Bayesian In Vivo Tracking of Synapses using Joint Poisson Deconvolution and Diffeomorphic Registration
使用联合泊松反卷积和微分同胚配准的贝叶斯体内突触追踪
Shashwat Kumar, Dominic M. Padova, Binish Narang, Gabrielle I. Coste, Austin R. Graves, Richard L. Huganir, Adam S. Charles, Michael I. Miller, Anuj Srivastava
AI总结 提出一种基于模板的贝叶斯框架,通过联合泊松反卷积和微分同胚配准,同时实现突触检测、去噪、荧光强度推断、组织运动校正和置信区间估计,用于低信噪比体内显微镜数据中的突触追踪。
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突触是密集排列的亚微米结构,在学习和记忆形成过程中动态重组。纵向体内成像荧光标记的突触受体为研究大规模突触动力学以及这些过程在神经疾病中如何被破坏提供了有希望的机会。然而,使用双光子显微镜的体内成像采用低激光功率,因此受到低信噪比和高散粒噪声、天与天之间的非线性组织运动、突触荧光的非平稳波动以及显微镜点扩散函数引起的显著模糊的影响。这些因素共同使得检测和追踪突触变得具有挑战性,尤其是在突触密度高的区域。本文提出了一种新颖的基于模板的框架,将突触建模为在非线性组织变形下移动的可变亮度点源。采用统一的贝叶斯方法,我们通过推导一个后验分布来将该模型应用于显微镜数据,该后验分布包含用于域扭曲的微分同胚映射、用于成像过程的高斯点扩散函数以及用于原始光子计数的泊松观测模型。贝叶斯解决方案同时:(1) 构建突触位置的概率模板,(2) 对图像数据进行去噪和反卷积,(3) 推断荧光强度,(4) 执行微分同胚图像配准以校正组织运动,以及(5) 为这些参数估计提供置信区域。我们在一个2D+t模拟数据集和一个在小鼠两周内成像的荧光突触的3D+t纵向体内显微镜数据集上展示了该框架。
Synapses are densely packed submicron structures that dynamically reorganize during learning and memory formation. Longitudinal \textit{in vivo} imaging of fluorescently tagged synaptic receptors offers a promising opportunity to study large-scale synaptic dynamics and how these processes are disrupted in neurological disease. However, in vivo imaging with 2-photon microscopy uses low laser power and therefore suffers from low signal-to-noise ratio (SNR) and high shot noise, nonlinear tissue motion between days, nonstationary fluctuations in synaptic fluorescence, and significant blur induced by the microscope point spread function (PSF). Together, these factors make it challenging to detect and track synapses, especially in regions with high synaptic density. This paper presents a novel template-based framework for modeling synapses as varying luminance point sources that move under a nonlinear tissue deformation. Taking a unified Bayesian approach, we apply this model to microscopy data by deriving a posterior that incorporates a diffeomorphic mapping for domain warping, a Gaussian point spread function for the imaging process, and a Poisson observation model for raw photon counts. The Bayesian solution simultaneously: (1) Constructs a probabilistic template of synapse locations, (2) denoises and deconvolves the image data, (3) infers fluorescence intensities, (4) performs diffeomorphic image registration to correct for tissue motion, and (5) provides confidence regions for these parameter estimates. We demonstrate the framework on both a 2D+t simulated dataset and a 3D+t longitudinal \textit{in vivo} microscopy dataset of fluorescent synapses imaged in a mouse over two weeks.