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Lin A, De Backer J, Quatannens D, Cuypers B, Verswyvel H, De La Hoz EC, Ribbens B, Siozopoulou V, Van Audenaerde J, Marcq E, Lardon F, Laukens K, Vanlanduit S, Smits E, Bogaerts A (2022) The effect of local non‐thermal plasma therapy on the<scp>cancer‐immunity</scp>cycle in a melanoma mouse model
Abstract: Melanoma remains a deadly cancer despite significant advances in immune checkpoint blockade and targeted therapies. The incidence of melanoma is also growing worldwide, which highlights the need for novel treatment options and strategic combination of therapies. Here, we investigate non-thermal plasma (NTP), an ionized gas, as a promising, therapeutic option. In a melanoma mouse model, direct treatment of tumors with NTP results in reduced tumor burden and prolonged survival. Physical characterization of NTP treatment in situ reveals the deposited NTP energy and temperature associated with therapy response, and whole transcriptome analysis of the tumor identified several modulated pathways. NTP treatment also enhances the cancer-immunity cycle, as immune cells in both the tumor and tumor-draining lymph nodes appear more stimulated to perform their anti-cancer functions. Thus, our data suggest that local NTP therapy stimulates systemic, anti-cancer immunity. We discuss, in detail, how these fundamental insights will help direct the translation of NTP technology into the clinic and inform rational combination strategies to address the challenges in melanoma therapy.
Keywords: University Hospital Antwerp; A1 Journal article; Pharmacology. Therapy; Engineering sciences. Technology; ADReM Data Lab (ADReM); Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE); Proteinscience, proteomics and epigenetic signaling (PPES)
DOI: 10.1002/btm2.10314
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“Non‐Thermal Plasma as a Unique Delivery System of Short‐Lived Reactive Oxygen and Nitrogen Species for Immunogenic Cell Death in Melanoma Cells”. Lin A, Gorbanev Y, De Backer J, Van Loenhout J, Van Boxem W, Lemière F, Cos P, Dewilde S, Smits E, Bogaerts A, Advanced Science 6, 1802062 (2019). http://doi.org/10.1002/advs.201802062
Keywords: A1 Journal article; Engineering sciences. Technology; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT); Center for Oncological Research (CORE)
Impact Factor: 9.034
Times cited: 39
DOI: 10.1002/advs.201802062
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“Quantifying a Heterogeneous Ru Catalyst on Carbon Black Using ADF STEM”. Varambhia AM, Jones L, De Backer A, Fauske VT, Van Aert S, Ozkaya D, Nellist PD, Particle and particle systems characterization 33, 438 (2016). http://doi.org/10.1002/ppsc.201600067
Abstract: Ru catalysts are part of a set of late transition metal nanocatalysts that have garnered much interest for catalytic applications such as ammonia synthesis and fuel cell production. Their performance varies greatly depending on their morphology and size, these catalysts are widely studied using electron microscopy. Using recent developments in Annular Dark Field (ADF) Scanning Transmission Electron Microscopy (STEM) quantification techniques, a rapid atom counting procedure was utilized to document the evolution of a heterogeneous Ru catalyst supported on carbon black. Areas of the catalyst were imaged for approximately 15 minutes using ADF STEM. When the Ru clusters were exposed to the electron beam, the clusters changed phase from amorphous to crystalline. To quantify the thickness of the crystalline clusters, two techniques were applied (simulation and statistical decomposition) and compared. These techniques show that stable face centredcubic crystal structures in the form of rafts, between 2 and 8 atoms thick, were formed after the initial wetting of the carbon support.
Keywords: A1 Journal article; Engineering sciences. Technology; Electron microscopy for materials research (EMAT)
Impact Factor: 4.474
Times cited: 4
DOI: 10.1002/ppsc.201600067
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“Cold atmospheric plasma treatment of melanoma and glioblastoma cancer cells”. Vermeylen S, De Waele J, Vanuytsel S, De Backer J, Van der Paal J, Ramakers M, Leyssens K, Marcq E, Van Audenaerde J, L J Smits E, Dewilde S, Bogaerts A, Plasma processes and polymers 13, 1195 (2016). http://doi.org/10.1002/ppap.201600116
Abstract: In this paper, two types of melanoma and glioblastoma cancer cell lines are treated with cold atmospheric plasma to assess the effect of several parameters on the cell viability. The cell viability decreases with treatment duration and time until analysis in all cell lines with varying sensitivity. The majority of dead cells stains both AnnexinV (AnnV) and propidium iodide, indicating that the plasma-treated non-viable cells are mostly late apoptotic or necrotic. Genetic mutations might be involved in the response to plasma. Comparing the effects of two gas mixtures, as well as indirect plasma-activated medium versus direct treatment, gives different results per cell line. In conclusion, this study confirms the potential of plasma for cancer therapy and emphasizes the influence of experimental parameters on therapeutic outcome.
Keywords: A1 Journal article; Plasma Lab for Applications in Sustainability and Medicine – Antwerp (PLASMANT)
Impact Factor: 2.846
Times cited: 26
DOI: 10.1002/ppap.201600116
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de Backer A (2015) Quantitative atomic resolution electron microscopy using advanced statistical techniques. Antwerpen
Keywords: Doctoral thesis; Electron microscopy for materials research (EMAT)
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“Three-dimensional elemental mapping at the atomic scale in bimetallic nanocrystals”. Goris B, de Backer A, Van Aert S, Gómez-Graña S, Liz-Marzán LM, Van Tendeloo G, Bals S, Nano letters 13, 4236 (2013). http://doi.org/10.1021/nl401945b
Abstract: A thorough understanding of the three-dimensional (3D) atomic structure and composition of coreshell nanostructures is indispensable to obtain a deeper insight on their physical behavior. Such 3D information can be reconstructed from two-dimensional (2D) projection images using electron tomography. Recently, different electron tomography techniques have enabled the 3D characterization of a variety of nanostructures down to the atomic level. However, these methods have all focused on the investigation of nanomaterials containing only one type of chemical element. Here, we combine statistical parameter estimation theory with compressive sensing based tomography to determine the positions and atom type of each atom in heteronanostructures. The approach is applied here to investigate the interface in coreshell Au@Ag nanorods but it is of great interest in the investigation of a broad range of nanostructures.
Keywords: A1 Journal article; Engineering sciences. Technology; Electron microscopy for materials research (EMAT)
Impact Factor: 12.712
Times cited: 90
DOI: 10.1021/nl401945b
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“Quantitative composition determination at the atomic level using model-based high-angle annular dark field scanning transmission electron microscopy”. Martinez GT, Rosenauer A, de Backer A, Verbeeck J, Van Aert S, Ultramicroscopy 137, 12 (2014). http://doi.org/10.1016/j.ultramic.2013.11.001
Abstract: High angle annular dark field scanning transmission electron microscopy (HAADF STEM) images provide sample information which is sensitive to the chemical composition. The image intensities indeed scale with the mean atomic number Z. To some extent, chemically different atomic column types can therefore be visually distinguished. However, in order to quantify the atomic column composition with high accuracy and precision, model-based methods are necessary. Therefore, an empirical incoherent parametric imaging model can be used of which the unknown parameters are determined using statistical parameter estimation theory (Van Aert et al., 2009, [1]). In this paper, it will be shown how this method can be combined with frozen lattice multislice simulations in order to evolve from a relative toward an absolute quantification of the composition of single atomic columns with mixed atom types. Furthermore, the validity of the model assumptions are explored and discussed.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT)
Impact Factor: 2.843
Times cited: 74
DOI: 10.1016/j.ultramic.2013.11.001
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“Estimation of unknown structure parameters from high-resolution (S)TEM images : what are the limits?”.den Dekker AJ, Gonnissen J, de Backer A, Sijbers J, Van Aert S, Ultramicroscopy 134, 34 (2013). http://doi.org/10.1016/j.ultramic.2013.05.017
Abstract: Statistical parameter estimation theory is proposed as a quantitative method to measure unknown structure parameters from electron microscopy images. Images are then purely considered as data planes from which structure parameters have to be determined as accurately and precisely as possible using a parametric statistical model of the observations. For this purpose, an efficient algorithm is proposed for the estimation of atomic column positions and intensities from high angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) images. Furthermore, the so-called CramérRao lower bound (CRLB) is reviewed to determine the limits to the precision with which continuous parameters such as atomic column positions and intensities can be estimated. Since this lower bound can only be derived for continuous parameters, alternative measures using the principles of detection theory are introduced for problems concerning the estimation of discrete parameters such as atomic numbers. An experimental case study is presented to show the practical use of these measures for the optimization of the experiment design if the purpose is to decide between the presence of specific atom types using STEM images.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT); Vision lab
Impact Factor: 2.843
Times cited: 31
DOI: 10.1016/j.ultramic.2013.05.017
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“General conclusions and future perspectives”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 243 (2021).
Abstract: This chapter provides an overview of statistical and quantitative methodologies that have pushed (scanning) transmission electron microscopy ((S)TEM) toward accurate and precise measurements of unknown structure parameters for understanding the relation between the structure of a material and its properties. Hereby, statistical parameter estimation theory has extensively been used which enabled not only measuring atomic column positions, but also quantifying the number of atoms, and detecting atomic columns as accurately and precisely as possible from experimental images. As a general conclusion, it can be stated that advanced statistical techniques are ideal tools to perform quantitative electron microscopy at the atomic scale. In the future, statistical methods will continue to be developed and novel quantification procedures will open up new possibilities for studying material structures at the atomic scale.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.008
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“Image-quality evaluation and model selection with maximum a posteriori probability”. Fatermans J, de Backer A, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 215 (2021).
Abstract: The maximum a posteriori (MAP) probability rule for atom column detection can also be used as a tool to evaluate the relation between scanning transmission electron microscopy (STEM) image quality and atom detectability. In this chapter, a new image-quality measure is proposed that correlates well with atom detectability, namely the integrated contrast-to-noise ratio (ICNR). Furthermore, the working principle of the MAP probability rule is described in detail showing a close relation to the principles of model-selection methods.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.007
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“Atom column detection”. Fatermans J, de Backer A, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 177 (2021).
Abstract: By combining statistical parameter estimation and model-order selection using a Bayesian framework, the maximum a posteriori (MAP) probability rule is proposed in this chapter as an objective and quantitative method to detect atom columns from high-resolution scanning transmission electron microscopy (HRSTEM) images. The validity and usefulness of this approach is demonstrated to both simulated and experimental annular dark-field (ADF) STEM images, but also to simultaneously acquired annular bright-field (ABF) and ADF STEM image data.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.006
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“Optimal experiment design for nanoparticle atom counting from ADF STEM images”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 145 (2021).
Abstract: In this chapter, the principles of detection theory are used to quantify the probability of error for atom counting from high-resolution scanning transmission electron microscopy (HRSTEM) images. Binary and multiple hypothesis testing have been investigated in order to determine the limits to the precision with which the number of atoms in a projected atomic column can be estimated. The probability of error has been calculated when using STEM images, scattering cross-sections or peak intensities as a criterion to count atoms. Based on this analysis, we conclude that scattering cross-sections perform almost equally well as images and perform better than peak intensities. Furthermore, the optimal STEM detector design can be derived for atom counting using the expression of the probability of error. We show that for very thin objects the low-angle annular dark-field (LAADF) regime is optimal and that for thicker objects the optimal inner detector angle increases.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.005
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“Atom counting”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 91 (2021).
Abstract: In this chapter, a statistical model-based method to count the number of atoms of monotype crystalline nanostructures from high-resolution annular dark-field (ADF) scanning transmission electron microscopy (STEM) images is discussed in detail together with a thorough study on the possibilities and inherent limitations. We show that this method can be applied to nanocrystals of arbitrary shape, size, and atom type. The validity of the atom-counting results is confirmed by means of detailed image simulations and it is shown that the high sensitivity of our method enables us to count atoms with single atom sensitivity.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.004
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“Efficient fitting algorithm”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 73 (2021).
Abstract: An efficient model-based estimation algorithm is introduced to quantify the atomic column positions and intensities from atomic-resolution (scanning) transmission electron microscopy ((S)TEM) images. This algorithm uses the least squares estimator on image segments containing individual columns fully accounting for overlap between neighboring columns, enabling the analysis of a large field of view. To provide end-users with this well-established quantification method, a user friendly program, StatSTEM, is developed which is freely available under a GNU public license. In this chapter, this efficient algorithm is applied to three different nanostructures for which the analysis of a large field of view is required.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT)
DOI: 10.1016/BS.AIEP.2021.01.003
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“Statistical parameter estimation theory : principles and simulation studies”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 29 (2021).
Abstract: In this chapter, the principles of statistical parameter estimation theory for a quantitative analysis of atomic-resolution electron microscopy images are introduced. Within this framework, electron microscopy images are described by a parametric statistical model. Here, parametric models are introduced for different types of electron microscopy images: reconstructed exit waves, annular dark-field (ADF) scanning transmission electron microscopy (STEM) images, and simultaneously acquired ADF and annular bright-field (ABF) STEM images. Furthermore, the Cramér-Rao lower bound (CRLB) is introduced, i.e. a theoretical lower bound on the variance of any unbiased estimator. This CRLB is used to quantify the precision of the structure parameters of interest, such as the atomic column positions and the integrated atomic column intensities.
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT); Vision lab
DOI: 10.1016/BS.AIEP.2021.01.002
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“Introduction”. de Backer A, Fatermans J, den Dekker AJ, Van Aert S Advances in imaging and electron physics
T2 – Advances in imaging and electron physics. page 1 (2021).
Keywords: H2 Book chapter; Electron microscopy for materials research (EMAT)
DOI: 10.1016/BS.AIEP.2021.01.001
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“Functional Respiratory Imaging as a tool to personalize respiratory treatment in subjects with unilateral diaphragmatic paralysis”. Van Holsbeke CS, Leemans G, Vos WG, de Backer JW, Vinchurkar SC, Geldof M, Verdonck PR, Parizel PM, van Schil PE, de Backer WA, Respiratory care , 1 (2013). http://doi.org/10.4187/respcare.02756
Abstract: In two subjects with a unilateral diaphragmatic paralysis and complaints of dyspnea, a completely different treatment approach was chosen despite similar anatomical and physiological abnormalities. These decisions were supported by the results generated by Functional Respiratory Imaging (FRI). FRI was able to generate functional information with respect to lobar ventilation and local drug deposition. In one subject, it was found that some lobes were poorly ventilated and drug deposition simulation showed that some regions were undertreated. This subject underwent a diaphragm plication to restore the ventilation. In the other subject, it was found that all lobes were still ventilated. A conservative approach with regular follow-up was chosen to wait for spontaneous recovery of the diaphragmatic function. Both subjects improved subjectively and objectively. These cases demonstrate how novel medical imaging techniques such as FRI can be used to personalize respiratory treatment in subjects with unilateral diaphragmatic paralysis.
Keywords: A1 Journal article; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 1.733
Times cited: 5
DOI: 10.4187/respcare.02756
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“A case series on lung deposition analysis of inhaled medication using functional imaging based computational fluid dynamics in asthmatic patients : effect of upper airway morphology and comparison with in vivo data”. Vinchurkar S, De Backer L, Vos W, Van Holsbeke C, de Backer J, de Backer W, Inhalation Toxicology 24, 81 (2012). http://doi.org/10.3109/08958378.2011.644351
Abstract: Context: Asthma affects 20 million Americans resulting in an economic burden of approximately $18 billion in the US alone (Allergies and Asthma Foundation 2000; National Center for Environmental Health (NCEH) 1999). Research studies based on differences in patient-specific airway morphology for asthma and the associated effect on deposition of inhaled aerosols are currently not available in the literature. Therefore, the role of morphological variations such as upper airway (extrathoracic) occlusion is not well documented. Objective: Functional imaging based computational fluid dynamics (CFD) of the respiratory airways for five asthmatic subjects is performed in this study using computed tomography (CT) based patient-specific airway models and boundary conditions. Methods: CT scans for 5 asthma patients were used to reconstruct 3D lung models using segmentation software. An averaged inhalation profile and patient-specific lobar flow distribution were used to perform the simulation. The simulations were used to obtain deposition for BDP/Formoterol (R) HFA pMDI in the patient-specific airway models. Results: The lung deposition obtained using CFD was in excellent agreement with available in vivo data using the same product. Specifically, CFD resulted in 30% lung deposition, whereas in vivo lung deposition was reported to be approximately 31%. Conclusion: It was concluded that a combination of patient-specific airway models and lobar boundary conditions can be used to obtain accurate lung deposition estimates. Lower lung deposition can be expected for patients with higher extrathoracic resistance. Novel respiratory drug delivery devices need to accommodate population subgroups based on these morphological and anatomical differences in addition to subject age.
Keywords: A1 Journal article; Pharmacology. Therapy; Biophysics and Biomedical Physics; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 1.751
Times cited: 36
DOI: 10.3109/08958378.2011.644351
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“The acute effect of budesonide/formoterol in COPD : a multi-slice computed tomography and lung function study”. De Backer LA, Vos W, de Backer J, Van Holsbeke C, Vinchurkar S, de Backer W, European Respiratory Journal 40, 298 (2012). http://doi.org/10.1183/09031936.00072511
Abstract: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of chronic obstructive pulmonary disease (COPD) does not always match with other clinical disease descriptors such as exacerbation frequency and quality of life, indicating that forced expiratory volume in 1 s (FEV1) is not a perfect descriptor of the disease. The aim of this study was to find out whether changes in airway geometry after inhalation of the most commonly used inhalation therapy in severe COPD can more adequately be described with an image-based approach than with spirometry. 10 COPD GOLD stage III patients were assessed in a double-blind crossover study. Airway volumes were analysed using segmentation of multi-slice computed tomography (MSCT) images; airway resistance was determined using computational fluid dynamics (CFD). Distal airway volume significantly increased (p=0.011) in patients 4 h after receiving a budesonide/formoterol combination from 9.6+/-4.67 cm(3) to 10.14+/-4.81 cm(3). Also CFD-determined airway resistance significantly decreased (p=0.047) from 0.051+/-0.021 kPa.s.L-1 to 0.043+/- 0.019 kPa.s.L-1. None of the lung function parameters showed a significant change. Only functional residual capacity (FRC) showed a trend to decline (p=0.056). Only the image-based parameters were able to predict the visit at which the combination product was administered. This study showed that imaging is a sensitive, complementary tool to describe changes in airway structure.
Keywords: A1 Journal article; Biophysics and Biomedical Physics; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 10.569
Times cited: 37
DOI: 10.1183/09031936.00072511
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de Backer W, Vos W, Van Holsbeke C, Vinchurkar S, Claes R, Hufkens A, Parizel PM, Bedert L, de Backer J (2014) The effect of roflumilast in addition to LABA/LAMA/ICS treatment in COPD patients. Copenhagen, 527–529
Keywords: L1 Letter to the editor; Biophysics and Biomedical Physics; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 10.569
Times cited: 26
DOI: 10.1183/09031936.00011714
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“Novel functional imaging of changes in small airways of patients treated with extrafine beclomethasone/formoterol”. Vos W, de Backer J, Poli G, De Volder A, Ghys L, Van Holsbeke C, Vinchurkar S, De Backer L, de Backer W, Respiration 86, 393 (2013). http://doi.org/10.1159/000347120
Abstract: Background: Inhaled formulations using extrafine particles of long-acting beta(2)-agonists and corticosteroids were developed to optimize asthma treatment. Findings that these combinations reach and treat smaller airways more effectively are predominantly based on general non-specific outcomes with little information on regional characteristics. Objectives: This study aims to assess long-term effects of extrafine beclomethasone/formoterol on small airways of asthmatic patients using novel functional imaging methods. Methods: Twenty-four stable asthma patients were subdivided into three groups (steroid naive, n = 7; partially controlled, n = 6; well controlled, n = 11). Current treatment was switched to a fixed combination of extrafine beclomethasone/formoterol (Foster (R); Chiesi Pharmaceuticals, Parma, Italy). Patients underwent lung function evaluation and thorax high-resolution computerized tomography (HRCT) scan. Local airway resistance was obtained from computational fluid dynamics (CFD). Results: After 6 months, the entire population showed improvement in pre-bronchodilation imaging parameters, including small airway volume (p = 0.0007), resistance (p = 0.011), and asthma control score (p = 0.016). Changes in small airway volume correlated with changes in asthma control score (p = 0.004). Forced expiratory volume in 1 s (p = 0.044) and exhaled nitric oxide (p = 0.040) also improved. Functional imaging provided more detail and clinical relevance compared to lung function tests, especially in the well-controlled group where only functional imaging parameters showed significant improvement, while the correlation with asthma control score remained. Conclusions: Extrafine beclomethasone/formoterol results in a significant reduction of small airway obstruction, detectable by functional imaging (HRCT/CFD). Changes in imaging parameters correlated significantly with clinically relevant improvements. This indicates that functional imaging is a useful tool for sensitive assessment of changes in the respiratory system after asthma treatment. Copyright (C) 2013 S. Karger AG, Basel
Keywords: A1 Journal article; Biophysics and Biomedical Physics; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 2.772
Times cited: 30
DOI: 10.1159/000347120
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“Validation of computational fluid dynamics in CT-based airway models with SPECT/CT1”. de Backer JW, Vos WG, Vinchurkar SC, Claes R, Drollmann A, Wulfrank D, Parizel PM, Germonpré, P, de Backer W, Radiology 257, 854 (2010). http://doi.org/10.1148/radiol.10100322
Abstract: Purpose: To compare the results obtained by using numerical flow simulations with the results of combined single photon emission computed tomography (SPECT) and computed tomography (CT) and to demonstrate the importance of correct boundary conditions for the numerical methods to account for the large amount of interpatient variability in airway geometry. Materials and Methods: This study was approved by all relevant institutional review boards. All patients gave their signed informed consent. In this study, six patients with mild asthma (three men; three women; overall mean age, 46 years ± 17 [standard deviation]) underwent CT at functional residual capacity and total lung capacity, as well as SPECT/CT. CT data were used for segmentation and computational fluid dynamics (CFD) simulations. A comparison was made between airflow distribution, as derived with (a) SPECT/CT through tracer concentration analysis, (b) CT through lobar expansion measurement, and (c) CFD through flow computer simulation. Also, the heterogeneity of the ventilation was examined. Results: Good agreement was found between SPECT/CT, CT, and CFD in terms of airflow distribution and hot spot detection. The average difference for the internal airflow distribution was less than 3% for CFD and CT versus SPECT/CT. Heterogeneity in ventilation patterns could be detected with SPECT/CT and CFD. Conclusion: This results of this study show that patient-specific computer simulations with appropriate boundary conditions yield information that is similar to that obtained with functional imaging tools, such as SPECT/CT.
Keywords: A1 Journal article; Condensed Matter Theory (CMT); Vision lab; Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 7.296
Times cited: 100
DOI: 10.1148/radiol.10100322
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“Clinical applications of image-based airway computational fluid dynamics: assessment of inhalation medication and endobronchial devices”. de Backer JW, Vos WG, Germonpré, P, Salgado R, Parizel PM, de Backer W, Proceedings of the Society of Photo-optical Instrumentation Engineers 7262, 72621p (2009). http://doi.org/10.1117/12.811476
Abstract: Computational fluid dynamics (CFD) is a technique that is used increasingly in the biomedical field. Solving the flow equations numerically provides a convenient way to assess the efficiency of therapies and devices, ranging from cardiovascular stents and heart valves to hemodialysis workflows. Also in the respiratory field CFD has gained increasing interest, especially through the combination of three dimensional image reconstruction which results in highend patient-specific models. This paper provides an overview of clinical applications of CFD through image based modeling, resulting from recent studies performed in our center. We focused on two applications: assessment of the efficiency of inhalation medication and analysis of endobronchial valve placement. In the first application we assessed the mode of action of a novel bronchodilator in 10 treated patients and 4 controls. We assessed the local volume increase and resistance change based on the combination of imaging and CFD. We found a good correlation between the changes in volume and resistance coming from the CFD results and the clinical tests. In the second application we assessed the placement and effect of one way endobronchial valves on respiratory function in 6 patients. We found a strong patientspecific result of the therapy where in some patients the therapy resulted in complete atelectasis of the target lobe while in others the lobe remained inflated. We concluded from these applications that CFD can provide a better insight into clinically relevant therapies.
Keywords: A3 Journal article; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP)
DOI: 10.1117/12.811476
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“Change in upper airway geometry between upright and supine position during tidal nasal breathing”. Van Holsbeke CS, Verhulst SL, Vos WG, de Backer JW, Vinchurkar SC, Verdonck PR, van Doorn JWD, Nadjmi N, de Backer WA, Journal Of Aerosol Medicine And Pulmonary Drug Delivery 27, 51 (2014). http://doi.org/10.1089/jamp.2012.1010
Keywords: A1 Journal article; Biophysics and Biomedical Physics; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP); Translational Neurosciences (TNW)
Impact Factor: 2.528
Times cited: 16
DOI: 10.1089/jamp.2012.1010
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“Particle deposition in airways of chronic respiratory patients exposed to an urban aerosol”. Horemans B, Van Holsbeke C, Vos W, Darchuk L, Novakovic V, Fontan AC, de Backer J, van Grieken R, de Backer W, De Wael K, Environmental science and technology 46, 12162 (2012). http://doi.org/10.1021/es302755s
Abstract: Urban atmospheres in modern cities carry characteristic mixtures of particulate pollution which are potentially aggravating for chronic respiratory patients (CRP). Although air quality surveys can be detailed, the obtained information is not always useful to evaluate human health effects. This paper presents a novel approach to estimate particle deposition rates in airways of CRP, based on real air pollution data. By combining computational fluid dynamics with physical-chemical characteristics of particulate pollution, deposition rates are estimated for particles of different toxicological relevance, that is, minerals, iron oxides, sea salts, ammonium salts, and carbonaceous particles. Also, it enables some qualitative evaluation of the spatial, temporal, and patient specific effects on the particle dose upon exposure to the urban atmosphere. Results show how heavy traffic conditions increases the deposition of anthropogenic particles in the trachea and lungs of respiratory patients (here, +0.28 and +1.5 μg·h1, respectively). In addition, local and synoptic meteorological conditions were found to have a strong effect on the overall dose. However, the pathology and age of the patient was found to be more crucial, with highest deposition rates for toxic particles in adults with a mild anomaly, followed by mild asthmatic children and adults with severe respiratory dysfunctions (7, 5, and 3 μg·h1, respectively).
Keywords: A1 Journal article; AXES (Antwerp X-ray Analysis, Electrochemistry and Speciation); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 6.198
Times cited: 5
DOI: 10.1021/es302755s
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“Tomographic spectroscopic imaging, an experimental proof of concept”. van den Broek W, Verbeeck J, Schryvers D, de Backer S, Scheunders P, Ultramicroscopy 109, 296 (2009). http://doi.org/10.1016/j.ultramic.2008.11.022
Abstract: Recording the electron energy loss spectroscopy data cube with a series of energy filtered images is a dose inefficient process because the energy slit blocks most of the electrons. When recording the data cube by scanning an electron probe over the sample, perfect dose efficiency is attained; but due to the low current in nanoprobes, this often is slower, with a smaller field of view. In W. Van den Broek et al. [Ultramicroscopy, 106 (2006) 269], we proposed a new method to record the data cube, which is more dose efficient than an energy filtered series. It produces a set of projections of the data cube and then tomographically reconstructs it. In this article, we demonstrate these projections in practice, we present a simple geometrical model that allows for quantification of the projection angles and we present the first successful experimental reconstruction, all on a standard post-column instrument.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT); Vision lab
Impact Factor: 2.843
Times cited: 1
DOI: 10.1016/j.ultramic.2008.11.022
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“Acquisition of the EELS data cube by tomographic reconstruction”. van den Broek W, Verbeeck J, de Backer S, Scheunders P, Schryvers D, Ultramicroscopy 106, 269 (2006). http://doi.org/10.1016/j.ultramic.2005.09.001
Abstract: Energy filtered TEM, EFTEM, provides three-dimensional data, two spatial and one spectral dimension. We propose to acquire these data by measuring a series of images with a defocused energy filter. It will be shown that each image is a projection of the data on the detector and that reconstruction of the data out of a sufficient number of such projections using a tomographic reconstruction algorithm is possible. This technique uses only a fraction of the electron dose an energy filtered series (EFS) needs for the same spectral and spatial resolution and the same mean signal-to-noise ratio. (c) 2005 Elsevier B.V. All rights reserved.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT); Vision lab
Impact Factor: 2.843
Times cited: 6
DOI: 10.1016/j.ultramic.2005.09.001
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“Novel imaging techniques using computer methods for the evaluation of the upper airway in patients with sleep-disordered breathing: a comprehensive review”. de Backer JW, Vos WG, Verhulst SL, de Backer W, Sleep medicine reviews 12, 437 (2008). http://doi.org/10.1016/j.smrv.2008.07.009
Abstract: Patients with sleep related breathing disorders (SRBD) can be treated with nasal continuous positive airway pressure (nCPAP) or with several upper airway (UA) interventions. While nCPAP is almost always effective when clinically well tolerated, the therapeutic outcome of UA surgery and UA devices is difficult to predict. The improvement of our capability to perform the latter predictions more accurately is of great clinical importance since it will prevent patients to be treated with ineffective, sometimes irreversible, techniques. In this review we describe the importance of new imaging methods in this respect. We first refer to the most important pathophysiological mechanisms known so far to play a role in SRBD, indicating that functional imaging could elucidate these mechanisms in a patient specific manner. Then we describe the new technologies that make UA imaging more functional referring to the data as they are presently available. Finally we summarise the studies that do indicate that the use of functional imaging of the UA in SRBD patients may significantly help to predict the clinical outcome after UA interventions.
Keywords: A1 Journal article; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 8.958
Times cited: 33
DOI: 10.1016/j.smrv.2008.07.009
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“Functional respiratory imaging as a tool to assess upper airway patency in children with obstructive sleep apnea”. Van Holsbeke C, Vos W, van Hoorenbeeck K, Boudewyns A, Salgado R, Verdonck PR, Ramet J, de Backer J, De Backer W, Verhulst SL, Sleep Medicine 14, 433 (2013). http://doi.org/10.1016/j.sleep.2012.12.005
Abstract: Objective: We aim to investigate if anatomical and functional properties of the upper airway using computerized 3D models derived from computed tomography (CT) scans better predict obstructive sleep apnea (OSA) severity than standard clinical markers. Methods: Consecutive children with suspected OSA underwent polysomnography, clinical assessment of upper airway patency, and a CT scan while awake. A three-dimensional (3D) reconstruction of the pharyngeal airway was built from these images, and computational fluid dynamics modeling of low inspiratory flow was performed using open-source software. Results: Thirty-three children were included (23 boys; mean age, was 6.0 +/- 3.2 y). OSA was diagnosed in 23 patients. Children with OSA had a significantly lower volume of the overlap region between tonsils and the adenoids (median volume, 1408 mm compared to 2173 mm; p = 0.04), a lower mean cross-sectional area at this location (median volume, 69.3 mm(2) compared to 114.3 mm(2); p = 0.04), and a lower minimal cross-sectional area (median volume, 17.9 mm(2) compared to 25.9 mm(2); p = 0.05). Various significant correlations were found between several imaging parameters and the severity of OSA, most pronounced for upper airway conductance (r = -0.46) (p < 0.01) for correlation between upper airway conductance and the apnea-hypopnea index. No differences or significant correlations were observed with clinical parameters of upper airway patency. Preliminary data after treatment showed that none of the patients with residual OSA had their smallest cross-sectional area located in segment 3, and this frequency was significantly lower than in their peers whose sleep study normalized (64%; p = 0.05). Conclusion: Functional imaging parameters are highly correlated with OSA severity and are a more powerful correlate than clinical scores of upper airway patency. Preliminary data also showed that we could identify differences in the upper airway of those subjects who did not benefit from a local upper airway treatment. (c) 2013 Elsevier B.V. All rights reserved.
Keywords: A1 Journal article; Condensed Matter Theory (CMT); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 3.391
Times cited: 18
DOI: 10.1016/j.sleep.2012.12.005
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“Flow analyses in the lower airways: patient-specific model and boundary conditions”. de Backer JW, Vos WG, Gorlé, CD, Germonpré, P, Partoens B, Wuyts FL, Parizel PM, de Backer W, Medical engineering and physics 30, 872 (2008). http://doi.org/10.1016/j.medengphy.2007.11.002
Abstract: Computational fluid dynamics (CFD) is increasingly applied in the respiratory domain. The ability to simulate the flow through a bifurcating tubular system has increased the insight into the internal flow dynamics and the particular characteristics of respiratory flows such as secondary motions and inertial effects. The next step in the evolution is to apply the technique to patient-specific cases, in order to provide more information about pathological airways. This study presents a patient-specific approach where both the geometry and the boundary conditions (BC) are based on individual imaging methods using computed tomography (CT). The internal flow distribution of a 73-year-old female suffering from chronic obstructive pulmonary disease (COPD) is assessed. The validation is performed through the comparison of lung ventilation with gamma scintigraphy. The results show that in order to obtain agreement within the accuracy limits of the gamma scintigraphy scan, both the patient-specific geometry and the BC (driving pressure) play a crucial role. A minimal invasive test (CT scan) supplied enough information to perform an accurate CFD analysis. In the end it was possible to capture the pathological features of the respiratory system using the imaging and computational fluid dynamics techniques. This brings the introduction of this new technique in the clinical practice one step closer.
Keywords: A1 Journal article; Condensed Matter Theory (CMT); Antwerp Surgical Training, Anatomy and Research Centre (ASTARC); Laboratory Experimental Medicine and Pediatrics (LEMP)
Impact Factor: 1.819
Times cited: 82
DOI: 10.1016/j.medengphy.2007.11.002
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