Pathology image-based lung cancer subtyping using deeplearning features and cell-density maps

2020 ◽  
Vol 2020 (10) ◽  
pp. 64-1-64-5
Author(s):  
Mustafa I. Jaber ◽  
Christopher W. Szeto ◽  
Bing Song ◽  
Liudmila Beziaeva ◽  
Stephen C. Benz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Density ◽  
Majority Voting ◽  
Training Set ◽  
Density Maps ◽  
Color Deconvolution ◽  
Map Generation ◽  
Density Map ◽  
Pathology Image ◽  
Whole Slide Images

In this paper, we propose a patch-based system to classify non-small cell lung cancer (NSCLC) diagnostic whole slide images (WSIs) into two major histopathological subtypes: adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Classifying patients accurately is important for prognosis and therapy decisions. The proposed system was trained and tested on 876 subtyped NSCLC gigapixel-resolution diagnostic WSIs from 805 patients – 664 in the training set and 141 in the test set. The algorithm has modules for: 1) auto-generated tumor/non-tumor masking using a trained residual neural network (ResNet34), 2) cell-density map generation (based on color deconvolution, local drain segmentation, and watershed transformation), 3) patch-level feature extraction using a pre-trained ResNet34, 4) a tower of linear SVMs for different cell ranges, and 5) a majority voting module for aggregating subtype predictions in unseen testing WSIs. The proposed system was trained and tested on several WSI magnifications ranging from x4 to x40 with a best ROC AUC of 0.95 and an accuracy of 0.86 in test samples. This fully-automated histopathology subtyping method outperforms similar published state-of-the-art methods for diagnostic WSIs.

High Resolution Microscopy of Multi-Layered Biological Crystals

1982 ◽  
Vol 40 ◽  
pp. 80-83
Author(s):  
H.A. Cohen ◽  
T.W. Jeng ◽  
W. Chiu
Keyword(s):  
High Resolution ◽  
Low Dose ◽  
Three Dimensional ◽  
Data Interpretation ◽  
Two Dimensional ◽  
Biological Objects ◽  
Density Maps ◽  
Density Map ◽  
Complex Crystal ◽  
High Resolution Microscopy

This tutorial will discuss the methodology of low dose electron diffraction and imaging of crystalline biological objects, the problems of data interpretation for two-dimensional projected density maps of glucose embedded protein crystals, the factors to be considered in combining tilt data from three-dimensional crystals, and finally, the prospects of achieving a high resolution three-dimensional density map of a biological crystal. This methodology will be illustrated using two proteins under investigation in our laboratory, the T4 DNA helix destabilizing protein gp32*I and the crotoxin complex crystal.

A Comparison of Two Algorithms for Electron-Density Map Improvement by Introduction of Atomicity: Skeletonization, and Map Sorting Followed by Refinement

1998 ◽  
Vol 54 (1) ◽  
pp. 81-85 ◽  
Author(s):  
F. M. D. Vellieux
Keyword(s):  
Electron Density ◽  
Initial Density ◽  
Acta Cryst ◽  
Density Maps ◽  
Resolution Electron ◽  
Crystallographic Symmetry ◽  
Density Map ◽  
Ornithine Transcarbamoylase ◽  
Electron Density Map ◽  
Pseudo Atom

A comparison has been made of two methods for electron-density map improvement by the introduction of atomicity, namely the iterative skeletonization procedure of the CCP4 program DM [Cowtan & Main (1993). Acta Cryst. D49, 148–157] and the pseudo-atom introduction followed by the refinement protocol in the program suite DEMON/ANGEL [Vellieux, Hunt, Roy & Read (1995). J. Appl. Cryst. 28, 347–351]. Tests carried out using the 3.0 Å resolution electron density resulting from iterative 12-fold non-crystallographic symmetry averaging and solvent flattening for the Pseudomonas aeruginosa ornithine transcarbamoylase [Villeret, Tricot, Stalon & Dideberg (1995). Proc. Natl Acad. Sci. USA, 92, 10762–10766] indicate that pseudo-atom introduction followed by refinement performs much better than iterative skeletonization: with the former method, a phase improvement of 15.3° is obtained with respect to the initial density modification phases. With iterative skeletonization a phase degradation of 0.4° is obtained. Consequently, the electron-density maps obtained using pseudo-atom phases or pseudo-atom phases combined with density-modification phases are much easier to interpret. These tests also show that for ornithine transcarbamoylase, where 12-fold non-crystallographic symmetry is present in the P1 crystals, G-function coupling leads to the simultaneous decrease of the conventional R factor and of the free R factor, a phenomenon which is not observed when non-crystallographic symmetry is absent from the crystal. The method is far less effective in such a case, and the results obtained suggest that the map sorting followed by refinement stage should be by-passed to obtain interpretable electron-density distributions.

Deep learning to predict subtypes of poorly differentiated lung cancer from biopsy whole slide images.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8536-8536
Author(s):  
Gouji Toyokawa ◽  
Fahdi Kanavati ◽  
Seiya Momosaki ◽  
Kengo Tateishi ◽  
Hiroaki Takeoka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Deep Learning ◽  
Learning Model ◽  
Test Set ◽  
Cancer Subtypes ◽  
Independent Test ◽  
Poorly Differentiated ◽  
Test Sets ◽  
Deep Learning Model ◽  
Whole Slide Images

8536 Background: Lung cancer is the leading cause of cancer-related death in many countries, and its prognosis remains unsatisfactory. Since treatment approaches differ substantially based on the subtype, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC) and small cell lung cancer (SCLC), an accurate histopathological diagnosis is of great importance. However, if the specimen is solely composed of poorly differentiated cancer cells, distinguishing between histological subtypes can be difficult. The present study developed a deep learning model to classify lung cancer subtypes from whole slide images (WSIs) of transbronchial lung biopsy (TBLB) specimens, in particular with the aim of using this model to evaluate a challenging test set of indeterminate cases. Methods: Our deep learning model consisted of two separately trained components: a convolutional neural network tile classifier and a recurrent neural network tile aggregator for the WSI diagnosis. We used a training set consisting of 638 WSIs of TBLB specimens to train a deep learning model to classify lung cancer subtypes (ADC, SCC and SCLC) and non-neoplastic lesions. The training set consisted of 593 WSIs for which the diagnosis had been determined by pathologists based on the visual inspection of Hematoxylin-Eosin (HE) slides and of 45 WSIs of indeterminate cases (64 ADCs and 19 SCCs). We then evaluated the models using five independent test sets. For each test set, we computed the receiver operator curve (ROC) area under the curve (AUC). Results: We applied the model to an indeterminate test set of WSIs obtained from TBLB specimens that pathologists had not been able to conclusively diagnose by examining the HE-stained specimens alone. Overall, the model achieved ROC AUCs of 0.993 (confidence interval [CI] 0.971-1.0) and 0.996 (0.981-1.0) for ADC and SCC, respectively. We further evaluated the model using five independent test sets consisting of both TBLB and surgically resected lung specimens (combined total of 2490 WSIs) and obtained highly promising results with ROC AUCs ranging from 0.94 to 0.99. Conclusions: In this study, we demonstrated that a deep learning model could be trained to predict lung cancer subtypes in indeterminate TBLB specimens. The extremely promising results obtained show that if deployed in clinical practice, a deep learning model that is capable of aiding pathologists in diagnosing indeterminate cases would be extremely beneficial as it would allow a diagnosis to be obtained sooner and reduce costs that would result from further investigations.

scholarly journals Multiscale Aggregate Networks with Dense Connections for Crowd Counting

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Pengfei Li ◽  
Min Zhang ◽  
Jian Wan ◽  
Ming Jiang
Keyword(s):  
Mean Squared Error ◽  
Absolute Error ◽  
Image Features ◽  
Convolutional Network ◽  
Crowd Counting ◽  
Squared Error ◽  
Crowd Density ◽  
Density Maps ◽  
Density Map ◽  
Map Decoder

The most advanced method for crowd counting uses a fully convolutional network that extracts image features and then generates a crowd density map. However, this process often encounters multiscale and contextual loss problems. To address these problems, we propose a multiscale aggregation network (MANet) that includes a feature extraction encoder (FEE) and a density map decoder (DMD). The FEE uses a cascaded scale pyramid network to extract multiscale features and obtains contextual features through dense connections. The DMD uses deconvolution and fusion operations to generate features containing detailed information. These features can be further converted into high-quality density maps to accurately calculate the number of people in a crowd. An empirical comparison using four mainstream datasets (ShanghaiTech, WorldExpo’10, UCF_CC_50, and SmartCity) shows that the proposed method is more effective in terms of the mean absolute error and mean squared error. The source code is available at https://github.com/lpfworld/MANet.

Machine learning to identify lung cancer with tuberculosis from isolated tuberculosis (Preprint)

2021 ◽  
Author(s):  
Zhenhao Li
Keyword(s):  
Machine Learning ◽  
Lung Cancer ◽  
Cancer Patients ◽  
Tumor Markers ◽  
Learning Algorithm ◽  
Laboratory Data ◽  
Pathological Examination ◽  
Training Set ◽  
Lung Cancer Patients ◽  
Tb Pcr

UNSTRUCTURED Tuberculosis (TB) is a precipitating cause of lung cancer. Lung cancer patients coexisting with TB is difficult to differentiate from isolated TB patients. The aim of this study is to develop a prediction model in identifying those two diseases between the comorbidities and TB. In this work, based on the laboratory data from 389 patients, 81 features, including main laboratory examination of blood test, biochemical test, coagulation assay, tumor markers and baseline information, were initially used as integrated markers and then reduced to form a discrimination system consisting of 31 top-ranked indices. Patients diagnosed with TB PCR ＞1mtb/ml as negative samples, lung cancer patients with TB were confirmed by pathological examination and TB PCR ＞1mtb/ml as positive samples. We used Spatially Uniform ReliefF (SURF) algorithm to determine feature importance, and the predictive model was built using machine learning algorithm Random Forest. For cross-validation, the samples were randomly split into four training set and one test set. The selected features are composed of four tumor markers (Scc, Cyfra21-1, CEA, ProGRP and NSE), fifteen blood biochemical indices (GLU, IBIL, K, CL, Ur, NA, TBA, CHOL, SA, TG, A/G, AST, CA, CREA and CRP), six routine blood indices (EO#, EO%, MCV, RDW-S, LY# and MPV) and four coagulation indices (APTT ratio, APTT, PTA, TT ratio). This model presented a robust and stable classification performance, which can easily differentiate the comorbidity group from the isolated TB group with AUC, ACC, sensitivity and specificity of 0.8817, 0.8654, 0.8594 and 0.8656 for the training set, respectively. Overall, this work may provide a novel strategy for identifying the TB patients with lung cancer from routine admission lab examination with advantages of being timely and economical. It also indicated that our model with enough indices may further increase the effectiveness and efficiency of diagnosis.

Electron-density maps

2002 ◽  
Author(s):  
David Blow
Keyword(s):  
Fourier Transform ◽  
Electron Density ◽  
Three Dimensional ◽  
Two Dimensions ◽  
Unit Cell ◽  
Density Maps ◽  
Wave Cycle ◽  
Density Map ◽  
The Fourier Transform ◽  
Electron Density Map

When everything has been done to make the phases as good as possible, the time has come to examine the image of the structure in the form of an electron-density map. The electron-density map is the Fourier transform of the structure factors (with their phases). If the resolution and phases are good enough, the electron-density map may be interpreted in terms of atomic positions. In practice, it may be necessary to alternate between study of the electron-density map and the procedures mentioned in Chapter 10, which may allow improvements to be made to it. Electron-density maps contain a great deal of information, which is not easy to grasp. Considerable technical effort has gone into methods of presenting the electron density to the observer in the clearest possible way. The Fourier transform is calculated as a set of electron-density values at every point of a three-dimensional grid labelled with fractional coordinates x, y, z. These coordinates each go from 0 to 1 in order to cover the whole unit cell. To present the electron density as a smoothly varying function, values have to be calculated at intervals that are much smaller than the nominal resolution of the map. Say, for example, there is a protein unit cell 50 Å on a side, at a routine resolution of 2Å. This means that some of the waves included in the calculation of the electron density go through a complete wave cycle in 2 Å. As a rule of thumb, to represent this properly, the spacing of the points on the grid for calculation must be less than one-third of the resolution. In our example, this spacing might be 0.6 Å. To cover the whole of the 50 Å unit cell, about 80 values of x are needed; and the same number of values of y and z. The electron density therefore needs to be calculated on an array of 80×80×80 points, which is over half a million values. Although our world is three-dimensional, our retinas are two-dimensional, and we are good at looking at pictures and diagrams in two dimensions.

scholarly journals Identifying Cross-Scale Associations between Radiomic and Pathomic Signatures of Non-Small Cell Lung Cancer Subtypes: Preliminary Results

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3663
Author(s):  
Charlems Alvarez-Jimenez ◽  
Alvaro A. Sandino ◽  
Prateek Prasanna ◽  
Amit Gupta ◽  
Satish E. Viswanath ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Density ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Ct Images ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Subtypes ◽  
Initial Results

(1) Background: Despite the complementarity between radiology and histopathology, both from a diagnostic and a prognostic perspective, quantitative analyses of these modalities are usually performed in disconnected silos. This work presents initial results for differentiating two major non-small cell lung cancer (NSCLC) subtypes by exploring cross-scale associations between Computed Tomography (CT) images and corresponding digitized pathology images. (2) Methods: The analysis comprised three phases, (i) a multi-resolution cell density quantification to identify discriminant pathomic patterns for differentiating adenocarcinoma (ADC) and squamous cell carcinoma (SCC), (ii) radiomic characterization of CT images by using Haralick descriptors to quantify tumor textural heterogeneity as represented by gray-level co-occurrences to discriminate the two pathological subtypes, and (iii) quantitative correlation analysis between the multi-modal features to identify potential associations between them. This analysis was carried out using two publicly available digitized pathology databases (117 cases from TCGA and 54 cases from CPTAC) and a public radiological collection of CT images (101 cases from NSCLC-R). (3) Results: The top-ranked cell density pathomic features from the histopathology analysis were correlation, contrast, homogeneity, sum of entropy and difference of variance; which yielded a cross-validated AUC of 0.72 ± 0.02 on the training set (CPTAC) and hold-out validation AUC of 0.77 on the testing set (TCGA). Top-ranked co-occurrence radiomic features within NSCLC-R were contrast, correlation and sum of entropy which yielded a cross-validated AUC of 0.72 ± 0.01. Preliminary but significant cross-scale associations were identified between cell density statistics and CT intensity values using matched specimens available in the TCGA cohort, which were used to significantly improve the overall discriminatory performance of radiomic features in differentiating NSCLC subtypes (AUC = 0.78 ± 0.01). (4) Conclusions: Initial results suggest that cross-scale associations may exist between digital pathology and CT imaging which can be used to identify relevant radiomic and histopathology features to accurately distinguish lung adenocarcinomas from squamous cell carcinomas.

Sign in / Sign up

Export Citation Format

Share Document