Due to the multiple scattering of light in biomedical tissue, the imaging depth of conventional optical coherence tomography is limited to 1-2 millimeters. In this research, a reflection-matrix-method-based optical coherence tomography has been developed to extend the imaging depth into scattering medium. After obtaining the matrix, singular value decomposition and imaging reconstruction are carried out in the post-process to recover the target image beneath turbid media. Specifically, in order to speed up the matrix measurement and reduce the phase noises during the acquisition process, wide-field heterodyne detection is adopted in our system by using a high-speed lock-in camera.
The mechanosensitivity of the optic nerve head (ONH) plays a pivotal role in the pathogenesis of glaucoma. Characterizing elasticity of the ONH over changing physiological pressure may provide a better understanding of how changes in intraocular pressure (IOP) lead to changes in the mechanical environment of the ONH. Optical coherence elastography (OCE) is an emerging technique that can detect tissue biomechanics noninvasively with both high temporal and spatial resolution compared with conventional ultrasonic elastography. We describe a confocal OCE system in measuring ONH elasticity in vitro, utilizing a pressure inflation setup in which IOP is controlled precisely. We further utilize the Lamb wave model to fit the phase dispersion curve during data postprocessing. We present a reconstruction of Young’s modulus of the ONH by combining our OCE system with a Lamb wave model for the first time. This approach enables the quantification of Young’s modulus of the ONH, which can be fit using a piecewise polynomial to the corresponding IOP.
Oviduct and fallopian tube cilia serve as the primary means of tubal transport in the human reproductive system, with ciliated cells increasing from the isthmus to the infundibulum portions. Ciliary health is directly related to reproductive conditions such as tubal infertility and ectopic pregnancy. The ciliary beat frequency (CBF) changes over the ovarian cycle and is affected by both hormonal and neuronal stimuli, but is poorly understood in the natural environment due to limitations in current technology. Current techniques to measure ciliary beat frequency include high-speed video imaging, video microscopy, and optical methods, but access to minimally invasive in vivo imaging remains a challenge. A technology that enables the high-speed, high resolution, in-vivo imaging of the oviduct is essential for gaining insight into the natural ciliary activity in the oviduct, as well as the changes that take place with reproductive diseases. In this study, we report on the development of a spectrally-encoded interferometric microscopy (SEIM) system to visualize and analyze the spatial CBF of porcine oviduct cilia. We demonstrate the change in CBF from (7 to 12 Hz) that occurs under different temperature conditions from 23 to 29 degrees as well as the effects of lidocaine, where synchronized ciliary motion is disrupted. In addition, we examine the differences in ciliary activity between the infundibulum and ampulla portions of the fallopian tube. The results show that the SEIM system has the feasibility to detect CBF and ciliary acitivity in ex-vivo tissues with the potential to translate to minimally invasive in-vivo imaging.
Ciliary motion in the upper airway is the primary mechanism by which the body transports foreign particulate 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, and phase-resolved Doppler (PRD) algorithm can be integrated to measure the ciliary beating direction and amplitude with nanometer sensitivity. However, since ciliary activity naturally happens on the tissue surface, enface imaging modalities should be more suitable than cross-sectional ones such as OCT. 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 with nanometer sensitivity. Rabbit tracheal CBF ranging from 9 to 13 Hz have 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 in clinics.
Colorectal cancer, the third most common type of cancer globally, has ~1.4 million new cases and 694,000 deaths annually. Endoscopic photoacoustic (PA) imaging is a non-invasive imaging modality that provides structural, functional and molecular information while maintaining a deep depth. Several groups have reported different designs of endoscopic PA imaging systems that represent a significant step forward for the characterization of gastrointestinal (GI) cancer. However, these imaging systems are still not adequate for in-vivo clinical translation due to insufficient field-of-view, large probe diameters, and slow imaging speed. Endoscopic dual-modality photoacoustic and ultrasound imaging has the potential for early detection of cancer in the gastrointestinal tract. Currently, slow imaging speed is one of the limitations for clinical translation. In this study, we demonstrate an integrated endoscopic PA and US imaging system. Utilizing a high repetition rate pulsed laser, optimized rotary joint as well as proximal scanning method, this integrated imaging system is able to obtain morphological tissue information and vasculature of the GI tract simultaneously at a high imaging speed up to 50 frames/s (the fastest speed reported to date). We conducted in-vivo animal studies to demonstrate the performance of our imaging system for evaluating the GI tract. The results obtained from the in-vivo rat experiment showed that the typical layered architecture and vasculature can be identified by this integrated system with a high imaging speed.
Age-related macular degeneration is the leading cause of blindness in the elderly population, with a high demand for early diagnosis since the symptoms are irreversible. Current structural and functional imaging modalities include fundus autofluorescence, optical coherence tomography, and angiography, and are often not sufficient for early stage detection, which is mostly characterized by changes in tissue composition. A technology that enables the in-vivo imaging of the posterior ocular globe is essential for gaining insight into the natural mechanical anatomy of the eye, as well as the changes that take place with ocular diseases. However, in-vivo mechanical imaging of the retina remains a challenge and is currently not available. In this study, we report on the development of acoustic radiation force optical coherence elastography (ARF-OCE) to visualize and quantify the stiffness map of in-vivo retinal tissues based on the Voigt model. We demonstrate the elasticity mapping of an in-vivo rabbit retina, showing the stiffness variations across 5 different layers, ranging from 3 kPa to 16 kPa on the ganglion to the sclera sides. In addition, we introduce a diseased rabbit model based primarily on blue light exposure, and have found a difference in the layered stiffness where inflammation occurred. The results show that the ARF-OCE system has the capability to noninvasively detect tissue abnormalities in-vivo, and represents a significant step toward the development of the ARF-OCE system for clinical use.
Age-related macular degeneration (AMD) is an eye condition that is considered to be one of the leading causes of blindness among people over 50. Recent studies suggest that the mechanical properties in retina layers are affected during the early onset of disease. Therefore, it is necessary to identify such changes in the individual layers of the retina so as to provide useful information for disease diagnosis. In this study, we propose using an acoustic radiation force optical coherence elastography (ARF-OCE) system to dynamically excite the porcine retina and detect the vibrational displacement with phase resolved Doppler optical coherence tomography. Due to the vibrational mechanism of the tissue response, the image quality is compromised during elastogram acquisition. In order to properly analyze the images, all signals, including the trigger and control signals for excitation, as well as detection and scanning signals, are synchronized within the OCE software and are kept consistent between frames, making it possible for easy phase unwrapping and elasticity analysis. In addition, a combination of segmentation algorithms is used to accommodate the compromised image quality. An automatic 3D segmentation method has been developed to isolate and measure the relative elasticity of every individual retinal layer. Two different segmentation schemes based on random walker and dynamic programming are implemented. The algorithm has been validated using a 3D region of the porcine retina, where individual layers have been isolated and analyzed using statistical methods. The errors compared to manual segmentation will be calculated.
KEYWORDS: Medical laser equipment, Optical testing, Elastography, Wave propagation, Near field optics, Tissue optics, Coherence (optics), Transducers, Tissues, 3D modeling
Shear wave measurement enables quantitative assessment of tissue viscoelasticity. In previous studies, a transverse shear wave was measured using optical coherence elastography (OCE), which gives poor resolution along the force direction because the shear wave propagates perpendicular to the applied force. In this study, for the first time to our knowledge, we introduce an OCE method to detect a longitudinally polarized shear wave that propagates along the force direction. The direction of vibration induced by a piezo transducer (PZT) is parallel to the direction of wave propagation, which is perpendicular to the OCT beam. A Doppler variance method is used to visualize the transverse displacement. Both homogeneous phantoms and a side-by-side two-layer phantom were measured. The elastic moduli from mechanical tests closely matched to the values measured by the OCE system. Furthermore, we developed 3D computational models using finite element analysis to confirm the shear wave propagation in the longitudinal direction. The simulation shows that a longitudinally polarized shear wave is present as a plane wave in the near field of planar source due to diffraction effects. This imaging technique provides a novel method for the assessment of elastic properties along the force direction, which can be especially useful to image a layered tissue.
Age-related macular degeneration and keratoconus are two ocular diseases occurring in the posterior and anterior eye, respectively. In both conditions, the mechanical elasticity of the respective tissues changes during the early onset of disease. It is necessary to detect these differences and treat the diseases in their early stages to provide proper treatment. Acoustic radiation force optical coherence elastography is a method of elasticity mapping using confocal ultrasound waves for excitation and Doppler optical coherence tomography for detection. We report on an ARF-OCE system that uses modulated compression wave based excitation signals, and detects the spatial and frequency responses of the tissue. First, all components of the system is synchronized and triggered such that the signal is consistent between frames. Next, phantom studies are performed to validate and calibrate the relationship between the resonance frequency and the Young’s modulus. Then the frequency responses of the anterior and posterior eye are detected for porcine and rabbit eyes, and the results correlated to the elasticity. Finally, spatial elastograms are obtained for a porcine retina. Layer segmentation and analysis is performed and correlated to the histology of the retina, where five distinct layers are recognized. The elasticities of the tissue layers will be quantified according to the mean thickness and displacement response for the locations on the retina. This study is a stepping stone to future in-vivo animal studies, where the elastic modulus of the ocular tissue can be quantified and mapped out accordingly.
Changes in tissue biomechanical properties often signify the onset and progression of diseases, such as in determining the vulnerability of atherosclerotic plaques. Acoustic radiation force optical coherence elastography (ARF-OCE) has been used in the detection of tissue elasticity to obtain high-resolution elasticity maps. We have developed a probe-based ARF-OCE technology that utilizes a miniature 10 MHz ring ultrasonic transducer for excitation and Doppler optical coherence tomography (OCT) for detection. The transducer has a small hole in the center for the OCT light to propagate through. This allows for a confocal stress field and light detection within a small region for high sensitivity and localized excitation. This device is a front-facing probe that is only 3.5 mm in diameter and it is the smallest ARF-OCE catheter to the best of our knowledge. We have tested the feasibility of the probe by measuring the point displacement of an agarose tissue-mimicking phantom using different ARF excitation voltages. Small displacement values ranging from 30 nm to 90 nm have been detected and are shown to be directly proportional to the excitation voltage as expected. We are currently working on obtaining 2D images using a scanning mechanism. We will be testing to capture 2D elastograms of phantoms to further verify feasibility, and eventually characterize the mechanical properties of cardiovascular tissue. With its high portability and sensitivity, this novel technology can be applied to the diagnosis and characterization of vulnerable atherosclerotic plaques.
Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.
High-resolution elasticity mapping of tissue biomechanical properties is crucial in early detection of many diseases. We report a method of acoustic radiation force optical coherence elastography (ARF-OCE) based on the methods of vibroacoustography, which uses a dual-ring ultrasonic transducer in order to excite a highly localized 3-D field. The single element transducer introduced previously in our ARF imaging has low depth resolution because the ARF is difficult to discriminate along the entire ultrasound propagation path. The novel dual-ring approach takes advantage of two overlapping acoustic fields and a few-hundred-Hertz difference in the signal frequencies of the two unmodulated confocal ring transducers in order to confine the acoustic stress field within a smaller volume. This frequency difference is the resulting “beating” frequency of the system. The frequency modulation of the transducers has been validated by comparing the dual ring ARF-OCE measurement to that of the single ring using a homogeneous silicone phantom. We have compared and analyzed the phantom resonance frequency to show the feasibility of our approach. We also show phantom images of the ARF-OCE based vibro-acoustography method and map out its acoustic stress region. We concluded that the dual-ring transducer is able to better localize the excitation to a smaller region to induce a focused force, which allows for highly selective excitation of small regions. The beat-frequency elastography method has great potential to achieve high-resolution elastography for ophthalmology and cardiovascular applications.
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