New technologies for improving the accuracy of neuroimaging: Stochastic Gaussian-masked denoiser enhances subcellular structures and neural dynamics

Gu, Yuanjie1,#; Wang, Yiqun1,#; Zhao, Zhenyao1; Lu, Jun1; Xu, Lei1; Lu, Zhi2,*; Dong, Biqin1,*


1College of Biomedical Engineering, Yiwu Research Institute, Fudan University, Shanghai, China

2Department of Psychological and Cognitive Sciences, Tsinghua University, Beijing, China

*Correspondence to: Biqin Dong, PhD, dongbq@fudan.edu.cn; Zhi Lu, PhD, luzhi@tsinghua.edu.cn

#Both authors contributed equally to this work and share first authorship.


Funding:This work was supported in part by the National Key R&D Program of China, No. 2022YFF0708700 (to BD), Shanghai Pilot Program for Basic Research, No. 22TQ020 (to BD), Young Scientists Fund of Beijing Natural Science Foundation, No. 4254114 (to ZL), and National Natural Science Foundation of China, No. 62575154 (to ZL).

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0.

Advanced Technology in Neuroscience 3(1):p 16-20, Jan–Mar 2026. | DOI: 10.4103/ATN.ATN-D-25-00020


Abstract

Fluorescence microscopy is inherently susceptible to acquisition noise, which obscures critical subcellular structures and crucial neural dynamics. To address this, we introduce the stochastic Gaussian-masked autoencoder (GaMA), a zero-shot denoising framework that leverages the intrinsic characteristics of microscopy noise.GaMA strategically applies stochastic Gaussian masks, statistically conjugate to the wide-band noise, to induce antipodal signal cancellation while preserving genuine biological structures. This approach exploits the physical correspondence between mask and noise distributions for effective noise nullification, eliminating the need for training data.Validated on diverse imaging modalities, GaMA robustly enhances super-resolution single-molecule localization microscopy (e.g., enabling precise microtubule reconstruction) and critically, faithfully recovers subtle neural dynamics in functional Drosophila whole brain calcium imaging. Operating at > 45 frames per second, GaMA facilitates real-time denoising of dynamic neural processes otherwise compromised by noise, significantly enhancing the accuracy of downstream quantitative analysis in neuroimaging applications.



摘要

荧光显微镜天生容易受到采集噪声的影响,这会遮蔽关键的亚细胞结构和重要的神经动力学。为解决这一问题,我们提出基于随机高斯掩码的自编码器(GaMA),这是一个无需训练数据的降噪框架,利用显微镜噪声的内在特性。GaMA通过战略性地应用与宽带噪声统计共轭的随机高斯掩码,实现对立信号抵消的同时保留真实生物结构。该方法利用掩码与噪声分布之间的物理对应关系实现有效降噪,无需训练数据。在多种成像模态中经过验证,GaMA 能够稳健地提升超分辨率单分子定位显微镜(例如实现精确的微管重建)的性能,并关键性地忠实恢复果蝇全脑钙成像中微妙的神经动态。以超过 45 帧每秒的速度运行,GaMA 能够实现动态神经过程的实时去噪,这些过程原本会因噪声而受损,从而显著提升神经成像应用中下游定量分析的准确性。