Literature DB >> 34337394

Lung Cancer Segmentation With Transfer Learning: Usefulness of a Pretrained Model Constructed From an Artificial Dataset Generated Using a Generative Adversarial Network.

Mizuho Nishio1,2, Koji Fujimoto1,3, Hidetoshi Matsuo2, Chisako Muramatsu4, Ryo Sakamoto1,5, Hiroshi Fujita6.   

Abstract

Purpose: The purpose of this study was to develop and evaluate lung cancer segmentation with a pretrained model and transfer learning. The pretrained model was constructed from an artificial dataset generated using a generative adversarial network (GAN). Materials and
Methods: Three public datasets containing images of lung nodules/lung cancers were used: LUNA16 dataset, Decathlon lung dataset, and NSCLC radiogenomics. The LUNA16 dataset was used to generate an artificial dataset for lung cancer segmentation with the help of the GAN and 3D graph cut. Pretrained models were then constructed from the artificial dataset. Subsequently, the main segmentation model was constructed from the pretrained models and the Decathlon lung dataset. Finally, the NSCLC radiogenomics dataset was used to evaluate the main segmentation model. The Dice similarity coefficient (DSC) was used as a metric to evaluate the segmentation performance.
Results: The mean DSC for the NSCLC radiogenomics dataset improved overall when using the pretrained models. At maximum, the mean DSC was 0.09 higher with the pretrained model than that without it.
Conclusion: The proposed method comprising an artificial dataset and a pretrained model can improve lung cancer segmentation as confirmed in terms of the DSC metric. Moreover, the construction of the artificial dataset for the segmentation using the GAN and 3D graph cut was found to be feasible.
Copyright © 2021 Nishio, Fujimoto, Matsuo, Muramatsu, Sakamoto and Fujita.

Entities:  

Keywords:  computed tomography; deep learning; generative adversarial network 3; lung cancer; lung nodule; segmentation

Year:  2021        PMID: 34337394      PMCID: PMC8322116          DOI: 10.3389/frai.2021.694815

Source DB:  PubMed          Journal:  Front Artif Intell        ISSN: 2624-8212


Introduction

Segmentation of lung cancer is an important research topic, and various studies have been conducted so far. Segmentation results are used to determine the effectiveness of anticancer drugs (Mozley et al., 2012; Hayes et al., 2016) and to perform texture analyses on medical images (Bashir et al., 2017; Yang et al., 2020). To use the segmentation results of lung cancer effectively, the segmentation accuracy is an important factor. Segmentation is typically done manually by radiologists; however, manual segmentation can sometimes yield inaccurate results because of interobserver variability. Semiautomatic segmentation has lower interobserver variability than manual segmentation (Pfaehler et al., 2020). To overcome this interobserver variability, an automatic segmentation of lung cancer is desirable. Recent years have witnessed significant development in the application of deep learning to various domains, including in the area of segmentation. For example, deep learning has been applied to the automatic segmentation of organs, such as the lungs, liver, pancreas, uterus, and bones, and to the automatic segmentation of tumors in these organs, with good segmentation performance (Roth et al., 2015; Chlebus et al., 2018; Isensee et al., 2018; Chen et al., 2019; Gordienko et al., 2019; Kurata et al., 2019; Noguchi et al., 2020; Hodneland et al., 2021). One of the problems in the application of deep learning is a dataset. Deep learning does not perform well when the dataset is small. In general, it is difficult to increase the size of datasets containing medical images compared with other domains. This is due to the high cost of acquiring medical images and the need to protect personal information. To this end, transfer learning with pretrained models (Shin et al., 2016; Tschandl et al., 2019), data augmentation (Zhang et al., 2017; Yun et al., 2019), and artificial generation of datasets using generative adversarial networks (GANs) (Muramatsu et al., 2020) have been developed. The GAN was first proposed by Goodfellow et al. (2014). The recent improvements made to the GAN have made it possible to generate high-quality, high-resolution images. Various attempts have been made to apply the GAN to medical image processing. Several studies have shown that it is possible to generate CT images of lung nodules using the GAN (Jin et al., 2018; Han et al., 2019; Onishi et al., 2019; Yang et al., 2019; Yi et al., 2019; Armanious et al., 2020). To overcome the small dataset problem for segmentation, we proposed to use deep learning models pretrained with an artificially generated dataset using the GAN. We hypothesized that transfer learning with the proposed pretrained models could improve the automatic segmentation accuracy when using the lung cancer dataset. In general, a segmentation model obtained through supervised learning requires an image and its label as the dataset. In our study, to generate a dataset for segmentation, we used the GAN for image generation and the 3D graph cut method for generating labels of the generated images. No manual task for labeling was required to generate the dataset for pretraining.

Materials and Methods

Our study used anonymized data extracted from public databases. Therefore, institutional review board approval was waived in accordance with the regulations of our country. Figure 1 shows the outline of the proposed method for the segmentation model.
FIGURE 1

Outline of the proposed method for the segmentation model.

Outline of the proposed method for the segmentation model.

Dataset

Three public datasets containing computed tomography (CT) images were used: LUng Nodule Analysis 2016 (LUNA16) dataset, Decathlon lung dataset, and NSCLC radiogenomics. Table 1 shows a summary of the three datasets.
TABLE 1

Summary of three datasets.

DatasetNumber of all CT scansNumber of CT scans used in this studySelection criteriaUsage of dataset
LUNA168881653D CT images with small lung nodules (the size of each nodule was <6 mm) were selectedFrom the LUNA16 dataset, the GAN generated an artificial dataset with generated lung nodules. The pretrained model for lung cancer segmentation was obtained from the artificial dataset with original nnUnet.
Decathlon (task06, lung)63■ 63 (Decathlonfull) ■ 30 (Decathlonmid) ■ 10 (Decathlonsmall)For Decathlonfull, no selection criteria. The image files of the Decathlon dataset were sorted by file name, and the first 10 or 30 files were selected for Decathlonsmall and Decathlonmid Decathlon dataset was used for training and validation sets of lung cancer segmentation. Modified nnUnet was trained based on the validation set of the Decathlon dataset and the pretrained model.
NSCLC radiogenomics211144Segmentation labels are availableNSCLC radiogenomics was used for test set of lung cancer segmentation (not used for the validation set).

Abbreviations: GAN, generative adversarial network.

Summary of three datasets. Abbreviations: GAN, generative adversarial network. The LUNA16 dataset includes 888 sets of 3D CT images (Grand-Challenges, 2016; Setio et al., 2017) constructed for lung nodule detection. Therefore, the original LUNA16 dataset is unsuitable for segmentation. A previous study used the LUNA16 dataset to generate images of lung nodules using the GAN (Nishio et al., 2020a). We used the same dataset and a GAN model to generate the dataset for segmentation. For image preprocessing, the voxel size of the 3D CT images in the LUNA16 dataset was changed (1 mm × 1 mm × 1 mm isotropic). To generate lung cancer–like nodules and their labels in the LUNA16 dataset, large true nodules are problematic because labels of true nodules are not available in the LUNA16. Therefore, sets of 3D CT images with small lung nodules (the size of each nodule was <6 mm) were selected. As a result, 165 sets of 3D CT images in the LUNA16 dataset were used to generate an artificial dataset for segmentation. The Decathlon challenge (http://medicaldecathlon.com/) was held to provide a fully open source and comprehensive benchmark for general purpose algorithmic validation and testing, covering several segmentation tasks. Decathlon includes several segmentation datasets, from which the Decathlon lung dataset (Task06) was used as the training and validation sets for our study. The Decathlon lung dataset includes 63 sets of 3D CT images and their segmentation labels. To simulate the small dataset, 10 and 30 sets of 3D CT images were selected from the Decathlon lung dataset; the image files of Decathlon lung dataset (NIfTI files) were sorted by file name, and the first 10 or 30 files were selected. As a result, three types of training datasets were prepared from the Decathlon lung dataset: 63 sets from the original Decathlon lung dataset (Decathlonfull), 30 sets (Decathlonmid), and 10 sets (Decathlonsmall). No image preprocessing was performed on the Decathlon lung dataset. The NSCLC radiogenomics dataset (https://wiki.cancerimagingarchive.net/display/Public/NSCLC-Radiomics) contains images from 211 patients with non–small-cell lung cancer (Cancer Imaging Archive, 2021; Bakr et al., 2018; Gevaert et al., 2012; Clark et al., 2013). The dataset comprises CT, positron emission tomography/CT images, and segmentation maps of tumors in the CT scans. From the 211 patients, 3D CT images of 144 patients and their segmentation labels were selected for the current study. Segmentation labels are not available for the other 67 patients. The NSCLC radiogenomics dataset was used as the test set. For image preprocessing, the voxel size of the 3D CT images in the NSCLC radiogenomics dataset was changed (1 mm × 1 mm × 1 mm isotropic). The median volume of the lung cancer was 8,219 mm3 (interquartile range: 3,461.5–25,357 mm3) in the NSCLC radiogenomics dataset.

Dataset Generation

The LUNA16 dataset was used to generate an artificial dataset for segmentation. First, lung segmentation was performed for the chest CT images of the LUNA16 dataset, covering the lungs entirely. A pretrained deep learning model (a variant of U-net (Ronneberger et al., 2015)) was used for the lung segmentation (https://github.com/JoHof/lungmask (Hofmanninger et al., 2020)). Subsequently, 3D images of the nodule were generated using the GAN model, which is based on the variant of 3D pix2pix (Nishio et al., 2020a). While the GAN model can generate lung nodules at any location in the lungs, we used locations of true nodules for nodule generation. In addition, we generated only one nodule per CT scan. To determine the location of the generated lung nodule, one location of true nodule was selected from the annotation of the LUNA16 dataset, for each CT scan. Therefore, the locations of generated lung nodules were fixed (no randomness). The true nodule was replaced with the nodule generated using the GAN model. For the nodule generation, 3D CT images were cropped with a volume of interest of 40 × 40 × 40 voxels for the location of the true nodules, and the cropped images were fed to the GAN model. While the size of the generated lung nodules can be adjusted with the GAN model, the GAN model generated the largest nodule as the model (the generation target size was 3 cm or higher). After nodule generation, the segmentation label was automatically generated using the 3D graph cut and Gaussian mixture (https://github.com/mjirik/imcut) (Jirík et al., 2013). Because the intensity of the seed point on the CT images was used to train the Gaussian mixture model, the center area of the generated images (40 × 40×40 voxels) was specified as seed points of the nodule, and the marginal area of the generated images was specified as seed points of the non-nodule (background). The output of the 3D graph cut was used as the segmentation label of the generated nodule. Next, the generated CT images of the nodule were merged with the original CT images. When merging the CT images of the generated nodules, only the areas that were assigned as lung labels in the lung segmentation were targeted for the merging. The areas of the generated CT images that were assigned as non-lung labels were not merged. Figure 2 shows the representative images of the generated nodules and their labels. In total, 165 lung nodules were generated for the 165 sets of 3D CT images in the LUNA16 dataset.
FIGURE 2

3D CT images of the chest. (A) Original CT images in the LUNA16 dataset. The red circle represents the true nodule specified in the LUNA16 dataset. (B) Lung nodule is artificially generated at the location of the true nodule. Label obtained with the 3D graph cut is superimposed on the 3D CT images.

3D CT images of the chest. (A) Original CT images in the LUNA16 dataset. The red circle represents the true nodule specified in the LUNA16 dataset. (B) Lung nodule is artificially generated at the location of the true nodule. Label obtained with the 3D graph cut is superimposed on the 3D CT images.

Segmentation Model

Open-source software (nnUnet) (Isensee et al., 2018) was used for the deep learning model of lung cancer segmentation, which is available at https://github.com/MIC-DKFZ/nnUNet. nnUnet is a variant of U-net (Ronneberger et al., 2015). Originally, nnUnet was used for the Decathlon datasets (Isensee et al., 2018). Because the original nnUnet has no functionality of transfer learning, we modified the source code of nnUnet. With the modification, nnUnet could use a pretrained model and perform transfer learning. In addition, the number of epochs in the training nnUnet could be changed. Except for these two points, no modifications were made to nnUnet. Dataset splitting (training and validation sets) was performed with the default setting of nnUnet. First, the generated dataset for segmentation obtained from the LUNA16 dataset was used to construct the pretrained model. Two pretrained models were built: one obtained from 300 epochs of training (PM300) and the other obtained from 500 epochs of training (PM500). Next, transfer learning using the two pretrained models was performed for the three Decathlon lung datasets (Decathlonfull, Decathlonmid, and Decathlonsmall) using the modified nnUnet. At this stage, no new layer was added to the model. Although several studies used layer freezing in transfer learning (Nishio et al., 2020b), no layers of the pretrained model were frozen in this study. To evaluate the effect of transfer learning, models were constructed without transfer learning (original nnUnet). Here, “original nnUnet” means that the source code of nnUnet was not changed, except for changing the number of epochs. The original nnUnet and its default setting were used for the model construction without transfer learning. In the model training, the epochs were set to 100, 300, and 500. The training of each model was started from epoch 1.

Evaluation of Segmentation Models

As the test dataset, 144 sets of 3D CT images from the NSCLC radiogenomics dataset were used. For each set, the Dice similarity coefficient (DSC) was used to evaluate the segmentation models. In addition, the Jaccard index (JI), sensitivity (SE), and specificity (SP) were calculated as the evaluation metrics, which is expressed as follows: where |P|, |L|, and |I| denote the number of voxels for the segmentation results, label of the lung cancer segmentation, and 3D CT images, respectively. |P ∩ L| represents the number of voxels where nnUnet can accurately segment the lung cancer (true positive). Before calculating the four metrics, a threshold of 0.5 was used to obtain the segmentation mask from the output of nnUnet. Differences of DSC were statistically tested with the Wilcoxon signed rank test. To control the family-wise error rate, the Bonferroni correction was used; p-values less than 0.01666 were considered statistically significant. Statistical analyses were performed using R (version 4.0.4, https://www.r-project.org/).

Results

Figures 3–5 show the mean DSC of the test set with and without PM300 and PM500 when Decathlonfull, Decathlonmid, and Decathlonsmall are used as the training sets, respectively. In these figures, the results without PM correspond to those of original nnUnet. Generally, PM300 and PM500 improved the mean DSC of nnUnet, compared with the original nnUnet (without the pretrained model). In particular, the effectiveness of the pretrained model was high when using Decathlonmid as the training set. Neither PM300 nor PM500 was useful for DSC improvement when Decathlonfull and Decathlonsmall were used in the 500-epoch training. The DSC improvement was greater in the 100 and 300 epochs than that in the 500 epochs.
FIGURE 3

Mean DSC of the test set when using Decathlonfull. Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

FIGURE 5

Mean DSC of the test set when using Decathlonsmall. Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

Mean DSC of the test set when using Decathlonfull. Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. Mean DSC of the test set when using Decathlonmid. Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. Mean DSC of the test set when using Decathlonsmall. Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. Tables 2–4 list the mean and standard deviation of the four metrics of the test set with and without PM300 and PM500 when Decathlonfull, Decathlonmid, and Decathlonsmall are used as the training sets, respectively. Because the volume ratio between cancer and noncancerous regions is extremely low, SP was extremely high in the current study. Regarding DSC, JI, and SE, the same trend can be observed. PM300 and PM500 improved the mean values of the three metrics; improvement in JI and SE was greater in the 100 and 300 epochs than that in the 500 epochs. Table 5 shows p-values for differences of DSC in Decathlonfull, Decathlonmid, and Decathlonsmall.
TABLE 2

Segmentation metrics of test set using Decathlonfull.

ModelDSC meanSDJI meanSDSE meanSDSP meanSD
W/o PM, epoch 1000.58130.24950.45050.23520.70490.25140.999840.00027
W/PM300, epoch 1000.65100.21040.51500.21100.76720.19470.999870.00024
W/PM500, epoch 1000.58100.24740.45100.24110.75110.21330.999820.00020
W/o PM, epoch 3000.69390.24090.57410.23600.73710.25420.999920.00011
W/PM300, epoch 3000.72210.20550.59950.21720.75800.21020.999910.00023
W/PM500, epoch 3000.69950.23020.57890.23470.75140.21190.999920.00012
W/o PM, epoch 5000.72730.22660.61200.23150.73340.24640.999950.00009
W/PM300, epoch 5000.73010.21450.61220.22390.76620.20610.999900.00025
W/PM500, epoch 5000.72550.24240.61390.23860.74280.24840.999930.00012

Abbreviations: DSC, Dice similarity coefficients; JI, Jaccard index; SE, sensitivity; SP, specificity; PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

TABLE 4

egmentation metrics of test set using Decathlonsmall.

ModelDSC meanSDJI meanSDSE meanSDSP meanSD
W/o PM, epoch 1000.51240.28570.39280.25550.46710.28380.999970.00007
W/PM300, epoch 1000.57020.25130.44000.23880.51830.25240.999960.00007
W/PM500, epoch 1000.56080.26810.43520.24910.51900.27610.999970.00006
W/o PM, epoch 3000.55150.27420.42740.25100.49500.28110.999970.00007
W/PM300, epoch 3000.60900.24140.47810.23610.55110.25100.999970.00007
W/PM500, epoch 3000.58440.26070.45740.24660.52150.27190.999970.00006
W/o PM, epoch 5000.55250.28550.43160.25730.51090.28510.999970.00006
W/PM300, epoch 5000.55360.28560.43380.26290.49340.28780.999980.00005
W/PM500, epoch 5000.56700.27310.44350.25570.50890.27860.999970.00006

Abbreviations: DSC, Dice similarity coefficients; JI, Jaccard index; SE, sensitivity; SP, specificity; PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

TABLE 5

p-values for differences of DSC in Decathlonfull, Decathlonmid, and Decathlonsmall.

PairDecathlonfull Decathlonmid Decathlonsmall
Epoch 100
 w/o PM vs. w/PM300 7.857 × 10−5 1.877 × 10−7 0.0006931
 w/o PM vs. w/PM500 0.96820.00010750.0009121
 w/o PM300 vs. w/PM500 1.606 × 10−5 0.46420.1499
Epoch 300
 w/o PM vs. w/PM300 0.23460.043816.662 × 10−5
 w/o PM vs. w/PM500 0.76640.0006490.001194
 w/o PM300 vs. w/PM500 0.14930.013250.3050
Epoch 500
 w/o PM vs. w/PM300 0.97430.23220.5990
 w/o PM vs. w/PM500 0.72430.0054350.8746
 w/o PM300 vs. w/PM500 0.95340.065950.9229

Abbreviations: DSC, Dice similarity coefficients; PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

Segmentation metrics of test set using Decathlonfull. Abbreviations: DSC, Dice similarity coefficients; JI, Jaccard index; SE, sensitivity; SP, specificity; PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. Segmentation metrics of test set using Decathlonmid. Abbreviations: DSC, Dice similarity coefficients; JI, Jaccard index; SE, sensitivity; SP, specificity; PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. egmentation metrics of test set using Decathlonsmall. Abbreviations: DSC, Dice similarity coefficients; JI, Jaccard index; SE, sensitivity; SP, specificity; PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. p-values for differences of DSC in Decathlonfull, Decathlonmid, and Decathlonsmall. Abbreviations: DSC, Dice similarity coefficients; PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. Figure 6 shows all the DSC values of the test set when using Decathlonmid with and without the pretrained model. Figures 7, 8 show the representative segmentation results. Figures 7, 8 show the CT images in which PM is ineffective and effective, respectively. Supplementary Table 1 includes the segmentation results when the generated dataset consisted of variable-size–generated nodules. In addition, the Supplementary Table 2 includes visual evaluation results of cases with low DSC values.
FIGURE 6

DSC values of the test set when using Decathlonmid with and without the pretrained model. (A) Cases 1–50, (B) cases 51–100, and (C) cases 101–144. Note: DSC values are obtained with models obtained from 500 epochs of training. Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

FIGURE 7

Results of segmentation in case 3 of test set. (A) CT images and ground-truth labels. (B) CT images and segmentation results without PM. (C) CT images and segmentation results with PM300. (D) CT images and segmentation results with PM500. Note: Because of PM, a part of the right upper field is incorrectly segmented as lung cancer in (C) and (D). Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

FIGURE 8

Results of segmentation in case 104 of the test set. (A) CT images and ground-truth labels. (B) CT images and segmentation results without PM. (C) CT images and segmentation results with PM300. (D) CT images and segmentation results with PM500. Note: With the aid of PM, lung cancer is correctly segmented in (C) and (D). Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

DSC values of the test set when using Decathlonmid with and without the pretrained model. (A) Cases 1–50, (B) cases 51–100, and (C) cases 101–144. Note: DSC values are obtained with models obtained from 500 epochs of training. Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. Results of segmentation in case 3 of test set. (A) CT images and ground-truth labels. (B) CT images and segmentation results without PM. (C) CT images and segmentation results with PM300. (D) CT images and segmentation results with PM500. Note: Because of PM, a part of the right upper field is incorrectly segmented as lung cancer in (C) and (D). Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training. Results of segmentation in case 104 of the test set. (A) CT images and ground-truth labels. (B) CT images and segmentation results without PM. (C) CT images and segmentation results with PM300. (D) CT images and segmentation results with PM500. Note: With the aid of PM, lung cancer is correctly segmented in (C) and (D). Abbreviation: PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

Discussion

In this study, we proposed a pretrained model for segmentation constructed from an artificial dataset of lung nodules generated using the GAN and 3D graph cut. Our results show that the accuracy of lung cancer segmentation could be improved when this pretrained model was used for transfer learning in the segmentation process. The effectiveness of the pretrained model was higher on the Decathlonmid and Decathlonsmall datasets than that of the pretrained model on the Decathlonfull dataset, suggesting that our proposed method may be effective on small datasets. The pretrained model was more effective when the number of training epochs was low. In other words, the number of epochs required to achieve a sufficient segmentation performance was lower with the pretrained model than without it. This may be attributed to the fact that the pretrained model provides good initial values for the trainable parameters of nnUnet. Previously, a study used U-net and GAN combinedly for multi-organ segmentation on 3D CT images (Dong et al., 2019). However, the study did not use a pretrained model. Another study was conducted on a classification model using a dataset generated with GANs and a pretrained model (Onishi et al., 2020). To the best of our knowledge, no studies have been reported on segmentation models with GANs and a pretrained model. Our results and those of Onishi et al. (2020) indicate that the GAN generated dataset, and its pretrained models may be useful for various tasks. Several studies have reported the use of artificially generated datasets using the GAN for data augmentation (Jin et al., 2018; Onishi et al., 2019; Yang et al., 2019; Muramatsu et al., 2020). Similarly, in this study, we tried to use a dataset generated using the GAN for data augmentation. However, we could not obtain effective results for lung cancer segmentation when the artificial dataset was used as data augmentation (data not shown in this article). Instead, we constructed a pretrained model for the segmentation using the generated lung nodules and performed transfer learning based on the pretrained model, yielding higher lung cancer segmentation accuracy. Although it was difficult to perform accurate classification between the generated lung nodules and the true lung nodules (Nishio et al., 2020a), the generated lung nodules had little variation as lung cancer. It is speculated that mixing the generated lung nodules with the true lung nodules could distort the distribution as the dataset of lung cancer segmentation and adversely affect the model training of nnUnet. Generally, supervised learning (e.g., nnUnet) requires annotation data as the dataset. On the datasets of lung cancer segmentation, clinicians frequently annotate lung cancer on CT images to build lung cancer datasets, which is time consuming and labor intensive. Although it is possible to manually annotate the generated data of our dataset, we decided to use the 3D graph cut to obtain annotation data of the generated lung nodules. This made it possible to build an artificial dataset for the segmentation without requiring any manual task. Although the generated lung nodules and the pretrained model based on them could effectively improve the accuracy of lung cancer segmentation, this pretrained model is not always effective. For example, the effectiveness of the pretrained model was not observed in the 500-epoch training of Decathlonfull and Decathlonsmall. For the former case, this was attributed to the fact that Decathlonfull had sufficient amount of data and the number of training epochs was high. In the latter, the number of datasets was very small (10 cases). Therefore, even when the pretrained model was used, the training segmentation model was unstable, and the effectiveness of the pretrained model was limited. Our study has some limitations. First, we used three public datasets containing images of lung nodules and/or lung cancer. However, we did not verify whether the generalizability of our segmentation model can be improved under external variation. Second, we focused on lung nodules and/or lung cancer in the current study. Therefore, the effectiveness of our method for other diseases or other organs has not been validated. In particular, it is necessary to confirm whether the automatic generation of annotation data using the 3D graph cut can be applied to other diseases and other organs. Third, because of the GAN model’s limitation (Nishio et al., 2020a), it was impossible to generate lung nodules larger than 40 mm. Therefore, the effect of large generated nodules is not investigated in the current study. In conclusion, the proposed method comprising an artificial dataset and a pretrained model can improve the accuracy of lung cancer segmentation; however, it should be further investigated for other diseases and other organs.
TABLE 3

Segmentation metrics of test set using Decathlonmid.

ModelDSC meanSDJI meanSDSE meanSDSP meanSD
W/o PM, epoch 1000.57440.27040.44930.24860.61220.28300.999930.00008
W/PM300, epoch 1000.66240.23050.53420.23030.69990.22210.999920.00012
W/PM500, epoch 1000.64520.23510.51550.23020.71440.23020.999900.00015
W/o PM, epoch 3000.66000.25720.53980.25090.67500.25790.999930.00013
W/PM300, epoch 3000.68220.24700.56310.24630.72340.22940.999910.00015
W/PM500, epoch 3000.70240.23080.58230.23440.72920.22010.999900.00022
W/o PM, epoch 5000.67080.26890.55700.26290.68920.26080.999910.00019
W/PM300, epoch 5000.70830.20390.58190.21600.74790.19360.999920.00012
W/PM500, epoch 5000.71120.22280.59090.22930.72660.22150.999930.00013

Abbreviations: DSC, Dice similarity coefficients; JI, Jaccard index; SE, sensitivity; SP, specificity; PM, pretrained model; PM300, pretrained model obtained from 300 epochs of training; PM500, pretrained model obtained from 500 epochs of training.

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5.  Automatic multiorgan segmentation in thorax CT images using U-net-GAN.

Authors:  Xue Dong; Yang Lei; Tonghe Wang; Matthew Thomas; Leonardo Tang; Walter J Curran; Tian Liu; Xiaofeng Yang
Journal:  Med Phys       Date:  2019-03-22       Impact factor: 4.071

6.  The Cancer Imaging Archive (TCIA): maintaining and operating a public information repository.

Authors:  Kenneth Clark; Bruce Vendt; Kirk Smith; John Freymann; Justin Kirby; Paul Koppel; Stephen Moore; Stanley Phillips; David Maffitt; Michael Pringle; Lawrence Tarbox; Fred Prior
Journal:  J Digit Imaging       Date:  2013-12       Impact factor: 4.056

7.  Comparison of CT volumetric measurement with RECIST response in patients with lung cancer.

Authors:  S A Hayes; M C Pietanza; D O'Driscoll; J Zheng; C S Moskowitz; M G Kris; M S Ginsberg
Journal:  Eur J Radiol       Date:  2016-01-02       Impact factor: 3.528

8.  A radiogenomic dataset of non-small cell lung cancer.

Authors:  Shaimaa Bakr; Olivier Gevaert; Sebastian Echegaray; Kelsey Ayers; Mu Zhou; Majid Shafiq; Hong Zheng; Jalen Anthony Benson; Weiruo Zhang; Ann N C Leung; Michael Kadoch; Chuong D Hoang; Joseph Shrager; Andrew Quon; Daniel L Rubin; Sylvia K Plevritis; Sandy Napel
Journal:  Sci Data       Date:  2018-10-16       Impact factor: 6.444

9.  Automatic classification between COVID-19 pneumonia, non-COVID-19 pneumonia, and the healthy on chest X-ray image: combination of data augmentation methods.

Authors:  Mizuho Nishio; Shunjiro Noguchi; Hidetoshi Matsuo; Takamichi Murakami
Journal:  Sci Rep       Date:  2020-10-16       Impact factor: 4.379

10.  Automated segmentation of endometrial cancer on MR images using deep learning.

Authors:  Erlend Hodneland; Julie A Dybvik; Kari S Wagner-Larsen; Veronika Šoltészová; Antonella Z Munthe-Kaas; Kristine E Fasmer; Camilla Krakstad; Arvid Lundervold; Alexander S Lundervold; Øyvind Salvesen; Bradley J Erickson; Ingfrid Haldorsen
Journal:  Sci Rep       Date:  2021-01-08       Impact factor: 4.379

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1.  Automated Final Lesion Segmentation in Posterior Circulation Acute Ischemic Stroke Using Deep Learning.

Authors:  Riaan Zoetmulder; Praneeta R Konduri; Iris V Obdeijn; Efstratios Gavves; Ivana Išgum; Charles B L M Majoie; Diederik W J Dippel; Yvo B W E M Roos; Mayank Goyal; Peter J Mitchell; Bruce C V Campbell; Demetrius K Lopes; Gernot Reimann; Tudor G Jovin; Jeffrey L Saver; Keith W Muir; Phil White; Serge Bracard; Bailiang Chen; Scott Brown; Wouter J Schonewille; Erik van der Hoeven; Volker Puetz; Henk A Marquering
Journal:  Diagnostics (Basel)       Date:  2021-09-04
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