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

Max Mowbray,Jonathan J S Rickard,Pola Goldberg Oppenheimer,David J Davies,Carl Banbury

doi:10.1021/acsbiomaterials.0c01156

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.

Highlights

Rapid in vivo healthcare point-of-care diagnostics are of critical importance to clinical medicine
In order to prevent the surgeon from drilling into the tissue, the drill should allow for an internal ledge
Several key factors need to be taken into consideration upon designing the probe including, the fine-tuning of probe working distance from the brain, secure and safe positioning within the calvarial bone, (Table 1 and Figure 1) alignment of the probe within the device, closure of the brain to the external environment, material selection, which ensures biocompatibility while avoiding fracture, facile, cheap, and repeatable manufacturing and the quantification of design through Finite element analysis (FEA)

Summary

Introduction

Rapid in vivo healthcare point-of-care diagnostics are of critical importance to clinical medicine They aid in providing optimized, individually tailored, efficient treatment. Invasive (placed into brain tissue) monitoring modalities including pressure transducers and oxygen tension sensors are used to provide data to support the maintenance of such favorable physiological conditions. As independent parameters, both intracranial pressure (ICP) and brain tissue oxygentension guided intervention provide minimal improvement in outcome after severe TBI.[3,4] The pathophysiology of injury evolution is multi-faceted and currently not understood well enough to provide effective pharmacological targeting to reduce injury burden or progression. Disease-indicative biomarkers provide insights into the biological pathways underpinning certain pathologies allowing effective stratification and classification of pathology

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Discussion

Conclusion