This PDF file contains the front matter associated with SPIE Proceedings Volume 8945, including the Title Page, Copyright Information, Table of Contents, and the Conference Committee listing.

Differential near infrared sensors recently sparked a growing interest as a promising measuring modality for brain computer interfacing. In our study we present the design and characterization of novel, differential functional NIRS sensors, intended to record hemodynamic changes of the human motor cortex in the hand-area during motor imagery tasks. We report on the spatial characterization of a portable, multi-channel NIRS system with one module consisting of two central light emitting diodes (LED) (770 nm and 850 nm) and four symmetric pairs of radially aligned photodiodes (PD) resembling a plus symbol. The other sensor module features four similar, differential light paths crossing in the center of a star. Characterization was performed on a concentric, double beaker phantom, featuring a PBS/intralipid/blood mixture (97/1/2%). In extension of previous work, the inner, oxygenated beaker was covered by neoprene sleeves with holes of various sizes, thus giving an estimate on the spatial limits of the NIRS sensor’s measurement volume. The star shaped sensor module formed a diffuse focus of approximately 3 cm in diameter at 1.4 cm depth, whereas the plus shaped arrangement suggested a concentric ring of four separate regions of interest, overall larger than 6 cm. The systems measurement sensitivity could be improved by removing ambient light from the sensing photodiodes by optical filtering. Altogether, we conclude that both our novel fNIRS design as well as its electronics perform well in the double-layered oxygenation phantom and are thus suitable for in-vivo testing.

Fluorescence guidance using 5-aminolevulinic acid (5-ALA) for brain tumor resection is a recent technique applied to the highly malignant brain tumors. Five-ALA accumulates as protoporphyrin IX fluorophore in the tumor cells in different concentrations depending on the tumor environment and cell properties. Our group has developed a fluorescence spectroscopy system used with a hand-held probe intra-operatively. The system has shown improvement of fluorescence detection and allows quantification that preliminarily correlates with tumor malignancy grade during surgery. However, quantification of fluorescence is affected by several factors including the initial fluorophore concentration, photobleaching due to operating lamps and attenuation from the blood. Accordingly, an optical phantom was developed to enable controlled fluorescence measurements and evaluation of the system outside of the surgical procedure. The phantom mimicked the optical properties of glioma at the specific fluorescence excitation wavelength when different concentrations of the fluorophore were included in the phantom. To allow evaluation of photobleaching, kinetics of fluorophore molecules in the phantom was restricted by solidifying the phantoms. Moreover, a model for tissue autofluorescence was added. The fluorescence intensity’s correlation with fluorophore concentration in addition to the photobleaching properties were investigated in the phantoms and were compared to the clinical data measured on the brain tumor.

Previously we developed an ultrathin, flexible, multimodal scanning fiber endoscope (SFE) for concurrent white light and fluorescence imaging. Autofluorescence (AF) arising from endogenous fluorophores (primarily collagen in the esophagus) act as major confounders in fluorescence-aided detection. To address the issue of AF, a real-time mitigation algorithm was developed and has been show to successfully remove AF during SFE imaging. To test our algorithm, we previously developed flexible, color-matched, synthetic phantoms featuring a homogenous distribution of collagen. In order to more rigorously test the AF mitigation algorithm, a phantom that better mimicked the in-vivo distribution of collagen in tissue was developed.

New imaging technologies are changing the field of digital pathology. This field faces numerous challenges and there is a pressing need for standardization, calibration protocols, quality control and quantitative assessment. We have designed a new calibration imaging slide (Cancer Imaging Slide), specifically to measure the characteristics of old or new imaging systems or scanners. The layout of the slide consists of 138 boxes with the side length of 1.6 mm, containing objects of known morphologic and photometric characteristics. Among them, 112 boxes contain different permutations of circles, ovals, and squares. The circles have different radii, radius/pitch ratios and step transmissions. The ovals have different sizes and orientations. The squares are consistent in size and orientation but have different step transmission values. Also, 16 boxes contain three resolution test targets: crosses, USAF target and Siemens star. The last 10 boxes are blank boxes with different transmission values. Four slides were scanned and imaged on one commercial whole-slide scanner and one high resolution imaging system. After segmenting the images, about 200 features (photometric, morphologic and architectural) were measured with our in-house image processing software. The objective of the project is to develop a statistical process control using this new slide. In this paper, we describe the characteristics of the slide and present our preliminary results.

Optical methods have been used to investigate electrical injury on animal models such as live mice, rats, and rabbits. Here we introduce a completely digital phantom of a mouse, with the aim of investigating electrical injury through spectroscopic imaging techniques. The basis of our phantom is a three-dimensional digital mouse reconstructed from co-registered computed tomographic images and cryosection by a different group. Image processing algorithms were applied to make the model suitable to Finite Element Analysis of thermal and electrical transport. Our digital model is capable of simulating temperature, voltage, current changes along the animal body during and after electrical shocks.

The performance of biomedical optical imaging devices heavily relies on appropriate calibration. However, many of existing calibration phantoms for biomedical optical devices are based on homogenous materials without considering the multi-layer heterogeneous structures observed in biological tissue. Using such a phantom for optical calibration may result in measurement bias. To overcome this problem, we propose a 3D printing method for freeform fabrication of tissue simulating phantoms with multilayer heterogeneous structure. The phantom simulates not only the morphologic characteristics of biological tissue but also absorption and scattering properties. The printing system is based on a 3D motion platform with coordinated control of the DC motors. A special jet nozzle is designed to mix base, scattering, and absorption materials at different ratios. 3D tissue structures are fabricated through layer-by-layer printing with selective deposition of phantom materials of different ingredients. Different mixed ratios of base, scattering and absorption materials have been tested in order to optimize the printing outcome. A spectrometer and a tissue spectrophotometer are used for characterizing phantom absorption and scattering properties. The goal of this project is to fabricate skin tissue simulating phantoms as a traceable standard for the calibration of biomedical optical spectral devices.

We will report newly developed polymer-based phantom for photoacoustic (PA) imaging systems. Phantoms are important for performance evaluation and calibration of new modalities; however, there is no established method for making phantoms with no long-term change. We have developed skin mimicking phantoms simulating both optical and acoustic properties (i.e. optical scattering and absorption coefficients, and sound velocity). Furthermore, the phantoms are able to give accurate simulation of blood vessels by Inkjet-printing. Newly developed phantoms are consisted of castor oil included acrylic block copolymer and we can fabricate 0.8mm or less thick sheets and pile them using their self-adhesiveness.

Tissue phantoms with defined, reliable and reproducible characteristics are crucial for the evaluation of biomedical imaging systems. For multimodal approaches, various demands on tissue phantoms have to be met in order to satisfy the needs of all modalities. We present and discuss a hydrogel phantom that was created for combined Raman spectroscopic and optoacoustic measurements imposing optical as well as acoustic requirements on the phantom. In this phantom, defined concentrations of carotenes should be available in an optically scattering and absorbing matrix to test and validate the capability of this combination of methods to quantify specific biomolecules in tissue. The main requirements on this phantom were tissue-like acoustic properties, scalable optical attenuation and incorporation of Raman active target molecules. We used a poly(vinyl alcohol) (PVA) hydrogel as the basic phantom material because of its suitable acoustic and optical characteristics but found that the incorporation of non-polar dyes like carotenoids in the hydrogel is difficult and the optical properties of the biomolecule are significantly altered by the hydrogel molecular environment and production procedure. We show and discuss challenges and solutions in the design process of a suitable tissue phantom.

A novel methodology is presented to mimic diffuse reflectance spectra of arbitrary biological tissues in the visible and near-infrared ranges. The prerequisite for this method is that the spectral information of basic components is sufficient to mimic an arbitrary tissue. Using a sterile disposable fiber optic probe the diffuse reflectance spectrum of a tissue (either in vivo or ex vivo) is measured, which forms the target spectrum. With the same type of fiber probe, a wide variety of basic components (ingredients) has been previously measured and all together forms a spectral database. A “recipe” for the optimal mixture of ingredients can then be derived using an algorithm that fits the absorption and scattering behavior of the target spectrum using the spectra of the basic components in the database. The spectral mimicking accuracy refines by adding more ingredients to the database. The validity of the principle is demonstrated by mimicking an arbitrary mixture of components. The method can be applied with different kinds of materials, e.g. gelatins, waxes and silicones, thus providing the possibility of mimicking the mechanical properties of target tissues as well. The algorithm can be extended from single point contact spectral measurement to contactless multi- and hyper-spectral camera acquisition. It can be applied to produce portable and durable tissue-like phantoms that provides consistent results over time for calibration, demonstration, comparison of instruments or other such tasks. They are also more readily available than living tissue or a cadaver and are not so limited by ease of handling and legislation; hence they are highly useful when developing new devices.

Optical spectroscopy is being used increasingly in medical applications to noninvasively investigate tissues below the skin. In order to assure adequate sampling of tissues underlying the skin, photon penetration depth must be known. Photon penetration in tissues has been studied with near-infrared (NIR) light, but experimental study of visible light propagation in tissue has been limited. In this study, a micro-motion system coupled with a reflectance spectroscopy system was used to determine the penetration depth of visible-range and NIR photons (535-800 nm) in phantoms composed of Intralipid and hemoglobin. An absorbing target was placed at intervals of 0.1mm along a 15mm line perpendicular to and bisecting the line between the ends of the source and detector optical fiber bundles. Comparisons between detected light intensities at different target positions were used to determine the most probable photon path depths at 576 nm and at 760 nm. Scattering coefficients, hemoglobin concentrations, and source-detector separations were varied to evaluate their effects on the penetration depth of photons. Results from phantoms containing Intralipid only showed that the most-probable penetration depth at 576 nm was comparable to that at 760 nm. Larger sourcedetector separations resulted in deeper photon penetration depths for both spectral regions. Changes in scattering over a 4-fold range did not affect the photon path depth appreciably. In the presence of hemoglobin with a source-detector separation of 13 mm, the most probable depth of photon penetration in the visible range was greater than 2.5 mm, and was within 1 mm of the most probable depth of photon penetration in the NIR. This study demonstrates the feasibility of using the visible and NIR regions in transcutaneous reflectance spectroscopy.

Optical coherence tomography (OCT) has shown potential as a complementary modality to white light cystoscopy (WLC), the gold standard for imaging bladder cancer. OCT can visualize sub-surface details of the bladder wall, which enables it to stage cancers and detect tumors that are otherwise invisible to WLC. Currently, OCT systems have too slow a speed and too small a field of view for comprehensive bladder imaging, which limits its clinical utility. Validation and feasibility testing of technological refinements aimed to provide faster imaging and wider fields of view necessitates a realistic bladder phantom. We present a novel process to fabricate the first such phantom that mimics both the optical and morphological properties of layers of the healthy and pathologic bladder wall as they characteristically appear with OCT. The healthy regions of the silicone-based phantom comprises three layers: the urothelium, lamina propria and muscularis propria, each containing an appropriate concentration of titanium dioxide to mimic its distinct scattering properties. As well, the layers each possess a unique surface appearance imposed by a textured mold. Within this phantom, pathologic tissue-mimicking regions are created by thickening specific layers or creating inclusions that disrupt the layered appearance of the bladder wall, as is characteristic of bladder carcinomas. This phantom can help to evaluate the efficacy of new OCT systems and software for tumor localization. Moreover, the procedure we have developed is highly generalizable for the creation of OCT-relevant, multi-layer phantoms for tissues that incorporate diseased states characterized by the loss of layered structures.

We report the design, manufacture and assessment of a phantom eye that can be used to measure the performance and accuracy of ophthalmic-OCT devices. We base our design on a wide-field schematic eye, R. Navarro, J. Opt. Soc. Am. A 2 (1985), to allow the assessment of device performance relative to ± 70° external field of view. We have fabricated the phantom eye and have verified the structural dimensions of the multi-material 3D-printed retinal targets using calibrated-OCT images.