University of Illinois

Purdue Research Foundation

Diagnostic Photonics, Inc.

Stephen A Boppart

Daniel L Marks

Paul Scott Carney

Haohua Tu

Ryan L Shelton

Adam M Zysk

Paritosh Pande

Kenneth S Suslick

Freddy T Nguyen

Nathan Shemonski

Steven G Adie

Sixian You

Guillermo Luciano Monroy

Farah Jean-Jacques Toublan

Alexander Wei

Yuan Liu

Chenyang Xu

Brynmor J Davis

Andrew J Cittadine

Chuanwu Xi

Janet Sorrells

Rishyashring Raman Iyer

Woonggyu Jung

Joseph B Geddes, Iii

Simon C Schlachter

Matthew S Leigh

Julian J Armstrong

David D Sampson

Darold R Spillman, Jr

Youbo Zhao

Amy L Oldenburg

Vasilica Crecea

Xing Liang

Tyler S Ralston

Roshan I Dsouza

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.

Digital domain photon peak event detection system and method

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.

Clipping-assisted dual-fluorophore sensing

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.

Low-coherence interferometry and optical coherence tomography for image-guided surgical treatment of solid tumors

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.

Compact briefcase OCT system for point-of-care imaging

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.

Handheld device for identification of microbiological constituents in the middle ear

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.

Handheld optical probe in combination with a fixed-focus fairing

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.

Phase measurement, analysis, and correction methods for coherent imaging systems

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.

Molecular imaging biomarkers

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.

Method and apparatus for obtaining a three-dimensional map of tympanic membrane thickness

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.

Method and apparatus for OCT-based viscometry

Methods and apparatus for performing interferometric measurements on ear tissue within a person's ear, wherein the measurements are performed as a function of pressure within the ear canal. Measurements may be performed at a plurality of pressures, including pressures greater than, and less than, atmospheric pressure. Using an apparatus in accordance with the invention, methods are provided for characterizing a tympanic membrane, as well as a biofilm adjacent to the tympanic membrane, and an effusion in the middle ear. The tympanic membrane may be characterized as to geometrical features and mobility. Characterizations provided by the apparatus serve to diagnose ear pathology.

Quantitative pneumatic otoscopy using coherent light ranging techniques

Methods and apparatus for tomographic imaging of a sample. Low-coherence light is split into a sample path and a reference path. A steering optic recombines light in the reference path with light scattered by a sample onto a camera having an areal focal plane array of detector elements such that light in the reference path and light scattered by the sample are characterized by respectively offset propagation vectors at incidence upon the camera. A processor derives depth information from light scattered by the sample on the basis of interference fringes between light in the reference path and light scattered by the sample. The apparatus tracks lateral motion and may be hand-held or attached to a mobile device such as a smartphone, thus enabling 3-D imaging with the mobile device.

Smart phone attachment for 3-D optical coherence tomography imaging

Methods and apparatus for obtaining an image of light scattering biological tissue. A series of pulses of substantially monochromatic light of a first wavelength is generated and split into two parts, of which one part illuminates a scattering biological tissue at an intensity too low to damage the tissue, while a second part is upconverted to generate a pump beam. Sample light from the biological tissue, which may be scattered (or transmitted) light, or fluorescence, or Raman scattering, etc., is collected and directed from the scattering biological tissue, along with the pump beam, into a non-linear optical element, in a single pass or multiple passes. Parametrically amplified sample light emerging from the non-linear optical element is detected and analyzed or displayed.

Optical parametric amplification of weak signals for imaging biological tissue

Methods and apparatus for generating ultrashort optical pulses. Pulses of an infrared source are launched into an optical fiber characterized by a zero-dispersion wavelength (ZDW), where the wavelength of the infrared source exceeds the ZDW of the optical fiber by at least 100 nm. A resonant dispersion wave (RDW) is generated in the optical fiber that has a central wavelength blue-shifted by more than 500 nm relative to the pump wavelength, and, in some cases, by more than 700 nm. The optical fiber has a core of a diameter exceeding the central wavelength of the RDW by at least a factor of five. In a preferred embodiment, the infrared source includes a master-oscillator-power-amplifier, embodied entirely in optical fiber, and may include an Erbium:fiber oscillator, in particular.

Bright few-cycle fiber source using resonant dispersive wave emission in an optical fiber

A method of forming an image of tissue. The method includes beginning an invasive procedure on a patient exposing tissue. The method then includes acquiring OCT data from the exposed tissue and converting the OCT data into at least one image. The method also includes ending the invasive procedure after the converting of the data.

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Champaign, IL, United States of America

Stephen A Boppart