Chrit Moonen

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (395)964.26 Total impact

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    ABSTRACT: Objectives: To assess the safety and feasibility of MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation in breast cancer patients using a dedicated breast platform. Methods: Patients with early-stage invasive breast cancer underwent partial tumour ablation prior to surgical resection. MR-HIFU ablation was performed using proton resonance frequency shift MR thermometry and an MR-HIFU system specifically designed for breast tumour ablation. The presence and extent of tumour necrosis was assessed by histopathological analysis of the surgical specimen. Pearson correlation coefficients were calculated to assess the relationship between sonication parameters, temperature increase and size of tumour necrosis at histopathology. Results: Ten female patients underwent MR-HIFU treatment. No skin redness or burns were observed in any of the patients. No correlation was found between the applied energy and the temperature increase. In six patients, tumour necrosis was observed with a maximum diameter of 3-11 mm. In these patients, the number of targeted locations was equal to the number of areas with tumour necrosis. A good correlation was found between the applied energy and the size of tumour necrosis at histopathology (Pearson = 0.76, p = 0.002). Conclusions: Our results show that MR-HIFU ablation with the dedicated breast system is safe and results in histopathologically proven tumour necrosis. Key points: • MR-HIFU ablation with the dedicated breast system is safe and feasible • In none of the patients was skin redness or burns observed • No correlation was found between the applied energy and the temperature increase • The correlation between applied energy and size of tumour necrosis was good.
    No preview · Article · Feb 2016 · European Radiology
  • P Ramaekers · M de Greef · J M M van Breugel · C T W Moonen · M Ries
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    ABSTRACT: This study investigated whether an MR-guided pulsed HIFU ablation strategy could be implemented under clinical conditions, using a transducer designed for uterine fibroid ablation, to obtain an ablation rate that is sufficiently high for clinical abdominal HIFU therapy in highly perfused organs. A pulsed HIFU ablation strategy, aimed at increasing the energy absorption in the HIFU focal area by local shock wave formation in the non-linear pressure regime, was compared to an energy-equivalent continuous wave sonication strategy in the linear pressure regime. Both ablation strategies were used for transcutaneous sonication of pre-defined treatment cells in the livers of 5 pigs in vivo . Temperature evolution in both the target area as well as the pre-focal muscle layer was monitored simultaneously using MR thermometry. Local energy absorption and thermal dose volumes were shown to be increased using the pulsed ablation strategy, while preserving healthy tissue in the near field of the acoustic beam. Respiratory motion compensation of both acoustic energy delivery and MR thermometry was applied through gating based on MR navigator echoes. Histopathology showed that confluent vacuolated thermal lesions were created when the pulsed ablation strategy was used. Additionally, it was shown that the heat sink effect caused by the presence of larger vessels could be overcome. The pulsed HIFU ablation strategy achieved an ablation rate of approximately 4 ml per hour in the in vivo porcine liver, without causing undesired damage to healthy tissues in the near field.
    No preview · Article · Jan 2016 · Physics in Medicine and Biology
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    ABSTRACT: Encapsulation of anticancer drugs in triggerable nanocarriers can beneficially modify pharmacokinetics and biodistribution of chemotherapeutic drugs, and consequently increase tumor drug concentration and efficacy, while reducing side effects. Thermosensitive liposomes release their contents triggered by hyperthermia, which can be, for example, precisely delivered using an MR Imaging-guided focused ultrasound procedure. In such a scenario, it is attractive to demonstrate the accumulation of liposomes before applying hyperthermia, as well as to document the release of liposome content using MRI. To address this need, thermosensitive liposomes were developed and characterized, which were doubly loaded by iron oxide nanoparticles and Gd-chelate, as opposed to loading with a single contrast agent. When intact, the transverse relaxivity of the liposomes is high allowing detection of carriers in tissue. After heating the longitudinal relaxivity steeply increases indicating release of the small molecular contents. By choosing the appropriate MR sequences, availability and release can be evaluated without interference of one contrast agent with the other. Copyright © 2016 John Wiley & Sons, Ltd.
    No preview · Article · Jan 2016 · Contrast Media & Molecular Imaging
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    ABSTRACT: We have previously demonstrated the feasibility of monitoring ultrasound-mediated uptake of a hydrophilic model drug in real time with dynamic confocal fluorescence microscopy. In this study, we evaluate and correct the impact of photobleaching to improve the accuracy of pharmacokinetic parameter estimates. To model photobleaching of the fluorescent model drug SYTOX Green, a photobleaching process was added to the current two-compartment model describing cell uptake. After collection of the uptake profile, a second acquisition was performed when SYTOX Green was equilibrated, to evaluate the photobleaching rate experimentally. Photobleaching rates up to 5.0 10−3 s−1 were measured when applying power densities up to 0.2 W.cm−2. By applying the three-compartment model, the model drug uptake rate of 6.0 10−3 s−1 was measured independent of the applied laser power. The impact of photobleaching on uptake rate estimates measured by dynamic fluorescence microscopy was evaluated. Subsequent compensation improved the accuracy of pharmacokinetic parameter estimates in the cell population subjected to sonopermeabilization.
    Full-text · Article · Dec 2015 · Physics in Medicine and Biology
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    ABSTRACT: Magnetic resonance (MR) guided high intensity focused ultrasound and external beam radiotherapy interventions, which we shall refer to as beam therapies/interventions, are promising techniques for the non-invasive ablation of tumours in abdominal organs. However, therapeutic energy delivery in these areas becomes challenging due to the continuous displacement of the organs with respiration. Previous studies have addressed this problem by coupling high-framerate MR-imaging with a tracking technique based on the algorithm proposed by Horn and Schunck (H and S), which was chosen due to its fast convergence rate and highly parallelisable numerical scheme. Such characteristics were shown to be indispensable for the real-time guidance of beam therapies. In its original form, however, the algorithm is sensitive to local grey-level intensity variations not attributed to motion such as those that occur, for example, in the proximity of pulsating arteries.In this study, an improved motion estimation strategy which reduces the impact of such effects is proposed. Displacements are estimated through the minimisation of a variation of the H and S functional for which the quadratic data fidelity term was replaced with a term based on the linear L(1)norm, resulting in what we have called an L(2)-L(1) functional.The proposed method was tested in the livers and kidneys of two healthy volunteers under free-breathing conditions, on a data set comprising 3000 images equally divided between the volunteers. The results show that, compared to the existing approaches, our method demonstrates a greater robustness to local grey-level intensity variations introduced by arterial pulsations. Additionally, the computational time required by our implementation make it compatible with the work-flow of real-time MR-guided beam interventions.To the best of our knowledge this study was the first to analyse the behaviour of an L(1)-based optical flow functional in an applicative context: real-time MR-guidance of beam therapies in moving organs.
    No preview · Article · Nov 2015 · Physics in Medicine and Biology
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    ABSTRACT: MRI-guided High Intensity Focused Ultrasound (MRI-HIFU) is a promising method for the non-invasive ablation of pathological tissue in many organs, including mobile organs such as liver and kidney. The possibility to locally deposit thermal energy in a non-invasive way opens a path towards new therapeutic strategies with improved reliability and reduced associated trauma, leading to improved efficacy, reduced hospitalization and costs. Liver and kidney tumors represent a major health problem because not all patients are suitable for curative treatment with surgery. Currently, radio-frequency is the most used method for percutaneous ablation. The development of a completely non-invasive method based on MR guided high intensity focused ultrasound (HIFU) treatments is of particular interest due to the associated reduced burden for the patient, treatment related patient morbidity and complication rate. The objective of MR-guidance is hereby to control heat deposition with HIFU within the targeted pathological area, despite the physiological motion of these organs, in order to provide an effective treatment with a reduced duration and an increased level of patient safety. Regarding this, several technological challenges have to be addressed: Firstly, the anatomical location of both organs within the thoracic cage requires inter-costal ablation strategies, which preserve the therapeutic efficiency, but prevent undesired tissue damage to the ribs and the intercostal muscle. Secondly, both therapy guidance and energy deposition have to be rendered compatible with the continuous physiological motion of the abdomen.
    No preview · Article · Oct 2015
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    ABSTRACT: The multi-gradient echo MR thermometry (MGE MRT) method is proposed to use at the interface of the muscle and fat layers found in the abdominal wall, to monitor MR-HIFU heating. As MGE MRT uses fat as a reference, it is field-drift corrected. Relative temperature maps were reconstructed by subtracting absolute temperature maps. Because the absolute temperature maps are reconstructed of individual scans, MGE MRT provides the flexibility of interleaved mapping of temperature changes between two arbitrary time points. The method's performance was assessed in an ex vivo water bath experiment. An ex vivo HIFU experiment was performed to show the method's ability to monitor heating of consecutive HIFU sonications and to estimate cooling time constants, in the presence of field drift. The interleaved use between scans of a clinical protocol was demonstrated in vivo in a patient during a clinical uterine fibroid treatment. The relative temperature measurements were accurate (mean absolute error 0.3 °C) and provided excellent visualization of the heating of consecutive HIFU sonications. Maps were reconstructed of estimated cooling time constants and mean ROI values could be well explained by the applied heating pattern. Heating upon HIFU sonication and subsequent cooling could be observed in the in vivo demonstration.
    No preview · Article · Sep 2015 · Physics in Medicine and Biology
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    ABSTRACT: Purpose: One of the major issues in high intensity focused ultrasound ablation of abdominal lesions is obstruction of the ultrasound beam by the thoracic cage. Beam shaping strategies have been shown by several authors to increase focal point intensity while limiting rib exposure. However, as rib obstruction leaves only part of the aperture available for energy transmission, conserving total emitted acoustic power, the intensity in the near-field tissues inherently increases after beam shaping. Despite of effective rib sparing, those tissues are therefore subjected to increased risk of thermal damage. In this study, for a number of clinically representative intercostal sonication geometries, modeling clinically available hardware, the effect of beam shaping on both the exposure of the ribs and near-field to acoustic energy was evaluated and the implications for the volumetric ablation rate were addressed.
    No preview · Article · Aug 2015 · Medical Physics
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    ABSTRACT: Microbubbles (MBs) in combination with ultrasound (US) can enhance cell membrane permeability, and have the potential to facilitate the cellular uptake of hydrophilic molecules. However, the exact mechanism behind US- and MB-mediated intracellular delivery still remains to be fully understood. Among the proposed mechanisms are formation of transient pores and endocytosis stimulation. In our study, we investigated whether endocytosis is involved in US- and MB-mediated delivery of small molecules. Dynamic fluorescence microscopy was used to investigate the effects of endocytosis inhibitors on the pharmacokinetic parameters of US- and MB-mediated uptake of SYTOX Green, a 600 Da hydrophilic model drug. C6 rat glioma cells, together with SonoVue(®) MBs, were exposed to 1.4 MHz US waves at 0.2 MPa peak-negative pressure. Collection of the signal intensity in each individual nucleus was monitored during and after US exposure by a fibered confocal fluorescence microscope designed for real-time imaging. Exposed to US waves, C6 cells pretreated with chlorpromazine, an inhibitor of clathrin-mediated endocytosis, showed up to a 2.5-fold significant increase of the uptake time constant, and a 1.1-fold increase with genistein, an inhibitor of caveolae-mediated endocytosis. Both inhibitors slowed down the US-mediated uptake of SYTOX Green. With C6 cells and our experimental settings, these quantitative data indicate that endocytosis plays a role in sonopermeabilization-mediated delivery of small molecules with a more predominant contribution of clathrin-mediated endocytosis.
    Full-text · Article · Jul 2015 · Physical Biology
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    ABSTRACT: Purpose: While respiratory motion compensation for magnetic resonance (MR)-guided high intensity focused ultrasound (HIFU) interventions has been extensively studied, the influence of slow physiological motion due to, for example, peristaltic activity, has so far been largely neglected. During lengthy interventions, the magnitude of the latter can exceed acceptable therapeutic margins. The goal of the present study is to exploit the episodic workflow of these therapies to implement a motion correction strategy for slow varying drifts of the target area and organs at risk over the entire duration of the intervention.
    No preview · Article · Jul 2015 · Medical Physics
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    ABSTRACT: The combination of microbubbles and ultrasound has emerged as a promising method for local drug delivery. Microbubbles can be locally activated by a targeted ultrasound beam, which can result in several bio-effects. For drug delivery, microbubble-assisted ultrasound is used to increase vascular- and plasma membrane permeability for facilitating drug extravasation and the cellular uptake of drugs in the treated region, respectively. In the case of drug-loaded microbubbles, these two mechanisms can be combined with local release of the drug following destruction of the microbubble. The use of microbubble-assisted ultrasound to deliver chemotherapeutic agents is also referred to as sonochemotherapy. In this review, the basic principles of sonochemotherapy are discussed, including aspects such as the type of (drug-loaded) microbubbles used, the routes of administration used in vivo, ultrasound devices and parameters, treatment schedules and safety issues. Finally, the clinical translation of sonochemotherapy is discussed, including the first clinical study using sonochemotherapy.
    Full-text · Article · Jul 2015 · Frontiers in Pharmacology
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    ABSTRACT: Thermal ablation with high intensity focused ultrasound (HIFU) is an emerging noninvasive technique for the treatment of solid tumors. HIFU treatment of malignant tumors requires accurate treatment planning, monitoring and evaluation, which can be facilitated by performing the procedure in an MR-guided HIFU system. The MR-based evaluation of HIFU treatment is most often restricted to contrast-enhanced T1 -weighted imaging, while it has been shown that the non-perfused volume may not reflect the extent of nonviable tumor tissue after HIFU treatment. There are multiple studies in which more advanced MRI methods were assessed for their suitability for the evaluation of HIFU treatment. While several of these methods seem promising regarding their sensitivity to HIFU-induced tissue changes, there is still ample room for improvement of MRI protocols for HIFU treatment evaluation. In this review article, we describe the major acute and delayed effects of HIFU treatment. For each effect, the MRI methods that have been-or could be-used to detect the associated tissue changes are described. In addition, the potential value of multiparametric MRI for the evaluation of HIFU treatment is discussed. The review ends with a discussion on future directions for the MRI-based evaluation of HIFU treatment. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Jun 2015 · Magnetic Resonance in Medicine
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    ABSTRACT: The tumor microenvironment is an interesting target for anticancer therapies but modifying this compartment is challenging. Here, we demonstrate the feasibility of a gene therapy strategy that combined targeting to bone marrow-derived tumor microenvironment using genetically modified bone-marrow derived cells and control of transgene expression by local hyperthermia through a thermo-inducible promoter. Chimera were obtained by engraftment of bone marrow from transgenic mice expressing reporter genes under transcriptional control of heat shock promoter and inoculated sub-cutaneously with tumors cells. Heat shocks were applied at the tumor site using a water bath or magnetic resonance guided high intensity focused ultrasound device. Reporter gene expression was followed by bioluminescence and fluorescence imaging and immunohistochemistry. Bone marrow-derived cells expressing reporter genes were identified to be mainly tumor-associated macrophages. We thus provide the proof of concept for a gene therapy strategy that allows for spatiotemporal control of transgenes expression by macrophages targeted to the tumor microenvironment.
    Preview · Article · Jun 2015 · Oncotarget
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    Full-text · Article · Jun 2015
  • P Borman · S Crijns · C Bos · C Moonen · B Raaymakers
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    ABSTRACT: To speed up PRFS thermometry using Simultaneous MultiSlice acquisitions (SMS) with a focus on HIFU treatments, where temperatures at multiple locations such as near field, far field and focus need to be monitored in real-time. The phantom is a 2% agar 2% silica gel. The gel was heated using an ultrasound transducer operating at 1.2MHz with a focus of 8mm, delivering 60W for 60 seconds. The temperature is measured with two optical probes; one at the focus and one 4cm above that. The probes are used to compare the PRFS thermometry results with. The images are made on a 1.5T Philips Achieva scanner with a SMS GRE acquisition using CAIPIRINHA: two slices are excited simultaneously with a Multi-Band pulse and one slice is shifted one half FOV, resulting in minimal overlap and optimal sensitivity.The images are reconstructed offline in MATLAB using ReconFrame (GyroTools). The temperature is calculated from the PRFS and averaged over an ROI at the focus. The SMS acquisition has acceleration factor 2 and can be combined with SENSE. Results are compared to M2D acquisitions with SENSE factors 1 and 2. The SMS temperature curves are in good qualitative agreement with the temperature curves of the probes. The difference is probably caused by the probes not being exactly at the focus. There is good agreement between the M2D and SMS curves, even though SMS scans have acceleration factor 2. We also showed that SMS can be combined with SENSE to achieve acceleration factor 3. The SMS temperature curves are in good qualitative agreement with the temperature curves of the probes. The difference is probably caused by the probes not being exactly at the focus. There is good agreement between the M2D and SMS curves, even though SMS scans have acceleration factor 2. We also showed that SMS can be combined withSENSE to achieve acceleration factor 3. This work showsthatPRFSthermometry inmultiple slices can be accelerated by SMS techniques. We demonstrated that the temperature measured using SMS scans is in agreement with the M2D scans, while the dynamic scan time of the former is almost half of that of the latter. This work shows that PRFS thermometry in multiple slices can be accelerated by SMS techniques. We demonstrated that the temperature measured using SMS scans is in agreement with the M2D scans, while the dynamic scan time of the former is almost half of that of the latter. This work was funded by the SoRTS consortium.
    No preview · Article · Jun 2015 · Medical Physics

Publication Stats

11k Citations
964.26 Total Impact Points

Institutions

  • 2012-2016
    • University Medical Center Utrecht
      • • Department of Radiology
      • • Division of Imaging
      Utrecht, Utrecht, Netherlands
  • 2003-2015
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 2014
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
  • 2000-2012
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1998-2012
    • Université Victor Segalen Bordeaux 2
      • Centre de Résonance Magnétique des Systèmes Biologiques
      Burdeos, Aquitaine, France
  • 2007-2009
    • Laboratory of Biomedical Imaging
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 2006
    • Aarhus University Hospital
      Aarhus, Central Jutland, Denmark
  • 2005
    • University of Tours
      Tours, Centre, France
  • 1989-2005
    • National Institutes of Health
      • Laboratory of Research Technologies
      Maryland, United States
  • 2004
    • Image Guided Therapy
      Pessac, Aquitaine, France
  • 1996
    • National Institute of Mental Health (NIMH)
      • Clinical Brain Disorders Branch
      Bethesda, MD, United States
  • 1994
    • College of Saint Elizabeth
      Washington, Washington, D.C., United States
  • 1993-1994
    • Johns Hopkins University
      • Department of Radiology
      Baltimore, Maryland, United States
    • Royal College of Surgeons of England
      Londinium, England, United Kingdom
  • 1991
    • NCI-Frederick
      Фредерик, Maryland, United States
    • Georgetown University
      • Department of Pharmacology
      Washington, Washington, D.C., United States
  • 1982-1991
    • Wageningen University
      • Laboratory of Biochemistry
      Wageningen, Provincie Gelderland, Netherlands
  • 1987-1988
    • University of California, Davis
      • Department of Pediatrics
      Davis, California, United States