Open cranium model for the study of cerebrovascular dynamics in intracranial hypertension

• Published in: Journal of neuroscience methods Vol. 409; p. 110196
• Main Authors: Jaishankar, Rohan, Teichmann, Daniel, Hayward, Alison, Holsapple, James W., Heldt, Thomas
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2024
• Subjects: Animals; Cerebrovascular Circulation - physiology; Disease Models, Animal; Hemicraniectomy; Intracranial hypertension; Intracranial Hypertension - diagnostic imaging; Intracranial Hypertension - physiopathology; Intracranial pressure; Intracranial Pressure - physiology; Porcine model; Skull - diagnostic imaging; Skull - surgery; Swine; Hemicraniectomy; Intracranial pressure; Intracranial hypertension; Porcine model
• ISSN: 0165-0270; 1872-678X; 1872-678X
• DOI: 10.1016/j.jneumeth.2024.110196

Significant research has been devoted to developing noninvasive approaches to neuromonitoring. Clinical validation of such approaches is often limited, with minimal data available in the clinically relevant elevated ICP range. To allow ultrasound-guided placement of an intraventricular catheter and to perform simultaneous long-duration ICP and ultrasound recordings of cerebral blood flow, we developed a large unilateral craniectomy in a swine model. We also used a microprocessor-controlled actuator for intraventricular saline infusion to reliably and reversibly manipulate ICP according to pre-determined profiles. The model was reproducible, resulting in over 80 hours of high-fidelity, multi-parameter physiological waveform recordings in twelve animals, with ICP ranging from 2 to 78 mmHg. ICP elevations were reversible and reproducible according to two predetermined profiles: a stepwise elevation up to an ICP of 30–35 mmHg and return to normotension, and a clinically significant plateau wave. Finally, ICP was elevated to extreme levels of greater than 60 mmHg, simulating extreme clinical emergency. Existing methods for ICP monitoring in large animals typically relied on burr-hole approaches for catheter placement. Accurate catheter placement can be difficult in pigs, given the thickness of their skull. Additionally, ultrasound is significantly attenuated by the skull. The open cranium model overcomes these limitations. The hemicraniectomy model allowed for verified placement of the intraventricular catheter, and reversible and reliable ICP manipulation over a wide range. The large dural window additionally allowed for long-duration recording of cerebral blood flow velocity from the middle cerebral artery. •ICP is often limited in range in clinical settings.•This limits validation of novel neuromonitoring approaches.•We developed an open-cranium large-animal model to vary ICP over a wide range.•A large hemicraniectomy allowed for multimodal monitoring over long durations.•The model allowed for reversible changes in ICP from 2 to over 70 mmHg.