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Open Access Publications from the University of California

Scholarly Works (28 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2018)

Mechanical elasticity often serves as a major indicator for pathological changes in ocular as well as intravascular diseases. For example, age-related macular degeneration is an ocular disease that occurs in the posterior eye, where central vision gets damaged due to drusen formation and neovascularization. The mechanical elasticity of the tissue is often altered during the onset of disease before structural changes are detectable with existing technologies. It is necessary to detect these changes early and provide timely treatment due to either the irreversible nature of the disease progression or the fatal consequences associated with late diagnosis. This thesis focuses on the development of an acoustic radiation force optical coherence elastography (ARF-OCE) system to map the mechanical elasticity of tissues, and the translation of this laboratory technology to in vivo animal studies. This technique uses ultrasonic excitation to apply a force onto the tissue and optical coherence elastography to detect the spatial and frequency responses of the tissue, which combines to quantify the elasticity and provide an elasticity map. The resonance frequency method is validated and used to measure the bulk modulus of the tissue while a Voigt spring model calculates the individual layer elasticity. We first test the feasibility of the system using tissue-mimicking phantoms. Then we perform tissue imaging on the ex vivo anterior and posterior eye, where we are able to provide quantified elasticity maps of the rabbit cornea and porcine retina The system is then translated to in vivo imaging, for which quantified elasticity mapping of the rabbit retinal layers can be obtained. In addition, we have also fabricated an ARF-OCE catheter with a diameter of 3.5 mm, which was validated using phantom studies, and intravascular imaging was performed on a human cadaver artery. This study is a major stepping stone to the translation of the ARF-OCE technology in measuring the mechanical properties of tissues in clinical settings. Future studies using this technology include monitoring the retinal elasticity during and after electrode stimulation treatment and also intravascular elasticity imaging to diagnose atherosclerosis.

    Cover page: Development of acoustic radiation force optical coherence elastography system for in vivo mapping of biological tissuesCreative Commons 'BY' version 4.0 license
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2018)
    We present a class of novel system characterization methods for spectral-domain optical coherence tomography (SD-OCT) particularly on getting optimized axial resolution performance. Our schemes uniquely utilize the autocorrelation interference response, also known as the self-interference product, which is generated by the optical fields from the imaging sample in automatic interferences. In our methods, an autocorrelation-inducing calibration sample was prepared which was made by sandwiching glass plates. OCT images of the calibration sample were captured by an SD-OCT system under testing. And the image data were processed to find various system characteristics based on the unique properties of autocorrelation interferograms, free of dispersion- and polarization-involved modulations. First, we could analyze the sampling characteristic of the SD-OCT's spectrometer for spectral calibration that enables accurate linear-k resampling of detected spectral fringes. Second, we could obtain the systematic polarization properties for quantifying their impact on the achieved axial resolutions. We found that our methods based on the autocorrelation response provide an easy way of self-characterization and self-validation that is useful in optimizing and maintaining axial resolution performances. It was found very attractive that a variety of system characteristics can be obtained in a single-shot measurement without any increased system complexity.
      Cover page: Characterization of spectral-domain OCT with autocorrelation interference response for axial resolution performance.
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2019)
      Ciliary activity, characterized by the coordinated beating of ciliary cells, generates the primary driving force for oviduct tubal transport, which is an essential physiological process for successful pregnancies. Malfunction of the cilium in the fallopian tube, or oviduct, may increase the risk of infertility and tubal pregnancy that can result in maternal death. While many ex-vivo studies have been carried out using bright field microscopy, this technique is not feasible for the in-vivo investigation of oviduct ciliary beating frequency (CBF). Optical coherence tomography (OCT) has been able to provide in-vivo CBF imaging in a mouse model, but its resolution may be insufficient to resolve the spatial and temporal features of the cilium. Our group has recently developed the phase resolved Doppler (PRD) OCT method to visualize ciliary strokes at ultra-high displacement sensitivity. However, the cross-sectional field of view (FOV) may not be ideal for visualizing the surface dynamics of ciliated tissue. In this study, we report on the development of phase resolved Doppler spectrally encoded interferometric microscopy (PRD-SEIM) to visualize the oviduct ciliary activity within an en face FOV. This novel real time imaging system offers micrometer spatial resolution, sub-nanometer displacement sensitivity, and the potential for in-vivo endoscopic adaptation. The feasibility of the approach has been validated through ex-vivo experiments where the porcine oviduct CBF has been measured across different temperature conditions and the application of a drug. CBF ranging from 8 to 12 Hz have been observed at different temperatures, while administration of lidocaine decreased the CBF and deactivated the motile cilia. This study will serve as a stepping stone to in-vivo oviduct ciliary endoscopy and future clinical translations.
        Cover page: Characterization of oviduct ciliary beat frequency using real time phase resolved Doppler spectrally encoded interferometric microscopy.
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2017)
        Shear wave measurements for the determination of tissue elastic properties have been used in clinical diagnosis and soft tissue assessment. A shear wave propagates as a transverse wave where vibration is perpendicular to the wave propagation direction. Previous transverse shear wave measurements could detect the shear modulus in the lateral region of the force; however, they could not provide the elastic information in the axial region of the force. In this study, we report the imaging and quantification of longitudinal shear wave propagation using optical coherence tomography to measure the elastic properties along the force direction. The experimental validation and finite element simulations show that the longitudinal shear wave propagates along the vibration direction as a plane wave in the near field of a planar source. The wave velocity measurement can quantify the shear moduli in a homogeneous phantom and a side-by-side phantom. Combining the transverse shear wave and longitudinal shear wave measurements, this system has great potential to detect the directionally dependent elastic properties in tissues without a change in the force direction.
          Cover page: Longitudinal shear wave imaging for elasticity mapping using optical coherence elastographyCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2019)
          Retinal diseases, such as age-related macular degeneration (AMD), are the leading cause of blindness in the elderly population. Since no known cures are currently present, it is crucial to diagnose the condition in its early stages so that disease progression is monitored. Recent advances show that the mechanical elasticity of the posterior eye changes with the onset of AMD. In this work, we present a quantitative method of mapping the mechanical elasticity of the posterior eye using confocal shear wave acoustic radiation force optical coherence elastography (SW-ARF-OCE). This technique has been developed and validated with both an ex-vivo porcine tissue model and a customized in-vivo rabbit model, which both showed the quantified elasticity variations between different layers. This study verifies the feasibility of using this technology for the quantification and diagnosis of retinal diseases from the in-vivo posterior eye.
            Cover page: Confocal Shear Wave Acoustic Radiation Force Optical Coherence Elastography for Imaging and Quantification of the <i>In Vivo</i> Posterior EyeCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2020)
            Ciliary motion in the upper airway is the primary mechanism by which the body transports foreign particulates out of the respiratory system in order to maintain proper respiratory function. The ciliary beating frequency (CBF) is often disrupted with the onset of disease as well as other conditions, such as changes in temperature or in response to drug administration. Current imaging of ciliary motion relies on microscopy and high-speed cameras, which cannot be easily adapted to in-vivo imaging. M-mode optical coherence tomography (OCT) imaging is capable of visualization of ciliary activity, but the field of view is limited. We report on the development of a spectrally encoded interferometric microscopy (SEIM) system using a phase-resolved Doppler (PRD) algorithm to measure and map the ciliary beating frequency within an en face region. This novel high speed, high resolution system allows for visualization of both temporal and spatial ciliary motion patterns as well as propagation of metachronal wave. Rabbit tracheal CBF ranging from 9 to 13 Hz has been observed under different temperature conditions, and the effects of using lidocaine and albuterol have also been measured. This study is the stepping stone to in-vivo studies and the translation of imaging spatial CBF to clinics.
              Cover page: Spatial Mapping of Tracheal Ciliary Beat Frequency Using Real Time Phase-Resolved Doppler Spectrally Encoded Interferometric MicroscopyCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2017)
              The main cause of acute coronary events, such as thrombosis, is the rupture of atherosclerotic plaques. Typical intravascular optical coherence tomography (IVOCT) imaging systems that utilize a 1.3 μm swept source laser are often used for identifying fibrous cap thickness of plaques, yet cannot provide adequate depth penetration to resolve the size of the lipid pool. Here, we present a novel  IVOCT system with a 1.7 μm center wavelength swept light source that can readily penetrate deeper into the tissue because of the longer wavelength and allows for better identification of plaques due to the lipid absorption spectrum at 1.7 μm. Using this system, we have imaged a human coronary artery to evaluate the performance of the novel OCT system and verified the results by hematoxylin and eosin (H&E) histology. The significantly improved imaging depth and better identification sensitivity suggest that the 1.7 μm OCT system holds great potential  that can be further translated for in-vivo applications of atherosclerosis characterization.
                Cover page: Intravascular Optical Coherence Tomography for Characterization of Atherosclerosis with a 1.7 Micron Swept-Source LaserCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2016)
                Elastography provides a powerful tool for histopathological identification and clinical diagnosis based on information from tissue stiffness. Benefiting from high resolution, three-dimensional (3D), and noninvasive optical coherence tomography (OCT), optical micro-elastography has the ability to determine elastic properties with a resolution of ~10 μm in a 3D specimen. The shear wave velocity measurement can be used to quantify the elastic modulus. However, in current methods, shear waves are measured near the surface with an interference of surface waves. In this study, we developed acoustic radiation force (ARF) orthogonal excitation optical coherence elastography (ARFOE-OCE) to visualize shear waves in 3D. This method uses acoustic force perpendicular to the OCT beam to excite shear waves in internal specimens and uses Doppler variance method to visualize shear wave propagation in 3D. The measured propagation of shear waves agrees well with the simulation results obtained from finite element analysis (FEA). Orthogonal acoustic excitation allows this method to measure the shear modulus in a deeper specimen which extends the elasticity measurement range beyond the OCT imaging depth. The results show that the ARFOE-OCE system has the ability to noninvasively determine the 3D elastic map.
                  Cover page: 3D mapping of elastic modulus using shear wave optical micro-elastographyCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2018)
                  Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly (over the age of 60 years) in western countries. In the early stages of the disease, structural changes may be subtle and cannot be detected. Recently it has been postulated that the mechanical properties of the retina may change with the onset of AMD. In this manuscript, we present a novel, non-invasive means that utilizes synchronized acoustic radiation force optical coherence elastography (ARF-OCE) to measure and estimate the elasticity of cadaver porcine retina. Both regions near the optic nerve and in the peripheral retina were studied. An acoustic force is exerted on the tissue for excitation and the resulting tissue vibrations, often in the nanometer scale, are detected with high-resolution optical methods. Segmentation has been performed to isolate individual layers and the Young's modulus has been estimated for each. The results have been successfully compared and mapped to corresponding histological results using H&E staining. Finally, 64 elastograms of the retina were analyzed, as well as the elastic properties, with stiffness ranging from 1.3 to 25.9 kPa in the ganglion to the photoreceptor sides respectively. ARF-OCE allows for the elasticity mapping of anatomical retinal layers. This imaging approach needs further evaluation but has the potential to allow physicians to gain a better understanding of the elasticity of retinal layers in retinal diseases such as AMD.
                    Cover page: Quantified elasticity mapping of retinal layers using synchronized acoustic radiation force optical coherence elastographyCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2017)
                    We present a tri-modality imaging system and fully integrated tri-modality probe for intravascular imaging. The tri-modality imaging system is able to simultaneously acquire optical coherence tomography (OCT), ultrasound (US), and fluorescence imaging. Moreover, for fluorescence imaging, we used the FDA-approved indocyanine green (ICG) dye as the contrast agent to target lipid-loaded macrophages. We conducted imaging from a male New Zealand white rabbit to evaluate the performance of the tri-modality system. In addition, tri-modality images of rabbit aortas were correlated with hematoxylin and eosin (H&E) histology to check the measurement accuracy. The fully integrated miniature tri-modality probe, together with the use of ICG dye suggest that the system is of great potential for providing a more accurate assessment of vulnerable plaques in clinical applications.
                      Cover page: Fully integrated optical coherence tomography, ultrasound, and indocyanine green-based fluorescence tri-modality system for intravascular imaging.Creative Commons 'BY' version 4.0 license
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