Cerebral Microdialysate Metabolite Monitoring using Mid-infrared Spectroscopy.

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.

Intracranial pulse pressure waveform analysis using the higher harmonics centroid.

BACKGROUND: The pulse waveform of intracranial pressure (ICP) is its distinctive feature almost always present in the clinical recordings. In most cases, it changes proportionally to rising ICP, and observation of these changes may be clinically useful. We introduce the higher harmonics centroid (HHC) which can be defined as the center of mass of harmonics of the ICP pulse waveform from the 2nd to 10th, where mass corresponds to amplitudes of these harmonics. We investigate the changes in HHC during ICP monitoring, including isolated episodes of ICP plateau waves. MATERIAL AND METHODS: Recordings from 325 patients treated between 2002 and 2010 were reviewed. Twenty-six patients with ICP plateau waves were identified. In the first step, the correlation between HHC and ICP was examined for the entire monitoring period. In the second step, the above relation was calculated separately for periods of elevated ICP during plateau wave and the baseline. RESULTS: For the values averaged over the whole monitoring period, ICP (22.3 ± 6.9 mm Hg) correlates significantly (R = 0.45, p = 0.022) with HHC (3.64 ± 0.46). During the ICP plateau waves (ICP increased from 20.9 ± 6.0 to 53.7 ± 9.7 mm Hg, p < 10-16), we found a significant decrease in HHC (from 3.65 ± 0.48 to 3.21 ± 0.33, p = 10-5). CONCLUSIONS: The good correlation between HHC and ICP supports the clinical application of pressure waveform analysis in addition to the recording of ICP number only. Mean ICP may be distorted by a zero drift, but HHC remains immune to this error. Further research is required to test whether a decline in HHC with elevated ICP can be an early warning sign of intracranial hypertension, whether individual breakpoints of correlation between ICP and its centroid are of clinical importance.