近日，美国波士顿大学的Lei Tian及其研究团队取得一项新进展。经过不懈努力，他们实现基于半监督数字染色和连续切片光学相干断层成像的增强型多尺度人脑成像。相关研究成果已于2025年1月20日在国际知名学术期刊《光：科学与应用》上发表。

该研究团队提出一种新颖的3D成像框架，将连续切片光学相干断层成像（S-OCT）与深度学习数字染色（DS）模型相结合。这种增强的成像方式集成了高通量3D成像、低样本变异性和高解释性，非常适用于3D组织学研究。研究人员开发了一种新型的半监督学习技术，以在弱配对图像上促进DS模型的训练，从而实现S-OCT到加利亚斯银染试剂的转换。

研究人员在多种人类大脑皮层样本上展示了数字染色的效果，实现了稳定的染色质量，并增强了皮层层边界的对比度。此外，研究人员还证明，数字染色在立方厘米级的组织块上能够保持3D几何形状，从而可以可视化白质中的中观尺度血管网络。研究人员相信，这一技术具有对脑组织进行高通量、多尺度成像的潜力，并可能促进对大脑结构的研究。

据悉，神经科学领域的一大挑战在于，如何在不同尺度下可视化人脑的结构。传统组织学方法能够揭示大脑在微观和中观尺度上的特征，但存在染色变异性、组织损伤和形变等问题，这阻碍了准确的三维重建。新兴的无标记连续切片光学相干断层成像（S-OCT）技术为样本提供了均匀的三维成像能力，尽管其对皮质特征敏感，但在组织学解释性方面表现欠佳。

附：英文原文

Title: Enhanced multiscale human brain imaging by semi-supervised digital staining and serial sectioning optical coherence tomography

Author: Cheng, Shiyi, Chang, Shuaibin, Li, Yunzhe, Novoseltseva, Anna, Lin, Sunni, Wu, Yicun, Zhu, Jiahui, McKee, Ann C., Rosene, Douglas L., Wang, Hui, Bigio, Irving J., Boas, David A., Tian, Lei

Issue&Volume: 2025-01-20

Abstract: A major challenge in neuroscience is visualizing the structure of the human brain at different scales. Traditional histology reveals micro- and meso-scale brain features but suffers from staining variability, tissue damage, and distortion, which impedes accurate 3D reconstructions. The emerging label-free serial sectioning optical coherence tomography (S-OCT) technique offers uniform 3D imaging capability across samples but has poor histological interpretability despite its sensitivity to cortical features. Here, we present a novel 3D imaging framework that combines S-OCT with a deep-learning digital staining (DS) model. This enhanced imaging modality integrates high-throughput 3D imaging, low sample variability and high interpretability, making it suitable for 3D histology studies. We develop a novel semi-supervised learning technique to facilitate DS model training on weakly paired images for translating S-OCT to Gallyas silver staining. We demonstrate DS on various human cerebral cortex samples, achieving consistent staining quality and enhancing contrast across cortical layer boundaries. Additionally, we show that DS preserves geometry in 3D on cubic-centimeter tissue blocks, allowing for visualization of meso-scale vessel networks in the white matter. We believe that our technique has the potential for high-throughput, multiscale imaging of brain tissues and may facilitate studies of brain structures.

DOI: 10.1038/s41377-024-01658-0

Source: https://www.nature.com/articles/s41377-024-01658-0