Proceedings Volume 10056

Design and Quality for Biomedical Technologies X

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Proceedings Volume 10056

Design and Quality for Biomedical Technologies X

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Volume Details

Date Published: 12 April 2017
Contents: 8 Sessions, 27 Papers, 16 Presentations
Conference: SPIE BiOS 2017
Volume Number: 10056

Table of Contents

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Table of Contents

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  • Front Matter: Volume 10056
  • Phantoms I
  • 3D Printed Phantoms
  • Phantoms II
  • Quality of Biomedical Technologies
  • OCT System Development and Applications
  • Imaging Systems and Applications
  • Poster Session
Front Matter: Volume 10056
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Front Matter: Volume 10056
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Phantoms I
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Label-free hyperspectral dark-field microscopy for quantitative scatter imaging
A hyperspectral dark-field microscope has been developed for imaging spatially distributed diffuse reflectance spectra from light-scattering samples. In this report, quantitative scatter spectroscopy is demonstrated with a uniform scattering phantom, namely a solution of polystyrene microspheres. A Monte Carlo-based inverse model was used to calculate the reduced scattering coefficients of samples of different microsphere concentrations from wavelength-dependent backscattered signal measured by the dark-field microscope. The results are compared to the measurement results from a NIST double-integrating sphere system for validation. Ongoing efforts involve quantitative mapping of scattering and absorption coefficients in samples with spatially heterogeneous optical properties.
Polydimethylsiloxane tissue-mimicking phantoms for quantitative optical medical imaging standards
Jeeseong Hwang, Hyun-Jin Kim, Paul Lemaillet, et al.
We report on a procedure to build and characterize solid tissue-mimicking phantoms of polydimethylsiloxane (PDMS) polymers. Controlled inclusion of light scattering titanium dioxide (TiO2) nanoparticles enables the creation of phantoms having tunable light scattering properties with reduced scattering coefficients consistent across different measurement platforms including an integrating sphere and a time-resolved diffuse optical spectroscopic system. Backscatter confocal microscopy is also used to characterize the shape and distribution of included TiO2 particles. The double integrating sphere and time-resolved diffuse spectroscopy were used to measure the reduced scattering coefficients of the phantoms. The results across different systems are in good agreement, suggesting that the PDMS/TiO2 composite is a promising tissue-mimicking material for developing standards useful to validate measurements by different devices for multiplatform and multi-laboratory tests.
Broadband spectral measurements of diffuse optical properties by an integrating sphere instrument at the National Institute of Standards and Technology
Diffuse materials that approximate the optical properties of human tissue are commonly used as phantoms. In order to use the phantoms in a manner that provides consistent results relative to independent measurements, the optical properties need to be tied to a physics based scale. Such a scale is needed for volume scattering of diffuse materials and this is currently being addressed by the development of a sphere based optical scattering reference instrument at the National Institute of Standards and Technology (NIST). Previous work towards that goal was constrained to the use of several laser lines at discrete wavelengths. Current work has expanded the spectral range for contiguous coverage. Here we report measurement results of the optical properties of solid phantoms, using two different base materials, acquired using NISTs diffuse optical properties reference instrument with visible or near infrared broadband illumination. The measurements of diffuse hemispherical reflectance and transmittance are analyzed using a custom inversion algorithm of the adding-doubling routine, and the expanded uncertainties on the results are provided. The broadband diffuse optical properties measured with the improved system agree to within the estimated uncertainty of the discrete measurements from two other institutes using alternative methods. This work expands the capabilities of the facility and can provide services for a wider range of applications.
3D Printed Phantoms
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3D printing of microtube in solid phantom to simulate tissue oxygenation and perfusion (Conference Presentation)
Xiang Lv, Yue Xue, Haili Wang, et al.
Tissue-simulating phantoms with interior vascular network may facilitate traceable calibration and quantitative validation of many medical optical devices. However, a solid phantom that reliably simulates tissue oxygenation and blood perfusion is still not available. This paper presents a new method to fabricate hollow microtubes for blood vessel simulation in solid phantoms. The fabrication process combines ultraviolet (UV) rapid prototyping technique with fluid mechanics of a coaxial jet flow. Polydimethylsiloxane (PDMS) and a UV-curable polymer are mixed at the designated ratio and extruded through a coaxial needle device to produce a coaxial jet flow. The extruded jet flow is quickly photo-polymerized by ultraviolet (UV) light to form vessel-simulating solid structures at different sizes ranging from 700 m to 1000 m. Microtube structures with adequate mechanical properties can be fabricated by adjusting material compositions and illumination intensity. Curved, straight and stretched microtubes can be formed by adjusting the extrusion speed of the materials and the speed of the 3D printing platform. To simulate vascular structures in biologic tissue, we embed vessel-simulating microtubes in a gel wax phantom of 10 cm x10 cm x 5 cm at the depth from 1 to 2 mm. Bloods at different oxygenation and hemoglobin concentration levels are circulated through the microtubes at different flow rates in order to simulate different oxygenation and perfusion conditions. The simulated physiologic parameters are detected by a tissue oximeter and a laser speckle blood flow meter respectively and compared with the actual values. Our experiments demonstrate that the proposed 3D printing process is able to produce solid phantoms with simulated vascular networks for potential applications in medical device calibration and drug delivery studies.
3D printed optical phantoms and deep tissue imaging for in vivo applications including oral surgery
Brian Z. Bentz, Alfonso Costas, Vaibhav Gaind, et al.
Progress in developing optical imaging for biomedical applications requires customizable and often complex objects known as "phantoms" for testing, evaluation, and calibration. This work demonstrates that 3D printing is an ideal method for fabricating such objects, allowing intricate inhomogeneities to be placed at exact locations in complex or anatomically realistic geometries, a process that is difficult or impossible using molds. We show printed mouse phantoms we have fabricated for developing deep tissue fluorescence imaging methods, and measurements of both their optical and mechanical properties. Additionally, we present a printed phantom of the human mouth that we use to develop an artery localization method to assist in oral surgery.
Cerebral NIRS performance testing with molded and 3D-printed phantoms (Conference Presentation)
Jianting Wang, Stanley Huang, Yu Chen, et al.
Near-infrared spectroscopy (NIRS) has emerged as a low-cost, portable approach for rapid, point-of-care detection of hematomas caused by traumatic brain injury. As a new technology, there is a need to develop standardized test methods for objective, quantitative performance evaluation of these devices. Towards this goal, we have developed and studied two types of phantom-based testing approaches. The first involves 3D-printed phantoms incorporating hemoglobin-filled inclusions. Phantom layers representing specific cerebral tissues were printed using photopolymers doped with varying levels of titanium oxide and black resin. The accuracy, precision and spectral dependence of printed phantom optical properties were validated using spectrophotometry. The phantom also includes a hematoma inclusion insert which was filled with a hemoglobin solution. Oxygen saturation levels were modified by adding sodium dithionite at calibrated concentrations. The second phantom approach involves molded silicone layers with a superficial region – simulating the scalp and skull – comprised of removable layers to vary hematoma size and depth, and a bottom layer representing brain matter. These phantoms were tested with both a commercial hematoma detector and a custom NIRS system to optimize their designs and validate their utility in performing inter-device comparisons. The effects of hematoma depth, diameter, and height, as well as tissue optical properties and biological variables including hemoglobin saturation level and scalp/skull thickness were studied. Results demonstrate the ability to quantitatively compare NIRS device performance and indicate the promise of using 3D printing to achieve phantoms with realistic variations in tissue optical properties for evaluating biophotonic device performance.
Phantoms II
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Design and fabrication of solid phantoms for NIR water fraction studies
Gordon T. Kennedy, Griffin R. Lentsch, Brandon Trieu, et al.
Tissue simulating phantoms provide a valuable platform for quantitative evaluation of the performance of diffuse optical devices. In this paper we report the development of a poly(dimethylsiloxane) (PDMS) tissue phantom that mimics the spectral characteristics of tissue water. We have developed these phantoms to mimic different water fractions in tissue for testing new devices within the context of clinical applications such as burn wound triage. Compared to liquid phantoms, PDMS phantoms are easier to transport and use, and have a longer usable life than gelatin based phantoms. The pthalocyanine dye 9606 was used to provide an absorption feature of in the vicinity of 970 nm. Scattering properties were independently determined by adding titanium dioxide powder to obtain reduced scattering coefficients similar to that of tissue in the near infrared. Phantom properties were characterized using the techniques of inverse adding doubling and spatial frequency domain imaging. Results presented here demonstrate that we can fabricate solid phantoms that can be used to simulate different water fractions.
Visibility of solid and liquid fiducial markers used for image-guided radiation therapy on optical coherence tomography: an esophageal phantom study (Conference Presentation)
Pouya Jelvehgaran, Tanja Alderliesten, Jelmer J. A. Weda, et al.
Radiation therapy (RT) is used in operable and inoperable esophageal cancer patients. Endoscopic ultrasound-guided fiducial marker placement allows improved translation of the disease extent on endoscopy to computed tomography (CT) images used for RT planning and enables image-guided RT. However, microscopic tumor extent at the time of RT planning is unknown. Endoscopic optical coherence tomography (OCT) is a high-resolution (10-30µm) imaging modality with the potential for accurately determining the longitudinal disease extent. Visibility of fiducial markers on OCT is crucial for integrating OCT findings with the RT planning CT. We investigated the visibility on OCT (NinePoint Medical, Inc.) of 13 commercially available solid (Visicoil, Gold Anchor, Flexicoil, Polymark, and QLRAD) and liquid (BioXmark, Lipiodol, and Hydrogel) fiducial markers of different diameter. We designed and manufactured a set of dedicated Silicone-based esophageal phantoms to perform imaging in a controlled environment. The esophageal phantoms consist of several layers with different TiO2 concentrations to simulate the scattering properties of a typical healthy human esophagus. Markers were placed at various depths (0.5, 1.1, 2.0, and 3.0mm). OCT imaging allowed detection of all fiducial markers and phantom layers. The signal to background ratio was 6-fold higher for the solid fiducial markers than the liquid fiducial markers, yet OCT was capable of visualizing all 13 fiducial markers at all investigated depths. We conclude that RT fiducial markers can be visualized with OCT. This allows integration of OCT findings with CT for image-guided RT.
Development and validation of a biologically realistic tissue-mimicking material for photoacoustics and other bimodal optical-acoustic modalities
William C. Vogt, Congxian Jia, Keith A. Wear, et al.
Recent years have seen rapid development of hybrid optical-acoustic imaging modalities with broad applications in research and clinical imaging, including photoacoustic tomography (PAT), photoacoustic microscopy, and ultrasound-modulated optical tomography. Tissue-mimicking phantoms are an important tool for objectively and quantitatively simulating in vivo imaging system performance. However, no standard tissue phantoms exist for such systems. One major challenge is the development of tissue-mimicking materials (TMMs) that are both highly stable and possess biologically realistic properties. To address this need, we have explored the use of various formulations of PVC plastisol (PVCP) based on varying mixtures of several liquid plasticizers. We developed a custom PVCP formulation with optical absorption and scattering coefficients, speed of sound, and acoustic attenuation that are tunable and tissue-relevant. This TMM can simulate different tissue compositions and offers greater mechanical strength than hydrogels. Optical properties of PVCP samples with varying composition were characterized using integrating sphere spectrophotometry and the inverse adding-doubling method. Acoustic properties were determined using a broadband pulse-transmission technique. To demonstrate the utility of this bimodal TMM, we constructed an image quality phantom designed to enable quantitative evaluation of PAT spatial resolution. The phantom was imaged using a custom combined PAT-ultrasound imaging system. Results indicated that this more biologically realistic TMM produced performance trends not captured in simpler liquid phantoms. In the future, this TMM may be broadly utilized for performance evaluation of optical, acoustic, and hybrid optical-acoustic imaging systems.
Comparison of the temperature accuracy between smart phone based and high-end thermal cameras using a temperature gradient phantom
Recently, low cost smart phone based thermal cameras are being considered to be used in a clinical setting for monitoring physiological temperature responses such as: body temperature change, local inflammations, perfusion changes or (burn) wound healing. These thermal cameras contain uncooled micro-bolometers with an internal calibration check and have a temperature resolution of 0.1 degree. For clinical applications a fast quality measurement before use is required (absolute temperature check) and quality control (stability, repeatability, absolute temperature, absolute temperature differences) should be performed regularly. Therefore, a calibrated temperature phantom has been developed based on thermistor heating on both ends of a black coated metal strip to create a controllable temperature gradient from room temperature 26 °C up to 100 °C. The absolute temperatures on the strip are determined with software controlled 5 PT-1000 sensors using lookup tables. In this study 3 FLIR-ONE cameras and one high end camera were checked with this temperature phantom. The results show a relative good agreement between both low-cost and high-end camera’s and the phantom temperature gradient, with temperature differences of 1 degree up to 6 degrees between the camera’s and the phantom. The measurements were repeated as to absolute temperature and temperature stability over the sensor area. Both low-cost and high-end thermal cameras measured relative temperature changes with high accuracy and absolute temperatures with constant deviations. Low-cost smart phone based thermal cameras can be a good alternative to high-end thermal cameras for routine clinical measurements, appropriate to the research question, providing regular calibration checks for quality control.
Study on the origin to change physicochemical properties of polydimethylsiloxane (PDMS) phantoms for biomedical application (Conference Presentation)
Han Saem S. Cho, Heh-Young Moon, Heung-Soon Lee, et al.
Polydimethylsiloxane (PDMS) has been widely used in a variety of biomedical applications: microfluidic device, implant, and biomedical phantom due to its unique physiochemical and mechanical properties. To use PDMS properly, in-depth study for properties of PDMS is needed. Many studies for analysis of PDMS properties are suggested, however, there are shortages of systematic analysis and study on the origin of PDMS properties. Typically, PDMS is produced by mixing and curing pre-polymer and curing agent with catalyst and thermal energy. The recommended mixing ratio (pre-polymer: curing agent) is typically 10:1 by raw materials suppliers. However, the reason why the mixing ratio 10:1 is considered proper than other mixing ratios has not been known clearly. In this research, we presented the change of physicochemical properties of PDMS according to the mixing ratio and figured out the origin to change PDMS physiochemical properties by Raman spectroscopy and absorption spectroscopy. We produced PDMS samples with various mixing ratios(1:1, 1.5:1, 2:1, 3:1, 5:1, 7:1, 9:1, 10:1, 12:1, 20:1, 30:1) and analyzed mechanical, optical, and surface properties of PDMS by measuring Young’s modulus, OCT, hydrophobicity, and surface profiles according to the mixing ratio of PDMS. Also, we demonstrated the chemical composition of PDMS is changed when the mixing ratio of PDMS is changed by measuring Raman spectra and absorption spectra. As a result, when the mixing ratio is about 9:1, the mechanical, optical, and surface properties of PDMS had extreme points and the reason was explained quantitatively with the data of Raman spectra and absorption spectra.
Simulating tissue fiberation and polarization properties in solid phantoms (Conference Presentation)
Haili Wang, Shu Wei Shen, Yingjie Qu, et al.
Polarization of biological tissue reflects birefringent characteristics of tissue components such as collagenous and elastic fibers. Polarimetry imaging techniques have been widely explored for disease diagnosis and therapeutic guidance. However, no traceable standard is available for calibration and validation of the polarimetry devices, partially due to the lack of reliable and stable tissue-simulating phantoms that simulate tissue birefringence properties. We propose a new method to fabricate tissue simulating phantoms that simulate tissue scattering and polarization characteristics. The substrate of the phantoms are made of polydimethylsiloxane (PDMS). The PDMS material is mixed with sucrose to simulate optical rotation characteristics of chiral molecules in tissue. Titanum dioxide (TiO2 ) particles are used to simulate organelle scattering properties of tissue. An electrostatic spinning method produces thin filaments with designated orientation and polarization characteristics to simulate collagen and elastic fiber orientation in biological tissue.By adjusting the concentration of the scattering particles and the arrangements of the fibers, the produced phantoms present different polarization characteristics. The proposed tissue-simulating phantoms can be potentially used to validate and calibrate the polarimetry medical devices.
Evaluation of a multi-layer diffuse reflectance spectroscopy system using optical phantoms
A fiber probe-based device for assessing microcirculatory parameters, especially red blood cell (RBC) tissue fraction, their oxygen saturation and speed resolved perfusion, has been evaluated using state-of-the-art multi-layer tissue simulating phantoms. The device comprises both diffuse reflectance spectroscopy (DRS) at two source-detector separations (0.4 and 1.2 mm) and laser Doppler flowmetry (LDF) and use an inverse Monte Carlo method for identifying the parameters of a multi-layered tissue model. First, model parameters affecting scattering, absorption and geometrical parameters are fitted to measured DRS spectra, then speed parameters are fitted to LDF spectra. In this paper, the accuracy of the spectral parameters is evaluated. The measured spectral shapes at the two source-detector separations were in good agreement with forward calculated spectral shapes. In conclusion, the multi-layer skin model based on spectral features of the included chromophores, can reliably estimate the tissue fraction of RBC, its oxygen saturation and the reduced scattering coefficient spectrum of the tissue. Furthermore, it was concluded that some freedom in the relative intensity difference between the two DRS channels is necessary in order to compensate for non-modeled surface structure effects.
Quality of Biomedical Technologies
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Standardized assessment of infrared thermographic fever screening system performance
Thermal modalities represent the only currently viable mass fever screening approach for outbreaks of infectious disease pandemics such as Ebola and SARS. Non-contact infrared thermometers (NCITs) and infrared thermographs (IRTs) have been previously used for mass fever screening in transportation hubs such as airports to reduce the spread of disease. While NCITs remain a more popular choice for fever screening in the field and at fixed locations, there has been increasing evidence in the literature that IRTs can provide greater accuracy in estimating core body temperature if appropriate measurement practices are applied – including the use of technically suitable thermographs. Therefore, the purpose of this study was to develop a battery of evaluation test methods for standardized, objective and quantitative assessment of thermograph performance characteristics critical to assessing suitability for clinical use. These factors include stability, drift, uniformity, minimum resolvable temperature difference, and accuracy. Two commercial IRT models were characterized. An external temperature reference source with high temperature accuracy was utilized as part of the screening thermograph. Results showed that both IRTs are relatively accurate and stable (<1% error of reading with stability of ±0.05°C). Overall, results of this study may facilitate development of standardized consensus test methods to enable consistent and accurate use of IRTs for fever screening.
Ray-traced Monte Carlo simulation tool for computer-aided design of tissue fluorescence sensing system
In designing fluorescence spectroscopy and imaging systems for biological applications, a sample's own optical properties can significantly affect system performance. The independent use of Monte Carlo codes or optical design software often does not provide complete and accurate modeling of the fluorescence excitation and emission path through the optical components and turbid sample. We have developed a ray-traced Monte Carlo (RTMC) simulation method to track the complete light path by combining MC codes and ray-tracing software. Computational and experimental verification results demonstrate that RTMC has the potential to become a useful tool for designing tissue fluorescence sensing systems.
Near-infrared fluorescence image quality test methods for standardized performance evaluation
Udayakumar Kanniyappan, Bohan Wang, Charles Yang, et al.
Near-infrared fluorescence (NIRF) imaging has gained much attention as a clinical method for enhancing visualization of cancers, perfusion and biological structures in surgical applications where a fluorescent dye is monitored by an imaging system. In order to address the emerging need for standardization of this innovative technology, it is necessary to develop and validate test methods suitable for objective, quantitative assessment of device performance. Towards this goal, we develop target-based test methods and investigate best practices for key NIRF imaging system performance characteristics including spatial resolution, depth of field and sensitivity. Characterization of fluorescence properties was performed by generating excitation-emission matrix properties of indocyanine green and quantum dots in biological solutions and matrix materials. A turbid, fluorophore-doped target was used, along with a resolution target for assessing image sharpness. Multi-well plates filled with either liquid or solid targets were generated to explore best practices for evaluating detection sensitivity. Overall, our results demonstrate the utility of objective, quantitative, target-based testing approaches as well as the need to consider a wide range of factors in establishing standardized approaches for NIRF imaging system performance.
Traceable working standards with SI units of radiance for characterizing the measurement performance of investigational clinical NIRF imaging devices
Banghe Zhu, John C. Rasmussen, Maritoni Litorja, et al.
All medical devices for Food and Drug market approval require specifications of performance based upon International System of Units (SI) or units derived from SI for reasons of traceability. Recently, near-infrared fluorescence (NIRF) imaging devices of a variety of designs have emerged on the market and in investigational clinical studies. Yet the design of devices used in the clinical studies vary widely, suggesting variable device performance. Device performance depends upon optimal excitation of NIRF imaging agents, rejection of backscattered excitation and ambient light, and selective collection of fluorescence emanating from the fluorophore. There remains no traceable working standards with SI units of radiance to enable prediction that a given molecular imaging agent can be detected in humans by a given NIRF imaging device. Furthermore, as technologies evolve and as NIRF imaging device components change, there remains no standardized means to track device improvements over time and establish clinical performance without involving clinical trials, often costly. In this study, we deployed a methodology to calibrate luminescent radiance of a stable, solid phantom in SI units of mW/cm2/sr for characterizing the measurement performance of ICCD and IsCMOS camera based NIRF imaging devices, such as signal-to-noise ratio (SNR) and contrast. The methodology allowed determination of superior SNR of the ICCD over the IsCMOS system; comparable contrast of ICCD and IsCMOS depending upon binning strategies.
Image quality assessment for teledermatology: from consumer devices to a dedicated medical device
Marine Amouroux, Sébastien Le Cunff, Alexandre Haudrechy, et al.
Aging population as well as growing incidence of type 2 diabetes induce a growing incidence of chronic skin disorders. In the meantime, chronic shortage of dermatologists leaves some areas underserved. Remote triage and assistance to homecare nurses (known as “teledermatology”) appear to be promising solutions to provide dermatological valuation in a decent time to patients wherever they live. Nowadays, teledermatology is often based on consumer devices (digital tablets, smartphones, webcams) whose photobiological and electrical safety levels do not match with medical devices’ levels. The American Telemedicine Association (ATA) has published recommendations on quality standards for teledermatology. This “quick guide” does not address the issue of image quality which is critical in domestic environments where lighting is rarely reproducible. Standardized approaches of image quality would allow clinical trial comparison, calibration, manufacturing quality control and quality insurance during clinical use. Therefore, we defined several critical metrics using calibration charts (color and resolution charts) in order to assess image quality such as resolution, lighting uniformity, color repeatability and discrimination of key couples of colors. Using such metrics, we compared quality of images produced by several medical devices (handheld and video-dermoscopes) as well as by consumer devices (digital tablet and cameras) widely spread among dermatologists practice. Since diagnosis accuracy may be impaired by “low quality-images”, this study highlights that, from an optical point of view, teledermatology should only be performed using medical devices. Furthermore, a dedicated medical device should probably be developed for the time follow-up of skin lesions often managed in teledermatology such as chronic wounds that require i) noncontact imaging of ii) large areas of skin surfaces, both criteria that cannot be matched using dermoscopes.
Simulating tissue oxygenation by encapsulating hemoglobin in polymer microcapsules (Conference Presentation)
We describe a combination of liquid-jet microencapsulation and molding techniques to fabricate tissue-simulating phantoms that mimick functional characteristics of tissue oxygen saturation (StO2). Chicken hemoglobin (Hb) was encapsulated inside a photocurable resin by a coaxial flow focusing process. The microdroplets were cured by ultraviolet (UV) illumination to form Hb loaded polymersome microdroplets. The microdroplets were further freeze-dried to form semipermeable solid microcapules with an outer transparent polymeric shell and an inner core of Hb. The diameter of the microcapsules ranged from 50 to100 μm. The absorption spectrum of the microcapsules was measured by a UV/VIS spectrophotometer over a wavelength range from 400 nm to 1100 nm. To fabricate the tissue-simulating phantom, the Hb loaded microcapsules were dispersed in transparent polydimethylsiloxane (PDMS). The optical properties of the phantom were determined by an vertical double integrating sphere with a reconstruction algorithm. The experimental results showed that the tissue-simulating phantom exhibited the spectral characteristics closely resembling that of oxy-hemoglobin. The phantom had a long-term optical stability when stored in 4 ℃, indicating that microencapsulation effectively protected Hb and improved its shelf time. With the Hb loaded microcapsules, we will produce skin-simulating phantoms for quantitative validation of multispectral imaging techniques. To the best of the authors’ knowledge, no solid phantom is able to mimick living tissue oxygenation with good agreement. Therefore, our work provided an engineering platform for validating and calibrating spectral optical devices in biomedical applications.
OCT System Development and Applications
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Depth-of-focus extended chromatic dual-foci OCT (Conference Presentation)
The depth scanning range of high-resolution OCT is limited by its depth-of-focus (DOF). To solve this problem, we developed a chromatic dual-foci technology to maintain a transverse resolution of 1-2 um over a DOF of about 300 micrometers, which is 2-3 times larger than the single-focus OCT system. In this OCT system, a supercontinuum source is used to provide illumination from 700 to 1600 nm. The interference fringe is detected by a dual-spectrometer system, which engages a Si camera and an InGaAs camera. The Si camera detects the spectral single from 700 to 950 nm, and InGaAs camera covers 1100 to 1600 nm spectral range. As the focal region for long wavelength section is deeper than the short one, the two spectral sections are processed separately to form two OCT images of different depths in the sample. After combining the two images, we obtained DOF extended OCT images.
A comparative study of noise in supercontinuum light sources for ultra-high resolution optical coherence tomography
Supercontinuum (SC) light is a well-established technology, which finds applications in several domains ranging from chemistry to material science and imaging systems [1-2]. More specifically, its ultra-wide optical bandwidth and high average power make it an ideal tool for Optical Coherence Tomography (OCT). Over the last 5 years, numerous examples have demonstrated its high potential [3-4] in this context. However, SC light sources present pulse-to-pulse intensity variation that can limit the performance of any OCT system [5] by degrading their signal to noise ratio (SNR). To this goal, we have studied and compared the noise of several SC light sources and evaluated how their noise properties affect the performance of Ultra-High Resolution OCT (UHR-OCT) at 1300 nm. We have measured several SC light sources with different parameters (pulse length, energy, seed repetition rate, etc.).

We illustrate the different noise measurements and their impact on a state of the art UHR-OCT system producing images of skin. The sensitivity of the system was higher than 95 dB, with an axial resolution below 4μm.
Analysis of polygonal mirror scanning heads: from industrial to high-end applications in swept sources for OCT
An analysis of polygonal mirror (PM) scanning heads has been performed, in order to provide a tool for their optimal design. The theory developed brings under the same umbrella applications that range from industrial dimensional measurements to high-end biomedical imaging, for example for broadband laser sources swept in frequency for Swept Source Optical Coherence Tomography (SS-OCT). The different characteristic parameters of the PM scanning heads were considered in order to achieve a rigorous analysis: number of PM facets, inner radius of the PM, eccentricity of the PM pivot with regard to the incident fixed laser beam, distance from this beam to the principal plane of the objective lens, and angular velocity of the PM. The functions that characterize the PM scanning head have been deduced: scanning function and velocity, characteristic angles, duty cycle, and two migration functions (longitudinal and transversal) that allow for an optimized designing calculus of the PM placed in different SS configurations. The analytic and numerical analysis of these functions has been performed with regard to the characteristic parameters of the scanning head. Experimental validations of the theory were further completed. While the above analysis has been carried out for a characteristic ray of the collimated laser beam (i.e., its central axes), it also allows for considering in a simple way the finite diameter of the beam. Thus, a discussion on the deformation of the beam – as produced by the eccentric rotational PM facet – can also be perfomed. A comparison of the PM scanner with the most common types of laser scanners highlights its advantages and drawbacks for OCT.
Integrated-optics based multi-beam imaging for speed improvement of OCT systems
B. Imran Akca, Nicolas M. Weiss, Frank A. W. Coumans, et al.
The speed improvement is a game-changer in optical coherence tomography (OCT) imaging because it opens up for new and very exciting applications. The frame rate of an OCT system is limited by the speed of the camera or the sweep rate of the light source. This problem can be overcome by multiple-beam imaging, in which different locations on the sample are illuminated by an array of light simultaneously. This technique allows parallel imaging from multiple sample locations and therefore improves OCT axial scan rate by a factor equal to the number of beams used simultaneously which can go up to very high frequency ranges (e.g. MHz) easily. In this work, we introduce a compact integrated-optics based multiple-beam illumination design in which several waveguides with certain length differences are combined with wavelength-independent couplers for space-division multiplexing. Electrodes will be placed on each beam path in order to separate desired signal from unwanted reflections at the optical surfaces or tissue. The imaging speed will be improved by the number of the beam paths used. In addition to fast imaging, the proposed design will be very compact which makes it very suitable to be used in endoscopic probes. The proof-of-concept of this idea was experimentally demonstrated using a design which consists of 2 times 4 parallel OCT channels that are realized with a total of 6 Y-couplers. Each individual OCT channel has an optical path length delay with respect to the other channels.
Imaging Systems and Applications
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Surgical instrument biocontaminant fluorescence detection in ambient lighting conditions for hospital reprocessing and sterilization department (Conference Presentation)
François Baribeau, Annie Bubel, Guillaume Dumont, et al.
Hospitals currently rely on simple human visual inspection for assessing cleanliness of surgical instruments. Studies showed that surgical site infections are in part attributed to inadequate cleaning of medical devices. Standards groups recognize the need to objectively quantify the amount of residues on surgical instruments and establish guidelines. We developed a portable technology for the detection of contaminants on surgical instruments through fluorescence following cleaning. Weak fluorescence signals are usually detected in the obscurity only with the lighting of the excitation source. The key element of this system is that it works in ambient lighting conditions, a requirement to not disturb the normal workflow of hospital reprocessing facilities. A biocompatible fluorescent dye is added to the detergent and labels the proteins of organic residues. It is resistant to the harsh environment in a washer-disinfector. Two inspection devices have been developed with a 488nm laser as the excitation source: a handheld scanner and a tabletop station using spectral-domain and time-domain ambient light cancellation schemes. The systems are eye safe and equipped with image processing and interfacing software to provide visual or audible warnings to the operator based on a set of adjustable signal thresholds. Micron-scale residues are detected by the system which can also evaluate soil size and mass. Unlike swabbing, it can inspect whole tools in real-time. The technology has been validated in an independent hospital decontamination research laboratory. It also has potential applications in the forensics, agro-food, and space fields. Technical aspects and results will be presented and discussed.
Laser assisted robotic surgery in cornea transplantation
Robotic surgery is a reality in several surgical fields, such as in gastrointestinal surgery. In ophthalmic surgery the required high spatial precision is limiting the application of robotic system, and even if several attempts have been designed in the last 10 years, only some application in retinal surgery were tested in animal models. The combination of photonics and robotics can really open new frontiers in minimally invasive surgery, improving the precision, reducing tremor, amplifying scale of motion, and automating the procedure. In this manuscript we present the preliminary results in developing a vision guided robotic platform for laser-assisted anterior eye surgery. The robotic console is composed by a robotic arm equipped with an "end effector" designed to deliver laser light to the anterior corneal surface. The main intended application is for laser welding of corneal tissue in laser assisted penetrating keratoplasty and endothelial keratoplasty. The console is equipped with an integrated vision system. The experiment originates from a clear medical demand in order to improve the efficacy of different surgical procedures: when the prototype will be optimized, other surgical areas will be included in its application, such as neurosurgery, urology and spinal surgery.
Design and implementation of a dual-wavelength intrinsic fluorescence camera system
Antonio Ortega-Martinez, Joseph J. Musacchia, Enoch Gutierrez-Herrera, et al.
Intrinsic UV fluorescence imaging is a technique that permits the observation of spatial differences in emitted fluorescence. It relies on the fluorescence produced by the innate fluorophores in the sample, and thus can be used for marker-less in-vivo assessment of tissue. It has been studied as a tool for the study of the skin, specifically for the classification of lesions, the delimitation of lesion borders and the study of wound healing, among others. In its most basic setup, a sample is excited with a narrow-band UV light source and the resulting fluorescence is imaged with a UV sensitive camera filtered to the emission wavelength of interest. By carefully selecting the excitation/emission pair, we can observe changes in fluorescence associated with physiological processes. One of the main drawbacks of this simple setup is the inability to observe more than a single excitation/emission pair at the same time, as some phenomena are better studied when two or more different pairs are studied simultaneously. In this work, we describe the design and the hardware and software implementation of a dual wavelength portable UV fluorescence imaging system. Its main components are an UV camera, a dual wavelength UV LED illuminator (295 and 345 nm) and two different emission filters (345 and 390 nm) that can be swapped by a mechanical filter wheel. The system is operated using a laptop computer and custom software that performs basic pre-processing to improve the image. The system was designed to allow us to image fluorescent peaks of tryptophan and collagen cross links in order to study wound healing progression.
On the origin of the visible light responsible for proton dose measurement using plastic optical fibers
Arash Darafsheh, Reza Taleei, Alireza Kassaee, et al.
We experimentally and by means of Monte Carlo simulations investigated the origin of the visible signal responsible for proton therapy dose measurement using bare plastic optical fibers. Experimentally, the fiber optic probe, embedded in tissue-mimicking plastics, was irradiated with a proton beam produced by a proton therapy cyclotron and the luminescence spectroscopy was performed by a CCD-coupled spectrograph to analyze the emission spectrum of the fiber tip. Monte Carlo simulations were performed using FLUKA Monte Carlo code to stochastically simulate radiation transport, ionizing radiation dose deposition, and optical emission of Čerenkov radiation. The spectroscopic study of proton-irradiated plastic fibers showed a continuous spectrum with shape different from that of Čerenkov radiation. The Monte Carlo simulations confirmed that the amount of the generated Čerenkov light does not follow the radiation absorbed dose in a medium. Our results show that the origin of the optical signal responsible for the proton dose measurement using bare optical fibers is not Čerenkov radiation. Our results point toward a connection between the scintillation of the plastic material of the fiber and the origin of the signal responsible for dose measurement.
Reliable determination of tissue optical properties from spatially resolved reflectance
Thomas Gladytz, Alexander Hoppe, Kathleen Cantow, et al.
Spatially resolved reflectance is a frequently used technique to derive optical properties and physiological parameters of tissue. We have evaluated the accuracy of this method by investigations on a set of phantoms with known optical properties derived from time-resolved measurements. The recorded profiles of spatially resolved reflectance were analyzed by a Monte Carlo model of photon transport. When we took only the shape of the measured profiles into account, we got only poor estimates of the optical properties. In particular, the absorption was strongly underestimated. The main reason for failing of this approach is that the shape of the measured profiles can be well described by many combinations of absorption and reduced scattering coefficients. The separation between scattering and absorption was strongly improved when the reflectance data were calibrated by using a reference phantom. We applied both the relative and the calibration based analysis method to reflectance data obtained from in vivo investigations on the kidney of rats. Despite the limited number of only 4 detector positions the calibration based analysis method yielded reliable estimates of the tissue optical properties.
Poster Session
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Development of an antimicrobial blended white LED system containing pulsed 405nm LEDs for decontamination applications
Jonathan B. Gillespie, Michelle Maclean, Mark P. Wilson, et al.
This study details the design, build and testing of a prototype antimicrobial blended white light unit containing pulsed red, yellow, green and 405nm LEDs. With a push for alternative methods of disinfection, optical methods have become a topic of interest. Ultra-violet (UV) light is widely known for its antimicrobial properties however; 405nm light has demonstrated significant antimicrobial properties against many common hospital acquired pathogens. In this study, a pulsed, blended, white-light prototype with a high content of 405 nm antimicrobial light, was designed, built and tested. Antimicrobial efficacy testing of the prototype was conducted using Staphylococcus aureus and Pseudomonas. aeruginosa, two bacteria which are common causes of hospital acquired infections. These were exposure to 3 different light outputs from the prototype and the surviving bacteria enumerated. Results showed that the mixed light output provided a much better CRI and light output under which to work. Also, the light output containing 405 nm light provided an antimicrobial effect, with decontamination of 103 CFUml-1 populations of both bacterial species. The other light content (red, yellow, green) had no beneficial or adverse effects on the antimicrobial properties of the 405nm light. The results suggest that with further development, it could be possible to produce an antimicrobial blended white light containing pulsed 405nm light that could supplement or even replace standard white lighting in certain environments.
Multispectral fluorescence diffuse optical tomography
Fluorescence diffuse optical tomography (FDOT) has been widely used for in vivo small animal studies and the illposed problem in reconstruction can be eased by utilizing structural a priori obtained from an anatomic imaging modality. In this study, a multispectral fluorescence tomography (FT) is used, which has shown the ability to detect subtle shifts in the ICG absorption spectrum in our previous study. The imaging system is in trans-illumination mode with a swept-wavelength laser and a CCD on a rotation gantry and the structural image from the X-ray computed tomography is used to guide and constrain the FT reconstruction algorithm. In this work, a phantom with two inclusions filled with different fluorophores is utilized to evaluate whether the spectral information obtained using sweptwavelength laser can distinguish these two inclusions. The images are captured from 8 different views with three different wavelengths.
3D splint prototype system for applications in muscular rehab by transcutaneous electrical nerve stimulation (TENS)
M. I. Saldaña-Martínez, J. V. Guzmán-González, O. G. Barajas-González, et al.
It is quite common that patients with ligamentous ruptures, tendonitis, tenosynovitis or sprains are foreseen the use of ad hoc splints for a swift recovery. In this paper, we propose a rehabilitation split that is focused on upper-limb injuries. By considering that upper-limb patient shows a set of different characteristics, our proposal personalizes and prints the splint custom made though a digital model that is generated by a 3D commercial scanner. To fabricate the 3D scanned model the Stereolithography material (SLA) is considered due to the properties that this material offers. In order to complement the recovery process, an electronic system is implemented within the splint design. This system generates a set of pulses for a fix period of time that focuses mainly on a certain group of muscles to allow a fast recovery process known as Transcutaneous Electrical Nerve Stimulation Principle (TENS).
Continuous control systems for non-contact ECG
Vladimir L. Kodkin, Galina V. Yakovleva, Alexey S. Smirnov
South Ural State University is still conducting the research work dedicated to innovations in biomedicine. Development of system for continuous control and diagnosis of the functional state in large groups of people is based on studies of non-contact ECG recording reported by the authors at the SPIE conference in 2016. The next stage of studies has been performed this year.
A capillary-mimicking optical tissue phantom for diffuse correlation spectroscopy
Jameson P. O'Reilly, Noah J. Kolodziejski, Daniel McAdams, et al.
Optical tissue phantoms are necessary for instrument benchmarking and providing a consistent baseline for experiments in various fields of tissue spectroscopy, including diffuse correlation spectroscopy (DCS). To provide the most useful comparisons, a phantom would ideally mimic tissue as closely as possible, including the geometry of static and dynamic scatterers. A branching design that keeps the capillary cross section constant ensures that the same flow velocity is found throughout the phantom while allowing for single input and output fittings to feed all of the capillaries simultaneously. The direction of each capillary is randomized every few millimeters by randomly allocating 2 by 2 "twisting" squares within each layer. These squares swap the locations of four adjacent artificial capillaries either clockwise or counterclockwise. Numerical simulations were used to verify the random walk-like behavior of the capillary paths resulting from this pattern. This is a step toward replicating the randomly varying directionality of actual capillaries. This design was verified by taking DCS measurements at different flow rates of Intralipid through the phantom, demonstrating the effect of the flow rate on the characteristic decay time of the autocorrelation.
Towards a clinical implementation of uOCT instrument for in vivo imaging of human airways
High resolution micro-optical coherence tomography (µOCT) technology has been demonstrated to be useful for imaging respiratory epithelial functional microanatomy relevant to the study of pulmonary diseases such as cystic fibrosis and COPD. We previously reported the use of a benchtop μOCT imaging technology to image several relevant respiratory epithelial functional microanatomy at 40 fps and at lateral and axial resolutions of 2 and 1.3μm, respectively. We now present the development of a portable μOCT imaging system with comparable optical and imaging performance, which enables the μOCT technology to be translated to the clinic for in vivo imaging of human airways.