Abstract: Systems and methods for phase-sensitive optical coherence tomography (“OCT”) and/or optical coherence microscopy (“OCM”) include imparting multiple phase shifts to the object beam, the reference beam, or both in an interferometer. Phase shifts can be imparted to the S-polarization and/or P-polarization modes of the object and/or reference beams. As an example, phase shifts can be imparted to the reference beam in the reference arm using a waveplate or other phase shifter. A non-polarizing beamsplitter can provide additional phase shifts to light reflected by the beamsplitter. Full field OCM can be provided by imaging the phase-shifted channels using an image sensor.

Abstract: A system for providing intraoperative feedback to a user during the course of surgery. A core imaging unit provides low-coherence optical radiation coupled to a sampling device and generates optical coherence tomography (OCT) data based on combining scattered light received from the sampling device together with a reference signal. The sampling device is adapted to receive the low-coherence optical radiation from the core imaging unit and to illuminate the tissue, and to collect light scattered by the tissue and to return said light to the core imaging unit. A core software unit receives the OCT data from the core imaging unit provides real-time feedback, such as an image, to the user via an indicator.

Abstract: Super-resolution label-free microscopy is provided using multiplexed, temporally modulated acquisition patterns of emission point spread functions (“PSFs”). Supercontinuum ultrafast pulses can be used to enhance nonlinear processes, such as autofluorescence and harmonic generation, in order to provide super-resolution imaging of nonlinear label-free signals. Images can be reconstructed using various reconstruction techniques, including pixel reassignment, wavelet reconstruction, and deep learning model-based reconstructions.

Abstract: A photon peak event detection system accepts an analog output from a photon sensor, directly digitizes the analogy output and includes a graphics processing unit (GPU) programmed to conduct a photon peak event detection in real-time via a photon count program that analyzes the digitized photon sensor output in sampling periods each having at least three consecutive data points to determine a local maximum among the consecutive data points and compare the local maximum to one or more predetermined thresholds to determine whether or not a photon was received in each sampling period, the algorithm providing photon counts to a phasor analysis program in the GPU. The phasor analysis program calculates pixelwise fluorescence lifetime phasor data in real-time and sends the data to a central processing unit.

Abstract: A speculum body is configured to attach to the otoscope. An array of radially situated microchannels is within the speculum body and extends to apertures in a distal end of the speculum body. A power electrode array is within the speculum body positioned with respect to the microchannels to excite plasma generation within the microchannels. An optically transparent central portion is in the body to permit viewing of an eardrum by a practitioner. A method of treatment of the middle ear and/or middle ear cavity incudes actuating plasma jets to extend into the ear canal from a speculum attached to the otoscope and continuing the plasma jet treatment for a period of time sufficient to inactivate or kill a bacterial biofilm in the middle ear and/or the middle ear cavity.

Abstract: A detector for characterizing at least one of a middle ear fluid and a middle ear biofilm includes a handheld probe outputting near-infrared and visible light, an OCT system to obtain A-scans at a plurality of positions on a tympanic membrane, and a camera to obtain surface sub-images at the plurality of positions. A-scans and surface sub-images are synchronized and the surface sub-images are mosaicked to generate a surface image of the tympanic membrane. Cross-sectional scan images or a thickness map are generated from the synchronized A-scans and segmented to extract a plurality of specified features. The specified features are then classified to characterize at least one of the middle ear fluid and the middle ear biofilm. The detector, including handheld probe with camera, OCT system, and a laptop computer, is sized to fit into a handheld, portable, compact, foam-padded briefcase weighing less than 10 kg.

Abstract: A calibration phantom, or related nanoparticle substrate, for multimodal optical system characterization includes a contrast layer and a localizing grid layer. The contrast layer may be a two-dimensional (2D) layer, a stack of 2D layers, a three-dimensional (3D) block, or combinations thereof. Nanoparticles are arranged on, embedded in, or coupled to the contrast layer(s). Nanoparticles provide sub-resolution point-sources that can provide optical contrast for multiple different imaging modalities. The localizing grid layer includes a grid, which may be etched in, or otherwise marked on, the localizing grid layer. By coupling the contrast layer to the localizing grid layer, the positions of the nanoparticles remain fixed relative to the localizing grid, which can be visualized by the imaging system. In this way, a reliable and repeatably imageable calibration phantom is provided.

Abstract: A method is provided for characterizing a biological sample having a plurality of fluorophores, including a red fluorophore and a blue fluorophore, comprises exciting the red fluorophore via absorption of a photon order of n by a single wavelength band of light that has longer wavelengths than a typical wavelength band of light known to excite the red fluorophore would have. The method further comprises exciting the blue fluorophore substantially via absorption of a photon order of n+1 by the single wavelength band of light. The method also comprises simultaneously detecting light emitted by the red fluorophore and the blue fluorophore. The method further comprises creating an image or a temporal series for sensing from the light detected in the plurality of orthogonal colors.

Abstract: Methods and apparatus for identifying microbiological constituents in the middle ear. A spectrometer receives Raman-scattered light from the region of the tympanic membrane and resolves spectral features of the Raman-scattered light. A processor receives the interferometry signal and the Raman signal, and generates a Raman spectrum of the tympanic membrane and material adjacent thereto. In some embodiments of the invention, low-coherence light and substantially monochromatic excitation light are directed onto a tympanic membrane of the ear of a person via an otoscopic tip that abuts the ear canal. An interferometer combines scattered low-coherence light from the ear tissue with a reference signal to generate an interferometric signal.

Abstract: An intraoperative probe and a system for optically imaging a surgically significant volume of tissue or other scattering medium. An illumination source generates an illuminating beam that is conveyed to the vicinity of the tissue and a beam splitter, that may be no more than an optical phase reference, splits the illuminating beam into a sample beam along a sample beam path and a reference beam along a reference beam path. A scanning mechanism scans a portion of the sample beam across a section of the scattering medium, while a detector detects return beams from both the reference beam path and the sample beam path and generates an interference signal. A processor computationally moves an effective focus of the sample beam without physical variation of focus of the sample beam. The probe may have a sterilizable fairing that may be detachable.

Abstract: Methods and apparatus for assessing and correcting phase variations and motion artifacts in a coherent tomogram of a sample. Coherent techniques are used scan a broadband optical beam across a sample in a specified scan pattern and to acquire a cube of complex data constituting a full tomogram. Generalized motion of the sample is then quantified based at least on a phase variation measured during the course of scanning the broadband optical beam in the specified scan pattern. Generalized motion includes both actual motion and apparent motion due to organized variation of some physical parameter such as temperature. Intensity structure of speckle imaged during the course of coherently acquiring the full tomograpm may be used to correct for motion of the sample in a plane transverse to a depth axis along the incident beam.

Abstract: A detector for characterizing at least one of a middle ear fluid and a middle ear biofilm includes a handheld probe outputting near-infrared and visible light, an OCT system to obtain A-scans at a plurality of positions on a tympanic membrane, and a camera to obtain surface sub-images at the plurality of positions. A-scans and surface sub-images are synchronized and the surface sub-images are mosaicked to generate a surface image of the tympanic membrane. Cross-sectional scan images or a thickness map are generated from the synchronized A-scans and segmented to extract a plurality of specified features. The specified features are then classified to characterize at least one of the middle ear fluid and the middle ear biofilm. The detector, including handheld probe with camera, OCT system, and a laptop computer, is sized to fit into a handheld, portable, compact, foam-padded briefcase weighing less than 10 kg.

Abstract: Methods for label-free characterization of untagged molecules within a biological sample in-situ. The untagged molecules may be constituent of extracellular vesicles, and are excited in the biological sample with at least one wavelength band of light derived from a single stream of optical pulses. Light emitted by the untagged molecules by SHG, THG, 2PAF and 3PAF processes is detected. Separate measures of the biological sample corresponding to light emitted by the untagged molecules in each of the SHG, THG, 2PAF and 3PAF processes are derived. On that basis, normal extracellular vesicles may be differentiated from extracellular vesicles associated with a tumor on the basis of a specified signature of characteristics of images of SHG, THG, 2PAF and 3PAF processes.

Abstract: Methods and apparatus for combining a low coherence interferometry (LCI) technique for single-point thickness measurement with videootoscopy for recording the image of a tissue such as the tympanic membrane (TM). TM thickness distribution maps are obtained by mapping the LCI imaging sites onto an anatomically accurate wide-field image of the TM, generated by mosaicking a sequence of multiple small field-of-view video-otoscopy images.

Abstract: A system for providing intraoperative feedback to a user during the course of surgery. A core imaging unit provides low-coherence optical radiation coupled to a sampling device and generates optical coherence tomography (OCT) data based on combining scattered light received from the sampling device together with a reference signal. The sampling device is adapted to receive the low-coherence optical radiation from the core imaging unit and to illuminate the tissue, and to collect light scattered by the tissue and to return said light to the core imaging unit. A core software unit receives the OCT data from the core imaging unit provides real-time feedback, such as an image, to the user via an indicator.

Abstract: Methods and apparatus for ascertaining a relative viscosity characterizing a fluid sample. The fluid sample is illuminated through a scattering membrane adjacent to the fluid with broadband radiation. Scattering from particles within the fluid sample characterized by a distribution of characteristic dimensions spanning at least two orders of magnitude is detected, generating a detector signal as a function of depth relative to a specified surface of the scattering membrane at a plurality of temporal delays. A cross-correlation function of at least one of amplitude, phase and intensity of a scattered optical field is derived for a plurality of depths relative to the specified surface. A mean cross-correlation function is then derived for each depth and fit to obtain a diffusion coefficient, from which a relative viscosity characterizing the fluid is derived.

Abstract: Methods and apparatus for identifying microbiological constituents in the middle ear. A spectrometer receives Raman-scattered light from the region of the tympanic membrane and resolves spectral features of the Raman-scattered light. A processor receives the interferometry signal and the Raman signal, and generates a Raman spectrum of the tympanic membrane and material adjacent thereto. In some embodiments of the invention, low-coherence light and substantially monochromatic excitation light are directed onto a tympanic membrane of the ear of a person via an otoscopic tip that abuts the ear canal. An interferometer combines scattered low-coherence light from the ear tissue with a reference signal to generate an interferometric signal.

Abstract: Methods for label-free characterization of untagged molecules within a biological sample in-situ. The untagged molecules may be constituent of extracellular vesicles, and are excited in the biological sample with at least one wavelength band of light derived from a single stream of optical pulses. Light emitted by the untagged molecules by SHG, THG, 2PAF and 3PAF processes is detected. Separate measures of the biological sample corresponding to light emitted by the untagged molecules in each of the SHG, THG, 2PAF and 3PAF processes are derived. On that basis, normal extracellular vesicles may be differentiated from extracellular vesicles associated with a tumor on the basis of a specified signature of characteristics of images of SHG, THG, 2PAF and 3PAF processes.

Abstract: Methods and apparatus for ascertaining a relative viscosity characterizing a fluid sample. The fluid sample is illuminated through a scattering membrane adjacent to the fluid with broadband radiation. Scattering from particles within the fluid sample characterized by a distribution of characteristic dimensions spanning at least two orders of magnitude is detected, generating a detector signal as a function of depth relative to a specified surface of the scattering membrane at a plurality of temporal delays. A cross-correlation function of at least one of amplitude, phase and intensity of a scattered optical field is derived for a plurality of depths relative to the specified surface. A mean cross-correlation function is then derived for each depth and fit to obtain a diffusion coefficient, from which a relative viscosity characterizing the fluid is derived.

Abstract: Methods and apparatus for combining a low coherence interferometry (LCI) technique for single-point thickness measurement with videootoscopy for recording the image of a tissue such as the tympanic membrane (TM). TM thickness distribution maps are obtained by mapping the LCI imaging sites onto an anatomically accurate wide-field image of the TM, generated by mosaicking a sequence of multiple small field-of-view video-otoscopy images.