Deep and Chronic Imaging of Alzheimer’s Circuit Evolution in Transparent Live Mouse Brain

My vision is simple yet ambitious: to “let there be light in vivo.” I aim to develop technologies that allow us to deliver light into — and detect light from — living biological tissue deeply, efficiently, and noninvasively.

Light underpins some of the most powerful tools in modern biology and medicine, from fluorescence imaging and optogenetics to photodynamic therapies. Yet the body is inherently opaque. This opacity prevents us from directly observing the molecular and cellular processes that drive health and disease, and it limits physicians’ ability to diagnose and treat conditions without surgery.

My research tackles this fundamental barrier. By combining materials science, physics, and chemistry, my lab develops new strategies to bring light deep into living systems and to reversibly render tissue transparent. Our long-term goal is transformative: to safely and noninvasively turn the body’s opacity “on and off” on demand, enabling real-time visualization of cellular function and disease progression inside the living body.

Dr. Guosong Hong received his Ph.D. in chemistry from Stanford University in 2014 and then carried out postdoctoral studies at Harvard University. Dr. Hong joined Stanford as a Wu Tsai Neurosciences Institute faculty scholar and assistant professor of materials science and engineering in September 2018. His research integrates materials science, physics, and chemistry to address fundamental challenges in biology and medicine. The Hong Lab is internationally recognized for pioneering technologies in in-vivo optical transparency, deep-tissue light delivery, and biophotonics-enabled neurotechnology. In 2024, the Hong Lab reported the world’s first live transparent mice in Science, demonstrating that optical transparency in living animals can be achieved transiently and reversibly through materials-based control of light-tissue interactions. This discovery has since catalyzed a wave of follow-up studies worldwide, enabling new approaches to deep-tissue imaging, neural modulation, and light-based therapeutic applications. Dr. Hong’s contributions have been recognized with several major honors, including the NIH Pathway to Independence (K99/R00) Award, the MIT Technology Review ‘35 Innovators Under 35’ Award, the Science PINS Prize for Neuromodulation, the NSF CAREER Award, the Walter J. Gores Award for Excellence in Teaching, the Rita Allen Foundation Scholars Award, the Camille Dreyfus Teacher-Scholars Award, the Presidential Early Career Award for Scientists and Engineers (PECASE), the Vilcek Prize for Creative Promise in Biomedical Science, the inaugural SPIE Biophotonics Discovery Impact of the Year Award, and the Alfred P. Sloan Research Fellowship in Physics.

Alzheimer’s disease unfolds slowly, over many years, as the brain’s communication networks gradually fall out of sync. Yet most existing tools either view the whole brain without enough detail, or zoom in on tiny regions without being able to see the “big picture” as those regions change over time. This project aims to change that limited view by making it possible, for the first time, to repeatedly observe the same living neurons deep inside the brain as Alzheimer’s progresses. Building on a newly developed, safe, and reversible method that temporarily makes brain tissue — and other living tissues — transparent, we will noninvasively “look through” the brain of a living mouse and track how individual neurons and their connections change over months. By following neural circuits as they gradually lose function — rather than examining the brain at a single place and a single moment — this work seeks to reveal how memory and cognition break down at their most fundamental level. The ultimate goal is to create a dynamic, four-dimensional map of Alzheimer’s disease in action, opening a new window into how neurodegeneration unfolds and providing a powerful framework for studying brain disorders that evolve over time. By making the invisible progression of Alzheimer’s visible over time, this work offers new hope for understanding and eventually easing the burden of memory loss for patients and their families.

"The innovation of this work lies in making the invisible visible. For the first time, we will be able to watch how memory circuits function — and how they progressively break down — at the level of individual neurons throughout the course of Alzheimer’s disease, with potential applications to other neurodegenerative disorders. The impact I envision is deeply human — by understanding precisely how brain circuits fail, we can help guide earlier diagnosis and the development of more effective treatments, ultimately easing the burden on patients and their families."