Digital Pathology

数字病理学
  • 文章类型: Journal Article
    The Banff classification is useful for diagnosing renal transplant rejection. However, it has limitations due to subjectivity and varying concordance in physicians\' assessments. Artificial intelligence (AI) can help standardize research, increase objectivity and accurately quantify morphological characteristics, improving reproducibility in clinical practice. This study aims to develop an AI-based solutions for diagnosing acute kidney transplant rejection by introducing automated evaluation of prognostic morphological patterns. The proposed approach aims to help accurately distinguish borderline changes from rejection. We trained a deep-learning model utilizing a fine-tuned Mask R-CNN architecture which achieved a mean Average Precision value of 0.74 for the segmentation of renal tissue structures. A strong positive nonlinear correlation was found between the measured infiltration areas and fibrosis, indicating the model\'s potential for assessing these parameters in kidney biopsies. The ROC analysis showed a high predictive ability for distinguishing between ci and i scores based on infiltration area and fibrosis area measurements. The AI model demonstrated high precision in predicting clinical scores which makes it a promising AI assisting tool for pathologists. The application of AI in nephropathology has a potential for advancements, including automated morphometric evaluation, 3D histological models and faster processing to enhance diagnostic accuracy and efficiency.
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  • 文章类型: Journal Article
    前哨淋巴结活检(SNB)中的淋巴结转移(NM)对于黑色素瘤分期至关重要。然而,结节内痣(INN)通常可能被错误分类为NM,导致潜在的误诊和不正确的分期。病理学家在评估SNB阳性时存在高度不一致,这可能会导致错误的分期。数字全载玻片成像为在数字病理学中实施人工智能(AI)提供了潜力。在这项研究中,我们评估了AI在SNB中检测NM和INN的能力。
    总共485张苏木精和曙红全幻灯片图像(WSI),包括来自196个SNB的NM和INN,收集并分为培训(279个WSI),验证(89个WSI),和测试集(117WSI)。深度学习模型使用5,956个手动像素注释进行了训练。AI和三名失明的皮肤病理学家评估了测试集,免疫组织化学作为参考标准。
    AI模型显示出优异的性能,用于检测NM的曲线下面积为0.965接收器工作特性(AUC)。相比之下,在皮肤病理学家中,NM检测的AUC在0.94~0.98之间.对于INN的检测,AI(0.781)和皮肤病理学家的AUC均较低(范围为0.63-0.79).
    总而言之,深度学习AI模型在检测NM方面表现出出色的准确性,在检测NM和INN方面实现皮肤病理学水平的表现。重要的是,AI模型显示出区分这两个实体的潜力。然而,进一步验证是必要的。
    UNASSIGNED: Nodal metastasis (NM) in sentinel node biopsies (SNB) is crucial for melanoma staging. However, an intra-nodal nevus (INN) may often be misclassified as NM, leading to potential misdiagnosis and incorrect staging. There is high discordance among pathologists in assessing SNB positivity, which may lead to false staging. Digital whole slide imaging offers the potential for implementing artificial intelligence (AI) in digital pathology. In this study, we assessed the capability of AI to detect NM and INN in SNBs.
    UNASSIGNED: A total of 485 hematoxylin and eosin whole slide images (WSIs), including NM and INN from 196 SNBs, were collected and divided into training (279 WSIs), validation (89 WSIs), and test sets (117 WSIs). A deep learning model was trained with 5,956 manual pixel-wise annotations. The AI and three blinded dermatopathologists assessed the test set, with immunohistochemistry serving as the reference standard.
    UNASSIGNED: The AI model showed excellent performance with an area under the curve receiver operating characteristic (AUC) of 0.965 for detecting NM. In comparison, the AUC for NM detection among dermatopathologists ranged between 0.94 and 0.98. For the detection of INN, the AUC was lower for both AI (0.781) and dermatopathologists (range of 0.63-0.79).
    UNASSIGNED: In conclusion, the deep learning AI model showed excellent accuracy in detecting NM, achieving dermatopathologist-level performance in detecting both NM and INN. Importantly, the AI model showed the potential to differentiate between these two entities. However, further validation is warranted.
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  • 文章类型: Journal Article
    计算机技术的飞速发展导致了人工智能(AI)辅助医疗保健的革命性转变。全载玻片成像技术与AI算法的集成促进了肺癌(LC)数字病理学的发展。然而,在这一领域缺乏全面的科学计量学分析。
    对来自39个国家/地区的502个机构的197种与LC数字病理学有关的出版物进行了文献计量分析。2004年至2023年在WebofScience核心合集的97种学术期刊上发表。
    我们的分析确定美国和中国是LC数字病理学领域的主要研究国家。然而,重要的是要注意,当前的研究主要包括国家之间的独立研究,强调加强国家间学术合作和数据共享的必要性。当前LC中数字病理学相关研究的焦点和挑战在于通过改进的深度学习算法来提高分类和预测的准确性。多组学研究的整合为未来的研究提供了一个有希望的方向。此外,研究人员越来越多地探索数字病理学在LC患者免疫治疗中的应用.
    总而言之,本研究为LC中的数字病理学提供了一个全面的知识框架,突出研究趋势,热点,和这个领域的差距。为AI在LC患者临床决策中的应用提供了理论依据。
    UNASSIGNED: The rapid development of computer technology has led to a revolutionary transformation in artificial intelligence (AI)-assisted healthcare. The integration of whole-slide imaging technology with AI algorithms has facilitated the development of digital pathology for lung cancer (LC). However, there is a lack of comprehensive scientometric analysis in this field.
    UNASSIGNED: A bibliometric analysis was conducted on 197 publications related to digital pathology in LC from 502 institutions across 39 countries, published in 97 academic journals in the Web of Science Core Collection between 2004 and 2023.
    UNASSIGNED: Our analysis has identified the United States and China as the primary research nations in the field of digital pathology in LC. However, it is important to note that the current research primarily consists of independent studies among countries, emphasizing the necessity of strengthening academic collaboration and data sharing between nations. The current focus and challenge of research related to digital pathology in LC lie in enhancing the accuracy of classification and prediction through improved deep learning algorithms. The integration of multi-omics studies presents a promising future research direction. Additionally, researchers are increasingly exploring the application of digital pathology in immunotherapy for LC patients.
    UNASSIGNED: In conclusion, this study provides a comprehensive knowledge framework for digital pathology in LC, highlighting research trends, hotspots, and gaps in this field. It also provides a theoretical basis for the application of AI in clinical decision-making for LC patients.
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  • 文章类型: Journal Article
    深度学习的最新进展已显示出通过使用点注释的密度图回归进行准确细胞检测的巨大潜力。然而,现有的深度学习模型往往难以在复杂的组织病理学图像中进行多尺度特征提取和集成。此外,在多类小区检测场景中,电流密度图回归方法通常独立预测每种细胞类型,没有考虑不同细胞类型的空间分布先验。为了应对这些挑战,我们提出了CellRegNet,一种使用点注释进行细胞检测的新型深度学习模型。CellRegNet集成了混合CNN/Transformer架构,具有创新的特征细化和选择机制,解决了有效的多尺度特征提取和集成的需求。此外,我们引入了一种对比正则化损失,该损失对多类细胞检测情况下的互斥先验进行建模。在三个组织病理学图像数据集上进行的大量实验表明,CellRegNet优于使用点注释进行细胞检测的现有最新方法,BCData(乳腺癌)的F1评分为86.38%,EndoNuke(子宫内膜组织)占85.56%,MBM(骨髓细胞)占93.90%,分别。这些结果突出了CellRegNet在数字病理学中提高细胞检测准确性和可靠性的潜力。
    Recent advances in deep learning have shown significant potential for accurate cell detection via density map regression using point annotations. However, existing deep learning models often struggle with multi-scale feature extraction and integration in complex histopathological images. Moreover, in multi-class cell detection scenarios, current density map regression methods typically predict each cell type independently, failing to consider the spatial distribution priors of different cell types. To address these challenges, we propose CellRegNet, a novel deep learning model for cell detection using point annotations. CellRegNet integrates a hybrid CNN/Transformer architecture with innovative feature refinement and selection mechanisms, addressing the need for effective multi-scale feature extraction and integration. Additionally, we introduce a contrastive regularization loss that models the mutual exclusiveness prior in multi-class cell detection cases. Extensive experiments on three histopathological image datasets demonstrate that CellRegNet outperforms existing state-of-the-art methods for cell detection using point annotations, with F1-scores of 86.38% on BCData (breast cancer), 85.56% on EndoNuke (endometrial tissue) and 93.90% on MBM (bone marrow cells), respectively. These results highlight CellRegNet\'s potential to enhance the accuracy and reliability of cell detection in digital pathology.
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  • 文章类型: Journal Article
    新辅助化疗(NAC)现已成为局部晚期乳腺癌(BC)患者的标准治疗方法。TIL评分具有预后性,并为NAC后的残留癌症负担评估增加了预测价值。然而,NAC诱导肿瘤的变化,尚未研究NAC后样本中TIL评分的可靠性。H&E-和双重CD3/CD20显色IHC-染色的组织由两名有经验的病理学家对治疗前和治疗后的BC组织进行基质和肿瘤内TIL评分。使用HALO®图像分析软件(版本2.2)进行数字TIL评分。在残留疾病患者中,我们在H&E染色的组织上显示了基质TIL的良好病理学家间相关性(CCC值0.73)。还观察到两种染色方法的评分(CCC0.81)和数字TIL评分(CCC0.77)的良好相关性。然而,完全缓解的患者TIL评分的总体一致性较差。这项研究表明,在NAC治疗后可检测到残留肿瘤的患者中,TIL评分具有良好的可靠性。这与未经治疗的乳腺癌患者的评分相当。基于数字TIL评分观察到的良好一致性,未来开发一个经过验证的算法可能是有利的。
    Neoadjuvant chemotherapy (NAC) is now the standard of care for patients with locally advanced breast cancer (BC). TIL scoring is prognostic and adds predictive value to the residual cancer burden evaluation after NAC. However, NAC induces changes in the tumor, and the reliability of TIL scoring in post-NAC samples has not yet been studied. H&E- and dual CD3/CD20 chromogenic IHC-stained tissues were scored for stromal and intra-tumoral TIL by two experienced pathologists on pre- and post-treatment BC tissues. Digital TIL scoring was performed using the HALO® image analysis software (version 2.2). In patients with residual disease, we show a good inter-pathologist correlation for stromal TIL on H&E-stained tissues (CCC value 0.73). A good correlation for scoring with both staining methods (CCC 0.81) and the digital TIL scoring (CCC 0.77) was also observed. Overall concordance for TIL scoring in patients with a complete response was however poor. This study reveals there is good reliability for TIL scoring in patients with detectable residual tumors after NAC treatment, which is comparable to the scoring of untreated breast cancer patients. Based on the good consistency observed with digital TIL scoring, the development of a validated algorithm in the future might be advantageous.
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  • 文章类型: Journal Article
    当前肾脏病学的研究越来越集中在阐明紧密交织的分子系统固有的复杂性及其与病理学和相关疗法的相关性。包括透析和肾移植。组学科学的快速发展,医疗设备传感器,和网络化的数字医疗设备使这种研究越来越以数据为中心。以数据为中心的科学需要强大的计算和复杂的工具的支持,这些工具能够处理新的生物标志物和治疗靶标的溢出。这是人工智能(AI)和,更具体地说,机器学习(ML)可以提供明显的分析优势,鉴于他们利用多模态数据的能力迅速提高,从基因组信息到信号,图像甚至异构电子健康记录(EHR)。然而,矛盾的是,只有一小部分基于ML的医疗决策支持系统经过验证并证明了临床有用性.为了有效地将所有这些新知识转化为临床实践,基于可解释和可解释的ML方法和明确的个性化医疗分析策略的临床合规支持系统的开发势在必行.智能肾脏病学,也就是说,设计和开发基于AI的以数据为中心的肾脏病学策略,只是迈出了第一步,而且还没有接近它的时代。这些最初的步骤甚至没有被均匀地采取,随着发达国家和发展中国家在获取技术方面的数字鸿沟变得明显,也影响到代表性不足的少数群体。考虑到这一切,这篇社论旨在提供对当前AI技术在肾脏病学中的使用的选择性概述,并预示着BMC肾脏病学推出的“肾脏病学人工智能”特刊。
    Current research in nephrology is increasingly focused on elucidating the complexity inherent in tightly interwoven molecular systems and their correlation with pathology and related therapeutics, including dialysis and renal transplantation. Rapid advances in the omics sciences, medical device sensorization, and networked digital medical devices have made such research increasingly data centered. Data-centric science requires the support of computationally powerful and sophisticated tools able to handle the overflow of novel biomarkers and therapeutic targets. This is a context in which artificial intelligence (AI) and, more specifically, machine learning (ML) can provide a clear analytical advantage, given the rapid advances in their ability to harness multimodal data, from genomic information to signal, image and even heterogeneous electronic health records (EHR). However, paradoxically, only a small fraction of ML-based medical decision support systems undergo validation and demonstrate clinical usefulness. To effectively translate all this new knowledge into clinical practice, the development of clinically compliant support systems based on interpretable and explainable ML-based methods and clear analytical strategies for personalized medicine are imperative. Intelligent nephrology, that is, the design and development of AI-based strategies for a data-centric approach to nephrology, is just taking its first steps and is by no means yet close to its coming of age. These first steps are not even homogeneously taken, as a digital divide in access to technology has become evident between developed and developing countries, also affecting underrepresented minorities. With all this in mind, this editorial aim to provide a selective overview of the current use of AI technologies in nephrology and heralds the \"Artificial Intelligence in Nephrology\" special issue launched by BMC Nephrology.
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  • 文章类型: Journal Article
    背景:深度学习彻底改变了癌症病理学中的医学图像分析,它通过支持癌症的诊断和预后评级而产生了重大的临床影响。在脑癌领域的第一个可用的数字资源是胶质母细胞瘤,最常见和最致命的脑癌.在组织学层面,胶质母细胞瘤以丰富的表型变异性为特征,与患者预后的相关性较差。在转录水平,3种分子亚型被区分为间质亚型肿瘤与增加的免疫细胞浸润和更差的结果相关。
    结果:我们通过将Xception卷积神经网络应用于具有分子亚型注释的276个数字血样蛋白和伊红(H&E)幻灯片的发现集和一个独立的基于癌症基因组图谱的178例病例验证队列,来解决基因型-表型相关性。使用这种方法,我们在基于H&E的分子亚型映射中实现了高精度(经典,间充质,分别为0.84、0.81和0.71;P<0.001)和与较差结局相关的区域(单变量生存模型P<0.001,多变量P=0.01)。后者的特点是较高的肿瘤细胞密度(P<0.001),肿瘤细胞表型变异(P<0.001),T细胞浸润减少(P=0.017)。
    结论:我们修改了胶质母细胞瘤数字幻灯片的众所周知的卷积神经网络架构,以准确绘制转录亚型和预测较差结果的区域的空间分布,从而展示了人工智能图像挖掘在脑癌中的相关性。
    BACKGROUND: Deep learning has revolutionized medical image analysis in cancer pathology, where it had a substantial clinical impact by supporting the diagnosis and prognostic rating of cancer. Among the first available digital resources in the field of brain cancer is glioblastoma, the most common and fatal brain cancer. At the histologic level, glioblastoma is characterized by abundant phenotypic variability that is poorly linked with patient prognosis. At the transcriptional level, 3 molecular subtypes are distinguished with mesenchymal-subtype tumors being associated with increased immune cell infiltration and worse outcome.
    RESULTS: We address genotype-phenotype correlations by applying an Xception convolutional neural network to a discovery set of 276 digital hematozylin and eosin (H&E) slides with molecular subtype annotation and an independent The Cancer Genome Atlas-based validation cohort of 178 cases. Using this approach, we achieve high accuracy in H&E-based mapping of molecular subtypes (area under the curve for classical, mesenchymal, and proneural = 0.84, 0.81, and 0.71, respectively; P < 0.001) and regions associated with worse outcome (univariable survival model P < 0.001, multivariable P = 0.01). The latter were characterized by higher tumor cell density (P < 0.001), phenotypic variability of tumor cells (P < 0.001), and decreased T-cell infiltration (P = 0.017).
    CONCLUSIONS: We modify a well-known convolutional neural network architecture for glioblastoma digital slides to accurately map the spatial distribution of transcriptional subtypes and regions predictive of worse outcome, thereby showcasing the relevance of artificial intelligence-enabled image mining in brain cancer.
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  • 文章类型: Journal Article
    背景:人类表皮生长因子受体2(HER2)-低位乳腺癌已成为一种新的肿瘤亚型,新的抗体-药物缀合物已经显示出有益的效果。如果将病例分类为HER22+,则HER2的评估需要进行几次免疫组织化学测试和额外的原位杂交测试。因此,加快HER2评估的新的经济有效的方法是非常可取的.
    方法:我们使用一种基于自我监督的基于注意力的弱监督方法,直接从1351例乳腺癌患者的1437张组织病理学图像中预测HER2-low。我们建立了六个不同的模型来探索分类器区分HER2阴性的能力,HER2低,和HER2高类在不同的情况下。基于注意力的模型用于理解针对相关组织区域的决策过程。
    结果:我们的结果表明,分类模型的有效性取决于基于检测的HER2测试的一致性和可靠性,因为这些测试的结果被用作训练我们模型的基线真理。通过使用可解释的人工智能,我们揭示了与HER2亚型相关的组织学模式.
    结论:我们的研究结果证明了如何应用深度学习技术来识别HER2亚群状态。潜在地丰富了可用于肿瘤学临床决策的工具包。
    BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a new subtype of tumor, for which novel antibody-drug conjugates have shown beneficial effects. Assessment of HER2 requires several immunohistochemistry tests with an additional in situ hybridization test if a case is classified as HER2 2+. Therefore, novel cost-effective methods to speed up the HER2 assessment are highly desirable.
    METHODS: We used a self-supervised attention-based weakly supervised method to predict HER2-low directly from 1437 histopathological images from 1351 breast cancer patients. We built six distinct models to explore the ability of classifiers to distinguish between the HER2-negative, HER2-low, and HER2-high classes in different scenarios. The attention-based model was used to comprehend the decision-making process aimed at relevant tissue regions.
    RESULTS: Our results indicate that the effectiveness of classification models hinges on the consistency and dependability of assay-based tests for HER2, as the outcomes from these tests are utilized as the baseline truth for training our models. Through the use of explainable AI, we reveal histologic patterns associated with the HER2 subtypes.
    CONCLUSIONS: Our findings offer a demonstration of how deep learning technologies can be applied to identify HER2 subgroup statuses, potentially enriching the toolkit available for clinical decision-making in oncology.
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  • 文章类型: Journal Article
    随着整个幻灯片数字扫描仪的可用性,现在可以在光学显微镜上进行相当准确的肾小球直径(GD)测量。这些测量在免疫球蛋白A肾病(IgAN)的预后和诊断中的价值尚未得到广泛研究。IgAN是全球终末期肾病(ESRD)的主要原因,它的进展目前是用牛津的分数来评估的,血清肌酐,和24小时尿蛋白。我们旨在将平均和最大GDs与血清肌酐相关联,24小时尿蛋白,IgAN患者的牛津评分。
    收集了100例IgAN活检,其中至少有8个有活力的肾小球,以及24小时蛋白尿的数据,血清肌酐,牛津得分。使用飞利浦IntelliSite病理学解决方案-超快速扫描仪扫描载玻片。每个肾小球的平均GD计算为两次测量的平均值,也就是说,肾小球的最大直径和垂直于最大直径的最大弦。还记录了每种情况下的最大GD。使用Spearmanrho/PearsonR相关系数进行这种相关性。P值<0.05被认为具有统计学意义。
    患者的平均年龄为34.67±12.03岁,他们表现出男性优势。总平均GD为151.82±28.69µm,最大GD为205.40±32.76µm。在平均或最大GD和24小时蛋白尿之间没有观察到统计学上显著的相关性,血清肌酐水平,牛津得分。
    IgAN中的GD与蛋白尿无关,血清肌酐,或者牛津的分数.
    UNASSIGNED: With the availability of whole slide digital scanners, fairly accurate glomerular diameter (GD) measurements are now possible on light microscopy. The value of these measurements in prognosis and diagnosis of immunoglobulin A nephropathy (IgAN) have not been studied widely. IgAN is a major cause of end-stage renal disease (ESRD) worldwide, and its progression is currently assessed using Oxford scores, serum creatinine, and 24-h urinary protein. We aimed to correlate the mean and maximum GDs with serum creatinine, 24-h urinary protein, and Oxford scores in patients with IgAN.
    UNASSIGNED: One hundred biopsies of IgAN with a minimum of eight viable glomeruli were collected along with data of their 24-h proteinuria, serum creatinine, and Oxford scores. The slides were scanned using the Philips IntelliSite Pathology Solution-Ultra Fast Scanner. Mean GD of each glomerulus was calculated as the mean of two measurements, that is, the maximal diameter of the glomerulus and the maximal chord perpendicular to the maximal diameter. Maximum GD was also recorded for each case. The Spearman rho/Pearson R correlation coefficient was used to make this correlation. P-values <0.05 were considered statistically significant.
    UNASSIGNED: The mean age of the patients was 34.67 ± 12.03 years, and they showed a male preponderance. The overall mean GD was 151.82 ± 28.69 µm, and maximum GD was 205.40 ± 32.76 µm. No statistically significant correlation was observed between the mean or maximum GD and the 24-h proteinuria, serum creatinine levels, and Oxford scores.
    UNASSIGNED: GD in IgAN does not correlate with proteinuria, serum creatinine, or Oxford scores.
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  • 文章类型: Journal Article
    数字病理学是一个快速发展的领域,深度学习方法可以用来提取有意义的成像特征。然而,训练深度学习模型的有效性往往受到注释病理图像稀缺的阻碍,特别是具有针对小图像补丁或图块的详细注释的图像。为了克服这一挑战,我们提出了一种创新的方法,利用配对的空间分辨转录组数据来注释病理图像。我们证明了这种方法的可行性,并引入了一种新颖的迁移学习神经网络模型,STpath(空间转录和病理图像),旨在预测细胞类型比例或对肿瘤微环境进行分类。我们的发现表明,来自预先训练的深度学习模型的特征与病理图像块中的细胞类型身份相关。使用三个不同的乳腺癌数据集评估STpath,尽管训练数据有限,我们仍观察到其有希望的性能。STpath擅长具有可变细胞类型比例和高分辨率病理图像的样品。随着空间分辨转录组数据的不断涌入,我们预计会持续更新STpath,将其发展成为一种宝贵的AI工具,用于协助病理学家完成各种诊断任务。
    Digital pathology is a rapidly advancing field where deep learning methods can be employed to extract meaningful imaging features. However, the efficacy of training deep learning models is often hindered by the scarcity of annotated pathology images, particularly images with detailed annotations for small image patches or tiles. To overcome this challenge, we propose an innovative approach that leverages paired spatially resolved transcriptomic data to annotate pathology images. We demonstrate the feasibility of this approach and introduce a novel transfer-learning neural network model, STpath (Spatial Transcriptomics and pathology images), designed to predict cell type proportions or classify tumor microenvironments. Our findings reveal that the features from pre-trained deep learning models are associated with cell type identities in pathology image patches. Evaluating STpath using three distinct breast cancer datasets, we observe its promising performance despite the limited training data. STpath excels in samples with variable cell type proportions and high-resolution pathology images. As the influx of spatially resolved transcriptomic data continues, we anticipate ongoing updates to STpath, evolving it into an invaluable AI tool for assisting pathologists in various diagnostic tasks.
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