Guy Marchal

KU Leuven, Leuven, VLG, Belgium

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Publications (125)278.87 Total impact

  • Article: Bipolar radiofrequency ablation with four electrodes: Ex vivo liver experiments and finite element method analysis. Influence of inter-electrode distance on coagulation size and geometry.
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    ABSTRACT: Purpose: The aim of this study was to develop an electrode system with simple needle electrodes which would allow a reliable and predictable ablation zone with radiofrequency ablation (RFA). Materials and methods: In the first step, four parallel electrodes (active length 3 cm, diameter 1.8 mm) were inserted in ex vivo bovine liver. A power of 50 W was applied between two pairs of electrodes for 10 min or until current shut-off due to impedance rise. In the second step, the influence of changing inter-electrode distance on coagulation size and geometry was measured. In the third step, a finite element method (FEM) analysis of the experiment was performed to better understand the experimental findings. Results: A bipolar four-electrode system with templates adjusting the inter-electrode distance was successfully developed for ex vivo experiments. A complete and reliable coagulation zone of a 3 × 2 × 2-cm block was obtained most efficiently with an inter-electrode distance of 2 cm in 5.12 ± 0.71 min. Above 2 cm, coagulation was incomplete due to a too low electric field, as demonstrated by the FEM analysis. Conclusions: The optimal inter-electrode distance of the present bipolar four-electrode system was 2 cm, allowing a reliable and predictable ablation zone in ex vivo liver. The FEM analysis correctly simulated and explained the findings in ex vivo liver. The experimental set-up may serve as a platform to gain more insight and to optimise the application of RFA by means of four or more simple needle electrodes.
    International Journal of Hyperthermia 09/2012; 28(7):686-97. · 1.92 Impact Factor
  • Article: Radiofrequency Ablation for Eradication of Renal Tumor in a Rabbit Model by Using a Cooled-tip Electrode Technique
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    ABSTRACT: Background:Radiofrequency ablation (RFA) has emerged as a potential alternative for surgery in clinical oncology. This animal experiment was conducted to evaluate the feasibility of RFA in the treatment of renal tumor.Methods:Eighteen rabbits with renal implantation of VX2 tumors were divided into two groups. Group A (n = 12) was treated with RFA by using a cooled-tip RF system at 30 W for 80 to 180 seconds. Group B (n = 6) received a sham operation. The therapeutic efficacy was evaluated by survival rate, magnetic resonance imaging (MRI), and histology.Results:All animals in group B died within 3 months after tumor implantation. Total tumor eradication was achieved in 10 of 12 rabbits (83.3%) in group A, of which 5 rabbits survived longer than 6 months (absolute eradication) and another 5 rabbits were found free of viable tumor when killed (relative eradication). Two rabbits experienced local tumor relapse, lung metastasis, or both. Six-month survival rate of RFA-treated rabbits was significantly higher (P < .01) than that of control rabbits. The typical MRI appearances of the acute RFA lesion consisted of five characteristic concentric zones, which corresponded to central needle track (zone A), tumor coagulation (zone B), renal tissue coagulation (zone C), peripheral hemorrhage (zone D), and inflammatory layer (zone E) on histology.Conclusions:RFA may become a promising therapy for the treatment of renal tumor. MRI is a useful modality for assessment of renal tumor ablation.
    Annals of Surgical Oncology 04/2012; 8(8):651-657. · 4.17 Impact Factor
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    Article: Enhanced antitumor efficacy of a vascular disrupting agent combined with an antiangiogenic in a rat liver tumor model evaluated by multiparametric MRI.
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    ABSTRACT: A key problem in solid tumor therapy is tumor regrowth from a residual viable rim after treatment with a vascular disrupting agent (VDA). As a potential solution, we studied a combined treatment of a VDA and antiangiogenic. This study was approved by the institutional ethical committee for the use and care of laboratory animals. Rats with implanted liver tumors were randomized into four treatment groups: 1) Zd6126 (Zd); 2) Thalidomide (Tha); 3) Zd in combination with Tha (ZdTha); and 4) controls. Multiparametric MRIs were performed and quantified before and after treatment. Circulating endothelial progenitor cells (EPCs) and plasma stromal cell-derived factor-1α (SDF-1α) were monitored. Tumor apoptosis, necrosis, and microvessels were verified by histopathology. A single use of Zd or Tha did not significantly delay tumor growth. The combined ZdTha showed enhanced antitumor efficacy due to synergistic effects; it induced a cumulative tumor apoptosis or necrosis, which resulted in significant delay in tumor growth and reduction in the viable tumor rim; it also reduced tumor vessel permeability; and it improved tumor hemodynamic indexes, most likely via a transient normalization of tumor vasculature induced by Tha. A stepwise linear regression analysis showed that the apparent diffusion coefficient was an independent predictor of tumor growth. We found no significant increases in Zd-induced circulating EPCs or plasma SDF-1α. ZdTha showed improved therapeutic efficacy in solid tumors compared to either agent alone. The therapeutic effects were successfully tracked in vivo with multiparametric MRI.
    PLoS ONE 01/2012; 7(7):e41140. · 4.09 Impact Factor
  • Article: Comparison of two vascular-disrupting agents at a clinically relevant dose in rodent liver tumors with multiparametric magnetic resonance imaging biomarkers.
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    ABSTRACT: We sought to compare the therapeutic efficacy between two vascular-disrupting agents, combretastatin A4 phosphate (CA4P) and ZD6126, at a clinically relevant dose on tumor models with magnetic resonance imaging (MRI). Thirty rats with liver rhabdomyosarcoma were randomized into CA4P (10 mg/kg), ZD6126 (10 mg/kg), and control group (n=10 for each group). Multiparametric MRI biomarkers including tumor volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC), and K (volume transfer constant) derived from T2-weighted, T1-weighted, contrast-enhanced T1-weighted, and diffusion-weighted imaging, and dynamic contrast-enhanced MRI were compared at pretreatment, 1 h, 6 h, 24 h, 48 h, and 120 h posttreatment; they were validated using ex-vivo techniques. Relative to rapidly growing tumors without necrosis in control rats, tumors grew slower in the CA4P group compared with the ZD6126 group with a higher necrosis ratio at 120 h (P<0.05), as proven by histopathology. In the CA4P group, K decreased from 1 h until 6 h, and partially recovered at 120 h. In the ZD6126 group, the reduced K at 1 h began to rebound from 6 h and exceeded the baseline value at 120 h (P<0.05), parallel to evolving enhancement ratios (P<0.05). ADC revealed more necrotic tumors with CA4P versus ZD6126 at 120 h (P<0.05). The different tumor responses were confirmed by ex-vivo microangiography and histopathology. CA4P was more effective than ZD6126 in impairing blood supply, inducing necrosis, and delaying growth in rat liver tumors at a clinically relevant dose. A single dose of vascular-disrupting agent was insufficient to destroy the tumor. The multiparametric MRI biomarkers enabled in-vivo noninvasive comparison of therapeutic efficacy between CA4P and ZD6126.
    Anti-cancer drugs 08/2011; 23(1):12-21. · 2.23 Impact Factor
  • Article: A dual-targeting anticancer approach: soil and seed principle.
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    ABSTRACT: To test the hypothesis that targeting the microenvironment (soil) may effectively kill cancer cells (seeds) through a small-molecular weight sequential dual-targeting theragnostic strategy, or dual-targeting approach. With approval from the institutional animal care and use committee, 24 rats were implanted with 48 liver rhabdomyosarcomas (R1). First, the vascular-disrupting agent combretastatin A4 phosphate (CA4P) was injected at a dose of 10 mg/kg to cause tumor necrosis, which became a secondary target. Then, the necrosis-avid agent hypericin was radiolabeled with iodine 131 to form (131)I-hypericin, which was injected at 300 MBq/kg 24 hours after injection of CA4P. Both molecules have small molecular weight, are naturally or synthetically derivable, are intravenously injectable, and are of unique targetablities. The tumor response in the dual-targeting group was compared with that in vehicle-control and single-targeting (CA4P or (131)I-hypericin) groups with in vivo magnetic resonance imaging and scintigrams and ex vivo gamma counting, autoradiography, and histologic analysis. Tumor volumes, tumor doubling time (TDT), and radiobiodistribution were analyzed with statistical software. P values below .05 were considered to indicate a significant difference. Eight days after treatment, the tumor volume of rhabdomyosarcoma in the vehicle-control group was double that in both single-targeting groups (P < .001) and was five times that in the dual-targeting group (P < .0001), without treatment-related animal death. The TDT was significantly longer in the dual-targeting group (P < .0001). Necrosis appeared as hot spots on scintigrams, corresponding to 3.13% of the injected dose of (131)I-hypericin per gram of tissue (interquartile range, 2.92%-3.97%) and a target-to-liver ratio of 20. The dose was estimated to be 100 times the cumulative dose of 50 Gy needed for radiotherapeutic response. Thus, accumulated (131)I-hypericin from CA4P-induced necrosis killed residual cancer cells with ionizing radiation and inhibited tumor regrowth. This dual-targeting approach may be a simple and workable solution for cancer treatment and deserves further exploitation.
    Radiology 06/2011; 260(3):799-807. · 5.73 Impact Factor
  • Article: Comparison between nonspecific and necrosis-avid gadolinium contrast agents in vascular disrupting agent-induced necrosis of rodent tumors at 3.0T.
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    ABSTRACT: : To compare a commercial contrast agent (CA) Dotarem and a necrosis-avid CA (NACA) for their ability to evaluate the therapeutic necrosis with a vascular disrupting agent (VDA) on magnetic resonance imaging in rodent liver tumors to determine which could better correlate with the histopathologic outcome. : After the VDA treatment, 16 rats with 32 liver rhabdomyosarcomas were randomized into Dotarem and NACA groups (n = 8 per group) for both interindividual and intraindividual comparisons. T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1-weighted imaging (CE-T1WI), and diffusion-weighted imaging were performed at baseline, after VDA treatment and CA injections. The enhancing efficacy of CAs at immediate and delayed enhancement on CE-T1WI in viable tumor and necrosis was compared. Tumor necrosis ratios calculated from NACA and Dotarem were compared and correlated with gold-standard histopathology. : On the immediate CE-T1WI, viable tumor was enhanced by either CA. On the delayed CE-T1WI at 30 minutes, both CAs failed to demarcate viable tumor from necrosis. At 24 hours post-NACA, the necrosis was clearly distinguished from viable tumor and thus derived necrosis ratio matched that from histopathology (P = 0.99); necrosis ratio from Dotarem was significantly lower than that from NACA and histopathology (P < 0.05, both), with a higher correlation of NACA than that of Dotarem with histopathology (r = 0.99 vs. r = 0.82). : NACA better evaluated VDA-induced tumor necrosis than nonspecific CA on T1WI in tumor models of rat liver. NACA showed a closer correlation with histopathology than nonspecific CA for the delineation of true necrosis. Delayed enhancement on T1WI with nonspecific CA is not suitable for the assessment of VDA-induced tumor necrosis.
    Investigative radiology 05/2011; 46(9):531-8. · 4.85 Impact Factor
  • Article: Multiparametric MRI biomarkers for measuring vascular disrupting effect on cancer.
    Huaijun Wang, Guy Marchal, Yicheng Ni
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    ABSTRACT: Solid malignancies have to develop their own blood supply for their aggressive growth and metastasis; a process known as tumor angiogenesis. Angiogenesis is largely involved in tumor survival, progression and spread, which are known to be significantly attributed to treatment failures. Over the past decades, efforts have been made to understand the difference between normal and tumor vessels. It has been demonstrated that tumor vasculature is structurally immature with chaotic and leaky phenotypes, which provides opportunities for developing novel anticancer strategies. Targeting tumor vasculature is not only a unique therapeutic intervention to starve neoplastic cells, but also enhances the efficacy of conventional cancer treatments. Vascular disrupting agents (VDAs) have been developed to disrupt the already existing neovasculature in actively growing tumors, cause catastrophic vascular shutdown within short time, and induce secondary tumor necrosis. VDAs are cytostatic; they can only inhibit tumor growth, but not eradicate the tumor. This novel drug mechanism has urged us to develop multiparametric imaging biomarkers to monitor early hemodynamic alterations, cellular dysfunctions and metabolic impairments before tumor dimensional changes can be detected. In this article, we review the characteristics of tumor vessels, tubulin-destabilizing mechanisms of VDAs, and in vivo effects of the VDAs that have been mostly studied in preclinical studies and clinical trials. We also compare the different tumor models adopted in the preclinical studies on VDAs. Multiparametric imaging biomarkers, mainly diffusion-weighted imaging and dynamic contrast-enhanced imaging from magnetic resonance imaging, are evaluated for their potential as morphological and functional imaging biomarkers for monitoring therapeutic effects of VDAs.
    World journal of radiology. 01/2011; 3(1):1-16.
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    Article: Formulation of 3D finite elements for hepatic radiofrequency ablation
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    ABSTRACT: Radiofrequency ablation (RFA) is being used as one of the minimally invasive treatments for unresectable primary and metastatic liver tumours. The variables identified to have significant impact on RF heating include electrical conductivity of the tumour and surrounding tissue, thermal conductivity of tissue, tissue perfusion and RF generator output. These constitute a dynamic and complex matter that makes it difficult to achieve an optimal RFA in clinical practice. This study was intended to propose a specialised three dimensional (3D) finite element modelling in order to develop a fast analysis tool for clinicians to optimise RFA parameters and to predict the ablation outcomes.. He received his PhD in Applied Sciences from State University of Liège, Belgium in 1987. He joined Polyflow company (now a part of ANSYS) in 1991 as a Software Engineer in developing finite element methods in non-Newtonian fluid mechanics. From 2005 to 2007, as Visiting Professor, he taught courses in Mechanical Engineering at Universidade Regional do Noroeste do Estado do Rio Grande do Sul, Brazil. He has been interested in developing various numerical methods in engineering such as boundary element methods, parallel computing and point collocation methods. His current research topic is finite element modelling of radiofrequency ablation of tumour.
    Int. J. Modelling, Identification and Control Int. J. Modelling, Identification and Control. 08/2010; 9(9):225-235.
  • Article: Does digital mammography in a decentralized breast cancer screening program lead to screening performance parameters comparable with film-screen mammography?
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    ABSTRACT: To evaluate if the screening performance parameters of digital mammography (DM) in a decentralized screening organization were comparable with film-screen mammography (FSM). A nationwide screening program was launched in 2001, and since 2005 screening with DM has been allowed. Firstly, the parameters of the three regional screening units (RSUs) that first switched to DM (11,355 women) were compared with the FSM period of the same three RSUs (23,325 women). Secondly, they were compared with the results of the whole central breast unit (CBU). The recall rate (RR) of the DM group in the initial round was 2.64% [2.40% for FSM (p = 0.43)] and in the subsequent round 1.20% [1.58% for FSM (p = 0.03)]. The cancer detection rate (CDR) was 0.59% for DM and 0.64% for FSM (p = 0.56). The percentage of ductal carcinoma in situ was 0.07% for DM and 0.16% for FSM (p = 0.02). The positive predictive value was high in the subsequent rounds (DM 48.00%, FSM 45.93%) and lower in the initial round (DM 24.05%, FSM 24.86%). Compared with the results of the whole CBU, DM showed no significant difference. DM can be introduced in a decentralized screening organization with a high CDR without increasing the RR.
    European Radiology 05/2010; 20(10):2307-14. · 3.22 Impact Factor
  • Article: Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours.
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    ABSTRACT: To evaluate effects of a vascular-disrupting agent on rodent tumour models. Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [(18)F]fluorodeoxyglucose micro-positron emission tomography ((18)F-FDG microPET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUV(max)) from FDG microPET were quantified and correlated with postmortem microangiography and histopathology. In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P < 0.05), corresponding well to histopathology; tumour K decreased from 1 h until 24 h, and partially recovered at 48 h (P < 0.05), parallel to the evolving enhancement ratios (P < 0.05); ADCs varied with tumour viability and perfusion; and SUV(max) dropped at 24 h (P < 0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r = 0.93, P < 0.05). The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment.
    European Radiology 02/2010; 20(8):2013-26. · 3.22 Impact Factor
  • Conference Proceeding: Software Framework for Simulating Clusters of Microcalcifications in Digital Mammography.
    Digital Mammography, 10th International Workshop, IWDM 2010, Girona, Catalonia, Spain, June 16-18, 2010. Proceedings; 01/2010
  • Article: Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis: revisited.
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    ABSTRACT: Voxel-based analyses (VBA) are increasingly being used to detect white matter abnormalities with diffusion tensor imaging (DTI) in different types of pathologies. However, the validity, specificity, and sensitivity of statistical inferences of group differences to a large extent depend on the quality of the spatial normalization of the DTI images. Using high-dimensional nonrigid coregistration techniques that are able to align both the spatial and orientational diffusion information and incorporate appropriate templates that contain this complete DT information may improve this quality. Alternatively, a hybrid technique such as tract-based spatial statistics (TBSS) may improve the reliability of the statistical results by generating voxel-wise statistics without the need for perfect image alignment and spatial smoothing. In this study, we have used (1) a coregistration algorithm that was optimized for coregistration of DTI data and (2) a population-based DTI atlas to reanalyze our previously published VBA, which compared the fractional anisotropy and mean diffusivity maps of patients with amyotrophic lateral sclerosis (ALS) with those of healthy controls. Additionally, we performed a complementary TBSS analysis to improve our understanding and interpretation of the VBA results. We demonstrate that, as the overall variance of the diffusion properties is lowered after normalizing the DTI data with such recently developed techniques (VBA using our own optimized high-dimensional nonrigid coregistration and TBSS), more reliable voxel-wise statistical results can be obtained than had previously been possible, with our VBA and TBSS yielding very similar results. This study provides support for the view of ALS as a multisystem disease, in which the entire frontotemporal lobe is implicated.
    Human Brain Mapping 05/2009; 30(11):3657-75. · 5.88 Impact Factor
  • Article: Evaluation of clinical image processing algorithms used in digital mammography.
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    ABSTRACT: Screening is the only proven approach to reduce the mortality of breast cancer, but significant numbers of breast cancers remain undetected even when all quality assurance guidelines are implemented. With the increasing adoption of digital mammography systems, image processing may be a key factor in the imaging chain. Although to our knowledge statistically significant effects of manufacturer-recommended image processings have not been previously demonstrated, the subjective experience of our radiologists, that the apparent image quality can vary considerably between different algorithms, motivated this study. This article addresses the impact of five such algorithms on the detection of clusters of microcalcifications. A database of unprocessed (raw) images of 200 normal digital mammograms, acquired with the Siemens Novation DR, was collected retrospectively. Realistic simulated microcalcification clusters were inserted in half of the unprocessed images. All unprocessed images were subsequently processed with five manufacturer-recommended image processing algorithms (Agfa Musica 1, IMS Raffaello Mammo 1.2, Sectra Mamea AB Sigmoid, Siemens OPVIEW v2, and Siemens OPVIEW v1). Four breast imaging radiologists were asked to locate and score the clusters in each image on a five point rating scale. The free-response data were analyzed by the jackknife free-response receiver operating characteristic (JAFROC) method and, for comparison, also with the receiver operating characteristic (ROC) method. JAFROC analysis revealed highly significant differences between the image processings (F = 8.51, p < 0.0001), suggesting that image processing strongly impacts the detectability of clusters. Siemens OPVIEW2 and Siemens OPVIEW1 yielded the highest and lowest performances, respectively. ROC analysis of the data also revealed significant differences between the processing but at lower significance (F = 3.47, p = 0.0305) than JAFROC. Both statistical analysis methods revealed that the same six pairs of modalities were significantly different, but the JAFROC confidence intervals were about 32% smaller than ROC confidence intervals. This study shows that image processing has a significant impact on the detection of microcalcifications in digital mammograms. Objective measurements, such as described here, should be used by the manufacturers to select the optimal image processing algorithm.
    Medical Physics 03/2009; 36(3):765-75. · 2.83 Impact Factor
  • Article: Diffusion-weighted MRI of hepatic tumor in rats: comparison between in vivo and postmortem imaging acquisitions.
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    ABSTRACT: To determine the feasibility of in vivo diffusion-weighted imaging (DWI) to distinguish between normal liver, viable tumor and necrosis compared to postmortem DWI in a rat model with vascular-targeting treatment. Fifteen rats with liver implantation of 30 rhabdomyosarcomas were treated with combretastatin A-4-phosphate (CA4P) at 10 mg/kg. Two days after treatment, T2-weighted imaging, precontrast T1-weighted imaging, postcontrast T1-weighted imaging, and DWI were performed in vivo and postmortem with a 1.5T scanner. Apparent diffusion coefficients (ADCs) calculated from DWIs with b values of 0, 50, and 100 seconds/mm2 (ADClow), 500, 750, and 1000 seconds/mm2 (ADChigh), 0, 500, and 1000 seconds/mm2 (ADC3b), and 0-1000 seconds/mm2 (ADC10b) for tumor, liver, therapeutic necrosis, and phantoms were compared and validated with ex vivo microangiographic and histopathologic findings. Except ADClow between tumor and necrosis, in vivo ADCs successfully differentiated liver, viable tumor, and necrosis (P<0.05). Compared to in vivo outcomes, postmortem ADCs significantly dropped in tumor and liver (P<0.05) except ADChigh of tumor, but not in necrosis and phantoms. Compared to ADClow, ADChigh was less affected by vital status. Advantageous over postmortem DWI, in vivo DWI provides a noninvasive easy-performing tool for distinguishing between liver, viable tumor, and necrosis. ADClow and ADChigh better reflect tissue perfusion and water diffusion, respectively.
    Journal of Magnetic Resonance Imaging 03/2009; 29(3):621-8. · 2.70 Impact Factor
  • Article: A modified rabbit model of reperfused myocardial infarction for cardiac MR imaging research.
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    ABSTRACT: We sought to obtain a rabbit myocardial infarction (MI) model for research with cardiac magnetic resonance imaging (cMRI) by overcoming a few technical difficulties. A novel endotracheal method was developed for intubation and ventilation. Fourteen rabbits were divided into group-1 (n = 8) with open-chest occlusion of left circumflex coronary artery and closed-chest reperfusion, and group-2 (n = 6) of non-ischemic control; and received ECG-triggered cMRI with delayed contrast enhancement (DE-cMRI) at a 1.5 T clinical scanner. The MI areas in group-1 were morphometrically compared between DE-cMRI and histochemically stained specimens. Left ventricular (LV) functions were compared between two groups.The success rate of intubation and reperfused MI was 8/8 and 6/8, respectively. Global and regional LV functions significantly decreased in group-1 as evidenced by significant hypokinesis of lateral LV-wall and wall thickening (P \ 0.001). Mean MI-area was 19.41 +/- 21.92% on DE-cMRI and 19.10 +/- 22.61% with histochemical staining (r = 0.985). Global MI-volume was 17.92 +/- 7.42% on DE-cMRI and 16.62 +/- 7.16% with histochemistry (r = 0.994). The usefulness of this model was successfully tested for assessing a new contrast agent. The present rabbit MI model may offer a practical platform for more translational research using clinical MRI-facilities.
    The international journal of cardiovascular imaging 01/2009; 25(3):289-98. · 2.15 Impact Factor
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    Article: Treatment of rodent liver tumor with combretastatin a4 phosphate: noninvasive therapeutic evaluation using multiparametric magnetic resonance imaging in correlation with microangiography and histology.
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    ABSTRACT: To document tumoricidal events after intravenous administration of a vascular targeting agent combretastatin A-4-phosphate (CA4P) in rodent liver tumors by using multiparametric magnetic resonance imaging (MRI) in correlation with microangiography and histopathology. Thirty rhabdomyosarcomas of 8 to 14 mm in diameter were obtained 16 days after implantation in liver lobes of 15 rats. Using a 1.5T magnet and a 4-channel wrist coil, T2-weighted imaging (T2WI), pre- and postcontrast T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), and dynamic susceptibility imaging (DSI) with relative blood volume (rBV) and flow (rBF) maps were acquired at baseline, 1 hour, 6 hours, and 48 hours after iv injection of CA4P at 10 mg/kg and vehicle in 9 treated and 6 control rats, respectively. In vivo data including signal intensity (SI), tumor volume, apparent diffusion coefficient (ADC), rBV, and rBF were correlated with ex vivo microangiographic and histopathologic findings. CA4P-treated tumors (n = 18) grew slower than those (n = 12) of controls (P < 0.05), with vascular shutdown evident on CE-T1WI at 1 hour but more prominent at 6 hours. However, enhanced rim occurred in the periphery 48 hours after treatment, indicating neovascularization. ADC map enabled distinction between necrotic and viable tumors. DSI-derived tumoral rBV and rBF decreased significantly at 1 hour through 6 hours and partly recovered at 48 hours. SI-time curve reflected diverse therapeutic responses between tumor and liver. MRI findings were verified by ex vivo techniques. Clinical MRI allowed monitoring of CA4P-related vascular shutdown, necrosis, and neovascularization of liver tumors in rats. Single dose of CA4P seemed insufficient for tumor eradication because of evident peripheral residue and recurrence.
    Investigative radiology 12/2008; 44(1):44-53. · 4.85 Impact Factor
  • Article: An improved method for simulating microcalcifications in digital mammograms.
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    ABSTRACT: The assessment of the performance of a digital mammography system requires an observer study with a relatively large number of cases with known truth which is often difficult to assemble. Several investigators have developed methods for generating hybrid abnormal images containing simulated microcalcifications. This article addresses some of the limitations of earlier methods. The new method is based on digital images of needle biopsy specimens. Since the specimens are imaged separately from the breast, the microcalcification attenuation profile scan is deduced without the effects of over and underlying tissues. The resulting templates are normalized for image acquisition specific parameters and reprocessed to simulate microcalcifications appropriate to other imaging systems, with different x-ray, detector and image processing parameters than the original acquisition system. This capability is not shared by previous simulation methods that have relied on extracting microcalcifications from breast images. The method was validated by five experienced mammographers who compared 59 pairs of simulated and real microcalcifications in a two-alternative forced choice task designed to test if they could distinguish the real from the simulated lesions. They also classified the shapes of the microcalcifications according to a standardized clinical lexicon. The observed probability of correct choice was 0.415, 95% confidence interval (0.284, 0.546), showing that the radiologists were unable to distinguish the lesions. The shape classification revealed substantial agreement with the truth (mean kappa = 0.70), showing that we were able to accurately simulate the lesion morphology. While currently limited to single microcalcifications, the method is extensible to more complex clusters of microcalcifications and to three-dimensional images. It can be used to objectively assess an imaging technology, especially with respect to its ability to adequately visualize the morphology of the lesions, which is a critical factor in the benign versus malignant classification of a lesion detected in screening mammography.
    Medical Physics 10/2008; 35(9):4012-8. · 2.83 Impact Factor
  • Article: A Place for Radiofrequency Ablation in the Treatment of Resectable Colorectal Liver Metastases?
    Annals of Surgical Oncology 08/2008; 15(7):2064-2065. · 4.17 Impact Factor
  • Chapter: One Year of Experience with Remote Quality Assurance of Digital Mammography Systems in the Flemish Breast Cancer Screening Program
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    ABSTRACT: The European Guidelines on Digital Mammography (EUREF) prescribe that regularly the homogeneity of the used digital systems should be tested. In a decentralized screening environment with centralized quality control (QC) supervision this can become a time consuming work. Therefore we developed a novel method to simplify remote QC. Exposures of a homogeneous plate of PMMA are made daily under clinical conditions and are sent to our locally installed analysis software. Several parameters are calculated for the complete image, for 6 reference regions of interest (ROIs) and for series of small adjacent ROIs all over the image. These calculated parameters are summarized in maps that are treated as thumbnail images. Analysis results are sent to the reference site where they are supervised by a trained physicist and compared with the results of previous tests. Several artifacts could be traced with the thumbnail images. These include: dirt on phosphor cassettes, scanline artifacts, scratches on the IP and burned-in markers for CR units. For DR units, increasing ghost image factors, lag images, crystallization of detector material, defective pixel artifacts and several electrical artifacts were noticed. Our initial experience indicates that failures with digital mammography devices can be traced remotely via thumbnail images of the above parameters that are electronically sent to our reference center, instead of the full-size image.
    07/2008: pages 703-710;
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    Article: Murine liver implantation of radiation-induced fibrosarcoma: characterization with MR imaging, microangiography and histopathology.
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    ABSTRACT: We sought to establish and characterize a mouse liver tumor model as a platform for preclinical assessment of new diagnostics and therapeutics. Radiation-induced fibrosarcoma (RIF-1) was intrahepatically implanted in 27 C3H/Km mice. Serial in vivo magnetic resonance imaging (MRI) with a clinical 1.5-T-magnet was performed using T1- (T1WI), T2- (T2WI), and diffusion-weighted sequences (DWI), dynamic contrast-enhanced MRI (DCE-MRI), and contrast-enhanced T1WI, and validated with postmortem microangiography and histopathology. Implantation procedure succeeded in 25 mice with 2 deaths from overdosed anesthesia or hypothermia. RIF-1 grew in 21 mice with volume doubling time of 2.55+/-0.88 days and final size of 216.2+/-150.4 mm(3) at day 14. Three mice were found without tumor growth and one only with abdominal seeding. The intrahepatic RIF-1 was hypervascularized with negligible necrosis as shown on MRI, microangiography and histology. On DCE-MRI, maximal initial slope of contrast-time curve and volume transfer constant per unit volume of tissue, K, differed between the tumor and liver with only the former significantly lower in the tumor than in the liver (P<0.05). Liver implantation of RIF-1 in mice proves a feasible and reproducible model and appears promising for use to screen new diagnostics and therapeutics under noninvasive monitoring even with a clinical MRI system.
    European Radiology 07/2008; 18(7):1422-30. · 3.22 Impact Factor

Institutions

  • 2002–2012
    • KU Leuven
      • • Theragnostic Laboratory
      • • Division of Radiology
      • • Department of Neurosciences
      • • Faculty of Medicine
      Leuven, VLG, Belgium
  • 2008–2011
    • Leuven University College
      • Department of Radiology
      Leuven, VLG, Belgium
  • 1999–2011
    • Universitair Ziekenhuis Leuven
      • Department of Radiology
      Leuven, VLG, Belgium
  • 2007
    • Säteilyturvakeskukseen
      Helsinki, Province of Southern Finland, Finland
  • 2005–2006
    • Centre Hospitalier Universitaire Mont-Godinne
      Yvoir, WAL, Belgium
  • 2001
    • Università degli Studi di Brescia
      Brescia, Lombardy, Italy
    • Nanjing Medical University
      • Department of General Surgery
      Nanjing, Jiangsu Sheng, China