Toward nanometer-scale resolution in fluorescence microscopy using spectral self-interference A. K. Swan, L. A. Moiseev, C. R. Cantor, B. J. Davis, S. B. Ippolito, W. C. Karl, B. B. Goldberg, and M. S. Ünlü IEEE Journal of Selected Topics in Quantum Electronics,
Vol. 9,
pp. 294-300
(2003)
PDF
We introduce a new fluorescence microscopy technique that maps the axial position of a fluorophore with subnanometer precision. The interference of the emission of fluorophores in proximity to a reflecting surface results in fringes in the fluorescence spectrum that provide a unique signature of the axial position of the fluorophore. The nanometer sensitivity is demonstrated by measuring the height of a fluorescein monolayer covering a 12-nm step etched in silicon dioxide. In addition, the separation between fluorophores attached to the top or the bottom layer in a lipid bilayer film is determined. We further discuss extension of this microscopy technique to provide resolution of multiple layers spaced as closely as 10 nm for sparse systems.
Stochastic modeling and generation of partially polarized or partially coherent electromagnetic waves B. J. Davis, E. Kim, and J. R. Piepmeier Radio Science,
Vol. 39,
RS1001
(2004)
PDF
Many new Earth remote-sensing instruments are embracing both the advantages and
added complexity that result from interferometric or fully polarimetric operation. To
increase instrument understanding and functionality, a model of the signals these
instruments measure is presented. A stochastic model is used as it recognizes the
nondeterministic nature of any real-world measurements, while also providing a tractable
mathematical framework. A wide-sense stationary, ergodic, Gaussian-distributed model
structure is proposed. Temporal and spectral correlation measures provide a statistical
description of the physical properties of coherence and polarization-state. From this
relationship, the model is mathematically defined. A method of realizing the model (necessary for applications such as synthetic calibration-signal generation) is given, and computer simulation results are presented. The signals are constructed using the output of a multi-input, multi-output linear filter system, driven with white noise.
The relationship of transform coefficients for differing transforms and/or differing subblock sizes B. J. Davis and S. H. Nawab IEEE Transactions on Signal Processing,
Vol. 52,
pp. 1458-1461
(2004)
PDF
Jiang and Feng have developed a relationship between the discrete cosine transform (DCT) coefficients of a block and those of its sub-blocks. Their derivation of this result can be significantly simplified. The new derivation also generalizes to all linear, invertible transforms and any separable subblock geometry.
Capabilities and limitations of pupil-plane filters for superresolution and image enhancement B. J. Davis, W. C. Karl, A. K. Swan, M. S. Ünlü, and B. B. Goldberg Optics Express,
Vol. 12,
pp. 4150-4156
(2004)
PDF
The use of pupil-plane filters in microscopes has been proposed as a method of producing superresolution. Here it is shown that pupil-plane filters cannot increase the support of the transfer function for a large class of optical systems, implying that resolution cannot be improved solely by adding pupil-plane filters to an instrument. However, pupil filters can improve signal-to-noise performance and modify transfer-function zero crossing positions, as demonstrated through a confocal fluorescence example.
Simulation of vector fields with arbitrary second-order correlations B. J. Davis Optics Express,
Vol. 15,
pp. 2837-2846
(2007)
PDFGS.aviRad.avi
Temporally-stationary electromagnetic fields with arbitrary second-order coherence functions are simulated using standard statistical tools. In cases where the coherence function takes a commonly-used separable form, a computationally-efficient variation of the approach can be applied. This work provides a generalization of previous spatio-temporal simulators which model only scalar fields and require either restrictions on the coherence function or consider only two points in space. The simulation of a partially-polarized Gaussian Schell-model beam and a partially-radially-polarized beam are demonstrated.
Autocorrelation artifacts in optical coherence tomography and interferometric synthetic aperture microscopy B. J. Davis, T. S. Ralston, D. L. Marks, S. A. Boppart, and P. S. Carney Optics Letters,
Vol. 32,
pp. 1441-1443
(2007)
PDF
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.
Nonparaxial vector-field modeling of optical coherence tomography and interferometric synthetic aperture microscopy B. J. Davis, S. C. Schlachter, D. L. Marks, T. S. Ralston, S. A. Boppart, and P. S. Carney Journal of the Optical Society of America A,
Vol. 24,
pp. 2527-2542
(2007)
PDF
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.
Observable coherence theory for statistically periodic fields B. J. Davis Physical Review A,
Vol. 76,
043843
(2007)
PDF
The framework of cyclostationary random processes is used to develop classical coherence theory for the measurement of statistically periodic stochastic optical fields, such as those produced by pulsed lasers. Cycloergodicity is invoked to show that precise and accurate inferences of the nonstationary process statistics can be made from a single field realization. In particular, many-pulse observations using nonlinear and/or nonstationary techniques, such as spectral shearing interferometry, can be used to fully characterize the standard two-time correlation function of a statistically periodic source. The theory is demonstrated through the simulation of spectral shearing interferometry and frequency-resolved optical gating measurements.
Spectral self-interference microscopy for low-signal nanoscale axial imaging B. J. Davis, A. K. Swan, M. S. Ünlü, W. C. Karl, B. B. Goldberg, J. C. Schotland, and P. S. Carney Journal of the Optical Society of America A,
Vol. 24,
pp. 3587-3599
(2007)
PDF
A theoretical and numerical analysis of spectral self-interference microscopy (SSM) is presented with the goal of expanding the realm of SSM applications. In particular, this work is intended to enable SSM imaging in low-signal applications such as single-molecule studies. A comprehensive electromagnetic model for SSM is presented, allowing arbitrary forms of the excitationf ield, detection optics, and tensor sample response. An evanescently excited SSM system, analogous to total internal reflection microscopy, is proposed and investigated through Monte Carlo simulations. Nanometer-scale axial localization for single-emitter objects is demonstrated, even in low-signal environments. The capabilities of SSM in imaging more general objects are also considered-specifically, imaging arbitrary fluorophore distributions and two-emitter objects. A data-processing method is presented that makes SSM robust to noise and uncertainties in the detected spectral envelope.
4Pi spectral self-interference microscopy B. J. Davis, M. Dogan, B. B. Goldberg, W. C. Karl, M. S. Ünlü, and A. K. Swan Journal of the Optical Society of America A,
Vol. 24,
pp. 3762-3771
(2007)
PDF
Spectral self-interference microscopy (SSM) relies on the balanced collection of light traveling two different paths from the sample to the detector, one direct and the other indirect from a reflecting substrate. The resulting spectral interference effects allow nanometer-scale axial localization of isolated emitters. To produce spectral fringes the difference between the two optical paths must be significant. Consequently, to ensure that both contributions are in focus, a low-numerical-aperture objective lens must be used, giving poor lateral resolution. Here this limitation is overcome using a 4Pi apparatus to produce the requisite two paths to the detector. The resulting instrument generalizes both SSM and 4Pi microscopy and allows a quantification of SSM resolution (rather than localization precision). Specifically, SSM is shown to be subject to the same resolution constraints as 4Pi microscopy.
Interferometric synthetic aperture microscopy: computed imaging for scanned coherent microscopy (invited review) B. J. Davis, D. L. Marks, T. S. Ralston, P. S. Carney, and S. A. Boppart Sensors,
Vol. 8,
pp. 3903-3931
(2008)
PDF
Three-dimensional image formation in microscopy is greatly enhanced by the use of computed imaging techniques. In particular, Interferometric Synthetic Aperture Microscopy (ISAM) allows the removal of out-of-focus blur in broadband, coherent microscopy. Earlier methods, such as optical coherence tomography (OCT), utilize interferometric ranging, but do not apply computed imaging methods and therefore must scan the focal depth to acquire extended volumetric images. ISAM removes the need to scan the focus by allowing volumetric image reconstruction from data collected at a single focal depth. ISAM signal processing techniques are similar to the Fourier migration methods of seismology and the Fourier reconstruction methods of Synthetic Aperture Radar (SAR). In this article ISAM is described and the close ties between ISAM and SAR are explored. ISAM and a simple strip-map SAR system are placed in a common mathematical framework and compared to OCT and radar respectively. This article is intended to serve as a review of ISAM, and will be especially useful to readers with a background in SAR.
Optical interferometry with pulsed fields R. W. Schoonover, B. J. Davis, R. A. Bartels, and P. S. Carney Journal of Modern Optics,
Vol. 55,
pp. 1541-1556
(2008)
PDF Fig9.mov Fig10.mov Fig11.mov
The problem of predicting and interpreting the results of interferometric optical experiments involving pulse trains is addressed. Specifically, a cyclostationary field arising from the modulation of a stationary, stochastic source is considered in the classical Young's experiment. It is shown that the effects of modulation may be identical to unrelated statistical interference effects.
Robust determination of the anisotropic polarizability of nanoparticles using coherent confocal microscopy B. J. Davis and P. S. Carney Journal of the Optical Society of America A,
Vol. 25,
pp. 2102-2113
(2008)
PDF
A coherent confocal microscope is proposed as a means to fully characterize the elastic scattering properties of a nanoparticle as a function of wavelength. Using a high numerical aperture lens, two-dimensional scanning, and a simple vector-beam shaper, the rank-2 polarizability tensor is estimated from a single confocal image. A method for computationally efficient data processing is described, and numerical simulations show that this algorithm is robust to noise and uncertainty in the focal plane position. The proposed method is a generalization of techniques that provide an estimate of a limited set of scattering parameters, such as a single orientation angle for rodlike particles. The measurement of the polarizability obviates the need for a priori assumptions about the nanoparticle.
Partially coherent illumination in full-field interferometric synthetic aperture microscopy D. L. Marks, B. J. Davis, S. A. Boppart, and P. S. Carney Journal of the Optical Society of America A,
Vol. 26,
pp. 376-386
(2009)
PDF
A model is developed for optical coherence tomography (OCT) and interferometric synthetic aperture microscopy (ISAM) systems employing full-field, frequency-scanned illumination with partial spatial coherence. This model is used to derive efficient ISAM inverse scattering algorithms that give diffraction-limited resolution in regions typically regarded as out of focus. Partial spatial coherence of the source is shown to have the advantage of mitigating multiple-scattering effects that can otherwise produce significant artifacts in full-field coherent imaging.
The generalized Wolf shift for cyclostationary fields R. W. Schoonover, B. J. Davis, and P. S. Carney Optics Express,
Vol. 17,
pp. 4705-4711
(2009)
PDF
Correlation dependent, propagation-induced shifts in the generalized spectra of cyclostationary, random fields are predicted. This result generalizes the Wolf shift for stationary fields and is applicable to periodic trains of fast pulses such as might be generated in comb spectroscopy or other mode-locked pulsed systems. Examples illustrate these shifts for intrinsically stationary fields and the fields generated by a mode-locked laser.
Computationally efficient coherent mode representations B. J. Davis and R. W. Schoonover Optics Letters,
Vol. 34,
pp. 923-925
(2009)
PDF
The numerical calculation of traditional coherent mode representations involves an eigenvalue decomposition of the cross-spectral density matrix. An efficient alternative modal representation of a partially coherent field can be realized using an LDL decomposition. Storage requirements are reduced by an amount on the order of the ratio between the coherence length and the source width. The efficiency of calculations requiring a coherent mode representation (e.g., numerical evaluation of partially coherent propagation effects) may thus be significantly improved, particularly when low-coherence fields are considered.
Modeling surface multipath effects in synthetic aperture sonar B. J. Davis, P. T. Gough, and B. R. Hunt IEEE Journal of Oceanic Engineering,
Vol. 34,
pp. 239-249
(2009)
PDF
Synthetic Aperture Sonar (SAS) imaging algorithms assume a specific ping-to-ping phase relation in the collected data. The line-of-sight signal from a non-moving object adds coherently from ping to ping in the image reconstruction process while any random multipath reflections or backscatter from the sea surface may add non-coherently, thus improving the image signal-to-clutter ratio (SCR). To move towards understanding just how effective a SAS is at suppressing surface multipath contributions, it is necessary to model the moving surface in a believable way and establish how the sound reflects from the undersurface of the sea. This work presents a method for simulating the effects of multipath propagation on sonar data and hence evaluating the SCR improvement realized with synthetic-aperture processing.
This paper first reviews the Pierson-Moskowitz and cos-2s surface-wave spectra, which together account for wind direction, wind speed and angular spread of the wave propagation direction. From these spectra a statistically appropriate random wave surface is generated which evolves in both time and space. In a first attempt to model the sea-surface multipath problem, a set of impulse responses are generated from this wave-surface as it evolves in time increments equal to the pulse repetition period. Two sea-surface scattering mechanisms are used in the simulations described in this paper. In the first, each surface facet reflects as a diffraction-limited radiating aperture and in the second, each facet reflects as an incoherent Lambertian scatterer. These describe two limiting situations: first, the acoustic wavelength is small compared with the roughness of the sea surface; and second, the acoustic wavelength is significant in proportion to the surface roughness. The effect of surface multipath is shown on raw data and also on processed SAS images. The calculation of the SCR as a function of sea state is also demonstrated. The SCR improvement seen with SAS imaging is consistent with the hypothesis that surface multipath signals are fully incoherent from ping to ping.
Propagation of spatial coherence in fast pulses R. W. Schoonover, B. J. Davis, R. A. Bartels, and P. S. Carney Journal of the Optical Society of America A,
Vol. 26,
pp. 1945-1953
(2009)
PDF
Diffraction and interferometry with fast pulses are analyzed for the case that the fields are partially correlated in time and in space. This generalizes a previous work [Schoonover et al., J. Mod. Opt. 55, 1541 (2008)], where only the temporal correlations of pulsed fields were considered in a Young's interferometer. The meaning of the interferograms is addressed for measurements taken in the near, Fresnel, and far zones of the source. It is shown that single-shot measurements cannot generally be used to infer statistical properties of the source, rather, data averaged over many pulses must be used.
Conference Proceedings
Stochastic modeling of correlation radiometer signals B. J. Davis, E. Kim, and J. R. Piepmeier IEEE Antennas and Propagation Society International Symposium
(2001)
PDF
Many new Earth remote-sensing instruments are embracing both the advantages and added complexity that result from interferometric or fully polarimetric operation. To improve our understanding of calibration options for such instruments, a model of the signals that they measure is presented. A stochastic model is used as it recognizes the non-deterministic nature of any real world measurements while also providing a tractable mathematical framework. A stationary, Gaussian-distributed model structure is proposed. Spectral correlation measures are used to provide a statistical description of the model. A method of realizing the model (necessary for applications such as synthetic calibration-signal generation) is given, and computer simulation results are presented. The signals are constructed using the output of a multi-input, multi-output linear filter system, driven with white noise.
Sea surface simulator for testing a synthetic aperture sonar B. J. Davis, P. Gough, and B. Hunt Impact of Littoral Environmental Variability on Acoustic Predictions and Sonar Performance
(2002)
PDF
With the move to use side-looking imaging sonars in very shallow waters as a component part of MCM operations, synthetic aperture sonars (SAS) appear to have some advantages over a conventional real aperture side-looking sonars. One significant advantage of SAS is that it is quite resiliant to image degradation caused by surface backscatter and surface multipath. The processing in all SAS imaging algorithm assumes the only thing moving between transmitted pings is the sonar platform. Since the algorithm uses coherent integration to assemble the final image, any movement of the sea surface between pings destroys the ping-to-ping coherence of the surface multipath as well as the ping-to-ping surface backscattered return. To move towards understanding just how effective a SAS is at supressing backscatter and surface multipath, we first need to model the moving sea surface in a believable way and establish just how the sound reflects off the undersurface of the sea. This paper first describes a commonly-used physically justifiable sea-surface autocorrelation function that accounts for wind direction, wave height, wave period and wave velocity. From this autocorrelation function, a statistically appropriate random wave surface is generated which evolves in both time and space. Finally in a first attempt to model the shallow-water sea surface multipath problem, a set of impulse responses are generated from this wave-surface as it evolves in time increments equal to the pulse repetition period. Here we model an isotropic one-way (reflected) acoustic path from the target at a depth of seven metres to the sonar platform at a depth of five metres separated by 25m with the surface above the path covering an area of 160m (cross-track) by 60m (along-track) and we ignore any seafloor multipath. Two sea-surface reflection/scattering mechanisms are used in this model. In the first, each surface facet acts as a diffraction-limited aperture and in the second, each facet acts as a Lambertian reflector. These descibe two limiting situations 1) when the acoustic wavelength is small compared with the roughness of any facet and 2) when the surface roughness is a significant proportion of the acoustic wavelength. Concentrating on the diffraction-limited model, we show the effect of surface multipath on the raw data collected by a SAS and its effect on the processed image. We also make some estimates of the signal to clutter ratio improvements as a function of the number of hits on target.
Reconstruction of objects with a limited number of non-zero components in fluroescence microscopy B. J. Davis, W. C. Karl, A. K. Swan, B. B. Goldberg, M. S. Ünlü, and M. B. Goldberg SPIE Photonics West
(2004)
PDF
A reconstruction algorithm is developed that uses specific a-priori knowledge to produce higher resolution images than standard approaches. Deconvolution is an important image reconstruction tool in fluorescence microscopy. This is especially true for modern interferometric instruments (such as I5M and 4Pi systems), as they may have complicated oscillatory point spread functions. Current methods are designed to work on an arbitrary object - i.e. it is assumed that there is no available a-priori knowledge of the object (with the possible exception of a non-negative condition on the fluorophore-emission intensities). In situations where there is a-priori knowledge of the object, it may be possible to use this information to produce a higher quality reconstruction of the object. A useful a-priori condition is investigated here.
It is assumed that the object can be represented by the sum of not more than L basis functions. The simplest example of this is when the basis functions are impulses - this leads to an object of L or less non-zero points on a background of zeros. This a-priori condition can be applied directly; applied to a limited region of the object; applied in one dimension (for an object with a layered structure such as lipid bilayers); or applied in two dimensions (for an object with a filamentary structure such as actin fibers.) A reconstruction algorithm is described and applied to some illustrative simulated examples. The results are found for several fluorescence microscopy methodologies and compared to the results produced by standard deconvolution methods.
Seeing inside chips and cells: high resolution subsurface imaging of integrated circuits, quantum dots and subcellular structures B. B. Goldberg, A. K. Swan, L. Moiseev, M. Dogan, W. C. Karl, B. J. Davis, C. R. Cantor, S. B. Ippolito, S. A. Thorne, M. G. Eraslan, Z. Liu, M. B. Goldberg, and M. S. Ünlü IEEE Quantum Electronics Conference
(2004)
PDF
In this work we examine two general approaches to subsurface imaging, the first using solid immersion lens technology to optimize the numerical aperture and the second an interferometric spectral fluorescence technique for buried emitters.
Sampling below the Nyquist rate in interferometric fluorescence microscopy with multi-wavelength measurements to remove aliasing B. J. Davis, W. C. Karl, B. B. Goldberg, A. K. Swan, and M. S. Ünlü IEEE Digital Signal Processing Workshop
(2004)
PDF
A multi-wavelength 3D fluorescence microscope, with transfer functions varying significantly with wavelength, is proposed. This microscope measures multiple wavelengths concurrently and scans through the object at a rate significantly below the Nyquist criterion, which gives a reduced image acquisition time. The sub-Nyquist sampling produces a set of images contaminated by aliasing. Due to the differing transfer functions, the aliasing effects are different in each image. This allows the aliasing operator to be inverted and a single unaliased image to be constructed. This is an application of the generalized sampling expansion first introduced by Papoulis. The instrument is demonstrated through simulation and shown to produce images of a similar quality to those that would be expected from a Nyquist-rate instrument.
Using out-of-focus light to improve image acquisition time in confocal microscopy B. J. Davis, W. C. Karl, B. B. Goldberg, A. K. Swan, and M. S. Ünlü SPIE Photonics West
(2005)
PDF
Light that would typically be discarded at a confocal microscope's detector pinhole will be collected and processed to allow a reduced spatial sampling rate and thus an improved image acquisition time. It is shown that collecting and appropriately processing the out-of-focus light will allow an axial sampling rate below that specified by the Nyquist criterion. To achieve this, a central detector pinhole and a number of out-of-focus regions are collected concurrently. This corresponds to imaging through several different channels, with differing point spread functions, in parallel. Since the spatial sampling rate is below the Nyquist frequency, aliasing occurs in the data from each of the channels. However, since the point spread functions are different, the aliasing effects are different in each channel. This allows the ensemble of aliased images to be processed into a single dealiased and deconvolved image. This potential utility of out-of-focus light is demonstrated through simulated examples for differing collection schemes and scanning rates. Results are shown for under-sampling by up to a factor of four. Collecting the out-of-focus light also improves instrument collection efficiency.
Using multi-element detectors to create optimal apertures in confocal microscopy B. J. Davis, M. S. Ünlü, A. K. Swan, B. B. Goldberg, and W. C. Karl IEEE Annual Meeting of Lasers and Electro-Optics Society
(2005)
PDF
A detection pinhole is used in confocal microscopy to reduce contributions from image planes outside of the focal plane. The size of this pinhole may be varied but the idea of a fixed circular aperture is ubiquitous. Here it is shown that an ideal detection aperture varies as a function of the spatial-frequency being imaged. A method for calculating such detection apertures is given, an example calculation is shown and a detector array is suggested as a means to approximate these varying detection apertures.
Making use of rejected light - improved imaging with multi-channel detection in confocal and 4Pi microscopy B. J. Davis, W. C. Karl, A. K. Swan, M. S. Ünlü, and B. B. Goldberg OSA Frontiers in Optics
(2006)
PDF
Light usually discarded in a microscope can be collected in additional channels and used to reduce noise sensitivity. Optimal Fourier-domain processing is used to construct a single superior image from the multi-channel image set.
Polarimetric interferometric synthetic aperture microscopy: vectorial computed imaging from optical coherence tomography data B. J. Davis, T. S. Ralston, D. L. Marks, S. A. Boppart, and P. S. Carney OSA Computational Optical Sensing and Imaging
(2007)
PDF
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.
Interferometric synthetic aperture microscopy (invited) P. S. Carney, B. J. Davis, T. S. Ralston, D. L. Marks, and S. A. Boppart OSA Computational Optical Sensing and Imaging
(2007)
PDF
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.
Optical interferometry with pulsed fields R. W. Schoonover, B. J. Davis, R. A. Bartels, and P. S. Carney OSA Coherence and Quantum Optics
(2007)
PDF
An analysis of coherence properties of pulsed fields in interferometric experiments is presented. The results bear on means to recover certain statistical properties of the source in a two-slit experiment.
Fluorescence imaging with nanometer precision using spectral self-interference microscopy B. J. Davis, P. S. Carney, A. K. Swan, M. S. Ünlü, W. C. Karl, and B. B. Goldberg IEEE International Conference on Electromagnetic Near-Field Characterization and Imaging
(2007)
PDF
Spectral Self-Interference Fluorescence Microscopy (SSFM) has been shown to allow nanometer-scale localization of fluorescent layers placed above a reflecting substrate. A Monte-Carlo analysis is used to show how this high localization accuracy can still be expected at the low signal levels associated with single-molecule studies. Discrimination of fluorophores separated by a few tens of nanometers is also demonstrated. The results achieved indicate that SSFM may be applied to total internal reflection fluorescence microscopy to axially resolve objects within the evanescent excitation volume.
Optical interferometry with pulsed fields R. W. Schoonover, B. J. Davis, R. A. Bartels, and P. S. Carney OSA Frontiers in Optics
(2007)
PDF
An analysis of coherence properties of pulsed fields in interferometric experiments is presented. The results bear on means to recover certain statistical properties of the source in a two-pinhole experiment.
Interferometric synthetic aperture microscopy: physics-based image reconstruction from optical coherence tomography data B. J. Davis, T. S. Ralston, D. L. Marks, S. A. Boppart, and P. S. Carney IEEE International Conference on Image Processing
(2007)
PDF
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.
Interferometric synthetic aperture microscopy: tissue structure inferred by computed imaging techniques (invited) D. L. Marks, T. S. Ralston, B. J. Davis, P. S. Carney, and S. A. Boppart SPIE Photonics West
(2008)
PDF
Interferometric Synthetic Aperture Microscopy (ISAM) is an optical microscopy computed-imaging technique for measuring the optical properties of three-dimensional structures and biological tissues. In this work, the principle of ISAM is reviewed, and its application to imaging tissue properties in various scanning geometries and instrument configurations is explored. The practicality of ISAM is demonstrated by imaging a rat heart and muscle using a real-time implementation of ISAM in conjunction with a clinical cart Optical Coherence Tomography instrument.
Partially coherent cyclostationary pulses in Young's interference experiment R. W. Schoonover, B. J. Davis, R. A. Bartels, and P. S. Carney OSA Frontiers in Optics
(2008)
PDF
Young's interference experiment is used to analyze the statistical properties of a certain class of spatially partially coherent, cyclostationary, optical fields.
Characterization of scattering from nanoparticles using far-field interferometric microscopy B. J. Davis and P. S. Carney OSA Frontiers in Optics
(2008)
PDF
Analysis and simulations show that coherent confocal microscopy techniques, such as Optical Coherence Microscopy, can be used to estimate the polarizability tensor of an imaged nanoparticle. The estimation process is robust to noise and defocus.
Histologic models for optical tomography and spectroscopy of tissues R. Bhargava and B. J. Davis SPIE Photonics West
(2009)
PDF
Histologic information is often the ground truth against which imaging technology performance is measured. Typically, this information is limited, however, due to the need to excise tissue, stain it and have the tissue section manually reviewed. As a consequence, histologic models of actual tissues are difficult to acquire and are generally prohibitively expensive. Models and phantoms for imaging development, hence, have to be simple and reproducible for concordance between different groups developing the same imaging methods but may not reflect tissue structure. Here, we propose a route to histologic information that does not involve the use of human review nor does it require specialized dyes or stains. We combine mid-infrared Fourier transform infrared (FT-IR) spectroscopy with imaging to record data from tissue sections. Attendant numerical algorithms are used to convert the data to histologic information. Additionally, the biochemical nature of the recorded information can be used to generate contrast for other modalities. We propose that this histologic model and spectroscopic generation of contrast can serve as standard for testing and design aid for tomography and spectroscopy of tissues. We discuss here the biochemical and statistical issues involved in creating histologic models and demonstrate the use of the approach in generating optical coherence tomography (OCT) images of prostate tissue samples.
Intellectual Property
Partially coherent illumination for inverse scattering full-field interferometric synthetic aperture microscopy D. L. Marks, B. J. Davis, S. A. Boppart, and P. S. Carney Continuation-in-Part of Pending PatentUS11/775,572
(2008)
Spectral near-field optical tomography B. J. Davis, J. Sun, J. C. Schotland, and P. S. Carney Pending PatentUS12/402,177
(2009)
Robust determination of the anisotropic polarizability of nanoparticles using coherent confocal microscopy B. J. Davis and P. S. Carney Pending PatentUS12/405,711
(2009)
Book Chapters
Interferometric Synthetic Aperture Microscopy S. G. Adie, B. J. Davis, T. S. Ralston, D. L. Marks, P. S. Carney, and S. A. Boppart Biomedical Applications of Light Scattering,McGraw-Hill
(in press)
Magazine and News Articles
Real-time interferometric synthetic aperture microscopy for clinical applications T. S. Ralston, S. G. Adie, D. L. Marks, B. J. Davis, P. S. Carney, and S. A. Boppart Optics and Photonics News,19,p. 32
(2008)
PDF
Theses
Analysis of multi-channel microscopy: spectral self-interference, multi-detector confocal and 4Pi systems B. J. Davis Boston University Doctoral Dissertation
(2006)
PDF
Fluorescence microscopy is an important and ubiquitous tool in biological imaging due to the high specificity with which fluorescent molecules can be attached to an organism and the subsequent nondestructive in-vivo imaging allowed. Focused-light microscopies allow three-dimensional fluorescence imaging but their resolution is restricted by diffraction. This effect is particularly limiting in the axial dimension as the diffraction-limited focal volume produced by a lens is more extensive along the optical axis than perpendicular to it. Approaches such as confocal microscopy and 4Pi microscopy have been developed to improve the axial resolution. Spectral Self-Interference Fluorescence Microscopy (SSFM) is another high-axial-resolution technique and is the principal subject of this dissertation. Nanometer-precision localization of a single fluorescent layer has been demonstrated using SSFM. This accuracy compares favorably with the axial resolutions given by confocal and 4Pi systems at similar operating parameters (these resolutions are approximately 350nm and 80nm respectively).
This theoretical work analyzes the expected performance of the SSFM system when imaging a general object, i.e. an arbitrary fluorophore density function rather than a single layer. An existing model of SSFM is used in simulations to characterize the system's resolution. Several statistically-based reconstruction methods are applied to show that the expected resolution for SSFM is similar to 4Pi microscopy for a general object but does give very high localization accuracy when the object is known to consist of a limited number of layers. SSFM is then analyzed in a linear systems framework and shown to have strong connections, both physically and mathematically, to a multi-channel 4Pi microscope. Fourier-domain analysis confirms that SSFM cannot be expected to outperform this multi-channel 4Pi instrument. Differences between the channels in spatial-scanning, multi-channel microscopies are then exploited to show that such instruments can operate at a sub-Nyquist scanning rate but still produce images largely free of aliasing effects. Multi-channel analysis is also used to show how light typically discarded in confocal and 4Pi systems can be collected and usefully incorporated into the measured image.
Investigation of the effects of first-order, multi-path propagation from the sea surface in synthetic aperture sonar systems B. J. Davis University of Arizona Master of Science Thesis
(2001)
PDF
Classical methods of analysis for Synthetic Aperture Sonar (SAS) systems do not account for any multi-path propagation effects. If multi-path effects are significant but not allowed for, they are likely to adversely affect image quality. This investigation addresses multi-path propagation from the sea surface and its effect on SAS
systems. To simplify the problem, only first-order reflections from the sea surface are considered. Other effects (such as Doppler shift and reflection from bubbles) are ignored. The propagation of the acoustic signal and its scattering at the surface must be considered.
The investigation is carried out primarily through computer simulations. Sea surface functions are constructed through the realization of a stochastic model. To make the problem computationally tractable, a facet-ensemble methodology is employed when simulating the multi-path returns. Two models are examined - one treats each facet as a Lambertian reflector, and the other treats each facet as a diffracting aperture. The theory needed to perform these simulations is developed.
Both models are applied to a simulated sea surface, a flat surface and an ensemble of sea surfaces. The results are examined in terms of the physics of each model and in terms of the possible effects on SAS imaging. The characteristics of the two models are seen to vary significantly but both are shown to produce significant multi-path returns. Despite the differences in the models, the general form of the multi-path response is observed to be similar.
