There is intense interest in adopting computer-aided diagnosis (CAD) systems, particularly those developed based on deep learning algorithms, for applications in a number of medical specialties. However, success of these CAD systems relies heavily on large annotated datasets; otherwise, deep learning often results in algorithms that perform poorly and lack generalizability. Therefore, this dissertation seeks to address this critical problem: How to develop efficient and effective deep learning algorithms for medical applications where large annotated datasets are unavailable. In doing so, we have outlined three specific aims: (1) acquiring necessary annotations efficiently from human experts; (2) utilizing existing annotations effectively from advanced architecture; and (3) extracting generic knowledge directly from unannotated images. Our extensive experiments indicate that, with a small part of the dataset annotated, the developed deep learning methods can match, or even outperform those that require annotating the entire dataset. The last part of this dissertation presents the importance and application of imaging in healthcare, elaborating on how the developed techniques can impact several key facets of the CAD system for detecting pulmonary embolism. Further research is necessary to determine the feasibility of applying these advanced deep learning technologies in clinical practice, particularly when annotation is limited. Progress in this area has the potential to enable deep learning algorithms to generalize to real clinical data and eventually allow CAD systems to be employed in clinical medicine at the point of care.

Background: This study aimed to compare one state-of-the-art deep learning method and four classical machine learning methods for classifying mediastinal lymph node metastasis of non-small cell lung cancer (NSCLC) from [superscript 18]F-FDG PET/CT images. Another objective was to compare the discriminative power of the recently popular PET/CT texture features with the widely used diagnostic features such as tumor size, CT value, SUV, image contrast, and intensity standard deviation. The four classical machine learning methods included random forests, support vector machines, adaptive boosting, and artificial neural network. The deep learning method was the convolutional neural networks (CNN). The five methods were evaluated using 1397 lymph nodes collected from PET/CT images of 168 patients, with corresponding pathology analysis results as gold standard. The comparison was conducted using 10 times 10-fold cross-validation based on the criterion of sensitivity, specificity, accuracy (ACC), and area under the ROC curve (AUC). For each classical method, different input features were compared to select the optimal feature set. Based on the optimal feature set, the classical methods were compared with CNN, as well as with human doctors from our institute.

Results: For the classical methods, the diagnostic features resulted in 81~85% ACC and 0.87~0.92 AUC, which were significantly higher than the results of texture features. CNN’s sensitivity, specificity, ACC, and AUC were 84, 88, 86, and 0.91, respectively. There was no significant difference between the results of CNN and the best classical method. The sensitivity, specificity, and ACC of human doctors were 73, 90, and 82, respectively. All the five machine learning methods had higher sensitivities but lower specificities than human doctors.

Conclusions: The present study shows that the performance of CNN is not significantly different from the best classical methods and human doctors for classifying mediastinal lymph node metastasis of NSCLC from PET/CT images. Because CNN does not need tumor segmentation or feature calculation, it is more convenient and more objective than the classical methods. However, CNN does not make use of the import diagnostic features, which have been proved more discriminative than the texture features for classifying small-sized lymph nodes. Therefore, incorporating the diagnostic features into CNN is a promising direction for future research.