Improving utility of brain tumor confocal laser endomicroscopy: objective value assessment and diagnostic frame detection with convolutional neural networks

Confocal laser endomicroscopy (CLE), although capable of obtaining images at cellular resolution during surgery of brain tumors in real time, creates as many non-diagnostic as diagnostic images. Non-useful images are often distorted due to relative motion between probe and brain or blood artifacts. Many images, however, simply lack diagnostic features immediately informative to the physician. Examining all the hundreds or thousands of images from a single case to discriminate diagnostic images from nondiagnostic ones can be tedious. Providing a real-time diagnostic value assessment of images (fast enough to be used during the surgical acquisition process and accurate enough for the pathologist to rely on) to automatically detect diagnostic frames would streamline the analysis of images and filter useful images for the pathologist/surgeon. We sought to automatically classify images as diagnostic or non-diagnostic. AlexNet, a deep-learning architecture, was used in a 4-fold cross validation manner. Our dataset includes 16,795 images (8572 nondiagnostic and 8223 diagnostic) from 74 CLE-aided brain tumor surgery patients. The ground truth for all the images is provided by the pathologist. Average model accuracy on test data was 91% overall (90.79 % accuracy, 90.94 % sensitivity and 90.87 % specificity). To evaluate the model reliability we also performed receiver operating characteristic (ROC) analysis yielding 0.958 average for the area under ROC curve (AUC). These results demonstrate that a deeply trained AlexNet network can achieve a model that reliably and quickly recognizes diagnostic CLE images.

Convolutional Neural Networks: Ensemble Modeling, Fine-Tuning and Unsupervised Semantic Localization for Intraoperative CLE Images

Confocal laser endomicroscopy (CLE) is an advanced optical fluorescence technology undergoing assessment for applications in brain tumor surgery. Despite its promising potential, interpreting the unfamiliar gray tone images of fluorescent stains can be difficult. Many of the CLE images can be distorted by motion, extremely low or high fluorescence signal, or obscured by red blood cell accumulation, and these can be interpreted as nondiagnostic. However, just one neat CLE image might suffice for intraoperative diagnosis of the tumor. While manual examination of thousands of nondiagnostic images during surgery would be impractical, this creates an opportunity for a model to select diagnostic images for the pathologists or surgeon's review. In this study, we sought to develop a deep learning model to automatically detect the diagnostic images using a manually annotated dataset, and we employed a patient-based nested cross-validation approach to explore generalizability of the model. We explored various training regimes: deep training, shallow fine-tuning, and deep fine-tuning. Further, we investigated the effect of ensemble modeling by combining the top-5 single models crafted in the development phase. We localized histological features from diagnostic CLE images by visualization of shallow and deep neural activations. Our inter-rater experiment results confirmed that our ensemble of deeply fine-tuned models achieved higher agreement with the ground truth than the other observers. With the speed and precision of the proposed method (110 images/second; 85% on the gold standard test subset), it has potential to be integrated into the operative workflow in the brain tumor surgery.