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P6 IDENTIFICATION AND CHARACTERIZATION OF CORONARY PLAQUES WITH CT VIRTUAL INTRAVASCULAR ENDOSCOPY: A PICTORIAL REVIEW
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Atherosclerosis Supplements 11, no. 2 (2010) 17–108
P5 COMMON CAROTID INTIMA MEDIA THICKNESS IS INDEPENDENTLY ASSOCIATED WITH PERIPHERAL ARTERIAL DISEASE IN UK 1ST GENERATION ASIAN AND BLACK MIGRANTS P. Bennett1 , S. Silverman2 , P. Gill3 , G. Lip1 . 1 Centre for Cardiovascular Sciences, University of Birmingham, 2 Department of Vascular Surgery, Sandwell & West Birmingham Hospitals NHS Trust, 3 School of Health & Population Sciences, University of Birmingham, Birmingham, UK Introduction: Little is known about common carotid intima media thickness (CCIMT) and its relationship to peripheral arterial disease (PAD) in Black and Indian subcontinent (Asian) 1st generation UK migrants. We compared CCIMT between these ethnic groups and its association with PAD. Methods: 293 Asian and 199 Black participants aged45 were recruited. Mean and maximum CCIMT was measured. PAD was diagnosed using ankle brachial pressure index < 0.9 and Intermittent Claudication (IC) using the Edinburgh Claudication Questionnaire. Results: Black participants had greater mean but not maximum, CCIMT than Asians in both men (0.67±0.14 mm vs. 0.63±0.14 mm; p = 0.04) and women (0.61±0.13 mm vs. 0.58±0.12 mm; p = 0.044). Black race was an independent predictor of both mean (p = 0.02) and maximum (p = 0.036) CCIMT after adjustment for cardiovascular risk factors. In Asians and Blacks, mean and maximum CCIMT were significantly greater in those with PAD than without (p < 0.05), independent of traditional cardiovascular risk factors. Asians with IC had higher mean and maximum CCIMT than those without (0.82±0.14 vs. 0.61±0.13 mm; p = 0.054 and 0.96±0.17 vs.0.73±0.16 mm p = 0.073 respectively) though this was not significant. Conclusions: Being Black is an independent predictor of mean and maximum CCIMT adjusting for traditional risk factors. PAD is an independent predictor of both mean and maximum CCIMT adjusting for traditional risk factors and racial group. P6 IDENTIFICATION AND CHARACTERIZATION OF CORONARY PLAQUES WITH CT VIRTUAL INTRAVASCULAR ENDOSCOPY: A PICTORIAL REVIEW T. Chaichana, Z. Sun. Imaging and Applied Physics, Curtin University of Technology, Perth, WA, Australia Purpose: To identify and characterize the coronary plaques, as well as the position of the plaques in relation to the coronary ostium using multislice CT virtual intravascular endoscopy (VIE). Materials and Methods: 20 patients suspected of coronary artery disease undergoing 64-slice CT angiography were included in the study. 3D VIE images were reconstructed to visualise the intraluminal appearance of normal coronary wall, coronary plaques in terms of characterization, location and degree of stenosis. Coronary plaques were characterized into non-calcified, calcified and mixed plaques. Results: VIE was successfully generated in all of the patients with clear demonstration of the spectrum of intraluminal findings of coronary plaques. Regular and smooth intraluminal appearance was commonly seen with VIE in non-calcified and focally calcified plaques, while irregular luminal changes were noticed in the extensively calcified and mixed plaques. VIE is able to accurately confirm the degree of coronary stenosis without being affected by the blooming artifacts resulting from severe calcification. Conclusion: VIE provides unique information about intraluminal changes due to presence of coronary plaques. Research findings from this study will provide additional information compared to conventional views, and so accurate assessment of coronary plaques with regard to corresponding coronary luminal changes and prediction of disease progression could be achieved. P7 MAGNETIC RESONANCE IMAGING OF HIGH RISK ATHEROSCLEROTIC PLAQUES USING GADOFLUORINE M IN A HYPERLIPIDEMIC ANIMAL MODEL AT 3 T H. Ittrich1 , T. Nielsen2 , K. Peldschus1 , S. Tobias3 , B. Misselwitz4 , H.-J. Weinmann4 , C. Weber1 , G. Adam1 . 1 Dept. of Diagnostic and Interventional Radiology, University Hospital Hamburg-Eppendorf, 2 Sector Medical Imaging Systems, Philips Research Europe, Hamburg, Germany, 3 Division of Imaging Sciences, School of Medicine, King’s College London, London, UK, 4 Research Laboratories, Bayer Schering Pharma AG, Berlin, Germany Purpose: To evaluate the plaque-enhancing potential, to find the lowest administration dose and to quantify the uptake of Gadofluorine M (GdF) in atherosclerotic plaques in an animal model in MRI at 3T. Material and Methods: The aorta of 12 Watanabe heritable hyperlipidemic (WHHL) and 8 New Zealand White rabbits (NZW, control) was estimated before and after administration (pa) of GdF (4 groups, injection dosages: 100, 50, 25, 12.5 mmol GdF/kg b.w.) in a 3T clinical MRI scanner (Philips Intera) using a 3D IR-TurboFLASH sequence and T1 relaxation Look-Locker (LL) − sequence. Aortic GdF uptake was quantified by SNR measurements. T1 relaxation data analyses were performed using a software tool (Philips Research Labs, Germany). The plaque burden of matched aortic regions was assessed
Poster Presentations
histologically (HE, macrophage antibody RAM11). Statistical differences were tested by student’s t-test. Results: Aortic wall enhancement was detected in WHHL after administration of 100, 50 and 25 mmol GdF (p < 0.05). No significant uptake was found in WHHL of the 12.5 mmol group and all NZW animals (p > 0.05). Histological sections showed a strong correlation between contrast-enhanced aortic regions and inflammatory, lipid-rich plaques of WHHL. NZW animals demonstrated normal aortic layering without plaque formations. R1 relaxation rate (pa) in the WHHL plaques correlated strongly with administered GdF dose (R2 = 0.99), whereas no significant R1 changes were measured in NZW controls. Conclusion: Gadofluorine-enhanced MRI improves detection of early, nonstenotic stages in atherosclerosis. The LL sequence allows a quantitative determination of GdF uptake in plaques. P8 SYNTHESIS, PHYSICOCHEMICAL AND TOXICOLOGICAL CHARACTERIZATION OF 59 FE-LABELLED NANOPARTICLES FOR TARGETING ARTERIOSCLEROTIC LESIONS B. Freund1 , A. Giemsa1 , H. Ittrich2 , O. Bruns3 , U. Tromsdorf4 , J. Heeren1 , H. Weller4 , H. Hohenberg3 , G. Adam2 , U. Beisiegel1 , P. Nielsen1 . 1 Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, 2 Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg, 3 Heinrich-Pette-Institute for Experimental Virology and Immunology, 4 Institute of Physical Chemistry, University Hamburg, Hamburg, Germany Objective: The detection of early arteriosclerotic lesions remains a challenging task for future diagnostic procedures. The application of specifically designed superparamagnetic nanoparticles (SPIOS) and magnetic resonance imaging technique (MRI) could allow a molecular targeting for this important pathological process. Recent work from our laboratory (Bruns et al. Nature Nanotechnology 2009) has for example used “chylomicron-like” lipoproteins (“nanosomes”) labeled with magnetic or fluorescent nanoparticles to follow pathways of lipid metabolism in mice. One problem in MRI studies is the difficulty to relate MR signals to the unknown local concentrations of SPIOS. Methods: Following known synthetic strategies, we synthesized crystalline and monodisperse maghemite nanoparticles with a diameter of 11 nm with different hydrophobic and hydrophilic shells. Results: 59 Fe-labelling was introduced by a postsynthetic procedure. Several analytical test methods (size-exclusion chromatography, controlled digestion with iron chelators, mineral acids) demonstrated a stable labelling of the iron oxide core with 59 Fe. Pilot in-vivo experiments using hydrophilic 59 Fe-NP and 59 Fe-NP-labeled nanosomes were performed in mice after i.v. injection. Conclusions: These early results show already that with radiolabelled NPs the distribution of nanoparticles in vivo can be analyzed more precisely than before. Among the feasible applications, specific MR proton T1 and T2 relaxivities in tissue, organs and lesions from functionalized NP can be measured, and the metabolism and toxicity of iron based NPs can be followed in closer details. P9 ATHEROSCLEROTIC BURDEN IN ASYMPTOMATIC PATIENTS WITH METABOLIC SYNDROME EVALUATED BY COMPUTED TOMOGRAPHY ANGIOGRAPHY M. Arca1 , G. Pigna1 , F. Zaccagna2 , B. Cavallo Marincola2 , A. Montali1 , L. Iuliano3 , A. Napoli2 , C. Catalano2 . 1 Department of Clinical and Medical Therapy − Ctr for Atherosclerosis, 2 Department of Radiology, University of Rome La Sapienza, Rome, 3 Internal Medicine Unit − Polo Pontino, University of Rome La Sapienza, Latina, Italy Introduction: Metabolic Syndrome (MetS) heightens the risk for atherogenesis. A question is if the vascular damage is better predicted by the MetS itself or by the MetS-related risk factors. The 64-slice computed tomography angiography (64-CTA) is a useful tool for detecting atherosclerotic lesions in vivo. Methods: 64 asymptomatic subjects with MetS (46 men, 18 women; age 55±10.1 yrs; BMI 30.5±3.4) and 52 subjects without MetS (25 men, 27 women; age 59.1±8.6 yrs; BMI 25.2±3.4) underwent 64-CTA examination following a contrast medium dose-saving protocol involving ECG modulation and reduced tube voltage. The diagnosis of MetS was performed according to the ATPIII criteria. The atherosclerotic burden was defined as the presence of lesions in at least one segment of coronary and/or carotid vessels. Results: The age-adjusted prevalence of coronary (60% vs. 51% respectively; p < 0.3) and carotid (29% vs. 33%, respectively; p < 0.1) plaques was not significantly different in MetS compared to subjects without MetS. The distribution of severity of stenosis did not differ between the groups. However, when study subjects were stratified according to the number of components of MetS (<2; 2−3; 4), those presenting 4 MetS-related factors showed a significantly increased prevalence of coronary and carotid lesions compared to the other groups (44.6%, 52% 82.6%, p < 0.012 for trend). Subjects with4 MetS-related factors showed the worst metabolic profile. Conclusions: These results suggest that in MetS patients the atherosclerosis burden is more strongly associated to the number of MetS-related factors than to the clinical diagnosis of MetS per se.
Atherosclerosis Supplements 11, no. 2 (2010) 17–108
P5 COMMON CAROTID INTIMA MEDIA THICKNESS IS INDEPENDENTLY ASSOCIATED WITH PERIPHERAL ARTERIAL DISEASE IN UK 1ST GENERATION ASIAN AND BLACK MIGRANTS P. Bennett1 , S. Silverman2 , P. Gill3 , G. Lip1 . 1 Centre for Cardiovascular Sciences, University of Birmingham, 2 Department of Vascular Surgery, Sandwell & West Birmingham Hospitals NHS Trust, 3 School of Health & Population Sciences, University of Birmingham, Birmingham, UK Introduction: Little is known about common carotid intima media thickness (CCIMT) and its relationship to peripheral arterial disease (PAD) in Black and Indian subcontinent (Asian) 1st generation UK migrants. We compared CCIMT between these ethnic groups and its association with PAD. Methods: 293 Asian and 199 Black participants aged45 were recruited. Mean and maximum CCIMT was measured. PAD was diagnosed using ankle brachial pressure index < 0.9 and Intermittent Claudication (IC) using the Edinburgh Claudication Questionnaire. Results: Black participants had greater mean but not maximum, CCIMT than Asians in both men (0.67±0.14 mm vs. 0.63±0.14 mm; p = 0.04) and women (0.61±0.13 mm vs. 0.58±0.12 mm; p = 0.044). Black race was an independent predictor of both mean (p = 0.02) and maximum (p = 0.036) CCIMT after adjustment for cardiovascular risk factors. In Asians and Blacks, mean and maximum CCIMT were significantly greater in those with PAD than without (p < 0.05), independent of traditional cardiovascular risk factors. Asians with IC had higher mean and maximum CCIMT than those without (0.82±0.14 vs. 0.61±0.13 mm; p = 0.054 and 0.96±0.17 vs.0.73±0.16 mm p = 0.073 respectively) though this was not significant. Conclusions: Being Black is an independent predictor of mean and maximum CCIMT adjusting for traditional risk factors. PAD is an independent predictor of both mean and maximum CCIMT adjusting for traditional risk factors and racial group. P6 IDENTIFICATION AND CHARACTERIZATION OF CORONARY PLAQUES WITH CT VIRTUAL INTRAVASCULAR ENDOSCOPY: A PICTORIAL REVIEW T. Chaichana, Z. Sun. Imaging and Applied Physics, Curtin University of Technology, Perth, WA, Australia Purpose: To identify and characterize the coronary plaques, as well as the position of the plaques in relation to the coronary ostium using multislice CT virtual intravascular endoscopy (VIE). Materials and Methods: 20 patients suspected of coronary artery disease undergoing 64-slice CT angiography were included in the study. 3D VIE images were reconstructed to visualise the intraluminal appearance of normal coronary wall, coronary plaques in terms of characterization, location and degree of stenosis. Coronary plaques were characterized into non-calcified, calcified and mixed plaques. Results: VIE was successfully generated in all of the patients with clear demonstration of the spectrum of intraluminal findings of coronary plaques. Regular and smooth intraluminal appearance was commonly seen with VIE in non-calcified and focally calcified plaques, while irregular luminal changes were noticed in the extensively calcified and mixed plaques. VIE is able to accurately confirm the degree of coronary stenosis without being affected by the blooming artifacts resulting from severe calcification. Conclusion: VIE provides unique information about intraluminal changes due to presence of coronary plaques. Research findings from this study will provide additional information compared to conventional views, and so accurate assessment of coronary plaques with regard to corresponding coronary luminal changes and prediction of disease progression could be achieved. P7 MAGNETIC RESONANCE IMAGING OF HIGH RISK ATHEROSCLEROTIC PLAQUES USING GADOFLUORINE M IN A HYPERLIPIDEMIC ANIMAL MODEL AT 3 T H. Ittrich1 , T. Nielsen2 , K. Peldschus1 , S. Tobias3 , B. Misselwitz4 , H.-J. Weinmann4 , C. Weber1 , G. Adam1 . 1 Dept. of Diagnostic and Interventional Radiology, University Hospital Hamburg-Eppendorf, 2 Sector Medical Imaging Systems, Philips Research Europe, Hamburg, Germany, 3 Division of Imaging Sciences, School of Medicine, King’s College London, London, UK, 4 Research Laboratories, Bayer Schering Pharma AG, Berlin, Germany Purpose: To evaluate the plaque-enhancing potential, to find the lowest administration dose and to quantify the uptake of Gadofluorine M (GdF) in atherosclerotic plaques in an animal model in MRI at 3T. Material and Methods: The aorta of 12 Watanabe heritable hyperlipidemic (WHHL) and 8 New Zealand White rabbits (NZW, control) was estimated before and after administration (pa) of GdF (4 groups, injection dosages: 100, 50, 25, 12.5 mmol GdF/kg b.w.) in a 3T clinical MRI scanner (Philips Intera) using a 3D IR-TurboFLASH sequence and T1 relaxation Look-Locker (LL) − sequence. Aortic GdF uptake was quantified by SNR measurements. T1 relaxation data analyses were performed using a software tool (Philips Research Labs, Germany). The plaque burden of matched aortic regions was assessed
Poster Presentations
histologically (HE, macrophage antibody RAM11). Statistical differences were tested by student’s t-test. Results: Aortic wall enhancement was detected in WHHL after administration of 100, 50 and 25 mmol GdF (p < 0.05). No significant uptake was found in WHHL of the 12.5 mmol group and all NZW animals (p > 0.05). Histological sections showed a strong correlation between contrast-enhanced aortic regions and inflammatory, lipid-rich plaques of WHHL. NZW animals demonstrated normal aortic layering without plaque formations. R1 relaxation rate (pa) in the WHHL plaques correlated strongly with administered GdF dose (R2 = 0.99), whereas no significant R1 changes were measured in NZW controls. Conclusion: Gadofluorine-enhanced MRI improves detection of early, nonstenotic stages in atherosclerosis. The LL sequence allows a quantitative determination of GdF uptake in plaques. P8 SYNTHESIS, PHYSICOCHEMICAL AND TOXICOLOGICAL CHARACTERIZATION OF 59 FE-LABELLED NANOPARTICLES FOR TARGETING ARTERIOSCLEROTIC LESIONS B. Freund1 , A. Giemsa1 , H. Ittrich2 , O. Bruns3 , U. Tromsdorf4 , J. Heeren1 , H. Weller4 , H. Hohenberg3 , G. Adam2 , U. Beisiegel1 , P. Nielsen1 . 1 Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, 2 Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg, 3 Heinrich-Pette-Institute for Experimental Virology and Immunology, 4 Institute of Physical Chemistry, University Hamburg, Hamburg, Germany Objective: The detection of early arteriosclerotic lesions remains a challenging task for future diagnostic procedures. The application of specifically designed superparamagnetic nanoparticles (SPIOS) and magnetic resonance imaging technique (MRI) could allow a molecular targeting for this important pathological process. Recent work from our laboratory (Bruns et al. Nature Nanotechnology 2009) has for example used “chylomicron-like” lipoproteins (“nanosomes”) labeled with magnetic or fluorescent nanoparticles to follow pathways of lipid metabolism in mice. One problem in MRI studies is the difficulty to relate MR signals to the unknown local concentrations of SPIOS. Methods: Following known synthetic strategies, we synthesized crystalline and monodisperse maghemite nanoparticles with a diameter of 11 nm with different hydrophobic and hydrophilic shells. Results: 59 Fe-labelling was introduced by a postsynthetic procedure. Several analytical test methods (size-exclusion chromatography, controlled digestion with iron chelators, mineral acids) demonstrated a stable labelling of the iron oxide core with 59 Fe. Pilot in-vivo experiments using hydrophilic 59 Fe-NP and 59 Fe-NP-labeled nanosomes were performed in mice after i.v. injection. Conclusions: These early results show already that with radiolabelled NPs the distribution of nanoparticles in vivo can be analyzed more precisely than before. Among the feasible applications, specific MR proton T1 and T2 relaxivities in tissue, organs and lesions from functionalized NP can be measured, and the metabolism and toxicity of iron based NPs can be followed in closer details. P9 ATHEROSCLEROTIC BURDEN IN ASYMPTOMATIC PATIENTS WITH METABOLIC SYNDROME EVALUATED BY COMPUTED TOMOGRAPHY ANGIOGRAPHY M. Arca1 , G. Pigna1 , F. Zaccagna2 , B. Cavallo Marincola2 , A. Montali1 , L. Iuliano3 , A. Napoli2 , C. Catalano2 . 1 Department of Clinical and Medical Therapy − Ctr for Atherosclerosis, 2 Department of Radiology, University of Rome La Sapienza, Rome, 3 Internal Medicine Unit − Polo Pontino, University of Rome La Sapienza, Latina, Italy Introduction: Metabolic Syndrome (MetS) heightens the risk for atherogenesis. A question is if the vascular damage is better predicted by the MetS itself or by the MetS-related risk factors. The 64-slice computed tomography angiography (64-CTA) is a useful tool for detecting atherosclerotic lesions in vivo. Methods: 64 asymptomatic subjects with MetS (46 men, 18 women; age 55±10.1 yrs; BMI 30.5±3.4) and 52 subjects without MetS (25 men, 27 women; age 59.1±8.6 yrs; BMI 25.2±3.4) underwent 64-CTA examination following a contrast medium dose-saving protocol involving ECG modulation and reduced tube voltage. The diagnosis of MetS was performed according to the ATPIII criteria. The atherosclerotic burden was defined as the presence of lesions in at least one segment of coronary and/or carotid vessels. Results: The age-adjusted prevalence of coronary (60% vs. 51% respectively; p < 0.3) and carotid (29% vs. 33%, respectively; p < 0.1) plaques was not significantly different in MetS compared to subjects without MetS. The distribution of severity of stenosis did not differ between the groups. However, when study subjects were stratified according to the number of components of MetS (<2; 2−3; 4), those presenting 4 MetS-related factors showed a significantly increased prevalence of coronary and carotid lesions compared to the other groups (44.6%, 52% 82.6%, p < 0.012 for trend). Subjects with4 MetS-related factors showed the worst metabolic profile. Conclusions: These results suggest that in MetS patients the atherosclerosis burden is more strongly associated to the number of MetS-related factors than to the clinical diagnosis of MetS per se.