Northeastern University

California Institute of Technology

Boston University

Raytheon Bbn Technologies Corp.

London School of Hygiene and Tropical Medicine

Charles A DiMarzio

Steven A Oliver

Stephen W McKnight

Scott C Lindberg

Changhuei Yang

Ying Min Wang

Zachary R Hoffman

Luis A Nieva

Max Diem

Carey M Rappaport

Benjamin Judkewitz

Meng Cui

Todd W Murray

Ronald A Roy

Gerhard O Sauermann

William C Warger, Ii

Anthony J Devaney

Florian J Blonigen

Lei Sui

Gopi Maguluri

Taner Oktar

Methods, systems, and devices described herein enable single-image optical sectioning, even at depth within turbid media, such as human skin or other tissue. Embodiments can eliminate the need for multiple image samples or raster scans, making in-vivo or live biological imaging easier and faster than multi-image sectioning techniques. Better contrast and resolution than traditional three-phase structured illumination microscopy (SIM) is possible in turbid media. Embodiments enable imaging of cell nuclei. Resolution and contrast resulting from disclosed embodiments are less sensitive to motion of or within patients or other targets than confocal microscopy and three-phase SIM techniques. Three-dimensional images of target specimens can be provided based on a group of single-image optical sections. Real-time imaging can also be provided.

Methods, systems, and devices for optical sectioning

An optical imaging system and method for performing random intensity illumination microscopy is disclosed. The system includes an incoherent signal light source, at least two diffusers having spatially random diffusion patterns, an image capture device that receives a reflected light signal from an object to be imaged, and a processor configured to perform digital image processing of the reflected signal. The method comprises acts of providing an incoherent light signal, diffusing the incoherent light signal with at least two diffusers having spatially random diffusion patterns to provide a diffused light signal, splitting the diffused light signal to provide a first light signal and a second light signal, reflecting the first light signal from a specimen to provide a reflected light signal, collecting the reflected light signal and the second light signal with an image capture device and processing the collected images to determine reflectance.

Systems and methods for random intensity illumination microscopy

A device and method for performing fluorescence imaging with digitally time reversed ultrasound encoded light, using a source of ultrasound waves, a coherent light source, a digital optical phase conjugation (DOPC) device comprising a camera and a spatial light modulator (SLM), a detector of fluorescence, and one or more computers, to obtain an output that at least approximates an interaction between a complete time reversed field, of all of the encoded light's fields, and the scattering medium.

Deep tissue focal fluorescence imaging with digitally time-reversed ultrasound-encoded light

Methods, devices, and systems for imaging tissue and other samples or samples using infrared (IR) transmissions from coherent transmission sources, such as a wide range, tunable, quantum cascade laser (QCL) designed for the rapid collection of infrared microscopic data for medical diagnostics across a wide range of discrete spectral increments. The infrared transmissions are transmitted through, reflected from, and/or transreflected through a sample, and then magnified and/or focused prior to being detected by a detector. After detection, the sample related image data is used to assess the sample. Such methods, devices, and systems may be used to detect abnormalities in tissue, for example, before such abnormalities can be diagnosed using art cytopathological methods. The methods, devices and systems may also optionally include a visible light detection subsystem and/or a motion control subsystem to assist in control and processing of imaging.

Tunable laser-based infrared imaging system and method of use thereof

A light microscope for imaging a sample containing one or more fluorescent agents, comprising a source for generating acoustic waves that are focused at a focus in the sample, wherein the acoustic waves frequency shift a frequency of light passing through the focus, thereby creating a frequency shifted light beam; at least one spatial light modulator (SLM) positioned to illuminate the sample with an output beam that is an optical phase conjugate of the frequency shifted light beam, wherein the output beam is a reflection of a first reference beam off one or more pixels of the SLM, and the pixels are for modulating the first reference beam to create the output beam; and a detector positioned to detect fluorescence generated by the output beam exciting the fluorescent agents at the focus in the sample, thereby imaging the sample.

Acoustic assisted phase conjugate optical tomography

A method and device are provided for counting cells in a sample of living tissue, such as an embryo. The method involves obtaining a microscopic image of the unstained tissue that reveals cell boundaries, such as a differential interference contrast (DIC) image, and an optical quadrature microscopy (OQM) image which is used to prepare an image of optical path length deviation (OPD) across the cell cluster. The boundaries of individual cells in the cell cluster are modeled as ellipses and used, together with the maximum optical path length deviation of a cell, to calculate ellipsoidal model cells that are subtracted from the OPD image. The process is repeated until the OPD image is depleted of phase signal attributable to cells of the cell cluster, and the cell count is obtained from the number of cells subtracted. The method is capable of accurately and non-invasively counting the number of cells in a living embryo at the 2-30 cell stage, and can be employed to assess the developmental stage and health of human embryos for fertility treatments.

Phase subtraction cell counting method

A microscopy apparatus includes a heating source to provide a pulse of heating energy focused on a target to heat a localized region of the target, such as human tissue, to generate motion. A measuring source provides a measuring light beam focused on the target. A coherent confocal microscopy assembly focuses the measuring light beam on the target and returns a reflected signal from the target. A detection assembly receives the reflected signal from the target and detects a Doppler shift of the reflected signal. A scanning assembly scans pulses from the heating source over the target and scans the measuring light beam from the measuring source over the target to build up an image of a plane of the target.

Opto-acoustic signal detection with coherent confocal microscopy

A system and method of detecting acousto-photonic emissions in optically turbid media that provide increased levels of detection sensitivity. The detection system includes an ultrasonic transducer, a laser, a photo-detector for detecting ultrasound-modulated laser light, and circuitry for processing the detected signals for subsequent analysis. The ultrasonic transducer generates an ultrasonic wave that propagates within an optically turbid medium. The laser generates a coherent light beam, which is split to form signal and reference beams. The signal beam is sent through the turbid medium, where it is phase modulated by the ultrasound. The ultrasound-modulated signal beam is provided to a photo-refractive crystal for subsequent interference with the reference beam to convert the phase modulation to intensity modulation. The DC offset of the signal beam intensity provides a measure of the magnitude of the mean phase shift induced by the ultrasound on the multiply scattered optical field within the turbid medium.

Enhanced detection of acousto-photonic emissions in optically turbid media using a photo-refractive crystal-based detection system

A microwave-enhanced infrared thermography technique for detecting buried objects exploits varying phase shifts experienced by different-frequency microwave signals reflected from objects back toward the surface, the phase shifts resulting in different interference patterns and therefore different temperature distribution patterns near the surface. Respective infrared images of an area are captured prior to microwave heating, after a first heating with a first frequency, and after heating with a second frequency different from the first. Pairs of the images are subtracted to form temperature rise images showing patterns of temperature rise in the two cycles, and the temperature rise images are subtracted to form a difference image which is analyzed to identify characteristics indicating the presence of buried objects.

Multiple wavelength microwave-enhanced infrared thermography

An underground object detector can locate and identify the shape of underground objects using a pulsed laser to generate acoustic waves in soil. A remotely located microphone detects an acoustic signal between the soil surface and subsurface objects. The amplitude of this acoustic signal is correlated with the position of the laser beam source and output on a visual display, resulting in an acoustic map of the ground. A raster scanning of the suspect ground in the vicinity reveals the shape of the underground object, allowing the operator to discriminate benign and natural objects.

Optical pulse induced acoustic mine detection

An optical quadrature interferometer is presented. The optical quadrature interferometer uses a different state of polarization in each of two arms of the interferometer. A light beam is split into two beams by a beamsplitter, each beam directed to a respective arm of the interferometer. In one arm, the measurement arm, the light beam is directed through a linear polarizer and a quarter wave plate to produce circularly polarized light, and then to a target being measured. In the other arm, the reference arm, the light beam is not subject to any change in polarization. After the light beams have traversed their respective arms, the light beams are combined by a recombining beamsplitter. As such, upon the beams of each arm being recombined, a polarizing element is used to separate the combined light beam into two separate fields which are in quadrature with each other. An image processing algorithm can then obtain the in-phase and quadrature components of the signal in order to construct an image of the target based on the magnitude and phase of the recombined light beam. The system may further be used for lensless imaging.

Optical quadrature Interferometer

An apparatus and method for measuring instantaneous power using a magneto-optic Kerr effect sensor are disclosed. The apparatus comprises and the method requires a magneto-optic Kerr effect magnetic field sensing element and an optical system including a light source, first and second polarizers, and a photoconductive detector. In a preferred embodiment, the sensing element and the optical system are arranged to sense the intensity of a magnetic field generated by current passing through a high voltage power line so as to provide an optical signal that is representative of the current to the photoconductive detector. A voltage signal is tapped off of the high voltage power line to provide a bias signal to the photoconductive detector. The photoconductive detector thereby effectively multiplies the optical current signal with the voltage signal so as to provide a photoconductive detector current signal that is proportional to instantaneous power passing through the high voltage power line.

Apparatus and method for measuring instantaneous power using a

An optical quadrature interferometer is presented. The optical quadrature interferometer uses a different state of polarization in each of two arms of the interferometer. A light beam is split into two beams by a beamsplitter, each beam directed to a respective arm of the interferometer. In one arm, the measurement arm, the light beam is directed through a linear polarizer and a quarter wave plate to produce circularly polarized light, and then to a target being measured. In the other arm, the to reference arm, the light beam is not subject to any change in polarization. After the light beams have traversed their respective arms, the light beams are combined by a recombining beamsplitter. As such, upon the beams of each arm being recombined, a polarizing element is used to separate the combined light beam into two separate fields which are in quadrature with each other. An image processing algorithm can then obtain the in-phase and quadrature components of the signal in order to construct an image of the target based on the magnitude and phase of the recombined light beam.

Optical quadrature interferometry utilizing polarization to obtain

An optical lock-in detection technique and circuit for coherent applications employing a photo-detector having a symmetric I-V curve is presented. The detection circuit includes a photo-detector operating as an optical lock-in amplifier, and a modulation source. The technique and circuit are used for coherent detection applications such as the determination of the frequency of modulation of an optical signal or the determination of the presence of an optical signal at a specified frequency. The technique and circuit are also used with one or more charge coupled devices in imaging applications.

Optical lock-in detection technique for coherent detection applications

A sensor system includes a magneto-optic Kerr effect magnetic field sensing element and an optical system including a light source, at least one polarizer or polarizing element and a detector disposed about the sensing element. The sensing element is responsive to an external magnetic field. In one embodiment, the optical system and sensing element can be arranged to measure the strength of a magnetic field. In another embodiment the optical system and sensing element can be arranged to measure the rotational speed of rotating members.

Growing community of inventors

Cambridge, MA, United States of America

Charles A DiMarzio