In Vivo Optical Imaging of Ultrasound Retinal Stimulation

Stanford University, Stanford CA

Investigators

Abstract

The goal of this project is to use a newly developed, transparent ultrasound transducer together with in vivo optical imaging to study the direct effects of ultrasound on retinal ganglion cell (RGC) activity. Ultrasound stimulation of the eye has been demonstrated to preserve RGCs after optic nerve injury, making it a promising strategy for neuroprotection and vision preservation. Although the physical mechanisms of ultrasound stimulation have been explored in the ex vivo retina, its range of effective parameters in vivo and underlying biophysical mechanisms are not well understood. Due to the optical accessibility of the retina, RGC activity can be noninvasively monitored in vivo using Ca2+ imaging with genetically encoded calcium indicators. However, conventional ultrasound transducers are opaque and will block the light path for Ca2+ imaging by microscopy. To address this limitation, we have developed a novel class of transparent ultrasound transducers that facilitates in vivo Ca2+ imaging while providing ultrasound stimulation. With this new tool, we will study the mechanisms and therapeutic efficacy of ultrasound retinal stimulation. We propose to determine effective parameters for ultrasound retinal stimulation, and test its physical mechanisms and clinical applications for neuroprotection using in vivo 2-photon imaging and animal models. A multi-disciplinary team with complementary expertise is assembled to perform the proposed aims. The team consists of experts in transducer fabrication, ultrasound neuromodulation, retinal physiology and optic nerve disease. Ultrasound is an emerging, noninvasive technology explored for vision-preserving therapies. To apply ultrasound retinal stimulation in a safe and predictable manner, a detailed understanding of the effects of ultrasound on neural activity is required. By using new technology, this project addresses a critical need to understand the effects of ultrasound neuromodulation in the retina and other nervous systems in vivo, and also carries significant translational potential. Information about how ultrasound modulates RGC activity should allow us to develop safer and more effective ultrasound-based therapies for optic nerve disorders and retinal degenerations.