1. Articles from Danielle J. Harper

    1-21 of 21
    1. Special Issue "Biomedical Applications of Optical Coherence Tomography" in the journal of Bioengineering

      Special Issue "Biomedical Applications of Optical Coherence Tomography" in the journal of Bioengineering

      Dear Colleagues, Since its invention in 1991, optical coherence tomography (OCT) has rapidly become one of the most important clinical tools in the field of ophthalmology. In recent years, applications of this inherently non-invasive and label-free three-dimensional imaging technique have extended far beyond retinal and corneal imaging. OCT applications are being increasingly used in medicine in fields including dermatology, endoscopy and neurology, and advances in system technology and image processing mean that the resultant images are approaching cellular resolution over a wide field of view. Through the constant development of new technologies and functional extensions, OCT continues to move into ...

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    2. Relationship between axial resolution and signal-to-noise ratio in optical coherence tomography

      Relationship between axial resolution and signal-to-noise ratio in optical coherence tomography

      In optical coherence tomography (OCT), axial resolution and signal-to-noise ratio (SNR) are typically viewed as uncoupled parameters. We show that this is true only for mirror-like surfaces and that in diffuse scattering samples such as biological tissues there is an inherent coupling between axial resolution and measurement SNR. We explain the origin of this coupling and demonstrate that it can be used to achieve increased imaging penetration depth at the expense of resolution. Finally, we argue that this coupling should be considered during OCT system design processes that seek to balance the competing needs of resolution, sensitivity, and system/source ...

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    3. THE RELATIONSHIP BETWEEN AXIAL RESOLUTION AND SIGNAL-TO-NOISE RATIO IN OPTICAL COHERENCE TOMOGRAPHY

      THE RELATIONSHIP BETWEEN AXIAL RESOLUTION AND SIGNAL-TO-NOISE RATIO IN OPTICAL COHERENCE TOMOGRAPHY

      In optical coherence tomography (OCT), axial resolution and signal-to-noise ratio (SNR) are typically viewed as uncoupled parameters. We show that this is only true for mirror-like surfaces, and that in diffuse scattering samples such as tissue there is an inherent coupling between axial resolution and measurement SNR. We explain the origin of this coupling and demonstrate that it can be used to achieve increased imaging penetration depth at the expense of resolution. Finally, we argue that this coupling should be considered during OCT system design processes that seek to balance competing needs of resolution, sensitivity, and system/source complexity.

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    4. High-resolution, depth-resolved vascular leakage measurements using contrast-enhanced, correlation-gated optical coherence tomography in mice

      High-resolution, depth-resolved vascular leakage measurements using contrast-enhanced, correlation-gated optical coherence tomography in mice

      Vascular leakage plays a key role in vision-threatening retinal diseases such as diabetic retinopathy and age-related macular degeneration. Fluorescence angiography is the current gold standard for identification of leaky vasculature in vivo, however it lacks depth resolution, providing only 2D images that complicate precise identification and localization of pathological vessels. Optical coherence tomography (OCT) has been widely adopted for clinical ophthalmology due to its high, micron-scale resolution and rapid volumetric scanning capabilities. Nevertheless, OCT cannot currently identify leaky blood vessels. To address this need, we have developed a new method called exogenous contrast-enhanced leakage OCT (ExCEL-OCT) which identifies the diffusion ...

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    5. Toward optical coherence tomography on a chip: in vivo three-dimensional human retinal imaging using photonic integrated circuit-based arrayed waveguide gratings

      Toward optical coherence tomography on a chip: in vivo three-dimensional human retinal imaging using photonic integrated circuit-based arrayed waveguide gratings

      In this work, we present a significant step toward in vivo ophthalmic optical coherence tomography and angiography on a photonic integrated chip. The diffraction gratings used in spectral-domain optical coherence tomography can be replaced by photonic integrated circuits comprising an arrayed waveguide grating. Two arrayed waveguide grating designs with 256 channels were tested, which enabled the first chip-based optical coherence tomography and angiography in vivo three-dimensional human retinal measurements. Design 1 supports a bandwidth of 22 nm, with which a sensitivity of up to 91 dB (830 µW ) and an axial resolution of 10.7 µm was measured. Design 2 ...

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    6. Improved accuracy of quantitative birefringence imaging by polarization sensitive OCT with simple noise correction and its application to neuroimaging

      Improved accuracy of quantitative birefringence imaging by polarization sensitive OCT with simple noise correction and its application to neuroimaging

      Polarization-sensitive optical coherence tomography (PS-OCT) enables three dimensional imaging of biological tissues based on the inherent contrast provided by scattering and polarization properties. In fibrous tissue such as the white matter of the brain, PS-OCT allows quantitative mapping of tissue birefringence. For the popular PS-OCT layout using a single circular input state, birefringence measurements are based on a straight-forward evaluation of phase retardation data. However, the accuracy of these measurements strongly depends on the signal-to-noise ratio (SNR) and is prone to mapping artifacts when the SNR is low. Here we present a simple yet effective approach for improving the accuracy ...

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    7. Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning

      Improved Diagnostic Imaging of Brain Tumors by Multimodal Microscopy and Deep Learning

      Fluorescence-guided surgery is a state-of-the-art approach for intraoperative imaging during neurosurgical removal of tumor tissue. While the visualization of high-grade gliomas is reliable, lower grade glioma often lack visible fluorescence signals. Here, we present a hybrid prototype combining visible light optical coherence microscopy (OCM) and high-resolution fluorescence imaging for assessment of brain tumor samples acquired by 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery. OCM provides high-resolution information of the inherent tissue scattering and absorption properties of tissue. We here explore quantitative attenuation coefficients derived from volumetric OCM intensity data and quantitative high-resolution 5-ALA fluorescence as potential biomarkers for tissue malignancy including otherwise ...

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    8. Indocyanine green provides absorption and spectral contrast for optical coherence tomography at 840  nm in vivo

      Indocyanine green provides absorption and spectral contrast for optical coherence tomography at 840  nm in vivo

      In recent years, there has been growing interest in the application of exogenous contrast agents to supplement the traditional strengths of optical coherence tomography (OCT) and provide additional biological information. In this Letter, we present how indocyanine green, a common fluorescent contrast agent approved by the United States Food and Drug Administration, can provide absorption and spectral contrast for OCT imaging in the mouse eye in vivo . We further demonstrate high stability of spectral contrast measurements for the long-term monitoring of contrast agents in spite of fluctuations in intensity.

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    9. Three-dimensional visualization of opacifications in the murine crystalline lens by in vivo optical coherence tomography

      Three-dimensional visualization of opacifications in the murine crystalline lens by in vivo optical coherence tomography

      Diagnostic classification techniques used to diagnose cataracts, the world’s leading cause of blindness, are currently based on subjective methods. Here, we present optical coherence tomography as a noninvasive tool for volumetric visualization of lesions formed in the crystalline lens. A custom-made swept-source optical coherence tomography (SS-OCT) system was utilized to investigate the murine crystalline lens. In addition to imaging cataractous lesions in aged wildtype mice, we studied the structure and shape of cataracts in a mouse model of Alzheimer’s disease. Hyperscattering opacifications in the crystalline lens were observed in both groups. Post mortem histological analysis were performed to ...

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    10. Optical Coherence Tomography Findings in the Retinas of SOD1 Knockout Mice

      Optical Coherence Tomography Findings in the Retinas of SOD1 Knockout Mice

      Purpose : The retinal phenotype of popular mouse models mimicking ophthalmic diseases, such as the superoxide dismutase 1 (SOD1) knockout (KO) mouse model, has mainly been assessed by ex vivo histology and in vivo fundus photography. We used multifunctional optical coherence tomography (OCT) to characterize the retinas of SOD1 KO mice in vivo. Methods : The custom-made ophthalmoscope featured a combination of conventional OCT, polarization-sensitive OCT, and OCT angiography. Seven SOD1 KO mice and nine age-matched controls were imaged between 6 and 17 months of age. A postprocessing framework was used to analyze total and outer retinal thickness changes. Drusenlike lesions were ...

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    11. Polarization-sensitive imaging with simultaneous bright- and dark-field optical coherence tomography

      Polarization-sensitive imaging with simultaneous bright- and dark-field optical coherence tomography

      We present a polarization-sensitive (PS) extension for bright- and dark-field (BRAD) optical coherence tomography imaging. Using a few-mode fiber detection scheme, the light backscattered at different angles is separated, and the BRAD images of tissue scattering are generated. A calibration method to correct for the fiber birefringence is proposed. Since particle scattering profiles are polarization dependent, a PS detection extends the capabilities for investigating the scattering properties of biological tissues. Both phantoms consisting of different-sized microparticles and a brain tissue specimen were imaged to validate the system performance and demonstrate the complementary image contrast.

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    12. Assessment of pathological features in Alzheimer’s disease brain tissue with a large field-of-view visible-light optical coherence microscope

      Assessment of pathological features in Alzheimer’s disease brain tissue with a large field-of-view visible-light optical coherence microscope

      We implemented a wide field-of-view visible-light optical coherence microscope (OCM) for investigating ex-vivo brain tissue of patients diagnosed with Alzheimer’s disease (AD) and of a mouse model of AD. A submicrometer axial resolution in tissue was achieved using a broad visible light spectrum. The use of various objective lenses enabled reaching micrometer transversal resolution and the acquisition of images of microscopic brain features, such as cell structures, vessels, and white matter tracts. Amyloid-beta plaques in the range of 10 to 70  μm were visualized. Large field-of-view images of young and old mouse brain sections were imaged using an automated ...

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    13. Beyond backscattering: optical neuroimaging by BRAD

      Beyond backscattering: optical neuroimaging by BRAD

      Optical coherence tomography (OCT) is a powerful technology for rapid volumetric imaging in biomedicine. The bright field imaging approach of conventional OCT systems is based on the detection of directly backscattered light, thereby waiving the wealth of information contained in the angular scattering distribution. Here we demonstrate that the unique features of few-mode fibers (FMF) enable simultaneous bright and dark field (BRAD) imaging for OCT. As backscattered light is picked up by the different modes of a FMF depending upon the angular scattering pattern, we obtain access to the directional scattering signatures of different tissues by decoupling illumination and detection ...

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    14. White light polarization sensitive optical coherence tomography for sub-micron axial resolution and spectroscopic contrast in the murine retina

      White light polarization sensitive optical coherence tomography for sub-micron axial resolution and spectroscopic contrast in the murine retina

      A white light polarization sensitive optical coherence tomography system has been developed, using a supercontinuum laser as the light source. By detecting backscattered light from 400–700 nm, an axial resolution of 1.0 µm in air was achieved. The system consists of a free-space interferometer and two homemade spectrometers that detect orthogonal polarization states. Following system specifications, images of a healthy murine retina as acquired by this non-contact system are presented, showing high resolution reflectivity images as well as spectroscopic and polarization sensitive contrast. Additional images of the very-low-density-lipoprotein-receptor (VLDLR) knockout mouse model were acquired. The high resolution allows ...

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    15. Polarization-sensitive optical coherence tomography in the anterior mouse eye

      Polarization-sensitive optical coherence tomography in the anterior mouse eye

      Polarization-sensitive optical coherence tomography (PS-OCT) provides intrinsic contrast related to tissue microstructure. In the past, PS-OCT has been successfully used for imaging the anterior eye of humans in a variety of pathologic conditions. Here, we present PS-OCT imaging of the anterior eye in mice. Spectral domain PS-OCT centered at a wavelength of 840 nm was performed in anaesthetized laboratory mice. Three dimensional data sets were acquired at a 70 kHz A-line rate. PS-OCT images displaying phase retardation, birefringent axis orientation and degree of polarization uniformity (DOPU) were computed. Similar to human anterior segments, depolarization was observed in the corneal stroma ...

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    16. Beyond backscattering: Optical neuroimaging by BRAD

      Beyond backscattering: Optical neuroimaging by BRAD

      Optical coherence tomography (OCT) is a powerful technology for rapid volumetric imaging in biomedicine. The bright field imaging approach of conventional OCT systems is based on the detection of directly backscattered light, thereby waiving the wealth of information contained in the angular scattering distribution. Here we demonstrate that the unique features of few-mode fibers (FMF) enable simultaneous bright and dark field (BRAD) imaging for OCT. As backscattered light is picked up by the different modes of a FMF depending upon the angular scattering pattern, we obtain access to the directional scattering signatures of different tissues by decoupling illumination and detection ...

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    17. Feature Of The Week 09/03/2017: Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples

      Feature Of The Week 09/03/2017: Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples

      A visible light spectral domain optical coherence microscopy system was developed. A high axial resolution of 0.88 μm in tissue was achieved using a broad visible light spectrum (425 – 685 nm). Healthy human brain tissue was imaged to quantify the difference between white (WM) and grey matter (GM) in intensity and attenuation. The high axial resolution enables the investigation of amyloid-beta plaques of various sizes in human brain tissue and animal models of Alzheimer’s disease (AD). By performing a spectroscopic analysis of the OCM data, differences in the characteristics for WM, GM, and neuritic amyloid-beta plaques were found ...

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    18. Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples

      Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples

      A visible light spectral domain optical coherence microscopy system was developed. A high axial resolution of 0.88 µm in tissue was achieved using a broad visible light spectrum (425 − 685 nm). Healthy human brain tissue was imaged to quantify the difference between white (WM) and grey matter (GM) in intensity and attenuation. The high axial resolution enables the investigation of amyloid-beta plaques of various sizes in human brain tissue and animal models of Alzheimer’s disease (AD). By performing a spectroscopic analysis of the OCM data, differences in the characteristics for WM, GM, and neuritic amyloid-beta plaques were found ...

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    19. Visible light spectral domain optical coherence microscopy system for ex vivo imaging

      Visible light spectral domain optical coherence microscopy system for ex vivo imaging

      A visible light spectral domain optical coherence microscopy system operating in the wavelength range of 450-680 nm was developed. The resulting large wavelength range of 230 nm enabled an ultrahigh axial resolution of 0.88μm in tissue. The setup consisted of a Michelson interferometer combined with a homemade spectrometer with a spectral resolution of 0.03 nm. Scanning of 1 x 1 mm 2 and 0.5 x 0.5 mm 2 areas was performed by an integrated microelectromechanical mirror. After scanning the light beam is focused onto the tissue by a commercial objective with a 10 x magnification ...

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    20. Multi-Functional OCT Enables Longitudinal Study of Retinal Changes in a VLDLR Knockout Mouse Model

      Multi-Functional OCT Enables Longitudinal Study of Retinal Changes in a VLDLR Knockout Mouse Model

      We present a multi-functional optical coherence tomography (OCT) imaging approach to study retinal changes in the very-low-density-lipoprotein-receptor (VLDLR) knockout mouse model with a threefold contrast. In the retinas of VLDLR knockout mice spontaneous retinal-chorodoidal neovascularizations form, having an appearance similar to choroidal and retinal neovascularizations (CNV and RNV) in neovascular age-related macular degeneration (AMD) or retinal angiomatous proliferation (RAP). For this longitudinal study, the mice were imaged every 4 to 6 weeks starting with an age of 4 weeks and following up to the age of 11 months. Significant retinal changes were identified by the multi-functional imaging approach offering a ...

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    21. The Application of Optical Coherence Tomography to Image Subsurface Tissue Structure of Antarctic Krill Euphausia superba

      The Application of Optical Coherence Tomography to Image Subsurface Tissue Structure of Antarctic Krill Euphausia superba

      Many small open ocean animals, such as Antarctic krill, are an important part of marine ecosystems. To discover what will happen to animals such as krill in a changing ocean, experiments are run in aquaria where conditions can be controlled to simulate water characteristics predicted to occur in the future. The response of individual animals to changing water conditions can be hard to observe, and with current observation techniques it is very difficult to follow the progress of an individual animal through its life. Optical coherence tomography (OCT) is an optical imaging technique that allows images at high resolution to ...

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    1-21 of 21
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    The Application of Optical Coherence Tomography to Image Subsurface Tissue Structure of Antarctic Krill Euphausia superba Multi-Functional OCT Enables Longitudinal Study of Retinal Changes in a VLDLR Knockout Mouse Model Visible light spectral domain optical coherence microscopy system for ex vivo imaging Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples Feature Of The Week 09/03/2017: Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples Beyond backscattering: Optical neuroimaging by BRAD Polarization-sensitive optical coherence tomography in the anterior mouse eye White light polarization sensitive optical coherence tomography for sub-micron axial resolution and spectroscopic contrast in the murine retina Assessment of pathological features in Alzheimer’s disease brain tissue with a large field-of-view visible-light optical coherence microscope Toward optical coherence tomography on a chip: in vivo three-dimensional human retinal imaging using photonic integrated circuit-based arrayed waveguide gratings The truth about invisible posterior vitreous structures Increased Macrophage-like Cell Density in Retinal Vein Occlusion as Characterized by en Face Optical Coherence Tomography