Dieter Dauwe
Katholieke Universiteit Leuven
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Publication
Featured researches published by Dieter Dauwe.
Journal of the American Heart Association | 2016
Dieter Dauwe; Beatriz Pelacho; Arief Wibowo; Ann-Sophie Walravens; Kristoff Verdonck; Hilde Gillijns; Ellen Caluwé; Peter Pokreisz; Nick van Gastel; Geert Carmeliet; Maarten Depypere; Frederik Maes; Nina Vanden Driessche; Walter Droogne; Johan Van Cleemput; Johan Vanhaecke; Felipe Prosper; Catherine M. Verfaillie; Aernout Luttun; Stefan Janssens
Background Blood outgrowth endothelial cells (BOECs) mediate therapeutic neovascularization in experimental models, but outgrowth characteristics and functionality of BOECs from patients with ischemic cardiomyopathy (ICMP) are unknown. We compared outgrowth efficiency and in vitro and in vivo functionality of BOECs derived from ICMP with BOECs from age‐matched (ACON) and healthy young (CON) controls. Methods and Results We isolated 3.6±0.6 BOEC colonies/100×106 mononuclear cells (MNCs) from 60‐mL blood samples of ICMP patients (n=45; age: 66±1 years; LVEF: 31±2%) versus 3.5±0.9 colonies/100×106 MNCs in ACON (n=32; age: 60±1 years) and 2.6±0.4 colonies/100×106 MNCs in CON (n=55; age: 34±1 years), P=0.29. Endothelial lineage (VEGFR2+/CD31+/CD146+) and progenitor (CD34+/CD133−) marker expression was comparable in ICMP and CON. Growth kinetics were similar between groups (P=0.38) and not affected by left ventricular systolic dysfunction, maladaptive remodeling, or presence of cardiovascular risk factors in ICMP patients. In vitro neovascularization potential, assessed by network remodeling on Matrigel and three‐dimensional spheroid sprouting, did not differ in ICMP from (A)CON. Secretome analysis showed a marked proangiogenic profile, with highest release of angiopoietin‐2 (1.4±0.3×105 pg/106 ICMP‐BOECs) and placental growth factor (5.8±1.5×103 pg/106 ICMP BOECs), independent of age or ischemic disease. Senescence‐associated β‐galactosidase staining showed comparable senescence in BOECs from ICMP (5.8±2.1%; n=17), ACON (3.9±1.1%; n=7), and CON (9.0±2.8%; n=13), P=0.19. High‐resolution microcomputed tomography analysis in the ischemic hindlimb of nude mice confirmed increased arteriogenesis in the thigh region after intramuscular injections of BOECs from ICMP (P=0.025; n=8) and CON (P=0.048; n=5) over vehicle control (n=8), both to a similar extent (P=0.831). Conclusions BOECs can be successfully culture‐expanded from patients with ICMP. In contrast to impaired functionality of ICMP‐derived bone marrow MNCs, BOECs retain a robust proangiogenic profile, both in vitro and in vivo, with therapeutic potential for targeting ischemic disease.
European Journal of Echocardiography | 2014
Dieter Dauwe; Dieter Nuyens; Stijn De Buck; Piet Claus; Olivier Gheysens; Michel Koole; Walter Coudyzer; Nina Vanden Driessche; Laurens Janssens; Joris Ector; Steven Dymarkowski; Jan Bogaert; Hein Heidbuchel; Stefan Janssens
AIM Biological therapies for ischaemic heart disease require efficient, safe, and affordable intramyocardial delivery. Integration of multiple imaging modalities within the fluoroscopy framework can provide valuable information to guide these procedures. We compared an anatomo-electric method (LARCA) with a non-fluoroscopic electromechanical mapping system (NOGA(®)). LARCA integrates selective three-dimensional-rotational angiograms with biplane fluoroscopy. To identify the infarct region, we studied LARCA-fusion with pre-procedural magnetic resonance imaging (MRI), dedicated CT, or (18)F-FDG-PET/CT. METHODS AND RESULTS We induced myocardial infarction in 20 pigs by 90-min LAD occlusion. Six weeks later, we compared peri-infarct delivery accuracy of coloured fluospheres using sequential NOGA(®)- and LARCA-MRI-guided vs. LARCA-CT- and LARCA-(18)F-FDG-PET/CT-guided intramyocardial injections. MRI after 6 weeks revealed significant left ventricular (LV) functional impairment and remodelling (LVEF 31 ± 3%, LVEDV 178 ± 15 mL, infarct size 17 ± 2% LV mass). During NOGA(®)-procedures, three of five animals required DC-shock for major ventricular arrhythmias vs. one of ten during LARCA-procedures. Online procedure time was shorter for LARCA than NOGA(®) (77 ± 6 vs. 130 ± 3 min, P < 0.0001). Absolute distance of injection spots to the infarct border was similar for LARCA-MRI (4.8 ± 0.5 mm) and NOGA(®) (5.4 ± 0.5 mm). LARCA-CT-integration allowed closer approximation of the targeted border zone than LARCA-PET (4.0 ± 0.5 mm vs. 6.2 ± 0.6 mm, P < 0.05). CONCLUSION Three-dimensional -rotational angiography fused with multimodal imaging offers a new, cost-effective, and safe strategy to guide intramyocardial injections. Endoventricular procedure times and arrhythmias compare favourably to NOGA(®), without compromising injection accuracy. LARCA-based fusion imaging is a promising enabling technology for cardiac biological therapies.
EJNMMI research | 2013
Olivier Gheysens; Vamsidhar Akurathi; Rufael Chekol; Tom Dresselaers; Sofie Celen; Michel Koole; Dieter Dauwe; Bernard Cleynhens; Piet Claus; Stefan Janssens; Alfons Verbruggen; Johan Nuyts; Uwe Himmelreich; Guy Bormans
BackgroundTo date, few PET tracers for in vivo labeling of red blood cells (RBCs) are available. In this study, we report the radiosynthesis and in vitro and in vivo evaluation of 11C and 18F sulfonamide derivatives targeting carbonic anhydrase II (CA II), a metallo-enzyme expressed in RBCs, as potential blood pool tracers. A proof-of-concept in vivo imaging study was performed to demonstrate the feasibility to assess cardiac function and volumes using electrocardiogram (ECG)-gated positron emission tomography (PET) acquisition in comparison with cine magnetic resonance imaging (cMRI) in rats and a pig model of myocardial infarction.MethodsThe inhibition constants (Ki) of CA II were determined in vitro for the different compounds by assaying CA-catalyzed CO2 hydration activity. Binding to human RBCs was estimated after in vitro incubation of the compounds with whole blood. Biodistribution studies were performed to evaluate tracer kinetics in NMRI mice. ECG-gated PET acquisition was performed in Wistar rats at rest and during pharmacological stress by infusing dobutamine at 10 μg/kg/min and in a pig model of myocardial infarction. Left ventricular ejection fraction (LVEF) and volumes were compared with values from cMRI.ResultsThe Ki of the investigated compounds for human CA II was found to be in the range of 8 to 422 nM. The fraction of radioactivity associated with RBCs was found to be ≥90% at 10- and 60-min incubation of tracers with heparinized human blood at room temperature for all tracers studied. Biodistribution studies in mice indicated that 30% to 67% of the injected dose was retained in the blood pool at 60 min post injection. A rapid and sustained tracer uptake in the heart region with an average standardized uptake value of 2.5 was observed from micro-PET images. The LVEF values obtained after pharmacological stress in rats closely matched between the cMRI and micro-PET values, whereas at rest, a larger variation between LVEF values obtained by both techniques was observed. In the pig model, a good agreement was observed between PET and MRI for quantification of left ventricular volumes and ejection fraction.ConclusionsThe 11C and 18F sulfonamide derivatives can be used for efficient in vivo radiolabeling of RBCs, and proof-of-concept in vivo imaging studies have shown the feasibility and potential of these novel tracers to assess cardiac function.
Proceedings of SPIE | 2013
Stijn De Buck; Dieter Dauwe; Jean-Yves Wielandts; Piet Claus; Stefan Janssens; Hein Heidbuchel; Dieter Nuyens
Cardiac rotational angiography (RA) is well suited for 3-D cardiac imaging during catheter based interventions but remained limited to static images or was characterized by high dose patient radiation dose. We present a new prospective imaging technique that is capable of imaging the dynamics of the cardiac cavities in a single C-arm run during the intervention with a relatively low dose. By combining slow atrial pacing to obtain a stable heart rhythm and a single C-arm rotation with imaging at a regular imaging interval, a prospective 4DRA is established. Pacing interval and imaging framerate can be adapted such that a single cardiac phase is imaged multiple times and a motion free state is imaged from different equiangular positions. A practical implementation of this technique was realized in which the cardiac cavities are imaged while pacing at 105 bpm (574 msec) and imaging at approximately 15 fps. A number of animal experiments were conducted in which the technique was applied and MR imaging was performed subsequently. Quantitative comparison was made by manual contouring of the left ventricle in the RA and MR images of both end-systolic and end-diastolic phases. Reconstructed images of the individual cardiac phases showed all four chambers and important vessels in spite of substantial image noise. 4DRA and MR absolute surface distance errors amounted to 2:8 ± 0:7 mm, which is acceptable. Further, no systematic difference could be identified. Finally, it is expected that the effective dose of a clinical protocol with 381 images will be lower than the current retrospective gated RA protocols.
Intensive Care Medicine | 2018
Dieter Dauwe; Joshua Ihle; Vincent Pellegrino
Aortic regurgitation (AR) is usually a diastolic phenomenon. We report on paradoxical isolated systolic AR in a 64-year-old woman, supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for inotroperefractory cardiogenic shock following recent diagnosis of a dilated cardiomyopathy. The aortic annulus is subjected to conformational changes during the cardiac cycle. Recent studies documented an approximately 10–30% increase of annulus short-axis area during systole. This can cause separation of the aortic leaflets isolated to the systolic phase, independent of the transvalvular pressure gradient. Extremely reduced left ventricle (LV) contractility results in delayed pressure build-up (reduced dp/dtmax) and severely reduced LV end-systolic pressure generation. In combination with the cardiac independent continuous afterload dictated by the VA-ECMO circuit, this induces reversal in the LV–ascending aorta pressure gradients in early and late systole. Only the peak LV end-systolic pressure generated at mid-systole is sufficient to overcome the ECMO-dictated afterload and generate some forward stroke volume. In combination with a regurgitant orifice area only present during the systolic phase, as explained above, a unique pathophysiological substrate for biphasic isolated systolic AR during early and late systole is generated. This was clearly documented by color Doppler (Fig. 1, Panel A and Video), color M-mode (Fig. 1, Panel B), and pulse wave Doppler (Fig. 1, Panel C) echocardiography.
Jacc-cardiovascular Interventions | 2016
Dieter Dauwe; Nick Hiltrop; Willem Schurmans; Philippe Moerman; Jan Bogaert; Stefan Janssens; Mark Coosemans
A 49-year-old male was admitted for surgical resection of a solitary pulmonary metastasis. A mixed germ cell testis tumor (mature teratoma and seminoma) was diagnosed 1 year before and treated with orchidectomy and adjuvant chemotherapy. Surgical resection of regional retroperitoneal disease
Minerva Cardioangiologica | 2009
Xs Liu; Dieter Dauwe; Abdulsamie Patel; Stefan Janssens
European Journal of Heart Failure | 2013
Dieter Dauwe; Kristoff Verdonck; Hilde Gillijns; Aernout Luttun; Stefan Janssens
Circulation | 2013
Dieter Dauwe; Kristoff Verdonck; Hilde Gillijns; Ellen Caluwé; Peter Pokreisz; Nick van Gastel; Geert Carmeliet; Maarten Depypere; Frederik Maes; Walter Droogne; Johan Vanhaecke; Aernout Luttun; Stefan Janssens
Circulation | 2013
Dieter Dauwe; Kristoff Verdonck; Hilde Gilllijns; Ellen Caluwé; Peter Pokreisz; Nick van Gastel; Geert Carmeliet; Maarten Depypere; Frederik Maes; Walter Droogne; Johan Vanhaecke; Aernout Luttun; Stefan Janssens