KAIST

< Professor Iksung Kang, KAIST >

Observing the depths of a living brain with clarity has traditionally required expensive, high-end equipment. However, a KAIST research team has advanced neuroscience research by developing a physics-based AI computational algorithm that restores blurred images into sharp ones without the need for additional optical measurement hardware.

KAIST (President Kwang Hyung Lee) announced on April 21st that Professor Iksung Kang (School of Electrical Engineering), in collaboration with Professor Na Ji's research team at UC Berkeley, has developed a technology that accurately corrects image aberrations in microscopes used for live biological imaging. Notably, the experimental design and algorithm development – the core components of this technology – were led by Professor Kang during his postdoctoral fellowship in Professor Na Ji’s group. This breakthrough was achieved using Neural Fields — a neural network-based technology that continuously represents 3D spatial structures to simultaneously reconstruct clear images and volumetric forms.

The research team utilized Two-Photon Fluorescence Microscopy, a core technology for observing deep within living biological tissues by using two low-energy photons simultaneously to selectively illuminate specific points. However, as light passes through thick tissue, it bends and scatters, causing the image to become blurred — much like how objects appear distorted underwater. This phenomenon is known as optical aberration.

Previously, correcting these distortions required adding complex and costly hardware, such as wavefront sensors, which measure exactly how much the light path has deviated.

< Framework for Integrated Distortion Correction in Two-Photon Fluorescence Microscopy >

In contrast, the research team developed an algorithm that inversely calculates how light was distorted using only the captured image data and corrects it. In other words, it is a method of restoring image clarity by analyzing blurred photos, without relying on any additional equipment.

The core of this technology is a machine learning algorithm based on the Neural Fields model. This algorithm tracks the distortion process that occurs as light travels, implementing an integrated technology that compensates not only for optical aberrations caused by biological tissue but also for microscopic movements of the living specimen and alignment errors of the microscope itself.

As a result, the team successfully and reliably obtained high-resolution, high-contrast images from deep within biological tissues, without any separate aberration measurement or correction devices.

This research is particularly significant because it overcomes the conventional limitation that “better images require more expensive equipment” by solving the problem through a software-based approach. This is expected to lower the burden of research equipment costs and allow more researchers to perform precise brain observations.

< Comparison of images using a framework that integrates correction for optical aberrations, sample motion, and microscope errors (AI-generated image) >

Professor Iksung Kang stated, “This research opens the way to see more accurately inside living organisms by combining optics and artificial intelligence technology. Moving forward, we plan to develop this into an intelligent optical imaging system where the microscope itself finds the optimal image.”

This study was published on April 13th in Nature Methods, a leading methodology journal in the field of life sciences.

• Paper Title: Adaptive optical correction for in vivo two-photon fluorescence microscopy with neural fields
• DOI: 10.1038/s41592-026-03053-6
• Authors: Iksung Kang (KAIST, Co-corresponding & First Author), Hyeonggeon Kim, Ryan Natan, Qinrong Zhang, Stella X. Yu, & Na Ji (UC Berkeley, Co-corresponding Author)