Marc Aubreville

Automatic Classification of Cancerous Tissue in Laserendomicroscopy Images of the Oral Cavity using Deep Learning

Oral Squamous Cell Carcinoma (OSCC) is a common type of cancer of the oral epithelium. Despite their high impact on mortality, sufficient screening methods for early diagnosis of OSCC often lack accuracy and thus OSCCs are mostly diagnosed at a late stage. Early detection and accurate outline estimation of OSCCs would lead to a better curative outcome and a reduction in recurrence rates after surgical treatment. Confocal Laser Endomicroscopy (CLE) records sub-surface micro-anatomical images for in vivo cell structure analysis. Recent CLE studies showed great prospects for a reliable, real-time ultrastructural imaging of OSCC in situ. We present and evaluate a novel automatic approach for OSCC diagnosis using deep learning technologies on CLE images. The method is compared against textural feature-based machine learning approaches that represent the current state of the art. For this work, CLE image sequences (7894 images) from patients diagnosed with OSCC were obtained from 4 specific locations in the oral cavity, including the OSCC lesion. The present approach is found to outperform the state of the art in CLE image recognition with an area under the curve (AUC) of 0.96 and a mean accuracy of 88.3% (sensitivity 86.6%, specificity 90%).

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.

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.

Patch-based Carcinoma Detection on Confocal Laser Endomicroscopy Images - A Cross-site Robustness Assessment

Deep learning technologies such as convolutional neural networks (CNN) provide powerful methods for image recognition and have recently been employed in the field of automated carcinoma detection in confocal laser endomicroscopy (CLE) images. CLE is a (sub-)surface microscopic imaging technique that reaches magnifications of up to 1000x and is thus suitable for in vivo structural tissue analysis. In this work, we aim to evaluate the prospects of a priorly developed deep learning-based algorithm targeted at the identification of oral squamous cell carcinoma with regard to its generalization to further anatomic locations of squamous cell carcinomas in the area of head and neck. We applied the algorithm on images acquired from the vocal fold area of five patients with histologically verified squamous cell carcinoma and presumably healthy control images of the clinically normal contra-lateral vocal cord. We find that the network trained on the oral cavity data reaches an accuracy of 89.45% and an area-under-the-curve (AUC) value of 0.955, when applied on the vocal cords data. Compared to the state of the art, we achieve very similar results, yet with an algorithm that was trained on a completely disjunct data set. Concatenating both data sets yielded further improvements in cross-validation with an accuracy of 90.81% and AUC of 0.970. In this study, for the first time to our knowledge, a deep learning mechanism for the identification of oral carcinomas using CLE Images could be applied to other disciplines in the area of head and neck. This study shows the prospect of the algorithmic approach to generalize well on other malignant entities of the head and neck, regardless of the anatomical location and furthermore in an examiner-independent manner.

Deep learning-based detection of motion artifacts in probe-based confocal laser endomicroscopy images

Purpose:Probe-based confocal laser endomicroscopy (pCLE) is a subcellular in vivo imaging technique capable of producing images that enable diagnosis of malign structural modifications in epithelial tissue. Images acquired with pCLE are, however, often tainted by significant artifacts that impair diagnosis. This is especially detrimental for automated image analysis, which is why said images are often excluded from recognition pipelines.MethodsWe present an approach for the automatic detection of motion artifacts in pCLE images and apply this methodology to a data set of 15 thousand images of epithelial tissue acquired in the oral cavity and the vocal folds. The approach is based on transfer learning from intermediate endpoints within a pre-trained Inception v3 network with tailored preprocessing. For detection within the non-rectangular pCLE images, we perform pooling within the activation maps of the network and evaluate this at different network depths.ResultsWe achieved area under the ROC curve values of 0.92 with the proposed method, compared to 0.80 for the best feature-based machine learning approach. Our overall accuracy with the presented approach is 94.8%.ConclusionOver traditional machine learning approaches with state-of-the-art features, we achieved significantly improved overall performance.

Classification of Mitotic Cells

Tumor diagnostics are based on histopathological assessments of tissue biopsies of the suspected carcinogen region. One standard task in histopathology is counting of mitotic cells, a task that provides great potential to be improved in speed, accuracy and reproducability. The advent of deep learning methods brought a significant increase in precision of algorithmic detection methods, yet it is dependent on the availability of large amounts of data, completely capturing the natural variability in the material. Fully segmented images are provided by the MITOS dataset with 300 mitotic events. The ICPR2012 dataset provides 326 mitotic cells and in AMIDA2014 dataset, 550 mitotic cells for training and 533 for testing. In contrast to these datasets, a dataset with high number of mitotic events is missing. For this, either one of two pathologist annotated at least 10 thousand cell images for cells of the type mitosis, eosinophilic granulocyte and normal tumor cell from canine mast cell tumor whole-slide images, exceeding all publicly available data sets by approximately one order of magnitude. We tested performance using a standard CNN approach and found accuracies of up to 0.93.

Classification of Polyethylene Particles and the Local CD3+ Lymphocytosis in Histological Slices

In 2014, about 400.000 endoprosthetic operations were performed in Germany [1]. Unfortunately, the lifespan is limited and already after 10 years 5 percent of the patients have primary complaints [2]. All the more important it is to clarify the causes for this failure. One main cause is an immune response to abrasion particles of the implant, an effect which is assumed to be correlated with occurrence and count of CD3+ immune/inflammatory cells [3]. For the further analysis of this effect, computer-aided classification and image analysis methods provide a high value for the medical research. Aim of this work was the development of an threshold-based algorithm for the segmentation of polyethylene abrasion particles and the CD3+ immune/inflammatory response of histological slice images.