Kohei Murao

Changhee Han, Leonardo Rundo, Kohei Murao et al.

Unsupervised learning can discover various unseen abnormalities, relying on large-scale unannotated medical images of healthy subjects. Towards this, unsupervised methods reconstruct a 2D/3D single medical image to detect outliers either in the learned feature space or from high reconstruction loss. However, without considering continuity between multiple adjacent slices, they cannot directly discriminate diseases composed of the accumulation of subtle anatomical anomalies, such as Alzheimer's Disease (AD). Moreover, no study has shown how unsupervised anomaly detection is associated with either disease stages, various (i.e., more than two types of) diseases, or multi-sequence Magnetic Resonance Imaging (MRI) scans. Therefore, we propose unsupervised Medical Anomaly Detection Generative Adversarial Network (MADGAN), a novel two-step method using GAN-based multiple adjacent brain MRI slice reconstruction to detect brain anomalies at different stages on multi-sequence structural MRI: (Reconstruction) Wasserstein loss with Gradient Penalty + 100 L1 loss-trained on 3 healthy brain axial MRI slices to reconstruct the next 3 ones-reconstructs unseen healthy/abnormal scans; (Diagnosis) Average L2 loss per scan discriminates them, comparing the ground truth/reconstructed slices. For training, we use two different datasets composed of 1,133 healthy T1-weighted (T1) and 135 healthy contrast-enhanced T1 (T1c) brain MRI scans for detecting AD and brain metastases/various diseases, respectively. Our Self-Attention MADGAN can detect AD on T1 scans at a very early stage, Mild Cognitive Impairment (MCI), with Area Under the Curve (AUC) 0.727, and AD at a late stage with AUC 0.894, while detecting brain metastases on T1c scans with AUC 0.921.

Changhee Han, Leonardo Rundo, Kohei Murao et al.

Despite the success of Convolutional Neural Network-based Computer-Aided Diagnosis research, its clinical applications remain challenging. Accordingly, developing medical Artificial Intelligence (AI) fitting into a clinical environment requires identifying/bridging the gap between AI and Healthcare sides. Since the biggest problem in Medical Imaging lies in data paucity, confirming the clinical relevance for diagnosis of research-proven image augmentation techniques is essential. Therefore, we hold a clinically valuable AI-envisioning workshop among Japanese Medical Imaging experts, physicians, and generalists in Healthcare/Informatics. Then, a questionnaire survey for physicians evaluates our pathology-aware Generative Adversarial Network (GAN)-based image augmentation projects in terms of Data Augmentation and physician training. The workshop reveals the intrinsic gap between AI/Healthcare sides and solutions on Why (i.e., clinical significance/interpretation) and How (i.e., data acquisition, commercial deployment, and safety/feeling safe). This analysis confirms our pathology-aware GANs' clinical relevance as a clinical decision support system and non-expert physician training tool. Our findings would play a key role in connecting inter-disciplinary research and clinical applications, not limited to the Japanese medical context and pathology-aware GANs.

Changhee Han, Leonardo Rundo, Kohei Murao et al.

Unsupervised learning can discover various unseen diseases, relying on large-scale unannotated medical images of healthy subjects. Towards this, unsupervised methods reconstruct a single medical image to detect outliers either in the learned feature space or from high reconstruction loss. However, without considering continuity between multiple adjacent slices, they cannot directly discriminate diseases composed of the accumulation of subtle anatomical anomalies, such as Alzheimer's Disease (AD). Moreover, no study has shown how unsupervised anomaly detection is associated with disease stages. Therefore, we propose a two-step method using Generative Adversarial Network-based multiple adjacent brain MRI slice reconstruction to detect AD at various stages: (Reconstruction) Wasserstein loss with Gradient Penalty + L1 loss---trained on 3 healthy slices to reconstruct the next 3 ones---reconstructs unseen healthy/AD cases; (Diagnosis) Average/Maximum loss (e.g., L2 loss) per scan discriminates them, comparing the reconstructed/ground truth images. The results show that we can reliably detect AD at a very early stage with Area Under the Curve (AUC) 0.780 while also detecting AD at a late stage much more accurately with AUC 0.917; since our method is fully unsupervised, it should also discover and alert any anomalies including rare disease.

Changhee Han, Kohei Murao, Shin'ichi Satoh et al.

Convolutional Neural Network (CNN)-based accurate prediction typically requires large-scale annotated training data. In Medical Imaging, however, both obtaining medical data and annotating them by expert physicians are challenging; to overcome this lack of data, Data Augmentation (DA) using Generative Adversarial Networks (GANs) is essential, since they can synthesize additional annotated training data to handle small and fragmented medical images from various scanners--those generated images, realistic but completely novel, can further fill the real image distribution uncovered by the original dataset. As a tutorial, this paper introduces GAN-based Medical Image Augmentation, along with tricks to boost classification/object detection/segmentation performance using them, based on our experience and related work. Moreover, we show our first GAN-based DA work using automatic bounding box annotation, for robust CNN-based brain metastases detection on 256 x 256 MR images; GAN-based DA can boost 10% sensitivity in diagnosis with a clinically acceptable number of additional False Positives, even with highly-rough and inconsistent bounding boxes.

Changhee Han, Kohei Murao, Tomoyuki Noguchi et al.

Accurate Computer-Assisted Diagnosis, associated with proper data wrangling, can alleviate the risk of overlooking the diagnosis in a clinical environment. Towards this, as a Data Augmentation (DA) technique, Generative Adversarial Networks (GANs) can synthesize additional training data to handle the small/fragmented medical imaging datasets collected from various scanners; those images are realistic but completely different from the original ones, filling the data lack in the real image distribution. However, we cannot easily use them to locate disease areas, considering expert physicians' expensive annotation cost. Therefore, this paper proposes Conditional Progressive Growing of GANs (CPGGANs), incorporating highly-rough bounding box conditions incrementally into PGGANs to place brain metastases at desired positions/sizes on 256 X 256 Magnetic Resonance (MR) images, for Convolutional Neural Network-based tumor detection; this first GAN-based medical DA using automatic bounding box annotation improves the training robustness. The results show that CPGGAN-based DA can boost 10% sensitivity in diagnosis with clinically acceptable additional False Positives. Surprisingly, further tumor realism, achieved with additional normal brain MR images for CPGGAN training, does not contribute to detection performance, while even three physicians cannot accurately distinguish them from the real ones in Visual Turing Test.