Raman spectroscopic applications towards the management of traumatic injuries to the central nervous system

Stickland, Clarissa Angela ORCID: 0009-0002-4682-1923 (2024). Raman spectroscopic applications towards the management of traumatic injuries to the central nervous system. University of Birmingham. Ph.D.

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Abstract

Traumatic central nervous system (CNS) injuries, or CNS trauma, are a leading cause of morbidity and mortality worldwide, with high-complication rates, prolonged post-traumatic neuro-disorders requiring long-term care, and are associated with important socio-economic costs such as prolonged medical care, rehabilitation costs, and loss of productivity and economic contribution. CNS trauma often affects individuals at their most economically active, yet no primary disease modifying interventions. Therapeutic strategies continue to be explored, including photobiomodulation (PBM). Given the limited regenerative capacity of CNS tissue, early insights into the biochemical changes that occur following trauma are essential for developing effective interventions. Traumatic brain injury (TBI) in particular, presents with notoriously inconsistent symptoms, complicating the development of reliable diagnostic tools. However, current hospital-based diagnostic modalities are often too slow or costly to support timely clinical decision-making in acute care settings, creating significant barriers to effective TBI management. This thesis aims to ascertain the use of Raman spectroscopy as a method of biochemical detection on CNS tissue to identify potential therapeutic pathways.

Here, we have developed an unprecedented Raman spectroscopy library of eighteen potential TBI biomarkers recorded on four laser wavelengths. Paired with the development of a probe as a portable technology capable of rapidly detecting TBI biochemical changes in the brain via Raman spectroscopy-based measurements of brain tissue, the biomarker library is a tool capable identifying therapeutic targets for TBIprimary injuries, as well as an experimental guide for researchers in the field of Raman diagnostics for CNS trauma. Using established and emergent cranial access in secondary care, we have successfully demonstrated the use of the probe to classify healthy from injured tissue to an accuracy of 94.5% (±0.03), temporally tracking the injury pathology and evolution. Using a 3D printed intracranial bolt, the developed probe-device demonstrates the differentiation between injured and healthy controls, classifying injury severities via the Self-Optimising Kohonen Index Network, and quantitatively attributing changes to the underlying biochemistry in a murine model of simulated TBI impact. An additional novel approach to transcranial Raman spectroscopy is featured in its early stages, yielding a preliminary 92.8% (±0.06) accuracy of classification between distinct brain biochemical environments. Real-time direct spectroscopy of rat brain tissue post-TBI enables improved interrogation of injury heterogeneity and subtypes, greater target management strategies, identification of novel targets for intervention, and allows for a clearer understanding of the fundamental biochemistry evolution and pathological dysregulation. Overall, this device demonstrates the feasibility for real-time optical brain spectroscopic interface. This technology can thus be directly translated for integration into current standards of CNS trauma care and is applicable in the research of primary disease modifying interventions.

Following the identification of therapeutic targets, Raman spectroscopy has been established as a monitoring tool to track PBM treatment efficacy for spinal cord injury. Through the examination of spinal cord tissue, dorsal root ganglia (DRG), and brain tissue, PBM was ascertained to accelerate dendrite growth and axonal regeneration in the DRG and showed evidence of recovering injured spinal cord tissue towards a healthy baseline.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):