Normal Pressure Hydrocephalus; Magnetic Resonance Imaging; Cerebrospinal Fluid; CSF Shunt; Shunt Infection; Computational Fluid Dynamics; Brain Mechanics; Control System; Biofilm; Bacterial Adhesion; Infection Prevention; Hydrogel; Surface Coating; Finite Element Method; Fluid-Structure Interaction; Porous Media; Intracranial Dynamics
(2012), Age-specific characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid dynamics., in PloS one
, 7(5), 37502-37502.
(2012), Craniospinal Pressure-Volume Dynamics in Phantom Models, in IEEE Transactions on Biomedical Engineering
(2012), Sparsity transform k-t principal component analysis for accelerating cine three-dimensional flow measurements, in Magnetic Resonance in Medicine
(2012), Phantom model of physiologic intracranial pressure and cerebrospinal fluid dynamics., in IEEE Transactions on Biomedical Engineering
, 59(6), 1532-8.
(2012), Bayesian multipoint velocity encoding for concurrent flow and turbulence mapping, in Magnetic Resonance in Medicine
(2012), Comparison of Velocity Vector Fields and Turbulent Kinetic Energy Measured by MRI and Particle Tracking Velocimetry in a Realistic Aortic Phantom, in Proceedings of the Annual Meeting of the International Society of Magnetic Resonance in Medicine
, Melbourne, Australia.
(2012), Multi-Point Velocity Encoding for Simultaneous Assessment of Arterial, Venous and Cerebrospinal Flow, in Proceedings of the Annual Meeting of the International Society of Magnetic Resonance in Medicine
, Melbourne, Australia.
(2012), Role of rifampin against propionibacterium acnes biofilm in vitro and in an experimental foreign-body infection model, in Antimicrobial Agents and Chemotherapy
(2011), Computational fluid dynamics for the assessment of cerebrospinal fluid flow and its coupling with cerebral blood flow, 169-187.
(2011), Gentamicin improves the activities of daptomycin and vancomycin against Enterococcus faecalis in vitro and in an experimental foreign-body infection model, in Antimicrobial Agents and Chemotherapy
, 55(10), 4821-4827.
(2011), Investigating the role of choroid plexus in CSF pulsation by combining in-vivo and post-mortem MRI, in Proceedings of the Annual Meeting of the International Society of Magnetic Resonance in Medicine
, Montreal, Canada.
(2011), Probabilistic streamline estimation from accelerated Fourier velocity encoded measurements, in Proceedings of the Annual Meeting of the International Society of Magnetic Resonance in Medicine
, Montreal, Canada.
(2010), Cerebrospinal fluid dynamics in the human cranial subarachnoid space: an overlooked mediator of cerebral disease. I. Computational model., in Journal of the Royal Society, Interface / the Royal Society
, 7(49), 1195-204.
(2010), Cerebrospinal fluid dynamics in the human cranial subarachnoid space: an overlooked mediator of cerebral disease. II. In vitro arachnoid outflow model., in Journal of the Royal Society, Interface / the Royal Society
, 7(49), 1205-18.
(2010), Hadamard-transform k-t PCA for cine 3D velocity vector field mapping of carotid flow, in Proceedings of the Annual Meeting of the International Society of Magnetic Resonance in Medicine
, Stokholm, Sweden.
(2009), Investigation of ventricular cerebrospinal fluid flow phase differences between the foramina of Monro and the aqueduct of Sylvius, in Biomedizinische Technik
, 54(4), 161-169.
, In vitro emergence of rifampin resistance in Propionibacterium acnes and molecular characterization of mutations in the rpoB gene, in Journal of Antimicrobial Chemotherapy
This multidisciplinary research project aims at conducting the basic research necessary for the subsequent development of a smart cerebrospinal fluid (CSF) shunt for normal pressure hydrocephalus (NPH) that addresses the key shortcomings of current shunt technology: infections, poor CSF flow control and mechanical failure.NPH is most commonly treated by the surgical placement of a ventriculoperitoneal shunt that drains CSF from the patient’s ventricular space to the peritoneal area. The mechanical failure rate of these shunts is up to 40% within the first year of implantation and 4 to 5% in the subsequent years. The shunt infection rate is about 5%. As a consequence, roughly half of the treated patients require follow-up surgery within the first two years.Current shunts rely on differential-pressure valves to control CSF drainage. In most of them, the opening pressure cannot be changed after implantation. Patients with this standard type of valve often suffer from the symptoms of CSF over- or underdrainage. Patients with externally adjustable valves return repeatedly to the neurosurgeon’s office for readjustment of the pressure setting, thereby considerably increasing the overall cost of the treatment.We have developed a novel shunt concept that addresses all of the above problems. The envisioned shunt regulates CSF drainage using an adaptive feedback control system that analyzes the patient’s intracranial dynamics to determine the required outflow rate, thereby addressing the experts’ call for a flow regulated rather than pressure regulated shunt. A single catheter with infection-inhibiting coating drains CSF from the ventricles to the peritoneal area. No other shunt elements are in contact with the cerebrospinal fluid, which reduces the risk of infection and mechanical failure.The funding requested in this proposal is aimed at financing the basic research that will subsequently enable the development of this smart shunt. The following tasks will be performed to this end:-Clinical multi-center study on explanted shunts to identify main infection pathways-Research and development of infection-inhibiting coating for the shunt-In-vitro and in-vivo testing of the developed coating-Research and development of MRI sequences for the non-invasive identification of NPH model parameters-Clinical external CSF drainage and MRI study on NPH patients to identify relevant NPH parameters-Research and development of analytical and computational NPH model-Research and development of feedback control algorithm for shunt valve control-Development of a functional model of the envisioned smart shunt-Development of a physical NPH phantom and test rig for testing of the smart shunt functional modelAll of the above tasks are intertwined and require the know-how of experts in their respective fields: the infection-inhibiting coating must not interfere with the sensors required for feedback control, the MRI sequence must allow for short scanning times to accommodate patients, yet must deliver accurate data for the NPH model and the clinical MRI study must provide the data necessary for the control algorithm design. This enmeshment of disciplines necessitates a multidisciplinary approach, without which the ultimate goal of providing the basis for the development of the smart shunt cannot be reached.The consortium convened for this project consists of partners from ETH Zurich with expertise in flow and mass transport in biofluids, control systems, computational modelling and surface science, the University of Zurich with expertise in MRI sequence design, the University Hospital Basel with expertise in neurosurgery, infectious diseases and neuroradiology, as well as the University of Western Australia with expertise in cerebral mechanics. Some of the project partners have successfully collaborated in the past, most recently in a related multidisciplinary project on CSF flow diagnostics and control.