L. Rodney Long

Harshit Parmar, Brian Nutter, Rodney Long et al.

Purpose: Functional Magnetic Resonance Imaging (fMRI) data acquired through resting-state studies have been used to obtain information about the spontaneous activations inside the brain. One of the approaches for analysis and interpretation of resting-state fMRI data require spatially and functionally homogenous parcellation of the whole brain based on underlying temporal fluctuations. Clustering is often used to generate functional parcellation. However, major clustering algorithms, when used for fMRI data, have their limitations. Among commonly used parcellation schemes, a tradeoff exists between intra-cluster functional similarity and alignment with anatomical regions. Approach: In this work, we present a clustering algorithm for resting state and task fMRI data which is developed to obtain brain parcellations that show high structural and functional homogeneity. The clustering is performed by multistage binary k-means clustering algorithm designed specifically for the 4D fMRI data. The results from this multistage k-means algorithm show that by modifying and combining different algorithms, we can take advantage of the strengths of different techniques while overcoming their limitations. Results: The clustering output for resting state fMRI data using the multistage k-means approach is shown to be better than simple k-means or functional atlas in terms of spatial and functional homogeneity. The clusters also correspond to commonly identifiable brain networks. For task fMRI, the clustering output can identify primary and secondary activation regions and provide information about the varying hemodynamic response across different brain regions. Conclusion: The multistage k-means approach can provide functional parcellations of the brain using resting state fMRI data. The method is model-free and is data driven which can be applied to both resting state and task fMRI.

Yuan Xue, Jiarong Ye, Qianying Zhou et al.

Histopathological analysis is the present gold standard for precancerous lesion diagnosis. The goal of automated histopathological classification from digital images requires supervised training, which requires a large number of expert annotations that can be expensive and time-consuming to collect. Meanwhile, accurate classification of image patches cropped from whole-slide images is essential for standard sliding window based histopathology slide classification methods. To mitigate these issues, we propose a carefully designed conditional GAN model, namely HistoGAN, for synthesizing realistic histopathology image patches conditioned on class labels. We also investigate a novel synthetic augmentation framework that selectively adds new synthetic image patches generated by our proposed HistoGAN, rather than expanding directly the training set with synthetic images. By selecting synthetic images based on the confidence of their assigned labels and their feature similarity to real labeled images, our framework provides quality assurance to synthetic augmentation. Our models are evaluated on two datasets: a cervical histopathology image dataset with limited annotations, and another dataset of lymph node histopathology images with metastatic cancer. Here, we show that leveraging HistoGAN generated images with selective augmentation results in significant and consistent improvements of classification performance (6.7% and 2.8% higher accuracy, respectively) for cervical histopathology and metastatic cancer datasets.

Jiarong Ye, Yuan Xue, L. Rodney Long et al.

Synthesizing realistic medical images provides a feasible solution to the shortage of training data in deep learning based medical image recognition systems. However, the quality control of synthetic images for data augmentation purposes is under-investigated, and some of the generated images are not realistic and may contain misleading features that distort data distribution when mixed with real images. Thus, the effectiveness of those synthetic images in medical image recognition systems cannot be guaranteed when they are being added randomly without quality assurance. In this work, we propose a reinforcement learning (RL) based synthetic sample selection method that learns to choose synthetic images containing reliable and informative features. A transformer based controller is trained via proximal policy optimization (PPO) using the validation classification accuracy as the reward. The selected images are mixed with the original training data for improved training of image recognition systems. To validate our method, we take the pathology image recognition as an example and conduct extensive experiments on two histopathology image datasets. In experiments on a cervical dataset and a lymph node dataset, the image classification performance is improved by 8.1% and 2.3%, respectively, when utilizing high-quality synthetic images selected by our RL framework. Our proposed synthetic sample selection method is general and has great potential to boost the performance of various medical image recognition systems given limited annotation.

Sudhir Sornapudi, R. Joe Stanley, William V. Stoecker et al.

Cervical cancer is one of the deadliest cancers affecting women globally. Cervical intraepithelial neoplasia (CIN) assessment using histopathological examination of cervical biopsy slides is subject to interobserver variability. Automated processing of digitized histopathology slides has the potential for more accurate classification for CIN grades from normal to increasing grades of pre-malignancy: CIN1, CIN2 and CIN3. Cervix disease is generally understood to progress from the bottom (basement membrane) to the top of the epithelium. To model this relationship of disease severity to spatial distribution of abnormalities, we propose a network pipeline, DeepCIN, to analyze high-resolution epithelium images (manually extracted from whole-slide images) hierarchically by focusing on localized vertical regions and fusing this local information for determining Normal/CIN classification. The pipeline contains two classifier networks: 1) a cross-sectional, vertical segment-level sequence generator (two-stage encoder model) is trained using weak supervision to generate feature sequences from the vertical segments to preserve the bottom-to-top feature relationships in the epithelium image data; 2) an attention-based fusion network image-level classifier predicting the final CIN grade by merging vertical segment sequences. The model produces the CIN classification results and also determines the vertical segment contributions to CIN grade prediction. Experiments show that DeepCIN achieves pathologist-level CIN classification accuracy.

Yuan Xue, Jiarong Ye, Rodney Long et al.

Supervised training of an automated medical image analysis system often requires a large amount of expert annotations that are hard to collect. Moreover, the proportions of data available across different classes may be highly imbalanced for rare diseases. To mitigate these issues, we investigate a novel data augmentation pipeline that selectively adds new synthetic images generated by conditional Adversarial Networks (cGANs), rather than extending directly the training set with synthetic images. The selection mechanisms that we introduce to the synthetic augmentation pipeline are motivated by the observation that, although cGAN-generated images can be visually appealing, they are not guaranteed to contain essential features for classification performance improvement. By selecting synthetic images based on the confidence of their assigned labels and their feature similarity to real labeled images, our framework provides quality assurance to synthetic augmentation by ensuring that adding the selected synthetic images to the training set will improve performance. We evaluate our model on a medical histopathology dataset, and two natural image classification benchmarks, CIFAR10 and SVHN. Results on these datasets show significant and consistent improvements in classification performance (with 6.8%, 3.9%, 1.6% higher accuracy, respectively) by leveraging cGAN generated images with selective augmentation.

Sudhir Sornapudi, G. T. Brown, Zhiyun Xue et al.

Liquid-based cytology (LBC) is a reliable automated technique for the screening of Papanicolaou (Pap) smear data. It is an effective technique for collecting a majority of the cervical cells and aiding cytopathologists in locating abnormal cells. Most methods published in the research literature rely on accurate cell segmentation as a prior, which remains challenging due to a variety of factors, e.g., stain consistency, presence of clustered cells, etc. We propose a method for automatic classification of cervical slide images through generation of labeled cervical patch data and extracting deep hierarchical features by fine-tuning convolution neural networks, as well as a novel graph-based cell detection approach for cellular level evaluation. The results show that the proposed pipeline can classify images of both single cell and overlapping cells. The VGG-19 model is found to be the best at classifying the cervical cytology patch data with 95 % accuracy under precision-recall curve.

Yuan Xue, Qianying Zhou, Jiarong Ye et al.

Cervical intraepithelial neoplasia (CIN) grade of histopathology images is a crucial indicator in cervical biopsy results. Accurate CIN grading of epithelium regions helps pathologists with precancerous lesion diagnosis and treatment planning. Although an automated CIN grading system has been desired, supervised training of such a system would require a large amount of expert annotations, which are expensive and time-consuming to collect. In this paper, we investigate the CIN grade classification problem on segmented epithelium patches. We propose to use conditional Generative Adversarial Networks (cGANs) to expand the limited training dataset, by synthesizing realistic cervical histopathology images. While the synthetic images are visually appealing, they are not guaranteed to contain meaningful features for data augmentation. To tackle this issue, we propose a synthetic-image filtering mechanism based on the divergence in feature space between generated images and class centroids in order to control the feature quality of selected synthetic images for data augmentation. Our models are evaluated on a cervical histopathology image dataset with a limited number of patch-level CIN grade annotations. Extensive experimental results show a significant improvement of classification accuracy from 66.3% to 71.7% using the same ResNet18 baseline classifier after leveraging our cGAN generated images with feature-based filtering, which demonstrates the effectiveness of our models.