Artificial intelligence solution to classify pulmonary nodules on CT.

PURPOSE: The purpose of this study was to create an algorithm to detect and classify pulmonary nodules in two categories based on their volume greater than 100 mm3 or not, using machine learning and deep learning techniques. MATERIALS AND METHOD: The dataset used to train the model was provided by the organization team of the SFR (French Radiological Society) Data Challenge 2019. An asynchronous and parallel 3-stages pipeline was developed to process all the data (a data "pre-processing" stage; a "nodule detection" stage; a "classifier" stage). Lung segmentation was achieved using 3D U-NET algorithm; nodule detection was done using 3D Retina-UNET and classifier stage with a support vector machine algorithm on selected features. Performances were assessed using area under receiver operating characteristics curve (AUROC). RESULTS: The pipeline showed good performance for pathological nodule detection and patient diagnosis. With the preparation dataset, an AUROC of 0.9058 (95% confidence interval [CI]: 0.8746-0.9362) was obtained, 87% yielding accuracy (95% CI: 84.83%-91.03%) for the "nodule detection" stage, corresponding to 86% specificity (95% CI: 82%-92%) and 89% sensitivity (95% CI: 84.83%-91.03%). CONCLUSION: A fully functional pipeline using 3D U-NET, 3D Retina-UNET and classifier stage with a support vector machine algorithm was developed, resulting in high capabilities for pulmonary nodule classification.

Differentiation of Benign from Malignant Pulmonary Nodules by Using a Convolutional Neural Network to Determine Volume Change at Chest CT.

Background Deep learning may help to improve computer-aided detection of volume (CADv) measurement of pulmonary nodules at chest CT. Purpose To determine the efficacy of a deep learning method for improving CADv for measuring the solid and ground-glass opacity (GGO) volumes of a nodule, doubling time (DT), and the change in volume at chest CT. Materials and Methods From January 2014 to December 2016, patients with pulmonary nodules at CT were retrospectively reviewed. CADv without and with a convolutional neural network (CNN) automatically determined total nodule volume change per day and DT. Area under the curves (AUCs) on a per-nodule basis and diagnostic accuracy on a per-patient basis were compared among all indexes from CADv with and without CNN for differentiating benign from malignant nodules. Results The CNN training set was 294 nodules in 217 patients, the validation set was 41 nodules in 32 validation patients, and the test set was 290 nodules in 188 patients. A total of 170 patients had 290 nodules (mean size ± standard deviation, 11 mm ± 5; range, 4-29 mm) diagnosed as 132 malignant nodules and 158 benign nodules. There were 132 solid nodules (46%), 106 part-solid nodules (36%), and 52 ground-glass nodules (18%). The test set results showed that the diagnostic performance of the CNN with CADv for total nodule volume change per day was larger than DT of CADv with CNN (AUC, 0.94 [95% confidence interval {CI}: 0.90, 0.96] vs 0.67 [95% CI: 0.60, 0.74]; P < .001) and CADv without CNN (total nodule volume change per day: AUC, 0.69 [95% CI: 0.62, 0.75]; P < .001; DT: AUC, 0.58 [95% CI: 0.51, 0.65]; P < .001). The accuracy of total nodule volume change per day of CADv with CNN was significantly higher than that of CADv without CNN (P < .001) and DT of both methods (P < .001). Conclusion Convolutional neural network is useful for improving accuracy of computer-aided detection of volume measurement and nodule differentiation capability at CT for patients with pulmonary nodules. © RSNA, 2020 Online supplemental material is available for this article.

Joint use of the radiomics method and frozen sections should be considered in the prediction of the final classification of peripheral lung adenocarcinoma manifesting as ground-glass nodules.

OBJECTIVES: To evaluate the diagnostic accuracy of radiomics method and frozen sections (FS) for the pathological classification of peripheral lung adenocarcinoma manifesting as ground-glass nodules (GGNs) in computer tomography (CT). MATERIALS AND METHODS: A dataset of 831 peripheral lung adenocarcinoma manifesting as GGNs in CT were divided into two cohorts: training cohort (n = 581) and validation cohort (n = 250). Combined with clinical features, the radiomics classifier was trained and validated to distinguish the pathological classification of these nodules. FS diagnoses in the validation cohort were collected. Diagnostic performance of the FS and radiomics methods was compared in the validation cohort. The predictive factors for the misdiagnosis of FS were determined via univariate and multivariate analyses. RESULTS: The accuracy of radiomics method in the training and validation cohorts was 72.5 % and 68.8 % respectively. The overall accuracy of FS in the validation cohort was 70.0 %. The concordance rate between FS and final pathology when FS had a different diagnosis from radiomics classifier was significantly lower than when FS had the same diagnosis as radiomics classifier (46 vs. 87 %, P < 0.001). Univariate and Multivariate analyses showed that different diagnosis between FS and radiomics classifier was the independent predictive factor for the misdiagnosis of FS (OR: 7.46; 95%CI: 4.00-13.91; P < 0.001). CONCLUSIONS: Radiomics classifier predictions may be a reliable reference for the classification of peripheral lung adenocarcinoma manifesting as GGNs when FS cannot provide a timely diagnosis. Intraoperative diagnoses of the cases where FS had a different diagnosis from radiomics method should be considered cautiously due to the higher misdiagnosis rate.

Primary solid lung cancerous nodules with different sizes: computed tomography features and their variations.

BACKGROUND: The computed tomography (CT) features of small solid lung cancers and their changing regularity as they grow have not been well studied. The purpose of this study was to analyze the CT features of solid lung cancerous nodules (SLCNs) with different sizes and their variations. METHODS: Between February 2013 and April 2018, a consecutive cohort of 224 patients (225 nodules) with confirmed primary SLCNs was enrolled. The nodules were divided into four groups based on tumor diameter (A: diameter ≤ 1.0 cm, 35 lesions; B: 1.0 cm < diameter ≤ 1.5 cm, 60 lesions; C: 1.5 cm < diameter ≤ 2.0 cm, 63 lesions; and D: 2.0 cm < diameter ≤ 3.0 cm, 67 lesions). CT features of nodules within each group were summarized and compared. RESULTS: Most nodules in different groups were located in upper lobes (groups A - D:50.8%-73.1%) and had a gap from the pleura (groups A - D:89.6%-100%). The main CT features of smaller (diameter ≤ 1 cm) and larger (diameter > 1 cm) nodules were significantly different. As nodule diameter increased, more lesions showed a regular shape, homogeneous density, clear but coarse tumor-lung interface, lobulation, spiculation, spinous protuberance, vascular convergence, pleural retraction, bronchial truncation, and beam-shaped opacity (p < 0.05 for all). The presence of halo sign in all groups was similar (17.5%-22.5%; p > 0.05). CONCLUSIONS: The CT features vary among SLCNs with different sizes. Understanding their changing regularity is helpful for identifying smaller suspicious malignant nodules and early determining their nature in follow-up.

Localized thin-section CT with radiomics feature extraction and machine learning to classify early-detected pulmonary nodules from lung cancer screening.

Lung cancer screening aims to detect small pulmonary nodules and decrease the mortality rate of those affected. However, studies from large-scale clinical trials of lung cancer screening have shown that the false-positive rate is high and positive predictive value is low. To address these problems, a technical approach is greatly needed for accurate malignancy differentiation among these early-detected nodules. We studied the clinical feasibility of an additional protocol of localized thin-section CT for further assessment on recalled patients from lung cancer screening tests. Our approach of localized thin-section CT was integrated with radiomics features extraction and machine learning classification which was supervised by pathological diagnosis. Localized thin-section CT images of 122 nodules were retrospectively reviewed and 374 radiomics features were extracted. In this study, 48 nodules were benign and 74 malignant. There were nine patients with multiple nodules and four with synchronous multiple malignant nodules. Different machine learning classifiers with a stratified ten-fold cross-validation were used and repeated 100 times to evaluate classification accuracy. Of the image features extracted from the thin-section CT images, 238 (64%) were useful in differentiating between benign and malignant nodules. These useful features include CT density (p = 0.002 518), sigma (p = 0.002 781), uniformity (p = 0.032 41), and entropy (p = 0.006 685). The highest classification accuracy was 79% by the logistic classifier. The performance metrics of this logistic classification model was 0.80 for the positive predictive value, 0.36 for the false-positive rate, and 0.80 for the area under the receiver operating characteristic curve. Our approach of direct risk classification supervised by the pathological diagnosis with localized thin-section CT and radiomics feature extraction may support clinical physicians in determining truly malignant nodules and therefore reduce problems in lung cancer screening.

Computer-aided diagnosis of lung cancer: the effect of training data sets on classification accuracy of lung nodules.

This study aims to develop a computer-aided diagnosis (CADx) scheme for classification between malignant and benign lung nodules, and also assess whether CADx performance changes in detecting nodules associated with early and advanced stage lung cancer. The study involves 243 biopsy-confirmed pulmonary nodules. Among them, 76 are benign, 81 are stage I and 86 are stage III malignant nodules. The cases are separated into three data sets involving: (1) all nodules, (2) benign and stage I malignant nodules, and (3) benign and stage III malignant nodules. A CADx scheme is applied to segment lung nodules depicted on computed tomography images and we initially computed 66 3D image features. Then, three machine learning models namely, a support vector machine, naïve Bayes classifier and linear discriminant analysis, are separately trained and tested by using three data sets and a leave-one-case-out cross-validation method embedded with a Relief-F feature selection algorithm. When separately using three data sets to train and test three classifiers, the average areas under receiver operating characteristic curves (AUC) are 0.94, 0.90 and 0.99, respectively. When using the classifiers trained using data sets with all nodules, average AUC values are 0.88 and 0.99 for detecting early and advanced stage nodules, respectively. AUC values computed from three classifiers trained using the same data set are consistent without statistically significant difference (p > 0.05). This study demonstrates (1) the feasibility of applying a CADx scheme to accurately distinguish between benign and malignant lung nodules, and (2) a positive trend between CADx performance and cancer progression stage. Thus, in order to increase CADx performance in detecting subtle and early cancer, training data sets should include more diverse early stage cancer cases.

Subsolid Lung Nodule Classification: A CT Criterion for Improving Interobserver Agreement.

Purpose To evaluate an objective computed tomographic (CT) criterion for distinguishing between part-solid (PS) and nonsolid (NS) lung nodules. Materials and Methods This study received institutional review board approval, and patients gave informed consent. Preoperative CT studies in all patients who underwent surgery for subsolid nodules between 2008 and 2015 were first reviewed by two senior radiologists, who subjectively classified the nodules as PS or NS. A second reading performed 1 month later used predefined classification criteria and involved a third senior radiologist as well as three junior radiologists. Subsolid nodules were classified as PS if a solid portion was detectable in the mediastinal window setting (nonmeasurable, < 50%, or > 50% of the entire nodule) and were otherwise classified as NS (subclassified as pure or heterogeneous). Interreader agreement was assessed with κ statistics and the intraclass correlation coefficient (ICC). Results A total of 99 nodules measuring a median of 20 mm (range, 5-47 mm) in lung window CT images were analyzed. Senior radiologist agreement on the PS/NS distinction increased from moderate (κ = 0.54; 95% confidence interval [CI]: 0.37, 0.71) to excellent (κ = 0.89; 95% CI: 0.80, 0.98) between the first and second readings. At the second readings, agreement among senior and junior radiologists was excellent for PS/NS distinction (ICC = 0.87; 95% CI: 0.83, 0.90) and for subcategorization (ICC = 0.82; 95% CI: 0.77, 0.87). When a solid portion was measurable in the mediastinal window, the specificity for adenocarcinoma invasiveness ranged from 86% to 96%. Conclusion Detection of a solid portion in the mediastinal window setting allows subsolid nodules to be classified as PS with excellent interreader agreement. If the solid portion is measurable, the specificity for adenocarcinoma invasiveness is high. © RSNA, 2017 Online supplemental material is available for this article.

Pulmonary subsolid nodules: value of semi-automatic measurement in diagnostic accuracy, diagnostic reproducibility and nodule classification agreement.

OBJECTIVES: We hypothesized that semi-automatic diameter measurements would improve the accuracy and reproducibility in discriminating preinvasive lesions and minimally invasive adenocarcinomas from invasive pulmonary adenocarcinomas appearing as subsolid nodules (SSNs) and increase the reproducibility in classifying SSNs. METHODS: Two readers independently performed semi-automatic and manual measurements of the diameters of 102 SSNs and their solid portions. Diagnostic performance in predicting invasive adenocarcinoma based on diameters was tested using logistic regression analysis with subsequent receiver operating characteristic curves. Inter- and intrareader reproducibilities of diagnosis and SSN classification according to Fleischner's guidelines were investigated for each measurement method using Cohen's κ statistics. RESULTS: Semi-automatic effective diameter measurements were superior to manual average diameters for the diagnosis of invasive adenocarcinoma (AUC, 0.905-0.923 for semi-automatic measurement and 0.833-0.864 for manual measurement; p<0.05). Reproducibility of diagnosis between the readers also improved with semi-automatic measurement (κ=0.924 for semi-automatic measurement and 0.690 for manual measurement, p=0.012). Inter-reader SSN classification reproducibility was significantly higher with semi-automatic measurement (κ=0.861 for semi-automatic measurement and 0.683 for manual measurement, p=0.022). CONCLUSIONS: Semi-automatic effective diameter measurement offers an opportunity to improve diagnostic accuracy and reproducibility as well as the classification reproducibility of SSNs. KEY POINTS: • Semi-automatic effective diameter measurement improves the diagnostic accuracy for pulmonary subsolid nodules. • Semi-automatic measurement increases the inter-reader agreement on the diagnosis for subsolid nodules. • Semi-automatic measurement augments the inter-reader reproducibility for the classification of subsolid nodules.

Measurement Variability of Persistent Pulmonary Subsolid Nodules on Same-Day Repeat CT: What Is the Threshold to Determine True Nodule Growth during Follow-Up?

PURPOSE: To assess the measurement variability of subsolid nodules (SSNs) in follow-up situations and to compare the degree of variability between measurement metrics. METHODS: Two same-day repeat-CT scans of 69 patients (24 men and 45 women) with 69 SSNs were randomly assigned as initial or follow-up scans and were read by the same (situation 1) or different readers (situation 2). SSN size and solid portion size were measured in both situations. Measurement variability was calculated and coefficients of variation were used for comparisons. RESULTS: Measurement variability for the longest and average diameter of SSNs was ±1.3 mm (±13.0%) and ±1.3 mm (±14.4%) in situation 1, and ±2.2 mm (±21.0%) and ±2.1 mm (±21.3%) in situation 2, respectively. For solid portion, measurement variability on lung and mediastinal windows was ±1.2 mm (±27.1%) and ±0.8 mm (±24.0%) in situation 1, and ±3.7 mm (±61.0%) and ±1.5 mm (±47.3%) in situation 2, respectively. There were no significant differences in the degree of variability between the longest and average diameters and between the lung and mediastinal window settings (p>0.05). However, measurement variability significantly increased when the follow-up and initial CT readers were different (p<0.001). CONCLUSIONS: A cutoff of ±2.2 mm can be reliably used to determine true nodule growth on follow-up CT. Solid portion measurements were not reliable in evaluating SSNs' change when readers of initial and follow-up CT were different.

Breath carbonyl compounds as biomarkers of lung cancer.

OBJECTIVE: Lung cancer dysregulations impart oxidative stress which results in important metabolic products in the form of volatile organic compounds (VOCs) in exhaled breath. The objective of this work is to use statistical classification models to determine specific carbonyl VOCs in exhaled breath as biomarkers for detection of lung cancer. MATERIALS AND METHODS: Exhaled breath samples from 85 patients with untreated lung cancer, 34 patients with benign pulmonary nodules and 85 healthy controls were collected. Carbonyl compounds in exhaled breath were captured by silicon microreactors and analyzed by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The concentrations of carbonyl compounds were analyzed using a variety of statistical classification models to determine which compounds best differentiated between the patient sub-populations. Predictive accuracy of each of the models was assessed on a separate test data set. RESULTS: Six carbonyl compounds (C(4)H(8)O, C(5)H(10)O, C(2)H(4)O(2), C(4)H(8)O(2), C(6)H(10)O(2), C(9)H(16)O(2)) had significantly elevated concentrations in lung cancer patients vs. CONTROLS: A model based on counting the number of elevated compounds out of these six achieved an overall classification accuracy on the test data of 97% (95% CI 92%-100%), 95% (95% CI 88%-100%), and 89% (95% CI 79%-99%) for classifying lung cancer patients vs. non-smokers, current smokers, and patients with benign nodules, respectively. These results were comparable to benchmarking based on established statistical and machine-learning methods. The sensitivity in each case was 96% or higher, with specificity ranging from 64% for benign nodule patients to 86% for smokers and 100% for non-smokers. CONCLUSION: A model based on elevated levels of the six carbonyl VOCs effectively discriminates lung cancer patients from healthy controls as well as patients with benign pulmonary nodules.

Using Clinical Risk Models for Lung Nodule Classification.

Evaluation and diagnosis of indeterminate pulmonary nodules is a significant and increasing burden on our health care system. The advent of lung cancer screening with low-dose computed tomography only exacerbates this problem, and more surgeons will be evaluating smaller and screening discovered nodules. Multiple calculators exist that can help the clinician diagnose lung cancer at the bedside. The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) model helps to determine who needs lung cancer screening, and the McWilliams and Mayo models help to guide the primary care clinician or pulmonologist with diagnosis by estimating the probability of cancer in patients with indeterminate pulmonary nodules. The Thoracic Research Evaluation And Treatment (TREAT) model assists surgeons to determine who needs a surgical biopsy among patients referred for suspicious lesions. Additional work is needed to develop decision support tools that will facilitate the use of these models in clinical practice, to complement the clinician's judgment and enhance shared decision making with the patient at the bedside.

Validation of a multiprotein plasma classifier to identify benign lung nodules.

INTRODUCTION: Indeterminate pulmonary nodules (IPNs) lack clinical or radiographic features of benign etiologies and often undergo invasive procedures unnecessarily, suggesting potential roles for diagnostic adjuncts using molecular biomarkers. The primary objective was to validate a multivariate classifier that identifies likely benign lung nodules by assaying plasma protein expression levels, yielding a range of probability estimates based on high negative predictive values (NPVs) for patients with 8 to 30 mm IPNs. METHODS: A retrospective, multicenter, case-control study was performed using multiple reaction monitoring mass spectrometry, a classifier comprising five diagnostic and six normalization proteins, and blinded analysis of an independent validation set of plasma samples. RESULTS: The classifier achieved validation on 141 lung nodule-associated plasma samples based on predefined statistical goals to optimize sensitivity. Using a population based nonsmall-cell lung cancer prevalence estimate of 23% for 8 to 30 mm IPNs, the classifier identified likely benign lung nodules with 90% negative predictive value and 26% positive predictive value, as shown in our prior work, at 92% sensitivity and 20% specificity, with the lower bound of the classifier's performance at 70% sensitivity and 48% specificity. Classifier scores for the overall cohort were statistically independent of patient age, tobacco use, nodule size, and chronic obstructive pulmonary disease diagnosis. The classifier also demonstrated incremental diagnostic performance in combination with a four-parameter clinical model. CONCLUSIONS: This proteomic classifier provides a range of probability estimates for the likelihood of a benign etiology that may serve as a noninvasive, diagnostic adjunct for clinical assessments of patients with IPNs.

Persistent pulmonary subsolid nodules: model-based iterative reconstruction for nodule classification and measurement variability on low-dose CT.

OBJECTIVES: To compare the pulmonary subsolid nodule (SSN) classification agreement and measurement variability between filtered back projection (FBP) and model-based iterative reconstruction (MBIR). METHODS: Low-dose CTs were reconstructed using FBP and MBIR for 47 patients with 47 SSNs. Two readers independently classified SSNs into pure or part-solid ground-glass nodules, and measured the size of the whole nodule and solid portion twice on both reconstruction algorithms. Nodule classification agreement was analyzed using Cohen's kappa and compared between reconstruction algorithms using McNemar's test. Measurement variability was investigated using Bland-Altman analysis and compared with the paired t-test. RESULTS: Cohen's kappa for inter-reader SSN classification agreement was 0.541-0.662 on FBP and 0.778-0.866 on MBIR. Between the two readers, nodule classification was consistent in 79.8 % (75/94) with FBP and 91.5 % (86/94) with MBIR (p = 0.027). Inter-reader measurement variability range was -5.0-2.1 mm on FBP and -3.3-1.8 mm on MBIR for whole nodule size, and was -6.5-0.9 mm on FBP and -5.5-1.5 mm on MBIR for solid portion size. Inter-reader measurement differences were significantly smaller on MBIR (p = 0.027, whole nodule; p = 0.011, solid portion). CONCLUSIONS: MBIR significantly improved SSN classification agreement and reduced measurement variability of both whole nodules and solid portions between readers. KEY POINTS: • Low-dose CT using MBIR algorithm improves reproducibility in the classification of SSNs. • MBIR would enable more confident clinical planning according to the SSN type. • Reduced measurement variability on MBIR allows earlier detection of potentially malignant nodules.

Investigating recurrent neural networks for OCT A-scan based tissue analysis.

OBJECTIVES: Optical Coherence Tomography (OCT) has been proposed as a high resolution image modality to guide transbronchial biopsies. In this study we address the question, whether individual A-scans obtained in needle direction can contribute to the identification of pulmonary nodules. METHODS: OCT A-scans from freshly resected human lung tissue specimen were recorded through a customized needle with an embedded optical fiber. Bidirectional Long Short Term Memory networks (BLSTMs) were trained on randomly distributed training and test sets of the acquired A-scans. Patient specific training and different pre-processing steps were evaluated. RESULTS: Classification rates from 67.5% up to 76% were archived for different training scenarios. Sensitivity and specificity were highest for a patient specific training with 0.87 and 0.85. Low pass filtering decreased the accuracy from 73.2% on a reference distribution to 62.2% for higher cutoff frequencies and to 56% for lower cutoff frequencies. CONCLUSION: The results indicate that a grey value based classification is feasible and may provide additional information for diagnosis and navigation. Furthermore, the experiments show patient specific signal properties and indicate that the lower and upper parts of the frequency spectrum contribute to the classification.

Current readings: the most influential and recent studies regarding resection of lung cancer in m1a disease.

M1A disease is a recent concept appearing in the 7th TNM classification of lung cancer. M1A encompasses two different entities, malignant pleural or pericardial effusions and separate tumor nodules in the contralateral lung, who constitute very different diseases, with very different management and prognoses. On one hand, patients with pleural dissemination have extremely poor survival, with median and 5-year survivals of 4 months and 3.1%, respectively. Only selected patients whose limited pleural extension has been diagnosed at the time of thoracotomy and completely resected, may experience prolonged survival. On the other hand, recent progress in molecular biology still failed to establish whether a contralateral lesion is a second primary or a metastasis. These contralateral lesions are now gathered as multiple lung cancers in the surgical literature, and misleadingly classified as M1A disease in the TNM classification. Patients with contralateral nodules may experience prolonged survival after the surgical treatment of both localizations. Changing the staging by establishing the diagnosis of metastasis is probably an important issue warranting further biologic research, but according to current results this diagnosis must not in any case preclude surgery.

Classification of pulmonary nodules by using hybrid features.

Early detection of pulmonary nodules is extremely important for the diagnosis and treatment of lung cancer. In this study, a new classification approach for pulmonary nodules from CT imagery is presented by using hybrid features. Four different methods are introduced for the proposed system. The overall detection performance is evaluated using various classifiers. The results are compared to similar techniques in the literature by using standard measures. The proposed approach with the hybrid features results in 90.7% classification accuracy (89.6% sensitivity and 87.5% specificity).