Prospects for Theranostics in Neurosurgical Imaging: Empowering Confocal Laser Endomicroscopy Diagnostics via Deep Learning

Confocal laser endomicroscopy (CLE) is an advanced optical fluorescence imaging technology that has the potential to increase intraoperative precision, extend resection, and tailor surgery for malignant invasive brain tumors because of its subcellular dimension resolution. Despite its promising diagnostic potential, interpreting the gray tone fluorescence images can be difficult for untrained users. In this review, we provide a detailed description of bioinformatical analysis methodology of CLE images that begins to assist the neurosurgeon and pathologist to rapidly connect on-the-fly intraoperative imaging, pathology, and surgical observation into a conclusionary system within the concept of theranostics. We present an overview and discuss deep learning models for automatic detection of the diagnostic CLE images and discuss various training regimes and ensemble modeling effect on the power of deep learning predictive models. Two major approaches reviewed in this paper include the models that can automatically classify CLE images into diagnostic/nondiagnostic, glioma/nonglioma, tumor/injury/normal categories and models that can localize histological features on the CLE images using weakly supervised methods. We also briefly review advances in the deep learning approaches used for CLE image analysis in other organs. Significant advances in speed and precision of automated diagnostic frame selection would augment the diagnostic potential of CLE, improve operative workflow and integration into brain tumor surgery. Such technology and bioinformatics analytics lend themselves to improved precision, personalization, and theranostics in brain tumor treatment.Comment: See the final version published in Frontiers in Oncology here: https://www.frontiersin.org/articles/10.3389/fonc.2018.00240/ful

Tailored for Real-World: A Whole Slide Image Classification System Validated on Uncurated Multi-Site Data Emulating the Prospective Pathology Workload.

Standard of care diagnostic procedure for suspected skin cancer is microscopic examination of hematoxylin & eosin stained tissue by a pathologist. Areas of high inter-pathologist discordance and rising biopsy rates necessitate higher efficiency and diagnostic reproducibility. We present and validate a deep learning system which classifies digitized dermatopathology slides into 4 categories. The system is developed using 5,070 images from a single lab, and tested on an uncurated set of 13,537 images from 3 test labs, using whole slide scanners manufactured by 3 different vendors. The system\u27s use of deep-learning-based confidence scoring as a criterion to consider the result as accurate yields an accuracy of up to 98%, and makes it adoptable in a real-world setting. Without confidence scoring, the system achieved an accuracy of 78%. We anticipate that our deep learning system will serve as a foundation enabling faster diagnosis of skin cancer, identification of cases for specialist review, and targeted diagnostic classifications

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Deep Active Learning for Classifying Cancer Pathology Reports

Background: Automated text classification has many important applications in the clinical setting; however, obtaining labelled data for training machine learning and deep learning models is often difficult and expensive. Active learning techniques may mitigate this challenge by reducing the amount of labelled data required to effectively train a model. In this study, we analyze the effectiveness of 11 active learning algorithms on classifying subsite and histology from cancer pathology reports using a Convolutional Neural Network as the text classification model. Results: We compare the performance of each active learning strategy using two differently sized datasets and two different classification tasks. Our results show that on all tasks and dataset sizes, all active learning strategies except diversity-sampling strategies outperformed random sampling, i.e., no active learning. On our large dataset (15K initial labelled samples, adding 15K additional labelled samples each iteration of active learning), there was no clear winner between the different active learning strategies. On our small dataset (1K initial labelled samples, adding 1K additional labelled samples each iteration of active learning), marginal and ratio uncertainty sampling performed better than all other active learning techniques. We found that compared to random sampling, active learning strongly helps performance on rare classes by focusing on underrepresented classes. Conclusions: Active learning can save annotation cost by helping human annotators efficiently and intelligently select which samples to label. Our results show that a dataset constructed using effective active learning techniques requires less than half the amount of labelled data to achieve the same performance as a dataset constructed using random sampling

Enhancing the Performance of the MtCNN for the Classification of Cancer Pathology Reports: From Data Annotation to Model Deployment

Information contained in electronic health records (EHR) combined with the latest advances in machine learning (ML) have the potential to revolutionize the medical sciences. In particular, information contained in cancer pathology reports is essential to investigate cancer trends across the country. Unfortunately, large parts of information in EHRs are stored in the form of unstructured, free-text which limit their usability and research potential. To overcome this accessibility barrier, cancer registries depend on expert personnel who read, interpret, and extract relevant information. Naturally, as the number of stored pathology reports increases every day, depending on human experts presents scalability challenges. Recently, researchers have attempted to automate the information extraction process from cancer pathology reports using ML techniques commonly found in natural language processing (NLP). However, clinical text is inherently different than other common forms of text, and state-of-the-art NLP approaches often exhibit mediocre performance. In this study, we narrow the literature gap by investigating methods to tackle overfitting and improve the performance of ML models for the classification of cancer pathology reports so that we can reduce the dependency on human expert annotators. We (1) show that using active learning can mitigate extreme class imbalance by increasing the representation of documents belonging to rare cancer types, (2) investigated the feasibility of ensemble learning and a mixture-of-expert variant to boost minority class performance, and (3) demonstrated that ensemble model distillation provides a strategy for quantifying the uncertainty inherent in labeled data, offering an effective low-resource solution that can be easily deployed by cancer registries

A Deep Learning Study on Osteosarcoma Detection from Histological Images

In the U.S, 5-10\% of new pediatric cases of cancer are primary bone tumors. The most common type of primary malignant bone tumor is osteosarcoma. The intention of the present work is to improve the detection and diagnosis of osteosarcoma using computer-aided detection (CAD) and diagnosis (CADx). Such tools as convolutional neural networks (CNNs) can significantly decrease the surgeon's workload and make a better prognosis of patient conditions. CNNs need to be trained on a large amount of data in order to achieve a more trustworthy performance. In this study, transfer learning techniques, pre-trained CNNs, are adapted to a public dataset on osteosarcoma histological images to detect necrotic images from non-necrotic and healthy tissues. First, the dataset was preprocessed, and different classifications are applied. Then, Transfer learning models including VGG19 and Inception V3 are used and trained on Whole Slide Images (WSI) with no patches, to improve the accuracy of the outputs. Finally, the models are applied to different classification problems, including binary and multi-class classifiers. Experimental results show that the accuracy of the VGG19 has the highest, 96\%, performance amongst all binary classes and multiclass classification. Our fine-tuned model demonstrates state-of-the-art performance on detecting malignancy of Osteosarcoma based on histologic images