      <link>http://repub.eur.nl/res/pub/25278/</link>
      <pubDate>2009-03-01T00:00:00Z</pubDate>
      <description></description>
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      <title>Three-dimensional and quantitative analysis of atherosclerotic plaque composition by automated differential echogenicity (Article)</title>
      <link>http://repub.eur.nl/res/pub/36954/</link>
      <pubDate>2007-12-01T00:00:00Z</pubDate>
      <description>Objective: To validate automated and quantitative three-dimensional analysis of coronary plaque composition using intracoronary ultrasound (ICUS). Background: ICUS displays different tissue components based on their acoustic properties in 256 grey-levels. We hypothesised that computer-assisted image analysis (differential echogenicity) would permit automated quantification of several tissue components in atherosclerotic plaques. Methods and Results: Ten 40-mm-long left anterior descending specimens were excised during autopsy of which eight could be successfully imaged by ICUS. Histological sections were taken at 5 mm intervals and analyzed. Since most of the plaques were calcified and having a homogeneous appearance, one specimen with a more heterogeneous composition was further examined: at each interval of 5 mm, 15 additional sections (every 100 μm) were evaluated. Plaques were scored for echogenicity against the adventitia: brighter (hyperechogenic) or less bright (hypoechogenic). Areas of hypoechogenicity correlated with the presence of smooth muscle cells. Areas of hyperechogenicity correlated with presence of collagen, and areas of hyperechogenicity with acoustic shadowing correlated with calcium. None of these comparisons showed statistical significant differences. Conclusion: This ex vivo feasibility study shows that automated three-dimensional differential echogenicity analysis of ICUS images allows identification of different tissue types within atherosclerotic plaques. This technology may play a role as an additional tool in longitudinal studies to trace possible changes in plaque composition. </description>
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      <title>Influence of convolution filtering on coronary plaque attenuation values: Observations in an ex vivo model of multislice computed tomography coronary angiography (Article)</title>
      <link>http://repub.eur.nl/res/pub/36441/</link>
      <pubDate>2007-07-01T00:00:00Z</pubDate>
      <description>Attenuation variability (measured in Hounsfield Units, HU) of human coronary plaques using multislice computed tomography (MSCT) was evaluated in an ex vivo model with increasing convolution kernels. MSCT was performed in seven ex vivo left coronary arteries sunk into oil followingthe instillation of saline (1/∞) and a 1/50 solution of contrast material (400 mgI/ml iomeprol). Scan parameters were: slices/ collimation, 16/0.75 mm; rotation time, 375 ms. Four convolution kernels were used: b30f-smooth, b36f-medium smooth, b46f-medium and b60f-sharp. An experienced radiologist scored for the presence of plaques and measured the attenuation in lumen, calcified and noncalcified plaques and the surrounding oil. The results were compared by the ANOVA test and correlated with Pearson's test. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The mean attenuation values were significantly different between the four filters (p&lt;0.0001) in each structure with both solutions. After clustering for the filter, all of the noncalcified plaque values (20.8±39.1, 14.2±35.8, 14.0±32.0, 3.2±32.4 HU with saline; 74.7±66.6, 68.2±63.3, 66.3±66.5, 48.5±60.0 HU in contrast solution) were significantly different, with the exception of the pair b36f-b46f, for which a moderate-high correlation was generally found. Improved SNRs and CNRs were achieved by b30f and b46f. The use of different convolution filters significantly modifief the attenuation values, while sharper filtering increased the calcified plaque attenuation and reduced the noncalcified plaque attenuation. </description>
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      <title>In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity. (Article)</title>
      <link>http://repub.eur.nl/res/pub/13907/</link>
      <pubDate>2005-10-01T00:00:00Z</pubDate>
      <description>AIMS: Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation. METHODS AND RESULTS: Plaques were experimentally induced in rabbit (n=11) aortas, and at the day of sacrifice, a pull-back was performed with a thermography catheter. Hot (n=10), cold (n=10), and reference (n=11) regions were dissected and analysed for smooth muscle cell (SMC), lipids (L), collagen (COL), and macrophage (MPhi) cell densities (%); a vulnerability index (VI) was calculated as VI=MPhi+L/(SMC+COL). In addition, accumulation and activity of MMP-2 and MMP-9 were determined with zymography. Ten hot regions were identified with an average temperature of 0.40+/-0.03 degrees C (P&lt;0.05 vs. reference) and 10 cold regions with 0.07+/-0.03 degrees C (P&lt;0.05 vs. hot). In the hot regions, a higher macrophage density (173%), less SMC density (77%), and a higher VI (100%) were identified. In addition, MMP-9 (673%) activity was increased. A detailed regression analysis revealed that MMP-9 predicted hot regions better than macrophage accumulation alone. CONCLUSION: In vivo temperature measurements enable to detect plaques that contain more macrophages, less SMCs, and a higher MMP-9 activity.</description>
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      <title>Intravascular thermography: Immediate functional and morphological vascular findings (Article)</title>
      <link>http://repub.eur.nl/res/pub/10291/</link>
      <pubDate>2004-01-01T00:00:00Z</pubDate>
      <description>AIMS: To investigate safety, feasibility, and injurious effect on endothelial cells of a thermography catheter as well as effect of flow on measured temperature in non-obstructive arteries. METHODS AND RESULTS: Safety and feasibility were tested in both rabbit aortas and pig coronary arteries. Evaluation of endothelial damage by the catheter (acute, 7 and 14 days) was performed in pig coronaries using Evans Blue, scanning electron microscopy (SEM) and Factor-VIII antibody and compared with normal arteries and arteries that underwent intravascular ultrasound (IVUS). The effect of flow on temperature heterogeneity was analysed both in vitro and in vivo conditions. All procedures were successful without any adverse events; intra- and inter-operator variability was low. Intracoronary use of the catheter was associated with acute but reversible de-endothelialization, paralleling the findings associated with IVUS use. Changes in flow velocities under physiologic flow conditions did not significantly influence the temperature differences measured both in vitro and in vivo; temperature heterogeneity was more pronounced in absence of flow. CONCLUSIONS: Intracoronary thermography using a dedicated catheter is safe and feasible with a similar degree of de-endothelialization as IVUS. Temperature heterogeneity remained unchanged under normal physiologic flow conditions allowing clinical use of thermography.</description>
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      <title>Augmentation of wall shear stress inhibits neointimal hyperplasia after stent implantation: inhibition through reduction of inflammation? (Article)</title>
      <link>http://repub.eur.nl/res/pub/13158/</link>
      <pubDate>2003-01-01T00:00:00Z</pubDate>
      <description>BACKGROUND: Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent. METHODS AND RESULTS: In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries (1 stent per vessel). Lumen diameters were measured by quantitative angiography before and after implantation and at 4-week follow-up, at which time, macrophage accumulation and interruption of the internal elastic lamina was determined. Cross sections of stent segments within the ARED (S+ARED), outside the ARED (S[minus]ARED), and in corresponding segments of the contralateral control stent (SCTRL) were analyzed. Changes in WSS induced by the ARED placement were derived by computational fluid dynamics. Computational fluid dynamics analysis demonstrated that WSS increased from 0.38 to 0.82 N/m2 in the S+ARED immediately after ARED placement. This augmentation of shear stress was accompanied by (1) lower mean late luminal loss by quantitative angiography ([minus]0.23+/-0.22 versus [minus]0.58+/-0.30 mm, P=0.02), (2) reduction in NH (1.48+/-0.58, 2.46+/-1.25, and 2.36+/-1.13 mm2, P&lt;0.01, respectively, for S+ARED, S[minus]ARED, and SCTRL), and (3) a reduced inflammation score and a reduced injury score. Increments in shear stress did not change the relationship between injury score and NH or between inflammation score and NH. CONCLUSIONS: The newly developed ARED flow divider significantly increases WSS, and this local increment in WSS is accompanied by a local reduction in NH and a local reduction in inflammation and injury. The present study is therefore the first to provide direct evidence for an important modulating role of shear stress in in-stent neointimal hyperplasia.</description>
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