This PDF file contains the front matter associated with SPIE Proceedings Volume 7186, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing

Proper treatment of diabetes includes maintenance of near normal blood glucose levels, which can only be achieved with frequent blood glucose monitoring. Current blood finger-stick methods for glucose sensing are invasive, often resulting in low patient compliance and poor disease control. The development of a noninvasive glucose sensor has the potential to provide optimal management of diabetes. Our proposed noninvasive approach is based on an optical polarimetry system for probing the anterior chamber of the eye. The sensor would eventually be used to measure the aqueous humor glucose concentration as a means to determine the blood glucose concentration. In this report, we present the development of a near real-time (less than 1 second) dual wavelength closed-loop polarimetric system to minimize glucose prediction error in the presence of varying birefringence due to motion artifact. The new dual wavelength polarimetric system and in vitro glucose measurement results will be presented which demonstrate the sensitivity and accuracy of the system in the presence of varying birefringence.

In-vitro analysis of flowing blood-saline mixtures is performed by time-domain optical coherence tomography imaging. The mixtures contain blood in concentrations ranging from 100% to 20%. For each image, a corresponding compounded profile is obtained by adding one thousand adjacent A-scans. The compounded profiles are used for characterizing the optical coherence tomography signal as it propagates within the studied blood-saline mixtures. The results obtained point toward the possibility of acquiring intra-vascular images of arterial tissue that is located behind slabs of flowing blood-saline. A threshold in the propagation distance beyond which the recorded signal becomes dominated by its multiple scattered components is established along the compounded profiles. The threshold location, at a depth of ~0.6 mm, is independent of blood concentration. Further investigation of the compounded profiles reveals that the region extending to a maximum depth of about 200 μm from the point where the probing beam enters blood-saline mixtures could reveal information about the flow regime. This opens the possibility of another application for time-domain optical coherence tomography in intravascular imaging: assessing the flow regime, i.e. laminar or turbulent.

Recently, various groups have developed wide field laser Doppler perfusion imaging systems based on high speed camera's. The limiting factor for the frame rate and measurement duration in whole field laser Doppler perfusion imaging is the speed of transfer and analysis of data. We present an algorithm for calculating perfusion estimations with much lower demands for data storage and computational effort than the conventional FFT-based method. Our algorithm works in the time domain and estimates perfusion through simple time differentiations and multiplications of speckle image values. The algorithm is partly based on mathematical reasoning, and partly on a hypothesis that cannot be proven with rigorous mathematics. We will compare our algorithm with the frequency-domain counterpart for phantom studies involving static and dynamic media, and in vivo experiments on human skin. It is found that both algorithms, applied on the same dataset, approximately give the same perfusion estimations. The random differences are similar to the random variations found in tissue perfusion. Systematic differences between the algorithms smaller than 15% are found. The algorithm is currently twice as fast as the FFT-counterpart. Another advantage is that our algorithm can be included in a moving average scheme, where a new perfusion value can be determined based on the previous value and a small number of new raw speckle images.

During extra-vehicular activities (EVAs) or space walks astronauts over use their fingertips under pressure inside the confined spaces of gloves/space-suite. The repetitive hand motion is a probable cause for discomfort and injuries to the finger-tips. We describe a new wireless fiber-optic probe that can be integrated inside the astronaut glove for non-invasive blood perfusion measurements in distal finger tips. In this preliminary study, we present blood perfusion measurements while performing hand-grip exercises simulating the use of space tools.

The cornea contributes about 65% of the eye's ability to refract light. Thus, any fluctuation in corneal thickness can cause noticeable changes in vision. The presence of glucose molecules induces a driving force for water to leave the collagen fibrils in the cornea due to the concentration gradient created, thus changing its thickness. In this study, the effect of various milli-molar glucose concentrations on corneal thickness was explored using Optical Coherence Tomography. Whole rabbit eyes were placed in a specially designed dish while immersed in saline to ensure proper hydration of the eye. The cornea was imaged for 10 minutes. In 30 minute increments, a higher concentration of glucose was added, bringing the overall glucose concentration to 10, 15, 20, 25, and 30 mM. The thickness of the cornea was measured every 2 minutes. Ultimately, an inverse relationship was observed, indicating that the increase in glucose concentration yielded a decrease in the corneal thickness. From three separate experiments, the cornea experienced 8 ± 1, 27 ± 1, 44 ± 3, 58 ± 3, and 64 ± 3 μm decrease in thickness from its starting value while exposed to 10, 15, 20, 25, and 30 mM solutions of glucose, respectively. This relationship provides insight on the physiological changes of the cornea as a result of different glucose concentrations. This could potentially be useful in monitoring blood-glucose levels through the eye.

The inherent barrier function of the stratum corneum (SC) makes optical clearing agents difficult to penetrate into skin. To date, several physicochemical methods have been studied to enhance skin optical clearing. In this study, the rat skin was initially irradiated by various light (Carbon-Dioxide Laser, Intensed Pulse Light, Nd:YAG Laser and its frequency-doubled laser) with different dose, and then topically applied anhydrous glycerol. A fiber spectrometer was used to monitor the change of skin diffuse reflectance spectrum so as to evaluate the optical clearing effect on skin. The results showed that Nd:YAG Laser(1,064 nm) with appropriate pulse width and energy density combined with glycerol could improve skin optical clearing effectively, and that Q-switched Nd:YAG Laser combining glycerol made the most significant decrease of skin diffuse reflectance. However, after the irradiation of Carbon-Dioxide Laser (ultra-pulsed), Intensed Pulse Light (400-700 nm) or frequency-doubled Q-switched Nd:YAG Laser(532 nm), the following application of glycerol didn't lead to skin optical clearing. Adversely, higher power of the former two light could result in erythema, the later one may harm skin apparently even lead to blood coagulation dot. This study provids a new idea to find out a noninvasive but high-effective approach to increase skin optical clearing, and available parameters of laser need to be further investigated.

A practical limitation encountered in alcohol research is the relatively small number of body compartments (e.g. blood, liver, tissue) that can be directly interrogated. In this work, an NIR spectroscopic device was investigated that provided a direct measurement of alcohol concentration in skin tissue (interstitial fluid). This work is intended to characterize the relationship of forearm interstitial fluid alcohol concentration relative to capillary blood using a first order kinetic model. Concurrent blood and tissue alcohol concentrations were collected on 101 test subjects while consuming alcohol. Estimates of the first order kinetic rate constant were calculated for each of the subjects. It is hoped that this characterization will lead to further improvements in optical based alcohol monitors for impairment detection.

Histologic diagnosis is the gold standard for evaluating the presence and severity of most cancers. Unfortunately, the manual nature of histologic recognition leads to low throughput and errors. Here, we report on the evaluation of an automated means to accurate histologic recognition using mid-infrared spectroscopic imaging. The method does not need dyes or probes and dispenses with human input but relies on computational approaches to provide decisions. Hence, the results must be rigorously validated. We present here a validation of two-class models for pixel-level histologic segmentation and pathologic classification by spatial polling for breast carcinoma. We also discuss optimization of spectral resolution and instrumentation for clinical translation.

Cortical spreading depression (CSD) is an important neurophysiological phenomenon correlating with some neural disorders, such as migraine, cerebral ischemia and epilepsy. By now, we are still not clear about the mechanisms of CSD's initiation and propagation, also the relevance between CSD and those neural diseases. Nevertheless, characterization of CSD, especially the spatiotemporal evolution, will promote the understanding of the CSD's nature and mechanisms. Besides the previous experimental work on charactering the spatiotemporal evolution of CSD in rats by optical intrinsic signal imaging, a computational study based on a generalized cellular automaton (CA) model was proposed here. In the model, we exploited a generalized neighborhood connection rule: a central CA cell is related with a group of surrounding CA cells with different weight coefficients. By selecting special parameters, the generalized CA model could be transformed to the traditional CA models with von Neumann, Moore and hexagon neighborhood connection means. Hence, the new model covered several properties of CSD simulated in traditional CA models: 1) expanding from the origin site like a circular wave; 2) annihilation of two waves traveling in opposite directions after colliding; 3) wavefront of CSD breaking and recovering when and after encountering an obstacle. By setting different refractory period in the different CA lattice field, different connection coefficient in different direction within the defined neighborhood, inhomogeneous propagation of CSD was simulated with high fidelity. The computational results were analogous to the reported time-varying CSD waves by optical imaging. So, the generalized CA model would be useful to study CSD because of its intuitive appeal and computational efficiency.

This study demonstrates a novel phase-sensitive surface plasman resonance biosensor (PS-SPRB) which is able to convert the phase modulation into amplitude modulation analytically via a differential amplifier. PS-SPRB is able to measure biomolecule interactions at ultra-low concentration relying on the properties of phase sensitive detection at shot-noise detection in a real-time. The common-phase noise-rejection mode is provided in PS-SPRB to be able to immune the background phase noise efficiently. The experimental results confirm the detection sensitivity of 0.00001 wt % concentration of sucrose solution and 10 fg/ml mouse IgG interaction with anti IgG in real time.

This paper details the current techniques for the detection of caries using non-invasive techniques, A promising option is tooth trans-illumination which is based on an increase of light scattering or light absorption in the affected tissue region. In this study trans-illumination applied to detect microscopic caries lesions was investigated using premolar teeth containing affected caries lesions. One line coincides with a carious absorption line, while the other is used as a reference. By this referencing the system is auto-calibrated continuously. Normal and carious human teeth were applied for the determination of NIR absorption by using a micro-spectrophotometer. Relative NIR absorption value for normal tooth and for carious one distributed in different quantity relating to the tooth structure, whereas the value showed much higher in enamel than in dentine. This paper suggests a way to use a commercially available system, which has the capability to carious detection. It is based on photomechanical and photothermal monitoring of teeth response. This technique is based on irradiation of the teeth with a short pulse Nd:YAG laser (1064 μm, 12 ns) and monitoring the laser-induced local thermal effects. This is realized with thermal imagers that locate the heated teeth absorbing zones. The photothermal (PT) image represents a two-dimensional depth-integrated temperature distribution in the irradiated volume and correlates with the conventional optical absorption coefficients. In addition to a description as to how each of the modalities function, consideration is given to recent advances and changes in the relevant technologies, and a comparison of relative benefits and shortfalls of the systems.

A reference position where the diffuse reflectance light intensity is insensitive to the variation of glucose concentration exists in the radial detection space for glucose measurement in the scattering medium such as skin. The signal measured in this position could be used as an inside reference to evaluate the influence on spectrum caused by other interferential factors. The relationship between the position of radial reference point and the skin tissue property is studied in this paper. Three-layer skin models with different optical parameters are designed to get sample sets at 1200~1700nm. In these sets, μ_a, μ_s and g of dermis varies respectively, so does the depth of epidermis or dermis. The distribution rule of dispersion of diffuse reflectance light intensity in the radial space is confirmed with the glucose concentration changes. And the distribution property of the radial reference position in every sample set is obtained through Monte Carlo simulation. The result shows that the distance of radial reference position from light source is insensitive to the variation of absorption coefficient or the depth of dermis, but an increased scattering coefficient will shorten the distance; an increased anisotropy coefficient or depth of epidermis will lengthen it. On the basis of that, the optical probes with different structures are designed according to the skin tissue properties. So they could be used for the measurement of corresponding patients, which enhances the practicability of floating reference method greatly.

As an effective noninvasive method for glucose doesn't come into clinical realization due to the weakness of glucose unique signal and complexity of background noise, a method based on a floating reference point and a measuring point, where the diffuse reflectance intensity is insensitive and most sensitive to the variation of glucose concentration, respectively, is applied. In this paper, the data processing method based on the information of reference point was investigated to improve the precision of glucose sensing. The diffuse reflectance of intralipid solution with different glucose concentration in different source-detector distances was obtained by Monte-Carlo simulation. And the radial region selection of reference position and measuring position were discussed. Then in order to simulate the actual measurement condition, the random noise and linear drift were added on the simulated spectra. And the spectra in the proper measuring region corrected by that in the reference point were used to build the multivariate model. Further more, the corresponding optical probe was designed according to the distribution of light intensity in the radial distance and an in vitro experiment about intralipid solution with different glucose concentration was conducted to verify the effect of the data correction based on the information from the reference point. Results showed that, three different measuring regions should be determined in the wavelength of 1100nm-1700nm according to the wavelength characteristic of reference point. And the measuring region should be about 0.2-0.3mm far away from the reference region. For the simulation and in vitro experiment, after the correction by the information from the reference point, the prediction error for glucose was reduced by 46.2% and 23.2%, respectively.

We describe a new method to separate ballistic from the scattered photons in a tissue characterization study. It is based on the concept that the scattered photons acquire a phase delay whose magnitude depends on the number of scatterings and the resulting path increment for photons transmitted in the direction of incidence. All other photons are eliminated with physical apertures in his scanning arrangement. We propose a Mach-Zehnder experimental setup where the ballistic photons pass through the sample with the delay caused uniquely by the sample indices of refraction, assuming multiple layers. The method is based on the capability of the photons, passing through the sample without scattering or absorption to preserve their coherence. With the incorporation of a movable mirror on the piezoelectric actuator in the reference arm, this method allows measuring only those photons that suffer no phase delay upon passing through the sample. We present the theory that predicts the feasibility of this method to differentiate between classes of tissues. The method is feasible for samples with transmission of ballistic photons down to 10^-18.

Regular monitoring of blood sugar level is important for the management of diabetes. The Near-Infra-Red (NIR) spectroscopy method is a promising approach and this involves some form of contact with the body skin. It is noted that the skin temperature does fluctuate with the environment and physiological conditions and the temperature has an influence on the glucose measurement. In this paper, in-vitro and in-vivo investigations on the temperature influence on blood glucose measurement were studied. The in-vitro results from FTIR spectrometer show that sample temperature has significant influence on water absorption, which significantly affects the glucose absorption measurement. The in-vivo results show that when skin temperature around the measurement site is taken into consideration, the prediction of blood glucose level greatly improves.

Fluidic measurement is a critical part of clinical care and homeostasis maintenance. This paper reports feasibility study of measuring flow velocities over a wide dynamic range using a non-contact measurement technique, optical time-of-flight (OTOF), with the objective of developing a compact instrument that can be used to measure fluid flow for IV medication delivery. In this study, a 1480nm laser diode focused to a 20μm spot introduces a heat bolus into the fluid. This localized temperature increase results in a correlated change in refractive index, detected downstream by observing defocusing of the visible beam, focused to a 10μm spot in the center of the fluid path. The OTOF measurement provides the centerline velocity of the fluid flow. CFD modeling ensured that laminar flow was fully developed; prior to the OTOF measurement point, thus providing a simple, empirical relationship between OTOF and fluid velocity, and hence volumetric flow rate. Measurements have been performed over a wide range of flow velocity from 1 mm/s to 1 m/s with approximately ±5% measurement error for broad ranges of fluid properties such as viscosity (0.77-13.88 cp), density (0.98-1.17 g/cm3) and temperature (5-35 °C). The dynamic range of measured velocity/flow rates is a function of the distance between the heating and the detection laser beams.