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1. Improving tumor co-segmentation on PET-CT images with 3D co-matting

   https://doi.org/10.1109/ISBI.2018.8363560  

   Zhong, Zisha ; Kim, Yusung ; Zhou, Leixin ; Plichta, Kristin ; Allen, Bryan ; Buatti, John ; Wu, Xiaodong ( April 2018 , 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018))

   null (Ed.)

   Positron emission tomography and computed tomography (PET-CT) plays a critically important role in modern cancer therapy. In this paper, we focus on automated tumor delineation on PET-CT image pairs. Inspired by co-segmentation model, we develop a novel 3D image co-matting technique making use of the inner-modality information of PET and CT for matting. The obtained co-matting results are then incorporated in the graph-cut based PET-CT co-segmentation framework. Our comparative experiments on 32 PET-CT scan pairs of lung cancer patients demonstrate that the proposed 3D image co-matting technique can significantly improve the quality of cost images for the co-segmentation, resulting in highly accurate tumor segmentation on both PET and CT scan pairs. 

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2. Deep segmentation networks predict survival of non-small cell lung cancer

   https://doi.org/10.1038/s41598-019-53461-2  

   Baek, Stephen ; He, Yusen ; Allen, Bryan G. ; Buatti, John M. ; Smith, Brian J. ; Tong, Ling ; Sun, Zhiyu ; Wu, Jia ; Diehn, Maximilian ; Loo, Billy W. ; et al ( December 2019 , Scientific Reports)

   Abstract Non-small-cell lung cancer (NSCLC) represents approximately 80–85% of lung cancer diagnoses and is the leading cause of cancer-related death worldwide. Recent studies indicate that image-based radiomics features from positron emission tomography/computed tomography (PET/CT) images have predictive power for NSCLC outcomes. To this end, easily calculated functional features such as the maximum and the mean of standard uptake value (SUV) and total lesion glycolysis (TLG) are most commonly used for NSCLC prognostication, but their prognostic value remains controversial. Meanwhile, convolutional neural networks (CNN) are rapidly emerging as a new method for cancer image analysis, with significantly enhanced predictive power compared to hand-crafted radiomics features. Here we show that CNNs trained to perform the tumor segmentation task, with no other information than physician contours, identify a rich set of survival-related image features with remarkable prognostic value. In a retrospective study on pre-treatment PET-CT images of 96 NSCLC patients before stereotactic-body radiotherapy (SBRT), we found that the CNN segmentation algorithm (U-Net) trained for tumor segmentation in PET and CT images, contained features having strong correlation with 2- and 5-year overall and disease-specific survivals. The U-Net algorithm has not seen any other clinical information (e.g. survival, age, smoking history, etc.) than the images and the corresponding tumor contours provided by physicians. In addition, we observed the same trend by validating the U-Net features against an extramural data set provided by Stanford Cancer Institute. Furthermore, through visualization of the U-Net, we also found convincing evidence that the regions of metastasis and recurrence appear to match with the regions where the U-Net features identified patterns that predicted higher likelihoods of death. We anticipate our findings will be a starting point for more sophisticated non-intrusive patient specific cancer prognosis determination. For example, the deep learned PET/CT features can not only predict survival but also visualize high-risk regions within or adjacent to the primary tumor and hence potentially impact therapeutic outcomes by optimal selection of therapeutic strategy or first-line therapy adjustment. 

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3. Robust explanation supervision for false positive reduction in pulmonary nodule detection

   https://doi.org/10.1002/mp.16937  

   Zhao, Qilong ; Chang, Chih‐Wei ; Yang, Xiaofeng ; Zhao, Liang ( January 2024 , Medical Physics)

   Lung cancer is the deadliest and second most common cancer in the United States due to the lack of symptoms for early diagnosis. Pulmonary nodules are small abnormal regions that can be potentially correlated to the occurrence of lung cancer. Early detection of these nodules is critical because it can significantly improve the patient's survival rates. Thoracic thin‐sliced computed tomography (CT) scanning has emerged as a widely used method for diagnosing and prognosis lung abnormalities.

   The standard clinical workflow of detecting pulmonary nodules relies on radiologists to analyze CT images to assess the risk factors of cancerous nodules. However, this approach can be error‐prone due to the various nodule formation causes, such as pollutants and infections. Deep learning (DL) algorithms have recently demonstrated remarkable success in medical image classification and segmentation. As an ever more important assistant to radiologists in nodule detection, it is imperative ensure the DL algorithm and radiologist to better understand the decisions from each other. This study aims to develop a framework integrating explainable AI methods to achieve accurate pulmonary nodule detection.

   A robust and explainable detection (RXD) framework is proposed, focusing on reducing false positives in pulmonary nodule detection. Its implementation is based on an explanation supervision method, which uses nodule contours of radiologists as supervision signals to force the model to learn nodule morphologies, enabling improved learning ability on small dataset, and enable small dataset learning ability. In addition, two imputation methods are applied to the nodule region annotations to reduce the noise within human annotations and allow the model to have robust attributions that meet human expectations. The 480, 265, and 265 CT image sets from the public Lung Image Database Consortium and Image Database Resource Initiative (LIDC‐IDRI) dataset are used for training, validation, and testing.

   Using only 10, 30, 50, and 100 training samples sequentially, our method constantly improves the classification performance and explanation quality of baseline in terms of Area Under the Curve (AUC) and Intersection over Union (IoU). In particular, our framework with a learnable imputation kernel improves IoU from baseline by 24.0% to 80.0%. A pre‐defined Gaussian imputation kernel achieves an even greater improvement, from 38.4% to 118.8% from baseline. Compared to the baseline trained on 100 samples, our method shows less drop in AUC when trained on fewer samples. A comprehensive comparison of interpretability shows that our method aligns better with expert opinions.

   A pulmonary nodule detection framework was demonstrated using public thoracic CT image datasets. The framework integrates the robust explanation supervision (RES) technique to ensure the performance of nodule classification and morphology. The method can reduce the workload of radiologists and enable them to focus on the diagnosis and prognosis of the potential cancerous pulmonary nodules at the early stage to improve the outcomes for lung cancer patients.

    

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4. Multi-scale segmentation using deep graph cuts: Robust lung tumor delineation in MVCBCT

   https://doi.org/10.1109/ISBI.2018.8363628  

   Wu, Xiaodong ; Zhong, Zisha ; Buatti, John ; Bai, Junjie ( April 2018 , 2018 IEEE 15th International Symposium on Biomedical Imaging (ISBI 2018))

   null (Ed.)

   Deep networks have been used in a growing trend in medical image analysis with the remarkable progress in deep learning. In this paper, we formulate the multi-scale segmentation as a Markov Random Field (MRF) energy minimization problem in a deep network (graph), which can be efficiently and exactly solved by computing a minimum s-t cut in an appropriately constructed graph. The performance of the proposed method is assessed on the application of lung tumor segmentation in 38 mega-voltage cone-beam computed tomography datasets. 

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5. Multi‐scale, domain knowledge‐guided attention + random forest: a two‐stage deep learning‐based multi‐scale guided attention models to diagnose idiopathic pulmonary fibrosis from computed tomography images

   https://doi.org/10.1002/mp.16053  

   Yu, Wenxi ; Zhou, Hua ; Choi, Youngwon ; Goldin, Jonathan G. ; Teng, Pangyu ; Wong, Weng Kee ; McNitt‐Gray, Michael F. ; Brown, Matthew S. ; Kim, Grace Hyun J. ( November 2022 , Medical Physics)

   Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, and usually fatal lung disease of unknown reasons, generally affecting the elderly population. Early diagnosis of IPF is crucial for triaging patients’ treatment planning into anti‐fibrotic treatment or treatments for other causes of pulmonary fibrosis. However, current IPF diagnosis workflow is complicated and time‐consuming, which involves collaborative efforts from radiologists, pathologists, and clinicians and it is largely subject to inter‐observer variability.

   The purpose of this work is to develop a deep learning‐based automated system that can diagnose subjects with IPF among subjects with interstitial lung disease (ILD) using an axial chest computed tomography (CT) scan. This work can potentially enable timely diagnosis decisions and reduce inter‐observer variability.

   Our dataset contains CT scans from 349 IPF patients and 529 non‐IPF ILD patients. We used 80% of the dataset for training and validation purposes and 20% as the holdout test set. We proposed a two‐stage model: at stage one, we built a multi‐scale, domain knowledge‐guided attention model (MSGA) that encouraged the model to focus on specific areas of interest to enhance model explainability, including both high‐ and medium‐resolution attentions; at stage two, we collected the output from MSGA and constructed a random forest (RF) classifier for patient‐level diagnosis, to further boost model accuracy. RF classifier is utilized as a final decision stage since it is interpretable, computationally fast, and can handle correlated variables. Model utility was examined by (1) accuracy, represented by the area under the receiver operating characteristic curve (AUC) with standard deviation (SD), and (2) explainability, illustrated by the visual examination of the estimated attention maps which showed the important areas for model diagnostics.

   During the training and validation stage, we observe that when we provide no guidance from domain knowledge, the IPF diagnosis model reaches acceptable performance (AUC±SD = 0.93±0.07), but lacks explainability; when including only guided high‐ or medium‐resolution attention, the learned attention maps are not satisfactory; when including both high‐ and medium‐resolution attention, under certain hyperparameter settings, the model reaches the highest AUC among all experiments (AUC±SD = 0.99±0.01) and the estimated attention maps concentrate on the regions of interests for this task. Three best‐performing hyperparameter selections according to MSGA were applied to the holdout test set and reached comparable model performance to that of the validation set.

   Our results suggest that, for a task with only scan‐level labels available, MSGA+RF can utilize the population‐level domain knowledge to guide the training of the network, which increases both model accuracy and explainability.

    

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