A 2023 Crick-King's College London Joint PhD project with Andreas Schaefer (Crick) and Anne Vanhoestenberghe (KCL)
Project background and description
Intra-cranial pressure (ICP) monitors are routinely implanted in a wide range of patients, including after traumatic brain injury, or other indications of a risk of brain edema such as ventilated patients with haemorrhagic stroke or subarachnoid haemorrhage. Whilst there are fully implanted solutions, many ICP monitors are inserted in the cortex through a hole in the skull, sealed with a “skullbolt”. Despite being the current standard of care, they give only limited information about brain tissue health. More information can be obtained with cortical electrodes recording local field potential (LFP), but their placement currently requires a significantly more invasive procedure than ICP insertion, which restricts their clinical use. The addition of an array of electrodes along the ICP shaft, with a modified skullbolt to connect the array to external recording along with the ICP, will enable recording single unit potentials to provide higher levels of sensitivity than LFPs without extra surgery. This approach integrates multi-modal physiological monitoring into the existing standard of care, without increasing the risks to the patients scheduled anyway for ICP monitor implantation.
Synchronous monitoring of brain activity at the site of the probe will provide an enhanced understanding of the evolution of the patient’s health. Acutely, this data could support the early detection of deteriorating condition whilst over time large datasets of activity would inform our understanding of neural activity in awake humans. In the longer term, combined pressure and activity data could lead to improved treatment and rehabilitation planning.
Delivering these patient benefits requires a multi-disciplinary approach, encompassing neuroscience and engineering. An intraparenchymal probe’s outer diameter is 2 to 3 mm, with a 5 mm metal tip. We must create an array of electrodes, complete with cable and modified skullbolt connector, that does not significantly change the dimensions and mechanical properties of the probe, so as not to increase the patient risks. Whilst there are several modern materials and methods to create micro-electrode arrays, few have been successfully translated to chronic use in humans. The array must be manufactured using technology and materials suitable for use in direct and prolonged (subacute) contact with the human brain, and capable of being attached to commercial ICP probes. A large animal model is required to test the multi-modal probes, optimise the electrode array, and develop our interpretation of the data. The latter is challenging as the probe will trigger a foreign body reaction that will cause the signals recorded to vary over time. This variation must be accounted for when analysing the data for signs of changes in the patient’s condition and prognostic markers of long-term recovery.
Both the device design and the interpretation of the data will be conceived in close collaboration with our neurosurgeon partners to ensure the solution meets their needs and does not significantly alter the surgical procedure and post-operative care.
We seek candidates with a degree in engineering or any applied science, who clearly demonstrate knowledge relevant to this project. Enthusiasm for systems neuroscience questions is essential. Practical experience, whether working with animal or device manufacture, is a strong advantage, though not essential.
1. Carnicer-Lombarte, A., Lancashire, H.T. and Vanhoestenberghe, A. (2017)
In vitro biocompatibility and electrical stability of thick-film platinum/gold alloy electrodes printed on alumina.
Journal of Neural Engineering 14: 036012. PubMed abstract
2. Obaid, A., Hanna, M.E., Wu, Y.W., Kollo, M., Racz, R., Angle, M.R., . . . Melosh, N.A. (2020)
Massively parallel microwire arrays integrated with CMOS chips for neural recording.
Science Advances 6: eaay2789. PubMed abstract
3. Ackels, T., Erskine, A., Dasgupta, D., Marin, A.C., Warner, T.P.A., Tootoonian, S., . . . Schaefer, A.T. (2021)
Fast odour dynamics are encoded in the olfactory system and guide behaviour.
Nature 593: 558-563. PubMed abstract
4. Marcus, H.J. and Wilson, M.H. (2015)
Insertion of an intracranial-pressure monitor.
New England Journal of Medicine 373: e25. PubMed abstract
5. Vomero, M., Ciarpella, F., Zucchini, E., Kirsch, M., Fadiga, L., Stieglitz, T. and Asplund, M. (2022)
On the longevity of flexible neural interfaces: Establishing biostability of polyimide-based intracortical implants.
Biomaterials 281: 121372. PubMed abstract