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
Department of Electrical and Computer Engineering, Boston University, Boston, MA, 02215, USA.
Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, 94720, USA.
Light Sci Appl. 2025 Jan 20;14(1):57. doi: 10.1038/s41377-024-01658-0.
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.
神经科学中的一个主要挑战是在不同尺度下可视化人类大脑的结构。传统组织学揭示了微观和中观尺度的大脑特征,但存在染色变异性、组织损伤和变形等问题,这阻碍了精确的三维重建。新兴的无标记连续切片光学相干断层扫描(S-OCT)技术在样本间提供了统一的三维成像能力,但尽管对皮质特征敏感,其组织学可解释性却很差。在此,我们提出了一种将S-OCT与深度学习数字染色(DS)模型相结合的新型三维成像框架。这种增强的成像方式整合了高通量三维成像、低样本变异性和高可解释性,使其适用于三维组织学研究。我们开发了一种新型半监督学习技术,以促进DS模型在弱配对图像上的训练,从而将S-OCT转换为加利亚斯银染色。我们在各种人类大脑皮质样本上展示了数字染色,实现了一致的染色质量,并增强了皮质层边界的对比度。此外,我们表明数字染色在立方厘米组织块上保留了三维几何结构,能够可视化白质中的中观尺度血管网络。我们相信,我们的技术具有对脑组织进行高通量、多尺度成像的潜力,并可能促进对脑结构的研究。