2010 — 2014 |
Meyers, Bryan F Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Photoacoustic Endoscopy of Barretts Esophagus
DESCRIPTION (provided by applicant): We propose to develop novel photoacoustic endoscopy by miniaturizing photoacoustic imaging probes. The primary motivation is to overcome the depth limitation of existing endoscopic imaging technologies and to provide functional information sensitive to disease states. The improved imaging capabilities have the potential for early detection of cancer in the gastrointestinal tract. In a preliminary study, we demonstrated the feasibility of photoacoustic endoscopy through in situ and ex vivo animal experiments with our endoscopic probe prototype. We will show its full endoscopic imaging potential and develop broader application through various in vivo animal and human experiments. Additionally, we will advance the current technology by constructing smaller endoscopic probes that fit into generic endoscopes and by improving overall system performance. The specific aims of this project are as follows. Aim 1. Develop a next-generation photoacoustic endoscope system. We will develop a next-generation photoacoustic endoscopic system and improve the image resolution, field of view, scanning speed, and probe size. We will establish the necessary supporting, peripheral subsystems including a laser source and light delivery path, a stepper motor drive, a data acquisition subsystem, and a master control of all subsystems. Aim 2. Design and develop a piezoelectric ring probe of improved sensitivity. We will design and engineer ultrasonic transducers optimized for the proposed photoacoustic endoscope. The ultrasonic transducer is an essential component of the photoacoustic endoscopic system. The optimization of photoacoustic endoscopy depends on several transducer parameters: size, noise figure, and sensitivity. Aim 3. Validate the endoscopic system through phantom and animal experiments. Through phantom experiments, we will validate the performance of the endoscopic system by measuring the spatial resolution, imaging depth, signal-to-noise ratio, and frame rate. Moreover, we will demonstrate its endoscopic imaging potential through various animal experiments. Parts of the gastrointestinal tract, including the esophagus, large intestine, and rectum, and/or parts of the cardiovascular system of animals, will be imaged in vivo or ex vivo. Aim 4. Image Barrett's esophagus in vivo. First, we will image a series of human esophagus in patients with an established diagnosis of Barrett's esophagus to fine tune the photoacoustic imaging system while simultaneously obtaining mucosal biopsies of the distal esophagus. Second, we will compare the targeted photoacoustic images to the ex vivo histology of esophageal mucosal specimens to develop a classification system for photoacoustic images of Barrett's epithelium. Lastly, we will prospectively assess the agreement between the photoacoustic imaging system and standard clinical practice of 4 quadrant esophageal biopsy in a comparative study. The hypothesis is that ultrasound and photoacoustic imaging technologies in combination provide sufficient spatial resolution and contrast to diagnose Barrett's epithelium and Barrett's-associated neoplasia with high sensitivity and specificity.
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0.948 |
2012 — 2015 |
Chen, Zhongping (co-PI) [⬀] Silverman, Ronald H Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Elastographic Imaging of the Retina/Choroid in Age-Related Macular Degeneration @ Columbia University Health Sciences
DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is a disease of the retinal pigment epithelium characterized by the appearance of protein/lipid deposits (drusen), geographic atrophy and neovascularization. Techniques currently used for diagnostic imaging of AMD include indocyanine green dye or fluorescein angiography, autofluorescence imaging and optical coherence tomography (OCT). OCT images depict optical backscatter, caused by variation in local optical refractive index. The high resolution provided by OCT has proved invaluable for imaging structural changes associated with AMD. Nevertheless, our understanding of the pathobiology of this disease is uncertain. The development of high-resolution retinal/choroidal imaging modalities not dependent upon optical scattering offers a potential means for gaining new insights into the AMD disease process, early diagnosis and clinical management. In this project we propose to develop and test means for imaging the elastic properties of the retina/choroid by detection of minute displacements generated within these structures induced by acoustic radiation force. Such elastic changes at the level of Bruch's membrane and the choroid would be expected as a consequence of drusen deposition and altered microvascular patterns. Furthermore, tissue elastic changes are also known to be associated with the development of neovascularization. A capacity to image elastic alteration may provide a means to visualize precursors to pathologic changes associated with AMD disease progression. We propose to image the retina/choroid with high speed, high-resolution, enhanced-depth OCT and to observe minute displacements occurring upon exposure to acoustic radiation force at safe, diagnostic levels. We will utilize two techniques: acoustic radiation force impulse (ARFI) imaging, in which displacements are induced by a brief (order of 1 msec) impulse, and vibro-acoustography, in which displacements are induced by low-frequency (order of 1 kHz) vibrations induced by interaction of two ultrasound sources of slightly different frequency. Studies will be conducted with tissue phantoms, rabbit eyes, in a primate model of AMD and finally normal and AMD human subjects in which we will demonstrate alterations in retinal/choroidal elastic properties associated with specific pathologic conditions including drusen, geographic atrophy, and neovascularization.
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0.939 |
2013 — 2017 |
Shung, Kirk Zhou, Qifa Chen, Yong Liu, Ruibin |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Goali: Novel Piezoelectric Device Fabrication Using Digital Projection Based Additive Manufacturing @ University of Southern California
The research objective of this Grant Opportunity for Academic Liaison with Industry (GOALI) award is to solicit fundamental knowledge and understanding in fabricating piezoelectric devices with controlled shape and functional characteristics in order to develop an innovative and cost-effective additive manufacturing process for the nation's biomedical imaging industry. In the planned research, both the green-part fabrication for desired accuracy and resolution and the heat treatment procedure for required piezoelectric properties will be studied. The process modeling and related controlling methods will be established for the piezo-composite based additive manufacturing process. The effects of the addition of Sol-Gel solutions and related heat treatment procedures will be evaluated to understand their relations to piezoelectric properties. The property measurement and experimental validation will be performed with industrial partners to verify the capability of the additive manufacturing process.
Novel piezoelectric devices used in electronics, photonics, sensors and actuators require more complex shapes and better precision for improved performance. Research results of this GOALI award will provide knowledge and understanding to meet the critical need of improved accuracy and resolution control as well as the densification control in the piezo-composite based additive manufacturing process for piezoelectric device fabrication. A globally competitive biomedical imaging industry will contribute to the nation's economy and healthcare, and new piezoelectric devices with better quality and lower manufacturing cost will benefit consumers and the society. The project will also enhance the infrastructure for ultrasonic imaging research and education at the University of Southern California by providing a digital fabrication method with increased shape flexibility. Graduate and undergraduate engineering students and mid-career professionals will benefit through classroom instruction and involvement in the research. Outreach programs to high school students will be utilized to increase minority participation. The designed hands-on learning experience and exposure to advanced manufacturing applications will increase the interest of domestic students in science and engineering.
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1 |
2014 — 2021 |
Chen, Zhongping [⬀] Patel, Pranav (co-PI) [⬀] Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Phase Resolved Arf Optical Coherence Elastography For Intravascular Imaging @ University of California-Irvine
DESCRIPTION (provided by applicant): The broad, long term objective of the proposed grant is to develop an integrated multimodal intravascular imaging system that combines intravascular optical coherence tomography (OCT), ultrasound (US), and phase-resolved acoustic radiation force optical coherence elastography (ARF-OCE). The multimodal intravascular imaging system is unique in that it combines the advantages of the high spatial resolution of OCT, the broad imaging depth of US, and the biomechanical contrast of ARF-OCE. Visualizing plaques to help understand the progression of disease and to aid in diagnosis and treatment is highly desirable. Both in vitro and in vivo studies have shown that fatty tissue has a higher strain than fibrous plaques and that vulnerable plaques are in high strain areas surrounded by low strain areas. More recent studies have pointed to the vulnerability and the risk of rupturing of plaques being related to the stress on the fibrous cap, the cap thickness, arterial remodeling, and the composition of the plaques. Therefore, it is important to measure the biomechanical properties of the artery tissue to monitor the atherosclerosis to reduce the rupture proneness of an artery and to correlate with clinical symptoms and inflammation markers. The combined multimodal vascular imaging system will permit cross-sectional visualization of vasculature with high spatial resolution, broad imaging depth, and high biomechanical sensitivity, which is not possible by any of these technologies alone. The integrated OCT/US/ARF-OCE will provide the physician with a powerful tool for imaging, diagnosing, and managing vulnerable plaques. Furthermore, this multi-modal imaging strategy in a single system permits the use of a single disposable guide wire and catheter, thereby reducing costs to hospitals and patients, and improving prognosis by early detection. The specific aims are: (1) Design and develop an integrated intravascular OCT/US/ARF-OCE imaging probe, (2) Design and develop an integrated intravascular OCT/US/ARF-OCE system, (3) Develop algorithms for image reconstruction and biomechanical property determination, (4) Image cardiovascular plaques in rabbits and porcine animal models using an integrated OCT/US/ARF-OCE system, and (5) Demonstrate clinical applications of the integrated multimodal imaging system in pilot in vivo human subject studies. The proposed research is expected to have significant impact in the earlier detection, prevention, and treatment of cardiovascular diseases. PHS 398
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0.981 |
2015 — 2018 |
Chen, Zhongping [⬀] Patel, Pranav (co-PI) [⬀] Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Combined Oct/Us/Pat System For Intravascular Imaging @ University of California-Irvine
? DESCRIPTION (provided by applicant): Atherosclerosis is a progressive disease that is characterized by the accumulation of lipids, cholesterol, fibrous constituents, monocytes, and various other inflammatory cells in the arterial wall. Atherosclerosis is one of the major causes of morbidity and mortality in developed countries. The major cause of deaths from heart attacks (86%) and brain aneurysm (45%) are due to vulnerable plaques that rupture suddenly and trigger a blood clot or thrombus that blocks blood flow. Early detection of plaque lesions is the first and necessary step in preventing the lethal consequences of atherosclerosis. Diagnosis of the latent vulnerability of a plaque lesion relies on both tissue structural and chemical compositions. Multimodality intravascular imaging that can provide both structure and molecular information will provide clinicians with a critically important tool for diagnosing vulnerable plaques, monitoring the progression of disease, and evaluating the efficacy of intervention. The broad, long term objective of this proposal is to develop an integrated multimodal intravascular imaging system that combines intravascular ultrasound (IVUS), optical coherence tomography (OCT), and photoacoustic tomography (PAT). The multimodal intravascular imaging system is unique in that it combines the advantages of high spatial resolution of OCT, broad imaging depth of US, and molecular contrast of PAT. The integrated IVUS/OCT/PAT will provide the physician with a powerful tool for imaging, diagnosing, and managing vulnerable plaques. The specific aims are: (1) Develop a high-speed nanosecond fiber laser centered at 1730 nm for PAT imaging with lipid contrast; (2) Develop an integrated IVUS/OCT/PAT imaging catheter; (3) Develop a multimodality imaging system that combines IVUS/OCT/PAT; (4) Demonstrate real-time in vivo multimodality imaging of cardiovascular plaques in rabbit and porcine animal models. The proposed research requires an interdisciplinary team of scientists, engineers, and clinicians. We have assembled such a team: OCT/PAT group (Dr. Chen from BLI at UCI); IVUS/PAT group (Drs. Zhou and Shung from NIH Transducer Resource Center at USC); and Interventional cardiology group (Dr. Patel from Dept. of Cardiology at UCI). The proposed research is expected to have significant impact in the earlier detection, prevention, and treatment of cardiovascular diseases. PHS 398
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0.981 |
2016 — 2019 |
Chen, Zhongping (co-PI) [⬀] Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
High Resolution Elastograpy of Retina Under Prosthetic Electrical Stimulation @ University of Southern California
? DESCRIPTION (provided by applicant): Visual prostheses based on electrical stimulation of the retina are an effective approach for treating blindness in individuals with photoreceptor degenerative diseases (e.g., retinitis pigmentosa). The epiretinal strategy, which was pioneered by our team, involves implanting the stimulating electrodes near the inner retinal surface. Compared with other strategies, epiretinal implantation surgeries are easier and are at risk of fewer complications. Epiretinal stimulation electrodes consist of metallic micro-disks of platinum, iridium, or titanium and their oxides, embedded in a flexible insulating polymer substrate such as polyimide, parylene, or silicone elastomer. The electrode array can be monitored with funduscopy and removed or readjusted post-implantation with minimal surgery. Our experience with chronic implantation suggests that mechanical damage to the retina is a significant concern for epiretinal prosthesis patients with electrical stimulation. Furthermore, preclinical studies hae shown that prolonged electrical stimulation can damage the retina. However, detailed knowledge of how this damage manifests in retinal implant patients is currently lacking. Ocular imaging technologies available in the clinic, such as optical coherence tomography (OCT), are useful for patient monitoring but provide only limited information about retinal structure. Thus, there is a need for novel imaging modalities that can measure the fundamental mechanical properties of the retina over time in retinal prosthesis patients. The goal of this study is to develop and characterize novel tools for imaging the elastic properties of the retina under prosthetic electrical stimulation. To address this goal, we propose to use phase-resolved OCT to detect minute displacements induced by acoustic radiation force (ARF) in the retinal tissue layers. This will enable us to generate images depicting local displacements with nanometer resolution, providing details about the elastic properties of the retina that cannot be obtained with current imaging methods. We will also develop ultrasound (US) convex transducer arrays that can monitor retinal detachment and edema through the thin stimulating electrodes in areas where tissue damage is most likely to occur. We'll design and develop two convex single crystal arrays for imaging and an ARF transducer and integrated convex array ARF-optical coherence elastography (OCE) system that enables co-registered OCT, US, and ARF- OCE imaging; Model and measure the elastic properties of the retina with electrode array and conduct ex-vivo and in-vivo rabbit eye imaging to assess performance. Use ARF-OCE to detect retinal damage caused by mechanical stress and electrical stimulation.
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1 |
2017 — 2021 |
Ferrara, Katherine W [⬀] Trahey, Gregg E. (co-PI) [⬀] Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Large Aperture and Wideband Modular Ultrasound Arrays For the Diagnosis of Liver Cancer @ University of California At Davis
Our project has two fundamental goals: 1) develop modular large aperture, high channel count arrays with associated electronics and make these modules widely available to the academic community, and 2) use these arrays to improve abdominal ultrasound (US) for the diagnosis of liver cancer, particularly for difficult to image patients. The overall 5-year relative survival rate for patients with primary liver cancer is 16%. Imaging is used to monitor liver disease resulting from viral infections or cirrhosis and to detect a transition to malignancy, and ultrasound is the only recommended method for screening such patients at risk for cancer. Yet, in patients with an abdominal wall thickness greater than 2.5 cm, only 33% of lesions were detected. More than 2/3 of Americans are now overweight or obese and larger channel count arrays and larger array footprints will improve imaging within this population and improve the detection of small lesions in the general population. Our approach addresses improved resolution (large aperture and bandwidth), sensitivity (single crystal transducers), high frame rate for super-resolution imaging (hundreds of frame/sec feasible), yield (array is composed of high yield modules), and image contrast (new switching capabilities enable new beamformation methods). Lateral US resolution is inversely proportional to the transducer aperture and consequently, improved resolution requires an increased number of transducer elements and electronic channels as well as advanced beam formation methods. Even in the presence of aberrating tissues the contrast achieved from an extended aperture facilitates the visualization of small structures. We propose to create PIN-PMN-PT array modules of dimension 16 elements (azimuth) by 32 elements (elevation) which will be combined to form large arrays. The user selectable ASIC matrices provide the opportunity to select: 512 elements from within a single module, to combine mirrored elements in elevation or to combine neighboring elements in azimuth or elevation. As a result, 4096 elements within the large aperture array can simultaneously be addressed from a programmable scanner. Preliminary work has resulted in the fabrication of prototype array and ASIC modules. The UC Davis team has been one of the first to produce multi-frequency arrays; USC has pioneered high frequency arrays and is currently home to Wodnicki (20 years of experience in ultrasound ASIC development at GE) and will collaborate with us on the development of high channel count arrays; Duke University has pioneered the development of strategies to use large apertures; Verasonics is the leading manufacturer of programmable ultrasound systems and will work with us to develop data handling methods and to distribute components to the ultrasound community; Sonic Concepts will manufacture the resulting arrays; and GE has offered support as an external advisor on the incorporation of these arrays into other commercial systems. This unique team will develop the technology, evaluate its use in a human study and will disseminate the technology.
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0.976 |
2018 — 2021 |
Chen, Zhongping (co-PI) [⬀] Sigal, Ian A Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
High-Resolution Elastographic Assessment of the Optic Nerve Head @ University of Southern California
Abstract Glaucoma is a leading cause of irreversible blindness worldwide, affecting over 2.2 million Americans. With an aging population, it is estimated that by 2020 the number of people suffering glaucoma will reach 80 million worldwide, with 11 bilaterally blind. The goal of this study is to develop a novel tool for imaging and measuring elastic properties of the optic nerve head (ONH) and lamina cribrosa (LC) non-invasively. To address this goal, we propose to use phase-resolved OCT to detect small displacements induced by acoustic radiation force (ARF) in the ONH. We further propose to build a novel single crystal 2D array operating in the 4~10 MHz range to generate the ARF pushing force. We propose to use single crystal ultrasound transducers for increased sensitivity. The combined system will enable us to generate images depicting local displacements with nanometer resolution. Using state-of-the-art numerical models this data will be integrated with the complex tissue macro and microstructure to determine the anisotropic, inhomogeneous elastic properties of the tissues of the ONH with high resolution and sensitivity. This will allow us to characterize in detail the association between age, race and gender on the mechanical properties of the tissues of the ONH. Our Specific Aims are: Specific Aim 1: Develop single crystal 2D ultrasound array for ARF pushing force generation. Specific Aim 2: Develop an integrated 2D array ARF-Optical coherence elastography (OCE) system that enables coregistered OCT, US, and ARF-OCE imaging. Specific Aim 3: Develop and validate numerical models that integrate the experimental data from Aims 1 and 2 to determine the local mechanical properties of the LC and ONH. Specific Aim 4: Conduct ex-vivo elastography of human cadaveric and rabbit eyes to establish the capability and assess the performance of the ARF-OCE system to detect changes in ONH and LC tissue properties associated with age, gender and species. In human eyes, we will also determine differences due to race or disease and between regions of the ONH. Specific Aim 5: Demonstrate preclinical imaging capability with in-vivo imaging of LC and ONH in rabbit eyes using ARF-OCE system and optimize system for in-vivo imaging.
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1 |
2019 — 2020 |
Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Non-Invasive Ultrasound Stimulated Retinal Prosthesis @ University of Southern California
Abstract Age-related macular degeneration and retinitis pigmentosa lead to loss of retinal photoreceptor cells, causing blindness in thousands of people each year. Retinal prosthetic devices treat these incurable conditions by electrically or chemically stimulating surviving retinal neurons with implanted devices in the eye. However, existing devices are very expensive, invasive, and require complex implantation surgeries. Here we propose to explore a new approach in retinal prosthetics that is entirely noninvasive. Previous studies have demonstrated the feasibility of ultrasound to elicit neural activity in the rat hippocampus and motor cortex, and salamander retina cell. We recently demonstrated that a focused single element ultrasound transducer can elicit spiking activity in mammalian retinal neurons. In order to develop potential ultrasound prosthetic devices, we have to overcome several technical challenges: 1) Engineer an ultrasound device that is safe and effective (i.e., optimized) for retinal stimulation. 2) Develop three-dimensional mapping of neural activity in the retinal neural network under acoustic stimulation. Such an imaging method is essential for studying the biological mechanism of ultrasound stimulation and functional evaluation of ultrasound stimulation protocols. The goal of this study is to develop ultrasound stimulation by using phased array that can potentially replace invasive prosthetic electrical stimulation for retina. The first, we will develop specialized ultrasonic single- element transducer/phased arrays for retinal stimulation; we will design an optimal ultrasound stimulation paradigm to produce controllable and consistent retinal responses with high spatiotemporal resolution. The purpose of this study is two-fold: 1) to investigate biophysical mechanisms of ultrasound stimulation on retinal neurons, and 2) to conduct functional testing of the ultrasound devices developed. Finally, in vitro and in vivo rabbit studies using integrated ultrasound stimulation will be developed.
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1 |
2021 |
Zhou, Qifa |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Biomechanical Mapping of the Optic Nerve Head and Peripapillary Sclera Using High Frequency Ultrasonic Elastography @ University of Southern California
Project Summary Glaucoma is a leading cause of irreversible blindness worldwide, affecting over 2.2 million Americans. With an aging population, it is estimated that by 2020 the number of people suffering from glaucoma will reach 80 million worldwide, with 11 million being bilaterally blind. Although elevated intraocular pressure (IOP) is the primary risk factor for the development of glaucomatous optic nerve damage , the mechanisms by which elevated IOP eventually leads to damage are still unclear. Thus, there is a need to develop novel non-invasive imaging modalities that can measure the fundamental mechanical properties of the posterior sclera, and characterize how they contribute to damage in patients particularly as it relates to age, race, and severity of glaucomatous damage. Such a tool would be an important step forward in ocular research and clinical practice, providing the much-needed ability to evaluate the risk of disease based on person- and eye-specific characteristics. The goal of this study is to develop a novel high-resolution ultrasound-based imaging platform non-invasively measure biomechanical properties of the posterior sclera. To address this goal, we propose two imaging systems utilizing dual frequency configuration. One system consists of a low-frequency (4.5 MHz) ring shape transducer to ?push? the tissue, and a needle single element transducer inside to ?track? micron-level displacement; Another system is to replace the needle transducer with a high-frequency single crystal linear phased array as receiver for elastography imaging to first acquire real time and high speed elastography imaging of the posterior sclera. 2D/3D acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) will be performed on ex-vivo unscaled rabbit sclera that will be preloaded with various IOP levels for evaluation. Our preliminary results have demonstrated the principle of using the dual frequency ultrasonic elastography technique on obtaining the biomechanical properties of the sclera and cornea. Integrating high-resolution ARFI imaging with quantified tissue stiffness measurements via the propagation speed of the associated shear wave can potentially allow us to characterize in detail the association between age and gender on the mechanical properties of the sclera and allow us to explore the relationship with glaucoma
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1 |