Showing papers by "Stephen A. Boppart published in 2007"

Interferometric synthetic aperture microscopy

Abstract: State-of-the-art methods in high-resolution three-dimensional optical microscopy require that the focus be scanned through the entire region of interest. However, an analysis of the physics of the light–sample interaction reveals that the Fourier-space coverage is independent of depth. Here we show that, by solving the inverse scattering problem for interference microscopy, computed reconstruction yields volumes with a resolution in all planes that is equivalent to the resolution achieved only at the focal plane for conventional high-resolution microscopy. In short, the entire illuminated volume has spatially invariant resolution, thus eliminating the compromise between resolution and depth of field. We describe and demonstrate a novel computational image-formation technique called interferometric synthetic aperture microscopy (ISAM). ISAM has the potential to broadly impact real-time three-dimensional microscopy and analysis in the fields of cell and tumour biology, as well as in clinical diagnosis where in vivo imaging is preferable to biopsy.

Multimodal biomedical imaging with asymmetric single-walled carbon nanotube/iron oxide nanoparticle complexes.

Abstract: Magnetic iron oxide nanoparticles and near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWNT) form heterostructured complexes that can be utilized as multimodal bioimaging agents. Fe catalyst-grown SWNT were individually dispersed in aqueous solution via encapsulation by oligonucleotides with the sequence d(GT)15, and enriched using a 0.5 T magnetic array. The resulting nanotube complexes show distinct NIR fluorescence, Raman scattering, and visible/NIR absorbance features, corresponding to the various nanotube species. AFM and cryo-TEM images show DNA-encapsulated complexes composed of a approximately 3 nm particle attached to a carbon nanotube on one end. X-ray diffraction (XRD) and superconducting quantum interference device (SQUID) measurements reveal that the nanoparticles are primarily Fe2O3 and superparamagnetic. The Fe2O3 particle-enriched nanotube solution has a magnetic particle content of approximately 35 wt %, a magnetization saturation of approximately 56 emu/g, and a magnetic relaxation time scale ratio (T1/T2) of approximately 12. These complexes have a longer spin-spin relaxation time (T2 approximately 164 ms) than typical ferromagnetic particles due to the smaller size of their magnetic component while still retaining SWNT optical signatures. Macrophage cells that engulf the DNA-wrapped complexes were imaged using magnetic resonance imaging (MRI) and NIR mapping, demonstrating that these multifunctional nanostructures could potentially be useful in multimodal biomedical imaging.

Interferometric synthetic aperture microscopy

Abstract: Interferometric synthetic aperture microscopy provides high-resolution three-dimensional optical images of semitransparent samples with large depth of field without scanning the focal plane. ISAM theory and experiments will be discussed.

Spectroscopic Optical Coherence Tomography and Microscopy

Abstract: Imaging biological tissues using optical coherence tomography is enhanced with spectroscopic analysis, providing new metrics for functional imaging. Recent advances in spectroscopic optical coherence tomography (SOCT) include techniques for the discrimination of endogenous tissue types and for the detection of exogenous contrast agents. In this paper, we review these techniques and their associated signal processing algorithms, while highlighting their potential for biomedical applications. We unify the theoretical framework for time- and frequency-domain SOCT and introduce a noise correction method. Differences between spectroscopic Mie scatterers are demonstrated with SOCT, and spectroscopic imaging of macrophage and fibroblast cells in a 3-D scaffold is shown.

Inverse scattering for frequency-scanned full-field optical coherence tomography

Abstract: Full-field optical coherence tomography (OCT) is able to image an entire en face plane of scatterers simultaneously, but typically the focus is scanned through the volume to acquire three-dimensional structure. By solving the inverse scattering problem for full-field OCT, we show it is possible to computationally reconstruct a three-dimensional volume while the focus is fixed at one plane inside the sample. While a low-numerical-aperture (NA) OCT system can tolerate defocus because the depth of field is large, for high NA it is critical to correct for defocus. By deriving a solution to the inverse scattering problem for full-field OCT, we propose and simulate an algorithm that recovers object structure both inside and outside the depth of field, so that even for high NA the focus can be fixed at a particular plane within the sample without compromising resolution away from the focal plane.

Method and apparatus for measurement of optical properties in tissue

Abstract: A method of analyzing tissue includes inserting a radiation source into tissue, impinging radiation upon the tissue, obtaining a sample signal of the radiation that impinges upon the tissue, and determining a refractive index of the tissue from the sample signal. The method may also include determining at least one other optical property of the tissue. The method may provide for identifying tissue as part of a biopsy method. A device for analyzing tissue may include a low-coherence interferometer and a probe optically coupled to the interferometer, where the probe includes a radiation source.

Nonparaxial vector-field modeling of optical coherence tomography and interferometric synthetic aperture microscopy

Abstract: A large-aperture, electromagnetic model for coherent microscopy is presented and the inverse scattering problem is solved. Approximations to the model are developed for near-focus and far-from-focus operations. These approximations result in an image-reconstruction algorithm consistent with interferometric synthetic aperture microscopy (ISAM): this validates ISAM processing of optical-coherence-tomography and optical-coherence-microscopy data in a vectorial setting. Numerical simulations confirm that diffraction-limited resolution can be achieved outside the focal plane and that depth of focus is limited only by measurement noise and/or detector dynamic range. Furthermore, the model presented is suitable for the quantitative study of polarimetric coherent microscopy systems operating within the first Born approximation.

Needle-based refractive index measurement using low-coherence interferometry

Abstract: We present a novel needle-based device for the measurement of refractive index and scattering using low-coherence interferometry. Coupled to the sample arm of an optical coherence tomography system, the device detects the scattering response of, and optical path length through, a sample residing in a fixed-width channel. We report use of the device to make near-infrared measurements of tissues and materials with known optical properties. The device could be used to exploit the refractive index variations of tissue for medical and biological diagnostics accessible by needle insertion.

Volumetric endoscopic coherence microscopy using a coherent fiber bundle

Abstract: Methods for employing coherent bundles of optical fibers, whether single- or multi-mode, for optical coherence tomography or optical coherence microscopy. Either a substantially monochromatic source or a broadband source is spatially decohered and/or spatially filtered prior to coupling into the fiber bundle for illumination of a sample. A scatter signal from features disposed beneath the surface of the sample is interfered with a reference signal derived, at either end of the fiber bundle, from the identical source of illumination.

Needle-based reflection refractometry of scattering samples using coherence-gated detection

Abstract: We present a novel method for in situ refractive index measurement of scattering samples using a needle device. The device employs a fiber-based reflectance refractometer and coherence-gated detection of the reflected optical signal that eliminates scattering-dependent backreflection contributions. Additionally, birefringence changes induced by fiber movement are neutralized by randomizing the source polarizations and averaging the measured Fresnel reflection coefficients over many incident polarization states. Experimental measurements of Intralipid scattering solutions are presented and compared with Monte Carlo simulations.

Imaging Cellular Responses to Mechanical Stimuli Within Three-Dimensional Tissue Constructs

Abstract: The cellular response to environmental cues is complex, involving both structural and functional changes within the cell. Our understanding of this response is facilitated by micros- copy techniques, but has been limited by our ability to image cell structure and function deep in highly-scattering tissues or 3D constructs. A novel multimodal microscopy technique that combines coherent and incoherent imaging for simultaneous visualization of structural and functional prop- erties of cells and engineered tissues is demonstrated. This microscopic technique allows for the si- multaneous acquisition of optical coherence microscopy and multiphoton microscopy data with par- ticular emphasis for applications in cell biology and tissue engineering. The capability of this tech- nique is shown using representative 3D cell and tissue engineering cultures consisting of primary fibroblasts from transgenic green fluorescent protein (GFP) mice and GFP-vinculin transfected fibroblasts. Imaging is performed following static and dynamic mechanically-stimulating culture conditions. The microscopy technique presented here reveals unique complementary data on the structure and function of cells and their adhesions and interactions with the surrounding microen- vironment. Microsc. Res. Tech. 70:361-371, 2007. V C 2007 Wiley-Liss, Inc.

Autocorrelation artifacts in optical coherence tomography and interferometric synthetic aperture microscopy.

Abstract: Interferometric synthetic aperture microscopy processing of optical coherence tomography data has been shown to allow computational focusing of en face planes that have traditionally been regarded as out of focus. It is shown that this focusing of the image also produces a defocusing effect in autocorrelation artifacts resulting from Fourier-domain data collection. This effect is verified experimentally and through simulation.

Stabilization of continuum generation from normally dispersive nonlinear optical fibers for a tunable broad bandwidth source for optical coherence tomography

Abstract: Continuum generation from normally dispersive ultrahigh-numerical-aperture fibers deteriorates in relatively short times, limiting its application as a practical optical source for high-resolution optical coherence tomography. We find that reversible light-induced structural modification of fiber optic materials, rather than permanent optical damage, is responsible for this deterioration. By examining how the optical properties of corresponding light-induced waveguides depend on pumping wavelength, we isolate a waveguide that is beneficial for stable continuum generation. The performance deterioration due to the formation of other waveguides can be reversed by overwriting them with this particular waveguide.

Real-time optical biopsy and analysis of breast cancer using clinical optical coherence tomography

Abstract: 10508 Background: Advances in high-resolution, real-time, optical imaging have enabled optical coherence tomography (OCT) for non-excisional optical biopsies of breast tissue. OCT is the optical an...

Interferometric Synthetic Aperture Microscopy: Physics-Based Image Reconstruction from Optical Coherence Tomography Data

Abstract: Optical coherence tomography (OCT) is an optical ranging technique analogous to radar - detection of back-scattered light produces a signal that is temporally localized at times-of-flight corresponding to the location of scatterers in the object. However the interferometric collection technique used in OCT allows, in principle, the coherent collection of data, i.e. amplitude and phase information can be extracted. Interferometric synthetic aperture microscopy (ISAM) adds phase-stable data collection to OCT instrumentation and employs physics-based processing analogous to that used in synthetic aperture radar (SAR). That is, the complex nature of the coherent data is exploited to give gains in image quality. Specifically, diffraction-limited resolution is achieved throughout the sample, not just within focal volume of the illuminating field. Simulated and experimental verifications of this effect are presented. ISAM's computational focusing obviates the trade-off between lateral resolution and depth-of-focus seen in traditional OCT.

Nonlinear interferometric vibrational imaging: A method for distinguishing coherent anti-stokes Raman scattering from nonresonant four-wave-mixing processes and retrieving Raman spectra using broadband pulses

Abstract: When utilizing broadband, short pulses to stimulate Coherent Anti-Stokes Raman Scattering (CARS), frequently the peak power is sufficient to excite other nonlinear, nonresonant processes in the material. These processes produce a four-wave-mixing component in the same frequency band as the CARS signal, so that the two signal types cannot be distinguished on the basis of frequency band alone. Typically in biological materials, the nonresonant component produced by the bulk medium can overwhelm the CARS signals produced by the usually much lower concentration target molecular species. Resonant processes can be distinguished from nonresonant processes in that molecular vibrations and rotations typically last longer than a picosecond, while nonresonant processes are not persistent and last shorter than 10 fs. Interferometry allows the arrival time of the signal to be determined to extremely high accuracy, limited by the bandwidth of the reference pulse. Because resonances are persistent, they can produce anti-Stokes radiation that persists after the nonresonant excitation is produced. Interferometry can distinguish the later arrival of the anti-Stokes radiation and therefore distinguish the resonant and nonresonant signals. More complicated pulse-shaping and interferometry schemes can allow additional flexibility to allow simultaneous sampling of the Raman spectrum while rejecting the nonresonant component. This technique enables an entire region of the Raman spectrum of a sample to be measured with a single brief broadband pulse.

microscopie à ouverture synthétique interférométrique

Abstract: La presente invention concerne des procedes et des appareils pour une imagerie tridimensionnelle d'un echantillon. Une source provient d'un faisceau de lumiere sensiblement collimatee caracterisee par un spectre dependant du temps. Le faisceau est concentre dans un plan caracterise par un deplacement fixe le long de l'axe de propagation du faisceau, et la lumiere diffusee en provenance de l'echantillon est superposee a un faisceau de reference derive de ladite source sur une mosaique de detecteurs de plan focal afin de donner un signal d'interference. Un modele de diffusion vers l'avant est derive mettant en relation les donnees mesurees avec la structure d'un objet pour permettre la resolution d'un probleme de diffusion inverse sur la base du signal d'interference de sorte qu'une structure tridimensionnelle de l'echantillon peut etre inferee presque en temps reel.

Intraoperative Needle-based Refractive Index Measurement of Ex Vivo Human Breast Tissue

Abstract: Refractive index measurements offer high contrast between normal fatty tissue and diagnostically significant structures. We have developed a needle-based device capable of measuring internal tissue properties. We present preliminary clinical data from human specimens.

Polarimetric interferometric synthetic aperture microscopy: Vectorial computed imaging from optical coherence tomography data

Abstract: Interferometric Synthetic Aperture Microscopy (ISAM) obviates the trade-off between depth-of-focus and resolution in interferometric coherence imaging. In this work, ISAM's quantitative image reconstruction techniques are applied in a vectorial setting, thus admitting polarization-sensitive imaging.

Intraoperative Optical Biopsy of Breast Cancer

Abstract: Optical coherence tomography (OCT) of breast tissue yields high-resolution optical biopsies that can be used to identify cancerous regions. We present intraoperative OCT studies of surgical margin scanning and biopsy needle guidance.