scholarly journals Deep learning identifies morphological features in breast cancer predictive of cancer ERBB2 status and trastuzumab treatment efficacy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dmitrii Bychkov ◽  
Nina Linder ◽  
Aleksei Tiulpin ◽  
Hakan Kücükel ◽  
Mikael Lundin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Deep Learning ◽  
Gene Amplification ◽  
Characteristic Curve ◽  
Disease Free Survival ◽  
Morphological Features ◽  
Training Data ◽  
Primary Breast Tumor ◽  
Trastuzumab Treatment

AbstractThe treatment of patients with ERBB2 (HER2)-positive breast cancer with anti-ERBB2 therapy is based on the detection of ERBB2 gene amplification or protein overexpression. Machine learning (ML) algorithms can predict the amplification of ERBB2 based on tumor morphological features, but it is not known whether ML-derived features can predict survival and efficacy of anti-ERBB2 treatment. In this study, we trained a deep learning model with digital images of hematoxylin–eosin (H&E)-stained formalin-fixed primary breast tumor tissue sections, weakly supervised by ERBB2 gene amplification status. The gene amplification was determined by chromogenic in situ hybridization (CISH). The training data comprised digitized tissue microarray (TMA) samples from 1,047 patients. The correlation between the deep learning–predicted ERBB2 status, which we call H&E-ERBB2 score, and distant disease-free survival (DDFS) was investigated on a fully independent test set, which included whole-slide tumor images from 712 patients with trastuzumab treatment status available. The area under the receiver operating characteristic curve (AUC) in predicting gene amplification in the test sets was 0.70 (95% CI, 0.63–0.77) on 354 TMA samples and 0.67 (95% CI, 0.62–0.71) on 712 whole-slide images. Among patients with ERBB2-positive cancer treated with trastuzumab, those with a higher than the median morphology–based H&E-ERBB2 score derived from machine learning had more favorable DDFS than those with a lower score (hazard ratio [HR] 0.37; 95% CI, 0.15–0.93; P = 0.034). A high H&E-ERBB2 score was associated with unfavorable survival in patients with ERBB2-negative cancer as determined by CISH. ERBB2-associated morphology correlated with the efficacy of adjuvant anti-ERBB2 treatment and can contribute to treatment-predictive information in breast cancer.

scholarly journals Deep Learning Using Multiple Degrees of Maximum-Intensity Projection for PET/CT Image Classification in Breast Cancer

Tomography ◽  
2022 ◽  
Vol 8 (1) ◽  
pp. 131-141
Author(s):  
Kanae Takahashi ◽  
Tomoyuki Fujioka ◽  
Jun Oyama ◽  
Mio Mori ◽  
Emi Yamaga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
Image Classification ◽  
Test Data ◽  
Characteristic Curve ◽  
Maximum Intensity Projection ◽  
Maximum Intensity ◽  
Training Data ◽  
Ct Image ◽  
Pet Ct

Deep learning (DL) has become a remarkably powerful tool for image processing recently. However, the usefulness of DL in positron emission tomography (PET)/computed tomography (CT) for breast cancer (BC) has been insufficiently studied. This study investigated whether a DL model using images with multiple degrees of PET maximum-intensity projection (MIP) images contributes to increase diagnostic accuracy for PET/CT image classification in BC. We retrospectively gathered 400 images of 200 BC and 200 non-BC patients for training data. For each image, we obtained PET MIP images with four different degrees (0°, 30°, 60°, 90°) and made two DL models using Xception. One DL model diagnosed BC with only 0-degree MIP and the other used four different degrees. After training phases, our DL models analyzed test data including 50 BC and 50 non-BC patients. Five radiologists interpreted these test data. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. Our 4-degree model, 0-degree model, and radiologists had a sensitivity of 96%, 82%, and 80–98% and a specificity of 80%, 88%, and 76–92%, respectively. Our 4-degree model had equal or better diagnostic performance compared with that of the radiologists (AUC = 0.936 and 0.872–0.967, p = 0.036–0.405). A DL model similar to our 4-degree model may lead to help radiologists in their diagnostic work in the future.

scholarly journals Morphological Estimation of Cellularity on Neo-Adjuvant Treated Breast Cancer Histological Images

2020 ◽  
Vol 6 (10) ◽  
pp. 101
Author(s):  
Mauricio Alberto Ortega-Ruiz ◽  
Cefa Karabağ ◽  
Victor García Garduño ◽  
Constantino Carlos Reyes-Aldasoro
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
Morphological Features ◽  
Training Data ◽  
Morphological Operations ◽  
Morphological Parameters ◽  
Learning Approaches ◽  
Residual Cancer Burden ◽  
Histological Images ◽  
Treated Breast

This paper describes a methodology that extracts key morphological features from histological breast cancer images in order to automatically assess Tumour Cellularity (TC) in Neo-Adjuvant treatment (NAT) patients. The response to NAT gives information on therapy efficacy and it is measured by the residual cancer burden index, which is composed of two metrics: TC and the assessment of lymph nodes. The data consist of whole slide images (WSIs) of breast tissue stained with Hematoxylin and Eosin (H&E) released in the 2019 SPIE Breast Challenge. The methodology proposed is based on traditional computer vision methods (K-means, watershed segmentation, Otsu’s binarisation, and morphological operations), implementing colour separation, segmentation, and feature extraction. Correlation between morphological features and the residual TC after a NAT treatment was examined. Linear regression and statistical methods were used and twenty-two key morphological parameters from the nuclei, epithelial region, and the full image were extracted. Subsequently, an automated TC assessment that was based on Machine Learning (ML) algorithms was implemented and trained with only selected key parameters. The methodology was validated with the score assigned by two pathologists through the intra-class correlation coefficient (ICC). The selection of key morphological parameters improved the results reported over other ML methodologies and it was very close to deep learning methodologies. These results are encouraging, as a traditionally-trained ML algorithm can be useful when limited training data are available preventing the use of deep learning approaches.

scholarly journals CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Paulino Tallón de Lara ◽  
Héctor Castañón ◽  
Marijne Vermeer ◽  
Nicolás Núñez ◽  
Karina Silina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Human Breast Cancer ◽  
Disease Free Survival ◽  
T Cell Response ◽  
Primary Breast Tumor ◽  
Human Breast ◽  
Primary Tumors ◽  
Metastatic Relapse ◽  
Discrete Population

AbstractSome breast tumors metastasize aggressively whereas others remain dormant for years. The mechanism governing metastatic dormancy remains largely unknown. Through high-parametric single-cell mapping in mice, we identify a discrete population of CD39+PD-1+CD8+ T cells in primary tumors and in dormant metastasis, which is hardly found in aggressively metastasizing tumors. Using blocking antibodies, we find that dormancy depends on TNFα and IFNγ. Immunotherapy reduces the number of dormant cancer cells in the lungs. Adoptive transfer of purified CD39+PD-1+CD8+ T cells prevents metastatic outgrowth. In human breast cancer, the frequency of CD39+PD-1+CD8+ but not total CD8+ T cells correlates with delayed metastatic relapse after resection (disease-free survival), thus underlining the biological relevance of CD39+PD-1+CD8+ T cells for controlling experimental and human breast cancer. Thus, we suggest that a primary breast tumor could prime a systemic, CD39+PD-1+CD8+ T cell response that favors metastatic dormancy in the lungs.

scholarly journals A Review of Computer-Aided Expert Systems for Breast Cancer Diagnosis

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2764
Author(s):  
Xin Yu Liew ◽  
Nazia Hameed ◽  
Jeremie Clos
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Deep Learning ◽  
Main Process ◽  
Learning Approaches ◽  
Learning Methods ◽  
Advantages And Disadvantages ◽  
Computer Aided ◽  
Conventional Methods ◽  
The Impact

A computer-aided diagnosis (CAD) expert system is a powerful tool to efficiently assist a pathologist in achieving an early diagnosis of breast cancer. This process identifies the presence of cancer in breast tissue samples and the distinct type of cancer stages. In a standard CAD system, the main process involves image pre-processing, segmentation, feature extraction, feature selection, classification, and performance evaluation. In this review paper, we reviewed the existing state-of-the-art machine learning approaches applied at each stage involving conventional methods and deep learning methods, the comparisons within methods, and we provide technical details with advantages and disadvantages. The aims are to investigate the impact of CAD systems using histopathology images, investigate deep learning methods that outperform conventional methods, and provide a summary for future researchers to analyse and improve the existing techniques used. Lastly, we will discuss the research gaps of existing machine learning approaches for implementation and propose future direction guidelines for upcoming researchers.

scholarly journals A Physics-Infused Deep Learning Model for the Prediction of Refractive Indices and Its Use for the Large-Scale Screening of Organic Compound Space

2019 ◽  
Author(s):  
Mojtaba Haghighatlari ◽  
Gaurav Vishwakarma ◽  
Mohammad Atif Faiz Afzal ◽  
Johannes Hachmann
Keyword(s):  
Machine Learning ◽  
Deep Learning ◽  
Large Scale ◽  
Organic Molecules ◽  
Learning Model ◽  
Training Data ◽  
Refractive Indices ◽  
Learning Models ◽  
Deep Learning Model ◽  
Machine Learning Models

<div><div><div><p>We present a multitask, physics-infused deep learning model to accurately and efficiently predict refractive indices (RIs) of organic molecules, and we apply it to a library of 1.5 million compounds. We show that it outperforms earlier machine learning models by a significant margin, and that incorporating known physics into data-derived models provides valuable guardrails. Using a transfer learning approach, we augment the model to reproduce results consistent with higher-level computational chemistry training data, but with a considerably reduced number of corresponding calculations. Prediction errors of machine learning models are typically smallest for commonly observed target property values, consistent with the distribution of the training data. However, since our goal is to identify candidates with unusually large RI values, we propose a strategy to boost the performance of our model in the remoter areas of the RI distribution: We bias the model with respect to the under-represented classes of molecules that have values in the high-RI regime. By adopting a metric popular in web search engines, we evaluate our effectiveness in ranking top candidates. We confirm that the models developed in this study can reliably predict the RIs of the top 1,000 compounds, and are thus able to capture their ranking. We believe that this is the first study to develop a data-derived model that ensures the reliability of RI predictions by model augmentation in the extrapolation region on such a large scale. These results underscore the tremendous potential of machine learning in facilitating molecular (hyper)screening approaches on a massive scale and in accelerating the discovery of new compounds and materials, such as organic molecules with high-RI for applications in opto-electronics.</p></div></div></div>

scholarly journals OpSeF: Open source Python framework for collaborative instance segmentation of bioimages

2020 ◽  
Author(s):  
Tobias M. Rasse ◽  
Réka Hollandi ◽  
Péter Horváth
Keyword(s):  
Machine Learning ◽  
Deep Learning ◽  
Complex Analysis ◽  
Ease Of Use ◽  
Problem Definition ◽  
Training Data ◽  
Post Processing ◽  
Gpu Clusters ◽  
User Tasks ◽  
Instance Segmentation

AbstractVarious pre-trained deep learning models for the segmentation of bioimages have been made available as ‘developer-to-end-user’ solutions. They usually require neither knowledge of machine learning nor coding skills, are optimized for ease of use, and deployability on laptops. However, testing these tools individually is tedious and success is uncertain.Here, we present the ‘Op’en ‘Se’gmentation ‘F’ramework (OpSeF), a Python framework for deep learning-based instance segmentation. OpSeF aims at facilitating the collaboration of biomedical users with experienced image analysts. It builds on the analysts’ knowledge in Python, machine learning, and workflow design to solve complex analysis tasks at any scale in a reproducible, well-documented way. OpSeF defines standard inputs and outputs, thereby facilitating modular workflow design and interoperability with other software. Users play an important role in problem definition, quality control, and manual refinement of results. All analyst tasks are optimized for deployment on Linux workstations or GPU clusters, all user tasks may be performed on any laptop in ImageJ.OpSeF semi-automates preprocessing, convolutional neural network (CNN)-based segmentation in 2D or 3D, and post-processing. It facilitates benchmarking of multiple models in parallel. OpSeF streamlines the optimization of parameters for pre- and post-processing such, that an available model may frequently be used without retraining. Even if sufficiently good results are not achievable with this approach, intermediate results can inform the analysts in the selection of the most promising CNN-architecture in which the biomedical user might invest the effort of manually labeling training data.We provide Jupyter notebooks that document sample workflows based on various image collections. Analysts may find these notebooks useful to illustrate common segmentation challenges, as they prepare the advanced user for gradually taking over some of their tasks and completing their projects independently. The notebooks may also be used to explore the analysis options available within OpSeF in an interactive way and to document and share final workflows.Currently, three mechanistically distinct CNN-based segmentation methods, the U-Net implementation used in Cellprofiler 3.0, StarDist, and Cellpose have been integrated within OpSeF. The addition of new networks requires little, the addition of new models requires no coding skills. Thus, OpSeF might soon become both an interactive model repository, in which pre-trained models might be shared, evaluated, and reused with ease.

scholarly journals Challenge for Diagnostic Assessment of Deep Learning Algorithm for Metastases Classification in Sentinel Lymph Nodes on Frozen Tissue Section Digital Slides in Women with Breast Cancer

2020 ◽  
Author(s):  
Young-Gon Kim ◽  
In Hye Song ◽  
Hyunna Lee ◽  
Dong Hyun Yang ◽  
Namkug Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
Lymph Nodes ◽  
Learning Algorithm ◽  
Medical Center ◽  
Characteristic Curve ◽  
Lobular Carcinoma ◽  
Sentinel Lymph Nodes ◽  
Neoadjuvant Systemic Therapy ◽  
Frozen Tissue

Abstract Assessing the status of metastasis in sentinel lymph nodes (SLNs) by pathologists is an essential task for the accurate staging of breast cancer. However, histopathological evaluation of sentinel lymph nodes by a pathologist is not easy and is a tedious and time-consuming task. The purpose of this study is to review a challenge competition (HeLP 2018) to develop automated solutions for the classification of metastases in hematoxylin and eosin–stained frozen tissue sections of SLNs in breast cancer patients. A total of 297 digital slides were obtained from frozen SLN sections, which include post–neoadjuvant cases (n = 144, 48.5%) in Asan Medical Center, South Korea. The slides were divided into training, development, and validation sets. All of the imaging datasets have been manually segmented by expert pathologists. A total of 10 participants were allowed to use the Kakao challenge platform for six weeks with two P40 GPUs. The algorithms were assessed in terms of the AUC (area under receiver operating characteristic curve). The top three teams showed 0.986, 0.985, and 0.945 AUCs for the development set and 0.805, 0.776, and 0.765 AUCs for the validation set. Micrometastatic tumors, neoadjuvant systemic therapy, invasive lobular carcinoma, and histologic grade 3 were associated with lower diagnostic accuracy. In a challenge competition, accurate deep learning algorithms have been developed, which can be helpful in making frozen diagnosis of intraoperative sentinel lymph node biopsy. Whether this approach has clinical utility will require evaluation in a clinical setting.

Convolutional Neural Network

2022 ◽  
pp. 1559-1575
Author(s):  
Mário Pereira Véstias
Keyword(s):  
Neural Network ◽  
Machine Learning ◽  
Neural Networks ◽  
Artificial Neural Networks ◽  
Deep Learning ◽  
Convolutional Neural Network ◽  
Machine Learning Algorithms ◽  
Training Data ◽  
Machine Learning Model ◽  
Artificial Neural

Machine learning is the study of algorithms and models for computing systems to do tasks based on pattern identification and inference. When it is difficult or infeasible to develop an algorithm to do a particular task, machine learning algorithms can provide an output based on previous training data. A well-known machine learning model is deep learning. The most recent deep learning models are based on artificial neural networks (ANN). There exist several types of artificial neural networks including the feedforward neural network, the Kohonen self-organizing neural network, the recurrent neural network, the convolutional neural network, the modular neural network, among others. This article focuses on convolutional neural networks with a description of the model, the training and inference processes and its applicability. It will also give an overview of the most used CNN models and what to expect from the next generation of CNN models.

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