This PDF file contains the front matter associated with SPIE Proceedings Volume 11231 including the Title Page, Copyright information, Table of Contents, Introduction, and Conference Committee listing.

The integration of multi-color laser excitation into biomedical instrumentation is associated with several challenges which must be overcome to meet the desired performance requirements of the instrument. Multi-color lasers are needed in fluorescence-analysis based applications such as flow cytometry, DNA sequencing, and various types of fluorescence microscopes such as scanning confocal microscopes, TIRF, Light-sheet, SIM, STORM and STED techniques. In many cases, these techniques require capability for excitation of multiple fluorophores and therefore access to several laser lines within the instrument. The advantages of lasers over other light-sources, such as LEDs, for these techniques are high-brightness and wavelength precision. Unfortunately, the inclusion of lasers also introduces complexity in the design. Laser combiners including individual lasers have been integrated with the intention of simplifying the design, as an alternative to traditional multiline gas lasers. This solution, however, is still susceptible to misalignment over time, and can increase the size and cost of the instrument. A compact, permanently aligned, multi-line laser simplifies the integration of multiple laser wavelengths by eliminating the need for in-field alignment and service, reducing manufacturing cost, and allowing for more compact designs. In addition to overcoming the initial design challenges of integrating lasers into bio-instrumentation, a multi-line laser is also an easy-to-upgrade field replacement for previous generations of technology, such as Argon Ion gas lasers. Here we demonstrate how a compact and robust permanently aligned multi-line solid-state laser can be achieved using novel techniques for optical assembly and miniaturization. We also show how the integration of such a multi-line laser can deliver the required optical performance while simplifying the design and enabling commercialization of a new bioimaging technology, and exemplify the integration of this solution as a drop-in replacement for an Argon Ion lasers in existing microscope set-ups.

In this study we investigate the possibility of spectra stitching in the context of Spectral Domain – Optical Coherence Tomography (SD-OCT). The aim is to reach a high axial resolution while keeping sampling issues to a low level (slow decay in depth) but still operating with the fastest camera line rate available. The paper focuses mainly on simulations of spectrometer signals and the stitching procedure. It briefly introduces the experimental system. The findings of this study are relevant to most of the SD-OCT systems and could also be transferred to Swept Source OCT (SS-OCT) where they will help to increase the axial resolution capabilities.

The availability of high quality laser diode based lasers in the visible range has boosted up many bio-medical applications like Confocal Microscopy and Flow Cytometry. These new lasers are enabling high resolution close to the diffraction limit and improved sensitivity in many biological and medical applications. We explain the most important performance parameters of these lasers which are required to achieve best test results and excellent resolution by using suited laser sources and accessories for these two applications. Some of these parameters are very low noise, low beam pointing, single TEM00 mode like beam quality for diffraction limited spots and the beam shape. Beside the laser sources the use of single mode fibers is essential to achieve excellent laser beam quality and tailored beam shapes in combination with very low beam pointing for highest resolution and superior test results. The paper will explain the important role of Spatial Filtering and how it is working based on apodization in the Fourier space.

The human body constantly undergoes heat exchange with the environment, and that can be imaged well by thermal imaging. Some application of thermal imaging is in neurology, vascular disorders, rheumatic diseases, oncology, dentistry, and ophthalmology. Every activity described above has unique characteristics. The temperature range for inflammatory condition of the human skin varies significantly from that of an ocular surface. Specific to ophthalmology, the thermal imaging should be able to capture the subtle changes of ocular surface temperature. The existing thermal sensors used in most ophthalmic studies have a dynamic range from -20°C to 350°C and accuracy of 2°C. This paper talks about the development and calibration of a new sensor with optimization in the desired dynamic range and its demonstration for capturing the ocular surface temperature.

In this paper we present a new design for diffractive multifocal intraocular lens with the primary goal to compensate as much as possible the effect of chromatic aberration. As LCA due to diffraction and refraction act in an opposite way it can in principle be compensated. However rules to create an achromatic lens based on refractive-diffractive lens are quite complex because of topology, dioptry , abbe number,… In this study, we will investigate the effect of wavelength on the through-focus modulation transfer function (MTF) and diffraction efficiency for different pupil apertures and different diffractive intraocular lenses.

Since the beginning of this year, the full screen mobile phone has been more and more popular. Because the traditional capacitive fingerprint sensor cannot work under the display, it should be placed on the side or back of the phone. However, it is unfavorable to the consumer experience. Therefore, the demand for in-display fingerprint recognition technology has arisen. The in-display fingerprint identification technology can be divided into optical and ultrasonic fingerprint identification. Because the ultrasonic fingerprint identification is limited by low yield rate and high cost at present, the optical fingerprint identification is more popular in market. The optical fingerprint identification is advantageous for the identification not affected by dry or greasy fingers, higher yield and lower cost. In this study, the miniature wide angle lens under the display is developed for the OLED panel. For optical fingerprint identification, the illumination is inevitable. In comparison with the LCD panel, the OLED panel needs not the backlighting because each pixel has its own light. The optical sensor is based on the principle of the frustrated total internal reflection (FTIR). The ridge of the finger destroys the total internal reflection (TIR), and then the dark pattern appears. On the contrary, the valley of the finger satisfies the TIR condition, and then the bright pattern generates. Because the camera is implemented in the narrow space of the mobile phone, the ultra-wide field of view and extremely short total track length are necessary. In this study, the optical design can successfully meet the requirement for fingerprint recognition.

Numerous pulmonary disorders are associated with fibrosis, however, current methodology falls short when studying turbid tissue. Optical clearing (OC) offers a chemical-based approach for deep tissue imaging. We optimized organ-level OC approach and combined it with large-scale, label-free multiphoton microscopy (MPM) and second harmonic generation microscopy (SHGM) to reveal fibrillar collagen in whole murine lungs. The standardization of several underlying steps allowed for a streamline approach. This method revealed significant differences in collagen deposition between control and treated lungs, while establishing a new approach based on OC and MPM/SHGM imaging for 3D analysis of lung fibrosis in the whole lung.

Measuring the heart rate is one critical piece of information that a health professional uses to diagnose the health state of an individual. Electrocardiogram (ECG/EKG) is essentially responsible for patient monitoring and diagnosis. The extracted feature from the ECG signal plays a vital role in diagnosis of cardiac disease. Therefore, this paper presents how to design, build, and test a cost-effective prototyping tool for ECG feature extraction and recognition. When testing a real ECG from a human subject, the developed tool can preserve useful ECG information while removing unwanted noise and interference components by adaptively determining the filtering values that directly translate to a real time analog circuit for rapid prototyping. Then a decisionmaking model which is based on the peak detection strategy is applied for automated heart rate state recognition in real-time.

A comprehensive understanding of microvascular networks is required to generate platforms that track treatment efficacy. Current approaches are labor intensive and limited to small tissue volumes. In this work we describe an acquisition and segmentation framework for low-cost imaging and microvascular modeling at resolution comparable to confocal with data rates comparable to light-sheet microscopy. Segmentation is performed using a GPU-based method that extracts microvascular structure and connectivity embedded in these images. The microvasculature network is stored such that the graph [G = V, E] structure can be exploited to quantify large-scale angiomes and facilitate data mining at the terabyte scale.

The concentration of free hemoglobin (FHb) in blood bag is an important index to evaluate blood quality. And the chemical method, which is widely used in clinic, not only wastes precious blood resources, but also consumes time, be labor-intensive, and pollutes the environment. Although spectral analysis can make up for the shortcomings of traditional chemical methods, its accuracy also be seriously affected due to unstable the optical parameters of the blood bag and complexity of blood composition. Therefore, this paper proposed a wavelength selection method based on modified ant colony optimization (ACO) algorithm. This algorithm firstly calculates the correlation coefficient between each wavelength and the FHb concentration as the initial pheromone for each wavelength to improve the convergence speed of ACO algorithm; Then, the optimized wavelengths are sorted according to the intensity of the pheromone, the number of optimized wavelengths for modeling is increased in turn, and the root-mean-square error of the model is used as an evaluation index to determine the final optimal wavelength. In this study, a small tube in the front of the blood bag was used as a container, and the transmission spectrum of plasma in the small tube was collected. The regression results of the optimized spectrum were compared with that of the original spectral. The experimental results showed that the method proposed in this paper can obviously improve the analysis accuracy of blood quality, which means this method can effectively inhibit the influence of non-target components and the difference in blood bags on the detection of blood quality.

Human blood analysis has provided rich information in rapid clinical diagnosis. Different from conventional blood cell counting method which is environment-dependent and costly, this study proposes an advanced blood cells imaging method at micron-scale to reduce the size of the equipment and decrease the total cost of testing. This approach applies the deep learning method and a convolutional neural network in reconstructing object images from the diffraction patterns. The holographic image is extracted by the convolution layer and the feature classification of the hidden layer rapidly identifies each diffraction pattern of the holographic image. The mean IoU for masks generated from the hologram is 0.876. Consequently, this deep learning approach is significantly more preferable to conventional calculation. It, thus, provides a portable, compact and cost-effective contrast-enhanced microholography system for clinical diagnosis.

Hyperspectral dark-field microscopy of resected breast tissues is being developed to assess tumor margins in breast-conserving surgery. Classification between normal/benign and malignancy subtypes is achieved by a spectral angle mapper algorithm, quantifying the similarity of an unclassified spectrum to a known type from a reference spectral library. A library of reference spectra of various tissue types was established by extracting spectra from pathology-confirmed regions of interest in resected breast tissues. The tumor margin analysis is performed by calculating the tissue-dependent angle threshold between the unknown sample and a reference spectrum, treating them as vectors in multi-dimensional hyperspectral space. This work presents methods to determine and validate the tissue type-dependent threshold angles, the reference spectral library of various tissue types, and tumor margin detection in resected human breast tissues.

Integrating spheres (IS) facilitate accurate measurements of the total reflectance and transmittance of turbid media, which can be used to determine optical properties of the sample measured. Translation of measurements into optical properties are achieved using theoretical photon migration models. A widely used approach with IS measurements is to use the inverse adding-doubling (IAD) method that utilizes the forward adding-doubling method, which is a rigorous numerical forward solver of the 1-D radiative transport equation. In order to experimentally satisfy the 1-D nature of the theoretical model, samples must be large enough to be modeled as infinite in extent along axes normal to incident beam. Here, we explore constraint on the required sample dimensions by comparing errors in modeled reflectance and transmittance between the adding-doubling and Monte Carlo simulations. We compare both the forward predictions and the inverse extraction of the optical properties for samples with varying dimensions, sample optical properties and beam profiles. Lateral losses (loss of light from sides of the sample) were observed to be significant when illumination beam diameters become comparable to sample length. Errors of 2-3% were noted between MC predictions vs. the adding-doubling estimates for reflectance and transmittance and these translated to 5-30% errors in IAD estimated optical absorption while the extracted scattering coefficients remained unaffected and had errors < 2%, relative to simulated values. We find that when the incident beam had diameter less than 80% of the sample length, the estimated optical properties of the medium were well extracted using the IAD.

Liposuction is one of the most common plastic surgery. Recently developed, a variety of technologies for lipolysis have been introduced to replace conventional liposuction. We have developed two types of laser lipolysis systems, which are non-invasive 1060 nm diode laser and minimally invasive laser system with 1980 nm and 2300 nm wavelengths. The developed laser lipolysis systems were used for preclinical experiments for a mini-pig. The thickness of the subcutaneous fat layer was measured by micro-CT, ultrasound and histopathology analysis. Our preclinical results showed that fat reduction was the most noticeable when using both non-invasive and invasive laser irradiation with combined all three laser wavelengths.

Radiochromic films, owing to their high spatial resolution, are well-suited for radiation therapy dosimetry and quality assurance purposes. However, their spectroscopic response to radiotherapy beams has not been comprehensively investigated, except for a limited subset of beam qualities. In this work, we explore the spectral response of the EBT3 and EBT-XD radiochromic film models to different clinical radiation beam qualities including photons and protons. The spectral response of EBT3 and EBT-XD films showed two peaks at 585 nm and 635 nm for both photon and proton irradiation. Beyond a certain batch- and model-dependent dose threshold a saturation behavior was observed in the primary absorption peak. For beam qualities studied in this work, the spectral response of proton-irradiated films showed a systematic under-response compared to their photon-irradiated counterparts in both EBT-3 and EBTXD radiochromic films models.

We present a simple approach to determine the refractive index of polystyrene microspheres which are frequently utilized as scatterers in turbid phantoms. The approach is based on Mie theory and transmittance measurements of polystyrene microspheres suspended in media with different refractive indices allowing simultaneous optimization of the diameter and refractive index of the polystyrene microspheres. The refractive index of the medium is changed through the addition of sucrose. Based on our preliminary results, the estimated refractive index of polystyrene microspheres deviates from the literature values by 0.2% and the estimated diameter by 20 nm from the nominal value provided by the manufacturer.

In surgery, the tips of energy delivery devices heat up far above 100 C. In this study, the typical thermal relaxation time of the tips after activation were measured using a thermal camera. The temperatures of the tips stayed over 60 C for tens of seconds. When touching nearby tissue for a few seconds, unintended thermal damage can be induced especially during endoscopic procedures where the space is narrow. Using water drops as irrigation, ambient temperatures were reached within several seconds. Surgeons should be aware of the residual heat of ablative devices.

Questions about the feasibility and risks of complex optical systems can be answered by ray-trace models evaluating the system performance. A problem is that these simulations require hours for each run, and months for a complete result. A solution is to automate the analysis using a programming language, but there remains the challenge of creating a ray-trace engine to perform the analysis. We instead utilize the Application Programming Interface (API) of existing ray-trace engines to perform many customized analyses. As an example, we computed an SNR map as a function of the field of view position of a forward scanning endoscope. The SNR was >20 at any field point. The origin of most noise was the uncoated cover plate and addressing the problem would increase the SNR to >40. Each ray-trace takes 2.7 hours representing several years to complete the analysis making it unpractical. The API code and a lower sampling for qualitative analysis reduced the required time by a factor of 1000x allowing for a reasonable workflow.

The pulse oximeter is perhaps the first biophotonics-based medical device, and standards have existed for decades to enable characterization of device performance in terms of quantitative metrics, including test methods for clinical validation in human subjects. As cerebral oximetry based on near-infrared spectroscopy has begun to mature, a standard is currently in development to address observed issues with device quality, robustness, and consistency. The availability of standards ensures devices are safe and effective and can improve confidence in their clinical utility. Significant challenges remain in developing clinically relevant test methods.

Photoacoustic imaging (PAI) is an exciting emerging modality with many potential clinical and preclinical applications. Due to its nascent status, at present, no standards exist to define system performance or establish well-validated, consensus-based performance test methods. The International Photoacoustic Standardisation Consortium (IPASC) is a community-led organization that seeks to reach consensus on PAI standardisation to improve the quality of preclinical studies and accelerate clinical translation. Current IPASC activities include: phantom development; establishment of standard terminology and image quality metrics; and open-source data file format development. These activities aim to help PAI become a mature, widely-adopted imaging technology.

The AAPM sanctioned a task group to study performance metrics for fluorescence guided surgery systems, with the goal of establishing professional guidance documentation which would initiate future efforts in standardization and ultimately a more standardized approach to this field. While tissue phantoms and test targets are widely used in radiology, the field of surgical guidance has not had any clear consensus around the idea of quantifying performance goals. The field is largely driven by manufacturers stating performance goals and training surgical users. There has been little interchangeability between systems, yet the field is now quite crowded with possible systems to use for indocyanine green imaging. The task group studied the problem and has converged towards a set of ideal goals and recommendations.

Developing standards and test requirements is difficult, as it involves coming to consensus with a group of people with different backgrounds, interests, and motivations. It is essential that standardization groups begin with a clear agreement on the purpose of whatever they are developing. This is usually relatively clear for safety standards and test targets, but sometimes more nebulous for performance standards. This agreement on purpose is critical not just to facilitate reaching consensus, but also to the future success of the tool or standard. As an example, the purpose of the ophthalmic safety standard is clear (avoid blinding people) and the standard is heavily used. The OCT standard, on the other hand, did not have a clearly agreed upon purpose, and has not been widely adopted. For phantoms that reduce the need for human testing, however, this need for consensus is much reduced, as the benefit can quickly become self-evident..

We have optimized our prior phantom-based test method for cerebral oximetry performance using a new 3D-printed cerebrovascular module (CVM). In addition, we have and added a surrogate for a thin perfused scalp layer to evaluate perfusion- related confounding factors. The new CVM’s optical properties better represented biological tissue and also incorporated a water-mimicking dye. The modular phantom also included biologically relevant scalp/skull and cerebrospinal fluid (CSF) layers. Performance testing of two commercially available clinical oximeters with the modified CVM over a range of oxygen saturation levels illustrates the utility of our solid phantom-based approach for standardized cerebral oximeter performance assessment.

Recent advances of medical technologies are demanding a new generation of phantoms that may encode the biophysical features needed for their assessment. Here, we propose hybrid materials based on emulsions of polydimethylsiloxane with glycerol or aqueous polyvinyl alcohol as a versatile platform for phantoms for applications such as optical, acoustic, magnetic resonance or X-ray imaging. These materials display intrinsic optical scattering, retain the acoustic features of polydimethylsiloxane, enable the inclusion of a broad taxonomy of hydrophobic and hydrophilic dyes of interest for photoacoustic imaging, may be suitable to simulate the cellularity of organs due to their peculiar microstructure, and, thanks to the possibility to include aqueous solutions of metabolites, may be of interest for magnetic resonance imaging and computed tomography

Tissue phantoms for near infrared fluorescence imaging consisting of quantum dots embedded in hard polymer has become the material of choice as calibrator for near infrared fluorescence imaging. Through a calibration process, it can acquire International Standard (SI) units of light, which advances its utility as a possible reference standard for the fluorescence guided imaging community. In this paper I will discuss the calibration steps, and how the calibrated tissue phantoms can be used as a standard by both the imaging device and contrast agent developer.

Objective: Pelvic organ prolapse (POP) can happen if the support tissues are weak or damaged, or if the pelvic floor muscles are weak and saggy. POP tends to be more likely after childbirth, menopause or overweight. Although it is better to prevent POP than try to fix it, there was little way to prevent except for the pelvic floor muscles training. Besides, this is an uncomfortable condition that affects one in three women, however, it is a hidden problem many people aren’t comfortable talking about. Thus, this study proposed a method to self-check with the vaginal endoscope which was made through a three-dimensional printing. Methods: The prototype design was divided into two parts: flexible material for inserting into and contacting with the wall of vagina, and rigid body for observing. While putting air in the material through the rigid body, the camera which was set to the tip of rigid body could observe the inside of vagina. The position and orientation of camera was measured with two sensors. The provided air pressure was possible to estimate the pressure inside of vagina. Results: The forced disturbance from the test bed which was made to confirm the effectiveness enabled us to perceive the position and degree of disturbance which was regarded as the early stage of prolapse. Discussion: It was discussed that the continuous observation through 3D-printing-based vaginal endoscope helped prevent POP because the low-cost design was possible to self-check anytime.