Point-by-point inscribed sapphire parallel fiber Bragg gratings in a fully multimode system for multiplexed high-temperature sensing.

We study the point-by-point inscription of sapphire parallel fiber Bragg gratings (sapphire pFBGs) in a fully multimode system. A parallel FBG is shown to be critical in enabling detectable and reliable high-order grating signals. The impacts of modal volume, spatial coherence, and grating location on reflectivity are examined. Three cascaded seventh-order pFBGs are fabricated in one sapphire fiber for wavelength multiplexed temperature sensing. Using a low-cost, fully multimode 850-nm interrogator, reliable measurement up to 1500°C is demonstrated.

In-plane and out-of-plane deformations of gilt utero-sacral ligaments.

The uterosacral ligaments (USLs) are supportive structures of the uterus and apical vagina. The mechanical function of these ligaments within the pelvic floor is crucial not only in normal physiological conditions but also in reconstructive surgeries for pelvic organ prolapse. Discrepancies in their anatomical and histological description exist in the literature, but such discrepancies are likely due to large variations of these structures. This makes mechanical testing very challenging, requiring the development of advanced methods for characterizing their mechanical properties. This study proposes the use of planar biaxial testing, digital image correlation (DIC), and optical coherence tomography (OCT) to quantify the deformations of the USLs, both in-plane and out-of-plane. Using the gilts as an animal model, the USLs were found to deform significantly less in their main direction (MD) of in vivo loading than in the direction perpendicular to it (PD) at increasing equibiaxial stresses. Under constant equibiaxial loading, the USLs deform over time equally, at comparable rates in both the MD and PD. The thickness of the USLs decreases as the equibiaxial loading increases but, under constant equibiaxial loading, the thickness increases in some specimens and decreases in others. These findings could contribute to the design of new mesh materials that augment the support function of USLs as well as noninvasive diagnostic tools for evaluating the integrity of the USLs.

Interferometric spectroscopy and high-speed orientation detection of individual gold nanorods.

Although 3D positional tracking of single nanoparticles in suspension is now an established technique, the small size of the particles compared to the wavelength of light has meant it is still challenging to optically characterize individual diffusing particles in other ways. Here we introduce Quantitative Optical Anisotropy Imaging (QOAI), an interferometric technique that fills some of this gap by allowing for real-time tracking of orientation as well as spectroscopic characterization of polarizability in nanoparticles at the microsecond timescale. Applying this to gold nanorods, we demonstrate measurement of nanorod orientation with high precision with simultaneous spectroscopic characterization of the rods' longitudinal plasmon resonance. We also show that we can quantify rotational diffusion in individual particles in both the azimuthal and polar directions near a solid wall, as well as detecting binding of particles to that wall. The simple optical configuration of QOAI will make combining it with positional nanoparticle tracking techniques straightforward, and this opens the door to measurements that are not reachable with current techniques, such as detailed characterization of correlations between rotational and translational diffusion in nanoparticles, real-time observation of particle aggregation and assembly, and measurements of fluctuations in the plasmon resonance in metal nanoparticles as they encounter a changing or heterogeneous environment.

Phase sensitivity of off-axis digital holography.

In off-axis digital holography, the Fourier transform-based algorithm is commonly used for signal processing. Here, we derive the theoretical phase sensitivity of this algorithm, which can be calculated from a single 2D hologram. This algorithm sensitivity represents the best achievable sensitivity of a system using this algorithm. Our derivation treats the signal in its most general form, considering non-uniform illumination and the effect of sideband filtering. As a result, phase sensitivity varies spatially, determined by local signal-to-noise ratio. Sensitivity expressions for both shot noise and uniform noise models are given. These results are validated with simulations and experiments. Significantly, this theoretical sensitivity can serve as a baseline metric for assessing performance of a phase-imaging system, such as experimental sensitivity and hardware stability, which are critical for high-sensitivity quantitative phase imaging. In addition, the results are equally applicable to other interferometric techniques with similar interferogram patterns and signal processing algorithms.

Phase sensitivity evaluation and its application to phase shifting interferometry.

In quantitative phase imaging, sensitivity is a key measure of system reproducibility. Despite continuous experimental breakthroughs in achieving highly sensitive detection, in-depth studies of theoretical constraints on sensitivity are inadequate and comparisons between different techniques are difficult. In this paper, we introduce the method to evaluate the sensitivity of phase shifting interferometry which is a major category of quantitative phase imaging techniques. The method discusses in detail several key concepts of sensitivity evaluation, including a general three-level evaluation framework, a complete interference signal model, Cramér-Rao bound and algorithm sensitivity, algorithm and system efficiencies, as well as energy efficiency of an algorithm. In discussions of specific phase shifting algorithms, we focus on the shot noise-limited model. This simplified model not only reflects the rapid developments in modern detectors that are often dominated by shot noise, but also permits the calculation of theoretical sensitivities based on measured data, which is important in evaluating experimental performance. As examples, we study several common phase shifting interferometric techniques. The results of different techniques are compared to provide insights into algorithm optimization and energy efficiency of sensitivity. A normalized algorithm sensitivity table is also provided for readers to conveniently estimate their system's algorithm sensitivity and compare against experiments.

Bounds of parameter estimation for interference signals.

Parameter estimation, especially frequency estimation, from noisy observations of interference is essential in optical interferometric sensing and metrology. The Cramer-Rao bound (CRB) of such estimation determines measurement sensitivity limit. Unlike the well-studied complex sinusoids in communication theory, an optical interference signal is distinctly different in its model parameters and noise statistics. The connection between these parameters and their estimation bounds has not been well understood. Here we propose a complete, realistic multiparameter interference model corrupted by a combination of shot noise, dark noise, and readout noise. We derive the Fisher information matrix and the CRBs for all model parameters, including intensity, visibility, optical path length (frequency), and initial phase. We show that the CRBs of frequency and phase are coupled but not affected by the knowledge of intensity and visibility. Knowing the initial phase offers significant sensitivity advantage, which is verified by both theoretical derivations and numerical simulations. In addition to the complete model, a shot noise-limited case is studied, permitting the calculation of the CRBs directly from measured data.

Sensitivity evaluation of quantitative phase imaging: a study of wavelength shifting interferometry.

Sensitivity is a critical figure of merit to quantify measurement performance in quantitative phase imaging. It is affected by various noise sources in the system and by signal processing algorithms. Here we propose a three-level framework for sensitivity evaluation, including the Cramér-Rao bound (CRB), algorithmic sensitivity, and experimental sensitivity. Comparing the first two determines the theoretical efficiency of an algorithm, while inspecting the gap between the latter two reveals system efficiency. As an example, we apply this framework to wavelength shifting interferometry, an important category of quantitative phase imaging techniques. In a shot-noise-limited regime, the CRB is derived, and the performance of a four-step Carré algorithm is studied in simulations and experiments. Importantly, the proposed procedure allows the algorithmic sensitivity to be conveniently estimated from a single set of measurement data, which serves as a basis for system efficiency evaluation.

Integrated quantitative phase and birefringence microscopy for imaging malaria-infected red blood cells.

A dual-modality birefringence/phase imaging system is presented. The system features a crystal retarder that provides polarization mixing and generates two interferometric carrier waves in a single signal spectrum. The retardation and orientation of sample birefringence can then be measured simultaneously based on spectral multiplexing interferometry. Further, with the addition of a Nomarski prism, the same setup can be used for quantitative differential interference contrast (DIC) imaging. Sample phase can then be obtained with two-dimensional integration. In addition, birefringence-induced phase error can be corrected using the birefringence data. This dual-modality approach is analyzed theoretically with Jones calculus and validated experimentally with malaria-infected red blood cells. The system generates not only corrected DIC and phase images, but a birefringence map that highlights the distribution of hemozoin crystals.

Low-coherence wavelength shifting interferometry for high-speed quantitative phase imaging.

We propose low-coherence wavelength shifting interferometry and demonstrate its application to quantitative phase imaging of dynamic specimens. By shifting the source wavelength, multiple interferograms of the sample can be acquired at different spectral bands. A sample phase is thus encoded in the phase step between consecutive acquisitions. For the particular case of four-band imaging, we show that the phase can be extracted with a modified Carré algorithm. We describe signal demodulation in detail and discuss its implication on system implementation. A swept laser-based Mach-Zehnder interferometer is used to demonstrate the technique for real-time imaging of live sperm cells at 62.5 Hz. The dynamic dry mass of the sperm head is measured with a full-scale error of ±2%, validating the technique's capability for high-sensitivity, high-speed quantitative phase imaging.

Swept source digital holographic phase microscopy.

We propose a swept source-based digital holographic phase microscopy technique. By scanning source wavelength, a series of on-axis interferograms can be obtained for accurate determination of the sample phase using spectral domain interferometry. With these sample spectra, sources of undesirable interference artifacts, often significant in holographic systems, can be identified and avoided by placing the sample signal at a spectral frequency with a clean background. Pathlength sensitivity better than 0.3 nm can, thus, be achieved. The quantitative pathlength image of live sperm cells is obtained with clear identification of morphological features. In addition, the availability of sample spectrum also permits the retrieval of its spectroscopic information. The wavelength-dependent refractive indices of indocyanine green solution are obtained to demonstrate this capability.

Quantitative polarized light microscopy using spectral multiplexing interferometry.

We propose an interferometric spectral multiplexing method for measuring birefringent specimens with simple configuration and high sensitivity. The retardation and orientation of sample birefringence are simultaneously encoded onto two spectral carrier waves, generated interferometrically by a birefringent crystal through polarization mixing. A single interference spectrum hence contains sufficient information for birefringence determination, eliminating the need for mechanical rotation or electrical modulation. The technique is analyzed theoretically and validated experimentally on cellulose film. System simplicity permits the possibility of mitigating system birefringence background. Further analysis demonstrates the technique's exquisite sensitivity as high as ∼20 pm for retardation measurement.

Spectral modulation interferometry for quantitative phase imaging.

We propose a spectral-domain interferometric technique, termed spectral modulation interferometry (SMI), and present its application to high-sensitivity, high-speed, and speckle-free quantitative phase imaging. In SMI, one-dimensional complex field of an object is interferometrically modulated onto a broadband spectrum. Full-field phase and intensity images are obtained by scanning along the orthogonal direction. SMI integrates the high sensitivity of spectral-domain interferometry with the high speed of spectral modulation to quantify fast phase dynamics, and its dispersive and confocal nature eliminates laser speckles. The principle and implementation of SMI are discussed. Its performance is evaluated using static and dynamic objects.

Validation of the iHealth BP5 wireless upper arm blood pressure monitor for self-measurement according to the European Society of Hypertension International Protocol revision 2010.

OBJECTIVE: The aim of this study was to validate the iHealth BP5 wireless upper arm blood pressure (BP) monitor according to the European Society of Hypertension International Protocol (ESH-IP) revision 2010. MATERIALS AND METHODS: The ESH-IP revision 2010 for validation of BP measuring devices in adults was followed precisely. A total of 99 pairs of test device and reference BP measurements (three pairs for each of the 33 participants) were obtained in the study. RESULTS: The device produced 71, 89, and 97 measurements within 5, 10, and 15 mmHg for systolic blood pressure (SBP) and 73, 90, and 99 mmHg for diastolic blood pressure (DBP), respectively. The mean ± SD device-observer difference was -1.21 ± 5.87 mmHg for SBP and -1.04 ± 5.28 mmHg for DBP. The number of participants with two or three device-observer differences within 5 mmHg was 25 for SBP and 28 for DBP. In addition, three participants had no device-observer difference within 5 mmHg for SBP and none of the participants had the same for DBP. CONCLUSION: According to the validation results on the basis of the ESH-IP revision 2010, the iHealth BP5 wireless upper arm BP monitor can be recommended for self/home measurement in an adult population.

Phase-sensitive OCT imaging of multiple nanoparticle species using spectrally multiplexed single pulse photothermal excitation.

We apply phase-sensitive optical coherence tomography to image multiple nanoparticle species with two excitation wavelengths matched to their distinct absorption peaks. Using different modulation frequencies, multiple species collocated within the sample can be distinguished. In addition, we characterize single-pulse excitation schemes as a method to minimize bulk heating of the sample. We demonstrate this new scheme with B-mode photothermal measurements of tissue phantoms.

Quantitative phase spectroscopy.

Quantitative phase spectroscopy is presented as a novel method of measuring the wavelength-dependent refractive index of microscopic volumes. Light from a broadband source is filtered to an ~5 nm bandwidth and rapidly tuned across the visible spectrum in 1 nm increments by an acousto-optic tunable filter (AOTF). Quantitative phase images of semitransparent samples are recovered at each wavelength using off-axis interferometry and are processed to recover relative and absolute dispersion measurements. We demonstrate the utility of this approach by (i) spectrally averaging phase images to reduce coherent noise, (ii) measuring absorptive and dispersive features in microspheres, and (iii) quantifying bulk hemoglobin concentrations by absolute refractive index measurements. Considerations of using low coherence illumination and the extension of spectral techniques in quantitative phase measurements are discussed.

Angle-resolved low-coherence interferometry: an optical biopsy technique for clinical detection of dysplasia in Barrett's esophagus.

Angle-resolved low-coherence interferometry (a/LCI) is an optical biopsy technique that measures scattered light from tissue to determine nuclear size with submicron-level accuracy. The a/LCI probe can be deployed through the accessory channel of a standard endoscope and provides feedback to physicians to guide physical biopsies. The technique has been validated in animal and ex vivo human studies, and has been used to detect dysplasia in Barrett's esophagus patients in vivo. In a recent clinical study of 46 Barrett's esophagus patients, a/LCI was able to detect dysplasia with 100% sensitivity and 84% specificity. This report reviews the technique and discusses its potential clinical utility.

Detection of intestinal dysplasia using angle-resolved low coherence interferometry.

Angle-resolved low coherence interferometry (a/LCI) is an optical biopsy technique that allows for depth-resolved, label-free measurement of the average size and optical density of cell nuclei in epithelial tissue to assess the tissue health. a/LCI has previously been used clinically to identify the presence of dysplasia in Barrett's Esophagus patients undergoing routine surveillance. We present the results of a pilot, ex vivo study of tissues from 27 patients undergoing partial colonic resection surgery, conducted to evaluate the ability of a/LCI to identify dysplasia. Performance was determined by comparing the nuclear morphology measurements with pathological assessment of co-located physical biopsies. A statistically significant correlation between increased average nuclear size, reduced nuclear density, and the presence of dysplasia was noted at the basal layer of the epithelium, at a depth of 200 to 300 µm beneath the tissue surface. Using a decision line determined from a receiver operating characteristic, a/LCI was able to separate dysplastic from healthy tissues with a sensitivity of 92.9% (13/14), a specificity of 83.6% (56/67), and an overall accuracy of 85.2% (69/81). The study illustrates the extension of the a/LCI technique to the detection of intestinal dysplasia, and demonstrates the need for future in vivo studies.

Development of angle-resolved low coherence interferometry for clinical detection of dysplasia.

This review covers the development of angle-resolved low coherence interferometry (a/LCI) from initial development through clinical application. In the first applications, the approach used a time-domain interferometry scheme and was validated using animal models of carcinogenesis to assess the feasibility of detecting dysplasia in situ. Further development of the approach led to Fourier-domain interferometry schemes with higher throughput and endoscope-compatible probes to enable clinical application. These later implementations have been applied to clinical studies of dysplasia in Barrett's esophagus tissues, a metaplastic tissue type that is associated with an increased risk of esophageal adenocarcinoma. As an alternative to systematic biopsy, the a/LCI approach offers high sensitivity and specificity for detecting dysplasia in these tissues while avoiding the need for tissue removal or exogenous contrast agents. Here, the various implementations of a/LCI are discussed and the results of the preliminary animal experiments and ex vivo human tissue studies are reviewed. A review of a recent in vivo clinical study is also presented.

Spectral-domain differential interference contrast microscopy.

We present a fiber-optic low-coherence imaging technique, termed spectral-domain differential interference contrast microscopy (SD-DIC), for quantitative DIC imaging of both reflective surfaces and transparent biological specimens. SD-DIC combines the common-path nature of a Nomarski DIC interferometer with the high sensitivity of spectral-domain low-coherence interferometry to obtain high-resolution, quantitative measurements of optical pathlength gradients from a single point on the sample. Full-field imaging can be achieved by scanning the sample. A reflected-light SD-DIC system was demonstrated using a USAF resolution target as the phase object. Live cardiomyocytes were also imaged, achieving a resolution of 36 pm for pathlength gradient measurements. The dynamics of cardiomyocyte contraction were recorded with high sensitivity at selected sites on the cells.

Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology.

We present a novel Fourier-domain angle-resolved low-coherence interferometry (a /LCI) fiber probe designed for in vivo clinical application in gastrointestinal endoscopy. The a/LCI technique measures the depth-resolved angular scattering distribution to determine the size distribution and optical density of cell nuclei for assessing the health of epithelial tissues. Clinical application is enabled by an endoscopic fiber-optic probe that employs a 2.3-m-long coherent fiber bundle and is compatible with the standard 2.8-mm-diam biopsy channel of a gastroscope. The probe allows for real-time data acquisition by collecting the scattering from multiple angles in parallel, enabled by the Fourier domain approach. The performance of the probe is characterized through measurement of critical parameters. The depth-resolved sizing capability of the system is demonstrated using single- and double-layer microsphere phantoms with subwavelength sizing precision and accuracy achieved. Initial results from a clinical feasibility test are also presented to show in vivo application in the human esophagus.