Optical imaging of tissue is the gold standard of biomedical imaging, especially in the central nervous system for high throughput structural and functional imaging of brain activity. The key advantage of optical methods is that light interacts with tissue non-invasively. Existing optical imaging techniques, however, suffer from an inability to deliver and collect light deep into the tissue with high spatial resolution. Scattering of light in tissue limits the resolution and penetration depth, rendering such methods based on external optics limited to the superficial layers of biological tissues. Additionally, in the context of the central nervous system, which harbors widely distributed neural circuits, system-wide interrogation would require either fast optical beam-steering capability or simultaneous multi-site illumination. Recent techniques based on patterning of light from outside the brain cannot reach deep into the tissue, since as light propagates through tissue, it undergoes diffraction, scattering, and absorption; as a result, the beam widens and the intensity of light rapidly falls below the threshold of excitation of opsins and optical reporters. The proposed project aims to address these shortcomings of the optical methods by using high frequency sound waves (ultrasound) to form a virtual relay lens in the tissue to access deep tissue for optical imaging. In this technique, the tissue itself is turned into an optical lens that enables imaging deeper structures. This ultrasonically defined lens can be moved around without disturbing the tissue for steerable imaging. This multidisciplinary project provides a unique educational and training environment for graduate and undergraduate students to learn about contemporary concepts in photonics, ultrasonics, and neural technologies for applications in functional and structural imaging of brain. Students from underrepresented minority groups will be trained through this research program.

In this interdisciplinary project, the researchers will develop a non-invasive alternative to endoscopic imaging of brain that usually involve implanting a graded-index (GRIN) lens into the brain. Non-invasive ultrasonic waves will be used to sculpt virtual optical relay lenses by confining and steering light deep into the tissue without having to insert physical GRIN lenses. The result of the proposed research on ultrasonic sculpting of virtual steerable optical lenses within the brain tissue for relay imaging will be a significant breakthrough to facilitate light-based methods for non-invasive imaging of brain tissue by addressing two unmet needs, i.e., noninvasive deep penetration and beam steering. This ultrasonically defined virtual lens can both deliver or collect light through the depth of the tissue. A phased array of ultrasonic transducers will be designed to form reconfigurable virtual relay lenses within the tissue. A model system in which to test and develop this technology is the mouse brain tissue. To further amplify the impact of the proposed project, the developed acousto-optic imaging technique will also be provided to different neurobiology labs for testing various neuroscience hypotheses using optical methods for brain imaging and stimulation. The proposed project advances frontiers of optical imaging by introducing a novel technique for non-invasive deep tissue penetration and real-time optical beam steering to enable targeted imaging of deep structures. This can potentially transform our ability to target specific pathways within the brain tissue in animal models. The results will have indirect clinical implications for humans.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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Carnegie-Mellon University
United States
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