Fourier domain mode locked (FDML) lasers provide high sweep rates, broad tuning ranges, and high output powers for
optical coherence tomography (OCT) systems. However, presently-known FDML lasers at 1300 nm have relatively
short coherence lengths, limiting the size of samples that can be imaged. Furthermore, FDML lasers produce only one
useable sweep direction. We report FDML coherence length extension by incorporating advanced dispersion
compensation modules (DCMs). DCMs eliminate group velocity dispersion in the cavity, doubling coherence lengths
and ensuring uniform axial resolution over the imaging range. Additionally, forward and backward sweeps are nearly
identical, removing the need for external buffering stages.
Coronary calcified plaque (CP) is both an important marker of atherosclerosis and major determinant of the success of coronary stenting. Intracoronary optical coherence tomography (OCT) with high spatial resolution can provide detailed volumetric characterization of CP. We present a semiautomatic method for segmentation and quantification of CP in OCT images. Following segmentation of the lumen, guide wire, and arterial wall, the CP was localized by edge detection and traced using a combined intensity and gradient-based level-set model. From the segmentation regions, quantification of the depth, area, angle fill fraction, and thickness of the CP was demonstrated. Validation by comparing the automatic results to expert manual segmentation of 106 in vivo images from eight patients showed an accuracy of 78±9%. For a variety of CP measurements, the bias was insignificant (except for depth measurement) and the agreement was adequate when the CP has a clear outer border and no guide-wire overlap. These results suggest that the proposed method can be used for automated CP analysis in OCT, thereby facilitating our understanding of coronary artery calcification in the process of atherosclerosis and helping guide complex interventional strategies in coronary arteries with superficial calcification.
We report clinical study results of three-dimensional (3D) in vivo imaging of human coronary arteries using frequency domain optical coherence tomography (FD-OCT). At the time of this report, over 2000 patients in over 10 countries have been imaged using FD-OCT systems and disposable fiberoptic catheters developed by LightLab Imaging Inc. The first commercial versions of the systems were introduced in Europe in May 2009. The system operates at 50,000 axial lines/s, performing a 50 mm spiral pullback in 2.5 seconds with a rotational frame rate of 100 Hz. The commercial system employs a proprietary micro-cavity swept laser, allowing imaging of vessel diameters up to 10 mm. Data compiled from early studies indicate that FD-OCT is being used for post-intervention imaging of deployed coronary stents in over 40% of cases. High-resolution 3D imaging of stent geometry immediately following deployment enables
detection of stent malapposition, which can increase the risk of thrombosis. Longer term follow-up imaging of stented vessels can detect thrombus formation, which can be treated pharmacologically, and excessive neointimal growth, which may require angioplasty or re-stenting. FD-OCT is also being used for pre-intervention imaging of stenotic lesions in about 60% of cases. Here FD-OCT is used to measure the minimum lumen area and to identify calcified deposits, side branches, or other vascular structures that could interfere with the stenting procedure. Overall, FD-OCT continues to be
adopted at an increasing rate and has provided interventional cardiologists with a powerful tool for pre- and postintervention
assessment of the coronary arteries.
Barrett's esophagus (BE) with high-grade dysplasia is generally treated by endoscopic mucosal resection or
esophagectomy. Radiofrequency ablation (RFA) is a recent treatment that allows broad and superficial
ablation for BE. Endoscopic three-dimensional optical coherence tomography (3D-OCT) is a volumetric
imaging technique that is uniquely suited for follow-up surveillance of RFA treatment. 3D-OCT uses a thin
fiberoptic imaging catheter placed down the working channel of a conventional endoscope. 3D-OCT enables
en face and cross-sectional evaluation of the esophagus for detection of residual BE, neo-squamous mucosa,
or buried BE glands. Patients who had undergone RFA treatment with the BARRX HALO90 system were
recruited and imaged with endoscopic 3D-OCT before and after (3-25 months) RFA treatment. 3D-OCT
findings were compared to pinch biopsy to confirm the presence or absence of squamous epithelium or buried
BE glands following RFA. Gastric, BE, and squamous epithelium were readily distinguished from 3D-OCT
over a large volumetric field of view (8mmx20mmx1.6 mm) with ~5μm axial resolution. In all patients, neosquamous
epithelium (NSE) was observed in regions previously treated with RFA. A small number of
isolated glands were found buried beneath the regenerated NSE and lamina propria. NSE is a marker of
successful ablative therapy, while buried glands may have malignant potential and are difficult to detect using
conventional video endoscopy and random biopsy. Buried glands were not observed with pinch biopsy due to
their extremely sparse distribution. These results indicate a potential benefit of endoscopic 3D-OCT for
follow-up assessment of ablative treatments for BE.
We report on the design of a frequency domain optical coherence tomography (FD-OCT) system, fiber optic imaging
catheter, and image processing algorithms for in vivo clinical use in the human coronary arteries. This technology
represents the third generation of commercially-available OCT system developed at LightLab Imaging Inc. over the last
ten years, enabling three-dimensional (3D) intravascular imaging at unprecedented speeds and resolutions for a
commercial system. The FD-OCT engine is designed around an exclusively licensed micro-cavity swept laser that was
co-developed with AXSUN Technologies Ltd. The laser's unique combination of high sweep rates, broad tuning ranges,
and narrow linewidth enable imaging at 50,000 axial lines/s with an axial resolution of < 16 μm in tissue. The disposable
2.7 French (0.9 mm) imaging catheter provides a spot size of < 30 μm at a working distance of 2 mm. The catheter is
rotated at 100 Hz and pulled back 50 mm at 20 mm/s to conduct a high-density spiral scan in 2.5 s. Image processing
algorithms have been developed to provide clinically important measurements of vessel lumen dimensions, stent
malapposition, and neointimal thickness. This system has been used in over 2000 procedures since August 2007 at over
40 clinical sites, providing cardiologists with an advanced tool for 3D assessment of the coronary arteries.
Intravascular optical coherence tomography (OCT) has been proven a powerful diagnostic tool for cardiovascular diseases. However, the optical mechanism for the qualitative observations are still absent. We address the fundamental issues that underlie the tissue characterization of OCT images obtained from coronary arteries. For this, we investigate both the attenuation and the backscattering properties of different plaque components of postmortem human cadaver coronary arteries. The artery samples are examined both from lumen surface using a catheter and from transversely cut surface using an OCT microscope, where OCT images could be matched to histology exactly. Light backscattering coefficient µb and attenuation coefficients µt are determined for three basic plaque types based on a single-scattering physical model: calcification (µb=4.9±1.5 mm−1, µt=5.7±1.4 mm−1), fibers (µb=18.4±6.4 mm−1, µt=6.4±1.2 mm−1), and lipid pool (µb=28.1±8.9 mm−1, µt=13.7±4.5 mm−1). Our results not only explain the origins of many qualitative OCT features, but also show that combination of backscattering and attenuation coefficient measurements can be used for contrast enhancing and better tissue characterization.
KEYWORDS: Optical coherence tomography, Data acquisition, Imaging systems, Colon, In vivo imaging, Endomicroscopy, 3D acquisition, Tissues, 3D image processing, Endoscopy
We report an endoscopic optical coherence tomography (OCT) system based on a Fourier Domain Mode Locked
(FDML) laser, a novel data acquisition (DAQ) system with optical frequency clocking, and a high-speed spiralscanning
fiber probe. The system is capable of acquiring three-dimensional (3D) in vivo datasets at 100,000 axial
lines/s and 50 frames/s, enabled by the high sweep rates of the FDML laser and the efficient data processing of
the DAQ system. This high imaging rate allows densely-sampled 3D datasets to be acquired, giving a resolvable
feature size of 9 &mgr;m x 20 &mgr;m x 7 &mgr;m (transverse x longitudinal x axial, XYZ). In vivo 3D endomicroscopy is
demonstrated in the rabbit colon, where individual colonic crypts are clearly visualized and measured. With
further improvements in DAQ technology, the imaging speed will be scalable to the hundreds of thousands of
axial lines/s supported by FDML lasers.
Recent advances in catheter-based optical coherence tomography (OCT) have provided the necessary resolution and acquisition speed for high-quality intravascular imaging. Complications associated with clearing blood from the vessel of a living patient have prevented its wider acceptance. We identify a surgical application that takes advantage of the vascular imaging powers of OCT but that circumvents the difficulties. Coronary artery bypass grafting (CABG) is the most commonly performed major surgery in America. A critical determinant of its outcome has been postulated to be injury to the conduit vessel incurred during the harvesting procedure or pathology preexistent in the harvested vessel. As a test of feasibility, intravascular OCT imaging is obtained from the radial arteries (RAs) and/or saphenous veins (SVs) of 35 patients scheduled for CABG. Pathologies detected by OCT are compared to registered histological sections obtained from discarded segments of each graft. OCT reliably detects atherosclerotic lesions in the RAs and discerns plaque morphology as fibrous, fibrocalcific, or fibroatheromatous. OCT is also used to assess intimal trauma and residual thrombi related to endoscopic harvest and the quality of the distal anastomosis. We demonstrate the feasibility of OCT imaging as an intraoperative tool to select conduit vessels for CABG.
Optical coherence tomography (OCT) is an emerging medical imaging technology that enables high-resolution, noninvasive, cross-sectional imaging of microstructure in biological tissues in situ and in real time. When combined with small-diameter catheters or needle probes, OCT offers a practical tool for the minimally invasive imaging of living tissue morphology. We evaluate the ability of OCT to image normal kidneys and discriminate pathological changes in kidney structure. Both control and experimental preserved rat kidneys were examined ex vivo by using a high-resolution OCT imaging system equipped with a laser light source at 1.3-µm wavelength. This system has a resolution of 3.3 µm (depth) by 6 µm (transverse). OCT imaging produced cross-sectional and en face images that revealed the sizes and shapes of the uriniferous tubules and renal corpuscles. OCT data revealed significant changes in the uriniferous tubules of kidneys preserved following an ischemic or toxic (i.e., mercuric chloride) insult. OCT data was also rendered to produce informative three-dimensional (3-D) images of uriniferous tubules and renal corpuscles. The foregoing observations suggest that OCT can be a useful non-excisional, real-time modality for imaging pathological changes in donor kidney morphology prior to transplantation.
Optical contrast is often the limiting factor in the imaging of live biological tissue. Studies were conducted in postmortem human brain to identify clinical applications where the structures of interest possess high intrinsic optical contrast and where the real-time, high-resolution imaging capabilities of optical coherence tomography (OCT) may be critical. Myelinated fiber tracts and blood vessels are two structures with high optical contrast. The ability to image these two structures in real time may improve the efficacy and safety of a neurosurgical procedure to treat Parkinson's disease called deep brain stimulation (DBS). OCT was evaluated as a potential optical guidance system for DBS in 25 human brains. The results suggest that catheter-based OCT has the resolution and contrast necessary for DBS targeting. The results also demonstrate the ability of OCT to detect blood vessels with high sensitivity, suggesting a possible means to avoid their laceration during DBS. Other microscopic structures in the human brain with high optical contrast are pathological vacuoles associated with transmissible spongiform encephalopathy (TSE). TSE include diseases such as Mad Cow disease and Creutzfeldt-Jakob disease (CJD) in humans. OCT performed on the brain from a woman who died of CJD was able to detect clearly the pathological vacuoles.
Optical coherence tomography (OCT) is an emerging medical imaging technology which can generate high resolution, cross-sectional images of tissue in situ and in real time, without the removal of tissue specimen. Although endoscopic OCT has been used successfully to identify certain pathologies in the gastrointestinal tract, the resolution of current endoscopic OCT systems has been limited to 10-15 um for clinical procedures. In this study, in vivo imaging of the gastrointestinal tract is demonstrated at a three-fold higher axial resolution (<5 um), using a portable, broadband, Cr4+:Forsterite laser as the optical light source. Images acquired from the esophagus and colon on animal model display tissue microstructures and architectural details at ultrahigh resolution, and the features observed in the OCT images are well-matched with histology. The clinical feasibility study is conducted through delivering OCT imaging catheter using the standard endoscope. OCT images of normal esophagus and Barrett's esophagus are demonstrated with distinct features.
Early detection of gastrointestinal cancer is essential for the patient treatment and medical care. Endoscopically guided biopsy is currently the gold standard for the diagnosis of early esophageal cancer, but can suffer from high false negative rates due to sampling errors. Optical coherence tomography (OCT) is an emerging medical imaging technology which can generate high resolution, cross-sectional images of tissue in situ and in real time, without the removal of tissue specimen. Although endoscopic OCT has been used successfully to identify certain pathologies in the gastrointestinal tract, the resolution of current endoscopic OCT systems has been limited to 10 - 15 m for clinical procedures. In this study, in vivo imaging of the gastrointestinal tract is demonstrated at a three-fold higher resolution (< 5 m), using a portable, broadband, Cr4+:Forsterite laser as the optical light source. Images acquired from the esophagus, gastro-esophageal junction and colon on animal model display tissue microstructures and architectural details at high resolution, and the features observed in the OCT images are well-matched with histology. The clinical feasibility study is conducted through delivering OCT imaging catheter using standard endoscope. OCT images of normal esophagus, Barrett's esophagus, and esophageal cancers are demonstrated with distinct features. The ability of high resolution endoscopic OCT to image tissue morphology at an unprecedented resolution in vivo would facilitate the development of OCT as a potential imaging modality for early detection of neoplastic changes.
Optical coherence tomography (OCT) systems normally operate in regions of the near-IR spectrum in which absorption losses are small compared to scattering losses. We have been exploring the concept of absorption imaging with OCT using a pair of sources that emit on either side of an edge of a strong absorption band of water. In this report a method is introduced for measurement of differential absorption that is based on Fourier transformation of partially coherent interference signals. In experiments designed to test the feasibility of the method, we measured local water concentrations in tissue phantoms and the hydrated epidermis of living skin using a specially configured interferometer illuminated by LEDs that emit in bands centered on 1310 nm and 1460 nm. The results show that absorption losses can be measured in spite of inherent noise form backscattering variations and speckle, but the need for signal averaging places a lower limit on the sampling volume. New inversion algorithms for true tomographic imaging are under development that take advantage of the multiple projections of a scanned conical beam.
The goal of OCT elastography is to quantify microscope strain induced inside a tissue by stress applied externally. Images of internal strain or displacement may provide valuable information about pathological processes such as edema and fibrosis which are known to alter the mechanical properties of tissue.In this sty we developed experimental methods for measuring internal deformation in highly scattering tissue with OCT and applied them to tissue phantoms and living tissue. Piezoelectric actuators were configured to compress the samples in steps of 5-10 micrometers as images were captured synchronously using either a frame or a line-by-line acquisition mode. The displacements of structures inside the samples were quantified using speckle- tracking algorithms based on cross correlation or optical flow of selected features. Displacements as small as a few micrometers were measurable in heterogeneous gelatin phantoms containing scattering particles and living skin. The rules suggest that the composition of tissue layers whose elasticities differ greatly can be deduced visually from image sequences without the need for complicated image processing. However, better models are needed to transform the displacement images into quantitative maps of subtle regional variations of the elastic modulus.
Speckle arises as a natural consequent of the limited spatial-frequency bandwidth of the interference signals measured in optical coherence tomography (OCT). In images of highly scattering biological tissues, speckle has a dual role as a source of noise and as a carrier of information about tissue microstructure. The first half of this paper provides an overview of the origin, statistical properties, and classification of speckle in OCT. The concepts of signal-carrying and signal-degrading speckle are defined in terms of the phase and amplitude disturbances of the sample beam. In the remaining half of the paper, four speckle- reduction methods--polarization diversity, spatial compounding, frequency compounding and digital signal processing--are discussed and the potential effectiveness of each method is analyzed briefly with the aid of examples. Finally, remaining problems that merit further research are suggested.
KEYWORDS: Optical coherence tomography, Speckle, Signal processing, Signal to noise ratio, Backscatter, Signal detection, Sensors, Point spread functions, Destructive interference, Clocks
NIR spectra of biological tissue consist of a number of broad, overlapping absorbance bands on a sloping vaseline. The interpretation and processing of such spectra are complicated by multiple-scattering interactions that distort the shapes of the absorbance bands and introduce wavelength- dependent scattering losses. In this paper we explain the dependence of the shape of the diffuse-reflection log(1/R) spectrum of a turbid medium on the scattering coefficient and probe geometry. From measurements on tissue phantoms and biological tissue, we observe that the separation distance between source and detector probes affects the sensitivity of the reflectance to changes in the density of scattering centers and alters the wavelength dependence of the baseline slope of the log(1/R) spectra. A new method, called fractional derivative processing (FDP), is introduced for extracting information from broad absorption bands corrupted by residual baseline variations and high-frequency noise. FDP was evaluated on spectra obtained from living tissue and tissue phantoms. Possible applications include NIR spectroscopy of hemoglobin, water, and other absorbers in human skin.
KEYWORDS: Optical coherence tomography, Speckle, Backscatter, Point spread functions, Destructive interference, Signal processing, Digital signal processing, Signal detection, Solids, Ultrasonography
OCT images, like those produced by ultrasound scanners, are contaminated with speckles. Speckle in OCT images occurs when light waves reflected by pairs of scatterers spaced by a distance of approximately (k + 1/2) (lambda) , for any integer k, add destructively to give a signal of very small amplitude. Rapid phase changes indicate the locations at which speckle occurs in OCT A-line signals. These changes can be detected by obtaining the unwrapped phase angle of quadrature- demodulated signals or zeros of z-transform of windowed A- lines. This paper discusses a zero-adjustment procedure (ZAP) that is capable of detecting and reducing speckle with the help of the signal phase. The method is evaluated on an analytical model and applied to OCT images of living skin.
Optical coherence tomography (OCT) has shown great promise for non-invasive and contact-less imaging of subsurface soft tissues. However, the problem of low image contrast caused by speckle noise has limited its applications in diagnosis. This paper present a wavelet-based method designed to improve OCT image contrast by reducing speckle noise. After transforming the image into a set of sub-images with different resolution levels in wavelet domain, we threshold high-frequency coefficients nonlinearity in horizontal, vertical, and diagonal directions. The experimental results show that wavelet processing suppresses speckle noise in OCT images of soft tissue effectively, while maintaining the sharpness of image features.
Resolution and contrast of optical coherence tomography (OCT) images are degraded by multiple scattering processes that give a speckled appearance. In this paper we examine the spatial-frequency characteristics of tissue structure and speckle, with the goal of distinguishing speckle form structure for noise reduction by wavelet-based algorithms. Real and simulated images provide the basis for evaluating the performance of the algorithms and the finite-difference time-domain algorithm simulates propagation of the backscattering waves in OCT system.
Knowledge of the size distribution of scatterers in tissue is necessary for understanding the physical processes involved in light-tissue interaction. In this paper we propose and test a model of light scattering in tissue on a microscopic scale. We start from the hypothesis that tissue can be treated as fractal over a certain range of dimensions and proceed to derive a simple scaling law for particle sizes. To test the model, we use a number of sizes of randomly distributed spheres to approximate the fractal structure. Our results show that the fractal model yields credible estimates of the magnitudes of the optical scattering cross sections of tissue, as well as their angle and wavelength dependencies. The numerical data are used to estimate the sizes of the particles that contribute most to the total scattering and backscattering coefficients at a several wavelengths in the visible and near-infrared bands.
Subsurface images of biological tissue obtained by optical coherence tomography (OCT) lack of contrast and are corrupted by coherent noise. In this study we investigated model-based deconvolution methods designed for improving the quality of optical-coherence tomograms of living skin. The methods incorporate a priori information about the point-spread function of the imaging optics, as well as optical properties of the tissue. Deconvolution of the aberrated point-spread function was carried out by using CLEAN, an iterative point reconstruction method. A modification of the standard CLEAN algorithm based on a Wiener filter was made to reduce corrugation artifacts in images of densely packed clusters of scatterers. The algorithms were evaluated first on simulated one-dimensional data arrays and then applied to two- dimensional optical coherence tomograms of skin. Our results suggest that significant improvement in image contrast and resolution can be achieved with the deconvolution algorithm.
This paper examines non-invasive methods for absolute determination of the hemoglobin content of arterial blood and the water content of skin. Both methods are based on diffuse reflectance spectrophotometry in the near-infrared band (800 - 1600 nm). Separation of blood and background tissue spectra is accomplished by a technique similar to pulse oximetry, with the added feature that the set of measurement wavelengths is chosen to be sensitive to both hemoglobin and water concentration in the blood. Regressions performed on a simulated tissue spectra suggest that {1060, 1160, 1200 and 1320 nm} is an optimal set of wavelengths for measurement of tissue hydration and {1040, 1120, 1140 and 1200 nm} is an optimal set of wavelengths for measurement of hemoglobin content under typical measurement conditions. A simple in vitro tissue phantom whose optical properties can be altered in a controlled manner was developed to test the feasibility of the methods. Measurements were made with a custom-designed NIR spectrophotometer.
The aim of this study was to develop quantitative methods for relating the microstructure of a tissue to the magnitude and wavelength dependence of its scattering coefficient. Two methods, cell counting and spatial frequency analysis, were used to estimate the distribution of sizes of structures imaged by light and electron microscopy. We found that scatterers in the epidermal layer of the skin exhibit a log-normal size distribution, whereas the spatial fluctuations in the index of refraction of dense fibrous tissues, such as the dermis, follow a power law. The correlations in the refractive indices of a variety of tissues exhibit characteristics of a random fractal with a Hurst coefficient between 0.3 and 0.5. Calculated from the measured distributions and volume fractions, the magnitudes of the scattering coefficient and anisotropy parameters of the tissue were found to be within the range 10 less than (mu) s less than 35 mm-1 and 0.7 less than g less than 0.97, depending on wavelength and tissue structure. Our results suggest that analysis of histological images of tissues is a viable method for estimating the optical parameters of tissues and their wavelength dependence.
KEYWORDS: Tissues, Speckle, Tissue optics, Scattering, Reflectivity, Signal to noise ratio, Refractive index, Monte Carlo methods, Backscatter, Light scattering
The mechanisms responsible for contrast in reflection mode imaging of turbid tissues at 1300 nm with an optical coherence microscope are addressed. A basic model is motivated and presented in which tissue backscatter is assumed to originate from substantially subwavelength scale refractive index fluctuations, while beam attenuation and decorrelation are attributed to structures larger than a wavelength. The sources of noise in OCM images are considered, particularly speckle, the behavior of which is calculated using the assumed properties of tissue. The speckle behavior is then used to estimate the contrast-detail performance of an OCM. The effects of multiple scattering on resolution and contrast are calculated numerically using a hybrid Monte Carlo/analytical model.
In this paper we compare the performance of confocal and optical- coherence (OC) microscopes designed for imaging structures in a dense biological tissue, like skin, to depths greater than several hundred micrometers. Simple theoretical models, supplemented by Monte-Carlo simulations, are developed for evaluating the optical-sectioning capabilities of the two types of microscopes. The OC microscope is shown to exhibit superior rejection of undesired scattered light when the available angular field of view is restricted. Results of experimental studies with tissue phantoms show a progressive degradation with optical depth in the contrast of objects viewed by a confocal microscope compared to that achieved with the heterodyne technique. We conclude by making a few observations and generalizations regarding the suitability of OC and confocal techniques for potential in-vivo applications.
We describe a new optical low-coherence reflectometer (interferometer) for depth profiling and lateral scanning without moving parts which can also be employed as a stationary FT-IR spectrometer. The reflectometer covers a range of 0.45 mm and 1 mm in the depth and lateral dimensions, respectively. The entire depth range is recorded simultaneously in one scan using a cooled 16-bit CCD camera; the lateral dimension is covered by scanning the probe beam sequentially across the sample with an acousto- optic deflector. The frequency shift generated by this deflector and an additional one placed in the reference arm creates an AC heterodyne signal with a frequency of 2kHz. Since the CCD camera cannot record the AC signal directly, a special readout scheme is employed. Stationary imaging was demonstrated using an artificial phantom. Using the same interferometer configured as a stationary FT-IR spectrometer, we measured the emission spectrum of a LED with a resolution of 0.74 nm at a central wavelength of 820 nm. We discuss the performance of the stationary CCD imaging system and compare it to that of a single-detector system employing moving parts.
In most of the optical methods proposed for imaging an absorbing object embedded in a turbid medium, data is collected using a single source and detector scanned mechanically across the surface of the medium. In this study we exploited destructive interference of diffusive photon- density waves originating from two sources to localize one absorbing (or fluorescent) object in a scattering medium. A frequency-domain instrument is described for scanning several laser- beam spots across the surface of a turbid medium using 1D (or 2D) acousto-optical deflectors and detecting the signals with a gated, intensified CCD camera at a modulation frequency of 246 MHz. The localization of multiple objects arranged in the form of a spatial grating was investigated theoretically with an analytic model by combining the magnitude and phase of the signals detected from the objects. A novel grating pattern comprising several destructively interfering lines, which acts as spatial frequency filter, is discussed. The results were compared with those obtained using a single-source/single-detector scanning configuration. We show that the FWHM (full-width half-maximum) of the signal detected using the single- source/single-detector configuration establishes a limiting spatial scale over which multiple objects can be resolved. Beyond this limit the resolution can only be increased under severe penalty of contrast and signal loss.
Reflectometers based on low-coherence interferometry are potentially useful tools for probing superficial biological structures. In this paper, we present results of theoretical and experimental investigations of the variables that affect the backscattered signals measured by low-coherence reflectometers from dense tissues. Using a single-backscatter model of a turbid biological sample, we examine the effects of the focal spot size and collection angle on the heterodyne efficiency for light backscattered over a range of sampling depths. Coherence losses resulting from multiple scattering are studied using a simple analytical model augmented by numerical simulations. Our results suggest that the single-backscatter model, which has been applied previously in atmospheric lidar and ultrasound studies, provides a good description of the relationship between the shape of the reflectance-vs-depth profiles and the optical properties of a turbid sample under certain conditions. Model predictions were tested by measuring reflectance profiles from dense suspensions of particles using a low-coherence reflectometer built in our laboratory and a commercially available fiber-optic reflectometer. Results of these measurements are compared with others obtained in vivo from human skin. To demonstrate that small structures located at depths of several hundred microns can be probed without contacting a biological specimen, we show an image of bone specimen obtained with the laboratory reflectometer.
Blood hematocrit is routinely determined in the clinic by analysis of blood samples. This paper introduces an non-invasive method for measuring arterial blood hematocrit which, when combined with pulse oximetry, potentially enables simultaneous monitoring of hemoglobin concentration and oxygen saturation. It is based on the same principles underlying pulse oximetry, except two light sources that emit close to isobestic wavelengths of oxy/deoxyhemoglobin in the near-infrared band (800 nm and 1300 nm) are employed. Hematocrjt is related to the ratios of the pulsatile and nonpulsatile components of the diffuse intensity transmitted through a blood-perfused tissue at these wavelengths. To test the feasibility of the method, we developed an in vitro light-scattering model with optical properties similar to those of skin tissue. Measurements were made using semiconductor light sources and detectors. We discuss the experimental results in the context of theoretical predictions that show the effect of variations in the volume fraction of blood and water in tissue. Finally, potential problems concerning calibration in a clinical setting are addressed.
The authors studied the use of destructive interference of two diffusive photon-density waves for localization of an absorbing body and a fluorescent probe embedded in a scattering medium. The effect of the position of the embedded objects on the magnitude and phase of the light re-emitted from the medium was evaluated theoretically and experimentally. The objectives, accomplished with an asymmetrical laser-beam arrangement, were to reduce sensitivity to absorbing bodies located in superficial layers, while maintaining sensitivity to those lying deeper; and to establish a confined region of maximum sensitivity in which the distance of an absorbing body could be determined via phase measurement. Intensity and phase data were acquired with a modified frequency-domain spectrometer at modulation frequencies up to 600 MHz. Fluorescent probes were spatially localized with a symmetrical laser-beam arrangement. Magnitude and phase images acquired with a gated intensified CCD camera further defined the probe location. Simulations and experiments show potential applications to imaging.
To gain insight into the migration of photons in optically dense heterogeneously structured media, scattering models have been developed which consist of polystyrene latex particles suspended in solutions containing varying amounts of absorptive dye. The amount and distribution of the dye affect the mean pathlength of emergent photons, the latter being proportional to < (eta) >, the average number of collisions of photons with moving scatterers. The quantity < (eta) > has been determined by cumulant analysis of the measured time autocorrelation function for photons which are injected and detected with a pair of fiber optodes positioned at the surface of the scattering medium. In agreement with theoretical predictions, < (eta) > is found to vary linearly with the spacing between the optodes if the medium is homogeneous. Moreover, when the scattering medium is composed of layers whose optical absorptions differ, the detected autocorrelation functions indicate that the photons which successfully traverse the medium move along paths which minimize the absorption probability.
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