利用人工智能对多重免疫荧光图像开发自动化综合阳性评分预测流程。
Development of an automated combined positive score prediction pipeline using artificial intelligence on multiplexed immunofluorescence images.
作者信息
Vahadane Abhishek, Sharma Shreya, Mandal Devraj, Dabbeeru Madan, Jakthong Josephine, Garcia-Guzman Miguel, Majumdar Shantanu, Lee Chung-Wein
机构信息
Rakuten India Enterprise Private Ltd, Bagmane Pallavi Tower #20, 1st Cross, Raja Ram Mohan Roy Road, S. R. Nagar, Bengaluru, Karnataka, 560027, India.
Rakuten Medical Inc., 11080 Roselle Street, San Diego, CA, 92121, USA.
出版信息
Comput Biol Med. 2023 Jan;152:106337. doi: 10.1016/j.compbiomed.2022.106337. Epub 2022 Nov 24.
Immunotherapy targeting immune checkpoint proteins, such as programmed cell death ligand 1 (PD-L1), has shown impressive outcomes in many clinical trials but only 20%-40% of patients benefit from it. Utilizing Combined Positive Score (CPS) to evaluate PD-L1 expression in tumour biopsies to identify patients with the highest likelihood of responsiveness to anti-PD-1/PD-L1 therapy has been approved by the Food and Drug Administration for several solid tumour types. Current CPS workflow requires a pathologist to manually score the two-colour PD-L1 chromogenic immunohistochemistry image. Multiplex immunofluorescence (mIF) imaging reveals the expression of an increased number of immune markers in tumour biopsies and has been used extensively in immunotherapy research. Recent rapid progress of Artificial Intelligence (AI)-based imaging analysis, particularly Deep Learning, provides cost effective and high-quality solutions to healthcare. In this article, we propose an imaging pipeline that utilizes three-colour mIF images (DAPI, PD-L1, and Pan-cytokeratin) as input and predicts the CPS using AI techniques. Our novel pipeline is composed of three modules employing algorithms of image processing, machine learning, and deep learning techniques. The first module of quality check (QC) detects and removes the image regions contaminated with sectioning and staining artefacts. The QC module ensures that only image regions free of the three common artefacts are used for downstream analysis. The second module of nuclear segmentation uses deep learning to segment and count nuclei in the DAPI images wherein our specialized method can accurately separate touching nuclei. The third module of cell phenotyping calculates CPS by identifying and counting PD-L1 positive cells and tumour cells. These modules are data-efficient and require only few manual annotations for training purposes. Using tumour biopsies from a clinical trial, we found that the CPS from the AI-based models shows a high Spearman correlation (78%, p = 0.003) to the pathologist-scored CPS.
针对免疫检查点蛋白(如程序性细胞死亡配体1,PD-L1)的免疫疗法在许多临床试验中都取得了令人瞩目的成果,但只有20%-40%的患者从中受益。利用综合阳性评分(CPS)来评估肿瘤活检中PD-L1的表达,以确定对抗PD-1/PD-L1治疗反应可能性最高的患者,这一方法已被美国食品药品监督管理局批准用于多种实体瘤类型。目前的CPS工作流程需要病理学家手动对双色PD-L1显色免疫组化图像进行评分。多重免疫荧光(mIF)成像揭示了肿瘤活检中更多免疫标志物的表达,并已在免疫治疗研究中广泛应用。基于人工智能(AI)的成像分析,尤其是深度学习,最近取得的快速进展为医疗保健提供了经济高效且高质量的解决方案。在本文中,我们提出了一种成像流程,该流程利用三色mIF图像(DAPI、PD-L1和全细胞角蛋白)作为输入,并使用AI技术预测CPS。我们新颖的流程由三个模块组成,采用了图像处理、机器学习和深度学习技术的算法。第一个质量检查(QC)模块检测并去除受切片和染色伪影污染的图像区域。QC模块确保只有没有这三种常见伪影的图像区域用于下游分析。第二个细胞核分割模块使用深度学习对DAPI图像中的细胞核进行分割和计数,其中我们的专门方法可以准确分离相互接触的细胞核。第三个细胞表型分析模块通过识别和计数PD-L1阳性细胞和肿瘤细胞来计算CPS。这些模块数据效率高,仅需要少量手动注释用于训练目的。使用来自一项临床试验的肿瘤活检样本,我们发现基于AI的模型得出的CPS与病理学家评分的CPS具有较高的斯皮尔曼相关性(78%,p = 0.003)。