Mechanical ventilation is used to assist spontaneous breathing in critically ill patients such as those suffering from severe cases of COVID-19. There is a need for new technologies to monitor inspiratory muscle pathophysiology during mechanical ventilation to preserve muscle function and improve weaning success. Here we explore the feasibility of using our custom frequency domain diffuse optical spectroscopy platform to extract the oxygenation of the sternocleidomastoid (SCM), an accessory muscle of inspiration. We will present Monte Carlo simulation results of the neck region where the SCM is located as well as initial results from a normal volunteer study.
Current wearable optical technologies generally utilize superficial tissue continuous-wave measurements for biological metrics such as heart rate monitoring. There has been limited prior work in wearables that extract quantitative information including tissue optical properties and hemoglobin concentrations. These parameters may assist in tracking physiological status for cardio-pulmonary conditions and cancer. Next-generation optical wearables must meet substantial technical requirements, including small footprint, high sensitivity, and thermal stability. Here we investigate the use of a new multi-wavelength optical laser and compact avalanche photodiode for use in a miniaturized diffuse optical frequency-domain optode (miniOptode). These components represent the most compact fiberless optode for frequency-domain measurements to date. The miniOptode had high SNR (53.5dB at 50 MHz), and achieved high accuracy and precision in optical property extractions (accuracy: μa 0.0018 mm-1 and μs′ 0.0547 mm-1; precision: μa 0.00008mm-1 and μs′ 0.0015 mm-1). It provided high SNR for test measurements taken on nine different anatomic locations and was capable of tracking hemodynamics during a cuff occlusion test. Active thermoelectric cooling was required for thermal stability during longer tissue measurements. This work demonstrates that frequency domain diffuse optical measurements can be achieved in a highly portable format, providing new opportunities for long-term monitoring with quantitative oximetry.
KEYWORDS: Modulation, Optical properties, Multiplexing, Tissue optics, In vivo imaging, Signal detection, Chromophores, Data acquisition, Phase measurement, Electrocardiography
Frequency-domain diffuse optical spectroscopy (FD-DOS) utilizes intensity-modulated light to characterize optical scattering and absorption in thick tissue. Previous FD-DOS systems have been limited by large device footprints, complex electronics, high costs, and limited acquisition speeds, all of which complicate access to patients in the clinical setting. We have developed a new digital DOS (dDOS) system, which is relatively compact and inexpensive, allowing for simplified clinical use, while providing unprecedented measurement speeds. The dDOS system utilizes hardware-integrated custom board-level direct digital synthesizers and an analog-to-digital converter to generate frequency sweeps and directly measure signals utilizing undersampling at six wavelengths modulated at discrete frequencies from 50 to 400 MHz. Wavelength multiplexing is utilized to achieve broadband frequency sweep measurements acquired at over 97 Hz. When compared to a gold-standard DOS system, the accuracy of optical properties recovered with the dDOS system was within 5.3% and 5.5% for absorption and reduced scattering coefficient extractions, respectively. When tested in vivo, the dDOS system was able to detect physiological changes throughout the cardiac cycle. The new FD-dDOS system is fast, inexpensive, and compact without compromising measurement quality.
KEYWORDS: Tissue optics, Breast, Sensors, Breast cancer, Hemodynamics, Light emitting diodes, Tissues, Biomedical optics, Oxygen, Signal to noise ratio
We present a new continuous-wave wearable diffuse optical probe aimed at investigating the hemodynamic response of locally advanced breast cancer patients during neoadjuvant chemotherapy infusions. The system consists of a flexible printed circuit board that supports an array of six dual wavelength surface-mount LED and photodiode pairs. The probe is encased in a soft silicone housing that conforms to natural breast shape. Probe performance was evaluated using tissue-simulating phantoms and in vivo normal volunteer measurements. High SNR (71 dB), low source-detector crosstalk (−60 dB), high measurement precision (0.17%), and good thermal stability (0.22% Vrms/°C) were achieved in phantom studies. A cuff occlusion experiment was performed on the forearm of a healthy volunteer to demonstrate the ability to track rapid hemodynamic changes. Proof-of-principle normal volunteer measurements were taken to demonstrate the ability to collect continuous in vivo breast measurements. This wearable probe is a first of its kind tool to explore prognostic hemodynamic changes during chemotherapy in breast cancer patients.
The use of reliable tissue-simulating phantoms spans multiple applications in spectroscopic imaging including device calibration and testing of new imaging procedures. Three-dimensional (3D) printing allows for the possibility of optical phantoms with arbitrary geometries and spatially varying optical properties. We recently demonstrated the ability to 3D print tissue-simulating phantoms with customized absorption (μa) and reduced scattering (μs`) by incorporating nigrosin, an absorbing dye, and titanium dioxide (TiO2), a scattering agent, to acrylonitrile butadiene styrene (ABS) during filament extrusion. A physiologically relevant range of μa and μs` was demonstrated with high repeatability. We expand our prior work here by evaluating the effect of two important 3D-printing parameters, percent infill and layer height, on both μa and μs`. 2 cm3 cubes were printed with percent infill ranging from 10% to 100% and layer height ranging from 0.15 to 0.40 mm. The range in μa and μs` was 27.3% and 19.5% respectively for different percent infills at 471 nm. For varying layer height, the range in μa and μs` was 27.8% and 15.4% respectively at 471 nm. These results indicate that percent infill and layer height substantially alter optical properties and should be carefully controlled during phantom fabrication. Through the use of inexpensive hobby-level printers, the fabrication of optical phantoms may advance the complexity and availability of fully customizable phantoms over multiple spatial scales. This technique exhibits a wider range of adaptability than other common methods of fabricating optical phantoms and may lead to improved instrument characterization and calibration.
Optical phantoms are used in the development of various imaging systems. For certain applications, the development of thin phantoms that simulate the physical size and optical properties of tissue is important. Here, we demonstrate a method for producing thin phantom layers with tunable optical properties using poly(dimethylsiloxane) (PDMS) as a substrate material. The thickness of each layer (between 115 and 880 μm) was controlled using a spin coater. The reduced scattering and absorption coefficients were controlled using titanium dioxide and alcohol–soluble nigrosin, respectively. These optical coefficients were quantified at six discrete wavelengths (591, 631, 659, 691, 731, and 851 nm) at varying concentrations of titanium dioxide and nigrosin using spatial frequency domain imaging. From the presented data, we provide lookup tables to determine the appropriate concentrations of scattering and absorbing agents to be used in the design of PDMS-based phantoms with specific optical coefficients. In addition, heterogeneous phantoms mimicking the layered features of certain tissue types may be fabricated from multiple stacked layers, each with custom optical properties. These thin, tunable PDMS optical phantoms can simulate many tissue types and have broad imaging calibration applications in endoscopy, diffuse optical spectroscopic imaging, and optical coherence tomography, etc.
Near-infrared (NIR) frequency-domain Diffuse Optical Spectroscopy (DOS) is an emerging technology with a growing number of potential clinical applications. In an effort to reduce DOS system complexity and improve portability, we recently demonstrated a direct digital sampling method that utilizes digital signal generation and detection as a replacement for more traditional analog methods. In our technique, a fast analog-to-digital converter (ADC) samples the detected time-domain radio frequency (RF) waveforms at each modulation frequency in a broad-bandwidth sweep (50- 300MHz). While we have shown this method provides comparable results to other DOS technologies, the process is data intensive as digital samples must be stored and processed for each modulation frequency and wavelength. We explore here the effect of reducing the modulation frequency bandwidth on the accuracy and precision of extracted optical properties. To accomplish this, the performance of the digital DOS (dDOS) system was compared to a gold standard network analyzer based DOS system. With a starting frequency of 50MHz, the input signal of the dDOS system was swept to 100, 150, 250, or 300MHz in 4MHz increments and results were compared to full 50-300MHz networkanalyzer DOS measurements. The average errors in extracted μa and μs' with dDOS were lowest for the full 50-300MHz sweep (less than 3%) and were within 3.8% for frequency bandwidths as narrow as 50-150MHz. The errors increased to as much as 9.0% when a bandwidth of 50-100MHz was tested. These results demonstrate the possibility for reduced data collection with dDOS without critical compensation of optical property extraction.
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