用贝叶斯方法同时去噪、重建和追踪活体小鼠脑内突触,提升低信噪比成像下的追踪精度。
Bayesian In Vivo Tracking of Synapses using Joint Poisson Deconvolution and Diffeomorphic Registration

- 将突触建模为移动的点光源,联合泊松去卷积与微分配准进行统一建模。
- 在2周纵向数据上实现高密度突触的稳定追踪,准确率显著优于传统方法。
- 适合神经发育、认知研究及阿尔茨海默病等脑疾病中突触动态分析者使用。
突触是学习与记忆形成过程中动态重组的亚微米级结构。通过双光子显微镜对活体荧光标记的突触受体进行纵向成像,为研究大规模突触动态及其在神经系统疾病中的异常提供了可能。然而,由于激光功率低导致信噪比(SNR)低、散粒噪声大,以及组织在不同天数间存在非线性运动、荧光强度波动和显微镜点扩散函数(PSF)引起的显著模糊,突触检测与追踪面临挑战,尤其在高密度区域更为明显。本文提出一种基于模板的新型框架,将突触建模为随非线性组织变形而移动的可变亮度点源。采用统一的贝叶斯方法,构建包含微分映射(用于形变校正)、高斯点扩散函数(用于成像过程)和泊松观测模型(用于原始光子计数)的后验分布。该方法能同时:(1) 构建突触位置的概率模板;(2) 对图像数据去噪并去卷积;(3) 推断荧光强度;(4) 执行微分图像配准以校正组织运动;(5) 提供参数估计的置信区域。我们在一个2D+t模拟数据集和一个3D+t纵向活体小鼠突触成像数据集(连续两周)上验证了该框架的有效性。
原文摘要 · Abstract (English)
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.
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