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Histopathological tissue classification is a simpler way to achieve semantic segmentation for the whole slide images, which can alleviate the requirement of pixel-level dense annotations. Existing works mostly leverage the popular CNN classification backbones in computer vision to achieve histopathological tissue classification. In this paper, we propose a super lightweight plug-and-play module, named Pyramidal Deep-Broad Learning (PDBL), for any well-trained classification backbone to improve the classification performance without a re-training burden. For each patch, we construct a multi-resolution image pyramid to obtain the pyramidal contextual information. For each level in the pyramid, we extract the multi-scale deep-broad features by our proposed Deep-Broad block (DB-block). We equip PDBL in three popular classification backbones, ShuffLeNetV2, EfficientNetb0, and ResNet50 to evaluate the effectiveness and efficiency of our proposed module on two datasets (Kather Multiclass Dataset and the LC25000 Dataset). Experimental results demonstrate the proposed PDBL can steadily improve the tissue-level classification performance for any CNN backbones, especially for the lightweight models when given a small among of training samples (less than 10%). It greatly saves the computational resources and annotation efforts. The source code is available at: https://github.com/linjiatai/PDBL. [ABSTRACT FROM AUTHOR]

Deep neural networks have achieved remarkable success in a wide variety of natural image and medical image computing tasks. However, these achievements indispensably rely on accurately annotated training data. If encountering some noisy-labeled images, the network training procedure would suffer from difficulties, leading to a sub-optimal classifier. This problem is even more severe in the medical image analysis field, as the annotation quality of medical images heavily relies on the expertise and experience of annotators. In this paper, we propose a novel collaborative training paradigm with global and local representation learning for robust medical image classification from noisy-labeled data to combat the lack of high quality annotated medical data. Specifically, we employ the self-ensemble model with a noisy label filter to efficiently select the clean and noisy samples. Then, the clean samples are trained by a collaborative training strategy to eliminate the disturbance from imperfect labeled samples. Notably, we further design a novel global and local representation learning scheme to implicitly regularize the networks to utilize noisy samples in a self-supervised manner. We evaluated our proposed robust learning strategy on four public medical image classification datasets with three types of label noise, i.e., random noise, computer-generated label noise, and inter-observer variability noise. Our method outperforms other learning from noisy label methods and we also conducted extensive experiments to analyze each component of our method. [ABSTRACT FROM AUTHOR]

Deep neural networks, in particular convolutional networks, have rapidly become a popular choice for analyzing histopathology images. However, training these models relies heavily on a large number of samples manually annotated by experts, which is cumbersome and expensive. In addition, it is difficult to obtain a perfect set of labels due to the variability between expert annotations. This paper presents a novel active learning (AL) framework for histopathology image analysis, named PathAL. To reduce the required number of expert annotations, PathAL selects two groups of unlabeled data in each training iteration: one “informative” sample that requires additional expert annotation, and one “confident predictive” sample that is automatically added to the training set using the model’s pseudo-labels. To reduce the impact of the noisy-labeled samples in the training set, PathAL systematically identifies noisy samples and excludes them to improve the generalization of the model. Our model advances the existing AL method for medical image analysis in two ways. First, we present a selection strategy to improve classification performance with fewer manual annotations. Unlike traditional methods focusing only on finding the most uncertain samples with low prediction confidence, we discover a large number of high confidence samples from the unlabeled set and automatically add them for training with assigned pseudo-labels. Second, we design a method to distinguish between noisy samples and hard samples using a heuristic approach. We exclude the noisy samples while preserving the hard samples to improve model performance. Extensive experiments demonstrate that our proposed PathAL framework achieves promising results on a prostate cancer Gleason grading task, obtaining similar performance with 40% fewer annotations compared to the fully supervised learning scenario. An ablation study is provided to analyze the effectiveness of each component in PathAL, and a pathologist reader study is conducted to validate our proposed algorithm. [ABSTRACT FROM AUTHOR]

Automatic liver tumor segmentation is of great importance for assisting doctors in liver cancer diagnosis and treatment planning. Recently, deep learning approaches trained with pixel-level annotations have contributed many breakthroughs in image segmentation. However, acquiring such accurate dense annotations is time-consuming and labor-intensive, which limits the performance of deep neural networks for medical image segmentation. We note that Couinaud segment is widely used by radiologists when recording liver cancer-related findings in the reports, since it is well-suited for describing the localization of tumors. In this paper, we propose a novel approach to train convolutional networks for liver tumor segmentation using Couinaud segment annotations. Couinaud segment annotations are image-level labels with values ranging from 1 to 8, indicating a specific region of the liver. Our proposed model, namely CouinaudNet, can estimate pseudo tumor masks from the Couinaud segment annotations as pixel-wise supervision for training a fully supervised tumor segmentation model, and it is composed of two components: 1) an inpainting network with Couinaud segment masks which can effectively remove tumors for pathological images by filling the tumor regions with plausible healthy-looking intensities; 2) a difference spotting network for segmenting the tumors, which is trained with healthy-pathological pairs generated by an effective tumor synthesis strategy. The proposed method is extensively evaluated on two liver tumor segmentation datasets. The experimental results demonstrate that our method can achieve competitive performance compared to the fully supervised counterpart and the state-of-the-art methods while requiring significantly less annotation effort. [ABSTRACT FROM AUTHOR]

As the labeled anomalous medical images are usually difficult to acquire, especially for rare diseases, the deep learning based methods, which heavily rely on the large amount of labeled data, cannot yield a satisfactory performance. Compared to the anomalous data, the normal images without the need of lesion annotation are much easier to collect. In this paper, we propose an anomaly detection framework, namely $\mathbb {SALAD}$ , extracting $\mathbb {S}$ elf-supervised and tr $\mathbb {A}$ ns $\mathbb {L}$ ation-consistent features for $\mathbb {A}$ nomaly $\mathbb {D}$ etection. The proposed SALAD is a reconstruction-based method, which learns the manifold of normal data through an encode-and-reconstruct translation between image and latent spaces. In particular, two constraints (i.e., structure similarity loss and center constraint loss) are proposed to regulate the cross-space (i.e., image and feature) translation, which enforce the model to learn translation-consistent and representative features from the normal data. Furthermore, a self-supervised learning module is engaged into our framework to further boost the anomaly detection accuracy by deeply exploiting useful information from the raw normal data. An anomaly score, as a measure to separate the anomalous data from the healthy ones, is constructed based on the learned self-supervised-and-translation-consistent features. Extensive experiments are conducted on optical coherence tomography (OCT) and chest X-ray datasets. The experimental results demonstrate the effectiveness of our approach. [ABSTRACT FROM AUTHOR]

With the development of deep learning, medical image classification has been significantly improved. However, deep learning requires massive data with labels. While labeling the samples by human experts is expensive and time-consuming, collecting labels from crowd-sourcing suffers from the noises which may degenerate the accuracy of classifiers. Therefore, approaches that can effectively handle label noises are highly desired. Unfortunately, recent progress on handling label noise in deep learning has gone largely unnoticed by the medical image. To fill the gap, this paper proposes a noise-tolerant medical image classification framework named Co-Correcting, which significantly improves classification accuracy and obtains more accurate labels through dual-network mutual learning, label probability estimation, and curriculum label correcting. On two representative medical image datasets and the MNIST dataset, we test six latest Learning-with-Noisy-Labels methods and conduct comparative studies. The experiments show that Co-Correcting achieves the best accuracy and generalization under different noise ratios in various tasks. Our project can be found at: https://github.com/JiarunLiu/Co-Correcting. [ABSTRACT FROM AUTHOR]

This paper introduces a new concept called “transferable visual words” (TransVW), aiming to achieve annotation efficiency for deep learning in medical image analysis. Medical imaging—focusing on particular parts of the body for defined clinical purposes—generates images of great similarity in anatomy across patients and yields sophisticated anatomical patterns across images, which are associated with rich semantics about human anatomy and which are natural visual words. We show that these visual words can be automatically harvested according to anatomical consistency via self-discovery, and that the self-discovered visual words can serve as strong yet free supervision signals for deep models to learn semantics-enriched generic image representation via self-supervision (self-classification and self-restoration). Our extensive experiments demonstrate the annotation efficiency of TransVW by offering higher performance and faster convergence with reduced annotation cost in several applications. Our TransVW has several important advantages, including (1) TransVW is a fully autodidactic scheme, which exploits the semantics of visual words for self-supervised learning, requiring no expert annotation; (2) visual word learning is an add-on strategy, which complements existing self-supervised methods, boosting their performance; and (3) the learned image representation is semantics-enriched models, which have proven to be more robust and generalizable, saving annotation efforts for a variety of applications through transfer learning. Our code, pre-trained models, and curated visual words are available at https://github.com/JLiangLab/TransVW. [ABSTRACT FROM AUTHOR]

Despite that deep learning has achieved state-of-the-art performance for medical image segmentation, its success relies on a large set of manually annotated images for training that are expensive to acquire. In this paper, we propose an annotation-efficient learning framework for segmentation tasks that avoids annotations of training images, where we use an improved Cycle-Consistent Generative Adversarial Network (GAN) to learn from a set of unpaired medical images and auxiliary masks obtained either from a shape model or public datasets. We first use the GAN to generate pseudo labels for our training images under the implicit high-level shape constraint represented by a Variational Auto-encoder (VAE)-based discriminator with the help of the auxiliary masks, and build a Discriminator-guided Generator Channel Calibration (DGCC) module which employs our discriminator’s feedback to calibrate the generator for better pseudo labels. To learn from the pseudo labels that are noisy, we further introduce a noise-robust iterative learning method using noise-weighted Dice loss. We validated our framework with two situations: objects with a simple shape model like optic disc in fundus images and fetal head in ultrasound images, and complex structures like lung in X-Ray images and liver in CT images. Experimental results demonstrated that 1) Our VAE-based discriminator and DGCC module help to obtain high-quality pseudo labels. 2) Our proposed noise-robust learning method can effectively overcome the effect of noisy pseudo labels. 3) The segmentation performance of our method without using annotations of training images is close or even comparable to that of learning from human annotations. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most prevalent cancer among men in Western countries, with 1.1 million new diagnoses every year. The gold standard for the diagnosis of prostate cancer is a pathologists’ evaluation of prostate tissue. To potentially assist pathologists deep $\overline {/}$ learning $\overline {/}$ based cancer detection systems have been developed. Many of the state-of-the-art models are patch $\overline {/}$ based convolutional neural networks, as the use of entire scanned slides is hampered by memory limitations on accelerator cards. Patch-based systems typically require detailed, pixel-level annotations for effective training. However, such annotations are seldom readily available, in contrast to the clinical reports of pathologists, which contain slide-level labels. As such, developing algorithms which do not require manual pixel-wise annotations, but can learn using only the clinical report would be a significant advancement for the field. In this paper, we propose to use a streaming implementation of convolutional layers, to train a modern CNN (ResNet $\overline {/}$ 34) with 21 million parameters end-to-end on 4712 prostate biopsies. The method enables the use of entire biopsy images at high-resolution directly by reducing the GPU memory requirements by 2.4 TB. We show that modern CNNs, trained using our streaming approach, can extract meaningful features from high-resolution images without additional heuristics, reaching similar performance as state-of-the-art patch-based and multiple-instance learning methods. By circumventing the need for manual annotations, this approach can function as a blueprint for other tasks in histopathological diagnosis. The source code to reproduce the streaming models is available at https://github.com/DIAGNijmegen/ pathology-streaming-pipeline. [ABSTRACT FROM AUTHOR]

This paper presents a client/server privacy-preserving network in the context of multicentric medical image analysis. Our approach is based on adversarial learning which encodes images to obfuscate the patient identity while preserving enough information for a target task. Our novel architecture is composed of three components: 1) an encoder network which removes identity-specific features from input medical images, 2) a discriminator network that attempts to identify the subject from the encoded images, 3) a medical image analysis network which analyzes the content of the encoded images (segmentation in our case). By simultaneously fooling the discriminator and optimizing the medical analysis network, the encoder learns to remove privacy-specific features while keeping those essentials for the target task. Our approach is illustrated on the problem of segmenting brain MRI from the large-scale Parkinson Progression Marker Initiative (PPMI) dataset. Using longitudinal data from PPMI, we show that the discriminator learns to heavily distort input images while allowing for highly accurate segmentation results. Our results also demonstrate that an encoder trained on the PPMI dataset can be used for segmenting other datasets, without the need for retraining. The code is made available at: https://github.com/bachkimn/Privacy-Net-An-Adversarial-Approach-forIdentity-Obfuscated-Segmentation-of-MedicalImages [ABSTRACT FROM AUTHOR]

Recently, automatic diagnostic approaches have been widely used to classify ocular diseases. Most of these approaches are based on a single imaging modality (e.g., fundus photography or optical coherence tomography (OCT)), which usually only reflect the oculopathy to a certain extent, and neglect the modality-specific information among different imaging modalities. This paper proposes a novel modality-specific attention network (MSAN) for multi-modal retinal image classification, which can effectively utilize the modality-specific diagnostic features from fundus and OCT images. The MSAN comprises two attention modules to extract the modality-specific features from fundus and OCT images, respectively. Specifically, for the fundus image, ophthalmologists need to observe local and global pathologies at multiple scales (e.g., from microaneurysms at the micrometer level, optic disc at millimeter level to blood vessels through the whole eye). Therefore, we propose a multi-scale attention module to extract both the local and global features from fundus images. Moreover, large background regions exist in the OCT image, which is meaningless for diagnosis. Thus, a region-guided attention module is proposed to encode the retinal layer-related features and ignore the background in OCT images. Finally, we fuse the modality-specific features to form a multi-modal feature and train the multi-modal retinal image classification network. The fusion of modality-specific features allows the model to combine the advantages of fundus and OCT modality for a more accurate diagnosis. Experimental results on a clinically acquired multi-modal retinal image (fundus and OCT) dataset demonstrate that our MSAN outperforms other well-known single-modal and multi-modal retinal image classification methods. [ABSTRACT FROM AUTHOR]

Nuclei segmentation is a fundamental task in histopathology image analysis. Typically, such segmentation tasks require significant effort to manually generate accurate pixel-wise annotations for fully supervised training. To alleviate such tedious and manual effort, in this paper we propose a novel weakly supervised segmentation framework based on partial points annotation, i.e., only a small portion of nuclei locations in each image are labeled. The framework consists of two learning stages. In the first stage, we design a semi-supervised strategy to learn a detection model from partially labeled nuclei locations. Specifically, an extended Gaussian mask is designed to train an initial model with partially labeled data. Then, self-training with background propagation is proposed to make use of the unlabeled regions to boost nuclei detection and suppress false positives. In the second stage, a segmentation model is trained from the detected nuclei locations in a weakly-supervised fashion. Two types of coarse labels with complementary information are derived from the detected points and are then utilized to train a deep neural network. The fully-connected conditional random field loss is utilized in training to further refine the model without introducing extra computational complexity during inference. The proposed method is extensively evaluated on two nuclei segmentation datasets. The experimental results demonstrate that our method can achieve competitive performance compared to the fully supervised counterpart and the state-of-the-art methods while requiring significantly less annotation effort. [ABSTRACT FROM AUTHOR]

Shortage of fully annotated datasets has been a limiting factor in developing deep learning based image segmentation algorithms and the problem becomes more pronounced in multi-organ segmentation. In this paper, we propose a unified training strategy that enables a novel multi-scale deep neural network to be trained on multiple partially labeled datasets for multi-organ segmentation. In addition, a new network architecture for multi-scale feature abstraction is proposed to integrate pyramid input and feature analysis into a U-shape pyramid structure. To bridge the semantic gap caused by directly merging features from different scales, an equal convolutional depth mechanism is introduced. Furthermore, we employ a deep supervision mechanism to refine the outputs in different scales. To fully leverage the segmentation features from all the scales, we design an adaptive weighting layer to fuse the outputs in an automatic fashion. All these mechanisms together are integrated into a Pyramid Input Pyramid Output Feature Abstraction Network (PIPO-FAN). Our proposed method was evaluated on four publicly available datasets, including BTCV, LiTS, KiTS and Spleen, where very promising performance has been achieved. The source code of this work is publicly shared at https://github.com/DIAL-RPI/PIPO-FAN to facilitate others to reproduce the work and build their own models using the introduced mechanisms. [ABSTRACT FROM AUTHOR]

Deep learning approaches have demonstrated remarkable progress in automatic Chest X-ray analysis. The data-driven feature of deep models requires training data to cover a large distribution. Therefore, it is substantial to integrate knowledge from multiple datasets, especially for medical images. However, learning a disease classification model with extra Chest X-ray (CXR) data is yet challenging. Recent researches have demonstrated that performance bottleneck exists in joint training on different CXR datasets, and few made efforts to address the obstacle. In this paper, we argue that incorporating an external CXR dataset leads to imperfect training data, which raises the challenges. Specifically, the imperfect data is in two folds: domain discrepancy, as the image appearances vary across datasets; and label discrepancy, as different datasets are partially labeled. To this end, we formulate the multi-label thoracic disease classification problem as weighted independent binary tasks according to the categories. For common categories shared across domains, we adopt task-specific adversarial training to alleviate the feature differences. For categories existing in a single dataset, we present uncertainty-aware temporal ensembling of model predictions to mine the information from the missing labels further. In this way, our framework simultaneously models and tackles the domain and label discrepancies, enabling superior knowledge mining ability. We conduct extensive experiments on three datasets with more than 360,000 Chest X-ray images. Our method outperforms other competing models and sets state-of-the-art performance on the official NIH test set with 0.8349 AUC, demonstrating its effectiveness of utilizing the external dataset to improve the internal classification. [ABSTRACT FROM AUTHOR]

Automated prostate segmentation in MRI is highly demanded for computer-assisted diagnosis. Recently, a variety of deep learning methods have achieved remarkable progress in this task, usually relying on large amounts of training data. Due to the nature of scarcity for medical images, it is important to effectively aggregate data from multiple sites for robust model training, to alleviate the insufficiency of single-site samples. However, the prostate MRIs from different sites present heterogeneity due to the differences in scanners and imaging protocols, raising challenges for effective ways of aggregating multi-site data for network training. In this paper, we propose a novel multi-site network (MS-Net) for improving prostate segmentation by learning robust representations, leveraging multiple sources of data. To compensate for the inter-site heterogeneity of different MRI datasets, we develop Domain-Specific Batch Normalization layers in the network backbone, enabling the network to estimate statistics and perform feature normalization for each site separately. Considering the difficulty of capturing the shared knowledge from multiple datasets, a novel learning paradigm, i.e., Multi-site-guided Knowledge Transfer, is proposed to enhance the kernels to extract more generic representations from multi-site data. Extensive experiments on three heterogeneous prostate MRI datasets demonstrate that our MS-Net improves the performance across all datasets consistently, and outperforms state-of-the-art methods for multi-site learning. [ABSTRACT FROM AUTHOR]

Recent advances in deep learning for medical image segmentation demonstrate expert-level accuracy. However, application of these models in clinically realistic environments can result in poor generalization and decreased accuracy, mainly due to the domain shift across different hospitals, scanner vendors, imaging protocols, and patient populations etc. Common transfer learning and domain adaptation techniques are proposed to address this bottleneck. However, these solutions require data (and annotations) from the target domain to retrain the model, and is therefore restrictive in practice for widespread model deployment. Ideally, we wish to have a trained (locked) model that can work uniformly well across unseen domains without further training. In this paper, we propose a deep stacked transformation approach for domain generalization. Specifically, a series of ${n}$ stacked transformations are applied to each image during network training. The underlying assumption is that the “expected” domain shift for a specific medical imaging modality could be simulated by applying extensive data augmentation on a single source domain, and consequently, a deep model trained on the augmented “big” data (BigAug) could generalize well on unseen domains. We exploit four surprisingly effective, but previously understudied, image-based characteristics for data augmentation to overcome the domain generalization problem. We train and evaluate the BigAug model (with ${n}={9}$ transformations) on three different 3D segmentation tasks (prostate gland, left atrial, left ventricle) covering two medical imaging modalities (MRI and ultrasound) involving eight publicly available challenge datasets. The results show that when training on relatively small dataset (n = 10~32 volumes, depending on the size of the available datasets) from a single source domain: (i) BigAug models degrade an average of 11%(Dice score change) from source to unseen domain, substantially better than conventional augmentation (degrading 39%) and CycleGAN-based domain adaptation method (degrading 25%), (ii) BigAug is better than “shallower” stacked transforms (i.e. those with fewer transforms) on unseen domains and demonstrates modest improvement to conventional augmentation on the source domain, (iii) after training with BigAug on one source domain, performance on an unseen domain is similar to training a model from scratch on that domain when using the same number of training samples. When training on large datasets (n = 465 volumes) with BigAug, (iv) application to unseen domains reaches the performance of state-of-the-art fully supervised models that are trained and tested on their source domains. These findings establish a strong benchmark for the study of domain generalization in medical imaging, and can be generalized to the design of highly robust deep segmentation models for clinical deployment. [ABSTRACT FROM AUTHOR]

Current deep supervised learning methods typically require large amounts of labeled data for training. Since there is a significant cost associated with clinical data acquisition and labeling, medical datasets used for training these models are relatively small in size. In this paper, we aim to alleviate this limitation by proposing a variational generative model along with an effective data augmentation approach that utilizes the generative model to synthesize data. In our approach, the model learns the probability distribution of image data conditioned on a latent variable and the corresponding labels. The trained model can then be used to synthesize new images for data augmentation. We demonstrate the effectiveness of the approach on two independent clinical datasets consisting of ultrasound images of the spine and magnetic resonance images of the brain. For the spine dataset, a baseline and a residual model achieve an accuracy of 85% and 92%, respectively, using our method compared to 78% and 83% using a conventional training approach for image classification task. For the brain dataset, a baseline and a U-net network achieve an accuracy of 84% and 88%, respectively, in Dice coefficient in tumor segmentation compared to 80% and 83% for the convention training approach. [ABSTRACT FROM AUTHOR]

Machine learning algorithms can have difficulties adapting to data from different sources, for example from different imaging modalities. We present and analyze three techniques for unsupervised cross-modality feature learning, using a shared autoencoder-like convolutional network that learns a common representation from multi-modal data. We investigate a form of feature normalization, a learning objective that minimizes cross-modality differences, and modality dropout, in which the network is trained with varying subsets of modalities. We measure the same-modality and cross-modality classification accuracies and explore whether the models learn modality-specific or shared features. This paper presents experiments on two public data sets, with knee images from two MRI modalities, provided by the Osteoarthritis Initiative, and brain tumor segmentation on four MRI modalities from the BRATS challenge. All three approaches improved the cross-modality classification accuracy, with modality dropout and per-feature normalization giving the largest improvement. We observed that the networks tend to learn a combination of cross-modality and modality-specific features. Overall, a combination of all three methods produced the most cross-modality features and the highest cross-modality classification accuracy, while maintaining most of the same-modality accuracy. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke is recognized as a common cerebral vascular disease in aging people. Accurate diagnosis and timely treatment can effectively improve the blood supply of the ischemic area and reduce the risk of disability or even death. Understanding the location and size of infarcts plays a critical role in the diagnosis decision. However, manual localization and quantification of stroke lesions are laborious and time-consuming. In this paper, we propose a novel automatic method to segment acute ischemic stroke from diffusion weighted images (DWIs) using deep 3-D convolutional neural networks (CNNs). Our method can efficiently utilize 3-D contextual information and automatically learn very discriminative features in an end-to-end and data-driven way. To relieve the difficulty of training very deep 3-D CNN, we equip our network with dense connectivity to enable the unimpeded propagation of information and gradients throughout the network. We train our model with Dice objective function to combat the severe class imbalance problem in data. A DWI data set containing 242 subjects (90 for training, 62 for validation, and 90 for testing) with various types of acute ischemic stroke was constructed to evaluate our method. Our model achieved high performance on various metrics (Dice similarity coefficient: 79.13%, lesionwise precision: 92.67%, and lesionwise F1 score: 89.25%), outperforming the other state-of-the-art CNN methods by a large margin. We also evaluated the model on ISLES2015-SSIS data set and achieved very competitive performance, which further demonstrated its generalization capacity. The proposed method is fast and accurate, demonstrating a good potential in clinical routines. [ABSTRACT FROM AUTHOR]

In recently published clinical trial results, hypoxia-modified therapies have shown to provide more positive outcomes to cancer patients, compared with standard cancer treatments. The development and validation of these hypoxia-modified therapies depend on an effective way of measuring tumor hypoxia, but a standardized measurement is currently unavailable in clinical practice. Different types of manual measurements have been proposed in clinical research, but in this paper we focus on a recently published approach that quantifies the number and proportion of hypoxic regions using high resolution (immuno-)fluorescence (IF) and hematoxylin and eosin (HE) stained images of a histological specimen of a tumor. We introduce new machine learning-based methodologies to automate this measurement, where the main challenge is the fact that the clinical annotations available for training the proposed methodologies consist of the total number of normoxic, chronically hypoxic, and acutely hypoxic regions without any indication of their location in the image. Therefore, this represents a weakly-supervised structured output classification problem, where training is based on a high-order loss function formed by the norm of the difference between the manual and estimated annotations mentioned above. We propose four methodologies to solve this problem: 1) a naive method that uses a majority classifier applied on the nodes of a fixed grid placed over the input images; 2) a baseline method based on a structured output learning formulation that relies on a fixed grid placed over the input images; 3) an extension to this baseline based on a latent structured output learning formulation that uses a graph that is flexible in terms of the amount and positions of nodes; and 4) a pixel-wise labeling based on a fully-convolutional neural network. Using a data set of 89 weakly annotated pairs of IF and HE images from eight tumors, we show that the quantitative results of methods (3) and (4) above are equally competitive and superior to the naive (1) and baseline (2) methods. All proposed methodologies show high correlation values with respect to the clinical annotations. [ABSTRACT FROM AUTHOR]

Training a deep convolutional neural network (CNN) from scratch is difficult because it requires a large amount of labeled training data and a great deal of expertise to ensure proper convergence. A promising alternative is to fine-tune a CNN that has been pre-trained using, for instance, a large set of labeled natural images. However, the substantial differences between natural and medical images may advise against such knowledge transfer. In this paper, we seek to answer the following central question in the context of medical image analysis: Can the use of pre-trained deep CNNs with sufficient fine-tuning eliminate the need for training a deep CNN from scratch? To address this question, we considered four distinct medical imaging applications in three specialties (radiology, cardiology, and gastroenterology) involving classification, detection, and segmentation from three different imaging modalities, and investigated how the performance of deep CNNs trained from scratch compared with the pre-trained CNNs fine-tuned in a layer-wise manner. Our experiments consistently demonstrated that 1) the use of a pre-trained CNN with adequate fine-tuning outperformed or, in the worst case, performed as well as a CNN trained from scratch; 2) fine-tuned CNNs were more robust to the size of training sets than CNNs trained from scratch; 3) neither shallow tuning nor deep tuning was the optimal choice for a particular application; and 4) our layer-wise fine-tuning scheme could offer a practical way to reach the best performance for the application at hand based on the amount of available data. [ABSTRACT FROM AUTHOR]

Convolutional neural networks (CNNs) are deep learning network architectures that have pushed forward the state-of-the-art in a range of computer vision applications and are increasingly popular in medical image analysis. However, training of CNNs is time-consuming and challenging. In medical image analysis tasks, the majority of training examples are easy to classify and therefore contribute little to the CNN learning process. In this paper, we propose a method to improve and speed-up the CNN training for medical image analysis tasks by dynamically selecting misclassified negative samples during training. Training samples are heuristically sampled based on classification by the current status of the CNN. Weights are assigned to the training samples and informative samples are more likely to be included in the next CNN training iteration. We evaluated and compared our proposed method by training a CNN with (SeS) and without (NSeS) the selective sampling method. We focus on the detection of hemorrhages in color fundus images. A decreased training time from 170 epochs to 60 epochs with an increased performance—on par with two human experts—was achieved with areas under the receiver operating characteristics curve of 0.894 and 0.972 on two data sets. The SeS CNN statistically outperformed the NSeS CNN on an independent test set. [ABSTRACT FROM AUTHOR]