Showing papers by "Brett E. Bouma published in 2006"

Comprehensive volumetric optical microscopy in vivo.

Abstract: Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

Method and apparatus for optical imaging via spectral encoding

Abstract: Exemplary method, apparatus and arrangement can be provided for obtaining information associated with a sample such as a portion of an anatomical structure. The information can be generated using first data, which can be based on a signal obtained from a location on the sample, and second data, where the second data can be obtained by combining a second signal received from the sample with a third reference signal. An image of a portion of the sample can also be generated based on the information. For example, the first data can be associated with spectral encoding microscopy data, and the second data can be associated with optical coherence tomography data.

Optical coherence tomography for imaging the vulnerable plaque

Abstract: While our understanding of vulnerable coronary plaque is still at an early stage, the concept that certain types of plaques predispose patients to developing an acute myocardial infarction continues to be at the forefront of cardiology research. Intracoronary optical coherence tomography (OCT) has been developed to both identify and study these lesions due to its distinct resolution advantage over other imaging modalities. We review clinical research conducted at the Massachusetts General Hospital over the past five years to develop, validate, and utilize this technology to improve our understanding of vulnerable plaque. Our results show that intracoronary OCT may be safely conducted in patients and that it provides abundant information regarding plaque microscopic morphology, which is essential to the identification and study of high-risk lesions. Even though many basic biological, clinical, and technological challenges must be addressed prior to widespread use of this technology, the unique capabilities of OCT ensure that it will have a prominent role in shaping the future of cardiology.

Speckle reduction in OCT using massively-parallel detection and frequency-domain ranging

Abstract: Speckle noise significantly limits the information content provided by coherent optical imaging methods such as optical coherence tomography and its recent derivative, optical frequency-domain imaging (OFDI). In this paper, we demonstrate a novel OFDI system that simultaneously acquires hundreds of angularly resolved images, which can be compounded to reduce speckle noise. The system comprises an InGaAs line-scan camera and an interferometer, configured so that the elements of the detector array simultaneously capture light spanning a backscattering angular range of 32 degrees. On successive read-outs of the array, the wavelength of the laser source was stepped through a range of 130 nm centered at 1295 nm to concurrently generate 400 angle-resolved OFDI images. A theory of angle-resolved OFDI and the design equations of the system are presented. Incoherent averaging of the angle-resolved data is shown to yield substantial speckle reduction (as high as an 8 dB SNR improvement) in images of a tissue phantom and esophageal tissue ex vivo.

Three-dimensional miniature endoscopy.

Abstract: A single optical fibre acts as a flexible probe to transmit a superior image of an internal landscape.

Arrangements and methods for providing multimodality microscopic imaging of one or more biological structures

Abstract: Method and apparatus according to an exemplary embodiment of the present invention can be provided. For example, first data associated with a first signal received from at least one region of at least one sample can be provided based on a first modality, and second data associated with a second signal received from the at least one sample can be provided based on a second modality which is different from the first modality. Third data associated with a reference can be received. Further data can be generated based on the first, second and third data. In addition, third data associated with a second signal received from the at least one sample can be obtained. Each of the third data can be based on a further modality which is different from the first modality and the second modality, and the further data can be further determined based on the third data. Further, the first modality can be a spectral-encoded modality, and the second modality can be a non-spectral-encoding modality.

Ultrahigh-speed optical frequency domain imaging and application to laser ablation monitoring

Abstract: We demonstrate a linear laser resonator incorporating a semiconductor optical amplifier and scanning filter for high repetition rate, broad wavelength, unidirectional scanning. The laser operates at up to 115kHz repetition rates and demonstrates a tuning-speed-independent power of >30mW. We apply this laser to enable ultrahigh-speed optical frequency domain imaging of the dynamics of laser ablation of biological tissue. The imaging system acquires single longitudinal scans (A-lines) in 8.7μs and complete cross-sectional images comprising 575A-lines at a rate of 200 frames per second.

Elimination of depth degeneracy in optical frequency-domain imaging through polarization-based optical demodulation

Abstract: A novel optical frequency-domain imaging system is demonstrated that employs a passive optical demodulation circuit and a chirped digital acquisition clock derived from a voltage-controlled oscillator. The demodulation circuit allows the separation of signals from positive and negative depths to better than 50 dB, thereby eliminating depth degeneracy and doubling the imaging depth range. Our system design is compatible with dual-balanced and polarization-diverse detection, important techniques in the practical biomedical application of optical frequency-domain imaging.

Technology Insight: optical coherence tomography—current status and future development

Abstract: The understanding of concepts in coronary artery disease, such as the vulnerable or high-risk plaque, which accounts for many acute coronary events arising from non-flow-limiting coronary lesions, has advanced remarkably. Although coronary angiography is an established imaging technique for visualizing atherosclerotic disease, it is limited by its two-dimensional imaging aspect and a low sensitivity for identifying lesions in the presence of positive remodeling and diffuse disease. Moreover, coronary atherosclerotic plaques cannot be characterized. Although intravascular ultrasound is currently the most commonly employed adjunctive method to better define lesions, it is limited by low resolution. The development of new technologies for improved coronary plaque characterization has, thus, been desired. Optical coherence tomography is a developing technique that uses near-infrared light for the cross-sectional visualization of the vessel wall at the microscopic level. It enables excellent resolution of coronary architecture and precise characterization of plaque architecture. Quantification of macrophages within the plaque is also possible. These capabilities allow precise identification of the most common type of vulnerable plaque, the thin-cap fibroatheroma. Here, we discuss results from clinical studies which indicate that optical coherence tomography is a promising imaging technique for improved characterization of the coronary atherosclerotic plaque.

Apparatus, method and system for performing phase-resolved optical frequency domain imaging

Abstract: Apparatus, system and method are provided which utilize signals received from a reference and a sample. In particular, a radiation is provided which includes at least one first electro-magnetic radiation directed to the sample and at least one second electro-magnetic radiation directed to the reference. A frequency of the radiation varies over time. An interference can be detected between at least one third radiation associated with the first radiation and at least one fourth radiation associated with the second radiation. It is possible to obtain a particular signal associated with at least one phase of at least one frequency component of the interference, and compare the particular signal to at least one particular information. Further, it is possible to receive at least one portion of the radiation and provide a further radiation, such that the particular signal can be calibrated based on the further signal.

Measurement of fibrous cap thickness in atherosclerotic plaques by spatiotemporal analysis of laser speckle images.

Abstract: Necrotic-core fibroatheromas (NCFA) with thin, mechanically weak fibrous caps overlying lipid cores comprise the majority of plaques that rupture and cause acute myocardial infarction. Laser speckle imaging (LSI) has been recently demonstrated to enable atherosclerotic plaque characterization with high accuracy. We investigate spatio-temporal analysis of LSI data, in conjunction with diffusion theory and Monte Carlo modeling of light transport, to estimate fibrous cap thickness in NCFAs. Time-varying laser speckle images of 20 NCFAs are selected for analysis. Spatio-temporal intensity fluctuations are analyzed by exponential fitting of the windowed normalized cross-correlation of sequential laser speckle patterns to obtain the speckle decorrelation time constant, tau(rho), as a function of distance rho from the source entry location. The distance, rho', at which tau(rho) dropped to 65% of its maximum value is recorded. Diffusion theory and Monte Carlo models are utilized to estimate the maximum photon penetration depth, zmax(rho'), for a distance equal to rho', measured from LSI. Measurements of zmax(rho') correlate well with histological measurements of fibrous cap thickness (R=0.78, p<0.0001), and paired t-tests show no significant difference between the groups (p=0.4). These results demonstrate that spatio-temporal LSI may allow the estimation of fibrous cap thickness in NCFAs, which is an important predictor of plaque stability.

Ultrahigh-resolution full-field optical coherence microscopy using InGaAs camera

Abstract: Full-field optical coherence microscopy (FFOCM) is an interferometric technique for obtaining wide-field microscopic images deep within scattering biological samples. FFOCM has primarily been implemented in the 0.8 μm wavelength range with silicon-based cameras, which may limit penetration when imaging human tissue. In this paper, we demonstrate FFOCM at the wavelength range of 0.9 - 1.4 μm, where optical penetration into tissue is presumably greater owing to decreased scattering. Our FFOCM system, comprising a broadband spatially incoherent light source, a Linnik interferometer, and an InGaAs area scan camera, provided a detection sensitivity of 86 dB for a 2 sec imaging time and an axial resolution of 1.9 μm in water. Images of phantoms, tissue samples, and Xenopus Laevis embryos were obtained using InGaAs and silicon camera FFOCM systems, demonstrating enhanced imaging penetration at longer wavelengths.

Spectrally-modulated full-field optical coherence microscopy for ultrahigh-resolution endoscopic imaging.

Abstract: Full-field optical coherence microscopy (FFOCM) utilizes coherence gating to obtain high-resolution optical sections in thick tissues. FFOCM is an attractive technology for endoscopic microscopy at the cellular level since it does not require a high NA objective lens or beam scanning and is therefore particularly amenable to miniaturization. In this manuscript, we present a novel scheme for conducting FFOCM that utilizes spectrally modulated, spatially incoherent illumination and a static Linnik interferometer. This approach is advantageous for endoscopic microscopy since it allows FFOCM to be conducted through a single multimode fiber optic imaging bundle and does not require moving parts in the endoscope probe. Images acquired from biological samples in free space demonstrate that this new method provides the same detailed microscopic structure as that of conventional FFOCM. High-resolution images were also obtained through a multimode fiber bundle, further supporting the potential of this method for endoscopic microscopy.

Arrangements and methods for facilitating photoluminescence imaging

Abstract: Exemplary systems and methods for obtaining a photoluminescence radiation from at least one portion of a sample can be provided. For example, using the exemplary embodiment, it is possible to receive a first radiation and disperse the first radiation into at least one second radiation and at least one third radiation. The second and third radiations can be provided to different locations of the portion. In addition, it is possible to receive the photoluminescence radiation from the portion based on the second and third radiations.

Numerical study of wavelength-swept semiconductor ring lasers: the role of refractive-index nonlinearities in semiconductor optical amplifiers and implications for biomedical imaging applications.

Abstract: Recent results have demonstrated unprecedented wavelength-tuning speed and repetition rate performance of semiconductor ring lasers incorporating scanning filters However, several unique operational characteristics of these lasers have not been adequately explained, and the lack of an accurate model has hindered optimization We numerically investigated the characteristics of these sources, using a semiconductor optical amplifier (SOA) traveling-wave Langevin model, and found good agreement with experimental measurements In particular, we explored the role of the SOA refractive-index nonlinearities in determining the intracavity frequency-shift-broadening and the emitted power dependence on scan speed and direction Our model predicts both continuous-wave and pulse operation and shows a universal relationship between the output power of lasers that have different cavity lengths and the filter peak frequency shift per round trip, therefore revealing the advantage of short cavities for high-speed biomedical imaging

Arterial wall imaging: evaluation with 16-section multidetector CT in blood vessel phantoms and ex vivo coronary arteries.

Abstract: Purpose: To evaluate the diagnostic performance of 16-section multidetector computed tomography (CT) for assessment of plaques in phantoms and ex vivo coronary arteries, with intravascular ultrasonography (US) and optical coherence tomography (OCT) as reference standards. Materials and Methods: Research protocol was HIPAA compliant and approved by institutional review board, without informed consent required. Blood vessel and lesion composition phantoms and ex vivo coronary arteries were imaged with 16-section CT. Wall areas of phantoms and ex vivo coronary arteries were measured with multidetector CT and intravascular US. Sensitivity and specificity for lipid detection were determined in lesion composition phantoms. CT numbers of blood vessel wall were determined in ex vivo coronary arteries and compared with lesion classification results from OCT. Agreement in dimensional measurements was compared (paired t tests). CT numbers within blood vessel wall of CT cross sections classified as lipid rich, fibrou...

A combined FEM/genetic algorithm for vascular soft tissue elasticity estimation

Abstract: Tissue elasticity reconstruction is a parameter estimation effort combining imaging, elastography, and computational modeling to build maps of soft tissue mechanical properties One application is in the characterization of atherosclerotic plaques in diseased arteries, wherein the distribution of elastic properties is required for stress analysis and plaque stability assessment In this paper, a computational scheme is proposed for elasticity reconstruction in soft tissues, combining finite element modeling (FEM) for mechanical analysis of soft tissues and a genetic algorithm (GA) for parameter estimation With a model reduction of the discrete elasticity values into lumped material regions, namely the plaque constituents, a robust, adaptive strategy can be used to solve inverse elasticity problems involving complex and inhomogeneous solution spaces An advantage of utilizing a GA is its insistence on global convergence The algorithm is easily implemented and adaptable to more complex material models and geometries It is meant to provide either accurate initial guesses of low-resolution elasticity values in a multi-resolution scheme or as a replacement for failing traditional elasticity estimation efforts

Spectral- and frequency- encoded fluorescence imaging

Abstract: A system and method for obtaining fluorescence images from a sample are provided. Broadband excitation light (302) is encoded with a wavelength-dependent frequency modulation and dispersed onto a sample (314), e.g. with a grating (316a), to simultaneously illuminate an entire image line. The frequency-encoded fluorescence emission is measured to provide one line of the image. Mechanical scanning along a direction orthogonal to the wavelength-encoded axis allows creation of a two-dimensional fluorescence image. The system and method is especially useful for obtaining fluorescence images via endoscopes, catheters, or small-diameter probes.

Systems, processes and software arrangements for evaluating information associated with an anatomical structure by an optical coherence ranging technique

Abstract: Software systems, arrangements and processes for evaluating an image associated with at least one portion of an anatomical structure are provided. For example, first information associated with the at least one portion of the anatomical structure second information associated with the at least one portion of the anatomical structure can be received. Third information can be generated by determining a relationship between the first information and the second information. Further, the image can be evaluated using a predetermined pathological scoring criteria and the third information.

Ultra-high speed and ultra-high resolution spectral-domain optical coherence tomography and optical Doppler tomography in ophthalmology.

Abstract: We present ultra-high resolution optical coherence tomography (OCT) structural intensity and optical Doppler tomography (ODT) flow velocity images of the human retina in vivo. The ultra-high speed OCT system is based on Spectral Domain or Fourier Domain technology, which provides a sensitivity advantage over conventional OCT of more than 2 orders of magnitude. This sensitivity improvement allows video rate OCT and ODT cross sectional imaging of retinal structures. Images will be presented with axial resolutions of 6 and 3.5 microns. We observed small features in the inner and outer plexiform layers, which are believed to be small blood vessels. Flow velocity images will be presented showing pulsatile flow in retinal arteries and veins.

Fluorescence coherence tomography.

Abstract: In this paper, we introduce a new form of cross-sectional, coherence-gated fluorescence imaging, which we term 'spectral-domain fluorescence coherence tomography' (SD-FCT). SD-FCT is accomplished by spectrally detecting self-interference of the spontaneous emission of fluorophores located along the axial (depth) dimension of the sample. We have built a first generation SD-FCT system that utilizes two opposing low numerical-aperture objective lenses in an interferometer and an imaging spectrometer for detecting self-interference of fluorescence emitted from a sample. Here, in proof-of-principle experiments we demonstrate cross-sectional profiling of layered fluorescence phantoms. Narrow (a few micrometers FWHM) axial point-spread functions, large ranging depths (a few hundreds of micrometers) and wide fields of view (>1 mm) were measured. Initial results suggest that SD-FCT may be a viable tool for the investigation of semi-transparent and selectively labeled fluorescent samples.

Differential near-field scanning optical microscopy.

Abstract: We theoretically and experimentally illustrate a new apertured near-field scanning optical microscopy (NSOM) technique, termed differential NSOM (DNSOM). It involves scanning a relatively large (e.g., 0.3-2 mum wide) rectangular aperture (or a detector) in the near-field of an object and recording detected power as a function of the scanning position. The image reconstruction is achieved by taking a two-dimensional derivative of the recorded power map. Unlike conventional apertured NSOM, the size of the rectangular aperture/detector does not determine the resolution in DNSOM; instead, the resolution is practically determined by the sharpness of the corners of the rectangular aperture/detector. Principles of DNSOM can also be extended to other aperture/detector geometries such as triangles and parallelograms.

Methods and Systems for Tissue Analysis

Abstract: The invention relates to methods and systems to optically analyze samples such as tissue based on speckle patterns of microscopic motion, such as Brownian motion.

A novel framework for elastography and modulus estimation: integration of tissue mechanics with imaging

Abstract: The feasibility of optical coherence elastography is examined and the steps necessary for registration of optical coherence tomography (OCT) images are developed. We address the drawbacks of conventional techniques for solving the "image registration problem and inverse elasticity problem (IEP)" and then propose a new scheme for simultaneous solution of both problems. We have previously exploited the kinematics of incompressible tissue as a side-constraint term in OCT registration, and we now assess how the integration of FEM-derived mechanics directly within the registration process, improves the overall quality. The new technique estimates fewer unknowns and still it generates more realistic strain/modulus maps with less sensitivity to local minima. It is composed of a series of computationally-efficient and robust algorithms to create elastograms and elastic modulus maps and it does not need to utilize a multi resolution grid. Finally, we apply our scheme to a porcine aorta and demonstrate its ability in recovering lipid pools both in the strain map and in the elastic modulus image.

Endoscopic polarization-sensitive optical coherence tomography

Abstract: Development of endoscope-compatible fiber-optic probes and polarization-sensitive detection schemes have each independently expanded the utility of optical coherence tomography. Several application areas have emerged which require polarization-sensitive measurements to be combined with endoscopic imaging techniques, in order to proceed to in vivo studies. Endoscopic-OCT typically requires a section of the sample arm fiber to be scanned during image acquisition, which produces a dynamically changing polarization state of light incident on the sample. Here, we demonstrate the effects of linear-scanning, and rotary-scanning probes in the sample arm of a PS-OCT system, and demonstrate the necessary modifications to be made for successful endoscopic PS-OCT imaging.

Mirror tunnel microscope

Abstract: A microscope paradigm, which the authors term the “mirror tunnel microscope” (MTM), is described. The MTM uses a low numerical aperture (NA) lens together with parallel mirrors positioned between the lens plane and the object plane to provide a relatively simple means for digital wide-field microscopy. In MTM, the mirror tunnel acts as a spatial periodic-bandpass filter, which creates low-resolution, bandpassed versions of the object function in the image plane. However, each low-resolution image formed by the MTM carries a unique band of spatial frequencies. Coherent addition of the phase and amplitude of the spatial frequency information contained in each of these low-resolution images enhances the effective NA of the lens without decreasing field of view. To demonstrate the proof of principle, they have utilized a two-mirror MTM to reconstruct an image of a pinhole. Along the axis perpendicular to the mirrors, the image was reconstructed with higher resolution, commensurate with an effective fivefold NA increase. Initial results indicate that MTM is a promising method for wide-field digital microscopy.

Evaluating optical coherence tomography information for an anatomical structure

Abstract: Software systems, arrangements and processes for evaluating an image associated with at least one portion of an anatomical structure are provided. For example, first information associated with the at least one portion of the anatomical structure second information associated with the least one portion of the anatomical structure can be received. Third information can be generated by determining a relationship between the first information and the second information. Further, the image can be evaluated using a predetermined pathological scoring criteria and the third information.