Abstract
The brains of patients suffering from traumatic brain-injury (TBI) undergo dynamic chemical changes in the days following the initial trauma. Accurate and timely monitoring of these changes is of paramount importance for improved patient outcome. Conventional brain-chemistry monitoring is performed off-line by collecting and manually transferring microdialysis samples to an enzymatic colorimetric bedside analyzer every hour, which detects and quantifies the molecules of interest. However, off-line, hourly monitoring means that any subhourly neurochemical changes, which may be detrimental to patients, go unseen and thus untreated. Mid-infrared (mid-IR) spectroscopy allows rapid, reagent-free, molecular fingerprinting of liquid samples, and can be easily integrated with microfluidics. We used mid-IR transmission spectroscopy to analyze glucose, lactate, and pyruvate, three relevant brain metabolites, in the extracellular brain fluid of two TBI patients, sampled via microdialysis. Detection limits of 0.5, 0.2, and 0.1 mM were achieved for pure glucose, lactate, and pyruvate, respectively, in perfusion fluid using an external cavity-quantum cascade laser (EC-QCL) system with an integrated transmission flow-cell. Microdialysates were collected hourly, then pooled (3–4 h), and measured consecutively using the standard ISCUSflex analyzer and the EC-QCL system. There was a strong correlation between the compound concentrations obtained using the conventional bedside analyzer and the acquired mid-IR absorbance spectra, where a partial-least-squares regression model was implemented to compute concentrations. This study demonstrates the potential utility of mid-IR spectroscopy for continuous, automated, reagent-free, and online monitoring of the dynamic chemical changes in TBI patients, allowing a more timely response to adverse brain metabolism and consequently improving patient outcomes.
Highlights
Traumatic brain injury (TBI) is the leading cause of death in those aged under 40 years in the developed world, typically resulting from road and sporting accidents, falls, and violence.[1]
The performance of mid-IR spectroscopy was evaluated as a technique to analyze and monitor the brain chemistry of TBI patients
An limit of detection (LOD) of 0.5, 0.2, and 0.1 mM was achieved for glucose, lactate, and pyruvate, respectively, the three main compounds of interest in TBI monitoring
Summary
Traumatic brain injury (TBI) is the leading cause of death in those aged under 40 years in the developed world, typically resulting from road and sporting accidents, falls, and violence.[1]. The microdialysis technique used in clinical practice requires the collection of microdialysate into vials and their manual transfer into a bedside analyzer (ISCUSflex, M Dialysis AB, Stockholm, Sweden) every hour.[6] The fact that microdialysis is limited to hourly readings means that any rapid changes in brain chemistry can be overlooked and opportunities for timely intervention are lost. It requires manual transfer of samples and is based on enzymatic colorimetric assays, which require a range of reagents. There is a clinical need for a sensor system, which would allow continuous online monitoring of glucose, lactate, and pyruvate, the three most clinically relevant substances in TBI-patient
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