Li Yuzhu, Pillar Nir, Liu Tairan, Ma Guangdong, Qi Yuxuan, Haan Kevin, Zhang Yijie, Yang Xilin, Correa Adrian J, Xiao Guangqian, Jen Kuang-Yu, Iczkowski Kenneth A, Wu Yulun, Wallace William Dean, Ozcan Aydogan
Electrical and Computer Engineering Department, University of California, Los Angeles, CA 90095, USA.
Bioengineering Department, University of California, Los Angeles, CA 90095, USA.
BME Front. 2025 Jul 2;6:0151. doi: 10.34133/bmef.0151. eCollection 2025.
We present a panel of virtual staining neural networks for lung and heart transplant biopsies, providing rapid and high-quality histological staining results while bypassing the traditional histochemical staining process. Allograft rejection is a common complication of organ transplantation, which can lead to life-threatening outcomes if not promptly managed. Histological examination is the gold standard method for evaluating organ transplant rejection status, as it provides detailed insights into rejection signatures at the cellular level. Nevertheless, the traditional histochemical staining process is time-consuming, costly, and labor-intensive since transplant biopsy evaluations typically necessitate multiple stains. Furthermore, once these tissue slides are stained, they cannot be reused for other ancillary tests. More importantly, suboptimal handling of very small tissue fragments from transplant biopsies may impede their effective histochemical staining, and color variations across different laboratories or batches can hinder efficient histological analysis by pathologists. To mitigate these challenges, we developed a panel of virtual staining neural networks for lung and heart transplant biopsies, which digitally convert autofluorescence microscopic images of label-free tissue sections into their bright-field histologically stained counterparts-bypassing the traditional histochemical staining process. Specifically, we virtually generated hematoxylin and eosin (H&E), Masson's Trichrome (MT), and elastic Verhoeff-Van Gieson stains for label-free transplant lung tissue, along with H&E and MT stains for label-free transplant heart tissue. Blind evaluations conducted by 3 board-certified pathologists confirmed that the virtual staining networks consistently produce high-quality histology images with high color uniformity, closely resembling their well-stained histochemical counterparts across various tissue features. The use of virtually stained images for the evaluation of transplant biopsies achieved comparable diagnostic outcomes to those obtained via traditional histochemical staining, with a concordance rate of 82.4% for lung samples and 91.7% for heart samples. Moreover, virtual staining models create multiple stains from the same autofluorescence input, eliminating structural mismatches observed between adjacent sections stained in the traditional workflow, while also saving tissue, expert time, and staining costs. The presented virtual staining panels provide an effective alternative to conventional histochemical staining for transplant biopsy evaluation. These virtual staining panels have the potential to enhance the clinical diagnostic workflow for organ transplant rejection and improve the performance of downstream automated models for the analysis of transplant biopsies.
我们展示了一组用于肺和心脏移植活检的虚拟染色神经网络,可绕过传统的组织化学染色过程,快速提供高质量的组织学染色结果。同种异体移植排斥是器官移植的常见并发症,若不及时处理,可能导致危及生命的后果。组织学检查是评估器官移植排斥状态的金标准方法,因为它能在细胞水平提供有关排斥特征的详细见解。然而,传统的组织化学染色过程耗时、成本高且劳动强度大,因为移植活检评估通常需要多种染色。此外,一旦这些组织切片染色,就不能再用于其他辅助检测。更重要的是,对移植活检中非常小的组织碎片处理不当可能会妨碍其有效的组织化学染色,不同实验室或批次之间的颜色差异会阻碍病理学家进行高效的组织学分析。为了应对这些挑战,我们开发了一组用于肺和心脏移植活检的虚拟染色神经网络,该网络可将无标记组织切片的自发荧光显微镜图像数字转换为明场组织学染色的对应图像,从而绕过传统的组织化学染色过程。具体而言,我们为无标记的移植肺组织虚拟生成了苏木精和伊红(H&E)、Masson三色染色(MT)以及弹性Verhoeff-Van Gieson染色,同时为无标记的移植心脏组织虚拟生成了H&E和MT染色。由3名获得委员会认证的病理学家进行的盲法评估证实,虚拟染色网络始终能产生高质量的组织学图像,颜色均匀性高,在各种组织特征上与染色良好的组织化学对应图像非常相似。使用虚拟染色图像评估移植活检获得的诊断结果与通过传统组织化学染色获得的结果相当,肺样本的一致性率为82.4%,心脏样本的一致性率为91.7%。此外,虚拟染色模型可从相同的自发荧光输入创建多种染色,消除了传统工作流程中相邻切片之间观察到的结构不匹配,同时还节省了组织、专家时间和染色成本。所展示的虚拟染色面板为移植活检评估提供了一种有效的替代传统组织化学染色的方法。这些虚拟染色面板有可能增强器官移植排斥的临床诊断工作流程,并提高下游用于分析移植活检的自动化模型的性能。