CLCNet: Deep learning-based Noise Reduction for Hearing Aids using Complex Linear Coding

Noise reduction is an important part of modern hearing aids and is included in most commercially available devices. Deep learning-based state-of-the-art algorithms, however, either do not consider real-time and frequency resolution constrains or result in poor quality under very noisy conditions. To improve monaural speech enhancement in noisy environments, we propose CLCNet, a framework based on complex valued linear coding. First, we define complex linear coding (CLC) motivated by linear predictive coding (LPC) that is applied in the complex frequency domain. Second, we propose a framework that incorporates complex spectrogram input and coefficient output. Third, we define a parametric normalization for complex valued spectrograms that complies with low-latency and on-line processing. Our CLCNet was evaluated on a mixture of the EUROM database and a real-world noise dataset recorded with hearing aids and compared to traditional real-valued Wiener-Filter gains.

Learning New Tricks from Old Dogs -- Inter-Species, Inter-Tissue Domain Adaptation for Mitotic Figure Assessment

For histopathological tumor assessment, the count of mitotic figures per area is an important part of prognostication. Algorithmic approaches - such as for mitotic figure identification - have significantly improved in recent times, potentially allowing for computer-augmented or fully automatic screening systems in the future. This trend is further supported by whole slide scanning microscopes becoming available in many pathology labs and could soon become a standard imaging tool. For an application in broader fields of such algorithms, the availability of mitotic figure data sets of sufficient size for the respective tissue type and species is an important precondition, that is, however, rarely met. While algorithmic performance climbed steadily for e.g. human mammary carcinoma, thanks to several challenges held in the field, for most tumor types, data sets are not available. In this work, we assess domain transfer of mitotic figure recognition using domain adversarial training on four data sets, two from dogs and two from humans. We were able to show that domain adversarial training considerably improves accuracy when applying mitotic figure classification learned from the canine on the human data sets (up to +12.8% in accuracy) and is thus a helpful method to transfer knowledge from existing data sets to new tissue types and species.

Deep Learning-Based Quantification of Pulmonary Hemosiderophages in Cytology Slides

Purpose: Exercise-induced pulmonary hemorrhage (EIPH) is a common syndrome in sport horses with negative impact on performance. Cytology of bronchoalveolar lavage fluid by use of a scoring system is considered the most sensitive diagnostic method. Macrophages are classified depending on the degree of cytoplasmic hemosiderin content. The current gold standard is manual grading, which is however monotonous and time-consuming. Methods: We evaluated state-of-the-art deep learning-based methods for single cell macrophage classification and compared them against the performance of nine cytology experts and evaluated inter- and intra-observer variability. Additionally, we evaluated object detection methods on a novel data set of 17 completely annotated cytology whole slide images (WSI) containing 78,047 hemosiderophages. Resultsf: Our deep learning-based approach reached a concordance of 0.85, partially exceeding human expert concordance (0.68 to 0.86, $\mu$=0.73, $\sigma$ =0.04). Intra-observer variability was high (0.68 to 0.88) and inter-observer concordance was moderate (Fleiss kappa = 0.67). Our object detection approach has a mean average precision of 0.66 over the five classes from the whole slide gigapixel image and a computation time of below two minutes. Conclusion: To mitigate the high inter- and intra-rater variability, we propose our automated object detection pipeline, enabling accurate, reproducible and quick EIPH scoring in WSI.

Transferability of Deep Learning Algorithms for Malignancy Detection in Confocal Laser Endomicroscopy Images from Different Anatomical Locations of the Upper Gastrointestinal Tract

Squamous Cell Carcinoma (SCC) is the most common cancer type of the epithelium and is often detected at a late stage. Besides invasive diagnosis of SCC by means of biopsy and histo-pathologic assessment, Confocal Laser Endomicroscopy (CLE) has emerged as noninvasive method that was successfully used to diagnose SCC in vivo. For interpretation of CLE images, however, extensive training is required, which limits its applicability and use in clinical practice of the method. To aid diagnosis of SCC in a broader scope, automatic detection methods have been proposed. This work compares two methods with regard to their applicability in a transfer learning sense, i.e. training on one tissue type (from one clinical team) and applying the learnt classification system to another entity (different anatomy, different clinical team). Besides a previously proposed, patch-based method based on convolutional neural networks, a novel classification method on image level (based on a pre-trained Inception V.3 network with dedicated preprocessing and interpretation of class activation maps) is proposed and evaluated. The newly presented approach improves recognition performance, yielding accuracies of 91.63% on the first data set (oral cavity) and 92.63% on a joint data set. The generalization from oral cavity to the second data set (vocal folds) lead to similar area-under-the-ROC curve values than a direct training on the vocal folds data set, indicating good generalization.

Field of Interest Prediction for Computer-Aided Mitotic Count

Manual counts of mitotic figures, which are determined in the tumor region with the highest mitotic activity, are a key parameter of most tumor grading schemes. It is however strongly dependent on the area selection. To reduce potential variability of prognosis due to this, we propose to use an algorithmic field of interest prediction to assess the area of highest mitotic activity in a whole-slide image. Methods: We evaluated two state-of-the-art methods, all based on the use of deep convolutional neural networks on their ability to predict the mitotic count in digital histopathology slides. We evaluated them on a novel dataset of 32 completely annotated whole slide images from canine cutaneous mast cell tumors (CMCT) and one publicly available human mamma carcinoma (HMC) dataset. We first compared the mitotic counts (MC) predicted by the two models with the ground truth MC on both data sets. Second, for the CMCT data set, we compared the computationally predicted position and MC of the area of highest mitotic activity with size-equivalent areas selected by eight veterinary pathologists. Results: We found a high correlation between the mitotic count as predicted by the models (Pearson's correlation coefficient between 0.931 and 0.962 for the CMCT data set and between 0.801 and 0.986 for the HMC data set) on the slides. For the CMCT data set, this is also reflected in the predicted position representing mitotic counts in mostly the upper quartile of the slide's ground truth MC distribution. Further, we found strong differences between experts in position selection. Conclusion: While the mitotic counts in areas selected by the experts substantially varied, both algorithmic approaches were consistently able to generate a good estimate of the area of highest mitotic count. To achieve better inter-rater agreement, we propose to use computer-based area selection for manual mitotic count.

Field Of Interest Proposal for Augmented Mitotic Cell Count: Comparison of two Convolutional Networks

Most tumor grading systems for human as for veterinary histopathology are based upon the absolute count of mitotic figures in a certain reference area of a histology slide. Since time for prognostication is limited in a diagnostic setting, the pathologist will often almost arbitrarily choose a certain field of interest assumed to have the highest mitotic activity. However, as mitotic figures are commonly very sparse on the slide and often have a patchy distribution, this poses a sampling problem which is known to be able to influence the tumor prognostication. On the other hand, automatic detection of mitotic figures can't yet be considered reliable enough for clinical application. In order to aid the work of the human expert and at the same time reduce variance in tumor grading, it is beneficial to assess the whole slide image (WSI) for the highest mitotic activity and use this as a reference region for human counting. For this task, we compare two methods for region of interest proposal, both based on convolutional neural networks (CNN). For both approaches, the CNN performs a segmentation of the WSI to assess mitotic activity. The first method performs a segmentation at the original image resolution, while the second approach performs a segmentation operation at a significantly reduced resolution, cutting down on processing complexity. We evaluate the approach using a dataset of 32 completely annotated whole slide images of canine mast cell tumors, where 22 were used for training of the network and 10 for test. Our results indicate that, while the overall correlation to the ground truth mitotic activity is considerably higher (0.94 vs. 0.83) for the approach based upon the fine resolution network, the field of interest choices are only marginally better. Both approaches propose fields of interest that contain a mitotic count in the upper quartile of respective slides.

Augmented Mitotic Cell Count using Field Of Interest Proposal

Histopathological prognostication of neoplasia including most tumor grading systems are based upon a number of criteria. Probably the most important is the number of mitotic figures which are most commonly determined as the mitotic count (MC), i.e. number of mitotic figures within 10 consecutive high power fields. Often the area with the highest mitotic activity is to be selected for the MC. However, since mitotic activity is not known in advance, an arbitrary choice of this region is considered one important cause for high variability in the prognostication and grading. In this work, we present an algorithmic approach that first calculates a mitotic cell map based upon a deep convolutional network. This map is in a second step used to construct a mitotic activity estimate. Lastly, we select the image segment representing the size of ten high power fields with the overall highest mitotic activity as a region proposal for an expert MC determination. We evaluate the approach using a dataset of 32 completely annotated whole slide images, where 22 were used for training of the network and 10 for test. We find a correlation of r=0.936 in mitotic count estimate.

Motion Artifact Detection in Confocal Laser Endomicroscopy Images

Confocal Laser Endomicroscopy (CLE), an optical imaging technique allowing non-invasive examination of the mucosa on a (sub)cellular level, has proven to be a valuable diagnostic tool in gastroenterology and shows promising results in various anatomical regions including the oral cavity. Recently, the feasibility of automatic carcinoma detection for CLE images of sufficient quality was shown. However, in real world data sets a high amount of CLE images is corrupted by artifacts. Amongst the most prevalent artifact types are motion-induced image deteriorations. In the scope of this work, algorithmic approaches for the automatic detection of motion artifact-tainted image regions were developed. Hence, this work provides an important step towards clinical applicability of automatic carcinoma detection. Both, conventional machine learning and novel, deep learning-based approaches were assessed. The deep learning-based approach outperforms the conventional approaches, attaining an AUC of 0.90.

SlideRunner - A Tool for Massive Cell Annotations in Whole Slide Images

Large-scale image data such as digital whole-slide histology images pose a challenging task at annotation software solutions. Today, a number of good solutions with varying scopes exist. For cell annotation, however, we find that many do not match the prerequisites for fast annotations. Especially in the field of mitosis detection, it is assumed that detection accuracy could significantly benefit from larger annotation databases that are currently however very troublesome to produce. Further, multiple independent (blind) expert labels are a big asset for such databases, yet there is currently no tool for this kind of annotation available. To ease this tedious process of expert annotation and grading, we introduce SlideRunner, an open source annotation and visualization tool for digital histopathology, developed in close cooperation with two pathologists. SlideRunner is capable of setting annotations like object centers (for e.g. cells) as well as object boundaries (e.g. for tumor outlines). It provides single-click annotations as well as a blind mode for multi-annotations, where the expert is directly shown the microscopy image containing the cells that he has not yet rated.

A Guided Spatial Transformer Network for Histology Cell Differentiation

Identification and counting of cells and mitotic figures is a standard task in diagnostic histopathology. Due to the large overall cell count on histological slides and the potential sparse prevalence of some relevant cell types or mitotic figures, retrieving annotation data for sufficient statistics is a tedious task and prone to a significant error in assessment. Automatic classification and segmentation is a classic task in digital pathology, yet it is not solved to a sufficient degree. We present a novel approach for cell and mitotic figure classification, based on a deep convolutional network with an incorporated Spatial Transformer Network. The network was trained on a novel data set with ten thousand mitotic figures, about ten times more than previous data sets. The algorithm is able to derive the cell class (mitotic tumor cells, non-mitotic tumor cells and granulocytes) and their position within an image. The mean accuracy of the algorithm in a five-fold cross-validation is 91.45%. In our view, the approach is a promising step into the direction of a more objective and accurate, semi-automatized mitosis counting supporting the pathologist.