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Mouse lung automated segmentation tool for quantifying lung tumors after micro-computed tomography.

ABSTRACT: Unlike the majority of cancers, survival for lung cancer has not shown much improvement since the early 1970s and survival rates remain low. Genetically engineered mice tumor models are of high translational relevance as we can generate tissue specific mutations which are observed in lung cancer patients. Since these tumors cannot be detected and quantified by traditional methods, we use micro-computed tomography imaging for longitudinal evaluation and to measure response to therapy. Conventionally, we analyze microCT images of lung cancer via a manual segmentation. Manual segmentation is time-consuming and sensitive to intra- and inter-analyst variation. To overcome the limitations of manual segmentation, we set out to develop a fully-automated alternative, the Mouse Lung Automated Segmentation Tool (MLAST). MLAST locates the thoracic region of interest, thresholds and categorizes the lung field into three tissue categories: soft tissue, intermediate, and lung. An increase in the tumor burden was measured by a decrease in lung volume with a simultaneous increase in soft and intermediate tissue quantities. MLAST segmentation was validated against three methods: manual scoring, manual segmentation, and histology. MLAST was applied in an efficacy trial using a Kras/Lkb1 non-small cell lung cancer model and demonstrated adequate precision and sensitivity in quantifying tumor growth inhibition after drug treatment. Implementation of MLAST has considerably accelerated the microCT data analysis, allowing for larger study sizes and mid-study readouts. This study illustrates how automated image analysis tools for large datasets can be used in preclinical imaging to deliver high throughput and quantitative results.

SUBMITTER: Montgomery MK

PROVIDER: S-EPMC8211241 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Lung segmentation is a fundamental step in many image analysis applications for lung diseases and abnormalities in thoracic computed tomography (CT). The authors have previously developed a lung segmentation method based on expectation-maximization (EM) analysis and morphological operations (EMM) for our computer-aided detection (CAD) system for pulmonary embolism (PE) in CT pulmonary angiography (CTPA). However, due to the large variations in pathology that may be present in thoracic CT images, it is difficult to extract the lung regions accurately, especially when the lung parenchyma contains extensive lung diseases. The purpose of this study is to develop a new method that can provide accurate lung segmentation, including those affected by lung diseases.An iterative neutrosophic lung segmentation (INLS) method was developed to improve the EMM segmentation utilizing the anatomic features of the ribs and lungs. The initial lung regions (ILRs) were extracted using our previously developed EMM method, in which the ribs were extracted using 3D hierarchical EM segmentation and the ribcage was constructed using morphological operations. Based on the anatomic features of ribs and lungs, the initial EMM segmentation was refined using INLS to obtain the final lung regions. In the INLS method, the anatomic features were mapped into a neutrosophic domain, and the neutrosophic operation was performed iteratively to refine the ILRs. With IRB approval, 5 and 58 CTPA scans were collected retrospectively and used as training and test sets, of which 2 and 34 cases had lung diseases, respectively. The lung regions manually outlined by an experienced thoracic radiologist were used as reference standard for performance evaluation of the automated lung segmentation. The percentage overlap area (POA), the Hausdorff distance (Hdist), and the average distance (AvgDist) of the lung boundaries relative to the reference standard were used as performance metrics.The proposed method achieved larger POAs and smaller distance errors than the EMM method. For the 58 test cases, the average POA, Hdist, and AvgDist were improved from 85.4±18.4%, 22.6±29.4 mm, and 3.5±5.4 mm using EMM to 91.2±6.7%, 16.0±11.3 mm, and 2.5±1.0 mm using INLS, respectively. The improvements were statistically significant (p<0.05). To evaluate the accuracy of the INLS method in the identification of the lung boundaries affected by lung diseases, the authors separately analyzed the performance of the proposed method on the cases with versus without the lung diseases. The results showed that the cases without lung diseases were segmented more accurately than the cases with lung diseases by both the EMM and the INLS methods, but the INLS method achieved better performance than the EMM method in both cases.The new INLS method utilizing the anatomic features of the rib and lung significantly improved the accuracy of lung segmentation, especially for the cases affected by lung diseases. Improvement in lung segmentation will facilitate many image analysis tasks and CAD applications for lung diseases and abnormalities in thoracic CT, including automated PE detection.

Project description:BackgroundIn vivo high-resolution micro-computed tomography allows for longitudinal image-based measurements in animal models of lung disease. The combination of repetitive high resolution imaging with fully automated quantitative image analysis in mouse models of lung fibrosis lung benefits preclinical research. This study aimed to develop and validate such an automated micro-computed tomography analysis algorithm for quantification of aerated lung volume in mice; an indicator of pulmonary fibrosis and emphysema severity.MethodologyMice received an intratracheal instillation of bleomycin (n = 8), elastase (0.25 U elastase n = 9, 0.5 U elastase n = 8) or saline control (n = 6 for fibrosis, n = 5 for emphysema). A subset of mice was scanned without intervention, to evaluate potential radiation-induced toxicity (n = 4). Some bleomycin-instilled mice were treated with imatinib for proof of concept (n = 8). Mice were scanned weekly, until four weeks after induction, when they underwent pulmonary function testing, lung histology and collagen quantification. Aerated lung volumes were calculated with our automated algorithm.Principal findingsOur automated image-based aerated lung volume quantification method is reproducible with low intra-subject variability. Bleomycin-treated mice had significantly lower scan-derived aerated lung volumes, compared to controls. Aerated lung volume correlated with the histopathological fibrosis score and total lung collagen content. Inversely, a dose-dependent increase in lung volume was observed in elastase-treated mice. Serial scanning of individual mice is feasible and visualized dynamic disease progression. No radiation-induced toxicity was observed. Three-dimensional images provided critical topographical information.ConclusionsWe report on a high resolution in vivo micro-computed tomography image analysis algorithm that runs fully automated and allows quantification of aerated lung volume in mice. This method is reproducible with low inherent measurement variability. We show that it is a reliable quantitative tool to investigate experimental lung fibrosis and emphysema in mice. Its non-invasive nature has the unique benefit to allow dynamic 4D evaluation of disease processes and therapeutic interventions.

Project description:ObjectiveWe aimed to develop a deep neural network for segmenting lung parenchyma with extensive pathological conditions on non-contrast chest computed tomography (CT) images.Materials and methodsThin-section non-contrast chest CT images from 203 patients (115 males, 88 females; age range, 31-89 years) between January 2017 and May 2017 were included in the study, of which 150 cases had extensive lung parenchymal disease involving more than 40% of the parenchymal area. Parenchymal diseases included interstitial lung disease (ILD), emphysema, nontuberculous mycobacterial lung disease, tuberculous destroyed lung, pneumonia, lung cancer, and other diseases. Five experienced radiologists manually drew the margin of the lungs, slice by slice, on CT images. The dataset used to develop the network consisted of 157 cases for training, 20 cases for development, and 26 cases for internal validation. Two-dimensional (2D) U-Net and three-dimensional (3D) U-Net models were used for the task. The network was trained to segment the lung parenchyma as a whole and segment the right and left lung separately. The University Hospitals of Geneva ILD dataset, which contained high-resolution CT images of ILD, was used for external validation.ResultsThe Dice similarity coefficients for internal validation were 99.6 ± 0.3% (2D U-Net whole lung model), 99.5 ± 0.3% (2D U-Net separate lung model), 99.4 ± 0.5% (3D U-Net whole lung model), and 99.4 ± 0.5% (3D U-Net separate lung model). The Dice similarity coefficients for the external validation dataset were 98.4 ± 1.0% (2D U-Net whole lung model) and 98.4 ± 1.0% (2D U-Net separate lung model). In 31 cases, where the extent of ILD was larger than 75% of the lung parenchymal area, the Dice similarity coefficients were 97.9 ± 1.3% (2D U-Net whole lung model) and 98.0 ± 1.2% (2D U-Net separate lung model).ConclusionThe deep neural network achieved excellent performance in automatically delineating the boundaries of lung parenchyma with extensive pathological conditions on non-contrast chest CT images.

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Mouse lung automated segmentation tool for quantifying lung tumors after micro-computed tomography.

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