This PDF file contains the front matter associated with SPIE Proceedings volume 7555, including the Title Page, Copyright information, Table of Contents, Introduction, and the Conference Committee listing.

We report data collected with a specialized transient digitizer, high repetition rate microchip laser sources, and fiber optic light delivery and collection for rapid remote sensing in tissue-simulating phantoms. The instrumentation is highly suitable for eventual translation to a clinical setting owing to the speed of data acquisition and small footprint. Ranges for data acquisition time and instrument sensitivity were determined by measuring wavelength time matrices (WTMs) from tissue-simulating phantoms. Accuracy of WTM data was validated by comparison with Monte-Carlo simulations of fluorescent light propagation in turbid media.

A novel optical method of guiding epidural catheter insertion is introduced due to high failure rate of traditional technique for epidural blocks. Experiments of ex-vivo and in-vivo in porcine were performed. In the ex-vivo study the optically reflective spectra of identified porcine tissues were obtained. By which wavelengths of 650 nm and 532 nm were selected to differentiate epidural space and ligamentum flavum. Then the typical stylet of an insertion needle set was replaced by a specially designed hollow stylet which contained optical fibers served for tissue illumination and receiving reflected light from tissue in the in-vivo experiment in pigs. The data was promising with mean magnitudes for 650 nm and 532 nm and their ratio at epidural space and ligamentum flavum were 3.565+/-0.194, 2.542+/-0.145, 0.958+/-0.172 and 3.842+/-0.191, 2.563+/-0.131, 1.228+/-0.244 respectively. Paired t test showed that significant differences occurred between epidural spaces and ligamentum flavum in both 650nm (p<0.001), 532nm (p=0.014) and their ratio (p <0.001). Two-way ANOVA for reflective lights of 650 and 532 nm indicates no significant difference at the different puncture sites for ligamentum flavum and epidural space (all p>0.05).

Health monitoring system (HMS) and drug delivery system (DDS) require accurate puncture by needle for automatic blood sampling. In this study, we develop a miniature and high accurate automatic 3D blood vessel searching system. The size of detecting system is 40x25x10 mm. Our searching system use Near-Infrared (NIR) LEDs, CMOS camera modules and image processing units. We employ the stereo method for searching system to determine 3D blood vessel location. Blood vessel visualization system adopts hemoglobin's absorption characterization of NIR light. NIR LED is set behind the finger and it irradiates Near Infrared light for the finger. CMOS camera modules are set in front of the finger and it captures clear blood vessel images. Two dimensional location of the blood vessel is detected by luminance distribution of the image and its depth is calculated by the stereo method. 3D blood vessel location is automatically detected by our image processing system. To examine the accuracy of our detecting system, we carried out experiments using finger phantoms with blood vessel diameters, 0.5, 0.75, 1.0mm, at the depths, 0.5 ~ 2.0 mm, under the artificial tissue surface. Experimental results of depth obtained by our detecting system showed good agreements with given depths, and the availability of this system is confirmed.

Hyperspectral imaging has tremendous potential to detect important molecular biomarkers of early cancer based on their unique spectral signatures. Several drawbacks have limited their use for in vivo screening applications: most notably their poor temporal and spatial resolution, high expense, and low optical throughput. We present the development of a new real-time hyperspectral endoscope (called the IMS Endoscope) based on an image mapping technique which makes it capable of addressing these challenges. The parallel, high throughput nature of this technique enables the device to operate at frame rates of 3-10 fps while collecting a 3D (x, y, λ) datacube of 350 x 350 x 48.

Two methods for analyzing OCT images of arterial tissues are tested. These methods are applied toward two types of samples: segments of arteries collected from atherosclerosis-prone Watanabe heritable hyper-lipidemic rabbits and pieces of porcine left descending coronary arteries without atherosclerosis. The first method is based on finding the attenuation coefficients for the OCT signal that propagates through various regions of the tissue. The second method involves calculating the fractal dimensions of the OCT signal textures in the regions of interest identified within the acquired images. A box-counting algorithm is used for calculating the fractal dimensions. Both parameters, the attenuation coefficient as well as the fractal dimension correlate very well with the anatomical features of both types of samples.

The blood pool agent indo-cyanine green (ICG) has been investigated in a prospective clinical study for detection of rheumatoid arthritis using fluorescence imaging. Temporal behavior as well as spatial distribution of fluorescence intensity are suited to differentiate healthy and inflamed finger joints after i.v. injection of an ICG bolus.

We propose a cancer diagnostics method using 3D reconstruction of fluorescence based optical imaging data. The reconstruction of luminescence sources in biological tissue is investigated using data obtained from Monte Carlo simulations as well as simulated data using the diffusion approximation. The absolute determination of the tumor locations is dependent on the information gathered by the recorded data. To tackle the forward problem we used the solution of the diffusion equation for a cube. The inverse problem is solved.­

This paper presents the use and evaluation of stepped frequency modulated continuous waves (FMCW) in a conformal ultrasound array-based medical imaging system currently in development. Conventional medical ultrasound systems featuring rigid transducer arrays are highly user-dependent and require manual rotation and translation to identify and image landmarks. Conformal ultrasound arrays have a larger aperture that can follow the surface curvature of the body, thereby enabling increased data capture without mechanical scanning. The complexity of image reconstruction in conformal ultrasound necessitates the use of step-FMCW, since it directly captures the frequency space thereby enabling image reconstruction techniques to operate directly on the data, greatly simplifying and allowing for real-time performance. Further, FMCW is advantageous in general since it requires lower peak power and produces better receiver noise characteristics than conventional pulse-echo signaling. In the proposed stepped FMCW signaling, packets of acoustic waves at stepped frequencies are emitted from transducers sequentially. Phase and magnitude information from each transmitter-receiver pair of the array are captured producing the frequency space representation of the conventional A-scan data. The results comprise of simulations and bistatic experimental data produced by the step-FMCW signaling method, and obtained using a multistatic transducer array with a stationary metal target. In experimental verification using, the step- FMCW signaling and processing method gave accurate target detection, thereby demonstrating its viability in a conformal ultrasound array and imaging system.

Diffuse optical spectroscopic imaging (DOSI) is a technique to assess the spatial variation in absorption and scattering properties of the biological tissues and provides the monitoring of changes in concentrations of oxy-hemoglobin and deoxy-hemoglobin. In our preliminary study, the temporal tracings of hemodynamic oxygenation are measured with DOSI and venous occlusion test (VOT) from normal subjects, patients with heart failure and patients with sepsis in intensive care unit (ICU). In experiments, the obvious differences of hemodynamic signals can be observed among the three groups. The physiological relevance of VOT hemodynamics with respect to diseases is also discussed in this paper.

A hand-held optical imaging device has been developed in our laboratory towards fast 2D imaging and 3D tomography for breast cancer diagnosis. The device has the unique abilities: (1) to contour to different tissue curvatures using a flexible probe face; (2) perform fast 2D imaging by employing simultaneous over sequential source illumination; and (3) self coregistration towards (future) 3D tomography. The objective of the current work is to demonstrate fast coregistered 2D imaging on breast tissue of healthy female subjects. Fluorescence imaging experiments are performed in vitro and in vivo to demonstrate coregistered imaging as well as the ability to detect deep targets from multiple surface scans. A 0.45 cc spherical target filled with 1 μM indocyanine green is embedded at various depths of a cubical phantom filled with chicken breast (in vitro models). For in vivo studies, the fluorescent target is placed under the flap of the breast tissue to represent a tumor for fluorescence imaging. Multiple scans (fast continuous-wave images of fluorescence intensity) are collected and coregistered at different locations on the breast tissue. This study demonstrates the potential of the hand-held optical device towards future in vivo surface imaging and tomographic imaging for 3D tumor localization.

The power density of optical excitation in microfluidic-photonic-integrated flow cytometers is typically provided from an integrated waveguide and the beam is therefore divergent within the microchannel due to the NA of the waveguide; a detrimental effect on detection capabilities as excitation is not uniform throughout the channel and will generate a long pulse for excitation. Through integration of a lens system specially designed and simulated to collect and reshape 100% of input power, the excitation power within the microchannel has been controlled to form an optimal spot size within the microchannel. The device was formed via a one-shot processing method where designs are patterned into a SU-8 layer on a Pyrex substrate. A poly(dimethylsiloxane) (PDMS) layer was used to seal the device and serve as an upper cladding for integrated waveguides. Spot sizes were improved from an unfocused width of 86um to less than 40um. Power densities were controlled throughout the width of the channel - an improvement for flow cytometry applications.

Clinical testing of human blood requires adherence to a number of regulatory standards, including maintaining a temperature that is representative of the human body (e.g. 37 C). The economics of private and public healthcare drives blood assays to be conducted using low cost, disposable assay devices that also eliminate the possibility of cross contamination. Unfortunately, the materials that meet the economic and disposable constraints of the marketplace are thermal insulators, not ideal for rapid heating. We present a novel means of optically heating blood samples in plastic assay devices within a time period suitable for point-of-care use. The novel approach uses LED's in the red portion of the visible spectrum. The lower absorption of optical radiation in the visible spectrum enables the absorption of energy deep into the assay device. This produces even heating, avoiding the gradients that can occur by surface heating (conduction) or surface absorption (highly absorbing wavelengths). Analytical and computational models will be discussed. A specific application to a point-of-care blood assay instrument will be reviewed. In this application, optical heating was achieved using a small array of high brightness LED's. Experimental results will be discussed. The experimental results with this instrument validated the predictions.

Endometriosis is one of the most common causes of chronic pelvic pain and infertility and is characterized by the presence of endometrial glands and stroma outside of the uterine cavity. A novel laparoscopic polarization imaging system was designed to detect endometriosis by imaging endometrial lesions. Linearly polarized light with varying incident polarization angles illuminated endometrial lesions. Degree of linear polarization image maps of endometrial lesions were constructed by using remitted polarized light. The image maps were compared with regular laparoscopy image. The degree of linear polarization map contributed to the detection of endometriosis by revealing structures inside the lesion. The utilization of rotating incident polarization angle (IPA) for the linearly polarized light provides extended understanding of endometrial lesions. The developed polarization system with varying IPA and the collected image maps could provide improved characterization of endometrial lesions via higher visibility of the structure of the lesions and thereby improve diagnosis of endometriosis.

A practical near-IR blood vessel imaging system, the 'VascuLuminator', was developed to facilitate the puncturing of blood vessels for different procedures. Technical solutions were found for certain difficulties, such as obtaining a maximum image contrast by reducing the interference of IR light present in the surroundings. In phantom studies it was shown that the device is able to visualize blood vessels of different sizes to a clinically relevant maximum depth. In a preliminary clinical study, the use of the VascuLuminator resulted in decrease of the failure rate in blood withdrawal in young children from 13% to 2% and the laboratory technicians were satisfied with the practical application of the device. After this study, the effectiveness of the VascuLuminator was investigated to facilitate arterial cannulation in a group of children undergoing cardiac surgery. In an ongoing study, 71 children up to 3 years of age were included and time of arterial cannulation, number of punctures and puncture site were recorded. In 38 patients, cannulation was performed without the VascuLuminator and in 33 patients with VascuLuminator by pediatric anesthesiologists. The initial results do not show significant differences in time and in number of punctures with and without the use of the VascuLuminator. However, the VascuLuminator was able to visualize the arteries in most cases. In 11 of the 33 cases, the artery was located by using only the near-infrared image was used, without palpating for a pulse or knowledge of anatomical landmarks. Further clinical studies are needed to identify the patients groups that will benefit the most from VascuLuminator-assisted vessel punctures.

Second harmonic generation and multiphoton excited fluorescence microscopy methods were used to examine structural remodeling of the extracellular matrix in human lung alveolar walls undergoing emphysematous destruction. Fresh lung samples removed from a patient undergoing lung transplantation for very severe chronic obstructive pulmonary disease were compared to similar samples from an unused donor lung that served as a control. The generated spatially resolved 3D images show the spatial distribution of collagen, elastin and other endogenously fluorescent tissue components such as macrophages. In the case of control lung tissue, we found well ordered alveolar walls with composite type structure made up of collagen matrix and relatively fine elastic fibers. In contrast, lung tissue undergoing emphysematous destruction was highly disorganized with increased alveolar wall thickness compared to control lung tissue.

A primary focus of neurointensive care is monitoring the injured brain to detect harmful events that can impair cerebral blood flow (CBF). Since current non-invasive bedside methods can only indirectly assess blood flow, the goal of this research was to develop an optical technique for measuring absolute CBF. A time-resolved near-infrared (NIR) apparatus was built and its ability to accurately measure changes in optical properties was demonstrated in tissue-mimicking phantoms. The time-resolved system was combined with a bolus-tracking method for measuring CBF using the dye indocyanine green (ICG) as an intravascular flow tracer. Cerebral blood flow was measured in newborn piglets and for comparison, CBF was concurrently measured using a previously developed continuous-wave NIR method. Measurements were acquired with both techniques under three conditions: normocapnia, hypercapnia and following occlusion of the carotid arteries. Mean CBF values (N = 3) acquired with the TR-NIR system were 31.9 ± 11.7 ml/100g/min during occlusion, 39.7 ± 1.6 ml/100g/min at normocapnia, and 58.8 ± 9.9 ml/100g/min at hypercapnia. Results demonstrate that the developed TR-NIR technique has the sensitivity to measure changes in CBF; however, the CBF measurements were approximately 25% lower than the values obtained with the CW-NIRS technique.

Improving the success of lumpectomies would reduce the number of procedures, cost, and morbidity. A light source could be placed in a lesion to assist in finding and removing the lesion. A quantitive measurement of the distance between such a light source and a detector would further aid in the procedure by providing surgeons with easy to use intra-operative guidance to the lesion. Two methods, continuous wave and frequency domain, of accomplishing this measurement were compared. Within one radio frequency experimental system, the amplitude at 15MHz was taken to represent the continuous wave signal and the phase at 100MHz was taken to represent the frequency domain signal. For the continuous wave method, data at source-detector separation distances of 20, 30 & 50mm were used to predict other distances of 10, 20, 30, 40, & 50 mm. Data at source-detector separation distances of 20 & 40mm was used to predict distances for the frequency domain method. When the difference between the predicted distance and the actual distance was compared to zero the continuous wave method was significantly different (student's t-test, p = 0.03) while the frequency domain method was not statistically different from zero (student'st-test, p > 0.05). The frequency domain method was more accurate at predicting the source-detector separation distance between 10 & 50 mm. This frequency domain method of measuring distance may be useful in locating and removing lesions during lumpectomy procedures.

Background: Medical and diagnostic applications of near infrared spectroscopy (NIRS) are increasing, especially in operating rooms (OR). Since NIRS is an optical technique, radio frequency (RF) interference from other instruments is unlikely to affect the raw optical data, however, NIRS data processing and signal output could be affected. Methods: We investigated the potential for three common OR instruments: an electrical cautery, an orthopaedic drill and an imaging system, to generate electromagnetic interference (EMI) that could potentially influence NIRS signals. The time of onset and duration of every operation of each device was recorded during surgery. To remove the effects of slow changing physiological variables, we first used a lowpass filter and then selected 2 windows with variable lengths around the moment of device onset. For each instant, variances (energy) and means of the signals in the 2 windows were compared. Results: Twenty patients were studied during ankle surgery. Analysis shows no statistically significant difference in the means and variance of the NIRS signals (p < 0.01) during operation of any of the three devices for all surgeries. Conclusion: This method confirms the instruments evaluated caused no significant interference. NIRS can potentially be used without EMI in clinical environments such as the OR.

A reflective terahertz (THz) system has been under development for imaging and monitoring of skin hydration, and through consideration of attenuation, scattering, spatial resolution and measurement of sensitivity, the frequency band 0.4 - 0.7 THz has been determined optimal for operation. THz, typically defined as the frequency range between 0.1-10 THz, has been proposed for skin hydration imaging and monitoring primarily due to being non-ionizing radiation and highly sensitivity to water concentrations. While it is important to maximize measurement sensitivity to changes in water concentration, the optimal operational frequency band must simultaneously minimize the scattering from the targets (i.e. skin) and attenuation, as well as maximize the spatial resolution. In terms of atmospheric attenuation, from 0.4 to 1 THz, there are broad absorption lines at 556 GHz and 750 GHz, and large transmission windows centered at 500, 650, and 870 GHz. Scattering of the energy reflected from skin was show, using modeling, that as the frequency increased there was a considerable decrease in the power fraction reflected in the specular direction. For measurement sensitivity, it was shown that a change in reflectivity per change in water volume at 100 GHz was nearly an order of magnitude higher at 1 THz. Finally, as should be expected, higher frequencies were better for spatial resolution. In consideration of the above criteria, the motivation for using the 0.4-0.7 THz band will be presented as well as an overview the developed THz pulse reflective imaging system for imaging of skin hydration.

Foot ulceration is a debilitating comorbidity of diabetes that may result in loss of mobility and amputation. Optical detection of cutaneous tissue changes due to inflammation and necrosis at the preulcer site could constitute a preventative strategy. A commercial hyperspectral oximetry system was used to measure tissue oxygenation on the feet of diabetic patients. A previously developed predictive index was used to differentiate preulcer tissue from surrounding healthy tissue with a sensitivity of 92% and specificity of 80%. To improve prediction accuracy, an optical skin model was developed treating skin as a two-layer medium and explicitly accounting for (i) melanin content and thickness of the epidermis, (ii) blood content and hemoglobin saturation of the dermis, and (iii) tissue scattering in both layers. Using this forward model, an iterative inverse method was used to determine the skin properties from hyperspectral images of preulcerative areas. The use of this information in lowering the false positive rate was discussed.

Electrochemical biosensors have been developed due to its potential to be a compact medical diagnostic devise with high sensitivity. So far we have developed a photoelectrochemical DNA sensor using transparent semiconductor films such as tin-doped indium oxide (ITO), in which probe DNAs that captures fluorescence-labeled target DNAs were immobilized on semiconductor via silane coupling reagent such as aminopropyl triethoxy silane (APTES). Here we aimed to provide an effective DNA immobilization technique using gold thin layer in order to obtain higher photocurrents to noise ratio. Gold thin film (1nm thickness) deposited over semiconductor electrode serves as a substrate to immobilize a thiol-modified DNA (24bases) at its end that can capture fluorescence-labeled target DNA by hybridization. The sensitivity in this method was approximately 4times higher than that in APTES.

Remote laser surgery lacks of haptic feedback during the laser ablation of tissue. Hence, there is a risk of iatrogenic damage or destruction of anatomical structures like nerves or salivary glands. Diffuse reflectance spectroscopy provides a straightforward and simple approach for optical tissue differentiation. We measured diffuse reflectance from seven various tissue types ex vivo. We applied Linear Discriminant Analysis (LDA) to differentiate the seven tissue types and computed the area under the ROC curve (AUC). Special emphasis was taken on the identification of nerves and salivary glands as the most crucial tissue for maxillofacial surgery. The results show a promise for differentiating tissues as guidance for oral and maxillofacial laser surgery by means of diffuse reflectance.

The use of Raman spectroscopy for biomedical applications requires overcoming the obstacle of the broad fluorescence background that is generally generated in biological samples. Recently, we have developed a new modulation method for separating the weak Raman peaks from the strong fluorescence background. The novel method is based on the periodical modulation of the excitation wavelength and uses the principle of multi-channel lock-in detection. By continuously modulating the excitation wavelength it is possible to shift the Raman peaks while the fluorescence background remains essentially constant. The powerful capabilities of this novel method are demonstrated by acquiring spectra from different location (nucleus, cytoplasm and membrane) inside a CHO cell. In fact, we show that our modulated Raman spectroscopy provides, with higher efficiency than the standard one, Raman spectra of different locations within a single cell, suggesting that this minimally invasive optical technology could be applied for bio-medical diagnosis and imaging.

The specific optical spectra of tissues contain information about the biochemical composition. We present a simple optical fiber probe spectrometer design for noninvasive measurement of oxygen saturation in the microvasculature of stomach tissue. In a human Esophagectomy model with 23 patients, we measured the spectrum following surgical ligation of two of the three arterial paths to the stomach tissue that will become the anastamosis. Combining a diffusion model for semi-infinite slab remittance with absorption spectroscopy, we are able to specify the ratio of oxy-hemoglobin to deoxy-hemoglobin present in the tissue. We show a resting state of 0.47 (oxy-hemaglobin/total-hemaglobin) saturation decrease of 29% (p < 0.01) when arterial supply is reduced by artery ligation.

Lab-on-a-chip or Micro total analysis systems (μTAS) technologies offer a lot of potential applications for biosensing and biomedical detections. This paper presents the design, fabrication and characterization of a fully integrated siliconpolymer based biophotonic Micro-Total Analysis System for the real-time detection of enzymes and antigens. This device uses optical detection methods i.e, optical absorption, Laser induced fluorescence and evanescence measurement technique to detect the presence, concentration and the activity of biomolecules. The main components of the proposed system are microfluidic unit and micromechanical fluid actuation system, integrated with the optical detection systems. An Echelle grating based Spectrometer-on-Chip on Silica-on-Silicon (SOS) is integrated with the opto-microfluidic assembly for fluorescence detection. On-Chip fabrication and integration of valveless micropump has been carried out in order to facilitate the transportation of fluid within the system. The important advantages of the proposed μTAS are functional independence of each module of the system, simultaneous multi-analyte detection, rapid, precise and discriminating results, low background/high signal-to-noise ratio, lack of moving parts, robust, portability, and feasibility of bulk fabrication.

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. There is great interest in studying the relationship among microstructures and molecular processes of colorectal cancer during its progression at early stages. In this study, we use our multi-modality optical system that could obtain co-registered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) images simultaneously to study CRC. The overexpressed carbohydrate α-L-fucose on the surfaces of polyps facilitates the bond of adenomatous polyps with UEA-1 and is used as biomarker. Tissue scattering coefficient derived from OCT axial scan is used as quantitative value of structural information. Both structural images from OCT and molecular images show spatial heterogeneity of tumors. Correlations between those values are analyzed and demonstrate that scattering coefficients are positively correlated with FMI signals in conjugated. In UEA-1 conjugated samples (8 polyps and 8 control regions), the correlation coefficient is ranged from 0.45 to 0.99. These findings indicate that the microstructure of polyps is changed gradually during cancer progression and the change is well correlated with certain molecular process. Our study demonstrated that multi-parametric imaging is able to simultaneously detect morphology and molecular information and it can enable spatially and temporally correlated studies of structure-function relationships during tumor progression.

Early imaging of tumor response to chemotherapy has the potential for significant clinical benefits. We are developing a family of fiber-optic sensors called Sencils^TM (sensory cilia), which are disposable, minimally invasive, and can provide in vivo monitoring of various analytes for several weeks. The objective of this study was to develop and test our sensor to image the labeling of phosphatidylserine by apoptotic cells in response to chemotherapeutic drugs. FM1-43 was a better fluorescent marker for detecting phosphatidylserine expression than Annexin V-FITC; both the proportion of labeled cells (Annexin V, 15%; FM1-43, 58%) and the relative fluorescent increase (Annexin V-FITC, 1.5-fold; FM1-43, 4.5-fold) was greater when FM1-43 was used to detect apoptosis. Initial testing of the optical sensing technology using Taxol-treated MCF-7 cells demonstrated that injection of FM1-43 resulted in a rapid, transient increase in fluorescence that was greater in apoptotic cells compared to control cells (apoptotic cells, 4-fold increase; control cells, 2-fold increase). Using an established animal model, mice were injected with cyclophosphamide and hepatic apoptosis was assessed by imaging of PS expression. Both the amplitude of fluorescence increase and the time taken for the amplitude to decay to half of its peak were increased in livers from animals treated with cyclophosphamide. Our optical sensing technology can be used to detect the early apoptotic response of cells to chemotherapeutic drugs both in vitro and in vivo. This novel technology represents a unique option for the imaging of tumor responses in vivo, and provides an inexpensive, specific system for the detection of early-stage apoptosis.

Some years ago, CE-marked clinical multiphoton systems for 3D imaging of human skin with subcellular resolution have been launched. These tomographs provide optical biopsies with submicron resolution based on two-photon excited autofluorescence (NAD(P)H, flavoproteins, keratin, elastin, melanin, porphyrins) and second harmonic generation by collagen. The 3D tomograph was now transferred into a 5D imaging system by the additional detection of the emission spectrum and the fluorescence lifetime based on spatially and spectrally resolved time-resolved single photon counting. The novel 5D intravital tomograph (5D-IVT) was employed for the early detection of atopic dermatitis and the analysis of treatment effects.

We provide a detailed signal-to-noise analysis for 3D imaging of luminescence from a biomarker to detect hypoxic tumors in deep tissue. Preliminary studies on phantom tissues with inclusions and having homogeneous scattering and absorption coefficient of μ_s' ~ 15-20 cm^-1 and μ_a ~ 2 cm^-1 respectively, are reported as a function of oxygen tension, luminophore concentration, and tissue depth. The technique's sensitivity in terms of determination of spatial resolution is discussed.

This paper presents a novel windowing interface pinch force measurement system that is basically based on an USB (Universal Series Bus) microcontroller which mainly processes the sensing data from the force sensing resistance sensors mounted on five digits. It possesses several friendly functions, such as the value and curve trace of the applied force by a hand injured patient displayed in real time on a monitoring screen, consequently, not only the physician can easily evaluate the effect of hand injury rehabilitation, but also the patients get more progressive during the hand physical therapy by interacting with the screen of pinch force measurement. In order to facilitate the pinch force measurement system and make it friendly, the detail hardware design and software programming flowchart are described in this paper. Through a series of carefully and detailed experimental tests, first of all, the relationship between the applying force and the FSR sensors are measured and verified. Later, the different type of pinch force measurements are verified by the oscilloscope and compared with the corresponding values and waveform traces in the window interface display panel to obtain the consistency. Finally, a windowing interface pinch force measurement system based on the USB microcontroller is implemented and demonstrated. The experimental results show the verification and feasibility of the designed system.

Conventionally, the diagnosis of hepatocellular carcinoma (HCC) is performed by qualitative examination of histopathological specimens, which takes times for sample preparation in fixation, section and stain. Our objective is to demonstrate an effective and efficient approach to apply multiphoton microscopy imaging the HCC specimens, with the advantages of being optical section, label-free, subcellular resolution, minimal invasiveness, and the acquisition of quantitative information at the same time. The imaging modality of multiphoton autofluorescence (MAF) was used for the qualitative imaging and quantitative analysis of HCC of different grades under ex-vivo, label-free conditions. We found that while MAF is effective in identifying cellular architecture in the liver specimens, and obtained quantitative parameters in characterizing the disease. Our results demonstrates the capability of using tissue quantitative parameters of multiphoton autofluorescence (MAF), the nuclear number density (NND), and nuclear-cytoplasmic ratio (NCR) for tumor discrimination and that this technology has the potential in clinical diagnosis of HCC and the in-vivo investigation of liver tumor development in animal models.

We present a calibration protocol to get the alignment factors of a custom-made spectrometer and the nonlinear fitting function between the measured CCD pixel domain and the wavelength domain to apply the Fourier-domain optical coherence tomography (FD-OCT) using optical fiber gratings. We have used 5 different center wavelength gratings covered the broadband source spectral range with a narrow spectral bandwidth (<0.05 nm) and the same reflectivity (>92 %) to calibrate and align the custom-made spectrometer. The implemented SD-OCT system following the proposed protocol showed the alignment factors as 44.37o incident angle, 53.11o diffraction angle, and 70.0 mm focal length. The spectral resolution of 0.187 nm was recalculated from the alignment factors.

We are developing fluorescence-free interferometric biosensors for the early detection of epithelial ovarian cancer (EOC) and prognosis of acute lymphocytic leukemia (ALL). We can detect potential early markers for EOC (CA125, human epididymus protein 4, osteopontin) spiked into serum as well as elevated CA125 in EOC patient serum. For ALL prognosis we are focusing on three intracellular protein markers (p73, p57/Kip2, and p15/Ink4b), the down-regulation of any two being indicative of a more aggressive cancer. We have detected p15 and p57 spiked into buffer and are preparing to test positive and negative control lysates from bone marrow biopsies.