432 results on '"Translational Imaging Research Alliance"'
Search Results
2. Direct Immobilization of Engineered Nanobodies on Gold Sensors
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Morgan R. Alexander, Paul A. Mulheran, David J. Scurr, Karina Kubiak-Ossowska, Nick Devoogdt, Serge Muyldermans, Bárbara Simões, Peter Adriaensens, Paula M. Mendes, Wanda Guedens, Alexis Broisat, Charlie Keene, Anna M. Kotowska, Steven Johnson, Vriendenkring VUB, Supporting clinical sciences, Medical Imaging, and Translational Imaging Research Alliance
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2019-20 coronavirus outbreak ,Circular dichroism ,Materials science ,Coronavirus disease 2019 (COVID-19) ,Protein Conformation ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Nanotechnology ,Biosensing Techniques ,02 engineering and technology ,Molecular Dynamics Simulation ,Protein Engineering ,010402 general chemistry ,01 natural sciences ,sensor ,General Materials Science ,Surface plasmon resonance ,TP155 ,single-domain antibody ,Medicine(all) ,Single-Domain Antibodies ,021001 nanoscience & nanotechnology ,molecular dynamic simulations ,0104 chemical sciences ,nanobody ,Single-domain antibody ,Clinical diagnosis ,Gold ,0210 nano-technology ,Antibodies, Immobilized ,surface plasmon resonance ,Research Article - Abstract
Single-domain antibodies, known as nanobodies, have great potential as biorecognition elements for sensors because of their small size, affinity, specificity, and robustness. However, facile and efficient methods of nanobody immobilization are sought that retain their maximum functionality. Herein, we describe the direct immobilization of nanobodies on gold sensors by exploiting a modified cysteine strategically positioned at the C-terminal end of the nanobody. The experimental data based on secondary ion mass spectrometry, circular dichroism, and surface plasmon resonance, taken together with a detailed computational work (molecular dynamics simulations), support the formation of stable and well-oriented nanobody monolayers. Furthermore, the nanobody structure and activity is preserved, wherein the nanobody is immobilized at a high density (approximately 1 nanobody per 13 nm(2)). The strategy for the spontaneous nanobody self-assembly is simple and effective and possesses exceptional potential to be used in numerous sensing platforms, ranging from clinical diagnosis to environmental monitoring. The authors acknowledge the financial support of this work by the EPSRC (EP/K027263/1, EP/P029868/1, EP/L01646X/1, and EP/P031684/1), ERC (Consolidator Grant 614787), and Hasselt University and the Research Foundation Flanders (FWO Vlaanderen) via the Hercules project AUHL/15/2 - GOH3816N. The MD simulations and analyses were performed using the ARCHIE-WeSt High-Performance Computer (www.archie-west.ac.uk). S.J. acknowledges the support of the EPSRC (EP/ P030017/1).
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- 2021
3. Signal quality as Achilles’ heel of graph theory in functional magnetic resonance imaging in multiple sclerosis
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Marie B. D'hooghe, Lars Costers, Guy Nagels, Stijn Denissen, Jeroen Van Schependom, Johan Baijot, Melissa Cambron, Johan De Mey, Miguel D'haeseleer, Jeroen Gielen, Anne-Marie Vanbinst, Clinical sciences, Faculty of Medicine and Pharmacy, Neuroprotection & Neuromodulation, Neurology, Radiology, Supporting clinical sciences, Body Composition and Morphology, Medical Imaging, Translational Imaging Research Alliance, and Electronics and Informatics
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0301 basic medicine ,Male ,Functional magnetic resonance imaging ,Audiology ,Signal-To-Noise Ratio ,0302 clinical medicine ,Signal-to-noise ratio ,Cognition ,Contrast (vision) ,media_common ,Brain Mapping ,Multidisciplinary ,medicine.diagnostic_test ,Brain ,Middle Aged ,Mental Status and Dementia Tests ,Magnetic Resonance Imaging ,Radiology Nuclear Medicine and imaging ,symbols ,Graph (abstract data type) ,Medicine ,Female ,Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,media_common.quotation_subject ,Science ,Models, Neurological ,Achilles Tendon ,Article ,03 medical and health sciences ,symbols.namesake ,Young Adult ,Contrast-to-noise ratio ,medicine ,Humans ,Aged ,business.industry ,Multiple sclerosis ,Reproducibility of Results ,medicine.disease ,Pearson product-moment correlation coefficient ,030104 developmental biology ,nervous system ,Case-Control Studies ,Linear Models ,Nerve Net ,business ,030217 neurology & neurosurgery - Abstract
Graph-theoretical analysis is a novel tool to understand the organisation of the brain.We assessed whether altered graph theoretical parameters, as observed in multiple sclerosis (MS), reflect pathology-induced restructuring of the brain's functioning or result from a reduced signal quality in functional MRI (fMRI). In a cohort of 49 people with MS and a matched group of 25 healthy subjects (HS), we performed a cognitive evaluation and acquired fMRI. From the fMRI measurement, Pearson correlation-based networks were calculated and graph theoretical parameters reflecting global and local brain organisation were obtained. Additionally, we assessed metrics of scanning quality (signal to noise ratio (SNR)) and fMRI signal quality (temporal SNR and contrast to noise ratio (CNR)). In accordance with the literature, we found that the network parameters were altered in MS compared to HS. However, no significant link was found with cognition. Scanning quality (SNR) did not differ between both cohorts. In contrast, measures of fMRI signal quality were significantly different and explained the observed differences in GTA parameters. Our results suggest that differences in network parameters between MS and HS in fMRI do not reflect a functional reorganisation of the brain, but rather occur due to reduced fMRI signal quality.
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- 2021
4. Therapeutic Efficacy of 213Bi-labeled sdAbs in a Preclinical Model of Ovarian Cancer
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Frank Bruchertseifer, Peter Covens, Mireille Gysemans, Yana Dekempeneer, Catarina Xavier, Quentin Lecocq, Vicky Caveliers, Thomas Cardinaels, Maarten Ooms, Ken Maes, Brian Miller, Tony Lahoutte, Matthias D'Huyvetter, Dominic Maertens, Alfred Morgenstern, Medical Imaging, Faculty of Medicine and Pharmacy, Supporting clinical sciences, Translational Imaging Research Alliance, Nuclear Medicine, Cyclotron, Clinical sciences, Basic (bio-) Medical Sciences, Medical Genetics, Hematology, Preventie- & Milieudienst, and UZB Other
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business.industry ,Pharmaceutical Science ,Cancer ,02 engineering and technology ,021001 nanoscience & nanotechnology ,medicine.disease ,030226 pharmacology & pharmacy ,In vitro ,Radioconjugate ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Trastuzumab ,Drug Discovery ,Toxicity ,Cancer research ,medicine ,Molecular Medicine ,Cytotoxic T cell ,0210 nano-technology ,Ovarian cancer ,business ,medicine.drug - Abstract
Targeted alpha-particle therapy (TAT) might be a relevant therapeutic strategy to circumvent resistance to conventional therapies in the case of HER2-positive metastatic cancer. Single-domain antibody fragments (sdAb) are promising vehicles for TAT because of their excellent in vivo properties, high target affinity, and fast clearance kinetics. This study combines the cytotoxic α-particle emitter bismuth-213 (213Bi) and HER2-targeting sdAbs. The in vitro specificity, affinity, and cytotoxic potency of the radiolabeled complex were analyzed on HER2pos cells. Its in vivo biodistribution through serial dissections and via Cherenkov and micro-single-photon emission computed tomography (CT)/CT imaging was evaluated. Finally, the therapeutic efficacy and potential associated toxicity of [213Bi]Bi-DTPA-2Rs15d were evaluated in a HER2pos tumor model that manifests peritoneal metastasis. In vitro, [213Bi]Bi-DTPA-2Rs15d bound HER2pos cells in a HER2-specific way. In mice, high tumor uptake was reached already 15 min after injection, and extremely low uptake values were observed in normal tissues. Co-infusion of gelofusine resulted in a 2-fold reduction in kidney uptake. Administration of [213Bi]Bi-DTPA-2Rs15d alone and in combination with trastuzumab resulted in a significant increase in median survival. We describe for the very first time the successful labeling of an HER2-sdAb with the α-emitter 213Bi, and after intravenous administration, revealing high in vivo stability and specific accumulation in target tissue and resulting in an increased median survival of these mice especially in combination with trastuzumab. These results indicate the potential of [213Bi]Bi-DTPA-sdAb as a new radioconjugate for TAT, alone and as an add-on to trastuzumab for the treatment of HER2pos metastatic cancer.
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- 2020
5. Hilbert sEMG data scanning for hand gesture recognition based on deep learning
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Bart Jansen, Athanassios N. Skodras, Bruno Cornelis, Jan Cornelis, Panagiotis Tsinganos, Electronics and Informatics, Faculty of Engineering, Vriendenkring VUB, Translational Imaging Research Alliance, and Audio Visual Signal Processing
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Contextual image classification ,Computer science ,business.industry ,Deep learning ,0206 medical engineering ,Pattern recognition ,Image processing ,Hilbert curve ,02 engineering and technology ,020601 biomedical engineering ,Convolutional neural network ,Field (computer science) ,Artificial Intelligence ,Gesture recognition ,0202 electrical engineering, electronic engineering, information engineering ,020201 artificial intelligence & image processing ,Artificial intelligence ,business ,Software - Abstract
Deep learning has transformed the field of data analysis by dramatically improving the state of the art in various classification and prediction tasks, especially in the area of computer vision. In biomedical engineering, a lot of new work is directed toward surface electromyography (sEMG)-based gesture recognition, often addressed as an image classification problem using convolutional neural networks (CNNs). In this paper, we utilize the Hilbert space-filling curve for the generation of image representations of sEMG signals, which allows the application of typical image processing pipelines such as CNNs on sequence data. The proposed method is evaluated on different state-of-the-art network architectures and yields a significant classification improvement over the approach without the Hilbert curve. Additionally, we develop a new network architecture (MSHilbNet) that takes advantage of multiple scales of an initial Hilbert curve representation and achieves equal performance with fewer convolutional layers.
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- 2020
6. Reshaping nanobodies for affinity purification on protein a
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Nick Devoogdt, Catarina Xavier, Neeme Benedict Kulaya, Nele Van Vaerenbergh, Maxine Crauwels, Serge Muyldermans, Matthias D'Huyvetter, Cécile Vincke, Medical Imaging, Cellular and Molecular Immunology, Vrije Universiteit Brussel, Supporting clinical sciences, Translational Imaging Research Alliance, and Clinical sciences
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0106 biological sciences ,Staphylococcus aureus ,Biodistribution ,Protein A ,Bioengineering ,Affinity chromatography ,medicine.disease_cause ,01 natural sciences ,Chromatography, Affinity ,law.invention ,03 medical and health sciences ,Antigen ,law ,010608 biotechnology ,medicine ,Staphylococcal Protein A ,Molecular Biology ,030304 developmental biology ,Thermostability ,Medicine(all) ,0303 health sciences ,biology ,Chemistry ,food and beverages ,General Medicine ,Single-Domain Antibodies ,Biochemistry ,embryonic structures ,Nanobody ,biology.protein ,Recombinant DNA ,Antibody ,Biotechnology - Abstract
Nanobodies (Nbs) are 15 kDa recombinant, single-domain, antigen-specific fragments derived from heavy-chain only antibodies (HCAbs) occurring naturally in species of Camelidae. The beneficial properties of Nbs make them suitable tracers for diagnostic and therapeutic purposes. Whereas Nbs with a terminal hexa-histidine tag (His-tag) are easily purified via immobilized metal affinity chromatography, previous studies revealed a negative impact of the His-tag on the biodistribution of Nb-based tracers. Thus, it is important to develop alternative purification methods for Nbs without a His-tag. Protein A (SpA), a surface protein of Staphylococcus aureus, binds the Fc-region of IgG molecules and also to a lesser extent human heavy chain family-3 variable (VH) regions. Nbs also belong to this VH family, although many fail to be recognized by SpA. Here it is demonstrated that non-SpA binding Nbs can be mutagenized for purification by SpA affinity chromatography and that these Nb variants retain their thermostability and antigen affinity, while biodistribution remains unaffected.
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- 2020
7. Gamma detector dead time correction using Lambert W function
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Jan W T Heemskerk, Michel Defrise, Medical Imaging, Supporting clinical sciences, Vriendenkring VUB, Translational Imaging Research Alliance, and Computational and Applied Mathematics Programme
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lcsh:Medical physics. Medical radiology. Nuclear medicine ,Point source ,lcsh:R895-920 ,Biomedical Engineering ,Imaging phantom ,030218 nuclear medicine & medical imaging ,law.invention ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Optics ,law ,Lambert W function ,Range (statistics) ,Radiology, Nuclear Medicine and imaging ,Time point ,Instrumentation ,Original Research ,Gamma camera ,Physics ,Radiation ,business.industry ,Detector ,Dead time ,030220 oncology & carcinogenesis ,symbols ,business - Abstract
BackgroundFor therapeutic applications of several isotopes (e.g.,131I,153Sm,177Lu) in nuclear medicine, the high activities typically applied require accurate dead time correction in early time point imaging. We present a novel, straightforward dead time correction method using the LambertWfunction, which is in principle exact for the paralyzable detector model with a single parameter τ (i.e., dead time).ResultsAs a proof of concept, the method is validated with a simple model: a commonly used isotope,99mTc, with a single photopeak. We measured count rates of a gamma camera both intrinsically and extrinsically (i.e., with collimators) with point sources in air and in a scatter phantom (extrinsic only). τ was estimated for both open window (τOW) and a99mTc photopeak window (τTc), using a “graphical” method for fitting the count rate of decaying sources. These values for τ were subsequently used for dead time correction.τ varied significantly between the different geometries for both energy windows, but τOWwas more reproducible than τTc, particularly for the scatter phantom measurements.τOWmeasured from the phantom measurements was approximately 30% lower than τOWfrom the intrinsic measurement but corresponded within 15% with the extrinsic point source measurements. Accordingly, using the intrinsic τOWled to an overcorrection of 8% at high count rates; τOWfrom the extrinsic point source measurements corrected the phantom measurement to within 2%.However, significant differences were observed between τTcvalues. All measured τTcvalues underestimated dead time losses in a second independent phantom measurement, with even τTcfrom the first phantom measurement underestimating activity with 5–10% at the highest count rates. Based on measurements of the effect of energy window settings and geometry, we tentatively attribute the added dead time losses to pulse pile-up.ConclusionsAnalytic dead time correction based on the LambertWfunction is accurate for the range in which gamma detectors behave as paralyzable systems. However, further investigation indicated measured τ values to be variable with geometry as well as window fraction. We propose that dead time correction should be based on the open window value, τOW, corrected for window fraction.
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- 2020
8. Fat misbehaving in the abdominal cavity: a pictorial essay
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Johan De Mey, Hannes Devos, Frederik Vandenbroucke, Yannick De Brucker, Lode Goethals, Dries Belsack, Bart Ilsen, Gert-Jan Allemeersch, Radiology, Supporting clinical sciences, Nuclear Medicine, Medical Imaging, Faculty of Medicine and Pharmacy, Body Composition and Morphology, and Translational Imaging Research Alliance
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Pathology ,medicine.medical_specialty ,Mesenteric Panniculitis ,Omental infarction ,Review Paper ,business.industry ,05 social sciences ,050801 communication & media studies ,computed tomography ,Abdominal cavity ,Diverticulitis ,medicine.disease ,Appendicitis ,necrosis ,Epiploic appendagitis ,0508 media and communications ,medicine.anatomical_structure ,Peritoneum ,inflammation ,medicine ,Fat necrosis ,business ,abdominal imaging - Abstract
Intra-abdominal fat is abundantly present in both the peritoneum and retroperitoneum. Fat necrosis or inflammation are common findings in abdominal imaging. The most common pathologies that we encounter are epiploic appendagitis, omental infarction, mesenteric panniculitis, and encapsulated fat necrosis. Less common entities that can occur are pancreatic saponification, heterotopic mesenteric ossification, and pseudolipoma of the capsule of Glisson. These entities can mimic more urgent pathologies such as appendicitis, diverticulitis, or malignancies.
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- 2020
9. The antigen-binding moiety in the driver's seat of CARs
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Heleen Hanssens, Karine Breckpot, Nick Devoogdt, Fien Meeus, Kim De Veirman, Supporting clinical sciences, Faculty of Medicine and Pharmacy, Laboratory of Molecullar and Cellular Therapy, Basic (bio-) Medical Sciences, Hematology, Medical Imaging, and Translational Imaging Research Alliance
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Computer science ,medicine.medical_treatment ,T cell ,T-Lymphocytes ,Computational biology ,Immunotherapy, Adoptive ,Epitope ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Drug Discovery ,medicine ,Humans ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Cell growth ,T-cell receptor ,Immunotherapy ,Chimeric antigen receptor ,Immune checkpoint ,medicine.anatomical_structure ,Ectodomain ,030220 oncology & carcinogenesis ,Molecular Medicine ,human activities - Abstract
Immuno-oncology has been at the forefront of cancer treatment in recent decades. In particular immune checkpoint and chimeric antigen receptor (CAR)-T cell therapy have achieved spectacular results. Over the years, CAR-T cell development has followed a steady evolutionary path, focusing on increasing T cell potency and sustainability, which has given rise to different CAR generations. However, there was less focus on the mode of interaction between the CAR-T cell and the cancer cell; more specifically on the targeting moiety used in the CAR and its specific properties. Recently, the importance of optimizing this domain has been recognized and the possibilities have been exploited. Over the last 10 years-in addition to the classical scFv-based CARs-single domain CARs, natural receptor-ligand CARs, universal CARs and CARs targeting more than one antigen have emerged. In addition, the specific parameters of the targeting domain and their influence on T cell activation are being examined. In this review, we concisely present the history of CAR-T cell therapy, and then expand on various developments in the CAR ectodomain. We discuss different formats, each with their own advantages and disadvantages, as well as the developments in affinity tuning, avidity effects, epitope location, and influence of the extracellular spacer.
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- 2022
10. Ultrasound Molecular Imaging of Atherosclerosis With Nanobodies
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Beat A. Kaufmann, Nick Devoogdt, Mukesh Punjabi, Lifen Xu, Thomas Wolff, Amanda Ochoa-Espinosa, Alexis Broisat, Ahmed Murtaja, Alexandra Kosareva, Supporting clinical sciences, Medical Imaging, and Translational Imaging Research Alliance
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0301 basic medicine ,Vascular Cell Adhesion Molecule-1 ,Aorta, Thoracic ,Inflammation ,030204 cardiovascular system & hematology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Brachiocephalic Trunk ,Cells, Cultured ,Ultrasonography ,Mice, Knockout ,Microbubbles ,Chemistry ,Cell adhesion molecule ,business.industry ,Endothelial Cells ,Ultrasound molecular imaging ,Atherosclerosis ,Molecular Imaging ,Disease Models, Animal ,030104 developmental biology ,Risk stratification ,Cancer research ,Molecular imaging ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objective: Contrast-enhanced ultrasound molecular imaging (CEUMI) of endothelial expression of VCAM (vascular cell adhesion molecule)-1 could improve risk stratification for atherosclerosis. The microbubble contrast agents developed for preclinical studies are not suitable for clinical translation. Our aim was to characterize and validate a microbubble contrast agent using a clinically translatable single-variable domain immunoglobulin (nanobody) ligand. Approach and Results: Microbubble with a nanobody targeting VCAM-1 (MB cAbVcam1-5 ) and microbubble with a control nanobody (MB VHH2E7 ) were prepared and characterized in vitro. Attachment efficiency to VCAM-1 under continuous and pulsatile flow was investigated using activated murine endothelial cells. In vivo CEUMI of the aorta was performed in atherosclerotic double knockout and wild-type mice after injection of MB cAbVcam1-5 and MB VHH2E7 . Ex vivo CEUMI of human endarterectomy specimens was performed in a closed-loop circulation model. The surface density of the nanobody ligand was 3.5×10 5 per microbubble. Compared with MB VHH2E7 , MB cAbVcam1-5 showed increased attachment under continuous flow with increasing shear stress of 1-8 dynes/cm 2 while under pulsatile flow attachment occurred at higher shear stress. CEUMI in double knockout mice showed signal enhancement for MB cAbVcam1-5 in early ( P =0.0003 versus MB VHH2E7 ) and late atherosclerosis ( P =0.007 versus MB VHH2E7 ); in wild-type mice, there were no differences between MB cAbVcam1-5 and MB VHH2E7 . CEUMI in human endarterectomy specimens showed a 100% increase in signal for MB cAbVcam1-5 versus MB VHH2E7 (20.6±27.7 versus 9.6±14.7, P =0.0156). Conclusions: CEUMI of the expression of VCAM-1 is feasible in murine models of atherosclerosis and on human tissue using a clinically translatable microbubble bearing a VCAM-1 targeted nanobody.
- Published
- 2019
11. Stromal-targeting radioimmunotherapy mitigates the progression of therapy-resistant tumors
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Ana Rita Pombo Antunes, Tony Lahoutte, Ahmet Krasniqi, Emile J. Clappaert, Aleksandar Murgaski, Kiavash Movahedi, Marnik Vuylsteke, Amanda Gonçalves, Geert Stangé, Nick Devoogdt, Jo A. Van Ginderachter, Geert Raes, Matthias D'Huyvetter, Evangelia Bolli, Danielle Berus, Sana M. Arnouk, Department of Bio-engineering Sciences, Faculty of Sciences and Bioengineering Sciences, Supporting clinical sciences, Medical Imaging, Preventie- & Milieudienst, Medicine and Pharmacy academic/administration, Diabetes Pathology & Therapy, Pathologic Biochemistry and Physiology, Basic (bio-) Medical Sciences, Faculty of Medicine and Pharmacy, Nuclear Medicine, Cellular and Molecular Immunology, and Translational Imaging Research Alliance
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Stromal cell ,Paclitaxel ,medicine.drug_class ,medicine.medical_treatment ,Pharmaceutical Science ,Receptors, Cell Surface ,02 engineering and technology ,Tumor-associated macrophage ,Adenocarcinoma ,Monoclonal antibody ,tumor-associated macrophage ,Mice ,03 medical and health sciences ,Radioresistance ,medicine ,Animals ,Lectins, C-Type ,Doxorubicin ,030304 developmental biology ,Mice, Inbred BALB C ,0303 health sciences ,hypoxia ,Chemistry ,Macrophages ,Mammary Neoplasms, Experimental ,immune checkpoint blockade ,Radioimmunotherapy ,Single-Domain Antibodies ,021001 nanoscience & nanotechnology ,Mannose-Binding Lectins ,Radionuclide therapy ,Cancer cell ,Nanobody ,Disease Progression ,Cancer research ,Female ,Stromal Cells ,0210 nano-technology ,Mannose Receptor ,medicine.drug - Abstract
Radioimmunotherapy (RIT) aims to deliver a high radiation dose to cancer cells, while minimizing the exposure of normal cells. Typically, monoclonal antibodies are used to target the radionuclides to cancer cell surface antigens. However, antibodies face limitations due to their poor tumor penetration and suboptimal pharmacokinetics, while the expression of their target on the cancer cell surface may be gradually lost. In addition, most antigens are expressed in a limited number of tumor types. To circumvent these problems, we developed a Nanobody (Nb)-based RIT against a prominent stromal cell (stromal-targeting radioimmunotherapy or STRIT) present in nearly all tumors, the tumor-associated macrophage (TAM). Macrophage Mannose Receptor (MMR) functions as a stable molecular target on TAM residing in hypoxic areas, further allowing the delivery of a high radiation dose to the more radioresistant hypoxic tumor regions. Since MMR expression is not restricted to TAM, we first optimized a strategy to block extra-tumoral MMR to prevent therapy-induced toxicity. A 100-fold molar excess of unlabeled bivalent Nb largely blocks extra-tumoral binding of Lu-177-labeled anti-MMR Nb and prevents toxicity, while still allowing the intra-tumoral binding of the monovalent Nb. Interestingly, three doses of Lu-177-labeled anti-MMR Nb resulted in a significantly retarded tumor growth, thereby outcompeting the effects of antiPD1, anti-VEGFR2, doxorubicin and paclitaxel in the TS/A mammary carcinoma model. Together, these data propose anti-MMR STRIT as a valid new approach for cancer treatment.
- Published
- 2019
12. The Next-Generation Immune Checkpoint LAG-3 and Its Therapeutic Potential in Oncology: Third Time’s a Charm
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Nick Devoogdt, Marleen Keyaerts, Karine Breckpot, Quentin Lecocq, Basic (bio-) Medical Sciences, Faculty of Medicine and Pharmacy, Supporting clinical sciences, Medical Imaging, Nuclear Medicine, and Translational Imaging Research Alliance
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,diagnosis ,Lymphocyte ,medicine.medical_treatment ,Review ,Catalysis ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Antigens, CD ,LAG-3 ,Internal medicine ,Neoplasms ,Biomarkers, Tumor ,Cytotoxic T cell ,Medicine ,Animals ,Humans ,cancer ,Physical and Theoretical Chemistry ,Molecular Biology ,Immune Checkpoint Inhibitors ,immune checkpoint ,lcsh:QH301-705.5 ,Spectroscopy ,business.industry ,Organic Chemistry ,Cancer ,General Medicine ,Immunotherapy ,medicine.disease ,Lymphocyte Activation Gene 3 Protein ,Immune checkpoint ,Computer Science Applications ,Blockade ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,lcsh:QD1-999 ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,Cancer cell ,oncology ,immunotherapy ,business - Abstract
The blockade of immune checkpoints (ICPs), such as cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed death-1 (PD-1) and its ligand (PD-L1), has propelled the field of immuno-oncology into its current era. Drugs targeting these ICPs have improved clinical outcome in a number of patients with solid and hematological cancers. Nonetheless, some patients have no benefit from these ICP-blocking therapies. This observation has instigated research into alternative pathways that are responsible for the escape of cancer cells from anti-cancer immune responses. From this research, a number of molecules have emerged as promising therapeutic targets, including lymphocyte activating gene-3 (LAG-3), a next-generation ICP. We will review the current knowledge on the biological activity of LAG-3 and linked herewith its expression on activated immune cells. Moreover, we will discuss the prognostic value of LAG-3 and how LAG-3 expression in tumors can be monitored, which is an aspect that is of utmost importance, as the blockade of LAG-3 is actively pursued in clinical trials.
- Published
- 2021
13. Phase I Trial of 131I-GMIB-Anti-HER2-VHH1, a New Promising Candidate for HER2-Targeted Radionuclide Therapy in Breast Cancer Patients
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Marleen Keyaerts, Frank van der Aa, Ilse Vaneycken, Matthias D'Huyvetter, Tony Lahoutte, Hendrik Everaert, Albert D. Windhorst, Vicky Caveliers, Nick Devoogdt, Pieterjan Gykiere, Geert Raes, N. Harry Hendrikse, Jens De Vos, Jos L E Eersels, Johannes Heemskerk, Christel Fontaine, Marian Vanhoeij, François Duhoux, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, CCA - Imaging and biomarkers, CCA - Cancer Treatment and quality of life, Supporting clinical sciences, Medical Imaging, Cellular and Molecular Immunology, Translational Imaging Research Alliance, Nuclear Medicine, Medical Oncology, Laboratory for Medical and Molecular Oncology, Surgical clinical sciences, Surgery, and Department of Bio-engineering Sciences
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Biodistribution ,business.industry ,Cancer ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,medicine.anatomical_structure ,Trastuzumab ,030220 oncology & carcinogenesis ,Radionuclide therapy ,Medicine ,Radiology, Nuclear Medicine and imaging ,Bone marrow ,Pertuzumab ,business ,Nuclear medicine ,Adverse effect ,medicine.drug - Abstract
Introduction:131I-GMIB-Anti-HER2-VHH1 is a targeted radionuclide theranostic agent directed at HER2 expressing cancers. VHH1 is a single domain antibody fragment covalently linked to therapeutic radio-iodine 131I via the linker SGMIB. The Phase I study presented was aimed at evaluating the safety, biodistribution, radiation dosimetry and tumor imaging potential of 131I-GMIB-Anti-HER2-VHH1 in healthy volunteers and breast cancer patients. Methods: In a first cohort, six healthy volunteers were included. The biodistribution of 131I-GMIB-Anti-HER2-VHH1 was assessed using whole body (anterior and posterior) planar images obtained at 40 min., 2, 4, 24 and 72 h following i.v. administered (38 ± 9 MBq) 131I-GMIB-VHH1. Imaging data were analyzed using OLINDA/EXM software 1.0 to determine the dosimetry. Blood and urine samples were obtained over 72h. In the second cohort, three patients with metastatic HER2 positive breast cancer were included. Planar whole-body imaging was performed at 2 h and 24 h after injection. Additional SPECT/CT images were obtained following the whole body images at 2 and 24 h in case of relevant uptake in known cancer lesions Results: No drug related adverse events (AEs) were observed throughout the study. The biological half-life of 131I-GMIB-Anti-HER2-VHH1 in healthy subjects was about 8 h. After i.v. administration, the compound is eliminated from the blood with a 2.5 h half-life. The drug is primarily eliminated via the kidneys. The drug was stable in circulation and there was no increased accumulation in thyroid or stomach. The absorbed dose to the kidneys was 1.54 ± 0.25 mGy/MBq, while to bone marrow 0.03 ± 0.01 mGy/MBq. SPECT/CT imaging in patients with advanced breast cancer showed focal uptake of 131I-GMIB-Anti-HER2-VHH1 in metastatic lesions. Conclusion: No AEs were observed after iv administration of 131I-GMIB-Anti-HER2-VHH1 at low activity. Unbound drug is rapidly eliminated via the kidneys. In patients with stage IV HER2 positive breast cancer accumulation of 131I-GMIB-Anti-HER2-VHH1in metastatic sites was observed. Dosimetry predicts kidneys as the dose limiting organ upon dose escalation, but kidney toxicity should only occur at very high injected activities. Dose escalation is planned in a subsequent phase I/II study to assess the therapeutic window of this compound (NCT04467515).
- Published
- 2021
14. Repeatability and reproducibility of ADC measurements
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Nicolas Michoux, Jakub Ceranka, Thierry Metens, Stephan Hahn, Frédéric Lecouvet, Johan De Mey, Jef Vandemeulebroucke, Laurence Collette, Olivier Debeir, Pierre Lu, Perrine Triqueneaux, Yan Liu, Carola Brussaard, Hubert Raeymaekers, François M. Peeters, Julie Absil, Inneke Willekens, Faculty of Engineering, Electronics and Informatics, Vrije Universiteit Brussel, Supporting clinical sciences, Medical Imaging, Radiology, Medicine and Pharmacy academic/administration, IR Academic Unit, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, Translational Imaging Research Alliance, UCL - SSS/IREC/IMAG - Pôle d'imagerie médicale, and UCL - (SLuc) Service de radiologie
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Reproducibility of results ,Male ,medicine.medical_specialty ,Coefficient of variation ,Whole body imaging ,Sciences de l'ingénieur ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Effective diffusion coefficient ,Humans ,Radiology, Nuclear Medicine and imaging ,Femur ,Prospective Studies ,Neuroradiology ,Cancer ,Reproducibility ,Disease progression ,Whole-body imaging ,business.industry ,Prostate ,General Medicine ,Repeatability ,Sciences bio-médicales et agricoles ,Magnetic Resonance Imaging ,Confidence interval ,body regions ,Diffusion Magnetic Resonance Imaging ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,oncology ,Disease Progression ,Radiology ,reproducibility of results ,business - Abstract
Multicenter oncology trials increasingly include MRI examinations with apparent diffusion coefficient (ADC) quantification for lesion characterization and follow-up. However, the repeatability and reproducibility (R&R) limits above which a true change in ADC can be considered relevant are poorly defined. This study assessed these limits in a standardized whole-body (WB)-MRI protocol., info:eu-repo/semantics/published
- Published
- 2021
15. Evaluating lower limb kinematics and pathology with dynamic CT
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Buzzatti, Luca, Keelson, Benyameen, Vanlauwe, Johan, Buls, Nico, Johan, De Mey, Vandemeulebroucke, Jef, Cattrysse, Erik, Scheerlinck, Thierry, Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physical Therapy, Multidimensional signal processing and communication, Supporting clinical sciences, Faculty of Medicine and Pharmacy, Surgical clinical sciences, Medical Imaging, Orthopaedics - Traumatology, Radiology, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, Translational Imaging Research Alliance, Electronics and Informatics, and Arthro-kinematics
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Dynamic CT ,kinematics ,Radiology Nuclear Medicine and imaging ,lower limb ,Musculoskeletal pathologies - Abstract
Evaluating musculoskeletal conditions of the lower limb and understanding the pathophysiology of complex bone kinematics is challenging. Static images do not take into account the dynamic component of relative bone motion and muscle activation. Fluoroscopy and dynamic MRI have important limitations. Dynamic CT (4D-CT) is an emerging alternative that combines high spatial and temporal resolution, with an increased availability in clinical practice. 4D-CT allows simultaneous visualization of bone morphology and joint kinematics. This unique combination makes it an ideal tool to evaluate functional disorders of the musculoskeletal system. In the lower limb, 4D-CT has been used to diagnose femoroacetabular impingement, patellofemoral, ankle and subtalar joint instability, or reduced range of motion. 4D-CT has also been used to demonstrate the effect of surgery, mainly on patellar instability. 4D-CT will need further research and validation before it can be widely used in clinical practice. We believe, however, itis here to stay, and will become a reference in the diagnosis of lower limb conditions and the evaluation of treatment options. Cite this article: Bone Joint J 2021;103-B(5):822-827.
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- 2021
16. A rare cause of unilateral breast swelling in a male infant caused by fibrous hamartoma of infancy combined with pseudoangiomatous stromal hyperplasia
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Ieva Garkalne, Jan Jonckheere, M. Antic, A. Schiettecatte, Marian Vanhoeij, Johan De Mey, Radiology, Supporting clinical sciences, Surgical clinical sciences, Surgery, Medical Imaging, Body Composition and Morphology, and Translational Imaging Research Alliance
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lcsh:Medical physics. Medical radiology. Nuclear medicine ,Male ,Pseudoangiomatous stromal hyperplasia ,Pathology ,medicine.medical_specialty ,lcsh:R895-920 ,Pseudoangiomatous Stromal Hyperplasia ,Breast swelling ,Unilateral Breast Swelling ,030218 nuclear medicine & medical imaging ,Resection ,Lesion ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Fibrous hamartoma ,Radiology, Nuclear Medicine and imaging ,Fibrous Hamartoma ,skin and connective tissue diseases ,Medicine(all) ,Pediatric ,business.industry ,Breast lumps ,medicine.disease ,medicine.symptom ,business ,Fibrous hamartoma of infancy ,030217 neurology & neurosurgery - Abstract
We report a case of a male infant who underwent resection of a unilateral breast mass with a histopathological diagnosis of a fibrous hamartoma of infancy (FHI) combined with a pseudoangiomatous stromal hyperplasia (PASH). Breast lumps are uncommon in infants and children, especially in boys. FHI and PASH are very rare causes of breast lumps, especially in infants. To our knowledge, this is the first report of a combination of both pathologies in 1 lesion in the breast of an infant.
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- 2019
17. Fluid distribution in ankle tendon sheaths in healthy volunteers: MRI findings
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Johan De Mey, Steven Provyn, Inneke Willekens, Michel De Maeseneer, Leon Lenchik, Maryam Shahabpour, Nico Buls, Supporting clinical sciences, Medical Imaging, Radiology, Body Composition and Morphology, Translational Imaging Research Alliance, Teacher Education, Anatomical Research and Clinical Studies, Vrije Universiteit Brussel, Physiotherapy, Human Physiology and Anatomy, and Basic (bio-) Medical Sciences
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Adult ,Male ,medicine.medical_specialty ,Pathology and Forensic Medicine ,Tendons ,Young Adult ,03 medical and health sciences ,Synovial Fluid ,Healthy volunteers ,medicine ,Peroneus longus ,Humans ,Radiology, Nuclear Medicine and imaging ,0303 health sciences ,business.industry ,Mean age ,Anatomy ,musculoskeletal system ,Magnetic Resonance Imaging ,Healthy Volunteers ,Tendon ,Tendon ankle ,medicine.anatomical_structure ,030301 anatomy & morphology ,Radiology Nuclear Medicine and imaging ,Flexor hallucis longus ,Orthopedic surgery ,Female ,Surgery ,Ankle ,business ,Ankle Joint ,Mri findings - Abstract
PURPOSE: To assess normal distribution of fluid in the tendon sheaths of the ankle. METHODS: 21 healthy volunteers were evaluated. Bilateral ankle MRI was performed on a 3T unit with PD-weighted images with fat saturation. The images were interpreted by two radiologists separately, and the short-axis dimension of fluid amount was measured. Bland-Altman plots and correlation plots were used to assess consistency between readers. RESULTS: There were 13 men and 8 women. The mean age was 24.7 years. Fluid in the retromalleolar part of the peroneus longus was seen in three ankles of three volunteers and in the inframalleolar part in three ankles of three volunteers. Fluid in the retromalleolar part of the peroneus brevis was seen in four ankles of three volunteers and in the inframalleolar part in three ankles of two volunteers. Fluid in the retromalleolar part of the tibialis posterior was seen in 37 ankles of 20 volunteers and in the inframalleolar part in 38 ankles of 21 volunteers Fluid in the retromalleolarpart of the flexor digitorum was seen in 14 ankles of eight volunteers and in the inframalleolar part in 11 ankles of eight volunteers Fluid in the retromalleolar part of the flexor hallucis longus was seen in 23 ankles of 16 volunteers and in the inframalleolar part in 17 ankles of 11 volunteers. CONCLUSION: Fluid is common in the retro- and inframalleolar parts of the medial tendons. Fluid is virtually absent in the peroneal tendons and anterior tendon sheaths in normal volunteers.
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- 2019
18. Nanobody-Facilitated Multiparametric PET/MRI Phenotyping of Atherosclerosis
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Giuseppe Carlucci, Max L. Senders, Jun Tang, Alexis Broisat, Thomas Reiner, Geert Raes, Claudia Calcagno, Samantha Baxter, Amr Alaarg, Willem J. M. Mulder, Seigo Ishino, Zahi A. Fayad, Brenda L. Sanchez-Gaytan, Jason S. Lewis, Mark E. Lobatto, Laura Zendman, Sophie Hernot, Nick Devoogdt, Jan C. van de Voort, Carlos Pérez-Medina, Yiming Zhao, Anu E. Meerwaldt, Philip M. Robson, Nicolas A. Karakatsanis, Anna Palmisano, Gilles Boeykens, Francois Fay, Sotirios Tsimikas, Biomaterials Science and Technology, Clinical sciences, Supporting clinical sciences, Medical Imaging, Department of Bio-engineering Sciences, Cellular and Molecular Immunology, Translational Imaging Research Alliance, ACS - Atherosclerosis & ischemic syndromes, Graduate School, 01 Internal and external specialisms, Radiology and Nuclear Medicine, and Medical Biochemistry
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Aging ,Pathology ,Scavenger Receptors ,Mice, Knockout, ApoE ,Cardiorespiratory Medicine and Haematology ,030204 cardiovascular system & hematology ,Cardiovascular ,Multimodal Imaging ,030218 nuclear medicine & medical imaging ,Neovascularization ,Mice ,0302 clinical medicine ,Lectins ,Receptors ,Medicine ,Macrophage ,Stage (cooking) ,Plaque ,Atherosclerotic ,screening and diagnosis ,C-Type ,medicine.diagnostic_test ,Scavenger Receptors, Class E ,Magnetic Resonance Imaging ,Plaque, Atherosclerotic ,Detection ,Phenotype ,Radiology Nuclear Medicine and imaging ,Positron emission tomography ,Cell Surface ,Disease Progression ,Biomedical Imaging ,Rabbits ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Mannose Receptor ,ApoE ,medicine.drug ,medicine.medical_specialty ,Knockout ,Clinical Sciences ,Vascular Cell Adhesion Molecule-1 ,Receptors, Cell Surface ,Inflammation ,Article ,03 medical and health sciences ,Humans ,Animals ,Genetic Predisposition to Disease ,Lectins, C-Type ,Radiology, Nuclear Medicine and imaging ,Multiparametric Magnetic Resonance Imaging ,Lighting ,Fluorodeoxyglucose ,Animal ,business.industry ,Magnetic resonance imaging ,Single-Domain Antibodies ,Atherosclerosis ,molecular imaging ,4.1 Discovery and preclinical testing of markers and technologies ,Disease Models, Animal ,nanobody ,Good Health and Well Being ,Early Diagnosis ,Mannose-Binding Lectins ,PET/MRI ,Cardiovascular System & Hematology ,Positron-Emission Tomography ,Disease Models ,Radiopharmaceuticals ,Molecular imaging ,atherosclerosis ,business ,Class E - Abstract
ObjectivesThis study sought to develop an integrative positron emission tomography (PET) with magnetic resonance imaging (MRI) procedure for accurate atherosclerotic plaque phenotyping, facilitated by clinically approved and nanobody radiotracers.BackgroundNoninvasive characterization of atherosclerosis remains a challenge in clinical practice. The limitations of current diagnostic methods demonstrate that, in addition to atherosclerotic plaque morphology and composition, disease activity needs to be evaluated.MethodsWe screened 3 nanobody radiotracers targeted to different biomarkers of atherosclerosis progression, namely vascular cell adhesion molecule (VCAM)-1, lectin-like oxidized low-density lipoprotein receptor (LOX)-1, and macrophage mannose receptor (MMR). The nanobodies, initially radiolabeled with copper-64 (64Cu), were extensively evaluated in Apoe-/- mice and atherosclerotic rabbits using a combination of invivo PET/MRI readouts and exvivo radioactivity counting, autoradiography, and histological analyses.ResultsThe 3 nanobody radiotracers accumulated in atherosclerotic plaques and displayed short circulation times due to fast renal clearance. The MMR nanobody was selected for labeling with gallium-68 (68Ga), a short-lived radioisotope with high clinical relevance, and used in an ensuing atherosclerosis progression PET/MRI study. Macrophage burden was longitudinally studied by 68Ga-MMR-PET, plaque burden by T2-weighted MRI, and neovascularization by dynamic contrast-enhanced (DCE) MRI. Additionally, inflammation and microcalcifications were evaluated by fluorine-18 (18F)-labeled fluorodeoxyglucose (18F-FDG) and 18F-sodium fluoride (18F-NaF) PET, respectively. We observed an increase in all the aforementioned measures as disease progressed, and the imaging signatures correlated with histopathological features.ConclusionsWe have evaluated nanobody-based radiotracers in rabbits and developed an integrative PET/MRI protocolthat allows noninvasive assessment of different processes relevant to atherosclerosis progression. This approachallowsthemultiparametric study of atherosclerosis and can aid in early stage anti-atherosclerosis drug trials.
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- 2019
19. Identification of the cerebral effects of paracetamol in healthy subjects: an fMRI study
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Patrice Forget, Peter Van Schuerbeek, Jan Poelaert, Olivier De Coster, Johan De Mey, Anesthesiology, Anesthesiology research group, Supporting clinical sciences, Body Composition and Morphology, Medical Imaging, Translational Imaging Research Alliance, and Radiology
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brain ,Analgesic ,Pharmacology ,behavioral disciplines and activities ,050105 experimental psychology ,03 medical and health sciences ,0302 clinical medicine ,Healthy volunteers ,Medicine ,0501 psychology and cognitive sciences ,Antipyretic ,business.industry ,Mechanism (biology) ,fMRI ,05 social sciences ,Healthy subjects ,Articles ,Pain management ,Paracetamol ,Anesthesiology and Pain Medicine ,nervous system ,Identification (biology) ,pharmacology ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Introduction: Paracetamol is commonly used for its antipyretic properties and analgesic effects, but the central mechanism remains elusive. We designed a study in healthy volunteers to detect the central functional working mechanism of paracetamol. Subjects, material and methods: A total of 20 subjects had a baseline functional magnetic resonance imaging (fMRI) before the intake of 1000 mg paracetamol orally; 60 minutes later, a second fMRI was made aiming detection of regional blood flow differences. Results: A decreased connectivity was observed in the ventral volume of interest (VOI), with the posterior cingulate (with both the left anterior cingulate cortex (ACC) and right ACC: respectively, Ke = 576; t = −6.8894 and Ke = 185; t = −4.8178) and the inferior temporal left (Ke = 103; t = −5.0993); in the combined ventral and dorsal VOIs, the posterior cingulate (with the left ACC; Ke = 149; t = −4.5658) and, both with the right ACC, the inferior temporal left (Ke = 88; t = −3.8456) and the inferior frontal gyrus (Ke = 86; t = −4.3937) had a decrease in connectivity. An increase was seen in other regions, including, among others, the middle frontal and temporal gyri (respectively, Ke = 85; t = 4.4256 and Ke = 85; t = 5.6851), the inferior frontal (with the left ACC: Ke = 165; t = 4.4998) and the superior frontal gyrus (with the right ACC; Ke = 281; t = 4.5992), and the post/precentral gyrus (with the right ACC, respectively, Ke = 102; t = 6.0582 and Ke = 105; t = 4.0776). Conclusions: On fMRIs in healthy volunteers, the ingestion of paracetamol affects connections with the ACC. This suggests a central effect of paracetamol in cerebral areas known to be associated with pain. Further studies are needed to demonstrate the same effects in acute and chronic pain states.
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- 2019
20. A Convergence Proof of MLEM and MLEM-3 With Fixed Background
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Michel Defrise, Koen Salvo, Medical Imaging, Supporting clinical sciences, and Translational Imaging Research Alliance
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positron emission tomography ,Computer science ,Maximum likelihood ,Physics::Medical Physics ,Iterative reconstruction ,030218 nuclear medicine & medical imaging ,Image (mathematics) ,03 medical and health sciences ,0302 clinical medicine ,Convergence (routing) ,Image Processing, Computer-Assisted ,medicine ,Humans ,positron emission tomography (PET) ,Electrical and Electronic Engineering ,Likelihood Functions ,convergence ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,image reconstruction ,Maximum likelihood estimation ,Computer Science Applications ,data models ,Positron emission tomography ,Positron-Emission Tomography ,Algorithm ,Algorithms ,Software - Abstract
Maximum Likelihood Expectation-Maximization (MLEM) is a popular algorithm to reconstruct the activity image in Positron Emission Tomography (PET). This paper introduces a 'fundamental equality' for the MLEM complete data from which two key properties easily follow that allows us to: (i) prove in an elegant and compact way the convergence of MLEM for a forward model with fixed background (i.e., counts such as random and scatter coincidences); and (ii) generalize this proof for the MLEM-3 algorithm. Moreover we give necessary and sufficient conditions for the solution to be unique.
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- 2019
21. Four-dimensional CT as a valid approach to detect and quantify kinematic changes after selective ankle ligament sectioning
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Benyameen Keelson, Jef Vandemeulebroucke, Johan De Mey, Erik Cattrysse, Nico Buls, Gert Van Gompel, Thierry Scheerlinck, Luca Buzzatti, Michel De Maeseneer, Jean-Pierre Baeyens, Jildert Apperloo, Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physical Therapy, Supporting clinical sciences, Faculty of Medicine and Pharmacy, Faculty of Engineering, Surgical clinical sciences, Medical Imaging, Orthopaedics - Traumatology, Movement and Sport Sciences, Biomechanics, Radiology, Electronics and Informatics, Anatomical Research and Clinical Studies, Body Composition and Morphology, Translational Imaging Research Alliance, and Arthro-kinematics
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0301 basic medicine ,Rotation ,Computer science ,Ankle inversion ,lcsh:Medicine ,Kinematics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Cadaver ,Orientation (geometry) ,medicine ,Humans ,Displacement (orthopedic surgery) ,Four-Dimensional Computed Tomography ,Range of Motion, Articular ,lcsh:Science ,Multidisciplinary ,lcsh:R ,030104 developmental biology ,medicine.anatomical_structure ,general ,Ligaments, Articular ,Ligament ,Female ,lcsh:Q ,Ankle ,Range of motion ,030217 neurology & neurosurgery ,Ankle Joint ,Biomedical engineering - Abstract
The objective of the current study was to explore the potential of dynamic computed tomography to detect kinematic changes, induced by sequential sectioning of the lateral collateral ligaments of the ankle, during full motion sequence of the talocrural joint. A custom-made device was used to induce cyclic controlled ankle inversion movement in one fresh frozen cadaver leg. A 256-slice CT scanner was used to investigate four different scenarios. Scenario 1 with all ligaments intact was first investigated followed by sequential section of the anterior talo-fibular ligament (Scenario 2), the calcaneo-fibular ligament (Scenario 3) and posterior talo-fibular ligament (Scenario 4). Off-line image processing based on semi-automatic segmentation and bone rigid registration was performed. Motion parameters such as translation, rotational angles and orientation and position of the axis of rotation were calculated. Differences between scenarios were calculated. Progressive increase of cranio-caudal displacement up to 3.9 mm and flexion up to 10° compared to Scenario 1 were reported. Progressive changes in orientation (up to 20.6°) and position (up to 4.1 mm) of the axis of rotation were also shown. Estimated effective dose of 0.005 mSv (1.9 mGy CTDIvol) was reported. This study demonstrated that kinematic changes due to the absence of ligament integrity can be detected with 4DCT with minimal radiation exposure. Identifying abnormal kinematic patterns could have future application in helping clinicians to choose patients’ optimal treatment. Therefore, further studies with bigger in vitro sample sizes and consequent investigations in vivo are recommended to confirm the current findings.
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- 2019
22. An Efficient Method for Labeling Single Domain Antibody Fragments with 18F Using Tetrazine-Trans-Cyclooctene Ligation and a Renal Brush Border Enzyme-Cleavable Linker
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Nick Devoogdt, Michael R. Zalutsky, Ganesan Vaidyanathan, Zhengyuan Zhou, Supporting clinical sciences, Medical Imaging, and Translational Imaging Research Alliance
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Fluorine Radioisotopes ,Brush border ,Biomedical Engineering ,Mice, Nude ,Pharmaceutical Science ,Bioengineering ,Kidney ,01 natural sciences ,Article ,030218 nuclear medicine & medical imaging ,Cyclooctanes ,Heterocyclic Compounds, 1-Ring ,Mice ,03 medical and health sciences ,Tetrazine ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Pharmacology ,Microvilli ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Single-Domain Antibodies ,Molecular biology ,0104 chemical sciences ,Single-domain antibody ,medicine.anatomical_structure ,Cell culture ,Female ,Radiopharmaceuticals ,Ligation ,Linker ,Biotechnology ,Conjugate - Abstract
Single domain antibody fragments (sdAbs) labeled with (18)F have shown promise for assessing the status of oncological targets such as the human epidermal growth factor receptor 2 (HER2) by positron emission tomography (PET). Earlier, we evaluated two residualizing prosthetic agents for (18)F-labeling of anti-HER2 sdAbs; however, these methods resulted in poor labeling yields and high uptake of (18)F activity in the kidneys. To potentially mitigate these limitations, we have now developed an (18)F labeling method that utilizes the trans-cyclooctene (TCO)-tetrazine (Tz)-based inverse-electron demand Diels-Alder reaction (IEDDAR) in tandem with a renal brush border enzyme-cleavable glycine-lysine (GK) linker in the prosthetic moiety. The HER2-targeted sdAb 2Rs15d was derivatized with TCO-GK-PEG(4)-NHS or TCO-PEG(4)-NHS, which lacks the cleavable linker. As an additional control, the non HER2-specific sdAb R3B23 was derivatized with TCO-GK-PEG(4)-NHS. The resultant sdAb conjugates were labeled with (18)F by IEDDAR using [(18)F]AlF-NOTA-PEG(4)-methyltetrazine. As a positive control, the 2Rs15d sdAb was radioiodinated using the well-characterized residualizing prosthetic agent, N-succinimidyl 4-guanidinomethyl-3-[(125)I]iodobenzoate ([(125)I]SGMIB). Synthesis of [(18)F]AlF-NOTA-Tz-TCO-GK-2Rs15d was achieved with an overall radiochemical yield (RCY) of 17.8 ± 1.5% (n=5) in 90 min, a significant improvement over prior methods (3–4% in 2–3 h). In vitro assays indicated that [(18)F]AlF-NOTA-Tz-TCO-GK-2Rs15d bound with high affinity and immunoreactivity to HER2. In normal mice, when normalized to co-injected [(125)I]SGMIB-2Rs15d, the kidney uptake of [(18)F]AlF-NOTA-Tz-TCO-GK-2Rs15d was 15- and 28-fold lower (P
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- 2018
23. Detection of parathyroid adenomas with multiphase 4DCT
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Raeymaeckers, Steven, De Brucker, Yannick, Vanderhasselt, Tim, Buls, Nico, De Mey, Johan, Faculty of Medicine and Pharmacy, Basic (bio-) Medical Sciences, Radiology, Medicine and Pharmacy academic/administration, Medical Imaging, Supporting clinical sciences, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, and Translational Imaging Research Alliance
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Adenoma ,Male ,Parathyroid ,lcsh:Medical technology ,Time Factors ,Contrast Media ,parathyroid adenomas ,Lesion ,Parathyroid Glands ,Hounsfield scale ,Medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Four-Dimensional Computed Tomography ,4DCT ,Hyperparathyroidism ,business.industry ,Thyroid ,Ultrasound ,Middle Aged ,medicine.disease ,Hyperparathyroidism, Primary ,Effective dose (pharmacology) ,Tumor Burden ,CT dose reduction ,medicine.anatomical_structure ,Parathyroid Neoplasms ,Technical Advance ,lcsh:R855-855.5 ,Radiology Nuclear Medicine and imaging ,Endocrine disorders ,Female ,Lymph Nodes ,medicine.symptom ,business ,Nuclear medicine ,Primary hyperparathyroidism ,Neck - Abstract
Background Four-dimensional computed tomography (4DCT) is a commonly performed examination in the management of primary hyperparathyroidism, combining three-dimensional imaging with enhancement over time as the fourth dimension. We propose a novel technique consisting of 16 different contrast phases instead of three or four different phases. The main aim of this study was to ascertain whether this protocol allows the detection of parathyroid adenomas within dose limits. Our secondary aim was to examine the enhancement of parathyroid lesions over time. Methods For this prospective study, we included 15 patients with primary hyperparathyroidism and a positive ultrasound prior to surgery. We performed 4DCT with 16 different phases: an unenhanced phase followed by 11 consecutive arterial phases and 4 venous phases. Continuous axial scanning centered on the thyroid was performed over a fixed 8 cm or 16 cm coverage volume after the start of contrast administration. Results In all patients, an enlarged parathyroid lesion was demonstrated, and the mean lesion size was 13.6 mm. The mean peak arterial enhancement for parathyroid lesions was 384 Hounsfield units (HU) compared to 333 HU for the normal thyroid. No significant difference could be found. The time to peak (TTP) was significantly earlier for parathyroid adenomas than for normal thyroid tissue: 30.8 s versus 32.3 s (p value 0.008). The mean slope of increase (MSI) of the enhancement curve was significantly steeper than that of normal thyroid tissue: 29.8% versus 22.2% (p value 0.012). The mean dose length product was 890.7 mGy cm with a calculated effective dose of 6.7 mSv. Conclusion Our 4DCT protocol may allow better visualization of the pattern of enhancement of parathyroid lesions, as enhancement over time curves can be drawn. In this way, wash-in and wash-out of contrast in suspected lesions can be readily demonstrated. Motion artifacts are less problematic as multiple phases are available. Exposure to our proposed 4DCT technique is comparable to that for classic helical 4DCT. Careful selection of parameters (lowering kV and SNR) can help to further reduce the dose.
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- 2021
24. Mechanisms Underlying Connexin Hemichannel Activation in Disease
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Raf Van Campenhout, Timo W.M. De Groof, Nick Devoogdt, Ana Rita Coelho Gomes, Serge Muyldermans, Mathieu Vinken, Pharmaceutical and Pharmacological Sciences, Faculty of Medicine and Pharmacy, Experimental in vitro toxicology and dermato-cosmetology, Supporting clinical sciences, Vriendenkring VUB, Medical Imaging, Translational Imaging Research Alliance, Liver Connexin and Pannexin Research Group, and Connexin Signalling Research Group
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Connexin ,Review ,Connexins ,lcsh:Chemistry ,0302 clinical medicine ,Cytosol ,Homeostasis ,Phosphorylation ,lcsh:QH301-705.5 ,Spectroscopy ,0303 health sciences ,Cell Death ,Chemistry ,Gap junction ,Gap Junctions ,General Medicine ,Hydrogen-Ion Concentration ,3. Good health ,Computer Science Applications ,Cell biology ,medicine.symptom ,Intracellular ,Programmed cell death ,mechanism ,Inflammation ,Catalysis ,Connexon ,Inorganic Chemistry ,03 medical and health sciences ,medicine ,Extracellular ,otorhinolaryngologic diseases ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,030304 developmental biology ,Organic Chemistry ,Cell Membrane ,Pathogen-Associated Molecular Pattern Molecules ,lcsh:Biology (General) ,lcsh:QD1-999 ,Connexin 43 ,pathology ,sense organs ,Stress, Mechanical ,Peptides ,connexin hemichannel ,030217 neurology & neurosurgery - Abstract
Gap junctions and connexin hemichannels mediate intercellular and extracellular communication, respectively. While gap junctions are seen as the “good guys” by controlling homeostasis, connexin hemichannels are considered as the “bad guys”, as their activation is associated with the onset and dissemination of disease. Open connexin hemichannels indeed mediate the transport of messengers between the cytosol and extracellular environment and, by doing so, fuel inflammation and cell death in a plethora of diseases. The present mini-review discusses the mechanisms involved in the activation of connexin hemichannels during pathology.
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- 2021
25. Pneumorrhachis, an underreported sign associated with pneumomediastinum
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Abid, Wiem, Raeymaeckers, Steven, Johan, De Mey, Faculty of Medicine and Pharmacy, Basic (bio-) Medical Sciences, Radiology, Artificial Intelligence supported Modelling in clinical Sciences, Supporting clinical sciences, Body Composition and Morphology, Medical Imaging, and Translational Imaging Research Alliance
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Occupational / Environmental hazards ,Emergency ,Mediastinum ,Clinical Cases ,Chest imaging ,Anatomy ,CT - Abstract
Clinical History: A 19-year-old Caucasian male with no medical or surgical history presented at the emergency department for intermittent diffuse abdominal pain since 5 days. He complained of nausea, incoercible vomiting and loss of appetite. The patient was a known user of cannabis. Physical examination showed abdominal, thoracic and dorsal widespread subcutaneous emphysema., 19 years, male
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- 2021
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26. Development and Characterization of Nanobodies Targeting the Kupffer Cell
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Fang Zheng, Jinhong Zhou, Zhenlin Ouyang, Jiaxin Zhang, Xinyi Wang, Serge Muyldermans, Jo Van Ginderachter, Nick Devoogdt, Yurong Wen, Steve Schoonooghe, Geert Raes, Department of Bio-engineering Sciences, Cellular and Molecular Immunology, Supporting clinical sciences, Medical Imaging, and Translational Imaging Research Alliance
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0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Phage display ,Immunology ,Antibody Affinity ,KUPFFER CELLS ,epitope binning ,Epitope ,law.invention ,Clec4F ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell surface receptor ,law ,Epitope binning ,medicine ,Animals ,Immunology and Allergy ,Lectins, C-Type ,Receptor ,Original Research ,X-ray crystallography ,Medicine(all) ,biology ,Chemistry ,Kupffer cell ,Single-Domain Antibodies ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Liver ,030220 oncology & carcinogenesis ,Recombinant DNA ,biology.protein ,Nanobody ,Antibody ,lcsh:RC581-607 - Abstract
Nanobodies that are derived from single-chain antibodies of camelids have served as powerful tools in diagnostics, therapeutics and investigation of membrane receptors' structure and function. In this study, we developed a series of nanobodies by a phage display screening building from lymphocytes isolated from an alpaca immunized with recombinant mouse Kupffer cell receptor Clec4F, which is involved in pathogen recognition by binding to galactose and N-acetylgalactosamine. Bio-panning selections retrieved 14 different nanobodies against Clec4F with an affinity ranging from 0.2 to 2 nM as determined by SPR. Those nanobodies mainly recognize 4 different epitopes as analyzed via competitive epitope binning. By analysis of the radioactivity in each organ after injection of 99mTc labeled Clec4F nanobodies in naïve mice, we found that these nanobodies are targeting the liver. Furthermore, we performed a structural characterization at atomic resolution of two of the Clec4F nanobodies from different epitope groups, which revealed distinct features within the CDR2 and CDR3 regions. Taken together, we developed a series of nanobodies targeting multiple distinct recognition epitopes of the Kupffer cell-specific receptor Clec4F which may be useful for its structural and functional investigation as well as for use as molecular imaging and therapeutic agents.
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- 2021
27. Therapeutic Nanobodies Targeting Cell Plasma Membrane Transport Proteins: A High-Risk/High-Gain Endeavor
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Nick Devoogdt, Timo W.M. De Groof, Serge Muyldermans, Raf Van Campenhout, Mathieu Vinken, Pharmaceutical and Pharmacological Sciences, Faculty of Medicine and Pharmacy, Experimental in vitro toxicology and dermato-cosmetology, Cellular and Molecular Immunology, Vriendenkring VUB, Liver Connexin and Pannexin Research Group, Connexin Signalling Research Group, Supporting clinical sciences, Medical Imaging, and Translational Imaging Research Alliance
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0301 basic medicine ,Drug ,High-gain antenna ,media_common.quotation_subject ,Cell ,lcsh:QR1-502 ,Review ,Biochemistry ,Models, Biological ,lcsh:Microbiology ,drug target ,03 medical and health sciences ,0302 clinical medicine ,Extracellular ,medicine ,Humans ,cell plasma membrane transport proteins ,Antigens ,Molecular Biology ,media_common ,therapy ,Cell plasma membrane ,Chemistry ,Cell Membrane ,Membrane Transport Proteins ,Single-Domain Antibodies ,Transmembrane protein ,nanobodies ,Cell biology ,Transport protein ,Cytosol ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis - Abstract
Cell plasma membrane proteins are considered as gatekeepers of the cell and play a major role in regulating various processes. Transport proteins constitute a subclass of cell plasma membrane proteins enabling the exchange of molecules and ions between the extracellular environment and the cytosol. A plethora of human pathologies are associated with the altered expression or dysfunction of cell plasma membrane transport proteins, making them interesting therapeutic drug targets. However, the search for therapeutics is challenging, since many drug candidates targeting cell plasma membrane proteins fail in (pre)clinical testing due to inadequate selectivity, specificity, potency or stability. These latter characteristics are met by nanobodies, which potentially renders them eligible therapeutics targeting cell plasma membrane proteins. Therefore, a therapeutic nanobody-based strategy seems a valid approach to target and modulate the activity of cell plasma membrane transport proteins. This review paper focuses on methodologies to generate cell plasma membrane transport protein-targeting nanobodies, and the advantages and pitfalls while generating these small antibody-derivatives, and discusses several therapeutic nanobodies directed towards transmembrane proteins, including channels and pores, adenosine triphosphate-powered pumps and porters.
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- 2021
28. The role of CT imaging for management of COVID-19 in epidemic area: early experience from a University Hospital
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Seema Döring, Johan De Mey, Koenraad Nieboer, Nico Buls, Vikram Rao Bollineni, Radiology, Faculty of Medicine and Pharmacy, Medicine and Pharmacy academic/administration, Medical Imaging, Supporting clinical sciences, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, and Translational Imaging Research Alliance
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lcsh:Medical physics. Medical radiology. Nuclear medicine ,medicine.medical_specialty ,medicine.diagnostic_test ,Coronavirus disease 2019 (COVID-19) ,Respiratory distress ,business.industry ,lcsh:R895-920 ,Ultrasound ,Chest ct ,RT-PCR ,COVID-19 ,Interventional radiology ,University hospital ,Chest CT ,Radiology Nuclear Medicine and imaging ,medicine ,Radiology, Nuclear Medicine and imaging ,Original Article ,Radiology ,Ct imaging ,business ,Neuroradiology - Abstract
Background To evaluate the clinical value of the chest CT scan compared to the reference standard real-time polymerase chain reaction (RT-PCR) in COVID-19 patients. Methods From March 29th to April 15th of 2020, a total of 240 patients with respiratory distress underwent both a low-dose chest CT scan and RT-PCR tests. The performance of chest CT in diagnosing COVID-19 was assessed with reference to the RT-PCR result. Two board-certified radiologists (mean 24 years of experience chest CT), blinded for the RT-PCR result, reviewed all scans and decided positive or negative chest CT findings by consensus. Results Out of 240 patients, 60% (144/240) had positive RT-PCR results and 89% (213/240) had a positive chest CT scans. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of chest CT in suggesting COVID-19 were 100% (95% CI: 97–100%, 144/240), 28% (95% CI: 19–38%, 27/240), 68% (95% CI: 65–70%) and 100%, respectively. The diagnostic accuracy of the chest CT suggesting COVID-19 was 71% (95% CI: 65–77%). Thirty-three patients with positive chest CT scan and negative RT-PCR test at baseline underwent repeat RT-PCR assay. In this subgroup, 21.2% (7/33) cases became RT-PCR positive. Conclusion Chest CT imaging has high sensitivity and high NPV for diagnosing COVID-19 and can be considered as an alternative primary screening tool for COVID-19 in epidemic areas. In addition, a negative RT-PCR test, but positive CT findings can still be suggestive of COVID-19 infection.
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- 2021
29. Functional Foreign Accent Syndrome in suspected Conversion Disorder: A case study
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C.M. van der Feltz-Cornelis, Roelien Bastiaanse, Stefanie Keulen, K van Dun, Jo Verhoeven, L. de Vroege, F Van Overwalle, Philippe Paquier, L de Page, Hubert Raeymaekers, Tine D’aes, P. Van Schuerbeek, Peter Mariën, J. De Mey, Linguistics and Literary Studies, Centre for Linguistics, Artificial Intelligence supported Modelling in clinical Sciences, Supporting clinical sciences, Medical Imaging, Radiology, Body Composition and Morphology, Translational Imaging Research Alliance, Psychology, Brain, Body and Cognition, Tranzo, Scientific center for care and wellbeing, and Geestelijke Gezondheidszorg
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Foreign accent syndrome ,Functional disorder ,medicine.medical_specialty ,Foreign Accent ,BF ,Audiology ,JARGON ,BEHAVIORAL STRESS ,Accent ,03 medical and health sciences ,0302 clinical medicine ,Aphasia ,Motor speech ,medicine ,Medical history ,030212 general & internal medicine ,Conversion disorder ,Language switching ,LANGUAGE REPRESENTATION ,Language mixing ,fMRI ,Neuropsychology ,Syndrome ,SPEECH ,FAS ,medicine.disease ,QP ,030227 psychiatry ,Psychiatry and Mental health ,Jargon ,RC0321 ,HIPPOCAMPAL CA1 ,Human medicine ,APHASIA ,medicine.symptom ,Psychology - Abstract
Background and objectives: We provide a case analysis for a 28-year-old, native Dutch-speaking lady who developed Foreign Accent Syndrome (FAS), a few weeks after falling down the staircase. In addition to FAS, which gave the impression she spoke with a German accent, German(-like) words and structures occurred. Speech symptoms were aggravated by increased stress, fatigue or emotional pressure, and this triggered jargon speech. It was hypothesized her FAS and jargon developed on a functional basis.Methods: In-depth analyses of the patient's medical background, neuropsychological and neurolinguistic tests and psychodiagnostic exams were done. The patient participated in an fMRI experiment. In a syllable repetition paradigm, motor speech activations were compared to those of healthy individuals, to see whether they were altered, which would be expected in case of a neurological etiology.Results: Medical history disclosed prior traumatic experiences for which she sought help, but no neurological incidents. Repeated neuropsychological and neurolinguistic tests showed deficits in recent memory and executive functioning. The patient demonstrated great difficulties with picture naming. Clinically, language switching and mixing as well as recurring jargon speech was found. Formal psychodiagnostic tests did not identify a clear disorder, but psychodiagnostic interviews were consistent with a DSM-5 conversion disorder. The fMRI study demonstrated that speech network activations corresponded to those found in healthy participants.Conclusion: The clinical neurolinguistic characteristics, outcome of the fMRI experiment, together with the clinical psychodiagnostic findings were strongly indicative for an underlying functional etiology for the FAS and jargon speech, presenting as symptoms of conversion disorder. (C) 2020 Asociacion Universitaria de Zaragoza para el Progreso de la Psiquiatria y la Salud Mental. Published by Elsevier Espana, S.L.U. All rights reserved.
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- 2021
30. Opposite effects of one session of 1 Hz rTMS on functional connectivity between pre-supplementary motor area and putamen depending on the dyskinesia state in Parkinson's disease
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Peter Van Schuerbeek, Chris Baeken, Guo-Rong Wu, Jacques De Keyser, Johan De Mey, Anja Flamez, Wietse Wiels, Clinical sciences, Medicine and Pharmacy academic/administration, Faculty of Medicine and Pharmacy, Neuroprotection & Neuromodulation, Neurology, Artificial Intelligence supported Modelling in clinical Sciences, Supporting clinical sciences, Medical Imaging, Radiology, Body Composition and Morphology, Translational Imaging Research Alliance, Vriendenkring VUB, Brain, Body and Cognition, and Psychiatry
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Male ,Neurology ,Parkinson's disease ,medicine.medical_treatment ,0302 clinical medicine ,LF rTMS ,Medicine ,Aged, 80 and over ,Supplementary motor area ,Putamen ,05 social sciences ,Motor Cortex ,Parkinson Disease ,Middle Aged ,Magnetic Resonance Imaging ,Transcranial Magnetic Stimulation ,Sensory Systems ,Psychiatry and Mental health ,medicine.anatomical_structure ,Radiology Nuclear Medicine and imaging ,Female ,medicine.symptom ,psychological phenomena and processes ,medicine.drug ,medicine.medical_specialty ,Levodopa ,Pre-SMA ,050105 experimental psychology ,03 medical and health sciences ,Physical medicine and rehabilitation ,Physiology (medical) ,mental disorders ,otorhinolaryngologic diseases ,Humans ,0501 psychology and cognitive sciences ,Aged ,Dyskinesias ,Resting state fMRI ,business.industry ,medicine.disease ,nervous system diseases ,Transcranial magnetic stimulation ,Dyskinesia ,nervous system ,Neurology (clinical) ,Nerve Net ,business ,030217 neurology & neurosurgery - Abstract
Objective To explore the effects of low-frequency repetitive transcranial magnetic stimulation (LF rTMS) on cortico-striatal-cerebellar resting state functional connectivity in Parkinson’s disease (PD), with and without dyskinesias. Methods Because there is increasing evidence of an involvement of the pre-supplementary motor area (pre-SMA) in the pathophysiology of levodopa induced dyskinesias, we targeted the right pre-SMA with LF rTMS in 17 PD patients. We explored the effects of one sham-controlled LF rTMS session on resting state functional connectivity of interconnected brain regions by using functional MRI, and how it is modified by levodopa. The clinical effect on motor function and dyskinesias was documented. Results As expected, one LF rTMS session did not alleviate dyskinesias. However, real, and not sham LF rTMS significantly increased the functional connectivity with the right putamen in patients with dyskinesias. In patients without dyskinesias, the real LF rTMS session significantly decreased functional connectivity in the right putamen and the cerebellum. We found no effects on functional connectivity after levodopa ingestion. Conclusion One session of 1 Hz rTMS has opposing effects on pre-SMA functional connectivity depending on the PD patients' dyskinesia state. Significance Patients dyskinesias state determines the way LF rTMS affects functional connectivity in late stage PD.
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- 2021
31. Synthetic MRI demonstrates prolonged regional relaxation times in the brain of preterm born neonates with severe postnatal morbidity
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Nico Buls, Jeroen Dudink, Roya Zolfaghari, Filip Cools, Maarten Naeyaert, Hubert Raeymaekers, Tim Vanderhasselt, Johan De Mey, Gert-Jan Allemeersch, Medicine and Pharmacy academic/administration, Medical Imaging, Radiology, Faculty of Medicine and Pharmacy, Artificial Intelligence supported Modelling in clinical Sciences, Supporting clinical sciences, Clinical sciences, Growth and Development, Neonatology, Body Composition and Morphology, and Translational Imaging Research Alliance
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Relaxometry ,medicine.medical_specialty ,Internal capsule ,ANCOVA, analysis of covariance ,Cognitive Neuroscience ,TEA, term equivalent age ,lcsh:Computer applications to medicine. Medical informatics ,050105 experimental psychology ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,Pediatrics, Perinatology, and Child Health ,Premature ,Neurorehabilitation ,lcsh:Neurology. Diseases of the nervous system ,Retrospective Studies ,PMA, postmenstrual age ,MANTiS, Morphologically Adaptive Neonatal Tissue Segmentation ,Receiver operating characteristic ,Term equivalent age ,business.industry ,05 social sciences ,Postmenstrual Age ,Infant, Newborn ,Brain ,Infant ,Retrospective cohort study ,Regular Article ,Quantitative MRI ,Newborn ,Magnetic Resonance Imaging ,Neurology ,Radiology Nuclear Medicine and imaging ,PLIC, posterior limb of the internal capsule ,Cardiology ,lcsh:R858-859.7 ,Neurology (clinical) ,Morbidity ,business ,Area under the roc curve ,030217 neurology & neurosurgery ,Infant, Premature ,Biomarkers - Abstract
Highlights • Early biomarkers are needed to identify preterm infants at risk for neurodevelopment impairment. • Synthetic MRI-based relaxometry is sensitive to age-related maturational changes. • Severe postnatal morbidity results in significantly prolonged regional tissue relaxation times. • Early myelinating structures appear to be more susceptible to brain injury. • Synthetic MRI may provide early prognostic biomarkers for neurodevelopment impairment., Background To identify preterm infants at risk for neurodevelopment impairment that might benefit from early neurorehabilitation, early prognostic biomarkers of future outcomes are needed. Objective To determine whether synthetic MRI is sensitive to age-related changes in regional tissue relaxation times in the brain of preterm born neonates when scanned at term equivalent age (TEA, 37–42 weeks), and to investigate whether severe postnatal morbidity results in prolonged regional tissue relaxation times. Materials and methods This retrospective study included 70 very preterm born infants scanned with conventional and synthetic MRI between January 2017 and June 2019 at TEA. Infants with severe postnatal morbidity were allocated to a high-risk group (n = 22). All other neonates were allocated to a low-risk group (n = 48). Linear regression analysis was performed to determine the relationship between relaxation times and postmenstrual age (PMA) at scan. Analysis of covariance was used to evaluate the impact of severe postnatal morbidity in the high-risk group on T1 and T2 relaxation times. Receiver operating characteristic (ROC) curves were plotted and analysed with area under the ROC curve (AUC) to evaluate the accuracy of classifying high-risk patients based on regional relaxation times. Results A linear age-related decrease of T1 and T2 relaxation times correlating with PMA at scan (between 37 and 42 weeks) was found in the deep gray matter, the cerebellum, the cortex, and the posterior limb of the internal capsule (PLIC) (p
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- 2021
32. Whole-Body MRI for the Detection of Recurrence in Melanoma Patients at High Risk of Relapse
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Carola Brussaard, Gil Awada, Yanina J L Jansen, Julia Katharina Schwarze, Johan De Mey, Teofila Seremet, Inneke Willekens, Bart Neyns, Surgery, Faculty of Medicine and Pharmacy, Supporting clinical sciences, Medical Imaging, Radiology, Clinical sciences, Internal Medicine, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, Translational Imaging Research Alliance, Medicine and Pharmacy academic/administration, Medical Oncology, Laboratory for Medical and Molecular Oncology, and Laboratory of Molecullar and Cellular Therapy
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Cancer Research ,medicine.medical_specialty ,Whole body mri ,Systemic therapy ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,melanoma ,Medicine ,030212 general & internal medicine ,Adverse effect ,Prospective cohort study ,Cancer staging ,medicine.diagnostic_test ,business.industry ,Melanoma ,screening ,whole-body MRI ,Magnetic resonance imaging ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,Cohort ,oncology ,Radiology ,business - Abstract
Introduction: No standard protocol for surveillance for melanoma patients is established. Whole-body magnetic resonance imaging (whole-body MRI) is a safe and sensitive technique that avoids exposure to X-rays and contrast agents. This prospective study explores the use of whole-body MRI for the early detection of recurrences. Material and Methods: Patients with American Joint Committee on Cancer Staging Manual (seventh edition, AJCC-7) stages IIIb/c or -IV melanoma who were disease-free following resection of macrometastases (cohort A), or obtained a durable complete response (CR) or partial response (PR) following systemic therapy (cohort B), were included. All patients underwent whole-body MRI, including T1, Short Tau Inversion Recovery, and diffusion-weighted imaging, every 4 months the first 3 years of follow-up and every 6 months in the following 2 years. A total body skin examination was performed every 6 months. Results: From November 2014 to November 2019, 111 patients were included (four screen failures, cohort A: 68 patients, cohort B: 39 patients). The median follow-up was 32 months. Twenty-six patients were diagnosed with suspected lesions. Of these, 15 patients were diagnosed with a recurrence on MRI. Eleven suspected lesions were considered to be of non-neoplastic origin. In addition, nine patients detected a solitary subcutaneous metastasis during self-examination, and two patients presented in between MRIs with recurrences. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were, respectively, 58%, 98%, 58%, 98%, and 98%. Sensitivity and specificity for the detection of distant metastases was respectively 88% and 98%. No patient experienced a clinically meaningful (>, grade 1) adverse event. Conclusions: Whole-body MRI for the surveillance of melanoma patients is a safe and sensitive technique sparing patients&prime, cumulative exposure to X-rays and contrast media.
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- 2021
33. Safety and feasibility evaluation of planning and execution of surgical revascularisation solely based on coronary CTA and FFR CT in patients with complex coronary artery disease: study protocol of the FASTTRACK CABG study
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Yoshinobu Onuma, Gregg W. Stone, Giulio Pompilio, Antonio L. Bartorelli, Torsten Doenst, Ulrich Schneider, Faisal Sharif, Hideyuki Kawashima, Saima Mushtaq, Charles A. Taylor, Francesco Maisano, Ulf Teichgräber, Ronny R. Buechel, Brian Thomsen, Campbell Rogers, Kaoru Tanaka, Daniele Andreini, Robbert J. de Winter, Enrico Ferrari, Patrick W. Serruys, Johan De Mey, Jonathon Leipsic, William Wijns, Mark La Meir, University of Zurich, Serruys, Patrick W, Radiology, Medical Imaging, Surgical clinical sciences, Cardiac Surgery, Artificial Intelligence supported Modelling in clinical Sciences, Supporting clinical sciences, Body Composition and Morphology, Translational Imaging Research Alliance, ACS - Atherosclerosis & ischemic syndromes, Cardiology, and ACS - Heart failure & arrhythmias
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medicine.medical_specialty ,cardiothoracic surgery ,medicine.medical_treatment ,610 Medicine & health ,Fractional flow reserve ,Coronary Artery Disease ,2700 General Medicine ,Coronary Angiography ,Surgical planning ,11171 Cardiocentro Ticino ,ischaemic heart disease ,Coronary artery disease ,surgery ,Coronary circulation ,Predictive Value of Tests ,Internal medicine ,Medicine ,Humans ,Prospective Studies ,cardiovascular imaging ,Coronary Artery Bypass ,coronary heart disease ,Radiation treatment planning ,business.industry ,Percutaneous coronary intervention ,General Medicine ,10181 Clinic for Nuclear Medicine ,medicine.disease ,Cardiac surgery ,10020 Clinic for Cardiac Surgery ,Fractional Flow Reserve, Myocardial ,medicine.anatomical_structure ,Cardiothoracic surgery ,Radiology Nuclear Medicine and imaging ,cardiology ,Cardiology ,Feasibility Studies ,business ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,cardiac surgery - Abstract
IntroductionThe previously published SYNTAX III REVOLUTION trial demonstrated that clinical decision-making between coronary artery bypass graft (CABG) and percutaneous coronary intervention based on coronary CT angiography (CCTA) had a very high agreement with the treatment decision derived from invasive coronary angiography (ICA). The study objective of the FASTTRACK CABG is to assess the feasibility of CCTA and fractional flow reserve derived from CTA (FFRCT) to replace ICA as a surgical guidance method for planning and execution of CABG in patients with three-vessel disease with or without left main disease.Methods and analysisThe FASTTRACK CABG is an investigator-initiated single-arm, multicentre, prospective, proof-of-concept and first-in-man study with feasibility and safety analysis. Surgical revascularisation strategy and treatment planning will be solely based on CCTA and FFRCT without knowledge of the anatomy defined by ICA. Clinical follow-up visit including CCTA will be performed 30 days after CABG in order to assess graft patency and adequacy of the revascularisation with respect to the surgical planning based on non-invasive imaging (CCTA) with functional assessment (FFRCT) and compared with ICA. Primary feasibility endpoint is CABG planning and execution solely based on CCTA and FFRCT in 114 patients. Primary safety endpoint based on 30 day CCTA is graft assessment and topographical adequacy of the revascularisation procedure. Automatic non-invasive assessment of functional coronary anatomy complexity is also evaluated with FFRCT for functional Synergy Between percutaneous coronary intervention With Taxus and Cardiac Surgery Score assessment on CCTA. CCTA with FFRCT might provide better anatomical and functional analysis of the coronary circulation leading to appropriate anatomical and functional revascularisation, and thereby contributing to a better outcome.Ethics and disseminationEach patient has to provide written informed consent as approved by the ethical committee of the respective clinical site. Results will be submitted for publication in peer-reviewed journals and will be disseminated at scientific conferences.Trial registration numberNCT04142021.
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- 2020
34. Predicted brain age as a cognitive biomarker in multiple sclerosis
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Denissen, Stijn, De Cock, Alexander, Costers, Lars, Baijot, Johan, Laton, Jorne, D'hooghe, Marie Beatrice, D'haeseleer, Miguel, Dive, Dominique, Johan, De Mey, Van Schependom, Jeroen, Sima, Diana Maria, Nagels, Guy, Artificial Intelligence supported Modelling in clinical Sciences, Faculty of Medicine and Pharmacy, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, Supporting clinical sciences, Body Composition and Morphology, Medical Imaging, Translational Imaging Research Alliance, Radiology, and Electronics and Informatics
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Brain Age ,multiple sclerosis ,artificial intelligence ,MRI - Published
- 2020
35. Performance of an artificial intelligence tool with real-time clinical workflow integration - Detection of intracranial hemorrhage and pulmonary embolism
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Koenraad Nieboer, Nina Watté, Johan De Mey, Bart Ilsen, Nico Buls, Supporting clinical sciences, Medical Imaging, Radiology, Faculty of Medicine and Pharmacy, Medicine and Pharmacy academic/administration, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, and Translational Imaging Research Alliance
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business.industry ,Biophysics ,MEDLINE ,General Physics and Astronomy ,General Medicine ,medicine.disease ,Pulmonary embolism ,Workflow ,Text mining ,Radiology Nuclear Medicine and imaging ,Artificial Intelligence ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Medical emergency ,business ,Pulmonary Embolism ,Intracranial Hemorrhages ,intracranial hemorrhage - Published
- 2020
36. Anti-human PD-L1 Nanobody for Immuno-PET Imaging
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Steven Ballet, Christian Vanhove, Pieterjan Debie, Catarina Xavier, Sara Neyt, Katrijn Broos, Jessica Bridoux, Vicky Caveliers, Quentin Lecocq, Karine Breckpot, Marleen Keyaerts, Charlotte Martin, Nick Devoogdt, Geert Raes, Supporting clinical sciences, Faculty of Medicine and Pharmacy, Laboratory of Molecullar and Cellular Therapy, Basic (bio-) Medical Sciences, Medical Imaging, Chemistry, WE Academic Unit, Department of Bio-engineering Sciences, Cellular and Molecular Immunology, Translational Imaging Research Alliance, Nuclear Medicine, and Clinical sciences
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EXPRESSION ,PD-L1 ,0301 basic medicine ,medicine.drug_class ,Lysine ,lcsh:QR1-502 ,Complementarity determining region ,Monoclonal antibody ,Biochemistry ,B7-H1 Antigen ,Article ,lcsh:Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,gallium-68 ,In vivo ,Cell Line, Tumor ,Neoplasms ,Medicine and Health Sciences ,medicine ,Humans ,cancer ,Tissue Distribution ,Molecular Biology ,biology ,Chemistry ,Sortase A ,Antibodies, Monoclonal ,Ligand (biochemistry) ,Molecular biology ,Antibodies, Anti-Idiotypic ,PET ,030104 developmental biology ,Isotope Labeling ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,Nanobody ,site-specific ,biology.protein ,Radiopharmaceuticals ,Conjugate - Abstract
Immune checkpoints, such as programmed death-ligand 1 (PD-L1), limit T-cell function and tumor cells use this ligand to escape the anti-tumor immune response. Treatments with monoclonal antibodies blocking these checkpoints have shown long-lasting responses, but only in a subset of patients. This study aims to develop a Nanobody (Nb)-based probe in order to assess human PD-L1 (hPD-L1) expression using positron emission tomography imaging, and to compare the influence of two different radiolabeling strategies, since the Nb has a lysine in its complementarity determining region (CDR), which may impact its affinity upon functionalization. The Nb has been conjugated with the NOTA chelator site-specifically via the Sortase-A enzyme or randomly on its lysines. [68Ga]Ga-NOTA-(hPD-L1) Nbs were obtained in >, 95% radiochemical purity. In vivo tumor targeting studies at 1 h 20 post-injection revealed specific tumor uptake of 1.89 ±, 0.40%IA/g for the site-specific conjugate, 1.77 ±, 0.29%IA/g for the random conjugate, no nonspecific organ targeting, and excretion via the kidneys and bladder. Both strategies allowed for easily obtaining 68Ga-labeled hPD-L1 Nbs in high yields. The two conjugates were stable and showed excellent in vivo targeting. Moreover, we proved that the random lysine-conjugation is a valid strategy for clinical translation of the hPD-L1 Nb, despite the lysine present in the CDR.
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- 2020
37. Multi-regional dosimetry of mouse kidneys for beta-emitters
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Vargas, C. Saldarriaga, Peter Covens, D Huyvetter, M., Caveliers, V., Miller, B. W., Struelens, L., Supporting clinical sciences, Faculty of Medicine and Pharmacy, Medical Imaging, UZB Other, Preventie- & Milieudienst, Nuclear Medicine, and Translational Imaging Research Alliance
- Subjects
Preclinical dosimetry ,Sub-organ dosimetry ,dosimetry ,Mouse kidney ,Autoradiography ,Stylized model ,Radiopharmaceutical therapy - Abstract
Aim/Introduction: Conventional preclinical internal dose estimates typically assume a uniform distribution of radioactivity and dose deposition throughout organ tissues. This assumption can deviate from reality for β-/α-emitting radioligands with a heterogeneous tissue activity distribution. In this study S-values for internal dosimetry of β- emitters were calculated for a multi-region model of a mouse kidney. The significance of regional S-values was demonstrated for the mouse kidney biodistribution of a 131I-labeled single-domain anti-HER2 antibody fragment with predominant uptake in the outer stripe of the outer medulla. Materials and Methods: A stylized computational model of a mouse kidney was developed, consisting on ellipsoids delimiting 5 tissue compartments: renal cortex, outer medulla outer/inner stripes (IS/OS), inner medulla and papilla. Energy absorbed fractions (ɸ) for the different kidney regions were calculated for 131I and 90Y, from photon-electron transport simulations using MCNP6.2 code. A sensitivity study on the influence of model specifications (kidney volume, cortex occupancy) was performed. For the 131I mouse study, time-dependent regional kidney-tissue activities were determined from the relative regional activity concentrations of kidney sections measured with digital β--particle autoradiography (using an iQID system), relative to the whole-kidney activity measured with conventional gamma counting. Results: For 131I, a large fraction of the emitted β- energy is absorbed within the sub-kidney source region itself (ɸ ≥0.60). Because of this and the smaller masses of sub-kidney tissues, the self-irradiation regional S-values are considerably higher (30% to >200% depending on kidney region) than whole-kidney S-values. Compared to 131I, 90Y regional self-absorbed fractions are lower (ɸ 0.10) between most regions for 90Y and between adjacent regions for 131I (e.g. cortex/OS, OS/IS). The sensitivity of self-absorbed fractions to the kidney model specifications was typically small for 131I (100% depending on region) from the uniform whole-kidney dose based on a homogeneous activity distribution. Conclusion: The calculated regional S-values, in combination with sub-kidney activity information, allow a more realistic estimation of the doses absorbed by different renal tissues from β--emitting radioligands with a heterogeneous kidney uptake. This provides new dose information relevant for preclinical investigations studying the risk of radiation-induced nephrotoxicity of these therapies.
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- 2020
38. Neuroanatomical Reconstruction of the Canine Visual Pathway Using Diffusion Tensor Imaging
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Olivier Jacqmot, Bert Van Thielen, Alex Michotte, Johan de Mey, Steven Provyn, Jonathan Tresignie, Faculty of Medicine and Pharmacy, Basic (bio-) Medical Sciences, Neuroprotection & Neuromodulation, Neurology, Pathology, Artificial Intelligence supported Modelling in clinical Sciences, Supporting clinical sciences, Body Composition and Morphology, Medical Imaging, Translational Imaging Research Alliance, Radiology, Physiotherapy, Human Physiology and Anatomy, Teacher Education, Anatomical Research and Clinical Studies, and Vrije Universiteit Brussel
- Subjects
0301 basic medicine ,Optic tract ,genetic structures ,Neuroscience (miscellaneous) ,Optic chiasm ,canine ,Lateral geniculate nucleus ,lcsh:RC321-571 ,lcsh:QM1-695 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cortex (anatomy) ,Fractional anisotropy ,Medicine ,visual pathway ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Original Research ,Retina ,business.industry ,Anatomy ,lcsh:Human anatomy ,stereotaxy ,eye diseases ,030104 developmental biology ,medicine.anatomical_structure ,Radiology Nuclear Medicine and imaging ,DTI ,Optic nerve ,business ,030217 neurology & neurosurgery ,Neuroscience ,Diffusion MRI ,MRI - Abstract
The first anatomical atlas of diffusion tensor imaging (DTI) of white matter pathways in the canine brain was published in 2013; however, the anatomical orientation of the entire visual pathway in the canine brain, from the retina to the cortex, has not yet been studied using DTI. In the present study, 3T DTI magnetic resonance (MR) images of three dogs euthanized for reasons other than neurological disorders were obtained. The process of obtaining combined fractional anisotropy and directional maps was initiated within 1 h of death. The heads were amputated immediately after MR imaging and stored in 10% formalin until dissection and histological sampling was performed. The trajectory of the visual pathway is dissimilar to the horizontal representation in other literature. To our knowledge, ours is the first study to visualize the entire canine visual pathway in its full antero-posterior extension. Fibers from the retina to the cortex passed through the optic nerve, optic chiasm, optic tracts, lateral geniculate nucleus, Meyer’s and Baum’s loops, and pretectal fibers. Their projections to the cortex were similar to those in the human visual pathway. The crossing of fibers at the optic chiasm occurred in 75% of fibers. In addition to advancing our knowledge in this field of study, these results could help plan neurosurgical and radiotherapeutic procedures to avoid unnecessary damage to the visual fiber system.
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- 2020
39. Ventilation heterogeneity in smokers: role of unequal lung expansion and peripheral lung structure
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Daniel Schuermans, Mathias Polfliet, Johan De Mey, Sylvia Verbanck, Jef Vandemeulebroucke, Bart Ilsen, Eef Vanderhelst, Clinical sciences, Pneumology, Faculty of Engineering, Electronics and Informatics, Medical Imaging, Radiology, Artificial Intelligence supported Modelling in clinical Sciences, Supporting clinical sciences, Body Composition and Morphology, Translational Imaging Research Alliance, Physiotherapy, Human Physiology and Anatomy, Medical Informatics, and Radiology & Nuclear Medicine
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0301 basic medicine ,medicine.medical_specialty ,Supine position ,Physiology ,Lung Clearance Index ,03 medical and health sciences ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,MULTIPLE BREATH WASHOUT ,Lung ,Smokers ,business.industry ,Respiration ,Washout ,Peripheral ,Lung structure ,030104 developmental biology ,medicine.anatomical_structure ,030228 respiratory system ,Pulmonary Emphysema ,Breathing ,Cardiology ,business - Abstract
Smoking-induced ventilation heterogeneity measured at the mouth via established washout indices [lung clearance index (LCI) and alveolar mixing efficiency (AME)] potentially results from unequal expansion, which can be quantified by computer tomography (CT), and structural changes down to the lung periphery, characterized by CT parametric response mapping indices [percentage of lung affected by functional small airway disease (PRMfSAD) and emphysema (PRMEmph)]. By combining CT imaging and nitrogen (N2) washout tests in smokers, we specifically examined the roles of unequal lung expansion and peripheral structure. We first extracted three-dimensional maps of local lung expansion from registered inspiratory/expiratory CT images in 50 smokers (GOLD 0-IV) to compute for each smoker the theoretical N2 washout concentration curve solely attributable to unequal local expansion. By a head-on comparison with washout N2 concentrations measured at the mouth in the same smokers supine, we observed that 1) LCI increased from 4.8 ± 0.2 (SD) to 6.6 ± 0.8 (SD) due to unequal lung expansion alone and further increased to 9.0 ± 1.5 (SD) independent of local expansion and 2) AME decreased (from 100% by definition) to 95 ± 2 (SD)% due to unequal expansion alone and further decreased to 75 ± 7(SD)% independent of local expansion. In a multiple regression between the washout indices and CT-derived PRMfSAD and PRMEmph, LCI was related to PRMfSAD (r = +0.58; P < 0.001), whereas AME was related to both PRMfSAD (rpartial = -0.44; P = 0.002) and PRMEmph (rpartial = -0.31; P = 0.033), in line with AME being dominated by alterations in peripheral structure. We conclude that smokers showing an increased LCI without corresponding AME decrease are predominantly affected by unequal lung expansion, whereas an AME decrease with a commensurate LCI increase indicates a smoking-induced alteration of peripheral structure.NEW & NOTEWORTHY A head-on comparison between imaging and multiple breath washout in supine smokers shows that computer tomography-measured unequal local lung expansion accounts for 50% or less of smoking-induced increase in ventilation heterogeneity. The contributions from unequal lung expansion and peripheral structure to the two main washout indices also explain their respective association with parametric response mapping indices.
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- 2020
40. The validation of iodine contrast flow velocity quantification from time- resolved CT-angiography in a flow phantom
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Boonen, Pieter, Buls, Nico, Vandemeulebroucke, Jef, Van Gompel, Gert, de Brucker, Yannick, Aerden, Dimitri, Leiner, Tim, Johan, De Mey, Multidimensional signal processing and communication, Supporting clinical sciences, Faculty of Medicine and Pharmacy, Medical Imaging, Radiology, Electronics and Informatics, Medicine and Pharmacy academic/administration, Surgical clinical sciences, Diabetes Clinic, Vascular surgery, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, and Translational Imaging Research Alliance
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- 2020
41. Synthetic MRI of Preterm Infants at Term-Equivalent Age
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G.-J. Allemeersch, M. Naeyaert, N. Watté, S. Raeymaeckers, Jeroen Dudink, J. de Mey, H. Raeymaekers, Tim Vanderhasselt, Medical Imaging, Radiology, Faculty of Medicine and Pharmacy, Basic (bio-) Medical Sciences, Supporting clinical sciences, Body Composition and Morphology, and Translational Imaging Research Alliance
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Male ,Image quality ,Neuroimaging ,Infant, Premature, Diseases ,Iterative reconstruction ,Pediatrics ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Image Processing, Computer-Assisted ,Humans ,Medicine ,Radiology, Nuclear Medicine and imaging ,Segmentation ,Tissue segmentation ,business.industry ,Term equivalent age ,Infant, Newborn ,Brain ,Infant ,Magnetic Resonance Imaging ,Mr imaging ,Very preterm ,Brain size ,Female ,Neurology (clinical) ,Artifacts ,Nuclear medicine ,business ,Infant, Premature ,030217 neurology & neurosurgery - Abstract
BACKGROUND AND PURPOSE: Neonatal MR imaging brain volume measurements can be used as biomarkers for long-term neurodevelopmental outcome, but quantitative volumetric MR imaging data are not usually available during routine radiologic evaluation. In the current study, the feasibility of automated quantitative brain volumetry and image reconstruction via synthetic MR imaging in very preterm infants was investigated. MATERIALS AND METHODS: Conventional and synthetic T1WIs and T2WIs from 111 very preterm infants were acquired at term-equivalent age. Overall image quality and artifacts of the conventional and synthetic images were rated on a 4-point scale. Legibility of anatomic structures and lesion conspicuity were assessed on a binary scale. Synthetic MR volumetry was compared with that generated via MANTiS, which is a neonatal tissue segmentation toolbox based on T2WI. RESULTS: Image quality was good or excellent for most conventional and synthetic images. The 2 methods did not differ significantly regarding image quality or diagnostic performance for focal and cystic WM lesions. Dice similarity coefficients had excellent overlap for intracranial volume (97.3%) and brain parenchymal volume (94.3%), and moderate overlap for CSF (75.6%). Bland-Altman plots demonstrated a small systematic bias in all cases (1.7%–5.9%) CONCLUSIONS: Synthetic T1WI and T2WI sequences may complement or replace conventional images in neonatal imaging, and robust synthetic volumetric results are accessible from a clinical workstation in less than 1 minute. Via the above-described methods, volume assessments could be routinely used in daily clinical practice.
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- 2020
42. The role of cardiovascular imaging for myocardial injury in hospitalized COVID-19 patients
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Johan De Mey, Steffen E. Petersen, Sabine D Allard, Marc R. Dweck, Maria Luiza Luchian, Gianluca Pontone, Stijn Lochy, Peter Rosseel, Alessia Gimelli, Bernard Cosyns, Thor Edvardsen, Clinical sciences, Cardio-vascular diseases, Cardiology, Intensive Care, Internal Medicine, Supporting clinical sciences, Body Composition and Morphology, Medical Imaging, Translational Imaging Research Alliance, Radiology, and UZB Other
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Male ,Cardiac magnetic resonance ,Myocardial Infarction ,Review ,Comorbidity ,030204 cardiovascular system & hematology ,030218 nuclear medicine & medical imaging ,Electrocardiography ,0302 clinical medicine ,Disease management (health) ,Computed tomography ,Cardiac imaging ,Lung ultrasound ,biology ,Disease Management ,General Medicine ,Prognosis ,Troponin ,Echocardiography, Doppler ,Radiology Nuclear Medicine and imaging ,Echocardiography ,Cardiovascular Diseases ,Myocardial injury ,Practice Guidelines as Topic ,Female ,Risk assessment ,Cardiology and Cardiovascular Medicine ,Coronavirus Infections ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Pneumonia, Viral ,Magnetic Resonance Imaging, Cine ,Context (language use) ,Risk Assessment ,03 medical and health sciences ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Intensive care medicine ,Pandemics ,Mechanism (biology) ,business.industry ,Troponin I ,Role ,COVID-19 ,medicine.disease ,Cardiac Imaging Techniques ,biology.protein ,business ,Biomarkers - Abstract
Recent EACVI recommendations described the importance of limiting cardiovascular imaging during the COVID-19 pandemic in order to reduce virus transmission, protect healthcare professionals from contamination, and reduce consumption of personal protective equipment. However, an elevated troponin remains a frequent request for cardiac imaging in COVID-19 patients, partly because it signifies cardiac injury due to a variety of causes and partly because it is known to convey a worse prognosis. The present paper aims to provide guidance to clinicians regarding the appropriateness of cardiac imaging in the context of troponin elevation and myocardial injury, how best to decipher the mechanism of myocardial injury, and how to guide patient management.
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- 2020
43. Preclinical Targeted α- and β−-Radionuclide Therapy in HER2-Positive Brain Metastasis Using Camelid Single-Domain Antibodies
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Pieterjan Debie, Quentin Lecocq, Matthias D'Huyvetter, Tony Lahoutte, Janik Puttemans, Heleen Hanssens, Marleen Keyaerts, Albert D. Windhorst, Frank Bruchertseifer, Yana Dekempeneer, Frank van der Aa, Nick Devoogdt, Karine Breckpot, Jos L E Eersels, Alfred Morgenstern, Supporting clinical sciences, Medical Imaging, Faculty of Medicine and Pharmacy, Nuclear Medicine, Basic (bio-) Medical Sciences, Translational Imaging Research Alliance, Radiology and nuclear medicine, and Amsterdam Neuroscience - Brain Imaging
- Subjects
0301 basic medicine ,Cancer Research ,medicine.drug_class ,Monoclonal antibody ,lcsh:RC254-282 ,radiation therapy ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,In vivo ,Trastuzumab ,HER2 ,Medicine ,brain metastasis ,skin and connective tissue diseases ,Cancer ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,targeted radionuclide therapy ,single-domain antibody fragment ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Radionuclide therapy ,Cancer research ,business ,medicine.drug ,Brain metastasis - Abstract
HER2-targeted therapies have drastically improved the outcome for breast cancer patients. However, when metastasis to the brain is involved, current strategies fail to hold up to the same promise. Camelid single-domain antibody-fragments (sdAbs) have been demonstrated to possess favorable properties for detecting and treating cancerous lesions in vivo using different radiolabeling methods. Here we evaluate the anti-HER2 sdAb 2Rs15d, coupled to diagnostic &gamma, and therapeutic &alpha, and &beta, &minus, emitting radionuclides for the detection and treatment of HER2pos brain lesions in a preclinical setting. 2Rs15d was radiolabeled with 111In, 225Ac and 131I using DTPA- and DOTA-based bifunctional chelators and Sn-precursor of SGMIB respectively and evaluated in orthotopic tumor-bearing athymic nude mice. Therapeutic efficacy as well as systemic toxicity were determined for 131I- and 225Ac-labeled sdAbs and compared to anti-HER2 monoclonal antibody (mAb) trastuzumab in two different HER2pos tumor models. Radiolabeled 2Rs15d showed high and specific tumor uptake in both HER2pos SK-OV-3-Luc-IP1 and HER2pos MDA-MB-231Br brain lesions, whereas radiolabeled trastuzumab was unable to accumulate in intracranial SK-OV-3-Luc-IP1 tumors. Administration of [131I]-2Rs15d and [225Ac]-2Rs15d alone and in combination with trastuzumab showed a significant increase in median survival in 2 tumor models that remained largely unresponsive to trastuzumab treatment alone. Histopathological analysis revealed no significant early toxicity. Radiolabeled sdAbs prove to be promising vehicles for molecular imaging and targeted radionuclide therapy of metastatic lesions in the brain. These data demonstrate the potential of radiolabeled sdAbs as a valuable add-on treatment option for patients with difficult-to-treat HER2pos metastatic cancer.
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- 2020
44. Computer-aided detection of focal bone metastases from whole-body multi-modal MRI
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Jakub Ceranka, Johan De Mey, Jef Vandemeulebroucke, Frédéric Lecouvet, Hahn, Horst K., Mazurowski, Maciej A., Faculty of Engineering, Electronics and Informatics, Artificial Intelligence supported Modelling in clinical Sciences, Supporting clinical sciences, Body Composition and Morphology, Medical Imaging, Translational Imaging Research Alliance, Radiology, UCL - SSS/IREC/IMAG - Pôle d'imagerie médicale, and UCL - (SLuc) Service de radiologie
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Computer-aided detection ,medicine.medical_specialty ,Bone disease ,business.industry ,computer.software_genre ,medicine.disease ,diffusion-weighted MRI ,Prostate cancer ,advanced prostate cancer ,medicine.anatomical_structure ,bone metastases ,Voxel ,Whole-body MRI ,medicine ,Segmentation ,False positive rate ,Radiology ,Bone marrow ,Stage (cooking) ,business ,computer ,Diffusion MRI - Abstract
The confident detection and monitoring of metastatic bone disease remains one of the major unfulfilled needs in oncology. Whole-body MRI offers excellent resolution and sensitivity for the detection of neoplastic cells within the bone marrow using so-called anatomical sequences. In combination with whole-body diffusion-weighted functional sequences, it has shown a great potential in the assessment of patient tumor involvement. However, metastatic bone disease can lead to a large amount of bone lesions spread across the skeleton, making it impractical and labor demanding to manually delineate by a radiologist. Computer-aided detection could alleviate the workflow, enabling automatic, accurate and reproducible study of the patient tumor load. In this paper, we propose a fully automated computer-aided detection system for bone metastases composed of two steps. First, whole-body multi-modal MR image preprocessing is performed consisting of intra- and inter-modality image spatial registration, intensity standardization and atlas-based segmentation of the skeleton. The second stage detects the metastases candidates using random forest voxel classification algorithm. The system is evaluated on the dataset of 6 male advanced prostate cancer patients with metastases to the bone using a leave-one-patient-out cross-validation with manual segmentation of the metastases as the reference standard. The proposed system showed metastases detection sensitivity of 0.74 with a median false positive rate of 9.67. In clinical workflow the system could potentially be used as the initial screening and treatment response assessment tool for whole-body multi-modal MRI of any advanced cancer with metastases to the bone.
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- 2020
45. Contrast media iodine concentration in the left ventricle affects the level of radiation-induced DNA damage during CCTA
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Van Cauteren, Toon, Belsack, Dries, Buls, Nico, Johan, De Mey, Droogmans, Steven, Jochmans, Kristin, Kersemans, Veerle, Tanaka, Kaoru, Van Gompel, Gert, Faculty of Medicine and Pharmacy, Supporting clinical sciences, Medical Imaging, Radiology, Body Composition and Morphology, Translational Imaging Research Alliance, Clinical sciences, Cardio-vascular diseases, Cardiology, Clinical Biology, Reproductive immunology and implantation, and Hematology
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- 2020
46. Evaluation of epicardial coronary resistance using computed tomography angiography
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Emanuelle Barbato, Danny Schoors, Takuya Mizukami, Johan De Mey, Dries Belsack, Bram Roosens, J. F. Argacha, Bert Vandeloo, Kaoru Tanaka, Stijn Lochy, Daniele Andreini, Carlos Collet, Jeroen Sonck, Bernard De Bruyne, Bernard Cosyns, Hiroshi Suzuki, Radiology, Medical Imaging, Clinical sciences, Cardiology, Cardio-vascular diseases, Intensive Care, Supporting clinical sciences, Body Composition and Morphology, Translational Imaging Research Alliance, Mizukami, T., Tanaka, K., Sonck, J., Vandeloo, B., Roosens, B., Lochy, S., Argacha, J. F., Schoors, D., Suzuki, H., Belsack, D., Andreini, D., Barbato, E., De Mey, J., De Bruyne, B., Cosyns, B., Collet, C., Graduate School, and ACS - Heart failure & arrhythmias
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Male ,medicine.medical_specialty ,Cardiac Catheterization ,medicine.medical_treatment ,Coronary Vessels/diagnostic imaging ,Fractional flow reserve ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Coronary Angiography ,Proof of Concept Study ,030218 nuclear medicine & medical imaging ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Pullback ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Coronary resistance ,Computed tomography angiography ,Cardiac catheterization ,Aged ,Medicine(all) ,medicine.diagnostic_test ,business.industry ,Coronary ct angiography ,Middle Aged ,medicine.disease ,Coronary Vessels ,medicine.anatomical_structure ,fractional flow reserve, myocardial ,Radiology Nuclear Medicine and imaging ,Vascular resistance ,Cardiology ,Feasibility Studies ,Female ,Vascular Resistance ,reproducibility of results ,Cardiology and Cardiovascular Medicine ,business ,computed tomography angiography ,Pericardium ,Coronary Artery Disease/diagnostic imaging - Abstract
Aims: Fractional flow reserve (FFR) pullback allows to assess the distribution of pressure loss along the coronary vessels. FFR derived from CT (FFR CT) provides a virtual pullback curve that may also aid in the assessment of the distribution of epicardial coronary resistance in the non-invasive setting. The present study aims to determine the accuracy of the virtual FFR CT pullback curve using a motorized invasive FFR pullback as reference in patients with stable coronary artery disease. Methods and results: FFR values were extracted from coronary vessels at approximately 1 mm to generate pullback curves. Invasive motorized FFR pullbacks were acquired using a dedicated device at a speed of 1 mm/s. A total of 3172 matched FFR CT and FFR values were obtained in 24 vessels. The correlation coefficient between FFR CT and FFR was 0.76 (95%CI 0.75 to 0.78; p < 0.001). The area under the pullback curve was similar between FFR CT and invasive FFR (79.0 ± 16.1 vs. 85.3 ± 16.4, p = 0.097). The mean difference in lesion gradient between FFR CT and FFR was −0.07 (LOA -0.26 to 0.13) whereas in non-obstructive segments was −0.01 (LOA -0.06 to 0.05). Conclusion: The evaluation of epicardial coronary resistance using coronary CT angiography with FFR CT was feasible. FFR CT virtual pullback appears to be accurate for the evaluation of pressure gradients. FFR CT has the potential to identify the pathophysiological pattern of coronary artery disease in the non-invasive setting.
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- 2020
47. Contrast Flow Velocity Quantification from Time-Resolved CT Angiography, a Phantom Study
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Yannick De Brucker, Johan De Mey, Pieter Thomas Boonen, Tim Leiner, Dimitri Aerden, Nico Buls, Gert Van Gompel, Jef Vandemeulebroucke, Supporting clinical sciences, Faculty of Medicine and Pharmacy, Medical Imaging, Radiology, Medicine and Pharmacy academic/administration, Surgical clinical sciences, Diabetes Clinic, Vascular surgery, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, Electronics and Informatics, Chen, Guang-Hong, Bosmans, Hilde, and Translational Imaging Research Alliance
- Subjects
Physics ,Accuracy and precision ,medicine.diagnostic_test ,business.industry ,time-resolved CTA ,Flow Velocity ,Digital subtraction angiography ,phantom ,Imaging phantom ,arteries ,Peripheral Arterial Disease ,Flow velocity ,computed tomograph angiography ,Angiography ,medicine ,Medical imaging ,COMPUTED TOMOGRAPHY ,Wide beam ,Nuclear medicine ,business ,Computed tomography angiography - Abstract
In recent years, there has been an increasing interest in replacing digital subtraction angiography (DSA) as method of choice for the diagnostic imaging of patients suffering from lower extremity peripheral arterial disease (PAD). Due to small vessel diameters and suboptimal resolution, examinations of below-the-knee arteries however remain extremely challenging. The advent of wide beam CT scanners allows to perform multiple CT acquisitions over a wide patient volume. A sequence of these CT acquisitions at timed intervals could provide additional hemodynamic information, and as such allows to track a contrast bolus that propagates through the arterial conduit. The aim of this study was to evaluate the accuracy and precision of flow velocity measurements using time-resolved computed tomography angiography (CTA). To this end, we constructed a mechanical flow phantom (single lumen, 6 mm inner-diameter). Six consecutive time-resolved CTA acquisitions were performed at a constant flow rate to achieve six referencevelocities (21.2 mm/s, 38.9 mm/s, 60.1 mm/s, 81.4 mm/s, 99.0 mm/s and 120.3 mm/s). The mean centerline flow velocity was obtained from the contrast propagation over three different segmental lengths (160 mm, 80 mm and 40 mm) and then compared to the reference flow velocity. The results of this study suggest that mean flow velocities within the range of typical blood flow velocities in the below-the-knee arteries (40 mm/s - 70 mm/s), can be accurately measured with high precision in a 6 mm flow phantom using time-resolved CTA when considering a minimal path length of 80 mm.
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- 2020
48. 18F-FDG PET/CT Findings in Neurofibromatosis Type 3
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Jan Jonckheere, Hendrik Everaert, Dirk Van Den Berge, Lode Goethals, Seema Döring, Johan de Mey, Radiology, Supporting clinical sciences, Medical Imaging, Nuclear Medicine, Radiation Therapy, Medicine and Pharmacy academic/administration, Artificial Intelligence supported Modelling in clinical Sciences, Body Composition and Morphology, and Translational Imaging Research Alliance
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- 2020
49. A nanobody-based nuclear imaging tracer targeting dipeptidyl peptidase 6 to determine the mass of human beta cell grafts in mice
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Julien Thevenet, Rita Garcia Ribeiro, Stéphane Demine, Lorella Marselli, Julie Kerr-Conte, François Pattou, Piero Marchetti, Decio L. Eizirik, Nick Devoogdt, Supporting clinical sciences, Medical Imaging, Translational Imaging Research Alliance, and Pathologic Biochemistry and Physiology
- Subjects
0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Islets of Langerhans Transplantation ,Cell Count ,Mice, SCID ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Insulin-Secreting Cells ,Human islet imaging ,Pancreatic beta cell imaging ,Pancreatic beta cells ,PET ,SPECT ,Type 1 diabetes ,Cells, Cultured ,geography.geographical_feature_category ,biology ,Organotechnetium Compounds ,Islet ,3. Good health ,Endocrinologie ,Molecular Imaging ,Médecine interne ,medicine.anatomical_structure ,Cell Tracking ,Heterografts ,Female ,Antibody ,Beta cell ,Single Photon Emission Computed Tomography Computed Tomography ,030209 endocrinology & metabolism ,Gallium Radioisotopes ,Mice, Transgenic ,Dipeptidyl peptidase ,03 medical and health sciences ,Islets of Langerhans ,Métabolisme ,In vivo ,Spect imaging ,Internal Medicine ,medicine ,Animals ,Humans ,Propidium iodide ,Radioactive Tracers ,Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ,geography ,Diabétologie ,Pancreatic islets ,Single-Domain Antibodies ,Molecular biology ,Mice, Inbred C57BL ,030104 developmental biology ,chemistry ,biology.protein - Abstract
Aims/hypothesis: Type 1 diabetes is characterised by a progressive decline in beta cell mass. This is also observed following implantation of pancreatic islet allografts, but there is no reliable information regarding the time course of beta cell loss. This is due to the limited availability of non-invasive pancreatic islet imaging techniques. We have previously described that dipeptidyl peptidase 6 (DPP6) is an alpha and beta cell-specific biomarker, and developed a camelid antibody (nanobody ‘4hD29’) against it. We demonstrated the possibility to detect DPP6-expressing cells by single-photon emission computed tomography (SPECT)/ computed tomography (CT), but the correlation between the number of cells grafted and the SPECT signal was not assessed. Here, we investigate whether the 4hD29 nanobody allows us to detect different amounts of human pancreatic islets implanted into immune-deficient mice. In addition, we also describe the adaptation of the probe for use with positron emission tomography (PET). Methods: DPP6 expression was assessed in human samples using tissue arrays and immunohistochemistry. The effect of the 4hD29 nanobody on cell death and glucose-stimulated insulin secretion was measured in EndoC-βH1 cells and in human islets using Hoechst/propidium iodide staining and an anti-insulin ELISA, respectively. We performed in vivo SPECT imaging on severe combined immunodeficient (SCID) mice transplanted with different amounts of EndoC-βH1 cells (2 × 106, 5 × 106 and 10 × 106 cells), human islets (1000 and 3000) or pancreatic exocrine tissue using 99mTc-labelled 4hD29 nanobody. This DPP6 nanobody was also conjugated to N-chlorosuccinimide (NCS)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), radiolabelled with either 67Ga (SPECT) or 68Ga (PET) and used in a proof-of-principle experiment to detect DPP6-expressing cells (Kelly neuroblastoma) grafted in SCID mice. Results: The DPP6 protein is mainly expressed in pancreatic islets. Importantly, the anti-DPP6 nanobody 4hD29 allows non-invasive detection of high amounts of EndoC-βH1 cells or human islets grafted in immunodeficient mice. This suggests that the probe must be further improved to detect lower numbers of islet cells. The 4hD29 nanobody neither affected beta cell viability nor altered insulin secretion in EndoC-βH1 cells and human islets. The conversion of 4hD29 nanobody into a PET probe was successful and did not alter its specificity. Conclusions/interpretation: These findings suggest that the anti-DPP6 4hD29 nanobody may become a useful tool for the quantification of human islet grafts in mice and, pending future development, islet mass in individuals with diabetes., SCOPUS: ar.j, info:eu-repo/semantics/published
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- 2020
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50. The impact of a child bike seat and trailer on the objective overtaking behaviour of motorized vehicles passing cyclists
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Romain Meeusen, B. de Geus, H. Durlet, B. Truyen, Ian Walker, Ben Serrien, Toon Ampe, UCL - SSH/IACS - Institute of Analysis of Change in Contemporary and Historical Societies, Physiotherapy, Human Physiology and Anatomy, Human Physiology and Sports Physiotherapy Research Group, Brussels Centre for Urban Studies, Faculty of Engineering, Translational Imaging Research Alliance, Computational and Applied Mathematics Programme, Electronics and Informatics, International Relations and Mobility, Advanced Rehabilitation Technology & Science, Spine Research Group, and Movement and Nutrition for Health and Performance
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Trailer ,Poison control ,Capital region ,Transportation ,Bike lane ,Aeronautics ,Overtaking ,Automotive Engineering ,Mixed effects ,Motorized vehicle ,Psychology ,Cycling ,Applied Psychology ,Civil and Structural Engineering - Abstract
Introduction: The lateral clearance distance of a motorized vehicle while overtaking a cyclist is a key indicator of safety. This lateral clearance distance has never been measured for cyclists transporting a child. Therefore the aim of this study was to investigate the behaviour of motorized vehicles in overtaking cyclists with and without a child on the same bicycle. Methods: The lateral clearance distance of the overtaking manoeuvres of motorized vehicles was measured using an instrumented bicycle when performing 19 cycling trips on one single road with two different types of cycling infrastructure (a bike lane and shared lane marking) in the Brussels Capital Region (Belgium). Mixed effect regression was used to examine the effect of cycling condition (cyclist without a child [control], cyclist with a child bike seat and cyclist with a child bike trailer) and secondary independent variables (i.e. cycling infrastructure, peak traffic hours and traffic density) on the lateral clearance distance. Results: Themean lateral clearance distance in ‘cyclists without child’ was significantly smaller (117.3 cm) than in ‘cyclists with child’ (128.8 cm) (95%CI [7.2;15.9]). Looking at ‘morning peak traffic hours’ (i.e. 7:00 to 9:00 a.m.) a cyclist with child bike seat was overtaken at greater lateral clearance distances than a cyclist with a child bike trailer or a cyclist without child (p=0.041). Furthermore, the percentage of passing manoeuvres under 100 cm was significantly higher in ‘cyclist without child’ (35.3%) in comparison to ‘cyclist with child bike seat’ (21.8%) and ‘cyclist with child bike trailer’ (21.8%) (Chi2=29.19, p
- Published
- 2020
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