The anterior refracting surface of the eye is the thin tear film that forms on the surface of the cornea. Following a blink, the tear film quickly smoothes and starts to become irregular after 10 seconds. This irregularity can affect comfort and vision quality. An in vivo method of characterizing dynamic tear films has been designed based upon a near-infrared phase-shifting interferometer. This interferometer continuously measures light reflected from the tear film, allowing sub-micron analysis of the dynamic surface topography. Movies showing the tear film behavior can be generated along with quantitative metrics describing changes in the tear film surface. This tear film measurement allows analysis beyond capabilities of typical fluorescein visual inspection or corneal topography and provides better sensitivity and resolution than shearing interferometry methods. The interferometer design is capable of identifying features in the tear film much less than a micron in height with a spatial resolution of about ten microns over a 6 mm diameter. This paper presents the design of the tear film interferometer along with the considerations that must be taken when designing an interferometer for on-eye diagnostics. Discussions include eye movement, design of null optics for a range of ocular geometries, and laser emission limits for on-eye interferometry.

Narrow band imaging (NBI) is a spectrally-selective reflectance imaging technique that is used as an adjunctive approach to endoscopic detection of mucosal abnormalities such as neoplastic lesions. While numerous clinical studies in tissue sites such as the esophagus, oral cavity and lung indicate the efficacy of this approach, it is not well theoretically understood. In this study, we performed Monte Carlo simulations to elucidate the factors that affect NBI device performance. The model geometry involved a two-layer turbid medium based on mucosal tissue optical properties and embedded cylindrical, blood-filled vessels at varying diameters and depths. Specifically, we studied the effect of bandpass filters (415±15 nm, 540±10 nm versus white light), blood vessel diameter (20-400 μm) and depth (30 - 450 μm), wavelength, and bandwidth on vessel contrast. Our results provide a quantitative evaluation of the two mechanisms that are commonly believed to be the primary components of NBI: (i) the increased contrast provided by high hemoglobin absorption and (ii) increase in the penetration depth produced by the decrease in scattering with increasing wavelength. Our MC model can provide novel, quantitative insight into NBI, may lead to improvements in its performance.

Contamination of the inner surface of indwelling (implanted) medical devices by microbial biofilm is a serious problem. Some microbial bacteria such as Escherichia coli form biofilms that lead to potentially lifethreatening infections. Other types of medical devices such as bronchoscopes and duodenoscopes account for the highest number of reported endoscopic infections where microbial biofilm is one of the major causes for these infections. We applied a hyperspectral imaging method to detect biofilm contamination on the surface of several common materials used for medical devices. Such materials include stainless steel, titanium, and stainless-steeltitanium alloy. Potential uses of hyperspectral imaging technique to monitor biofilm attachment to different material surfaces are discussed.

In minimal invasive surgery, rigid endoscopes are used to view inside the body through natural or artificial made orifices. As the price of a rigid endoscope is high, they are being constantly re-used after a cleaning and steam sterilization procedure at the Department of Central Sterilization. However, due to mechanical, chemical and thermal stresses, endoscopes degrade over time. To determine whether an endoscope still provides sufficient quality, personnel of the Department of Central Sterilization visually inspect the outside and inside of an endoscope. In practice this check is hard as it appears difficult to tell whether an image is good enough as it should be compared to the image of an new endoscope of the same type. Because of the large diversity in endoscopes, the variation of image quality of new endoscope is already so large, that it is difficult to perform this manual check objectively. In this paper we describe the results of using an experimental test bench to measure the optical quality of endoscopes over the years 2007-2011. The system is based on measuring the illumination pathway using a white LED and photo cell and the viewing pathway using a LCD generated test pattern and high resolution camera. The measurements show that endoscopes roughly degrade 20% per year, but also that the variation in degradation is so high and uncorrelated to the type of endoscope that structural measurement of the quality of endoscopes may be a prerequisite. Looking at the system itself, it appeared that although the system had sufficient stability over these years to allow conclusions, it has too much drawbacks to be used at the Department of Central Sterilization, like the stability of the LCD screen, loosing track of endoscopes when they are placed in another basket and the large number of manual steps needed to perform a measurement. For this reasons we present a new design of an endoscope measurement system, called the MDE, a Measurement Device for Endoscopes. It is based on comparing the endoscope image of the inside of a marker sphere with that of a new one. After a test run at the St Jansdal clinic in Harderwijk, the Netherlands, from March to December 2011, the system will be re-designed the coming months to include endoscope labeling with a data matrix, detection of broken illumination fibers and lenses and scanning of water and dust particles. Aimed to be commercially available from the end of 2012, we hope that this system will be a valuable device for assuring the optical quality of endoscopes in clinical practice.

Optical radiation hazards of scanning light sources are often evaluated using pulsed light source criteria, with the relevant pulse parameter equivalent to the scanning light source determined by the energy delivered through a measurement aperture. This study utilizes a numerical analysis based upon the melanin granule model to compare the thermal effects of scanning and pulsed light sources through a measurement aperture in the pigmented retinal layer. The numerical analysis calculates the thermal contribution of individual melanin granules with varying temporal sequence, and finds that temperature changes and thermal damage thresholds for the two different types of light sources were not equal.

Hyper-spectral imaging has gained recognition as an important non-invasive research tool in the field of biomedicine. Among the variety of available hyperspectral imaging systems, systems comprising an imaging spectrograph, lens, wideband illumination source and a corresponding camera stand out for the short acquisition time and good signal to noise ratio. The individual images acquired by imaging spectrograph-based systems contain full spectral information along one spatial dimension. Due to the imperfections in the camera lens and in particular the optical components of the imaging spectrograph, the acquired images are subjected to spatial and spectral distortions, resulting in scene dependent nonlinear spectral degradations and spatial misalignments which need to be corrected. However, the existing correction methods require complex calibration setups and a tedious manual involvement, therefore, the correction of the distortions is often neglected. Such simplified approach can lead to significant errors in the analysis of the acquired hyperspectral images. In this paper, we present a novel fully automated method for correction of the geometric and spectral distortions in the acquired images. The method is based on automated non-rigid registration of the reference and acquired images corresponding to the proposed calibration object incorporating standardized spatial and spectral information. The obtained transformation was successfully used for sub-pixel correction of various hyperspectral images, resulting in significant improvement of the spectral and spatial alignment. It was found that the proposed calibration is highly accurate and suitable for routine use in applications involving either diffuse reflectance or transmittance measurement setups.

Key properties of polyimide-coated optical fibers, unaged and exposed to various harsh environments, were investigated. The main intent was to model extreme conditions that can be encountered in medical applications of the fibers. A fiber designed by OFS showed good strength and was able to withstand exposure to extreme heat and humidity, multiple autoclave cycles, extended water soak and immersion in organic solvents. Similar fibers offered by other suppliers displayed shortcomings in some of the tested properties.

In recent years there has been increasing interest in development of consensus, tissue-phantom-based approaches for assessment of biophotonic imaging systems, with the primary goal of facilitating clinical translation of novel optical technologies. Well-characterized test methods based on tissue phantoms can provide useful tools for performance assessment, thus enabling standardization and device inter-comparison during preclinical development as well as quality assurance and re-calibration in the clinical setting. In this review, we study the role of phantom-based test methods as described in consensus documents such as international standards for established imaging modalities including X-ray CT, MRI and ultrasound. Specifically, we focus on three image quality characteristics - spatial resolution, spatial measurement accuracy and image uniformity - and summarize the terminology, metrics, phantom design/construction approaches and measurement/analysis procedures used to assess these characteristics. Phantom approaches described are those in routine clinical use and tend to have simplified morphology and biologically-relevant physical parameters. Finally, we discuss the potential for applying knowledge gained from existing consensus documents in the development of standardized, phantom-based test methods for optical coherence tomography.

We have developed a fluorescence goggle device for intraoperative oncologic imaging. With our system design, the surgeon can directly visualize the fluorescence information from the eyepieces in real time without any additional monitor, which can improve one's coordination and surgical accuracy. In conjunction with targeting fluorescent dyes, the goggle device can successfully detect tumor margins and small nodules that are not obvious to naked eye. This can potentially decrease the incidence of incomplete resection.

Two-dimensional beam steering is often required in medical laser scanning systems such as OCT or confocal microscopy. Usually two linear galvo mirrors are used for their large apertures and large scan angles. The galvos are placed at the vicinity of the scan lens entrance pupil and separated by a "displacement distance." This distance limits the scan fields and/or reduces the effective aperture of the scan lens. Another option is to use a beam relay to relay one galvo on to the other. However, beam (or pupil) relays are usually complicated, expensive and can add significant aberrations. This paper discusses a simple, all reflective, diffraction limited, color corrected, beam relay, capable of large scan angles and large deflecting mirrors. The design is based on a unique combination of an Offner configuration with a Schmidt aspheric corrector, which allows a significantly larger scan field than scanners using galvos separated by the displacement distance. Design example for 12 mm diameter pupil and 30 degrees optical field are shown. The design details and performance are presented as well as different possible configurations for use in high performance microscopic systems and laser projection systems.

Time-resolved measurement of early-arriving photons has been shown by a number of groups to effectively reduce photon scatter and improve resolution in diffuse optical tomography (DOT) and fluorescence mediated tomography (FMT). Recently, we experimentally showed that measurement of early-arriving photons resulted in the reduction of the instrument photon density sensitivity function (PDSF) width by a factor of 2 to 2.5 over a wide range of relevant small-animal imaging conditions using a picosecond pulsed laser and time-resolved photon counting combination. However, we also showed that this experimental improvement was less than predicted from time-resolved Monte Carlo simulations. Specifically, a reduction by a factor of 4 or better was predicted, but this could not be achieved with our system. To better understand this, in this work we have experimentally tested the effect of a series instrumentation (hardware) parameters on the experimentally measured time-dependant PDSFs including, i) source and detector geometry, ii) detector sensitivity, iii) laser illumination intensity, and iv) instrument temporal impulse response function. Our ongoing research indicates that all of these parameters affected the relative PDSF width by as much as 10-25%, particularly at early time points. The results of this work are significant because they show in a number of cases that significant disagreement between experimental PDSFs and theoretical models exist as a result of minor changes in experimental configuration. We also anticipate that these results will be useful in the design of future time-resolved DOT and DFT imaging systems.

Erythema is a common visual sign of gingivitis. In this work, a new and simple low-cost image capture and analysis method for erythema assessment is proposed. The method is based on digital still images of gingivae and applied on a pixel-by-pixel basis. Multispectral images are acquired with a conventional digital camera and multiplexed LED illumination panels at 460nm and 630nm peak wavelength. An automatic work-flow segments teeth from gingiva regions in the images and creates a map of local blood oxygenation levels, which relates to the presence of erythema. The map is computed from the ratio of the two spectral images. An advantage of the proposed approach is that the whole process is easy to manage by dental health care professionals in clinical environment.

Hyperspectral imaging provides means for characterizing large biological samples with microscopic spatial resolution and a narrow spectral sampling interval. However, this approach requires having a measurable light signal in each spectral band. Overcoming the limitations imposed by working with biological samples requires the use of a highly sensitive sensor to detect weak signals. For this study we have built and compared the performance of two imaging spectrometers using optimized for low light environments: an electron-multiplying CCD (EMCCD) and a scientific CMOS (sCMOS). Both systems have been designed to lower the risk of damaging photosensitive samples, delay the bleaching of fluorophores and detect weak fluorescence signals. The cameras work within the VNIR spectral region (400 nm - 900 nm) with a spectral sampling lower than 4 nm. The produced images have scene pixel sizes smaller than 25 μm and a field of view larger than 25 mm. The systems have been tested side to side measuring the diffusion front of a fluorescent tag in samples of porcine skin in challenging light conditions. The study aimed to show the advantages and limitations of each approach. Preliminary results show good performance of the EMCCD for fluorescence applications, whereas more experimental results are needed to be able to conclude on the performance of the sCMOS sensor. However, the sCMOS appears promising for imaging scenes with high dynamics in low light settings.

Spatial resolution of hyperspectral imaging systems can vary significantly due to axial optical aberrations that originate from wavelength-induced index-of-refraction variations of the imaging optics. For systems that have a broad spectral range, the spatial resolution will vary significantly both with respect to the acquisition wavelength and with respect to the spatial position within each spectral image. Variations of the spatial resolution can be effectively characterized as part of the calibration procedure by a local image-based estimation of the pointspread function (PSF) of the hyperspectral imaging system. The estimated PSF can then be used in the image deconvolution methods to improve the spatial resolution of the spectral images. We estimated the PSFs from the spectral images of a line grid geometric caliber. From individual line segments of the line grid, the PSF was obtained by a non-parametric estimation procedure that used an orthogonal series representation of the PSF. By using the non-parametric estimation procedure, the PSFs were estimated at different spatial positions and at different wavelengths. The variations of the spatial resolution were characterized by the radius and the fullwidth half-maximum of each PSF and by the modulation transfer function, computed from images of USAF1951 resolution target. The estimation and characterization of the PSFs and the image deconvolution based spatial resolution enhancement were tested on images obtained by a hyperspectral imaging system with an acousto-optic tunable filter in the visible spectral range. The results demonstrate that the spatial resolution of the acquired spectral images can be significantly improved using the estimated PSFs and image deconvolution methods.

In recent years, using the detection of interstitial fluid glucose concentration to realize the real-time continuous monitoring of blood glucose concentration gets more and more attention, because for one person, the relationship between blood glucose concentration and interstitial fluid glucose concentration satisfies specific rules. However, the glucose concentration in interstitial fluid is not entirely equal to the glucose concentration in blood and has a physiological lag because of the physiological difference of cells in blood and interstitial fluid. Because the clinical diagnostic criteria of diabetes are still blood glucose concentration, the evaluation model of the physiological lag parameter between the glucose concentration in blood and the glucose concentration in interstitial fluid should be established. The physiological difference in glucose molecules uptake, utilization, and elimination by cells in blood and interstitial fluid and the diffusion velocity of glucose molecule from blood to interstitial fluid will be induced to the mass transfer model to express the physiological lag parameter. Based on the continuous monitoring of glucose concentration in interstitial fluid, the project had studied the mass transfer model to establish the evaluation model of the physiological lag parameter between the glucose concentration in blood and the glucose concentration in interstitial fluid. We have preliminary achieved to evaluate the physiological lag parameter exactly and predict the glucose concentration in blood through the glucose concentration in interstitial fluid accurately.