Chrit Moonen

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (381)945.87 Total impact

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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.
    Physics in Medicine and Biology 11/2015; 60(23). DOI:10.1088/0031-9155/60/23/9003 · 2.76 Impact Factor
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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.
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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.
    Physics in Medicine and Biology 09/2015; 60(19):7729-7746. DOI:10.1088/0031-9155/60/19/7729 · 2.76 Impact Factor
  • M de Greef · G Schubert · J W Wijlemans · J Koskela · L W Bartels · C T W Moonen · M Ries ·
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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.
    Medical Physics 08/2015; 42(8):4685. DOI:10.1118/1.4925056 · 2.64 Impact Factor
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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.
    Physical Biology 07/2015; 12(4):046010. DOI:10.1088/1478-3975/12/4/046010 · 2.54 Impact Factor
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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.
    Medical Physics 07/2015; 42(7):4137. DOI:10.1118/1.4922403 · 2.64 Impact Factor
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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.
    Frontiers in Pharmacology 07/2015; 6:138. DOI:10.3389/fphar.2015.00138 · 3.80 Impact Factor
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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.
    Magnetic Resonance in Medicine 06/2015; DOI:10.1002/mrm.25758 · 3.57 Impact Factor
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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.
    Oncotarget 06/2015; 6(27). DOI:10.18632/oncotarget.4288 · 6.36 Impact Factor
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    06/2015; 3(Suppl 1):O74. DOI:10.1186/2050-5736-3-S1-O74
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    06/2015; 3(Suppl 1):P43. DOI:10.1186/2050-5736-3-S1-P43

  • 06/2015; 3(Suppl 1):O102. DOI:10.1186/2050-5736-3-S1-O102
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    06/2015; 3(Suppl 1):P60. DOI:10.1186/2050-5736-3-S1-P60

  • 06/2015; 3(Suppl 1):O86. DOI:10.1186/2050-5736-3-S1-O86
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    06/2015; 3(Suppl 1):P54. DOI:10.1186/2050-5736-3-S1-P54
  • 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.
    Medical Physics 06/2015; 42(6):3263. DOI:10.1118/1.4924090 · 2.64 Impact Factor
  • C Moonen ·
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    ABSTRACT: MR guided focused ultrasound (MRgFUS), or alternatively high-intensity focused ultrasound (MRgHIFU), is approved for thermal ablative treatment of uterine fibroids and pain palliation in bone metastases. Ablation of malignant tumors is under active investigation in sites such as breast, prostate, brain, liver, kidney, pancreas, and soft tissue. Hyperthermia therapy with MRgFUS is also feasible, and may be used in conjunction with radiotherapy and for local targeted drug delivery. MRI allows in situ target definition and provides continuous temperature monitoring and subsequent thermal dose mapping during HIFU. Although MRgHIFU can be very precise, treatment of mobile organs is challenging and advanced techniques are required because of artifacts in MR temperature mapping, the need for intercostal firing, and need for gated HIFU or tracking of the lesion in real time. The first invited talk, "MR guided Focused Ultrasound Treatment of Tumors in Bone and Soft Tissue", will summarize the treatment protocol and review results from treatment of bone tumors. In addition, efforts to extend this technology to treat both benign and malignant soft tissue tumors of the extremities will be presented. The second invited talk, "MRI guided High Intensity Focused Ultrasound - Advanced Approaches for Ablation and Hyperthermia", will provide an overview of techniques that are in or near clinical trials for thermal ablation and hyperthermia, with an emphasis of applications in abdominal organs and breast, including methods for MRTI and tracking targets in moving organs. 1.Learn background on devices and techniques for MR guided HIFU for cancer therapy2.Understand issues and current status of clinical MRg HIFU3.Understand strategies for compensating for organ movement during MRgHIFU4.Understand strategies for strategies for delivering hyperthermia with MRgHIFUCM - research collaboration with Philips.
    Medical Physics 06/2015; 42(6):3598. DOI:10.1118/1.4925564 · 2.64 Impact Factor
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    ABSTRACT: To investigate the effect of the aqueous and fatty tissue magnetic susceptibility distribution on absolute and relative temperature measurements as obtained directly from the water/fat (w/f) frequency difference. Absolute thermometry was investigated using spherical phantoms filled with pork and margarine, which were scanned in three orthogonal orientations. To evaluate relative fat referencing, multigradient echo scans were acquired before and after heating pork tissue via high-intensity focused ultrasound (HIFU). Simulations were performed to estimate the errors that can be expected in human breast tissue. The sphere experiment showed susceptibility-related errors of 8.4°C and 0.2°C for pork and margarine, respectively. For relative fat referencing measurements, fat showed pronounced phase changes of opposite polarity to aqueous tissue. The apparent mean temperature for a numerical breast model assumed to be 37°C was 47.2 ± 21.6°C. Simulations of relative fat referencing for a HIFU sonication (ΔT = 29.7°C) yielded a maximum temperature error of 6.6°C compared with 2.5°C without fat referencing. Variations in the observed frequency difference between water and fat are largely due to variations in the w/f spatial distribution. This effect may lead to considerable errors in absolute MR thermometry. Additionally, fat referencing may exacerbate rather than correct for proton resonance frequency shift-temperature measurement errors. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 05/2015; DOI:10.1002/mrm.25727 · 3.57 Impact Factor
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Publication Stats

11k Citations
945.87 Total Impact Points


  • 2012-2015
    • University Medical Center Utrecht
      • Division of Imaging
      Utrecht, Utrecht, Netherlands
  • 2014
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
  • 2003-2012
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 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
  • 1991-2011
    • Georgetown University
      • Department of Pharmacology
      Rockville, MD, United States
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2007-2009
    • Laboratory of Biomedical Imaging
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Bordeaux
      Burdeos, Aquitaine, France
  • 2006
    • Aarhus University Hospital
      • Institute of Clinical Medicine
      Århus, Central Jutland, Denmark
  • 2005
    • University of Tours
      Tours, Centre, France
  • 1989-2005
    • National Institutes of Health
      • Laboratory of Research Technologies
      Maryland, United States
  • 1996
    • National Institute of Mental Health (NIMH)
      • Clinical Brain Disorders Branch
      Bethesda, MD, United States
  • 1994
    • Johns Hopkins University
      • Department of Radiology
      Baltimore, Maryland, United States
    • College of Saint Elizabeth
      Washington, Washington, D.C., United States
  • 1993
    • Royal College of Surgeons of England
      Londinium, England, United Kingdom
  • 1982-1991
    • Wageningen University
      • Laboratory of Biochemistry
      Wageningen, Provincie Gelderland, Netherlands
  • 1987-1988
    • University of California, Davis
      • Department of Pediatrics
      Davis, California, United States