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.

Public Health Relevance

In this proposal, we aim to use phase-resolved OCT to detect small displacements in the optic nerve head (ONH) induced by acoustic radiation force (ARF). We further propose to build a novel single crystal 2D array operating in the 4~10MHz range to generate the ARF pushing force. The combined system will enable us to generate images depicting local displacements of the ONH with a level of detail that cannot be obtained with the current imaging methods, and that can potentially be used as a clinical tool.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY028662-02
Application #
9663955
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Liberman, Ellen S
Project Start
2018-04-01
Project End
2022-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Southern California
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089