This PDF file contains the front matter associated with SPIE Proceedings Volume 9700, including the Title Page, Copyright information, Table of Contents, Introduction, and the Conference Committee listing.

The National Institute of Standards and Technology (NIST) has maintained scales for reflectance and transmittance over several decades. The scales are primarily intended for regular transmittance, mirrors, and solid surface scattering diffusers. The rapidly growing area of optical medical imaging needs a scale for volume scattering of diffuse materials that are used to mimic the optical properties of tissue. Such materials are used as phantoms to evaluate and validate instruments under development intended for clinical use. To address this need, a double-integrating sphere based instrument has been installed to measure the optical properties of tissue-mimicking phantoms. The basic system and methods have been described in previous papers. An important attribute in establishing a viable calibration service is the estimation of measurement uncertainties. The use of custom models and comparisons with other established scales enabled uncertainty measurements. Here, we describe the continuation of those efforts to advance the understanding of the uncertainties through two independent measurements: the bidirectional reflectance distribution function and the bidirectional transmittance distribution function of a commercially available solid biomedical phantom. A Monte Carlo-based model is used and the resulting optical properties are compared to the values provided by the phantom manufacturer.

The goal of this work was to develop phantoms that match the refractive indices and absorption coefficients between 0.15 and 2.0 THz of the freshly excised tissues commonly found in breast tumors. Since a breast cancer tumor can contain fibrous and fatty tissues alongside the cancerous tissues, a phantom had to be developed for each. In order to match the desired properties of the tissues, oil in water emulsions were solidified using the proven phantom component TX151. The properties of each potential phantom were verified through THz time-domain spectroscopy on a TPS Spectra 3000. Using this method, phantoms for fibrous and cancerous tissue were successfully developed while a commercially available material was found which matched the optical properties of fatty tissue.

Solid homogeneous turbid phantoms can be employed to mimic the attenuation and angular distribution of light emerging from tissue, e.g., to assess the responsivity of the detection system of diffuse optics instrumentation and to support standardized performance tests of functional near-infrared spectroscopy devices. We present three methods to quantify the wavelength-dependent diffuse transmittance, relying on (1) measurement of radiance exiting the phantom by a detector far from the exit aperture, (2) simple recording of radiance by a power meter close to the exit aperture and correction for the finite distance between phantom surface and detector, (3) determination of the reduced scattering and absorption coefficients by time-resolved diffuse transmittance measurements and forward calculation of the time-integrated diffuse transmittance based on the diffusion model. The implications of the different approximations related to these approaches are discussed. The various methods were applied to characterize solid slab phantoms, and the results were compared. Specifically, for an epoxy-resin based phantom having a thickness of 2 cm, a reduced scattering coefficient of about 0.5/mm and an absorption coefficient of about 0.01/mm, the diffuse transmittance values obtained by the three different methods were found to agree within about 10%.

Tissue-simulating phantoms provide the opportunity to evaluate the performance of optical and spectroscopic instruments under controlled experimental conditions. Recent efforts have advanced phantom fabrication methods to provide more tissue realistic phantoms, both in terms of a) incorporating absorbing agents that more faithfully mimic in vivo tissue chromophores spanning visible and near infrared regimes and b) accounting for multi-layer tissue structures with distinct optical properties. The spectral scattering properties in these phantoms, however, are typically based only on a single scattering agent, thereby locking the spectral scattering properties to a single particle size distribution. However, in both healthy tissue as well as pathologic tissue, regions of distinct and differentiated scattering may be present. With differing mean size and distribution of scattering objects in these tissue regions, the relative wavelength-dependent scattering spectra may vary. For example, partial thickness burns exhibit significant cellular damage and collagen denaturation that will significantly alter the wavelength-dependent scattering properties resembling large Mie-like scatterer distributions in both visible and near infrared regimes. We present a low-cost method to fabricate silicone tissue-simulating phantoms with tunable scattering spectra properties that span visible and near infrared wavelengths. We use optical polishing agents (white aluminum oxides powders) at various grit sizes to approximate Mie scattering across multiple mean particle sizes. Mean particle sizes used in this study range from 17-3 micron. The optical properties of these phantoms are verified using an integrating sphere in combination with inverse adding-doubling methods. The tolerances of this fabrication method will be discussed.

Increasing numbers of devices are emerging which involve biophotonic imaging on a mobile platform. Therefore, effective test methods are needed to ensure that these devices provide a high level of image quality. We have developed novel phantoms for performance assessment of near infrared fluorescence (NIRF) imaging devices. Resin molding and 3D printing techniques were applied for phantom fabrication. Comparisons between two imaging approaches – a CCD-based scientific camera and an NIR-enabled mobile phone – were made based on evaluation of the contrast transfer function and penetration depth. Optical properties of the phantoms were evaluated, including absorption and scattering spectra and fluorescence excitation-emission matrices. The potential viability of contrastenhanced biological NIRF imaging with a mobile phone is demonstrated, and color-channel-specific variations in image quality are documented. Our results provide evidence of the utility of novel phantom-based test methods for quantifying image quality in emerging NIRF devices.

Endoscopic catheter-based imaging systems that employ a 2-dimensional rotary or 3-dimensional rotary-pullback scanning mechanism require constant angular velocity at the distal tip to ensure correct angular registration of the collected signal. Non-uniform rotational distortion (NURD) – often present due to a variety of mechanical issues – can result in inconsistent position and velocity profiles at the tip, limiting the accuracy of any measurements. Since artifacts like NURD are difficult to identify and characterize during tissue imaging, phantoms with well-defined patterns have been used to quantify position and/or velocity error. In this work we present a fast, versatile, and cost-effective method for making fused deposition modeling 3D printed phantoms for identifying and quantifying NURD errors along an arbitrary user-defined pullback path. Eight evenly-spaced features are present at the same orientation at all points on the path such that deviations from expected geometry can be quantified for the imaging catheter. The features are printed vertically and then folded together around the path to avoid issues with printer head resolution. This method can be adapted for probes of various diameters and for complex imaging paths with multiple bends. We demonstrate imaging using the 3D printed phantoms with a 1mm diameter rotary-pullback OCT catheter and system as a means of objectively evaluating the mechanical performance of similarly constructed probes.

The use of reliable tissue-simulating phantoms spans multiple applications in spectroscopic imaging including device calibration and testing of new imaging procedures. Three-dimensional (3D) printing allows for the possibility of optical phantoms with arbitrary geometries and spatially varying optical properties. We recently demonstrated the ability to 3D print tissue-simulating phantoms with customized absorption (μ_a) and reduced scattering (μ_s`) by incorporating nigrosin, an absorbing dye, and titanium dioxide (TiO<sub>2</sub>), a scattering agent, to acrylonitrile butadiene styrene (ABS) during filament extrusion. A physiologically relevant range of μ<sub>a</sub> and μ<sub>s</sub>` was demonstrated with high repeatability. We expand our prior work here by evaluating the effect of two important 3D-printing parameters, percent infill and layer height, on both μ_a and μ_s`. 2 cm<sup>3</sup> cubes were printed with percent infill ranging from 10% to 100% and layer height ranging from 0.15 to 0.40 mm. The range in μ<sub>a</sub> and μ<sub>s</sub>` was 27.3% and 19.5% respectively for different percent infills at 471 nm. For varying layer height, the range in μ_a and μ_s` was 27.8% and 15.4% respectively at 471 nm. These results indicate that percent infill and layer height substantially alter optical properties and should be carefully controlled during phantom fabrication. Through the use of inexpensive hobby-level printers, the fabrication of optical phantoms may advance the complexity and availability of fully customizable phantoms over multiple spatial scales. This technique exhibits a wider range of adaptability than other common methods of fabricating optical phantoms and may lead to improved instrument characterization and calibration.

Appropriate surgical planning is important for improved clinical outcome and minimal complications in many surgical operations, such as a conjoined twin separation surgery. We combine 3D printing with casting and assembling to produce a solid phantom of high fidelity to help surgeons for better preparation of the conjoined twin separation surgery. 3D computer models of individual organs were reconstructed based on CT scanned data of the conjoined twins. The models were sliced, processed, and converted to an appropriate format for Fused Deposition Modeling (FDM). The skeletons of the phantom were printed directly by FDM using Acrylonitrile-Butadiene-Styrene (ABS) material, while internal soft organs were fabricated by casting silicon materials of different compositions in FDM printed molds. The skeleton and the internal organs were then assembled with appropriate fixtures to maintain their relative positional accuracies. The assembly was placed in a FMD printed shell mold of the patient body for further casting. For clear differentiation of different internal organs, CT contrast agents of different compositions were added in the silicon cast materials. The produced phantom was scanned by CT again and compared with that of the original computer models of the conjoined twins in order to verify the structural and positional fidelity. Our preliminary experiments showed that combining 3D printing with casting is an effective way to produce solid phantoms of high fidelity for the improved surgical planning in many clinical applications.

Accurate characterization of absorption and scattering properties for biologic tissue and tissue-simulating materials enables 3D printing of traceable tissue-simulating phantoms for medical spectral device calibration and standardized medical optical imaging. Conventional double integrating sphere systems have several limitations and are suboptimal for optical characterization of liquid and soft materials used in 3D printing. We propose a vertical double integrating sphere system and the associated reconstruction algorithms for optical characterization of phantom materials that simulate different human tissue components. The system characterizes absorption and scattering properties of liquid and solid phantom materials in an operating wavelength range from 400 nm to 1100 nm. Absorption and scattering properties of the phantoms are adjusted by adding titanium dioxide powder and India ink, respectively. Different material compositions are added in the phantoms and characterized by the vertical double integrating sphere system in order to simulate the human tissue properties. Our test results suggest that the vertical integrating sphere system is able to characterize optical properties of tissue-simulating phantoms without precipitation effect of the liquid samples or wrinkling effect of the soft phantoms during the optical measurement.

Scanning the retinae of the human eyes with a laser beam is an approved diagnosis method in ophthalmology; moreover the retinal blood vessels form a biometric modality for identifying persons. Medical applied Scanning Laser Ophthalmoscopes (SLOs) usually contain galvanometric mirror systems to move the laser spot with a defined speed across the retina. Hence, the load of laser radiation is uniformly distributed and eye safety requirements can be easily complied. Micro machined mirrors also known as Micro Electro Mechanical Systems (MEMS) are interesting alternatives for designing retina scanning systems. In particular double-resonant MEMS are well suited for mass fabrication at low cost. However, their Lissajous-shaped scanning figure requires a particular analysis and specific measures to meet the requirements for a Class 1 laser device, i.e. eye-safe operation. The scanning laser spot causes a non-uniform pulsing radiation load hitting the retinal elements within the field of view (FoV). The relevant laser safety standards define a smallest considerable element for eye-related impacts to be a point source that is visible with an angle of maximum 1.5 mrad. For non-uniform pulsing expositions onto retinal elements the standard requires to consider all particular impacts, i.e. single pulses, pulse sequences in certain time intervals and cumulated laser radiation loads. As it may be expected, a Lissajous scanning figure causes the most critical radiation loads at its edges and borders. Depending on the applied power the laser has to be switched off here to avoid any retinal injury.

Fluorescence microscopes have become ubiquitous in life sciences laboratories, including those focused on pharmaceu¬ticals, diagnosis, and forensics. For the past few years, the need for both per¬formance guarantees and quantifiable results has driven development in this area. However, the lack of appropri¬ate standards and reference materials makes it difficult or impossible to com¬pare the results of two fluorescence mi¬croscopes, or to measure performance fluctuations of one microscope over time. Therefore, the operation of fluo¬rescence microscopes is not monitored as often as their use warrants - an is¬sue that is recognized by both systems manufacturers and national metrolo¬gy institutes. We have developed a new process that enables the etching of long-term stable fluorescent patterns with sub-micrometer sizes in three dimensions inside glass. In this paper, we present, based on this new process, a fluorescent multi-dimensional ruler and a dedicated software that are suitable for monitoring and quality management of fluorescence-based imaging systems (wide-field, confocal, multiphoton, high content machines). In addition to fluorescence, the same patterns exhibit bright- and dark-field contrast, DIC, and phase contrast, which make them also relevant to monitor these types of microscopes. Non-exhaustively, this new solution enables the measurement of: The stage repositioning accuracy; The illumination and detection homogeneities; The field flatness; The detectors’ characteristics; The lateral and axial spatial resolutions; The spectral response (spectrum, intensity and lifetime) of the system. Thanks to the stability of the patterns, microscope performance assessment can be carried out as well in a daily basis as in the long term.

Hyperspectral reflectance imaging (HRI) is an emerging imaging modality being applied for clinical indications such as tissue oximetry, and cancer detection based on endogenous biological constituents including plasmonic nanoparticles. However, there is currently a lack of standardized test methods for objective, quantitative evaluation of HRI system performance. Contrast-detail analysis (CDA) is a phantom-based test method commonly used to evaluate medical imaging devices (e.g., mammography systems) in terms of their lower detection limit. We investigated a modified CDA (mCDA) method to quantify the detectability of gold nanoparticles by HRI systems. Silicone-based turbid phantoms containing micro-fluidic channels were developed for the mCDA tests. Polydimethylsiloxane (PDMS) phantom materials were doped with chromophores and scatterers to achieve biologically relevant optical properties (OPs). Molds were used to produce cylindrical channels of diameters 0.3 to 1.65 mm and depths of 0.2 mm inside the phantoms. Channels were filled with a mixture of hemoglobin and concentrations of gold nanorods (GNR) and measured with our HRI system. The contrast of GNRs was solved with a spectral unmixing algorithm from the reflectance spectra. The lowest detectable concentration was determined as a function of inclusion size and depth and plotted as modified contrast detail curve (mCDC). mCDCs were used to compare the detectabilities of the HRI system with different data processing algorithms. It is demonstrated that our mCDA test method involving turbid microchannel phantoms can help to elucidate the combined performance of imaging devices and plasmonic nanoparticle contrast agents. This approach may be useful for performing clinical trial standardization and device re-calibration, thus ensuring quality control and clinical performance.

The 488nm laser is the most important excitation light source of flow cytometry. The indirect diode (frequency-doubled diode) 488nm lasers are used in the excitation of Becton Dickinson (BD) Accuri^TM C6. For using cost effective lasers, we have validated direct diode 488nm lasers as the replacement component of frequency-doubled diode laser. BD Bioscience issued the protocols to cover wavelength, power, noise, and polarization at the operation temperature range of cytometer. Pavilion Integration Corporation (PIC) tested 6 samples as the component validation of direct diode 488nm lasers based on the protocols from BD Biosciences. BD Bioscience also tested one of laser samples to further validate the test results of power, noise, and polarization from PIC.

Photoacoustic Tomography (PAT) employs high-power near-infrared (near-IR) laser pulses to generate structural and functional information on tissue chromophores up to several centimeters below the surface. Such insights may facilitate detection of breast cancer – the most common cancer in women. PAT mammography has been the subject of extensive research, including techniques based on exogenous agents for PAT contrast enhancement and molecular specificity. However, photothermal safety risks of PAT due to strong chromophores such as epidermal melanin and plasmonic nanoparticles have not been rigorously studied. We have used computational and experimental approaches to elucidate highly dynamic optical-thermal processes during PAT. A Monte Carlo model was used to simulate light propagation at 800 and 1064 nm in a multi-layer breast tissue geometry with different epidermal pigmentation levels and a tumorsimulating inclusion incorporating nanoparticles. Energy deposition results were then used in a bioheat transfer model to simulate temperature transients. Experimental measurements involved multi-layer hydrogel phantoms with inclusions incorporating gold nanoparticles. Phantom optical properties were measured using the inverse adding-doubling technique. Thermal imaging was performed as phantoms were irradiated with 5 ns near-IR pulses. Scenarios using 10 Hz laser irradiation of breast tissue containing various nanoparticle concentrations were implemented experimentally and computationally. Laser exposure levels were based on ANSI/IEC limits. Surface temperature measurements were compared to corresponding simulation data. In general, the effect of highly pigmented skin on temperature rise was significant, whereas unexpectedly small levels of temperature rise during nanoparticle irradiation were attributed to rapid photodegradation. Results provide key initial insights into light-tissue interactions impacting the safety and effectiveness of PAT.

Polydimethylsiloxane (PDMS) has been a popular medium to fabricate tissue simulating optical phantoms. Recently, its use has significantly expanded in instrument calibration and performance testing, validation of advanced models of light transport of complex tissue geometries and evaluation of novel measurement modalities. To meet these demands, fabrication methods of these optical phantoms have become more refined and its structure and constituent components (i.e. dyes and scattering agents) have evolved to better mimic optical properties of tissue spanning both visible and near infrared regimes. We present efforts at the Beckman Laser Institute that address these challenges through PDMS phantoms.

The contrast in photoacoustic (PA) imaging depends on the mechanical and elastic properties of the tissue, as well as on his optical absorption and scatter properties. Thanks to these futures, this novel modality could offer additional specificity compared to conventional ultrasound techniques, being able to reveal the signal of absorbing materials and chomophores, e.g. endogenous molecules like haemoglobin or specific near infrared dyes or plasmonic contrast agents. The development of semi-quantitative protocols for the assessment of the contrast enhancement, is one of the key aspect of the ongoing research, that could open new routes to the use of PA imaging for a variety of applications in preclinical research of cancer and cardiovascular diseases. In this work, we designed and tested a tissue mimicking polydimethylsiloxane (PDMS) phantom for photoacoustic applications, with tailored biomechanical/optical and geometrical properties. In order to modulate the light fluence and penetration, that remains one of the major challenge for this technique, we added titanium dioxide and black ink, rendering the optical absorption and scattering coefficients similar to those of biological tissues. The PDMS phantom can become a particularly promising tool in the field of photoacoustics for the evaluation of the performance of a PA system and as a model of the structure of vascularized soft tissues.

This work focuses on pulsed terahertz imaging for the application of surgical margin assessment of breast cancer. Various phantom tissue types and orientations are tested here to refine imaging methodology that can detect breast cancer up to 0.5-1.0 mm from the edge of the sample. The depth of the cancer within the sample is estimated using time of flight analysis of the reflected peaks in the pulsed time domain signal. Breast tissue phantoms have been designed to resemble fresh infiltrating ductal carcinoma, fibroglandular tissue, and fatty tissue of the breast to accomplish this work.

The abstract is not available

We will present unique applications of a label-free, hyperspectral scatter imaging technique in different microscopy platforms including conventional wide-field, dark-field, and confocal. In different platforms, we conducted label-free imaging of cells undergoing biological processes such as nanoparticle uptake, apoptosis, and metabolic flux change in response to the variation of the osmotic pressure. Hyperspectral image analyses resolved spectral endmembers corresponding to unique scattering and absorption characteristics as a result of such processes at the single particle, single organelle, and single cell level, delineating the details of nanomaterial-cell interactions in a 2D cell culture, cell apoptotic characteristics in a 3D culture, and volumetric changes of single cells under the variation of osmotic pressure. Our label-free scatter imaging has the potential for a broad range of biological and biomedical applications such as the development of scatter-based imaging contrast agents and the measurement of scatter parameters of subcellular organelles to identify the sub-micron scale origins of scattering signals in tissue scattering measurements.

The abstract is not available

Spatially–resolved diffuse reflectance (SRDR) measurements provide photon path information, and enable layered tissue analysis. This paper presents experimental SRDR measurements on two-layer PDMS skin tissue-mimicking phantoms of varying top layer thicknesses, and bulk phantoms of varying optical properties using concentric multi-pixel photodiode array (CMPA) probes, and corresponding forward Monte Carlo simulations. The CMPA is the most densely packed semiconductor SRDR probe reported to date. Signal contrasts between the single layer phantom and bi-layer phantoms with varying top layer thicknesses are as high as 80%. The mean error between the Monte Carlo simulations and the experiment is less than 6.2 %.

The abstract is not available

We investigated the feasibility of using fiber optics probes with rare-earth-based phosphor tips for proton beam radiation dosimetry. We designed and fabricated a fiber probe with submillimeter resolution based on TbF₃ phosphors and evaluated its performance for measurement of proton beams including profiles and range. The fiber optic probe, embedded in tissue-mimicking plastics, was irradiated with a clinical proton beam and the luminescence spectroscopy was performed by a CCD-coupled spectrograph to analyze the emission spectra of the fiber tip. By using a linear fitting algorithm we extracted the contribution of the ionoluminescence signal to obtain the percentage depth dose in phantoms and compared that with measurements performed with a standard ion chamber. We observed a quenching effect in the spread out Bragg peak region, manifested as an under-responding of the signal due to the high linear energy transfer of the beam. However, the beam profiles measurements were not affected by the quenching effect indicating that the fiber probes can be used for high-resolution measurements of proton beams profile.

The pupil response to light can reflect various kinds of diseases which are related to physiological health. Pupillary abnormalities may be influenced on people by autonomic neuropathy, glaucoma, diabetes, genetic diseases, and high myopia. In the early stage of neuropathy, it is often asymptomatic and difficulty detectable by ophthalmologists. In addition, the position of injured nerve can lead to unsynchronized pupil response for human eyes. In our study, we design the pupilometer to measure the binocular pupil response simultaneously. It uses the different wavelength of LEDs such as white, red, green and blue light to stimulate the pupil and record the process. Therefore, the pupilometer mainly contains two systems. One is the image acquisition system, it use the two cameras modules with the same external triggered signal to capture the images of the pupil simultaneously. The other one is the illumination system. It use the boost converter ICs and LED driver ICs to supply the constant current for LED to maintain the consistent luminance in each experiments for reduced experimental error. Furthermore, the four infrared LEDs are arranged nearby the stimulating LEDs to illuminate eyes and increase contrast of image for image processing. In our design, we success to implement the function of synchronized image acquisition with the sample speed in 30 fps and the stable illumination system for precise measurement of experiment.

Low-level light therapy (LLLT) has been clinically applied. Recently, more and more cases are reported with positive therapeutic effect by using transcranial light emitting diodes (LEDs) illumination. Here, we developed a LLLT helmet for treating brain injuries based on LED arrays. We designed the LED arrays in circle shape and assembled them in multilayered 3D printed helmet with water-cooling module. The LED arrays can be adjust to touch the head of subjects. A control circuit was developed to drive and control the illumination of the LLLT helmet. The software portion provides the control of on and off of each LED arrays, the setup of illumination parameters, and 3D distribution of LLLT light dose in human subject according to the illumination setups. This LLLT light dose distribution was computed by a Monte Carlo model for voxelized media and the Visible Chinese Human head dataset and displayed in 3D view at the background of head anatomical structure. The performance of the whole system was fully tested. One stroke patient was recruited in the preliminary LLLT experiment and the following neuropsychological testing showed obvious improvement in memory and executive functioning. This clinical case suggested the potential of this Illumination-parameter adjustable and illuminationdistribution visible LED helmet as a reliable, noninvasive, and effective tool in treating brain injuries.

Wollaston prisms and the modified Wollaston prisms, which are interesting for various applications like optical metrology, topography of surfaces and biological imaging, has been theoretically studied and also been practically applied. The previous studies are mostly based on ray tracing analysis and, as a result, the information that can be obtained are somehow restricted. In this paper, we propose a geometric field tracing technique for the simulation of light propagation through Wollaston prisms. In geometric field tracing we seek for the solutions to Maxwell's equations under the geometrical optics approximation, so that all the properties of light as electromagnetic field are retained. Using the proposed simulation technique, we present the simulation of a differential interference contrast (DIC) microscopy, in which the modified Wollaston prism is used as the key component.

Optical projection tomography (OPT) creates isotropic 3D imaging of tissue. Two approaches exist today: Wide-field OPT illuminates the entire sample and acquires projection images with a camera; Scanning-laser optical tomography (SLOT) generates the projection with a moving laser beam and point detector. SLOT has superior light collecting efficiency than wide-field optical tomography, making it ideal for tissue fluorescence imaging. Regardless the approach, traditional OPT has to compromise between the resolution and the depth of view. In traditional SLOT, the focused Gaussian beam diverges quickly from the focused plane, making it impossible to achieve high resolution imaging through a large volume specimen. We report using Bessel beam instead of Gaussian beam to perform SLOT. By illuminating samples with a narrow Bessel beam throughout an extended depth, high-resolution projection images can be measured in large volume. Under Bessel illumination, the projection image contains signal from annular-rings of the Bessel beam. Traditional inverse Radon transform of these projections will result in ringing artifacts in reconstructed imaging. Thus a modified 3D filtered back projection algorithm is developed to perform tomography reconstructing of Bessel-illuminated projection images. The resulting 3D imaging is free of artifact and achieved cellular resolution in extended sample volume. The system is applied to in-vivo imaging of transgenic Zebrafish embryos. Results prove Bessel SLOT a promising imaging method in development biology research.

The abstract is not available

Oral cancer is one of the serious and growing problem in many developing and developed countries. The simple oral visual screening by clinician can reduce 37,000 oral cancer deaths annually worldwide. However, the conventional oral examination with the visual inspection and the palpation of oral lesions is not an objective and reliable approach for oral cancer diagnosis, and it may cause the delayed hospital treatment for the patients of oral cancer or leads to the oral cancer out of control in the late stage. Therefore, a device for oral cancer detection are developed for early diagnosis and treatment. A portable LED Induced autofluorescence (LIAF) imager is developed by our group. It contained the multiple wavelength of LED excitation light and the rotary filter ring of eight channels to capture ex-vivo oral tissue autofluorescence images. The advantages of LIAF imager compared to other devices for oral cancer diagnosis are that LIAF imager has a probe of L shape for fixing the object distance, protecting the effect of ambient light, and observing the blind spot in the deep port between the gumsgingiva and the lining of the mouth. Besides, the multiple excitation of LED light source can induce multiple autofluorescence, and LIAF imager with the rotary filter ring of eight channels can detect the spectral images of multiple narrow bands. The prototype of a portable LIAF imager is applied in the clinical trials for some cases in Taiwan, and the images of the clinical trial with the specific excitation show the significant differences between normal tissue and oral tissue under these cases.

Near-infrared fluorescence imaging (NIRF) is a powerful wide-field optical imaging tool that has a potential to visualize molecular-specific exogenous fluorescence agents, such as FDA approved Indocyanine Green (ICG), in thick tissue. Indeed, ICG is sensitive to biochemical environment such that it can be used to detect micro- or macroscopic environmental changes in tissue by solvatochromic shift that is defined by the dependence of absorption and emission spectra with the solvent polarity. For example, dimethyl sulfoxide (DMSO) is a very powerful drug carrier that can penetrate biological barriers such as the skin, the membranes, and the blood-brain-barrier. In presence of DMSO, ICG in tissue shows the excitation blue shift. However, NIRF imaging of microenvironment dependent changes of ICG has been challenging for the following reasons. First, the Stoke’s shift of ICG is too small to separate the excitation and emission spectra easily. Second, the solvatochromic shift of ICG is too small to be detected by conventional NIRF techniques. Last but not least, the multiple scattering in tissue degrades not only the spatial information but also the spectral contents by the red-shift. We developed a wavelength-swept laser-based NIRF system that can resolve the excitation shift of ICG in tissue such that DMSO can be indirectly visualized. We plan to conduct an in-vivo lymph-node drug-delivery study in a mouse model to show feasibility of the indirect imaging of the drug-carrier with the wavelength-swept-laser based NIRF system.

The abstract is not available

The abstract is not available

We developed a spectral domain optical coherence tomography (SD-OCT) system employing dual-balanced detection (DBD) for direct current term suppression and SNR enhancement, especially for auto-autocorrelation artifacts reduction. The DBD was achieved by using a beam splitter to building a free-space Michelson interferometer, which generated two interferometric spectra with a phase difference of π. These two phase-opposed spectra were guided to the spectrometer through two single mode fibers of the 8 fiber v-groove array and acquired by ultizing the upper two lines of a three-line CCD camera. We rotated this fiber v-groove array by 1.35 degrees to focus two spectra onto the first and second line of the CCD camera. Two spectra were aligned by optimum spectrum matching algorithm. By subtracting one spectrum from the other, this dual-balanced detection system achieved a direct current term suppression of ~30 dB, SNR enhancement of ~3 dB, and auto-autocorrelation artifacts reduction of ~10 dB experimentally. Finally we respectively validated the feasibility and performance of dual-balanced detection by imaging a glass plate and swine corneal tissue ex vivo. The quality of images obtained using dual-balanced detection was significantly improved with regard to the conventional single-detection (SD) images.

A new set-up is proposed to measure the full polarimetric properties of a sample through an optical fiber, paving the way to full-Mueller endoscopic imaging. The technique combines a channeled spectrum polarimeter and an interferometer. This permits high-speed measurement of two Mueller matrices simultaneoulsy. The first matrix characterizes only the fiber while the second characterizes both fiber and sample. The instrument is validated on vacuum, a quarter-wave plate and a linear polarizer for single-point measurements. Insensitivity of the polarimetric measurement to fiber disturbances is proven while manipulating the fiber.

Optical Neuroimaging is a highly dynamical field of research owing to the combination of many advanced imaging techniques and computational tools that uncovered unexplored paths through the functioning of the brain. Light propagation modelling through such complicated structures has always played a crucial role as the basis for a high resolution and quantitative imaging where even the slightest improvement could lead to significant results. Fluorescence Diffuse Optical Tomography (fDOT), a widely used technique for three dimensional imaging of small animals and tissues, has been proved to be inaccurate for neuroimaging the mouse head without the knowledge of a-priori anatomical information of the subject. Commonly a normalized Born approximation model is used in fDOT reconstruction based on forward photon propagation using Diffusive Equation (DE) which has strong limitations in the optically clear regime. The presence of the Cerebral Spinal Fluid (CSF) instead, a thin optically clear layer surrounding the brain, can be more accurately taken into account using Monte Carlo approaches which nowadays is becoming more usable thanks to parallelized GPU algorithms. In this work we discuss the results of a synthetic experimental comparison, resulting to the increase of the accuracy for the Born approximation by introducing the CSF layer in a realistic mouse head structure with respect to the current model. We point out the importance of such clear layer for complex geometrical models, while for simple slab phantoms neglecting it does not introduce a significant error.

The underdeterminedness of the inverse problems encountered in diffuse optical tomography (DOT) becomes especially severe when detecting breast cancers, because much more variables are needed to be reconstructed due to the big-size. With the addition of ill-condition caused by the diffusive nature of light propagation, the ill-posedness makes it very difficult to improve the image reconstruction. Fortunately, from the anatomy viewpoint, we have known that the cancer is distributed locally and only amounts to a small percentage of the whole breast. This makes it possible to employ the compressive sensing theory to mitigate the ill-posedness, based on the prior knowledge about the sparsity of the signal to be reconstructed. Specifically speaking, sparsity regularizations can be used in DOT to improve the image reconstruction under the premise that un-increase the number of measurements required in the reconstruction. In this paper, we primarily focus on comparing the performances of different kinds of L_p-norm-based regularizations in terms of theory and real effects, respectively. The numerical and phantom experiments have proven that the sparsity regularizations can dramatically improve the image reconstruction. Furthermore, as the p in the L_p-norm decreasing to zero, the solutions become sparser and the corresponding image quality gets higher, with smooth L₀-norm-based regularization providing the highest image quality.

To evaluate the spatial resolution performance of cone beam computed tomography (CBCT) system, accurate measurement of the modulation transfer function (MTF) is required. This accuracy depends on the MTF measurement method and CBCT reconstruction algorithms. In this work, the accuracy of MTF measurement of CBCT system using wire phantom is validated by Monte Carlo simulation. A Monte Carlo simulation software tool BEAMnrc/EGSnrc was employed to model X-ray radiation beams and transport. Tungsten wires were simulated with different diameters and radial distances from the axis of rotation. We adopted filtered back projection technique to reconstruct images from 360° acquisition. The MTFs for four reconstruction kernels were measured from corresponding reconstructed wire images, while the ram-lak kernel increased the MTF relative to the cosine, hamming and hann kernel. The results demonstrated that the MTF degraded radially from the axis of rotation. This study suggested that an increase in the MTF for the CBCT system is possible by optimizing scanning settings and reconstruction parameters.

The research is dedicated to non-contact methods of electrocardiography. The authors describe the routine of experimental procedure and suggest the approach to solving the problems which arise at indirect signal recording. The paper presents the results of experiments conducted by the authors, covers the flow charts of ECG recorders and reviews the drawbacks of filtering methods used in foreign equivalents.

The strong scattering and absorption of light in biological tissue makes it challenging to model the propagation of light, especially in deep tissue. This is especially true in fluorescent tomography, which aims to recover the internal fluorescence source distribution from the measured light intensities on the surface of the tissue. The inherently ill-posed and underdetermined nature of the inverse problem along with strong tissue scattering makes Fluorescence Tomography (FT) extremely challenging. Previously, multispectral detection fluorescent tomography (FT) has been shown to improve the image quality of FT by incorporating the spectral filtering of biological tissue to provide depth information to overcome the inherent absorption and scattering limitations. We investigate whether multi-wavelength fluorescent tomography can be used to distinguish the signals from multiple fluorophores with overlapping fluorescence spectrums using a unique near-infrared (NIR) swept laser. In this work, a small feasibility study was performed to see whether multi-wavelength FT can be used to detect subtle shifts in the absorption spectrum due to differences in fluorophore microenvironment.

In a typical laminar optical tomography (LOT) system, the dip-angle between the incident light (or the emitting light) and the normal of the detection plane randomly changes during raster-scanning. The inconstant dip-angle causes consistency between the measurement and the light transportation model where a fixed dip-angle of the incident light is generally required. To eliminate the effect from this dip angle, methods such as keeping the angle unchangeable by moving the phantom instead of scanning the light were investigated. In this paper, a LOT system with small dip-angle over the whole detection range is developed. Simulation and experimental evaluation show that the dip-angle of the modified system is much smaller than that of the traditional system. For example, the relative angle between the two incident light at (x=0mm, y=0mm) and (x=0mm, y=2.5mm) on the image plane is about 0.7° for the traditional system while that is only about 0.02° for the modified system. The main parameters of the system are also evaluated and an image reconstruction algorithm is developed based on Monte Carlo simulation. The reconstructed images show that the spatial resolution and quantitative ratio is improved by the modified system without loss of the scanning speed.

A stereoscopic imaging modality was developed for the application of ophthalmology surgical microscopes. A previous study has already introduced a single-channel stereoscopic video imaging modality based on a transparent rotating deflector (SSVIM-TRD), in which two different view angles, image disparity, are generated by imaging through a transparent rotating deflector (TRD) mounted on a stepping motor and is placed in a lens system. In this case, the image disparity is a function of the refractive index and the rotation angle of TRD. Real-time single-channel stereoscopic ophthalmology microscope (SSOM) based on the TRD is improved by real-time controlling and programming, imaging speed, and illumination method. Image quality assessments were performed to investigate images quality and stability during the TRD operation. Results presented little significant difference in image quality in terms of stability of structural similarity (SSIM). A subjective analysis was performed with 15 blinded observers to evaluate the depth perception improvement and presented significant improvement in the depth perception capability. Along with all evaluation results, preliminary results of rabbit eye imaging presented that the SSOM could be utilized as an ophthalmic operating microscopes to overcome some of the limitations of conventional ones.