Paper Submission & Registration
8th Dutch Bio-Medical Engineering Conference
13:40   Brain - III
Chair: Elisabeth Wilhelm
15 mins
Robotic transfer of a preoperative plan for open reconstructive craniosynostosis surgery: A pilot study
Adriana J.M. Pilon, Rémi van der Woude, Lisanne P.J. Venix, Eva Koot, Vincent Groenhuis, Luc Verhamme, Jene Meulstee
Abstract: Open cranial vault reconstruction (OCVR) is a major surgical procedure that could be used to treat craniosynostosis patients. Using preoperative three dimensional (3D) virtual surgical planning (VSP), could assist the surgical team to determine the optimal surgical strategy for every individual patient. However, it remains challenging to transfer this surgical plan to the patient. Therefore, this study has explored the possibility of using a robot during this complex task. The Adept Viper s850, a six degrees of freedom robot, was used to overcome the shortcomings of all current methods and transfer the VSP on a phantom of a patient with trigonocephaly. After manual calibration the coordinates of the VSP were transformed into robot coordinates and used to navigate the robot. The results demonstrated that the robot was able to draw the VSP precise, fast and automatic. The first results of this pilot study are promising. Nevertheless, adjustments have to be made to reduce operating time, complying with all safety standards of medical robotics, and make the robot easier to operate. After completing these improvements, this study shows a large potential for the clinical implementation of robots in OCVR for patients with craniosynostosis.
15 mins
Tensor-based joint estimation of hemodynamic response and stimulus function in functional ultrasound
Aybüke Erol, Simon Van Eyndhoven, Sebastiaan Koekkoek, Pieter Kruizinga, Borbala Hunyadi
Abstract: Functional ultrasound (fUS) is a novel neuroimaging modality that indirectly measures brain activity by recording changes in cerebral blood flow (CBF) and volume. Functional ultrasound imaging relies on neurovascular coupling (NVC) similar to functional magnetic resonance imaging (fMRI), yet fUS provides higher spatiotemporal resolution at a lower cost than fMRI. When a brain region becomes active, its metabolic demands are met by an increase in CBF to the region. NVC describes this interaction between neural activity and CBF, whereas the associated changes in CBF is known as the hemodynamic response (HR). The correct modelling of HR is one of the most prevalent topics in functional neuroimaging. HR is commonly expressed as the convolution of an impulse response (hemodynamic response function- HRF) and a stimulus signal. In order to incorporate multiple HR signals in a setting with multiple stimuli (meaning that there might be more than one stimulus that triggers a response in the brain simultaneously), a multiple-input-multiple-output system is required. Furthermore, empirical studies show that HRF varies across different events and brain regions [1]. Convolutive mixtures satisfy both requirements as they employ convolutive mixing filters which relate multiple source signals to multiple measurements and whose characteristics depend on the source type and measurement number. In the context of fUS; measurements, sources and convolutive mixing filters correspond to the time-series of selected voxels, the stimuli that occur during the experiment and the HRFs that may differ for each stimulus and voxel combination respectively. The blind deconvolution problem (assuming both HRFs and stimuli are unknown) is solved by applying block term decomposition on the tensor of lagged output autocorrelation matrices while presuming uncorrelated source signals. We tested our method on simulations and a visual stimulation experiment on a mouse. Simulations proved the robustness of the proposed method to noise and the estimated stimulus signal from the mouse experiment recovered most of the actual paradigm while assigning different HRFs to different voxels. [1] Lindquist, M. A., Meng Loh, J., Atlas, L. Y., & Wager, T. D. (2009). Modeling the Hemodynamic Response Function in fMRI: Efficiency, Bias and Mis-modeling. Neuroimage, 45(1), S187–S198.
15 mins
Minimalistic scaffolds produced with the use o melt electrowriting for blood-brain barrier in vitro studies
Magdalena Gladysz, Marleen Kamperman, Malgorzata Wlodarczyk-Biegun, Anika Nagelkerke
Abstract: Introduction: The barrier function of the blood-brain barrier (BBB) is achieved by a semipermeable endothelial cell layer restricting perfusion of non-selective substances from the systemic circulation into the brain tissue. This primarily protective function hinders effective delivery of therapeutics into brain tumours. Therefore, despite the indisputable progress in cancer research, it is still necessary to work on the development of new treatment strategies. For this purpose biologically relevant BBB-tumour models need to be invented, as the BBB is the critical obstacle hindering drug delivery to the brain. Main research questions: This project aims to design a thin polymeric membrane on which relevant cells form confluent layers with tight junctions. The membrane will serve as a minimalistic supporting scaffold, favouring cell-cell interactions instead of cell-material interactions. The properties of the membranes, such as architecture, porosity and fiber thickness, are investigated in relation to cell behaviour and tissue formation. Relevant cell types for the BBB, such as endothelial cells, astrocytes and pericytes, can be seeded on the membrane. Methods and results: Membranes are produced from poly(ε-caprolactone) with high precision and desirable qualities, using melt electrowriting (MEW). MEW is a novel bioprinting technique which allows polymer melt deposition into sub-millimetre range fibers*, with flexibility of the design, high resolution and accuracy. Different designs (overall architecture, porosity, fiber thickness) are currently being investigated in relation to cell behaviour and tissue formation. The most effective ways of seeding membranes with cells are being tested. Conclusions and outlook: The proposed membranes are created for the purpose of cell culture and their design aims at influencing cellular response. Membrane coating and methods of cell seeding can also be important factors affecting cell behaviour on fabricated structures. In the future the emphasis will be put on co-culturing several types of cells and on optimizing the material properties to accommodate the required cell types. Significance: This is the first step to obtain BBB models with biological relevance. Ultimately, the developed system will allow fabrication of a testing platform which can closely imitate the environment in living organisms.
15 mins
Impedance-based monitoring of Blood-Brain Barrier formation in Organ-on-chip
Mariia Zakharova, Elsbeth Bossink, Douwe de Bruijn, Mathieu Odijk, Loes Segerink
Abstract: The endothelial tight junctions (TJs) in the blood-brain barrier (BBB) are responsible for maintaining the tight barrier and regulation of the passage of molecules between blood and the central neural system [1]. Transendothelial electrical resistance (TEER) measurements can provide non-invasive, quantitative information about the formation of the TJs in in vitro models. Currently, a great interest is focused on organ-on-chip (OoC) as an alternative system to animal models and non-physiological static Transwell [2]. Unfortunately, it is not always possible to integrate electrodes inside such systems without blocking the view and leaving the ability to increase the throughput. In this work, we present a simple and reproducible method of electrode integration in the multiplexed OoC for real-time monitoring of the barrier tightness with an increased throughput per chip.

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