Keith S Cover

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (35)150.23 Total impact

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    ABSTRACT: The back-to-back (BTB) acquisition of MP-RAGE MRI scans of the Alzheimer's Disease Neuroimaging Initiative (ADNI1) provides an excellent data set with which to check the reproducibility of brain atrophy measures. As part of ADNI1, 131 subjects received BTB MP-RAGEs at multiple time points and two field strengths of 3T and 1.5T. As a result, high quality data from 200 subject-visit-pairs was available to compare the reproducibility of brain atrophies measured with FSL/SIENA over 12 to 18 month intervals at both 3T and 1.5T. Although several publications have reported on the differing performance of brain atrophy measures at 3T and 1.5T, no formal comparison of reproducibility has been published to date. Another goal was to check whether tuning the SIENA options, including -B, -S, -R and the fractional intensity threshold (f) had a significant impact on the reproducibility. The BTB reproducibility for SIENA was quantified by the 50th percentile of the absolute value of the difference in the percentage brain volume change (PBVC) for the BTB MP-RAGES. At both 3T and 1.5T the SIENA option combination of “-B f=0.2”, which is different form the default values of f=0.5, yielded the best reproducibility as measured by the 50th percentile yielding 0.28 (0.23–0.39)% and 0.26 (0.20–0.32)%. These results demonstrated that in general 3T had no advantage over 1.5T for the whole brain atrophy measure – at least for SIENA. While 3T MRI is superior to 1.5T for many types of measurements, and thus worth the additional cost, brain atrophy measurement does not seem to be one of them.
    Psychiatry Research Neuroimaging 10/2014; 224(1). DOI:10.1016/j.pscychresns.2014.07.002 · 2.83 Impact Factor
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    Alzheimer's and Dementia 07/2014; 10(4):P390-P391. DOI:10.1016/j.jalz.2014.05.474 · 17.47 Impact Factor
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    ABSTRACT: Background To measure hippocampal volume change in Alzheimer's disease (AD) or mild cognitive impairment (MCI), expert manual delineation is often used because of its supposed accuracy. It has been suggested that expert outlining yields poorer reproducibility as compared to automated methods, but this has not been investigated. Aim To determine the reproducibilities of expert manual outlining and two common automated methods for measuring hippocampal atrophy rates in healthy aging, MCI and AD. Methods From the Alzheimer's Disease Neuroimaging Initiative (ADNI), 80 subjects were selected: 20 patients with AD, 40 patients with mild cognitive impairment (MCI) and 20 healthy controls (HCs). Left and right hippocampal volume change between baseline and month-12 visit was assessed by using expert manual delineation, and by the automated software packages FreeSurfer (longitudinal processing stream) and FIRST. To assess reproducibility of the measured hippocampal volume change, both back-to-back (BTB) MPRAGE scans available for each visit were analyzed. Hippocampal volume change was expressed in μL, and as a percentage of baseline volume. Reproducibility of the 1-year hippocampal volume change was estimated from the BTB measurements by using linear mixed model to calculate the limits of agreement (LoA) of each method, reflecting its measurement uncertainty. Using the delta method, approximate p-values were calculated for the pairwise comparisons between methods. Statistical analyses were performed both with inclusion and exclusion of visibly incorrect segmentations. Results Visibly incorrect automated segmentation in either one or both scans of a longitudinal scan pair occurred in 7.5% of the hippocampi for FreeSurfer and in 6.9% of the hippocampi for FIRST. After excluding these failed cases, reproducibility analysis for 1-year percentage volume change yielded LoA of ± 7.2% for FreeSurfer, ± 9.7% for expert manual delineation, and ± 10.0% for FIRST. Methods ranked the same for reproducibility of 1-year μL volume change, with LoA of ± 218 μL for FreeSurfer, ± 319 μL for expert manual delineation, and ± 333 μL for FIRST. Approximate p-values indicated that reproducibility was better for FreeSurfer than for manual or FIRST, and that manual and FIRST did not differ. Inclusion of failed automated segmentations led to worsening of reproducibility of both automated methods for 1-year raw and percentage volume change. Conclusion Quantitative reproducibility values of 1-year microliter and percentage hippocampal volume change were roughly similar between expert manual outlining, FIRST and FreeSurfer, but FreeSurfer reproducibility was statistically significantly superior to both manual outlining and FIRST after exclusion of failed segmentations.
    NeuroImage 05/2014; 92:169–181. DOI:10.1016/j.neuroimage.2014.01.058 · 6.36 Impact Factor
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    ABSTRACT: Background: In many retrospective studies and large clinical trials, high-resolution, good-contrast 3DT1 images are unavailable, hampering detailed analysis of brain atrophy. Ventricular enlargement then provides a sensitive indirect measure of ongoing central brain atrophy. Validated automated methods are required that can reliably measure ventricular enlargement and are robust across magnetic resonance (MR) image types. Aim: To validate the automated method VIENA for measuring the percentage ventricular volume change (PVVC) between two scans. Materials and Methods: Accuracy was assessed using four image types, acquired in 15 elderly patients (five with Alzheimer's disease, five with mild cognitive impairment, and five cognitively normal elderly) and 58 patients with multiple sclerosis (MS), by comparing PVVC values from VIENA to manual outlining. Precision was assessed from data with three imaging time points per MS patient, by measuring the difference between the direct (one-step) and indirect (two-step) measurement of ventricular volume change between the first and last time points. The stringent concordance correlation coefficient (CCC) was used to quantify absolute agreement. Results: CCC of VIENA with manual measurement was 0.84, indicating good absolute agreement. The median absolute difference between two-step and one-step measurement with VIENA was 1.01%, while CCC was 0.98. Neither initial ventricular volume nor ventricular volume change affected performance of the method. Discussion: VIENA has good accuracy and good precision across four image types. VIENA therefore provides a useful fully automated method for measuring ventricular volume change in large datasets. Conclusion: VIENA is a robust, accurate, and precise method for measuring ventricular volume change. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2014; 35(4). DOI:10.1002/hbm.22237 · 6.92 Impact Factor
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    ABSTRACT: Purpose To compare the reproducibility of the hippocampal atrophy rates over one year generated by the fully automated FreeSurer/ReconAll and FSL/FIRST software packages using a back-to-back (BTB) reproducibility test based on the ADNI1 data set [1] . Conclusions Study funding was provided by neuGRID4you (N4U), an European Community FP7 project (grant agreement 283562), and the VU University Medical Center, Amsterdam, The Netherlands ADNI1 Back-to-Back MPRAGEs While rarely mentioned in the literature, as part of the first Alzheimer's Disease Neuroimaging Initiative (ADNI1) study, the 3D T1-weighted MRI scans (also know as MPRAGE scans) were acquired in duplicate during each patient visit -with the acquisition of the second MPRAGE starting within seconds of completion of the first. As ADNI has over 800 subjects -with an average of 6 visits each – spread over several years, roughly 9,000 back-to-back (BTB) MPRAGE were available to probe the performance of brain atrophy measures [1]. Table 1. The reproducibility of hippocampal atrophy rates for FreeSurfer/ReconAll and FSL/FIRST using back-to-back (BTB) ADNI1 MPRAGEs MRI scans . Units are percentage difference in the atrophy rate over 1 year. Smaller is better.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 07/2013; 9(4):592-P592. DOI:10.1016/j.jalz.2013.05.1180 · 17.47 Impact Factor
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    ABSTRACT: Infection following neurosurgery is all too common. One possible source of infection is the transportation of dust and other contaminates into the open wound by airflow within the operating theatre. While many modern operating theatres have a filtered, uniform and gentle flow of air cascading down over the operating table from a large area fan in the ceiling, many obstacles might introduce turbulence into the laminar flow including lights, equipment and personal. Schlieren imaging - which is sensitive to small disturbances in the laminar flow such as breathing and turbulence caused by air warmed by a hand at body temperature – was used to image the air flow due to activities in an operating theatre. Color intensity projections (CIPs) were employed to reduce the workload of analyzing the large amount of video data. CIPs – which has been applied to images in angiography, 4D CT, nuclear medicine and astronomy – summarizes the changes over many gray scale images in a single color image in a way which most interpreters find intuitive. CIPs uses the hue, saturation and brightness of the color image to encode the summary. Imaging in an operating theatre showed substantial disruptions to the airflow due to equipment such as the lighting. When these disruptions are combined with such minor factors as heat from the hand, reversal of the preferred airflow patterns can occur. These reversals of preferred airflow patterns have the potential to transport contaminates into the open wound. Further study is required to understand both the frequency of the reversed airflow patterns and the impact they may have on infection rates.
    Conference on Advanced Biomedical and Clinical Diagnostic Systems XI; 03/2013
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    ABSTRACT: Color intensity projections (CIPs) has been employed to improve the accuracy and reduce the workload of interpreting a series of grayscale images by summarizing the grayscale images in a single color image. CIPs – which has been applied to grayscale images in angiography, 4D CT, nuclear medicine and astronomy – uses the hue, saturation and brightness of the color image to encode the summary information. In CIPs, when a pixel has the same value over the grayscale images, the corresponding pixel in the color image has the identical grayscale color. The arrival time of a signal at each pixel, such as the arrival time of contrast in angiography, is often encoded in the hue (red-yellow-green-light blue-blue-purple) of the corresponding pixel in the color image. In addition, the saturation and brightness of each pixel in the color image encodes the amplitude range and amplitude maximum of the corresponding pixel in the grayscale images. In previous applications of CIPs the hue has been limited to less than one cycle over the color image to avoid the aliasing due to a hue corresponding to more than one arrival time. However, sometimes in applications such as angiography and astronomy, in some instances the aliasing due to increasing the number of cycles of hue over the color image is tolerable as it increases the resolution of arrival time. Key to applying hue cycling effectively is interpolating several grayscale images between each pair of grayscale images. Ideally, the interpreter is allowed to adjust the amount of hue cycling in realtime to find the best setting for each particular CIPs image. CIPs with hue cycling should be a valuable tool in many fields where interpreting a series of grayscale images is required.
    03/2013
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    ABSTRACT: Background Brain atrophy studies often use FSL-BET (Brain Extraction Tool) as the first step of image processing. Default BET does not always give satisfactory results on 3DT1 MR images, which negatively impacts atrophy measurements. Finding the right alternative BET settings can be a difficult and time-consuming task, which can introduce unwanted variability.AimTo systematically analyze the performance of BET in images of MS patients by varying its parameters and options combinations, and quantitatively comparing its results to a manual gold standard.Methods Images from 159 MS patients were selected from different MAGNIMS consortium centers, and 16 different 3DT1 acquisition protocols at 1.5 T or 3 T. Before running BET, one of three pre-processing pipelines was applied: (1) no pre-processing, (2) removal of neck slices, or (3) additional N3 inhomogeneity correction. Then BET was applied, systematically varying the fractional intensity threshold (the “f” parameter) and with either one of the main BET options (“B” — bias field correction and neck cleanup, “R” — robust brain center estimation, or “S” — eye and optic nerve cleanup) or none. For comparison, intracranial cavity masks were manually created for all image volumes. FSL-FAST (FMRIB's Automated Segmentation Tool) tissue-type segmentation was run on all BET output images and on the image volumes masked with the manual intracranial cavity masks (thus creating the gold-standard tissue masks). The resulting brain tissue masks were quantitatively compared to the gold standard using Dice overlap coefficient (DOC). Normalized brain volumes (NBV) were calculated with SIENAX. NBV values obtained using for SIENAX other BET settings than default were compared to gold standard NBV with the paired t-test.ResultsThe parameter/preprocessing/options combinations resulted in 20,988 BET runs. The median DOC for default BET (f = 0.5, g = 0) was 0.913 (range 0.321–0.977) across all 159 native scans. For all acquisition protocols, brain extraction was substantially improved for lower values of “f” than the default value. Using native images, optimum BET performance was observed for f = 0.2 with option “B”, giving median DOC = 0.979 (range 0.867–0.994). Using neck removal before BET, optimum BET performance was observed for f = 0.1 with option “B”, giving median DOC 0.983 (range 0.844–0.996). Using the above BET-options for SIENAX instead of default, the NBV values obtained from images after neck removal with f = 0.1 and option “B” did not differ statistically from NBV values obtained with gold-standard.Conclusion Although default BET performs reasonably well on most 3DT1 images of MS patients, the performance can be improved substantially. The removal of the neck slices, either externally or within BET, has a marked positive effect on the brain extraction quality. BET option “B” with f = 0.1 after removal of the neck slices seems to work best for all acquisition protocols.
    NeuroImage 07/2012; 61(4):1484–1494. DOI:10.1016/j.neuroimage.2012.03.074 · 6.36 Impact Factor
  • Alzheimer's and Dementia 07/2012; 8(4):P338. DOI:10.1016/j.jalz.2012.05.932 · 17.47 Impact Factor
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    Keith S. Cover
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    ABSTRACT: Color intensity projections (CIPs) have been shown to improve the visualisation of greyscale angiography images by combining greyscale images into a single color image. A key property of the combined CIPs image is the encoding of the arrival time information from greyscale images into the hue of the color in the CIPs image. A few minor improvements to the calculation of the CIPs image are introduced that substantially improve the quality of the visualisation. One improvement is interpolating of the greyscale images in time before calculation of the CIPs image. A second is the use of hue cycling - where the hue of the color is cycled through more than once in an image. The hue cycling allows the variation of the hue to be concentrated in structures of interest. An angiogram of a brain is used to demonstrate the substantial improvements hue cycling brings to CIPs images. A third improvement is the use of maximum intensity projection for 2D rendering of a 3D CIPs image volume. Other potential applications of CIPs are also mentioned.
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    Keith S. Cover
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    ABSTRACT: While fully automated methods for detecting faint moving objects in astronomical images - such as Kuiper belt objects (KBOs) - are constantly improving, visual detection still has a role to play especially when the fixed background is cluttered with stars. Color intensity projections (CIPs) using hue cycling - which combines a sequence of greyscale images into a single color image - aids in the visual detection of moving objects by highlighting them using color in an intuitive way. To demonstrate the usefulness of CIPs in detecting faint moving objects a sequence of 16 images from the SuprimeCam camera of the Subaru telescope were combined into a CIPs image. As well has making even faint moving objects easier to visually detect against a cluttered background, CCD artefacts were also more easily recognisable. The new Hyper SuprimeCam for the Subaru telescope - which will allow many short exposure images to be acquired with little dead time between images - should provide ideal data for use with the CIPs algorithm. In addition, the current search for KBOs to be targeted by the New Horizon's spacecraft after its flyby of Pluto provides an excellent test case for the state of the art in faint moving object detection against a cluttered background.
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    Neurobiology of aging 01/2012; 33:1486.e9-15. · 4.85 Impact Factor
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    Neurobiology of aging 01/2012; 33:1486.e9-15. · 4.85 Impact Factor
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    Neurobiology of aging 01/2012; 33:1486.e9-15. · 4.85 Impact Factor
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    ABSTRACT: SienaX and Siena are widely used and fully automated algorithms for measuring whole brain volume and volume change in cross-sectional and longitudinal MRI studies and are particularly useful in studies of brain atrophy. The reproducibility of the algorithms was assessed using the 3D T1 weighted MP-RAGE scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. The back-to-back (BTB) MP-RAGE scans in the ADNI data set makes it a valuable benchmark against which to assess the performance of algorithms of measuring atrophy in the human brain with MRI scans. A total of 671 subjects were included for SienaX and 385 subjects for Siena. The annual percentage brain volume change (PBVC) rates were -0.65±0.82%/year for the healthy controls, -1.15±1.21%/year for mild cognitively impairment (MCI) and -1.84±1.33%/year for AD, in line with previous findings. The median of the absolute value of the reproducibility of SienaX's normalized brain volume (NBV) was 0.96% while the 90th percentile was 5.11%. The reproducibility of Siena's PBVC had a median of 0.35% and a 90th percentile of 1.37%. While the median reproducibility for SienaX's NBV was in line with the values previously reported in the literature, the median reproducibility of Siena's PBVC was about twice that reported. Also, the 90th percentiles for both SienaX and Siena were about twice the size that would be expected for a Gaussian distribution. Because of the natural variation of the disease among patients over a year, a perfectly reproducible whole brain atrophy algorithm would reduce the estimated group size needed to detect a specified treatment effect by only 30% to 40% as compared to Siena's.
    Psychiatry Research 09/2011; 193(3):182-90. DOI:10.1016/j.pscychresns.2011.02.012 · 2.68 Impact Factor
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    ABSTRACT: Use of planning 4-dimensional CT (4DCT) scans often permits use of smaller target volumes for thoracic tumors but this assumes a reproducible pattern of motion during radiotherapy. We compared cranio-caudal (CC) motion on MV cine-images acquired during treatment with that seen on planning 4DCT. A pre-programmable respiratory motion phantom and a software tool for motion assessment were used to validate the use of MV cine-images for motion detection. MV cine-images acquired in 20 patients with node-positive lung cancer were analyzed using the same software. Intra-fraction CC motion on 6 MV cine-images from each patient was compared with CC motion on their planning 4DCT. Software-based motion measurement on MV cine-images from the phantom corresponded to actual motion. Mean CC motion of primary tumor, carina and hilus on 4DCT was 7.3mm (range 2-13.8mm), 6.8mm (1.8-21.2) and 11.0mm (4.2-15.1), respectively. Corresponding intra-fraction motion on MV cine was 4.1mm (0.6-13.6mm); 2.7mm (0-10mm) and 6.0mm (1.8-14.4mm), respectively. The tumor, hilus and carina could be tracked in 95%, 88% and 38% of the MV cine-images, respectively. Intra-fraction motion can be reliably measured using MV-cine images from a phantom. Motion discrepancies identified on MV cine-images can identify patients in whom planning 4DCT scans are not representative.
    Radiotherapy and Oncology 05/2011; 99(2):155-60. DOI:10.1016/j.radonc.2011.05.037 · 4.86 Impact Factor
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    ABSTRACT: We investigated progression of atrophy in vivo, in Alzheimer’s disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 ± 0.7years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1–6.2) for occipital atrophy and 15.8 (95% CI = 3.5–71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD.
    European Radiology 12/2009; 19(12):2826-2833. DOI:10.1007/s00330-009-1512-5 · 4.34 Impact Factor
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    Keith S. Cover
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    ABSTRACT: The recent release of the first light sky map of the cosmic microwave background (CMB) from the Planck satellite provides an initial opportunity for comparison with the WMAP and COBE sky maps and their reconstruction algorithms. The precision of the match between Planck's and WMAP's anisotropies below several degrees in size, which corresponds to spherical harmonics with high l, provides confidence that the differences between the anisotropies at low l are substantial. If the Planck first light sky map is taken as the gold standard, the results seem to suggest the low l components of the WMAP map and a considerable part of the COBE sky map have a similar reconstruction artefact. As the Planck first light sky map covers only about 10% of the sky, any conclusions drawn from this comparison are speculative but deserving of further investigation. Comment: 10 pages and 3 figures in manuscript - added some references and improved the discussion
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    Keith S. Cover
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    ABSTRACT: The purpose of this reanalysis of the WMAP uncalibrated time ordered data (TOD) was two fold. The first was to reassess the reliability of the detection of the anisotropies in the official WMAP sky maps of the cosmic microwave background (CMB). The second was to assess the performance of a proposed criterion in avoiding systematic error in detecting a signal of interest. The criterion was implemented by testing the null hypothesis that the uncalibrated TOD was consistent with no anisotropies when WMAP's hourly calibration parameters were allowed to vary. It was shown independently for all 20 WMAP channels that sky maps with no anisotropies were a better fit to the TOD than those from the official analysis. The recently launched Planck satellite should help sort out this perplexing result.
    EPL (Europhysics Letters) 10/2009; 87(6):69003. DOI:10.1209/0295-5075/87/69003 · 2.27 Impact Factor
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    ABSTRACT: Diffusion tensor imaging (DTI) measures have shown to be sensitive to white matter (WM) damage in multiple sclerosis (MS), not only inside focal lesions but also in user-defined regions in the so-called normal-appearing white matter (NAWM). New analysis techniques for DTI measures are now available that allow for hypothesis-free localization of damage. We performed DTI measurements of 30 MS patients selected for low focal lesion loads, and of 31 age-matched healthy controls and analyzed these using tract-based spatial statistics (TBSS). Patients were found to have a lower fractional anisotropy (FA) compared to controls in a number of brain regions, including the fornices, the left corona radiata, the inferior longitudinal fasciculus in both hemispheres, both optic radiations, and parts of the corpus callosum. In the regions of reduced FA, an increase in radial diffusivity and a less pronounced increase of axial diffusivity were found. Neurocognitive assessment showed that patients had normal visuospatial memory performance, just-normal attention, and impaired processing speed; the latter was associated with abnormal FA in the corpus callosum, an area which was relatively devoid of lesions visible on proton density-weighted images in our patients. TBSS can be useful in future studies with other MS patient samples to provide an unbiased localization of damage and generate location-specific hypotheses.
    NeuroImage 12/2008; 44(4):1397-403. DOI:10.1016/j.neuroimage.2008.10.026 · 6.36 Impact Factor

Publication Stats

546 Citations
150.23 Total Impact Points

Institutions

  • 2004–2014
    • VU University Medical Center
      • • Department of Physics and Medical Technology (FMT)
      • • Department of Radiation Oncology
      Amsterdamo, North Holland, Netherlands
  • 2006–2013
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2009
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada