The label-free technique of optofluidic intracavity spectroscopy (OFIS) utilizes the optical transmission spectrum of a cell in a microfluidic Fabry-Pérot (F-P) cavity to distinguish cells from cancerous cell lines and baseline normal blood cells. The classification between canine hemangiosarcoma (HSA) cancer cells and monocytes in canine normal peripheral blood mononuclear cells (PBMCs) had been demonstrated with 95% sensitivity and 98% specificity. Now with a new optical model that treats the cell settled at the bottom of the cavity as a thin lens, the focal length of cells was extracted and used as an individual cell malignancy indicator.

There have been enormous progresses in developing a class of multimodal contrast agents, which combine MRI with optical imaging. Contrast agent targeting can provide enhanced diagnostic information, allowing differentiation between variable and stable atherosclerotic plaques. Recently an intensive efforts have been working on the development of contrast agents that can improve the ability to detect and characterize atherosclerosis in clinical and preclinical applications. Earlier studies on hyperlipidemic rabbits using in vivo MRI have shown accumulation of USPIOs in plaques with a high macrophage content that induces magnetic resonance (MR) signal changes correlated to the absolute iron content in the aortic arch. A potent new class of nanoparticles contrast agents have recently drawn much attention for its wide diverse diagnostic and potential therapeutic applications particularly in monitoring the inflammatory responses. In our previous studies we have investigated SPIO contrast agents uptakes in hepatic and spleen tissues taken from NZW rabbits. The scope of this work encompasses application of an emerging hybrid imaging modality, SERSbased nonlinear optical microscopy, in investigating atherosclerosis experimental models. In this work experiments are performed on contrast treated tissue sections taken from aortic arch of atherosclerotic animal model. Marked contrast enhancement has been observed in the treated aortic sections compared with the untreated control. The obtained images are compared with immunohistochemistry .The work presented can be promising for future studies on in vivo detection of macrophages in human plaques and early detection of atherosclerotic diseases.

Joint cartilage thickness has been estimated using spatially resolved steady-state reflectance spectroscopy noninvasively and in-real time. The system consists of a miniature UV-VIS spectrometer, a halogen tungsten light source, and an optical fiber probe with six 400 um diameter fibers. The first fiber was used to deliver the light to the cartilage and the other five were used to detect back-reflected diffused light. Distances from the detector fibers to the source fiber were 0.8 mm, 1.6 mm, 2.4 mm, 3.2 mm and 4 mm. Spectra of back-reflected diffused light were taken on 40 bovine patella cartilages. The samples were grouped into four; the first group was the control group with undamaged cartilages, in the 2nd, 3rd and 4th groups cartilage thickness was reduced approximately 25%, 50% and 100%, respectively. A correlation between cartilage thicknesses and hemoglobin absorption of light in the wavelength range of 500 nm- 600 nm for source-detector pairs was found. The proposed system with an optical fiber probe less than 4 mm in diameter has the potential for cartilage thickness assessment through an arthroscopy channel in real-time without damaging the cartilage.

Medical shock is still a common cause for the unacceptably high mortality rate in trauma patient in Intensive Care Units (ICU), because limitations of the monitoring/ diagnostic techniques and short time span of shock development. In this paper we introduce a method for monitoring of the vessel density spatial pattern, using spatially resolved diffuse reflectance measurement. The setup contains a spatially resolved optical fiber probe coupled to supersensitive spectrometer and high power light source. The experiment was done on skin tissue phantom model containing grid pattern which mimicks optical properties of the skin and capillary network. The spatially resolved diffuse reflectance spectra are collected over the phantom with various detector to source distance. The measured spatially resolved diffuse reflectance spectra were analyzed yielding grid spatial pattern. This novel technique of the vessel density spatial pattern monitoring will help to detect the early signs of shock development in intensive care units.

An implanted system is being developed to monitor transplanted liver health during the critical 7-10 day period posttransplantation. The unit will monitor organ perfusion and oxygen consumption using optically-based probes placed on both the inflow and outflow blood vessels, and on the liver parenchymal surface. Sensing probes are based on a 3- wavelength LED source and a photodiode detector. Sample diffuse reflectance is measured at 735, 805, and 940 nm. To ascertain optimal source-to-photodetector spacing for perfusion measurement in blood vessels, an ex vivo study was conducted. In this work, a dye mixture simulating 80% blood oxygen saturation was developed and perfused through excised porcine arteries while collecting data for various preset probe source-to-photodetector spacings. The results from this study demonstrate a decrease in the optical signal with decreasing LED drive current and a reduction in perfusion index signal with increasing probe spacing. They also reveal a 2- to 4-mm optimal range for blood vessel perfusion probe source-to-photodetector spacing that allows for sufficient perfusion signal modulation depth with maximized signal to noise ratio (SNR). These findings are currently being applied to guide electronic configuration and probe placement for in vivo liver perfusion porcine model studies.

There is clinical utility for a wide-field, spectroscopic imaging device for quantitative tissue absorption and scattering in a number of applications. We present the design of a compact, cost-effective spectroscopic imaging system, which consists of a broadband source with bandpass filters and a light guide for illumination and an inexpensive array of silicon photodiodes for detection. A single-pixel version of the system was tested in liquid phantoms simulating a wide range of human breast tissue and optical properties can be extracted with absorption and reduced scattering errors of 12.6% and 4.7%, respectively. We show proof-of-concept for performing fast, wide-field spectroscopic imaging with a simple design. The design also allows for scaling and expansion into higher pixel number and density in future iterations of custom device design, which includes in-house photodiode array fabrication processes and integration of on-board current amplifier circuits.

Due to the large number of women diagnosed with breast cancer and the lack of intra-operative tools, breast cancer margin assessment presents a significant unmet clinical need. Diffuse reflectance spectral imaging provides a method for quantitatively interrogating margins of lumpectomy specimens. We have previously found that [β- carotene]/μ_s' is a diagnostically important parameter but both parameters, [β-carotene] and μ_s', were derived from a low resolution parameter map and are subject to the tissue type and heterogeneity present in the breast. In this study, we used diffuse reflectance measurements from individual sites co-registered with high resolution microendoscopy (HRME) images to determine if the combined performance of these technologies could improve margin assessment. By comparing the optical parameters of [β-carotene] and μ_s' to the quantitative HRME image endpoints of feature size, feature density and normalized fluorescence, we determined that adding HRME to spectral imaging can improve the specificity of our diffuse reflectance spectral imaging system.

Confocal mosaicing microscopy enables rapid imaging of large areas of fresh tissue, without the processing that is necessary for conventional histology. Using acridine orange (1 milliMolar, 20 seconds) to stain nuclei, basal cell carcinomas were detected in fluorescence confocal mosaics of Mohs surgical excisions with sensitivity of 96.6% and specificity of 89.2%. A possible barrier toward clinical acceptance is that confocal mosaics are based on a single mode of contrast and appear in grayscale, whereas histology is based on two (hematoxylin for nuclei, eosin for cellular cytoplasm and dermis) and appears purple-and-pink. Toward addressing this barrier, we report progress in developing a multispectral analytical model for digital staining: fluorescence confocal mosaics, which show only nuclei, are digitally stained purple and overlaid on reflectance confocal mosaics, which show only cellular cytoplasm and dermis, and digitally stained pink, to mimic the appearance of histology. Comparison of digitally stained confocal mosaics by our Mohs surgeon to the corresponding Mohs histology shows good correlation for normal and tumor detail. Digitally stained confocal mosaicing microscopy may allow direct examination of freshly excised tissue and serve as an adjunct for rapid pathology at-the-bedside.

Most human cancers arise from epithelium, the superficial layer covering the exterior of body or lining the internal body cavities. Endogenous fluorophores such as aromatic amino acids, reduced nicotinamide adenine dinucleotide (NADH), flavoprotein (FAD), keratin, collagen, and elastin can provide abundant information to reveal the changes in biochemistry, metabolism, and morphology of living tissues. Thus, autofluorescence spectroscopy and microscopy have been recognized as potential tools for discrimination of cancer from normal tissues. However, current fluorescence diagnostic studies mostly rely on spectral analysis or morphological differentiation. It is challenged since the emission spectra of endogenous fluorophores are broad and usually overlapping with each other and the fluorescence intensity could be affected by many factors. In this study, we instrumented a nonlinear optical microscopy system to characterize the morphologic and biochemical features in the epithelial precancer in vivo. The 7,12-dimethylbenz(a)anthracenetreated hamster cheek pouch were used as a living animal carcinogenesis model. And the autofluorescence signals of NADH, collagen and elastin were recorded by a time- and spectral- resolved detection system. The results show that there are obvious differences in the morphology of three-dimensional autofluorescence images between normal and precancerous epithelial tissues. The fluorescence lifetime of NADH and the SHG signal from collagen could provide additional approaches to identify cancer from normal tissue.

Treatment of lymphatic disease is complicated and controversial, due in part to the limited understanding of the lymphatic system. Lymphedema (LE) is a frequent complication after surgical resection and radiation treatment in cancer survivors, and is especially debilitating in regions where treatment options are limited. Although some extremity LE can be effectively treated with manual lymphatic drainage (MLD) therapy or compression devices to direct proximal lymph transport, head and neck LE is more challenging, due to complicated geometry and complex lymphatic structure in head and neck region. Herein, we describe the compassionate use of an investigatory technique of near-infrared (NIR) fluorescence imaging to understand the lymphatic anatomy and function, and to help direct MLD in a patient with head and neck LE. Immediately after 9 intradermal injections of 25 μg indocyanine green each around the face and neck region, NIR fluorescence images were collected using a custom-built imaging system with diffused excitation light illumination. These images were then used to direct MLD therapy. In addition, 3-dimensional (3D) surface profilometry was used to monitor response to therapy. NIR fluorescence images of functioning lymphatic vessels and abnormal structures were obtained. Precise geometries of facial structures were obtained using 3D profilometry, and detection of small changes in edema between therapy sessions was achieved. NIR fluorescence imaging provides a mapping of lymphatic architecture to direct MLD therapy and thus improve treatment efficacy in the head and neck LE, while 3D profilometry allowed longitudinal assessment of edema to evaluate the efficacy of therapy.

We present a study on the effectiveness of computer-aided diagnosis (CAD) of rheumatoid arthritis (RA) from frequency-domain diffuse optical tomographic (FDOT) images. FDOT is used to obtain the distribution of tissue optical properties. Subsequently, the non-parametric Kruskal-Wallis ANOVA test is employed to verify statistically significant differences between the optical parameters of patients affected by RA and healthy volunteers. Furthermore, quadratic discriminate analysis (QDA) of the absorption (μ_a) and scattering (μ_a or μ'_s) distributions is used to classify subjects as affected or not affected by RA. We evaluate the classification efficiency by determining the sensitivity (Se), specificity (Sp), and the Youden index (Y). We find that combining features extracted from μ_a and μ_a or μ'_s images allows for more accurate classification than when μ_a or μ_a or μ'_s features are considered individually on their own. Combining μ_a and μ_a or μ'_s features yields values of up to Y = 0.75 (Se = 0.84 and Sp = 0.91). The best results when μ_a or μ'_s features are considered individually are Y = 0.65 (Se = 0.85 and Sp = 0.80) and Y = 0.70 (Se = 0.80 and Sp = 0.90), respectively.

The sensitivity of Near Infrared Spectroscopy (NIRS) signals to motion artifact can limit practical applications of NIRS monitoring. We describe a wavelet based method for removing motion artifact from NIRS signals. This method was tested on monitoring data collected from leg muscle in 3 patients undergoing surgery to stabilize leg fractures. The results show an average of 18.36 dB attenuation in motion artifact energy in the NIRS signal for our test subjects when using the proposed method, without the introduction of significant distortion in the artifact-free regions of the signal.

Line-scanning, using 8-10 optical components, linear-array detectors and custom-FPGA electronics, may enable smaller, simpler and lower-cost confocal microscopes to accelerate translation to the clinic. The adaptability of commercially available low-cost array detectors for confocal microscopy is being investigated. Measurements of optical sectioning and lateral resolution showed good agreement with theory, and are comparable to that of point-scanning systems. LSFs through full thickness of human epidermis show a two-fold degradation in sectioning performance. Imaging of human epidermis in vivo demonstrates nuclear and cellular detail down to the basal layer with a bench top setup and also a compact clinical prototype. Blood flow in oral mucosa can be imaged using the clinical prototype. However, speckle and background noise degrade contrast and resolution of the image.

Decubitus ulcers are a costly and widespread issue in healthcare today, that result from impaired blood flow in skin and underlying muscle and tissue. To address this need, a point of care multi-wavelength diagnostic imaging system has been developed to monitor hemodynamic processes via use of optical imaging of deep tissue. The resulting measurements demonstrate changes in light-tissue interaction to differentiate healthy and pathologic tissue without disturbing patients in a hospital setting. The identification of light source-detector illumination patterns uniquely map to spatial depths of tissue. The additional time dependent component, allows a novel four-dimensional analysis of tissue. The portable, noninvasive, and non-contact features provide quantitative in-situ measurements.

The accuracy rates of the clinical assessment techniques used in grading burn injuries remain significantly low for partial thickness burns. In this paper, we present experimental results from terahertz characterization of 2^nd and 3^rd degree burn wounds induced on a rat model. Reflection measurements were obtained from the surface of both burned and normal skin using pulsed terahertz spectroscopy. Signal processing techniques are described for interpretation of the acquired terahertz waveform and differentiation of burn wounds. Furthermore, the progression of burn injuries is shown by comparison between acute characterization and 72-hours survival studies. While the water content of healthy and desiccated skin has been considered as a source of terahertz signal contrast, it is demonstrated that other biological effects such as formation of post-burn interstitial edema as well as the density of the discrete scattering structures in the skin (such as hair follicles, sweat glands, etc.) play a significant role in the terahertz response of the burn wounds.

To observe local variations in temperature, oxygenation and blood perfusion over time, four imaging systems were developed and compared: Two systems consisting of white broadband light source and a CCD camera in combination with a Liquid Crystal Tunable Filter, one in the visual domain, 420-730 nm, and one in the infrared domain, 650-1100 nm. Thirdly, a CCD camera in combination with a software controlled hyper-spectral light source consisting of a panel with 600 LEDs divided in 17 spectral groups in the range from 370 to 880 nm so that specific spectral distributions can be generated at high repetition rate (>1000 Hz) and, fourthly a standard IR thermal camera for comparison. From the acquired images at the selected wavelengths chromophores concentration images of oxy and deoxy hemoglobin can be calculated applying different algorithms. These imaging techniques were applied and compared for various clinical applications: Tumor demarcation, early inflammation, effectiveness of peripheral nerve block anesthesia, and localization of epileptic seizure. The relative changes in oxygenation and temperature could be clearly observed in good correlation with the physiological condition. The algorithms and data collection/processing can be optimized to enable a real-time diagnostic technique.

Liposarcoma (LS) is a rare and heterogeneous group of malignant mesenchymal neoplasms exhibiting characteristics of adipocytic differentiation. Currently, radical surgical resection represents the most effective and widely used therapy for patients with abdominal/retroperitoneal LS, but the presence of contiguous essential organs, such as the kidney, pancreas, spleen, adrenal glands, esophagus or colon, as well as often reoccurrence of LS in A/RP calls for the enhancement of surgical techniques to minimize resection and avoid LS reoccurrences. Difficulty in detecting the margins of neoplasms due to their affinity to healthy fat tissue accounts for the high reoccurrence of LS within A/RP. Nowadays, the microscopic detection of margins is possible only by use of biopsy, and the minimization of surgical resection of healthy tissues is challenging. In this presentation we'll demonstrate the initial OCT results for the imaging and distinction of LS and normal human fat tissues and clear detection of tumor boundaries.

We report imaging studies on site-specific peptide-targeting in tumor tissues using newly developed optical peptide probes and spectral-domain optical coherence tomography (SD-OCT). The system used two broadband superluminescent light emission diodes with different central wavelengths. An electro-optic modulation in the reference beam was used to get full-range deep imaging inside tumor tissues. The optical probes were based on Bombesin (BBN) that is a fourteen amino acid peptide. BBN has high binding affinity to gastrin-releasing peptide (GRP) receptors overexpressed on several human cancer cell lines. Fluorescence BBN probes were developed by conjugating the last eight residues of BBN, -Q-W-A-V-G-H-L-M-(NH₂), with Alexa Flour 680 or Alexa Fluor 750 dye molecules via amino acid linker -G-G-G. The SD-OCT imaging can identify normal tissue and tumor tissue through the difference in scattering coefficient, and trace the BBN conjugate probes through the absorption of the dye molecules using the twowavelength algorithm. We performed the specific uptake and receptor-blocking experiments of the optical BBN probes in severely compromised immunodeficient mouse model bearing human PC-3 prostate tumor xenografts. Tumor and muscle tissues were collected and used for SD-OCT imaging. The SD-OCT images showed fluorescence traces of the BBN probes in the peptide-targeted tumor tissues. Our results demonstrated that SD-OCT is a potential tool for preclinical and clinical early cancer detection.

Our goal is to use optical imaging to detect cancer development on the sub cellular scale. By determining the microscopic changes that precede ovarian cancer we hope to develop a minimally invasive screening test for high risk patients. A mouse ovarian cancer model has been developed by treating mice with 4-Vinylcyclohexene Diepoxide to induce ovarian failure and 7, 12-Dimethylbenz[a]anthracene (DMBA) to induce ovarian cancer. Using optical coherence tomography (OCT) and multiphoton microscopy (MPM) we have obtained co-registered en face images of sixty-seven mouse ovaries ex vivo and forty-two ovaries in vivo. Preliminary analysis indicates that OCT and MPM can visualize ovarian microstructure. During the next year we will be completing a long term survival study using post-menopausal mice that have been treated with DMBA to induce cancer and imaged in vivo at time points before and after treatment.

We present a new automatic spectral calibration (ASC) method for spectral Domain optical coherence tomography (SD-OCT). Our ASC method calibrates the spectral mapping of the spectrometer in SD-OCT, and does not require external calibrating light source or a commercial spectral analyzer. The ASC method simultaneously calibrates the physical pixel spacing of the A-scan in static and dynamic environments. Experimental results show that the proposed ASC method can provide satisfactory calibration for SD-OCT to achieve high axial resolution and high ranging accuracy, without increasing hardware complexity.

The effectiveness of microbicidal gels, topical products developed to prevent infection by sexually transmitted diseases including HIV/AIDS, is governed by extent of gel coverage, pharmacokinetics of active pharmaceutical ingredients (APIs), and integrity of vaginal epithelium. While biopsies provide localized information about drug delivery and tissue structure, in vivo measurements are preferable in providing objective data on API and gel coating distribution as well as tissue integrity. We are developing a system combining confocal fluorescence microscopy with optical coherence tomography (OCT) to simultaneously measure local concentrations and diffusion coefficients of APIs during transport from microbicidal gels into tissue, while assessing tissue integrity. The confocal module acquires 2-D images of fluorescent APIs multiple times per second allowing analysis of lateral diffusion kinetics. The custom Fourier domain OCT module has a maximum a-scan rate of 54 kHz and provides depth-resolved tissue integrity information coregistered with the confocal fluorescence measurements. The combined system is validated by imaging phantoms with a surrogate fluorophore. Time-resolved API concentration measured at fixed depths is analyzed for diffusion kinetics. This multimodal system will eventually be implemented in vivo for objective evaluation of microbicide product performance.

Dispersive-based spectrometers may be qualified by their spectral resolving power and their throughput efficiency. A device known as a virtual slit is able to improve the resolving power by factors of several with a minimal loss in throughput, thereby fundamentally improving the quality of the spectrometer. A virtual slit was built and incorporated into a low performing spectrometer (R ~ 300) and was shown to increase the performance without a significant loss in signal. The operation and description of virtual slits is also given. High-performance, lowlight, and high-speed imaging instruments based on a dispersive-type spectrometer see the greatest impact from a virtual slit. The impact of a virtual slit on spectral domain optical coherence tomography (SD-OCT) is shown to improve the imaging quality substantially.

Lung carcinoma is the most prevalent type of cancer in the world, and it is responsible for more deaths than other types of cancer. During diagnosis, a pathologist primarily aims to differentiate small cell carcinoma from non-small cell carcinoma on biopsy and cytology specimens, which is time consuming due to the time required for tissue processing and staining. To speed up the diagnostic process, we investigated the feasibility of using coherent anti-Stokes Raman scattering (CARS) microscopy as a label-free strategy to image lung lesions and differentiate subtypes of lung cancers. Different mouse lung cancer models were developed by injecting human lung cancer cell lines, including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, into lungs of the nude mice. CARS images were acquired from normal lung tissues and different subtypes of cancer lesions ex vivo using intrinsic contrasts from symmetric CH₂ bonds. These images showed good correlation with the hematoxylin and eosin (H&E) stained sections from the same tissue samples with regard to cell size, density, and cell-cell distance. These features are routinely used in diagnosing lung lesions. Our results showed that the CARS technique is capable of providing a visualizable platform to differentiate different kinds of lung cancers using the same pathological features without histological staining and thus has the potential to serve as a more efficient examination tool for diagnostic pathology. In addition, incorporating with suitable fiber-optic probes would render the CARS technique as a promising approach for in vivo diagnosis of lung cancer.

Recent technological advances in fiber optics, light sources, detectors, and molecular biology have stimulated unprecedented development of optical methods to detect pathological changes in tissues. These methods, collectively termed "optical biopsy," are nondestructive in situ and real-time assays. Optical biopsy techniques as fluorescence spectroscopy, polarized light scattering spectroscopy, optical coherence tomography, confocal reflectance microscopy, and Raman spectroscopy had been extensively used to characterize several pathological tissues. In special, Raman spectroscopy technique had been able to probe several biochemical alterations due to pathology development as change in the DNA, glycogen, phospholipid, non-collagenous proteins. All studies claimed that the optical biopsy methods were able to discriminate normal and malignant tissues. However, few studies had been devoted to the discrimination of very common subtle or early pathological states as inflammatory process, which are always present on, e.g., cancer lesion border. In this work we present a systematic comparison of optical biopsy data on several kinds of lesions were inflammatory infiltrates play the role (breast, cervical, and oral lesion). It will be discussed the essential conditions for the optimization of discrimination among normal and alterated states based on statistical analysis.

Preterm birth is the second leading cause of neonatal mortality and leads to a myriad of complications like delayed development and cerebral palsy. Currently, there is no way to accurately predict preterm labor, making its prevention and treatment virtually impossible. While there are some at-risk patients, over half of all preterm births do not fall into any high-risk category. This study seeks to predict and prevent preterm labor by using Raman spectroscopy to detect changes in the cervix during pregnancy indicative of labor. Since Raman spectroscopy has been used to detect cancers in vivo in organs like the cervix and skin, it follows that spectra will change over the course of pregnancy. Previous studies have shown that fluorescence decreased during pregnancy and increased during post-partum exams to pre-pregnancy levels. We believe significant changes will occur in the Raman spectra obtained during the course of pregnancy. In this study, Raman spectra from the cervix of pregnant mice and women will be acquired. Specific changes that occur due to cervical softening or changes in hormonal levels will be observed to understand the likelihood that a female mouse or a woman will enter labor.

The range of applications of Raman-based classification has expanded significantly, including applications in bacterial identification. The first stage in the classification of Raman spectra is commonly some form of preprocessing. This pre-processing greatly affects the accuracy of the results and introduces user bias and over-fitting effects. In this paper, we propose the use of Support Vector Machines with a novel correlation kernel. Results, obtained from the analysis of Raman spectra of bacteria, illustrate that the correlation kernel is "self-normalizing" and produces superior classification performance with minimal pre-processing, even on highly-noisy data obtained using inexpensive equipment. In addition, the performance does not degrade when applied to distinct test sets, a key feature of a clinically viable diagnostic application of Raman Spectroscopy.

Characterizing and locating sub-surface tumors will greatly enhance the detection and treatment of breast cancer. In this paper, a novel tactile sensation imaging system, that is capable of detecting and characterizing the subsurface object, was designed, implemented, and tested. A multi-layer Polydimethylsiloxane optical waveguide has been fabricated as the sensing probe. The light was illuminated below the acceptance angle to totally reflect within the flexible and transparent waveguide. When a waveguide is compressed by an external force, the contact area of the waveguide deforms and causes the light to scatter. The scattered light is captured by a high resolution camera and saved as an image. Using the salient features of the captured image, we estimated inclusion characteristics such as size, depth, and Young's modulus. To test the performance of the proposed system, we use a realistic tissue phantom with embedded stiff inclusions. The experimental results showed that the proposed system can detect inclusions and provide the relative values of inclusion's mechanical properties. Using these relative values, we can discern malignant and benign tumors.

Noise characterization through estimation of the noise power spectrum (NPS) is a central component of the evaluation of digital X-ray systems. Extensive works have been conducted to achieve accurate and precise measurement of NPS. One approach to improve the accuracy of the NPS measurement is to reduce the statistical variance of the NPS results. However, this method is based on the assumption that the noise in a radiographic image is arising from stochastic (random) processes. In the practical data, the artifactuals always superimpose on the stochastic noise as low-frequency background trends and prevent us from achieving accurate NPS. In this study, NPS measurement was implemented and compared before and after background trends removal, the results showed that background detrending reduced the variance of the low-frequency spectral components, hence improving the accuracy of NPS measurement. Our results also showed that involving more samples for ensemble averaging had little effect in reducing the variance of the low-frequency spectral components. All results implied that it is necessary and feasible to get better NPS estimate by appropriate background detredning.

The devising of a general engineering theory of multifunctional diagnostic systems for non-invasive medical spectrophotometry is an important and promising direction of modern biomedical engineering. We aim in this study to formalize in scientific engineering terms objectives for multifunctional laser non-invasive diagnostic system (MLNDS). The structure-functional model as well as a task-function of generalized MLNDS was formulated and developed. The key role of the system software for MLNDS general architecture at steps of ideological-technical designing has been proved. The basic principles of block-modules composition of MLNDS hardware are suggested as well.

Monitoring gastric pH for long periods, usually 24 h, may be essential in analyzing the physiological pattern of acidity, in obtaining information on changes in activity during peptic ulcer disease, and in assessing the effect of antisecretory drugs. Gastro-esophageal reflux, which causes a pH decrease in the esophagus content from pH 7 even down to pH 2, can determine esophagitis with possible strictures and Barrett's esophagus. One of the difficulties of the optical measurement of pH in the gastro-esophageal apparatus lies in the required extended working range from 1 to 8 pH units. The present paper deals with a novel optical pH sensor, using methyl red as optical pH indicator. Contrary to all acidbase indicators characterized by working ranges limited to 2-3 pH units, methyl red, after its covalent immobilization on controlled pore glass (CPG), is characterized by a wide working range which fits with the clinical requirements. The novel probe design here described is suitable for gastro-esophageal applications and allows the optimization of the performances of the CPG with the immobilised indicator. This leads to a very simple configuration characterized by a very fast response time.

For optimal performance of a high-precision optical system, careful and stable alignment is necessary. To achieve robust alignment in a commercial system, performance tradeoffs or significant redesigns are often made. We have developed subsystems that allow us to automatically monitor and control the optical system alignment, allowing us to minimize the changes necessary between high-performance research systems and practical commercial designs. In addition, this can allow ruggedization of systems that would be too unstable otherwise. We have implemented such an alignment system in a high-performance medical interferometric imaging device with a focus on maintaining high throughput and allowing for significant system customization. The system is able to maintain near-optimal alignment without any user interaction over a large thermal range and can compensate for misalignments during initial system construction or resulting from shock events. With careful planning, the cost of such a system can be kept reasonably low and it requires minimal interruption to a normal user's workflow. We will discuss the basic principles and necessary considerations for the implementation of such a system, using the developed system as a case study. Similar technology can be used in many optical devices and is especially relevant if access by a trained technician is difficult or costly.