Hemodynamics of the sternocleidomastoid measured with frequency domain near-infrared spectroscopy towards non-invasive monitoring during mechanical ventilation.

Mechanical ventilation (MV) is used to assist spontaneous breathing in critically ill patients in the intensive care unit (ICU). MV is a cornerstone of critical care medicine but it is now known that inspiratory muscle dysfunction due to injury, disuse, and/or atrophy during MV plays a major role in outcomes for these patients. For example, prolonged MV is strongly correlated with dysfunction of the sternocleidomastoid (SCM), an accessory inspiratory muscle that has been linked to weaning failure from MV. Hemodynamic monitoring of the SCM may provide an important non-invasive and real-time means to monitor MV. In this work, we first conducted multi-layer Monte Carlo simulations to confirm the ability of near infrared light to detect changes in the oxygenation of the SCM over wide ranges of skin tones and adipose layer thicknesses. We then optimized a custom digital frequency domain near-infrared spectroscopy (FD-NIRS) system for continuous 10 Hz measurements of the SCM at 730 nm and 850 nm. A healthy volunteer study was conducted (N=10); subjects performed sets of isometric neck flexions of the SCM. Substantial changes in oxyhemoglobin + oxymyoglobin (oxy[Hb + Mb]), deoxyhemoglobin + deoxymyoglobin (deoxy[Hb + Mb]), and total hemoglobin + myoglobin (total[Hb + Mb]) were observed during sustained and intermittent isometric flexions. There were notable sex differences observed in the magnitude of hemodynamic changes (∼2x larger changes in males for oxy[Hb + Mb] and deoxy[Hb + Mb]). The magnitude of hemodynamic changes when taking into account µs' changes during flexions was ∼ 2-2.5x larger as compared to assuming constant scattering (CS), which is a common assumption used for continuous wave (CW) NIRS methods. This study suggests that FD-NIRS provides improved accuracy for hemodynamic monitoring of the SCM compared to CW-NIRS, and that FD-NIRS may provide value for SCM monitoring during MV.

Deep learning model for ultrafast multifrequency optical property extractions for spatial frequency domain imaging.

Spatial frequency domain imaging (SFDI) is emerging as an important new method in biomedical imaging due to its ability to provide label-free, wide-field tissue optical property maps. Most prior SFDI studies have utilized two spatial frequencies (2-fx) for optical property extractions. The use of more than two frequencies (multi-fx) can vastly improve the accuracy and reduce uncertainties in optical property estimates for some tissue types, but it has been limited in practice due to the slow speed of available inversion algorithms. We present a deep learning solution that eliminates this bottleneck by solving the multi-fx inverse problem 300× to 100,000× faster, with equivalent or improved accuracy compared to competing methods. The proposed deep learning inverse model will help to enable real-time and highly accurate tissue measurements with SFDI.

Quantitative real-time pulse oximetry with ultrafast frequency-domain diffuse optics and deep neural network processing.

Pulse oximetry is a ubiquitous optical technology, widely used for diagnosis and treatment guidance. Current pulse oximeters provide indications of arterial oxygen saturation. We present here a new quantitative methodology that extends the capability of pulse oximetry and provides real-time molar concentrations of oxy- and deoxy-hemoglobin at rates of up to 27 Hz by using advanced digital hardware, real-time firmware processing, and ultra-fast optical property calculations with a deep neural network (DNN). The technique utilizes a high-speed frequency domain spectroscopy system with five frequency-multiplexed wavelengths. High-speed demultiplexing and data reduction were performed in firmware. The DNN inversion algorithm was benchmarked as five orders of magnitude faster than conventional iterative methods for optical property extractions. The DNN provided unbiased optical property extractions, with an average error of 0 ± 5.6% in absorption and 0 ± 1.4% in reduced scattering. Together, these improvements enabled the measurement, calculation, and real-time continuous display of hemoglobin concentrations. A proof-of-concept cuff occlusion measurement was performed to demonstrate the ability of the device to track oxy- and deoxy-hemoglobin, and measure quantitative photoplethysmographic changes during the cardiac cycle. This technique substantially extends the capability of pulse oximetry and provides unprecedented real-time non-invasive functional information with broad applicability for cardiopulmonary applications.

Ultrafast wavelength multiplexed broad bandwidth digital diffuse optical spectroscopy for in vivo extraction of tissue optical properties.

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.

Wearable near-infrared optical probe for continuous monitoring during breast cancer neoadjuvant chemotherapy infusions.

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% V rms / ° 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.

Feasibility of spatial frequency domain imaging (SFDI) for optically characterizing a preclinical oncology model.

Determination of chemotherapy efficacy early during treatment would provide more opportunities for physicians to alter and adapt treatment plans. Diffuse optical technologies may be ideally suited to track early biological events following chemotherapy administration due to low cost and high information content. We evaluated the use of spatial frequency domain imaging (SFDI) to characterize a small animal tumor model in order to move towards the goal of endogenous optical monitoring of cancer therapy in a controlled preclinical setting. The effects of key measurement parameters including the choice of imaging spatial frequency and the repeatability of measurements were evaluated. The precision of SFDI optical property extractions over repeat mouse measurements was determined to be within 3.52% for move and replace experiments. Baseline optical properties and chromophore values as well as intratumor heterogeneity were evaluated over 25 tumors. Additionally, tumor growth and chemotherapy response were monitored over a 45 day longitudinal study in a small number of mice to demonstrate the ability of SFDI to track treatment effects. Optical scattering and oxygen saturation increased as much as 70% and 25% respectively in treated tumors, suggesting SFDI may be useful for preclinical tracking of cancer therapies.

Three-dimensional printed optical phantoms with customized absorption and scattering properties.

Three-dimensional (3D) printing offers the promise of fabricating optical phantoms with arbitrary geometry, but commercially available thermoplastics provide only a small range of physiologically relevant absorption (µa) and reduced scattering (µs`) values. Here we demonstrate customizable acrylonitrile butadiene styrene (ABS) filaments for dual extrusion 3D printing of tissue mimicking optical phantoms. µa and µs` values were adjusted by incorporating nigrosin and titanium dioxide (TiO2) in the filament extrusion process. A wide range of physiologically relevant optical properties was demonstrated with an average repeatability within 11.5% for µa and 7.71% for µs`. Additionally, a mouse-simulating phantom, which mimicked both the geometry and optical properties of a hairless mouse with an implanted xenograft tumor, was printed using dual extrusion methods. 3D printed tumor optical properties matched the live tumor with less than 3% error at a wavelength of 659 nm. 3D printing with user defined optical properties may provide a viable method for durable optically diffusive phantoms for instrument characterization and calibration.

Characterization of thin poly(dimethylsiloxane)-based tissue-simulating phantoms with tunable reduced scattering and absorption coefficients at visible and near-infrared wavelengths.

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.

Note: A simple broad bandwidth undersampling frequency-domain digital diffuse optical spectroscopy system.

Near-Infrared frequency-domain technologies, such as Diffuse Optical Spectroscopy (DOS), have demonstrated growing potential in a number of clinical applications. The broader dissemination of this technology is limited by the complexity and cost of instrumentation. We present here a simple system constructed with off-the-shelf components that utilizes undersampling for digital frequency-domain dDOS measurements. Broadband RF sweeps (50-300 MHz) were digitally sampled at 25 MSPS; amplitude, phase, and optical property extractions were within 5% of network analyzer derived values. The use of undersampling for broad bandwidth dDOS provides a significant reduction in complexity, power consumption, and cost compared with high-speed ADCs and analog techniques.