Development and Characterization of a Probe Device toward Intracranial Spectroscopy of Traumatic Brain Injury

Abstract

Traumatic brain injury is a leading cause of mortality worldwide, often affecting individuals at their most economically active yet no primary disease-modifying interventions exist for their treatment. Real-time direct spectroscopic examination of the brain tissue within the context of traumatic brain injury has the potential to improve the understanding of injury heterogeneity and subtypes, better target management strategies and organ penetrance of pharmacological agents, identify novel targets for intervention, and allow a clearer understanding of fundamental biochemistry evolution. Here, a novel device is designed and engineered, delivering Raman spectroscopy-based measurements from the brain through clinically established cranial access techniques. Device prototyping is undertaken within the constraints imposed by the acquisition and site dimensions (standard intracranial access holes, probe’s dimensions), and an artificial skull anatomical model with cortical impact is developed. The device shows a good agreement with the data acquired via a standard commercial Raman, and the spectra measured are comparable in terms of quality and detectable bands to the established traumatic brain injury model. The developed proof-of-concept device demonstrates the feasibility for real-time optical brain spectroscopic interface while removing the noise of extracranial tissue and with further optimization and in vivo validation, such technology will be directly translatable for integration into currently available standards of neurological care.

Raman Spectroscopy as a Neuromonitoring Tool in Traumatic Brain Injury: A Systematic Review and Clinical Perspectives

“…Mowbray et al [ 51 ] utilised a controlled cortical impact model of TBI from Sprague Dawley rats. The group observed a fall in 1266 and 1660 cm −1 peaks in injured specimens when compared with control.…”

“…Clear and reproducible shifts in peaks are identified across multiple studies and models. A notable contradiction is the 1660 cm −1 peak: TBI models have identified a consistent reduction in 1660 cm −1 intensity in comparison with control [ 48 , 51 , 52 , 72 ]. In contrast, an ischaemia–reperfusion model of brain injury identified an increase in the 1660 cm −1 intensity.…”

“…One consideration is the access to brain parenchyma: unlike near-infrared spectroscopy, the Raman scattering return signal does not display skull penetrance rendering a transcranial approach vulnerable to excessive ‘noise’ from extracranial tissue scatter, to the extent of rendering it impractical. Subsequently, there are three options: (1) intraoperative cortical access; (2) a probe device which allows optical passage across the skull via a ‘window’ [ 51 ]; (3) a temporarily implanted fibre optic probe array capable of excitation and detection, either as an intraparenchymal or cortical monitoring device.…”

“…Our group has explored a quartz lens as a ‘window’ technique as a means for gaining optical access to the intracranial compartment [ 51 ]. Mowbray et al [ 51 ] designed and engineered a novel device which functions as a means of eliminating extra- and cranial tissue, with a polished quartz disc as a transparent window to facilitate spectral interrogation of brain tissue intermittently.…”

Photobiomodulation reduces hippocampal apoptotic cell death and produces a Raman spectroscopic “signature”

“…The development of this novel concept has resulted in a patent pending application from our group relating to the invasive delivery of PBM, together with the use of temporarily implanted apparatus to establish an optimal dose feedback loop via an optical spectroscopic brain interface (UK Patent Application No 2006201.4). The conceivable optical apparatus required to deliver a meaningful dose of PBM directly onto or into the brain substance (fibre optical), could be utilised for the Raman spectroscopic examination of the brain surface (an emission and detection fibre) and integrated into a single device [ 56 ]. As PBM treatment is only potentially required for a short time (1 minute) each day, the scope for establishing a spectroscopic interface to monitoring pathology, metering PBM dose and also tracking the deposition of pharmacological therapeutic agents is an exciting potential prospect for TBI care.…”