This PDF file contains the front matter associated with SPIE Proceedings Volume 10486 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

We report a novel yet simple 3D-printed tubing holder for characterizing photoacoustic contrast agents. This device supports up to 12 plastic tubing with sample-to-sample spacing as low as 0.3 mm and provides a consistent distance (± 0.12 mm) between the tubing and the transducer, which is critical for validating photoacoustic contrast agents. An immersion media containing both 40% India ink and lipid that mimics tissue scattered the incident irradiation. We further studied different types of tubing and distance between tubing and transducer. Statistical analysis shows that tubing with a larger outside diameter has more inherent signal, and the signal decayed following a linear relationship (R2=0.997) with respect to distance from the laser focal point. We finally provide a computer-assisted drafting code for the community to customize and print their own phantoms.

One of the challenges in high-resolution in vivo lipid-based photoacoustic tomography (PAT) is improving penetration depth and signal-to-noise ratio (SNR) past subcutaneous fat absorbers. A potential solution is to create optical manipulation techniques to maximize the photon density within a region of interest. Here, we present a motorized PAT probe that is capable of tuning the depth in which light is focused, as well as substantially reducing probe-skin artifacts that can obscure image interpretation. Our PAT system consists of a Nd:YAG laser (Surelite EX, Continuum) coupled with a 40 MHz central frequency ultrasound transducer (Vevo2100, FUJIFILM Visual Sonics). This system allows us to deliver 10 Hz, 5 ns light pulses with fluence of 40 mJ/cm² to the tissue interest and reconstruct PAT and ultrasound images with axial resolutions of 125 µm and 40 µm, respectively. The motorized PAT holder was validated by imaging a polyethylene-50 tubing embedded polyvinyl alcohol phantom and periaortic fat on apolipoprotein-E deficient mice. We used 1210 nm light for this study, as this wavelength generates PAT signal for both lipids and polyethylene-50 tubes. Ex vivo results showed a 2 mm improvement in penetration depth and in vivo experiments showed an increase in lipid SNR of at least 62%. Our PAT probe also utilizes a 7 μm aluminum filter to prevent in vivo probe-skin reflection artifacts that have been previously resolved using image post-processing techniques. Using this optimized PAT probe, we can direct light to various depths within tissue to improve image quality and prevent reflection artifacts.

The unique viscoelastic properties of tissues throughout the human body can be utilized in a variety of clinical applications. Palpation techniques, for instance, enable surgeons to distinguish malignancies in tissue composition during surgical procedures. Additionally, imaging devices have begun utilizing the viscoelastic properties of tissue to delineate tumor margins. Vibroacoustography (VA), a non-invasive, high resolution imaging modality, has the ability to detect sub-millimeter differences in tissue composition. VA images tissue using a low frequency acoustic radiation force, which perturbs the target and causes an acoustic response that is dependent on the target’s viscoelastic properties. Given the unique properties specific to human and animal tissues, there are far-reaching clinical applications of VA. To date, however, a comprehensive model that relates viscoelasticity to VA tissue response has yet to be developed. Utilizing tissue-mimicking phantoms (TMPs) and fresh ex vivo tissues, a mechanical stress relaxation model was developed to compare the viscoelastic properties of known and unknown specimens. This approach was conducted using the Hertz theory of contact mechanics. Fresh hepatic tissue was obtained from porcine subjects (n=10), while gelatin and agar TMPs (n=12) were fabricated from organic extracts. Each specimen’s elastic modulus (E), long term shear modulus (η), and time constant (τ) were found to be unique. Additionally, each specimen’s stress relaxation profiles were analyzed using Weichert-Maxwell viscoelastic modeling, and retained high precision (R²>0.9) among all samples.

Near-infrared fluorescence (NIRF) angiography has been applied for intraoperative visualization of neurovascular circulation and pathologies such as aneurysms, as well as to enhance contrast in clinical imaging of retinal fundus microvasculature. The ability to quantitatively evaluate and compare the performance of NIRF imaging devices including contrast, resolution and linearity under biologically realistic, yet reproducible conditions would facilitate innovation and clinical translation of this technology. Towards development of methods that can fill this role, we have generated 3D-printed, image-defined tissue simulating phantoms at macro and micro scales. The macro-scale phantom was developed based on an MRI image volume of a human head. This map was segmented into white matter, gray matter and vessel regions and edited to provide a suitable file for 3D printing. The phantom was then printed with an Objet260 Connex3 printer using a material with a biologically relevant NIR scattering coefficient. The micro-scale phantom is based on a fundus camera image of a human retina. This phantom was printed using a Nanoscribe Photonic Professional GT printer with sub-micron resolution, but a maximum print volume of approximately 1 mm3. To demonstrate the neurovascular phantoms for NIRF imaging system, channels were injected with a solution of hemoglobin and Indocyanine Green and then imaged with CCD-based macro- and micro- NIRF imaging system. Overall, these approaches for fabricating biomimetic phantoms hold significant promise for evaluation of NIRF angiography devices image quality in a standardized, yet realistic manner.

Fluorescence measurements are a staple in biomedicine, from research and discovery to more recently, for fluorescenceguided imaging systems for diagnostics and surgery. Measurement validation for clinical imagers is a challenge as it is applied to many different optical systems and probe through matrices with different optical properties in a demanding field environment. In this paper we will present approaches to fluorescence calibration for a field system, in comparison to those used in laboratory instruments for cell measurements or benchtop fluorometers. We will present the common challenges and differences, and lessons from the standardization effort of laboratory fluorescence measurements. We will discuss the conceptually different pathways to measurement traceability, between counting moles of substance and measuring light.

Diffuse correlation spectroscopy (DCS) has a potential to noninvasively and quantitatively measure the blood flow in the exercising muscle that could contribute to the fields of sports physiology and medicine. However, the blood flow index (BFI) measured from skin surface by DCS reflects hemodynamic signals from both superficial tissue and muscle layer. Thus, an appropriate calibration technology is required to quantify the absolute blood flow in the muscle layer. We therefore fabricated a realistic two-layer phantom model consisted of a static silicon layer imitating superficial tissue and a dynamic flow layer imitating the muscle blood flow and investigated the relationship between the simulated blood flow rate in the muscle layer and the BFI measured from the surface of the phantom. The absorption coefficient and the reduced scattering coefficient of the forearm were measured from 25 healthy young adults using a time-resolved nearinfrared spectroscopy. The depths of the superficial and muscle layers of forearm were also determined by ultrasound tomography images from 25 healthy young adults. The phantoms were fabricated to satisfy these optical coefficients and anatomical constraints. The simulated blood flow rate were set from 0 mL/ min to 68.7 mL/ min in ten steps, which is considered to cover a physiological range of mean blood flow of the forearm between per 100g of muscle tissue at rest to heavy dynamic handgrip exercise. We found a proportional relationship between the flow rates and BFIs with significant correlation coefficient of R = 0.986. Our results suggest that the absolute exercising muscle blood flow could be estimated by DCS with optimal calibration using phantom models.

Laser-based diagnostics and therapeutics show promise for many neurological disorders. However, the poor transparency of cranial bone limits the spatial resolution and interaction depth that can be achieved. We addressed this limitation previously, by introducing a novel cranial prosthesis made of a transparent nanocrystalline yttria-stabilized zirconia (nc-YSZ) which aims to enhance the diagnosis and treatment of neurological diseases by providing chronic optical access to the brain. By using optical coherence tomography, we have demonstrated the initial feasibility of ncYSZ implants for cortical imaging in an acute murine model. Although zirconia-based implants have been known for their excellent mechanical properties, the in vivo application was found to be affected by long-term failures, due to low temperature degradation. Accelerated aging simulations in humid environments at slightly elevated temperatures and over long periods typically transforms the ceramic surface into a monoclinic structure through a stress-corrosion-type mechanism. It was expected that the new nc-YSZ would show sufficient resistance to humid environments in comparison to the conventional zirconia implant. However, even a modest amount of transformation can change optical characteristics such as transparency. Herein we present the results of a simulated ageing study following the guidelines from the ISO 13356:2008 on aging of surgical zirconia ceramics. Comparison of %monoclinic transformation, optical transparency and mechanical hardness of nc-YSZ samples at baseline and following 25 and 100 h hydrothermal treatments shows our implant can withstand these extended ageing treatments.

Toxicology of the male reproductive system has received increased interest in recent years partly fueled by the growing reports of falling sperm counts and rising reproductive disorders in the human population. Testicular toxicity (TT) in pharmaceutical development is a challenging issue due to the lack of simple and robust screening methods. Currently, histopathologic examination and hormonal evaluation are the commonly used methods to assess TT. Improved biomarker or screening platforms that would allow identification of TT at an earlier stage can have a significant impact on the safety evaluation of pharmaceutical candidates. We investigated the potential of label-free optical nonlinear imaging technologies such as fluorescence lifetime imaging microscopy (FLIM), multi-photon microscopy (MPM) and coherent anti-Stokes Raman scattering (CARS) microscopy to identify novel biomarkers for effective detection of TT. In this study, testicular damage was induced in rats by intraperitoneal injection with 3 mg/kg cisplatin, a chemotherapy drug. Multimodal optical images were obtained from the fixed, unstained testicular tissue sections of untreated and treated rats using a custom-built near-infrared multiphoton imaging system. Structural and biochemical parameters extracted from these images were compared between both groups to identify abnormal features associated with TT in the treated group. By analyzing the complimentary information obtained using these label-free optical imaging technologies, it may be possible to develop a novel platform for evaluation of TT in safety assessment of pharmaceuticals on reproduction and fertility, which reveal these changes at the molecular level and allow observation of these changes at an earlier time point than available today.

Soft contact lens materials are fabricated from polymers that have a relatively lower material rigidity. The flexible soft contact lens materials could reshape itself and deform to a different lens shape after placing on a rigid surface. Besides its flexibility, typically, lens material (such as hydrogel) contains water. The deformed lens shape along with posterior lens liquid films and lens liquid evaporation could further modify its in air optical performances. Thus, it is important to quantitatively study the soft material wavefront aberration correction properties directly in air. In this study, contact lenses were covered on a hard plastic phantom which has a similar surface curvature as the lens posterior surface. Appropriate lens hydration was maintained to minimize evaporation introduced surface deformation. A Shack-Hartmann wavefront measurement system was installed to measure lens-phantom system wavefront aberration in air. Transmission wavefront aberrations with and without covering spherical lenses (on phantom) were measured and the wavefront aberration difference were compared with labeled lens power. For a 0.5D negative lens, measured lens power is -0.53±0.07D and within 4-mm pupil size, higher order aberration RMS is 0.08 µm. Other lens power was also measured with an averaged power error less than 7%. The results indicate the measurement introduces minimized lens surface deformations (due to liquid evaporation) and has precise measurement repeatability. The technology offers a metrology to be potentially used to study lens deformations on different surface curvatures, which potentially provides a guidance for lens on-eye fitting performance investigation.

Human vocal fold vibration is a complex 3D movement, and its frequency varies from 85-150 Hz (typical males) to 165-250 Hz (typical females). The unusual 3D shape of vocal folds is a hallmark for a variety of vocal diseases, such as polyps, nodules, recurrent nerve paralysis, and cancer. The standard in-office methods for diagnosing voice disorders encompass videostroboscopy and high-speed videoendoscopy. Both techniques image only the horizontal movement of vocal folds. They cannot measure the absolute vibrational movement of vocal folds along the air flow direction. Despite the vital importance, currently, very few methods are available for 3D laryngeal imaging. To overcome above limitation, we introduce the paradigm of light field imaging into laryngoscopy. The resultant method, which we term light field laryngoscopy (LFL), will enable 3D imaging of vocal folds in a single camera exposure. Moreover, to alleviate the trade-off between the spatial- and depth-resolution in light field imaging, we developed a hybrid imaging scheme which comprises an additional camera to provide a high-resolution 2D reference. Herein we will present the optical design of LFL, and characterize the imaging performance of the prototype.

With tissue samples less than 1 mm in thickness, optical projection tomography (OPT) has proven to be a very powerful imaging modality that can achieve high spatial resolution images. This high resolution is achieved by collecting the photons with non-significant scattering through 1 mm of tissue, the so-called diffusion limit. But, with samples thicker than 1 mm, scattered photons dominate and the highly resolved images give way to significantly “blurred” images in OPT[1]. However, as increased scattering relates to increased time of travel of the photons so time-domain OPT has been used to only collect the early-arriving photons that have travelled a more direct route through the tissue to reduce detection of scattered photons. Yet very early photons are extremely rare compared to scattered photons. Our recent suggested early photon count rates can be significantly enhanced by running the detector in a “deadtime” regime where the deadtime incurred by early-arriving photons acts as a shutter to later-arriving scattered photons[2]. In this work, we will demonstrate that running in the deadtime also had the unexpected advantage of significantly reducing the number of background photons detected. Proposed approach increases the early photon detection rate by 3-orders-of-magnitude in comparison with conventional approaches in 4-mm thick tissues with 780 nm light while the laser power is far below the level that would significantly damage the tissue. In addition, the signal to background (caused by after pulsing) was improved by 70-fold compared to conventional approaches designed to collect an equal number of early photons.

Hyperspectral Imaging (HSI) is a growing field in tissue optics due to its ability to collect continuous spectral features of a sample without a contact probe. Spatial Frequency Domain Imaging (SFDI) is a non-contact wide-field spectral imaging technique that is used to quantitatively characterize tissue structure and chromophore concentration. In this study, we designed a Hyperspectral SFDI (H-SFDI) instrument which integrated a supercontinuum laser source to a wavelength tuning optical configuration and a sCMOS camera to extract spatial (Field of View: 2cm×2cm) and broadband spectral features (580nm-950nm). A preliminary experiment was also performed to integrate the hyperspectral projection unit to a compressed single pixel camera and Light Labeling (LiLa) technique.

Multispectral imaging (MSI) could be useful for many applications in surgery, including tumor detection and perfusion monitoring. Acquisition of many bands however leads to long imaging times and/or low resolution, hampering widespread adoption of the technique. To overcome this issue, current research focusses on reducing the number of recorded bands. Yet, the methods proposed are not able to consider both the target domain (e.g. liver surgery) and the specific task (e.g. oxygenation or blood volume fraction monitoring) when selecting bands. In this work we present the first approach to domain and task specific band selection. Our method relies on highly generic Monte Carlo-based tissue simulations that aim to capture a large range of optical tissue parameters potentially observed during surgical interventions. The adaptation of the model to a specific clinical application is based on label-free in vivo hyperspectral recordings using a recently published approach to multispectral domain adaptation. The bands are selected based on their performance to estimate a task-dependent physiological parameter. This performance is evaluated on the adapted simulations, which come with ground truth values. According to in vivo experiments with hyperspectral recordings of tumors in a mouse model, a small subset of bands is enough for accurate oxygenation and blood volume fraction estimation. Compared to state-of-the-art baseline methods, bands selected by our method show more accurate results in oxygenation estimation. Our work could thus help remove one of the last barriers for interventional usage of MSI.

Hyperspectral fluorescence microscopy requires light sources with a number of excitation wavelength bands from deep UV to visible range to excite native fluorophores of cells and tissues. Achieving adequate optical power and wavelength range in the UV is difficult because the excitation light must be channelled to the sample through the microscope which results in power loss. We report the design of a light source for fluorescence microscopy which can combine the optical power available from multiple LEDs with the same wavelength range. The light source has the shape of a truncated cone with the exit aperture size of 9 mm which is equivalent to the aperture of a conventional mercury lamp used for fluorescence excitation. We used aluminium reflective coating for all inner surfaces of the cone with 92% reflectivity. We analysed its performance by using a ray tracing software; the efficiency of this light source found to be optimised for the diameter to length ratio of unity, and it was the highest for the smallest size (25mm). Variations of the cone’s efficiency with the positions of LEDs, inter-LED distance, and the angle of LED were determined. The efficiency of the cone depends upon the inner surface area of cone’s lid and slanting sides, and decreases with increasing area. The optimised source has the efficiency of around 28% for 60 mm diameter and length. This efficient design for multi-LEDs illumination is applicable to hyperspectral microscopy and it can be used with any other fluorescence microscopy as a retrofit.

Modern instruments for molecular diagnostics are continuously optimized for diagnostic accuracy, versatility and throughput. The latest progress in LED technology together with tailored optics solutions allows developing highly efficient photonics engines perfectly adapted to the sample under test. Super-bright chip-on-board LED light sources are a key component for such instruments providing maximum luminous intensities in a multitude of narrow spectral bands. In particular the combination of white LEDs with other narrow band LEDs allows achieving optimum efficiency outperforming traditional Xenon light sources in terms of energy consumption, heat dissipation in the system, and switching time between spectral channels. Maximum sensitivity of the diagnostic system can only be achieved with an optimized optics system for the illumination and imaging of the sample. The illumination beam path must be designed for optimum homogeneity across the field while precisely limiting the angular distribution of the excitation light. This is a necessity for avoiding spill-over to the detection beam path and guaranteeing the efficiency of the spectral filtering. The imaging optics must combine high spatial resolution, high light collection efficiency and optimized suppression of excitation light for good signal-to-noise ratio. In order to achieve minimum cross-talk between individual wells in the sample, the optics design must also consider the generation of stray light and the formation of ghost images. We discuss what parameters and limitations have to be considered in an integrated system design approach covering the full path from the light source to the detector.

The prevalence of major ophthalmic disorders such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy are also expected to increase as the elderly populations of Europe, China and the U.S. grow, fueling new demand for improved diagnostic and surgical systems to help physicians manage and treat these diseases. Optical coherence tomography (OCT) devices currently represent the gold standard for ophthalmic diagnostics, providing high-resolution imaging and proven clinical benefit in improving the patient’s quality of life. Despite the success of OCT, however, the full potential of this imaging modality has yet to be realized. While other imaging methods such as MRI and PET have been revolutionized with the development of functional imaging (e.g. fMRI), functional OCT remains an emerging technology. Visible-light OCT (Vis-OCT) represents a cutting-edge functional OCT imaging technique that aims to dramatically improve the diagnostic capabilities and clinical benefit of OCT in ophthalmology. Vis-OCT is currently the only OCT technology capable of combining both high-resolution structural imaging (~ 1 µm) with precise measurements of metabolic activity, such as retinal oxygen saturation and retinal blood flow. Using dual band scanning with visible light and NIR light wavelengths, Vis-OCT represents a next generation functional OCT tool with the potential to fundamentally change how ophthalmologist use OCT in the diagnosis, treatment and monitoring of numerous major ocular disorders.

In optical coherence tomography (OCT) systems, axial resolution improves with increasing light source bandwidth. However, dispersion imbalance between the sample and reference arms can degrade axial resolution and signal to noise ratio, a significant issue for ultrahigh-resolution OCT systems. In this work, we demonstrate a novel technique for estimating and compensating for OCT system dispersion, that is unique from previously reported methods in that it compensates all orders of system dispersion. Dispersion phase was estimated by first measuring the phase from of the spectrogram at two different, reference-sample arm optical path length differences (OPLD) around zero OPLD and then subtracting the two phase values to obtain the dispersion phase. This phase can be used to compensate the dispersion term in the spectrum by multiplying the interference pattern with where k is the wave-vector. This method was tested to compensate the dispersion caused by a 3-mm fused silica window in one arm of an ultrahigh spectral domain OCT system in our laboratory that utilizes a light source with a 850 nm center wavelength, 300 nm bandwidth. Using our dispersion compensation technique, the experimentally measured axial resolution of the system was fully recovered to match the theoretical resolution, improving from 10.6µm to 1.85µm in air. These results suggest that this dispersion compensation method may be useful to avoid axial resolution degradation due to dispersion effects in ultrahigh-resolution OCT systems that employ extremely broad band light sources.

Supercontinuum (SC) sources are of great interest for many applications due to their ultra-broad optical bandwidth, good beam quality and high power spectral density [1]. In particular, the high average power over large bandwidths makes SC light sources excellent candidates for ultra-high resolution optical coherence tomography (UHR-OCT) [2-5]. However, conventional SC sources suffer from high pulse-to-pulse intensity fluctuations as a result of the noise-sensitive nonlinear effects involved in the SC generation process [6-9]. This intensity noise from the SC source can limit the performance of OCT, resulting in a reduced signal-to-noise ratio (SNR) [10-12]. Much work has been done to reduce the noise of the SC sources for instance with fiber tapers [7,8] or increasing the repetition rate of the pump laser for averaging in the spectrometer [10,12]. An alternative approach is to use all-normal dispersion (ANDi) fibers [13,14] to generate SC light from well-known coherent nonlinear processes [15-17]. In fact, reduction of SC noise using ANDi fibers compared to anomalous dispersion SC pumped by sub-picosecond pulses has been recently demonstrated [18], but a cladding mode was used to stabilize the ANDi SC. In this work, we characterize the noise performance of a femtosecond pumped ANDi based SC and a commercial SC source in an UHR-OCT system at 1300 nm. We show that the ANDi based SC presents exceptional noise properties compared to a commercial source. An improvement of ~5 dB in SNR is measured in the UHR-OCT system, and the noise behavior resembles that of a superluminiscent diode. This preliminary study is a step forward towards development of an ultra-low noise SC source at 1300 nm for ultra-high resolution OCT.

Optical coherence tomography (OCT) has been widely used in clinic studies due to the capability to provide high resolution cross sectional images in biological tissue. To achieve real-time imaging display, Graphics Processing Unit (GPU) acceleration is usually used in data processing including Fast Fourier Transform, linearization in k space, and logarithm scaling, however, with additional cost and requirement of complex coding tools such as CUDA. In this paper，a hash table method is used to accelerate the computing speed of logarithm scaling without GPU. For original logarithm scaling in C library, the procession time for an A-line with 2048 points is approximately 10 times longer than this optimized method. A swept source OCT was employed to test this method and the results demonstrated that a high speed real-time OCT imaging display can be achieved with this low cost method.

Intraocular injections are routinely performed for delivery of anti-VEGF and anti-inflammatory therapies in humans. While these injections are also performed in mice to develop novel models of ophthalmic diseases and screen novel therapeutics, the injection location and volume are not well-controlled and reproducible. We overcome limitations of conventional injections methods by developing a multimodality, long working distance, non-contact optical coherence tomography (OCT) and fluorescence confocal scanning laser ophthalmoscopy (cSLO) system for retinal imaging before and after injections. Our OCT+cSLO system combines a custom-built spectraldomain OCT engine (875±85 nm) with 125 kHz line-rate with a modified commercial cSLO with a maximum frame-rate of 30 fps (512 x 512 pix.). The system was designed for an overlapping OCT+cSLO field-of-view of 1.1 mm with a 7.76 mm working distance to the pupil. cSLO excitation light sources and filters were optimized for simultaneous GFP and tdTomato imaging. Lateral resolution was 3.02 µm for OCT and 2.74 μm for cSLO. Intravitreal injections of 5%, 10%, and 20% intralipid with Alex Fluor 488 were manually injected intraocularly in C57BL/6 mice. Post-injection imaging showed structural changes associated with retinal puncture, including the injection track, a retinal elevation, and detachment of the posterior hyaloid. OCT enables quantitative analysis of injection location and volumes whereas complementary cSLO improves specificity for identifying fluorescently labeled injected compounds and transgenic cells. The long working distance of our non-contact OCT+cSLO system is uniquely-suited for concurrent imaging with intraocular injections and may be applied for imaging of ophthalmic surgical dynamics and real-time image-guided injections.

Clinical cerebral oximeters based on near-infrared spectroscopy (NIRS) are a commonly used, non-invasive tool for intraoperative monitoring of hemoglobin saturation. Research to verify performance of cerebral oximeters in human subject trials has shown differences between commercially available devices. Test methods based on tissue-simulating phantoms have been proposed to augment clinical findings. While prior studies have focused on liquid phantoms, this work is aimed at developing methods based on solid polymer phantoms that are stable. Specifically, we have designed and fabricated a neonatal/pediatric head mimicking layered phantoms based on a 3D-printed cerebral matrix incorporating an array of vessel-simulating linear channels. Superficial layers incorporating homogeneous molded polydimethylsiloxane (PDMS) slabs were fabricated to represent CSF, scalp and skull regions. The cerebral matrix was filled with bovine blood desaturated with sodium dithionite to achieve oxygenation levels across the 40-90% range. Measurements were performed with a commercially available cerebral oximeter using two probes with different illumination-collection geometries, as designed for neonatal and pediatric patients. Reference measurements of samples were performed with a CO-oximeter before injection and after extraction. Results from applied cerebral oximeters indicate a strong sensitivity to the thickness of the superficial layer of the phantom. Better correlation with the reference CO-oximeter results were obtained in the superficial layer thickness of 0.8-2.5 mm range. Channel array phantoms with modular superficial layers represent a promising approach for performance testing of NIRS-based cerebral oximeters.

The ability to gather physiological parameters such as heart rate (HR) and oxygen saturation (SpO2%) during physical movement allows to continuously monitor personal health status without disrupt their normal daily activities. Photoplethysmography (PPG) based pulse oximetry and similar principle devices are unable to extract the HR and SpO2% reliably during physical movement due to interference in the signals that arise from motion artefacts (MAs). In this research, a flexible reflectance multi-wavelength optoelectronic patch sensor (OEPS) has been developed to overcome the susceptibility of conventional pulse oximetry readings to MAs. The OEPS incorporates light embittered diodes as illumination sources with four different wavelengths, e.g. green, orange, red, and infrared unlike the conventional pulse oximetry devices that normally measure the skin absorption of only two wavelengths (red and infrared). The additional green and orange wavelengths were found to be distinguish to the absorption of deoxyhemoglobin (RHb) and oxyhemoglobin (HbO2). The reliability of extracting physiological parameters from the green and orange wavelengths is due to absorbed near to the surface of the skin, thereby shortening the optical path and so effectively reducing the influence of physical movements. To compensate of MAs, a three-axis accelerometer was used as a reference with help of adaptive filter to reduce MAs. The experiments were performed using 15 healthy subjects aged 20 to 30. The primary results show that there are no significant difference of heart rate and oxygen saturation measurements between commercial devices and OEPS Green (r=0.992), Orange(r=0.984), Red(r=0.952) and IR(r=0.97) and SpO2% (r = 0.982, p = 0.894).

Tissue oxygen saturation (StO₂) is a valuable clinical parameter e.g. for intensive care applications or monitoring during surgery. Studies showed that near-infrared spectroscopy (NIRS) based tissue oximeters of different brands give systematically different readings of StO₂. Usually these readings are linearly correlated and therefore StO₂ readings from one instrument can easily be converted to those of another instrument. However, it is interesting to understand why there is this difference. One reason may be that different brands employ different spectra of hemoglobin. The aim here was to investigate how these different absorption spectra of hemoglobin affect the StO₂ readings. Therefore, we performed changes in StO₂ in a phantom experiment with real human hemoglobin at three different concentrations (26.5, 45 and 70 μM): desaturation by yeast consuming the oxygen and re-saturation by bubbling oxygen gas. The partial pressure of O₂ in the liquid changed from at least 10 kPa to ~0 kPa and ISS OxiplexTS, a frequency-domain NIRS instrument, was used to monitor changes of StO₂. When we employed two different absorption spectra for hemoglobin, StO₂ values were comparable in the normal physiological range. However, particularly at high and low StO₂ values, a difference of >6% between these two spectra were noticed. Such a difference of >6% is substantial and relevant for medical applications. This may partly explain why different brands of NIRS instruments provide different StO₂ readings. The hemoglobin spectra are therefore a factor to be considered for future developments and applications of NIRS oximeters.

It is known that wide-field fundus photography is essential for screening, diagnosis and treatment evaluation of eye diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinopathy of premature (ROP), etc. However, the high equipment cost of existing devices is a limiting factor for clinical deployment of wide-field fundus photography, particularly in rural and underserved areas where both expensive instruments and skilled operators are not available. Low-cost smartphone fundus cameras promise convenient assessment of eye diseases at point-of-care environments, and may also enable affordable telemedicine screening to foster the access to medical cares in rural and underserved areas. However, practical application of existing smartphone fundus cameras is limited by the small field of view (FOV) in single-shot images. We have recently demonstrated the feasibility of trans-pars-planar illumination, i.e., delivering illuminating light through pars plana outside of the pupil. By freeing the whole pupil for image purpose only, the trans-pars-planar illumination provides one unique opportunity to develop snapshot, low-cost, but high-quality wide-field fundus camera. Using all off-the-shelf parts, a smartphone-based prototype fundus camera was constructed to achieve a 152-degree FOV in single-shot images, without the need for pharmacological pupil dilation. Moreover, we have also explored miniaturized indirect ophthalmoscopy to achieve wide-field fundus video photography. A totally wireless smartphone fundus camera was constructed, with a whole weight of 255 g. This device allowed both snapshot fundus photography and continuous video recording.

Oral cancer is a rising health issue in many low and middle income countries (LMIC). Proposed is an implementation of autofluorescence imaging (AFI) and white light imaging (WLI) on a smartphone platform providing inexpensive early detection of cancerous conditions in the oral cavity. Interchangeable modules allow both whole mouth imaging for an overview of the patients’ oral health and an intraoral imaging probe for localized information. Custom electronics synchronize image capture and external LED operation for the excitation of tissue fluorescence. A custom Android application captures images and an image processing algorithm provides likelihood estimates of cancerous conditions. Finally, all data can be uploaded to a cloud server where a convolutional neural network classifies the images and a remote specialist can provide diagnosis and triage instructions.

Mobile dark-field microscope image analysis for biomolecule quantification is feasible upon mating an LED light source, a dark-field condenser and a 20× objective lens to a mobile phone camera. This system can achieve performance analogous to that of a standard dark-field microscope, allowing the use of stable, nanoparticle-based quantitation assays in resource-limited areas where standard assay approaches are not practical.

Smartphone optosensors with integrated optical components make mobile point-of-care (MPoC) diagnostics be done near patients’ side. It’ll especially have a significant impact on healthcare delivery in rural or remote areas. Current FDA-approved PoC devices achieving clinical level are still at high cost and not affordable in rural hospitals. We present a series of ultra low-cost smartphone optical sensing devices for mobile point-of-care diagnosis. Aiming different targeting analytes and sensing mechanisms, we developed custom required optical components for each smartphone optosensros. These optical devices include spectrum readers, colorimetric readers for microplate, lateral flow device readers, and chemiluminescence readers. By integrating our unique designed optical components into smartphone optosening platform, the anlaytes can be precisely detected. Clinical testing results show the clinical usability of our smartphone optosensors. Ultra low-cost portable smartphone optosensors are affordable for rural/remote doctors.

Smartphones are currently used in many medical applications and are more frequently being integrated into medical imaging devices. The regulatory requirements in existence today however, particularly the standardization of smartphone imaging through validation and verification testing, only partially cover imaging characteristics with a smartphone. Specifically, it has been shown that smartphone camera specifications are of sufficient quality for medical imaging, and there are devices which comply with the FDA’s regulatory requirements for a medical device such as a device’s field of view, direction of viewing and optical resolution and optical distortion. However, these regulatory requirements do not call specifically for color testing. Images of the same object using automatic settings or different light sources can show different color composition. Experimental results showing such differences are presented. Under some circumstances, such differences in color composition could potentially lead to incorrect diagnoses. It is therefore critical to control the smartphone camera and illumination parameters properly. This paper examines different smartphone camera settings that affect image quality and color composition. To test and select the correct settings, a test methodology is proposed. It aims at evaluating and testing image color correctness and white balance settings for mobile phones and LED light sources. Emphasis is placed on color consistency and deviation from gray values, specifically by evaluating the ΔC values based on the CIEL*a*b* color space. Results show that such standardization minimizes differences in color composition and thus could reduce the risk of a wrong diagnosis.

Pharmacokinetic diffuse fluorescence tomography (DFT) can describe the metabolic processes of fluorescent agents in biomedical tissue and provide helpful information for tumor differentiation. In this paper, a dynamic DFT system was developed by employing digital lock-in-photon-counting with square wave modulation, which predominates in ultra-high sensitivity and measurement parallelism. In this system, 16 frequency-encoded laser diodes (LDs) driven by self-designed light source system were distributed evenly in the imaging plane and irradiated simultaneously. Meanwhile, 16 detection fibers collected emission light in parallel by the digital lock-in-photon-counting module. The fundamental performances of the proposed system were assessed with phantom experiments in terms of stability, linearity, anti-crosstalk as well as images reconstruction. The results validated the availability of the proposed dynamic DFT system.

In this study, the Carelight multi-wavelength opto-electronic patch sensor (OEPS) was adopted to assess the effectiveness of a new approach for estimating the systolic blood pressure (SBP) through the changes in the morphology of the OEPS signal. Specifically, the SBP was estimated by changing the pressure exerted on an inflatable cuff placed around the left upper arm. Pressure acquisitions were performed both with gold standard (i.e. electronic sphygmomanometer), and Carelight sensor (experimental procedure), on subjects from a multiethnic cohort (aged 28 ± 7). The OEPS sensor was applied together with a manual inflatable cuff, going slightly above the level of the SBP with increases of +10mmHg and subsequently deflated by 10mmHg until reaching full deflation. The OEPS signals were captured using four wavelength illumination sources (i.e., green 525 nm, orange 595 nm, red 650 nm and IR 870 nm) on three different measuring sites, namely forefinger, radial artery and wrist. The implemented algorithm provides information on the instant when the SBP was reached and the signal is lost since the vessel is completely blocked. Similarly, it detected the signal resumption when the external pressure dropped below the SBP. The findings demonstrated a good correlation between the variation of the pressure and the corresponding OEPS signal with the most accurate result achieved in the fingertip among all wavelengths, with a temporal identification error of 8.07 %. Further studies will improve the clinical relevance on a cohort of patients diagnosed with hyper- or hypotension, in order to develop a wearable blood-pressure device.

In tissue optics, it is important to measure the wavelength-dependent scattering, absorption and anisotropy coefficients of tissues to describe interactions of light with such turbid media. Here, we use the inverse adding-doubling (IAD) technique coupled to measurements acquired using an integrating sphere (IS). The IS system provides a method to acquire highly accurate measurements for the total reflectance and transmittance for thin turbid samples. The IAD is an iterative technique that uses a numerical solver to radiative transport capable of fitting a set of measured reflectance and transmittance values and thereby yield optical absorption and reduced scattering coefficients of thin samples. We test the validity and performance of the IS/IAD system by obtaining measurements on a set of liquid phantoms prepared with controlled absorption and scattering properties. We explore sources of errors and discuss how the the accuracy these techniques may be improved. We demonstrate that the IAD/IS technique allows the accurate recovery of chromophore spectral properties.

The continuous-wave Near-infrared spectroscopy (NIRS) devices have been highlighted for its clinical and health care applications in noninvasive hemodynamic measurements. The baseline shift of the deviation measurement attracts lots of attentions for its clinical importance. Nonetheless current published methods have low reliability or high variability. In this study, we found a perfect polynomial fitting function for baseline removal, using NIRS. Unlike previous studies on baseline correction for near-infrared spectroscopy evaluation of non-hemodynamic particles, we focused on baseline fitting and corresponding correction method for NIRS and found that the polynomial fitting function at 4th order is greater than the function at 2nd order reported in previous research. Through experimental tests of hemodynamic parameters of the solid phantom, we compared the fitting effect between the 4th order polynomial and the 2nd order polynomial, by recording and analyzing the R values and the SSE (the sum of squares due to error) values. The R values of the 4th order polynomial function fitting are all higher than 0.99, which are significantly higher than the corresponding ones of 2nd order, while the SSE values of the 4th order are significantly smaller than the corresponding ones of the 2nd order. By using the high-reliable and low-variable 4th order polynomial fitting function, we are able to remove the baseline online to obtain more accurate NIRS measurements.

A focused-scanning photoacoustic microscopy (PAM) is available to help advancing life science research in neuroscience, cell biology, and in vivo imaging. At this early stage, the only one manufacturer of PAM systems, MicroPhotoAcoustics (MPA; Ronkonkoma, NY), MPA has developed a commercial PAM system with switchable optical and acoustic resolution (OR- and AR-PAM), using multiple patents licensed from the lab of Lihong Wang, who pioneered photoacoustics. The system includes different excitation sources. Two kilohertz-tunable, Q-switched, Diode Pumped Solid-State (DPSS) lasers offering a up to 30kHz pulse repetition rate and 9 ns pulse duration with 532 and 559 nm to achieve functional photoacoustic tomography for sO₂ (oxygen saturation of hemoglobin) imaging in OR-PAM. A Ti:sapphire laser from 700 to 900 nm to achieve deep-tissue imaging. OR-PAM provides up to 1 mm penetration depth and 5 μm lateral resolution. while AR-PAM offers up to 3 mm imaging depth and 45 μm lateral resolution. The scanning step sizes for OR- and AR-PAM are 0.625 and 6.25 μm, respectively. Researchers have used the system for a range of applications, including preclinical neural imaging; imaging of cell nuclei in intestine, ear, and leg; and preclinical human imaging of finger cuticle. With the continuation of new technological advancements and discoveries, MPA plans to further advance PAM to achieve faster imaging speed, higher spatial resolution at deeper tissue layer, and address a broader range of biomedical applications.

A measurement system was developed to acquire and analyze subdiffusive spatially resolved reflectance using an optical fiber probe with short source-detector separations. Since subdiffusive reflectance significantly depends on the scattering phase function, the analysis of the acquired reflectance is based on a novel inverse Monte Carlo model that allows estimation of phase function related parameters in addition to the absorption and reduced scattering coefficients. In conjunction with our measurement system, the model allowed real-time estimation of optical properties, which we demonstrate for a case of dynamically induced changes in human skin by applying pressure with an optical fiber probe.