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.

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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.

Abstract. 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. © The Authors.Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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.

, "Ultrafast wavelength multiplexed broad bandwidth digital diffuse optical spectroscopy for in vivo extraction of tissue optical properties," J. Biomed. Opt. Abstract. 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. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Diffuse optical imaging (DOI) is a label-free, safe, inexpensive, and quantitative imaging modality that provides metabolic and molecular contrast in tissue using visible or near-infrared light. DOI modalities can image up to several centimeters deep in tissue, providing access to a wide range of human tissues and organ sites. DOI technologies have benefitted from several decades of academic research, which has provided a variety of platforms that prioritize imaging depth, resolution, field-of-view, spectral content, and other application-specific criteria. Until recently, however, acquisition and processing speeds have represented a stubborn barrier to further clinical exploration and implementation. Over the last several years, advances in high-speed data acquisition enabled by high-speed digital electronics, newly available sources and detectors, and innovative new scanning methods have led to major improvements in DOI rates. These advances are now being coupled with new data processing algorithms that utilize deep learning and other computationally efficient methods to provide rapid or real-time feedback in the clinic. Together, these improvements have the potential to help advance DOI technologies to the point where major impacts can be made in clinical care. Here, we review recent advances in acquisition and processing speed for several important DOI modalities.

, "Wearable near-infrared optical probe for continuous monitoring during breast cancer neoadjuvant chemotherapy infusions," J. Biomed. Opt. 22(1), 014001 (2017), doi: 10.1117/1.JBO.22.1.014001. Abstract. 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.