This PDF file contains the front matter associated with SPIE Proceedings Volume 8936, including the Title Page, Copyright information, Table of Contents, Invited Panel Discussion, and Conference Committee listing.

Rheumatoid arthritis is a disease that frequently leads to joint destruction. It has high incidence rates worldwide, and the disease significantly reduces patient’s quality of life due to pain, swelling and stiffness of the affected joints. Early diagnosis is necessary to improve course of the disease, therefore sensitive and accurate diagnostic tools are required. Optical imaging techniques have capability for early diagnosis and monitoring of arthritis. As compared to conventional diagnostic techniques optical technique is a noninvasive, noncontact and fast way of collecting diagnostic information. However, a realistic model of light transport in human joints is needed for understanding and developing of such optical diagnostic tools. The aim of this study is to develop a 3D numerical model of light transport in a human finger. The model will guide development of a hyperspectral imaging (HSI) diagnostic modality for arthritis in human fingers. The implemented human finger geometry is based on anatomical data. Optical data of finger tissues are adjusted to represent either an arthritic or an unaffected finger. The geometry and optical data serve as input into a 3D Monte Carlo method, which calculate diffuse reflectance, transmittance and absorbed energy distributions. The parameters of the model are optimized based on HIS-measurements of human fingers. The presented model serves as an important tool for understanding and development of HSI as an arthritis diagnostic modality. Yet, it can be applied to other optical techniques and finger diseases.

Photoacoustic imaging (PAI) has grown rapidly as a biomedical imaging technique in recent years, with key applications in cancer diagnosis and oximetry. In spite of these advances, the literature provides little insight into thermal tissue interactions involved in PAI. To elucidate these basic phenomena, we have developed, validated, and implemented a three-dimensional numerical model of tissue photothermal (PT) response to repetitive laser pulses. The model calculates energy deposition, fluence distributions, transient temperature and damage profiles in breast tissue with blood vessels and generalized perfusion. A parametric evaluation of these outputs vs. vessel diameter and depth, optical beam diameter, wavelength, and irradiance, was performed. For a constant radiant exposure level, increasing beam diameter led to a significant increase in subsurface heat generation rate. Increasing vessel diameter resulted in two competing effects – reduced mean energy deposition in the vessel due to light attenuation and greater thermal superpositioning due to reduced thermal relaxation. Maximum temperatures occurred either at the surface or in subsurface regions of the dermis, depending on vessel geometry and position. Results are discussed in terms of established exposure limits and levels used in prior studies. While additional experimental and numerical study is needed, numerical modeling represents a powerful tool for elucidating the effect of PA imaging devices on biological tissue.

The purpose of this study is to correct baseline shift in absorbance spectrums caused by light source fluctuation. To improve quantitative evaluation performance of blood glucose level, baseline shift is corrected by multiple scatter correction (MSC). Moreover, to increase the effect of the MSC, water vapor absorbance is subtracted, and relative glucose absorbance are calculated by dividing with hemoglobin absorbance at 1544 [cm-1]. In order to verify the effectiveness of the proposed spectrum correction method, light source fluctuation is simulated on the Fourier transform infrared spectroscopy (FT-IR), and we apply the proposed method to the spectrums measured by FT-IR. From the simulation results, the baseline shift was successfully reduced by proposed method.

Tuberculosis (TB) is an ancient disease constituted a long-term menace to public health. According to World Health Organization (WHO), mycobacterium tuberculosis (MTB) infected nearly a third of people of the world. There is about one new TB occurrence every second. Interferon-gamma (IFN-γ) is associated with susceptibility to TB, and interferongamma release assays (IGRA) is considered to be the best alternative of tuberculin skin test (TST) for diagnosis of latent tuberculosis infection (LTBI). Although significant progress has been made with regard to the design of enzyme immunoassays for IFN-γ, adopting this assay is still labor-intensive and time-consuming. To alleviate these drawbacks, we used IFN-γ antibody to facilitate the detection of IFN-γ. An experimental verification on the performance of IGRA was done in this research. We developed two biosensor configurations, both of which possess high sensitivity, specificity, and rapid IFN-γ diagnoses. The first is the electrochemical method. The second is a circular polarization interferometry configuration, which incorporates two light beams with p-polarization and s-polarization states individually along a common path, a four photo-detector quadrature configuration to arrive at a phase modulated ellipsometer. With these two methods, interaction between IFN-γ antibody and IFN-γ were explored and presented in detail.

Telemedicine is an emerging technology that aims to provide clinical healthcare at a distance. Among its goals, the transfer of diagnostic images over telecommunication channels has been quite appealing to the medical community. When viewed as an adjunct to biomedical device hardware, one highly important consideration aside from the transfer rate and speed is the accuracy of the reconstructed image at the receiver end. Although optical coherence tomography (OCT) is an established imaging technique that is ripe for telemedicine, the effects of OCT data compression, which may be necessary on certain telemedicine platforms, have not received much attention in the literature. We investigate the performance and efficiency of several lossless and lossy compression techniques for OCT data and characterize their effectiveness with respect to achievable compression ratio, compression rate and preservation of image quality. We examine the effects of compression in the interferogram vs. A-scan domain as assessed with various objective and subjective metrics.

Ovarian cancer is particularly deadly because it is usually diagnosed after it has begun to spread. Transvaginal sonography (TVS) is the most common imaging screening technique. However, routine use of TVS has not reduced ovarian cancer mortality. The superior resolution of optical imaging techniques may make them attractive alternatives to TVS. We have previously identified features of ovarian cancer using optical coherence tomography (OCT) and secondharmonic generation (SHG) microscopy (with collagen as the targeted fluorophore). OCT provides a gross anatomical image of the ovary while SHG provides a closer look at a particular region. Knowing these anatomical features, we sought to investigate the diagnostic potential of OCT and SHG. We conducted a fully crossed, multi-reader, multi-case study using seven human observers. Each observer classified 44 ex vivo mouse ovaries as normal or abnormal from OCT, SHG, and simultaneous, co-registered OCT and SHG images and provided a confidence rating on a three-point ordinal scale. We determined the average receiver operating characteristic (ROC) curves, area under the ROC curves (AUC), and other quantitative figures of merit. The results show that OCT has diagnostic potential with an average AUC of 0.91 ± 0.03. The average AUC for SHG was less promising at 0.71 ± 0.06. Interestingly, the average AUC for simultaneous, co-registered OCT and SHG was not significantly different from OCT alone. This suggests that collagen may not be a useful fluorophore for ovarian cancer screening. The high performance of OCT warrants further investigation.

The prevalence of Dry Eye Disease (DED) in the USA is approximately 40 million in aging adults with about $3.8 billion economic burden. However, a comprehensive understanding of tear film dynamics, which is the prerequisite to advance the management of DED, is yet to be realized. To extend our understanding of tear film dynamics, we investigate the simultaneous estimation of the lipid and aqueous layers thicknesses with the combination of optical coherence tomography (OCT) and statistical decision theory. In specific, we develop a mathematical model for Fourier-domain OCT where we take into account the different statistical processes associated with the imaging chain. We formulate the first-order and second-order statistical quantities of the output of the OCT system, which can generate some simulated OCT spectra. A tear film model, which includes a lipid and aqueous layer on top of a rough corneal surface, is the object being imaged. Then we further implement a Maximum-likelihood (ML) estimator to interpret the simulated OCT data to estimate the thicknesses of both layers of the tear film. Results show that an axial resolution of 1 μm allows estimates down to nanometers scale. We use the root mean square error of the estimates as a metric to evaluate the system parameters, such as the tradeoff between the imaging speed and the precision of estimation. This framework further provides the theoretical basics to optimize the imaging setup for a specific thickness estimation task.

The metrological basis for optical non-invasive diagnostic devices is an unresolved issue. A major challenge for laser Doppler flowmetry (LDF) is the need to compare the outputs from individual devices and various manufacturers to identify variations useful in clinical diagnostics. The most common methods for instrument calibration are simulants or phantoms composed of colloids of light-scattering particles which simulate the motion of red blood cells based on Brownian motion. However, such systems have limited accuracy or stability and cannot calibrate for the known rhythmic components of perfusion (0.0095-1.6 Hz). To solve this problem, we propose the design of a novel technique based on the simulation of moving particles using an electromechanical transducer, in which a precision piezoelectric actuator is used (e.g., P-602.8SL with maximum movement less than 1 mm). In this system, Doppler shift is generated in the layered structure of different solid materials with different optical light diffusing properties. This comprises a fixed, light transparent upper plane-parallel plate and an oscillating fluoroplastic (PTFE) disk. Preliminary studies on this experimental setup using the LDF-channel of a “LAKK-M” system demonstrated the detection of the linear portion (0-10 Hz with a maximum signal corresponding to Doppler shift of about 20 kHz) of the LDF-signal from the oscillating frequency of the moving layer. The results suggest the possibility of applying this technique for the calibration of LDF devices.

Mechanical eye models are used to validate ex vivo the optical quality of intraocular lenses (IOLs). The quality measurement and test instructions for IOLs are defined in the ISO 11979-2. However, it was mentioned in literature that these test instructions could lead to inaccurate measurements in case of some modern IOL designs. Reproducibility of alignment and measurement processes are presented, performed with a semiautomatic mechanical ex vivo eye model based on optical properties published by Liou and Brennan in the scale 1:1. The cornea, the iris aperture and the IOL itself are separately changeable within the eye model. The adjustment of the IOL can be manipulated by automatic decentration and tilt of the IOL in reference to the optical axis of the whole system, which is defined by the connection line of the central point of the artificial cornea and the iris aperture. With the presented measurement setup two quality criteria are measurable: the modulation transfer function (MTF) and the Strehl ratio. First the reproducibility of the alignment process for definition of initial conditions of the lateral position and tilt in reference to the optical axis of the system is investigated. Furthermore, different IOL holders are tested related to the stable holding of the IOL. The measurement is performed by a before-after comparison of the lens position using a typical decentration and tilt tolerance analysis path. Modulation transfer function MTF and Strehl ratio S before and after this tolerance analysis are compared and requirements for lens holder construction are deduced from the presented results.

This study presents a non-invasive and wearable optical technique to continuously monitor vital human signs as required for personal healthcare in today’s increasing ageing population. The study has researched an effective way to capture human critical physiological parameters, i.e., oxygen saturation (SaO2%), heart rate, respiration rate, body temperature, heart rate variability by a closely coupled wearable opto-electronic patch sensor (OEPS) together with real-time and secure wireless communication functionalities. The work presents the first step of this research; an automatic noise cancellation method using a 3-axes MEMS accelerometer to recover signals corrupted by body movement which is one of the biggest sources of motion artefacts. The effects of these motion artefacts have been reduced by an enhanced electronic design and development of self-cancellation of noise and stability of the sensor. The signals from the acceleration and the opto-electronic sensor are highly correlated thus leading to the desired pulse waveform with rich bioinformatics signals to be retrieved with reduced motion artefacts. The preliminary results from the bench tests and the laboratory setup demonstrate that the goal of the high performance wearable opto-electronics is viable and feasible.

Near-infrared (NIR) frequency-domain Diffuse Optical Spectroscopy (DOS) is an emerging technology with a growing number of potential clinical applications. In an effort to reduce DOS system complexity and improve portability, we recently demonstrated a direct digital sampling method that utilizes digital signal generation and detection as a replacement for more traditional analog methods. In our technique, a fast analog-to-digital converter (ADC) samples the detected time-domain radio frequency (RF) waveforms at each modulation frequency in a broad-bandwidth sweep (50- 300MHz). While we have shown this method provides comparable results to other DOS technologies, the process is data intensive as digital samples must be stored and processed for each modulation frequency and wavelength. We explore here the effect of reducing the modulation frequency bandwidth on the accuracy and precision of extracted optical properties. To accomplish this, the performance of the digital DOS (dDOS) system was compared to a gold standard network analyzer based DOS system. With a starting frequency of 50MHz, the input signal of the dDOS system was swept to 100, 150, 250, or 300MHz in 4MHz increments and results were compared to full 50-300MHz networkanalyzer DOS measurements. The average errors in extracted μ_a and μ_s' with dDOS were lowest for the full 50-300MHz sweep (less than 3%) and were within 3.8% for frequency bandwidths as narrow as 50-150MHz. The errors increased to as much as 9.0% when a bandwidth of 50-100MHz was tested. These results demonstrate the possibility for reduced data collection with dDOS without critical compensation of optical property extraction.

In biophotonic imaging, turbid phantoms that are low-cost, biologically-relevant, and durable are desired for standardized performance assessment. Such phantoms often contain inclusions of varying depths and sizes in order to quantify key image quality characteristics such as penetration depth, sensitivity and contrast detectability. The emerging technique of rapid prototyping with three-dimensional (3D) printers provides a potentially revolutionary way to fabricate these structures. Towards this goal, we have characterized the optical properties and morphology of phantoms fabricated by two 3D printing approaches: thermosoftening and photopolymerization. Material optical properties were measured by spectrophotometry while the morphology of phantoms incorporating 0.2-1.0 mm diameter channels was studied by μCT, optical coherence tomography (OCT) and optical microscopy. A near-infrared absorbing dye and nanorods at several concentrations were injected into channels to evaluate detectability with a near-infrared hyperspectral reflectance imaging (HRI) system (650-1100 nm). Phantoms exhibited biologically-relevant scattering and low absorption across visible and near-infrared wavelengths. Although limitations in resolution were noted, channels with diameters of 0.4 mm or more could be reliably fabricated. The most significant problem noted was the porosity of phantoms generated with the thermosoftening-based printer. The aforementioned three imaging methods provided a valuable mix of insights into phantom morphology and may also be useful for detailed structural inspection of medical devices fabricated by rapid prototyping, such as customized implants. Overall, our findings indicate that 3D printing has significant potential as a method for fabricating well-characterized, standard phantoms for medical imaging modalities such as HRI.

We have developed a wearable, fluorescence goggle based system for intraoperative imaging of tumors and image guidance in oncologic surgery. Our system can detect fluorescence from cancer selective near infra-red (NIR) contrast agent, facilitating intraoperative visualization of surgical margins and tumors otherwise not apparent to the surgeon. The fluorescence information is displayed directly to the head mounted display (HMD) of the surgeon in real time, allowing unhindered surgical procedure under image guidance. This system has the potential of improving surgical outcomes in oncologic surgery and reduce the chances of cancer recurrence.

Fluorescence-labeled molecular probes can be used during endoscopy for early cancer detection. As many tumors express multiple cell surface markers and these molecular signatures are heterogeneous across patients, simultaneous imaging of numerous different molecular targets is important for increasing the sensitivity of early cancer diagnosis and personalized treatment. For this purpose, a wide-field, multi-spectral fluorescence-reflectance scanning fiber endoscope (SFE) has been developed. Using a set of calibrated fluorescent test targets at in vivo dye concentration, algorithms and methodologies were developed and demonstrated. Preliminary results showed the promise of fluorescence molecular imaging in clinical applications using the multi-spectral SFE.

The scanning speed for conventional confocal fluorescence imaging systems is limited due to several factors. To improve the speed of scanning, we develop an array confocal fluorescence microscope (ACFM) that can image large 3D volumes faster than conventional confocal microscopes over a large field of view (FOV). This paper will discuss the design and evaluation of the array confocal fluorescence microscope.

In production of ophthalmic freeform optics like progressive eyeglasses, the specimens are tested according to a standardized method which is based on the measurement of the vertex power on usually less than 10 points. For a better quality management and thus to ensure more reliable and valid tests, a more comprehensive measurement approach is required. For Shack Hartmann Sensors (SHS) the dynamic range is defined by the number of micro-lenses and the resolution of the imaging sensor. Here, we present an approach for measuring wavefronts with increased dynamic range and lateral resolution by the use of a scanning procedure. Therefore, the proposed innovative setup is based on galvo mirrors that are capable of measuring the vertex power with a lateral resolution below one millimeter since this is sufficient for a functional test of progressive eyeglasses. Expressed in a more abstract way, the concept is based on a selection and thereby encoding of single sub-apertures of the wave front under test. This allows measuring the wave fronts slope consecutively in a scanning procedure. The use of high precision galvo systems allows a lateral resolution below one millimeter as well as a significant fast scanning ability. The measurement concept and performance of this method will be demonstrated for different spherical and freeformed specimens like progressive eye glasses. Furthermore, approaches for calibration of the measurement system will be characterized and the optical design of the detector will be discussed.

Galvanometer-based scanners (GSs) are the most utilized devices for lateral scanning. Their applications range from commercial and industrial to biomedical imaging. They are used mostly for 2-D scanning (with typically two GSs), but also for 1-D or 3-D scanning (the latter by example with GSs in combination with Risley prisms). This paper presents an overview of our contributions in the field of GSs with regard to the requirements of their most challenging applications. Specifically, we studied the optimal scanning functions - to produce the maximum possible duty cycleη, and we found that, contrary to what has been stated in the literature, the scanning function that provides the highest η is not linear plus sinusoidal, but linear plus parabolic. The most common GS input signals (i.e., sawtooth, triangular, and sinusoidal) were investigated experimentally to determine the scanning regimes that produce the minimum image artifacts, for example in Optical Coherence Tomography (OCT). The triangular signal was thus shown to be the best from this point of view, and several rules-of-thumb were extracted to make the best of GSs in OCT. We also discuss aspects of the command functions of GSs that are necessary to achieve a trade-off between a performance criteria related to the duty cycle and voltage regimes of the device. We finally review aspects of the control solutions of GSs we investigated, to obtain the highest possible precision or the fastest possible response of the scanner.

The modulation transfer function (MTF) is widely used to describe the spatial resolution of x-ray imaging systems. Extensive works have been conducted to achieve accurate and precise measurement of MTF by using a slanted edge test device. The noise level of the slanted edge image is an important factor influencing the accuracy of MTF measurement. Thus in this work, a comparison study was made on the MTF measurement results obtained by using different curve fitting algorithms for ESF determination when analyzing the same image data with different noise levels. The results indicated that the averaged MTF measurement errors got increased with the decrease of the signal-to-noise ratio of the slanted edge images for all of the ESF processing algorithms. But for the same noisy slanted edge image, monotonic fitting algorithm outperformed Gaussian smoothing method or moving polynominal fitting method on MTF measurement.

Glaucoma is the second main cause of the blindness in the world and there is a tendency to increase this number due to the lifetime expectation raise of the population. Glaucoma is related to the eye conditions, which leads the damage to the optic nerve. This nerve carries visual information from eye to brain, then, if it has damage, it compromises the visual quality of the patient. In the majority cases the damage of the optic nerve is irreversible and it happens due to increase of intraocular pressure. One of main challenge for the diagnosis is to find out this disease, because any symptoms are not present in the initial stage. When is detected, it is already in the advanced stage. Currently the evaluation of the optic disc is made by sophisticated fundus camera, which is inaccessible for the majority of Brazilian population. The purpose of this project is to develop a specific fundus camera without fluorescein angiography and red-free system to accomplish 3D image of optic disc region. The innovation is the new simplified design of a stereo-optical system, in order to make capable the 3D image capture and in the same time quantitative measurements of excavation and topography of optic nerve; something the traditional fundus cameras do not do. The dedicated hardware and software is developed for this ophthalmic instrument, in order to permit quick capture and print of high resolution 3D image and videos of optic disc region (20° field-of-view) in the mydriatic and nonmydriatic mode.

Extraction of optical absorption and scattering coefficients from experimental measurements of spatially and/or spectrally resolved diffuse reflectance typically requires that measurements made on unknown samples be calibrated using those made on reference phantoms with well characterized optical properties. Here, we derive the optical scattering and absorption spectra of a solid homogenous resin-phantom using two analytical methods: radially resolved diffuse reflectance (RRDR) based fitting and spectrally resolved diffuse reflectance (SRDR) based fitting. Radially resolved data was acquired using a fabricated probe holder which connected one source fiber to 7 detector fibers with distances ranging between 1.65 to 12.5 mm. Each detector fiber was connected to a spectrometer and spectra ranging 450 to 800 nm were measured when a broadband halogen lamp was used as the source. Diffusion theory based, as well as scaled Monte Carlo based models were used to fit the spectrally and radially resolved reflectance (on a per wavelength basis) to derive the absorption and scattering spectra of the solid phantom. To assess the accuracy of these derived absorption and scattering properties, they were used as reference measurements to reconstruct the optical properties of liquid phantoms, with well-determined absorption and scattering. Reference optical properties determined using the SRDR methods were more accurate in reconstructing the optical properties in liquid phantoms. However, RRDR methods are useful to obtain a spectral profile of the absorption coefficient of an unknown media, for subsequent analyses using SRDR.

Push-broom hyperspectral imaging system ideally disperses the spectral and spatial information in two orthogonal directions preferably aligned with the columns and rows of the imaging sensor. Due to the imperfections in the camera lens and in particular the optical components of spectrograph, wavelength dependent spectral and spatial distortions along with spatial and spectral blur are introduced in the recorded image. In this study, we propose and evaluate a novel method for characterization and resolution enhancement of push-broom hyperspectral imaging systems. First, the spatially and spectrally dependent response function is characterized by measuring the response of the system to spectral and spatial reference objects. The relevant variability of the response function in the imaging plane is captured by a global parametric model. Finally, the response function estimate is used to remove distortions and enhance the spectral and spatial resolution of the system. The resolution enhancements were assessed by observing the change in full width at half-maximum of spectral response function and rise width of the spatial response function. The results of validation show that the proposed method affectively removes geometric distortions and significantly enhances the spectral and spatial resolution of the recorded images.