Noninvasive in vivo measurement of pH in cerebrospinal fluid
Inventors
Assignees
Publication Number
US-11559203-B2
Publication Date
2023-01-24
Expiration Date
2040-01-31
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Abstract
A system and method for determining the pH of tissue in vivo. A Raman spectrometer is used to collect Raman spectra from the target tissue. The Raman spectra are baseline subtracted and assessed to determine the concentration of HPO4−2 and H2PO4−1 for the purposes of calculating the pH. The approach was validate in vitro using PBS solutions of known pH. The approach was confirmed in vivo using rat and swine models by probing the immediate vicinity of a contusive spinal cord injury (SCI) in the first minutes and hours after injury. Using a dynamic analysis and the Henderson-Hasselbalch equation, the average of (N=12) noninvasive Raman-based pH measurements of CSF was 7.073±0.156 and at >95% confidence there is no statistically significant difference between the Raman-based and the physically sampled results.
Core Innovation
The invention introduces a system and method for noninvasively measuring the pH of cerebrospinal fluid (CSF) in vivo using Raman spectroscopy. By directing a near infrared (NIR) laser onto the target tissue and collecting the inelastically scattered Raman spectra, the concentrations of specific phosphate ions (HPO4−2 and H2PO4−1) can be determined. The resulting Raman spectra are subjected to baseline subtraction using a ‘101-7’ process to isolate relevant features for accurate analysis.
The calculated concentrations of HPO4−2 and H2PO4−1 from the baseline-subtracted spectra are used to compute the pH of CSF via the Henderson-Hasselbalch equation. The approach was validated with in vitro measurements using phosphate-buffered saline (PBS) solutions of known pH and confirmed in vivo through animal models, including rats and swine, by probing the area near a spinal cord injury. Results indicated no significant difference between Raman-based and physically sampled pH measurements.
The problem addressed is the lack of noninvasive, real-time methods to quantitatively measure pH in bodily fluids such as CSF, especially in scenarios involving inflammation or injury (e.g., spinal cord injury), where timely and detailed chemical monitoring could support improved medical outcomes. Existing methods do not allow for label-free, in situ chemical analysis of pH changes, limiting the ability to dynamically assess injury progression and healing.
Claims Coverage
The patent contains two independent claims with distinct inventive features focusing on noninvasive pH measurement of cerebrospinal fluid using Raman spectroscopy, both as a system and a method.
System for noninvasive pH determination in cerebrospinal fluid using Raman spectrometry and automated spectral analysis
The inventive feature describes a system comprising: - A Raman spectrometer configured to collect Raman spectra from a target of cerebral spinal fluid in vivo using a predetermined excitation wavelength over a predetermined exposure time. - A microprocessor programmed to exclude elastically scattered light, crop the collected Raman spectra to a predetermined range of Raman shift, smooth the list of resulting counts, baseline subtract the smoothed function, and calculate the pH of the cerebral spinal fluid based on the baseline subtracted spectra. - Automated exclusion of elastically scattered light and cropping of spectral data. - Utilization of smoothing and baseline subtraction steps prior to pH calculation.
Method of measuring pH in vivo in cerebrospinal fluid using processed Raman spectroscopy data
The inventive feature outlines a method comprising the steps of: 1. Using a Raman spectrometer to collect Raman spectra from a target of cerebral spinal fluid in vivo at a predetermined excitation wavelength and exposure time. 2. Receiving the collected Raman spectra. 3. Baseline subtracting the collected spectra by excluding elastically scattered light, cropping the spectra to a predetermined range, smoothing with equal weights, and subtracting the smoothed function to produce a baseline-subtracted spectrum. 4. Calculating the pH of the cerebral spinal fluid from the processed Raman spectra.
In summary, the claims cover the use of a Raman spectrometer and automated spectral processing for noninvasively measuring pH in cerebrospinal fluid, both as an integrated system and as a step-wise analytical method.
Stated Advantages
Enables noninvasive, label-free, in vivo measurement of pH in cerebrospinal fluid using Raman spectroscopy.
Provides quantitative agreement between Raman-based pH measurements and conventional physical sampling methods.
Allows for real-time, in situ analysis of chemical changes, such as pH, following spinal cord or other injuries.
Reduces need for physical sampling, minimizing patient risk and potential tissue damage.
Documented Applications
Noninvasive in vivo measurement of pH in cerebrospinal fluid of rats and swine, particularly near sites of spinal cord injury.
Potential to create dynamic pH images or maps of injured spinal cord tissue for research or clinical use.
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