Low-cost slide scanners, in conjunction with remote reading and AI-powered diagnostic workflows, have been proposed to democratize digital slide scanning for histopathologic diagnosis. However, scan speed is limited because proposed systems scan only one slide at a time. We developed a high-speed, low-cost, multicamera slide scanning system using a 3d printer and a Raspberry Pi with 4 motorized focus cameras. Motorized focus results in an adjustable working distance, which allows for multi-camera fine-tuning of the focus plane without additional delay to adjust the z-position. By supporting parallel-acquisition of 4 cameras at once at a fixed z-position, scanning speed increases fourfold.
A compact, low-cost (<$150), wearable device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) was used to measure changes in blood flow in human subjects during a set of physiological challenges. One group (A) of subjects underwent arm occlusion followed by exercise (n=3) and a second group (B) of subjects underwent arm occlusion, cold stimulation, and exercise (n=4). Cold stimulation alone did not cause significant changes from baseline LSFI. The rate of increase of the LSFI signal over the 5-minute exercise period was 3 times larger in group A compared to group B. Although cold stimulation alone did not appear to cause vasoconstriction in the wrist, it did impact the rate at which perfusion increases during exercise. The low-cost device consistently monitored changes in hemodynamics in all subjects, including both increases and decreases in blood flow caused by occlusion and sympathetic nervous system stimulation.
Nonmelanoma skin cancer is the most common malignancy in the US, and while Mohs microsurgery is curative in the majority of cases, inaccurate presurgical visual estimation of tumor margins leads to the need for more than one stage in 30% of cases. Dual wavelength optical polarization imaging (OPI) provides accurate presurgical delineation of tumor margins, but existing OPI devices are not easily translated to the dermatology clinical setting. We found that the clinically ubiquitous dermatascope can be repurposed as a handheld OPI system that has functionality on par with existing OPI devices at a fraction of the cost.
Skin disease is primarily diagnosed visually, but this subjective approach can lead to misdiagnosis, particularly for darkly-pigmented patients where increased melanin leads to more subtle disease appearance. Inflammation is characterized by shifts in tissue fluid, and the short-wave infrared (SWIR 900-1700 nm) regime, where water absorbs strongly and melanin absorbs weakly, may therefore be a pigment-insensitive modality for assessing skin inflammation. We built a multispectral SWIR imaging system and tested its ability to detect tissue fluid after intradermal saline injection in 24 healthy subjects with diverse pigmentation. Saline injection regions had 20-50 times more contrast than unaffected skin in SWIR images compared to visible photography, regardless of the degree of pigmentation. SWIR multispectral imaging may offer a new window into assessing inflammatory skin diseases in a pigmentation-independent manner.
To combat the unmet need of early detection and monitoring of postpartum hemorrhage (PPH), the leading cause of maternal death, a wearable short-wave infrared (SWIR) photoplethysmography (PPG) sensor was developed for real-time detection and monitoring of hemodilution, a compensatory response to PPH. The device uses wavelengths at 900 and 1300nm, ideal for monitoring hemoglobin and water contributions in blood, respectively. These wavelengths minimally absorb melanin, which has been shown to bias PPG results in pulse oximetry. High signal-to-noise PPG signals have been acquired from both the 900nm and 1300nm channels in human volunteers. Further, the hemodilution sensing capabilities were tested by flowing sheep blood through a pulsatile flow phantom. The ratio of the peak amplitudes of the PPG waveforms from both LEDs showed a linear correlation, demonstrating feasibility to detect hemodilution and provide a low-cost, fully wireless, continuous monitoring tool for early diagnosis and monitoring of PPH.
Understanding pigmentation’s effect on pulse oximetry is critical amid evidence that pulse oximetry is less accurate for patients with pigmented skin. Optical phantoms can help validate oximeters, but commercial phantoms do not vary pigmentation. We develop a resin-based 3D printing method that generates mechanically flexible phantoms with tunable optical properties and <100 µm diameter channels. Using a reflectance-mode Maxim 86171 pulse oximeter, we evaluate how photoplethysmogram waveforms change as phantom pigmentation increases, and test an algorithm for estimating pigmentation from waveforms alone. 3D-printed phantoms can provide a platform for testing pulse oximeter performance across the spectrum of human pigmentation.
Pulse oximeters are widely used in healthcare systems to estimate blood oxygen saturation level (SpO2) using red and infrared light. Recent clinical and simulation studies reported that in darkly pigmented subjects oximeter over-estimates SpO2 which could lead to higher rates of occult hypoxemia in highly pigmented subjects. The probable solutions to solve this over-estimation bias could be modification of the current oximeter design, calibration enrollment or modification of oximeter ratio (R). In this study, a modification of the current oximeter ratio (R) was presented by using different combinations of currently estimated oximeter parameters. Simulation results showed that modified oximeter ratio reduces over-estimation bias in highly pigmented subjects compared to the conventional oximeter ratio. In the regions near hypoxemia threshold (90% oxygenation level), the over-estimation bias in the simulated test cohort could reduce from 1.36% to -0.01% if modified oximeter ratio is used. Results show that modification of oximeter ratio could be used in future to improve oximeter accuracy and produce pigmentation independent outcomes.
Women’s health problems ranging from pregnancy complications to cancer do not have sufficient physiologic understanding nor clinical interventions, resulting in poor outcomes. Light-based technologies can be specifically designed to gain new insights into women’s health. They can be used at the point of care, be non-contact and re-usable, provide objective and real-time results, generate label-free or exogenous molecular contrast, and have significantly lower costs than most non-optical modalities. Successful application of optical technologies for furthering our understanding of cervical change during pregnancy and improving breast cancer surgery outcomes and access will be presented.
We provide a framework for a wireless, low-cost, wearable laser speckle contrast imaging device for early detection of postpartum hemorrhage. The developed device was validated in vitro using optical flow phantoms and in vivo in a swine hemorrhage model.
Whispering Gallery Mode (WGM) microresonators are a class of optical sensors with the ability to trap and confine light under optical resonance conditions. Typically, this resonance is excited inside a WGM resonator using expensive and bulky tunable diode lasers, which can be a limiting factor in low-resource settings and in developing economies. In the manuscript, we describe a method of “reverse tuning” to modify the resonance conditions, paving the way for lower cost WGM excitation and ultimately lower cost sensing. We demonstrate three different methods of reverse tuning the WGM using temperature, pressure, and refractive index in a microbubble resonator (MBR), a subclass of WGM sensors that is particularly well-suited for reverse tuning using the three aforementioned methods. By reducing the cost of the MBR platform through reverse tuning, we can make these ultra-sensitive devices more practical and accessible in low-resource settings.
Fluorescence guided surgery has high potential for improved patient outcomes but often lacks quantification of fluorophore depth which is needed to determine surgical margins of solid tumors. To address this need, a dual wavelength excitation approach was applied that capitalizes on the wavelength-dependent attenuation of light in tissue to provide depth information independent of fluorophore concentration. A portable near infrared dual wavelength excitation fluorescence imaging system was built and tested using tissue mimicking phantoms and is currently being tested to determine breast tumor margin status in a first-in-human clinical trial investigating LS301, a novel near infrared tumor-targeted contrast agent.
Near infrared (NIR) in-vivo fluorescence imaging is a powerful modality capable of interrogating biological tissue in real time, at high spatial resolution, without the need for ionizing radiation, and at depths exceeding visible light imaging modalities.
Several fluorescence guided surgery (FGS) imaging systems have been developed, but their complexity and cost effectively excludes low resource settings from this technology. To help make NIR FGS available globally, we developed a fluorescence imaging augmented reality Raspberry Pi-based goggle system (FAR-Pi), open-source-hardware-inspired low cost, fully wearable, compact, and battery powered redesign of our previously described goggle-based FGS system.
WGM sensors are a class of optical sensors in which light is tightly confined due to optical resonance within a circular geometry. Expensive tunable diode lasers are typically used to excite resonance in a WGM device, which can be a cost limiting factor in developing economies. Herein, we developed a “reverse tuning” method that eliminates the need for such expensive laser sources. We show the microbubble resonator (MBR), a sub class of WGM devices, is ideally suited for the reverse tuning method by tuning with temperature, pressure and refractive index changes. Reducing the cost of the MBR platform, by utilizing less expensive laser sources with fixed wavelength, increases the practicality of these devices for use in low resource settings. We expect our methods to reduce the total cost of the sensing platform from thousands to a few hundred dollars.
This Conference Presentation, “Noninvasive quantification of cutaneous inflammation with hyperspectral short wave infrared imaging,” was recorded for the Photonics West 2021 Digital Forum.
KEYWORDS: Cancer, Tissues, Thermography, Tumor growth modeling, Thermal modeling, Tumors, 3D modeling, Thermal energy technology, Systems modeling, Real time imaging
Dynamic thermal imaging has improved bulk tissue characterization, but fails to capture subtle thermal property differences in heterogeneous systems. We present focal dynamic thermal imaging (FDTI), a simple, label-free, and high-resolution technology for delineating tissue heterogeneity. Stimulation of focal regions of absorptive materials with a narrow beam, low power, and low cost 405 nm laser locally perturbs the thermal equilibrium. Measurement of phantoms, ex vivo tissue, and in vivo animal models of cancer reveals finite structures of materials and delineates diseased from healthy tissue. Portable FDTI holds promise to capture the heterogeneous nature of malignant tissue.
Significance: Detection and characterization of circulating tumor cells (CTCs), a key determinant of metastasis, are critical for determining risk of disease progression, understanding metastatic pathways, and facilitating early clinical intervention.
Aim: We aim to demonstrate label-free imaging of suspected melanoma CTCs.
Approach: We use a linear-array-based photoacoustic tomography system (LA-PAT) to detect melanoma CTCs, quantify their contrast-to-noise ratios (CNRs), and measure their flow velocities in most of the superficial veins in humans.
Results: With LA-PAT, we successfully imaged suspected melanoma CTCs in patients in vivo, with a CNR >9. CTCs were detected in 3 of 16 patients with stage III or IV melanoma. Among the three CTC-positive patients, two had disease progression; among the 13 CTC-negative patients, 4 showed disease progression.
Conclusions: We suggest that LA-PAT can detect suspected melanoma CTCs in patients in vivo and has potential clinical applications for disease monitoring in melanoma.
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