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IMMC

Greet Kerckhofs
Professor
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Recent publications

is Associate Professor at the iMMC, running the Biomechanics lab. The lab aims to apply an interdisciplinary, combinatory research approach, encompassing experiments, characterization and computational modelling, to solve different biomedical and biomechanical research questions. Her research will build further upon the expertise she has obtained during her PhD and postdoc.
Prof. Greet Kerckhofs obtained her PhD in 2009 at the Dept. Materials Engineering (MTM - KU Leuven), of which the aim was to optimize and validate microfocus X-ray computed tomography (microCT) to characterize porous materials. This non-destructive 3D imaging technique allows to visualize the entire internal structure of materials without destroying them. She performed her PhD and postdoc within Prometheus, the division of Skeletal Tissue Engineering of the KU Leuven. This interdisciplinary platform aims to repair large bone defects using tissue engineering constructs (i.e. biomaterial with cells and/or growth factors). Trained as an engineer, within Prometheus she has been capable of integrating biology and engineering technology (such as imaging, biomaterials testing and production/design) into her research and as a result, she now belongs to the small group of researchers that have grown into a genuine interdisciplinary profile.
During her postdoc, she has been optimizing contrast-enhanced microCT (CE-CT) for the 3D visualization and characterization of not only mineralized, but also soft biological tissues in different fields of application. As a result, she has become a pioneer and recognized expert in the field CE-CT. She has started collaborations worldwide and she is setting the stage for a new era of virtual 3D histology of soft tissues. She is currently also 10% Visiting Professor at the Dept. MTM (KU Leuven) and she is member of the scientific board of Prometheus (KU Leuven).

IMMC main research direction(s):
Biomedical engineering
Processing and characterisation of materials

Keywords:
biomechanics
contrast-enhanced computed tomography

Research group(s): MEED

    

PhD and Post-doc researchers under my supervision:


A microCT-based approach for high-resolution characterization of biodegradable metallic intravascular stent materials
Lisa Leyssens

The goal of my research project is to assess different potential biodegradable metallic intravascular stent materials using high-resolution 3D microfocus X-ray computed tomography (microCT). In a first step, the optimization of microCT and contrast-enhanced microCT (CECT) for the characterization of the 3D microstructure of different blood vessels is performed (aorta, femoral artery, vena cava) in different species (rat, porcine, human). Then, this technique is applied to study the degradation behaviour of potential materials for biodegradable metallic intravascular stents. Structural properties are investigated. They are critical because they will influence the mechanical and in vivo behaviour of the stents. The materials (in the shape of wires) are screened to analyze the corrosion and surface changes, before and after immersion tests (in vitro part) and before and after implantation in rat arteries to additionally study interactions between the tissue (artery) and the metal (in vivo part).


Ex vivo microfocus computed tomography and contrast-enhanced computed tomography applied to the heart and the heart valves
Camille Pestiaux

The goal of my research project is to characterize in depth the morphological properties of heart and especially heart valves. Their characterization is currently limited to a qualitative description and quantitative information is still highly lacking. The full 3D microstructure of healthy and diseased heart valves is investigated using high-resolution computed tomography (microCT) and contrast-enhanced computer tomography (CECT).


Synthesis and development of novel contrast agents for 3D multitissue imaging using contrast-enhanced computed tomography.
Sarah Vangrunderbeeck

The project aims to set the stage for a new era of virtual 3D histology using contrast-enhanced microfocus computed tomography (CE-CT) by developing and validating novel contrast-enhancing staining agents (CESAs). A multidisciplinary approach is applied, crossing the boundaries between biology, engineering, imaging and chemical synthesis. We will develop and synthesize novel CESAs that specifically stain different components of the extracellular matrix in whole tissues. One example within this project is the development of antigen-specific CESAs, which are comparable to immunohistochemistry. Hence, we propose ex-vivo high-resolution CE-CT imaging to become a non-invasive quantitative 3D anatomical tool that will allow unprecedented 3D characterization of the biological tissues.


Towards a new era of ex vivo 3D virtual histology: X-ray contrast-enhancing staining agents
Tim Balcaen


Combining contrast-enhanced microCT imaging and mechanical testing to enhance the biofidelity of computational models of healthy and diseased vascular tissues
Maïté Pétré

Cardiovascular diseases are still the leading cause of death worldwide. Treatment options such as intravascular stent deposition or balloon angioplasty often tend to fail. The hypothesis is that this failure is partly due the application of too large mechanical forces on the vascular tissue during treatment. However, the exact mechanisms are not yet fully understood. To better understand these mechanisms and to evaluate potential new treatment techniques, biomechanical characterization of vascular tissue could provide a solution. The goal of this thesis is, therefore, two-fold. The first aim is to create a database of microstructural and mechanical properties of healthy and diseased vascular tissues. For this, I will optimize contrast-enhanced 3D microfocus X-ray computed tomography (CECT) for vascular tissues. I will also develop, validate and apply a novel methodology for dynamic testing of vascular tissues, named 4D CE-CT. 4D CE-CT combines in-situ mechanical testing of soft tissues with CE-CT imaging. The second objective is to create a more comprehensive computational model to evaluate and predict the outcome of a medical treatment. For this, we will use the microstructural information provided by CE-CT of native and diseased vascular tissues. The results of the 4D CE-CT imaging will serve as validation of the model. The combined imaging and modelling approach should improve the insights into the failure mechanisms of some current treatments of cardiovascular diseases.


Advanced Characterization of the 3D Morphology of the Bone-Tendon Interface and the Relationship to the Functional Properties
Arne Maes

Within my research project I aim to develop insights in the morphology and the structure-function relationships of the bone-tendon interface. To this end, contrast-enhanced microCT (CE-CT) will be applied for advanced structural characterization. A better understanding of this complex biological tissue is believed to greatly improve the probability of success of regenerative strategies aiming to treat injuries of the bone-tendon interface.


Form follows function: design, development and application of a new tool to assess how the 3D microstructure of biological tissues changes during mechanical loading
Lara Mazy

Most biological tissues undergo physiological mechanical loading during their functioning in vivo. To be able to properly respond to these mechanical signals, tissues have a highly complex microstructural organization. However, to date there is not yet sufficient knowledge about the link between the microstructural organization of tissues and their mechanical behaviour.

Therefore, this PhD project aims to design and optimize a novel tool that allows to dynamically assess in 3D how the microstructure of biological tissues changes during mechanical loading, namely 4D contrast-enhanced microfocus computed tomography (µCT) or 4D-CECT. It combines high-resolution 3D µCT imaging of unmineralized biological tissues using X-ray contrast-enhancing staining agents with in-situ mechanical loading. As only limited research has been done using this technique, the goal of this project is to improve the overall performance of 4D-CECT.

More specifically, this project aims to provide an answer to the following research questions:

How does the image acquisition (application of X-rays, heating up and potential dehydration of the tissues) affect the mechanical properties of the biological tissues, and how can these effects be minimized?


Can we design an in-situ loading stage with more complex loading regimes than uniaxial tensile or compression?


Which level of image quality is required to accurately detect changes in the microstructure and quantify the local strains occurring in the entire tissue during loading, using dedicated image postprocessing on the 4D-CECT data?


Can this novel technique be applied to study the effect of disease on the mechanical behaviour of both hard and soft unmineralized tissues, such as cartilage and vascular tissue?


To do this, the first objective is to improve the current in-situ tensile/compression loading stages by incorporating temperature and humidity control. We will also extend the stages to more complex loading modes, such as biaxial testing, since biological tissues are most often in vivo not just imposed to simple uniaxial forces. The second objective is to optimize the image acquisition and reconstruction, and this to avoid tissue damage as well as to obtain sufficient image quality to be able to determine the microstructural changes during loading and to obtain accurate quantitative data on the local strain distribution. To achieve these objectives, healthy vascular tissues and cartilage will be used; two unmineralized tissues, but strongly different in their structure and function. Finally, our novel and optimized technique will be applied to try to better understand how diseases alter the mechanical behaviour of tissues.







Recent publications

See complete list of publications

Journal Articles


1. Starovoyt, Anastasiya; Shaheen, Eman; Putzeys, Tristan; Kerckhofs, Greet; Politis, Constantinus; Wouters, Jan; Verhaert, Nicolas. Anatomically and mechanically accurate scala tympani model for electrode insertion studies. In: Hearing Research, Vol. 430, no.-, p. 108707 (2023). doi:10.1016/j.heares.2023.108707. http://hdl.handle.net/2078.1/272437

2. Figeac, Florence; Tencerova, Michaela; Ali, Dalia; Andersen, Thomas L; Appadoo, Dan Rémi Christiansen; Kerckhofs, Greet; Ditzel, Nicholas; Kowal, Justyna M; Rauch, Alexander; Kassem, Moustapha. Impaired bone fracture healing in type 2 diabetes is caused by defective functions of skeletal progenitor cells. In: Stem Cells, Vol. -, no.-, p. - (2022). doi:10.1093/stmcls/sxab011. http://hdl.handle.net/2078.1/257948

3. Pascart, Tristan; Falgayrac, Guillaume; Cortet, Bernard; Paccou, Julien; Bleuse, Maverick; Coursier, Raphaël; Putman, Sophie; Quinchon, Jean-François; Bertheaume, Nicolas; Delattre, Jerome; Marchandise, Pierre; Cultot, Aurélie; Norberciak, Laurène; Kerckhofs, Greet; Budzik, Jean-François. Subchondral involvement in osteonecrosis of the femoral head: insight on local composition, microstructure and vascularization.. In: Osteoarthritis and cartilage, (2022). doi:10.1016/j.joca.2022.05.003 (Accepté/Sous presse). http://hdl.handle.net/2078.1/260877

4. Ali, Dalia; Figeac, Florence; Caci, Atenisa; Ditzel, Nicholas; Schmal, Clarissa; Kerckhofs, Greet; Havelund, Jesper; Færgeman, Nils; Rauch, Alexander; Tencerova, Michaela; Kassem, Moustapha. High‐fat diet‐induced obesity augments the deleterious effects of estrogen deficiency on bone: Evidence from ovariectomized mice. In: Aging Cell, Vol. -, no.-, p. - (2022). doi:10.1111/acel.13726. http://hdl.handle.net/2078.1/266031

5. Benova, Andrea; Ferencakova, Michaela; Bardova, Kristina; Funda, Jiri; Prochazka, Jan; Spoutil, Frantisek; Cajka, Tomas; Dzubanova, Martina; Balcaen, Tim; Kerckhofs, Greet; Willekens, Wouter; van Lenthe, G. Harry; Alquicer, Glenda; Pecinova, Alena; Mracek, Tomas; Horakova, Olga; Rossmeisl, Martin; Kopecky, Jan; Tencerova, Michaela. Novel thiazolidinedione analog reduces a negative impact on bone and mesenchymal stem cell properties in obese mice compared to classical thiazolidinediones. In: Molecular Metabolism, Vol. 65, no.-, p. 101598 (2022). doi:10.1016/j.molmet.2022.101598 (Accepté/Sous presse). http://hdl.handle.net/2078.1/265281

6. Maes, Arne; Pestiaux, Camille; Marino, Alice; Balcaen, Tim; Leyssens, Lisa; Vangrunderbeeck, Sarah; Pyka, Grzegorz; De Borggraeve, Wim M.; Bertrand, Luc; Beauloye, Christophe; Horman, Sandrine; Wevers, Martine; Kerckhofs, Greet. Cryogenic contrast-enhanced microCT enables nondestructive 3D quantitative histopathology of soft biological tissues. In: Nature Communications, Vol. 13, no.1, p. - (2022). doi:10.1038/s41467-022-34048-4. http://hdl.handle.net/2078.1/266029

7. Frangi, Giulia; Guicheteau, Marie; Jacquot, Frederic; Pyka, Grzegorz; Kerckhofs, Greet; Feyeux, Magalie; Veziers, Joëlle; Guihard, Pierre; Halgand, Boris; Sourice, Sophie; Guicheux, Jérôme; Prieur, Xavier; Beck, Laurent; Beck-Cormier, Sarah. PiT2 deficiency prevents increase of bone marrow adipose tissue during skeletal maturation but not in OVX-induced osteoporosis. In: Frontiers in Endocrinology, Vol. 13, p. 1-11 (2022). doi:10.3389/fendo.2022.921073 (Soumis). http://hdl.handle.net/2078.1/267201

8. Starovoyt, Anastasiya; Quirk, Bryden C.; Putzeys, Tristan; Kerckhofs, Greet; Nuyts, Johan; Wouters, Jan; McLaughlin, Robert A.; Verhaert, Nicolas. An optically-guided cochlear implant sheath for real-time monitoring of electrode insertion into the human cochlea. In: Scientific Reports, Vol. 12, no.1, p. 19234 (2022). doi:10.1038/s41598-022-23653-4. http://hdl.handle.net/2078.1/267197

9. Léger, Jean; Leyssens, Lisa; Kerckhofs, Greet; De Vleeschouwer, Christophe. Ensemble learning and test-time augmentation for the segmentation of mineralized cartilage versus bone in high-resolution microCT images. In: Computers in Biology and Medicine, Vol. 148, no.-, p. 105932 (2022). doi:10.1016/j.compbiomed.2022.105932. http://hdl.handle.net/2078.1/264450

10. de Bournonville, Sébastien; Geris, Liesbet; Kerckhofs, Greet. Micro computed tomography with and without contrast enhancement for the characterization of microcarriers in dry and wet state. In: Scientific Reports, Vol. 11, no. 1 (2021). doi:10.1038/s41598-021-81998-8. http://hdl.handle.net/2078.1/243552


Conference Papers


1. Leyssens, Lisa; Pétré, Maïté; Kerckhofs, Greet. Optimization of contrast-enhanced microCT for vascular applications. 2022 xxx. http://hdl.handle.net/2078.1/263186

2. Pétré, Maïté; Balcaen, Tim; El Aazmani, Walid; Pyka, Grzegorz; Fehervary, Heleen; Famaey, Nele; Kerckhofs, Greet. Effect of X-ray contrast-enhancing staining agents on the mechanical properties of blood vessels.. 2022 xxx. http://hdl.handle.net/2078.1/263328

3. Pétré, Maïté; Ghasemi, Milad; Vervenne, Thibault; Pyka, Grzegorz; Kerckhofs, Greet; Cox, Martijn; Fehervary, Heleen; Fameay, Nele. Image-based mechanical modeling of an electrospun scaffold. 2022 xxx. http://hdl.handle.net/2078.1/263327

4. Pétré, Maïté; Leyssens, Lisa; El Aazmani, Walid; Balcaen, Tim; Fehervary, Heleen; Famaey, Nele; Kerckhofs, Greet. Screening of contrast-enhancing staining agents for 4D contrast-enhanced microCT of vascular tissues. 2022 xxx. http://hdl.handle.net/2078.1/263329

5. Pestiaux, Camille; Quirynen, Louise; Beauloye, Christophe; Vanoverschelde, Jean-Louis; Pyka, Grzegorz; Kerckhofs, Greet. X-ray based 3D histology of heart valves using microfocus computed tomography and contrast-enhanced computed tomography. 2022 xxx. http://hdl.handle.net/2078.1/264497

6. Pestiaux, Camille; Quirynen, Louise; Beauloye, Christophe; Vanoverschelde, Jean-Louis; Kerckhofs, Greet. X-ray-based 3D histology and quantitative microstructural analysis of heart valves using ex vivo microCT and contrast-enhanced microCT. 2022 xxx. http://hdl.handle.net/2078.1/264498

7. Tim Balcaen; Catherine Piens; Hoffmann, Delia; Fabien Chauveau; Wim De Borggraeve; Kerckhofs, Greet. Revealing the murine brain anatomy by contrast-enhanced computed tomography – a screening study. 2022 xxx. http://hdl.handle.net/2078.1/267781

8. Laurenz Schröer; Tim De Kock; Balcaen, Tim; Kerckhofs, Greet; Nico Boon; Veerle Cnudde. Distinguishing biofilms from water using X-ray micro-computed tomography. 2022 xxx. http://hdl.handle.net/2078.1/267783

9. Pestiaux, Camille; Maes, Arne; Balcaen, Tim; Leyssens, Lisa; Vangrunderbeeck, Sarah; Pyka, Grzegorz; De Borggraeve, Wim M.; Bertrand, Luc; Beauloye, Christophe; Horman, Sandrine; Wevers, Martine; Kerckhofs, Greet. Cryogenic Contrast-Enhanced MicroCT (cryo-CECT): a Novel Nondestructive Approach to 3D Quantitative Histopathology of Soft Biological Tissues. 2022 xxx. http://hdl.handle.net/2078.1/265599

10. Rougier, G; Maistriaux, Louis; Fievé, Lies; Xhema, Daela; Manon, Julie; Evrard, Robin; de Ville de Goyet, Christine; Olszewski, Raphael; Kerckhofs, Greet; Szmytka, F; Thurieau, N; Boisson, J; Kadlub, N; Gianello, Pierre; Behets Wydemans, Catherine; Lengelé, Benoît. Perfusion-decellularization of vascularized bone matrix: Application to the porcine forelimb. In: Transplant International. Vol. 34, no.Suppl.1, p. 69 (2021). Oxford : Blackwell Pub.: England, 2021 xxx. http://hdl.handle.net/2078.1/258781


Book Chapters


1. Wevers, Martine; Nicolai, Bart; Verboven, Pieter; Swennen, Rudy; Roels, Staf; Verstrynge, Els; Lomov, Stepan Vladimirovitch; Kerckhofs, Greet; Van Meerbeek, Bart; Mavridou, Athina; Bergmans, Lars; Lambrechts, Paul; Soete, Jeroen; Claes, Steven; Claes, Hannes. Applications of CT for non-destructive testing and materials characterization. In: Industrial X-Ray Computed Tomography , Springer, 2018, p. 267-331. 978-3-319-59571-9. xxx xxx. http://hdl.handle.net/2078/194668

2. Verboven, P.; Ho, Q.; Herremans, E.; Mebatsion, H.; Nicolai, B.; Kerckhofs, Greet; Wevers, M.; Cloetens, P.. Fruit Microstructure Evaluation Using Synchrotron X-Ray Computed Tomography. In: Food Engineering Interfaces , Springer: New York, 2011, p. Chapter 24. 978-1-4419-7475-4. xxx xxx. http://hdl.handle.net/2078/202848