通过组合手工制作特征和深度学习特征来确定肝转移的原发肿瘤部位。
Identifying primary tumor site of origin for liver metastases via a combination of handcrafted and deep learning features.
机构信息
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
出版信息
J Pathol Clin Res. 2024 Jan;10(1):e344. doi: 10.1002/cjp2.344. Epub 2023 Oct 11.
Liver is one of the most common sites for metastases, which can occur on account of primary tumors from multiple sites of origin. Identifying the primary site of origin (PSO) of a metastasis can help in guiding therapeutic options for liver metastases. In this pilot study, we hypothesized that computer extracted handcrafted (HC) histomorphometric features can be utilized to identify the PSO of liver metastases. Cellular features, including tumor nuclei morphological and graph features as well as cytoplasm texture features, were extracted by computer algorithms from 175 slides (114 patients). The study comprised three experiments: (1) comparing and (2) fusing a machine learning (ML) model trained with HC pathomic features and deep learning (DL)-based classifiers to predict site of origin; (3) identifying the section of the primary tumor from which metastases were derived. For experiment 1, we divided the cohort into training sets composed of primary and matched liver metastases [60 patients, 121 whole slide images (WSIs)], and a hold-out validation set (54 patients, 54 WSIs) composed solely of liver metastases of known site of origin. Using the extracted HC features of the training set, a combination of supervised machine classifiers and unsupervised clustering was applied to identify the PSO. A random forest classifier achieved areas under the curve (AUCs) of 0.83, 0.64, 0.82, and 0.64 in classifying the metastatic tumor from colon, esophagus, breast, and pancreas on the validation set. The top features related to nuclear and peri-nuclear shape and textural attributes. We also trained a DL network to serve as a direct comparison to our method. The DL model achieved AUCs for colon: 0.94, esophagus: 0.66, breast: 0.79, and pancreas: 0.67 in identifying PSO. A decision fusion-based strategy was deployed to fuse the trained ML and DL classifiers and achieved slightly better results than ML or DL classifier alone (colon: 0.93, esophagus: 0.68, breast: 0.81, and pancreas: 0.69). For the third experiment, WSI-level attention maps were also generated using a trained DL network to generate a composite feature similarity heat map between paired primaries and their associated metastases. Our experiments revealed that epithelium-rich and moderately differentiated tumor regions of primary tumors were quantitatively similar to paired metastatic tumors. Our findings suggest that a combination of HC and DL features could potentially help identify the PSO for liver metastases while at the same time also potentially identify the spatial sites of origin for the metastases within primary tumors.
肝脏是转移瘤最常见的部位之一,可由来自多个原发部位的原发性肿瘤转移而来。确定转移瘤的原发部位(PSO)有助于指导肝转移瘤的治疗选择。在这项初步研究中,我们假设计算机提取的手工(HC)组织形态计量特征可用于识别肝转移瘤的 PSO。通过计算机算法从 175 张切片(114 例患者)中提取了细胞特征,包括肿瘤核形态和图形特征以及细胞质纹理特征。该研究包括三个实验:(1)比较和(2)融合使用 HC 病理特征训练的机器学习(ML)模型和基于深度学习(DL)的分类器以预测起源部位;(3)识别转移瘤起源的原发性肿瘤的切片。在实验 1 中,我们将队列分为由原发性和匹配的肝转移瘤组成的训练集(60 例患者,121 张全幻灯片图像(WSI))和仅由已知起源部位的肝转移瘤组成的保留验证集(54 例患者,54 WSI)。使用训练集的提取 HC 特征,应用监督机器分类器和无监督聚类来识别 PSO。随机森林分类器在验证集上对转移性肿瘤来自结肠、食管、乳腺和胰腺的分类中获得了 0.83、0.64、0.82 和 0.64 的曲线下面积(AUCs)。与核和核周形状和纹理属性相关的最高特征。我们还训练了一个 DL 网络作为与我们方法的直接比较。DL 模型在识别 PSO 时,结肠的 AUC 为 0.94,食管为 0.66,乳腺为 0.79,胰腺为 0.67。部署了基于决策融合的策略来融合训练的 ML 和 DL 分类器,并且比单独使用 ML 或 DL 分类器获得了稍好的结果(结肠:0.93,食管:0.68,乳腺:0.81,胰腺:0.69)。对于第三个实验,还使用经过训练的 DL 网络生成了 WSI 级别的注意力图,以生成配对原发性肿瘤及其相关转移瘤之间的复合特征相似性热图。我们的实验表明,原发性肿瘤中富含上皮和中等分化的肿瘤区域在定量上与配对的转移性肿瘤相似。我们的研究结果表明,HC 和 DL 特征的组合可能有助于确定肝转移瘤的 PSO,同时还可能确定原发性肿瘤内转移瘤的空间起源部位。