Sergey A. Alexandrov

In vivo size and shape measurement of the human upper airway using endoscopic long-range optical coherence tomography

We describe a long-range optical coherence tomography system for size and shape measurement of large hollow organs in the human body. The system employs a frequency-domain optical delay line of a configuration that enables the combination of high-speed operation with long scan range. We compare the achievable maximum delay of several delay line configurations, and identify the configurations with the greatest delay range. We demonstrate the use of one such long-range delay line in a catheter-based optical coherence tomography system and present profiles of the human upper airway and esophagus in vivo with a radial scan range of 26 millimeters. Such quantitative upper airway profiling should prove valuable in investigating the pathophysiology of airway collapse during sleep (obstructive sleep apnea).

Audio frequency in vivo optical coherence elastography

We present a new approach to optical coherence elastography (OCE), which probes the local elastic properties of tissue by using optical coherence tomography to measure the effect of an applied stimulus in the audio frequency range. We describe the approach, based on analysis of the Bessel frequency spectrum of the interferometric signal detected from scatterers undergoing periodic motion in response to an applied stimulus. We present quantitative results of sub-micron excitation at 820 Hz in a layered phantom and the first such measurements in human skin in vivo.

Coherent aperture-synthesis, wide-field, high-resolution holographic microscopy of biological tissue

We show for the first time, to our knowledge, high-resolution wide-field images of biological samples recorded using coherent aperture-synthesis Fourier holography. To achieve this, we combined off-axis plane-wave polarized illumination with an axial sample rotation and polarization-sensitive collection of backscattered light. We synthesized 180 Fourier holograms using an efficient postdetection phase-matching correlation scheme. The result was an annular spatial frequency-space synthetic aperture (NA=0.93) with an effective area 25 times larger than that due to a single hologram. A high-resolution high-contrast microscopic reconstruction of biological tissue was computed over a sample area of 9 mm(2) from holograms acquired at 34 mm working distance.

Spatially resolved Fourier holographic light scattering angular spectroscopy

We utilize Fourier-holographic light scattering angular spectroscopy to record the spatially resolved complex angular scattering spectra of samples over wide fields of view in a single or few image captures. Without resolving individual scatterers, we are able to generate spatially-resolved particle size maps for samples composed of spherical scatterers, by comparing generated spectra with Mie-theory predictions. We present a theoretical discussion of the fundamental principles of our technique and, in addition to the sphere samples, apply it experimentally to a biological sample which comprises red blood cells. Our method could possibly represent an efficient alternative to the time-consuming and laborious conventional procedure in light microscopy of image tiling and inspection, for the characterization of microscopic morphology over wide fields of view.

Spatial information transmission beyond a system?s diffraction limit using optical spectral encoding of the spatial frequency

We propose optical spectral encoding of an objects spatial frequencies as a means of transmitting, through a low-numerical-aperture optical system, spatial information with an instantaneous spatial frequency bandwidth wider than the optical systems diffraction-limited bandwidth. We validate this new superresolution approach experimentally and demonstrate one of its possible practical implementations—wide-field spectrally encoded imaging that is sensitive to nanometre-scale local variations in the microstructure of centimetre-scale samples.

Bifocal optical coherenc refractometry of turbid media

We propose and demonstrate a novel technique, which we term bifocal optical coherence refractometry, for the rapid determination of the refractive index of a turbid medium. The technique is based on the simultaneous creation of two closely spaced confocal gates in a sample. The optical path-length difference between the gates is measured by means of low-coherence interferometry and used to determine the refractive index. We present experimental results for the refractive indices of milk solutions and of human skin in vivo. As the axial scan rate determines the acquisition time, which is potentially of the order of tens of milliseconds, the technique has potential for in vivo refractive-index measurements of turbid biological media under dynamic conditions.

Microscopic particle discrimination using spatially-resolved Fourier-holographic light scattering angular spectroscopy

We utilize Fourier-holographic light scattering angular spectroscopy to record the spatially resolved complex angular scattering spectra of samples over wide fields of view in a single or few image captures. Without resolving individual scatterers, we are able to generate spatially-resolved particle size maps for samples composed of spherical scatterers, by comparing generated spectra with Mie-theory predictions. We present a theoretical discussion of the fundamental principles of our technique and, in addition to the sphere samples, apply it experimentally to a biological sample which comprises red blood cells. Our method could possibly represent an efficient alternative to the time-consuming and laborious conventional procedure in light microscopy of image tiling and inspection, for the characterization of microscopic morphology over wide fields of view.

Tomographic imaging via spectral encoding of spatial frequency.

Three-dimensional optical tomographic imaging plays an important role in biomedical research and clinical applications. We introduce spectral tomographic imaging (STI) via spectral encoding of spatial frequency principle that not only has the capability for visualizing the three-dimensional object at sub-micron resolution but also providing spatially-resolved quantitative characterization of its structure with nanoscale accuracy for any volume of interest within the object. The theoretical basis and the proof-of-concept numerical simulations are presented to demonstrate the feasibility of spectral tomographic imaging.

Investigation of depth-resolved nanoscale structural changes in regulated cell proliferation and chromatin decondensation

We present depth-resolved spatial-domain low-coherence quantitative phase microscopy, a simple approach that utilizes coherence gating to construct a depth-resolved structural feature vector quantifying sub-resolution axial structural changes at different optical depths within the sample. We show that this feature vector is independent of sample thickness variation, and identifies nanoscale structural changes in clinically prepared samples. We present numerical simulations and experimental validation to demonstrate the feasibility of the approach. We also perform experiments using unstained cells to investigate the nanoscale structural changes in regulated cell proliferation through cell cycle and chromatin decondensation induced by histone acetylation.

Spectral encoding of spatial frequency approach for characterization of nanoscale structures

An approach to acquire axial structural information at nanoscale is demonstrated. It is based on spectral encoding of spatial frequency principle to reconstruct the structural information about the axial profile of the three-dimensional (3D) spatial frequency for each image point. This approach overcomes the fundamental limitations of current optical techniques and provides nanoscale accuracy and sensitivity in characterizing axial structures. Numerical simulation and experimental results are presented.