Remarkable progress has been made in image recognition, primarily due to the availability of large-scale annotated datasets (i.e. ImageNet) and the revival of deep convolutional neural networks (CNN). CNNs enable learning data-driven, highly representative, layered hierarchical image features from sufficient training data. However, obtaining datasets as comprehensively annotated as ImageNet in the medical imaging domain remains a challenge. There are currently three major techniques that successfully employ CNNs to medical image classification: training the CNN from scratch, using off-the-shelf pre-trained CNN features, and conducting unsupervised CNN pre-training with supervised fine-tuning. Another effective method is transfer learning, i.e., fine-tuning CNN models (supervised) pre-trained from natural image dataset to medical image tasks (although domain transfer between two medical image datasets is also possible). In this paper, we exploit three important, but previously understudied factors of employing deep convolutional neural networks to computer-aided detection problems. We first explore and evaluate different CNN architectures. The studied models contain 5 thousand to 160 million parameters, and vary in numbers of layers. We then evaluate the influence of dataset scale and spatial image context on performance. Finally, we examine when and why transfer learning from pre-trained ImageNet (via fine-tuning) can be useful. We study two specific computeraided detection (CADe) problems, namely thoraco-abdominal lymph node (LN) detection and interstitial lung disease (ILD) classification. We achieve the state-of-the-art performance on the mediastinal LN detection, with 85% sensitivity at 3 false positive per patient, and report the first five-fold cross-validation classification results on predicting axial CT slices with ILD categories. Our extensive empirical evaluation, CNN model analysis and valuable insights can be extended to the design of high performance CAD systems for other medical imaging tasks.

Interstitial lung diseases (ILD) involve several abnormal imaging patterns observed in computed tomography (CT) images. Accurate classification of these patterns plays a significant role in precise clinical decision making of the extent and nature of the diseases. Therefore, it is important for developing automated pulmonary computer-aided detection systems. Conventionally, this task relies on experts’ manual identification of regions of interest (ROIs) as a prerequisite to diagnose potential diseases. This protocol is time consuming and inhibits fully automatic assessment. In this paper, we present a new method to classify ILD imaging patterns on CT images. The main difference is that the proposed algorithm uses the entire image as a holistic input. By circumventing the prerequisite of manual input ROIs, our problem set-up is significantly more difficult than previous work but can better address the clinical workflow. Qualitative and quantitative results using a publicly available ILD database demonstrate state-of-the-art classification accuracy under the patch-based classification and shows the potential of predicting the ILD type using holistic image.

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Long non-coding RNAs (lncRNAs) are known players in the regulatory circuitry of the self-renewal in human embryonic stem cells (hESCs). However, most hESC-specific lncRNAs remain uncharacterized. Here we demonstrate that growth-arrest-specific transcript 5 (GAS5), a known tumour suppressor and growth arrest-related lncRNA, is highly expressed and directly regulated by pluripotency factors OCT4 and SOX2 in hESCs. Phenotypic analysis shows that GAS5 knockdown significantly impairs hESC self-renewal, but its overexpression significantly promotes hESC self-renewal. Using RNA sequencing and functional analysis, we demonstrate that GAS5 maintains NODAL signalling by protecting NODAL expression from miRNA-mediated degradation. Therefore, we propose that the above pluripotency factors, GAS5 and NODAL form a feed-forward signalling loop that maintains hESC self-renewal. As this regulatory function of GAS5 is stem cell specific, our findings also indicate that the functions of lncRNAs may vary in different cell types due to competing endogenous mechanisms.

Abstract. Computed tomography imaging is a standard modality for detecting and assessing lung cancer. In order to evaluate the malignancy of lung nodules, clinical practice often involves expert qualitative ratings on several criteria describing a nodule's appearance and shape. Translating these features for computer-aided diagnostics is challenging due to their subjective nature and the difficulties in gaining a complete description. In this paper, we propose a computerized approach to quantitatively evaluate both appearance distinctions and 3D surface variations. Nodule shape was modeled and parameterized using spherical harmonics, and appearance features were extracted using deep convolutional neural networks. Both sets of features were combined to estimate the nodule malignancy using a random forest classifier. The proposed algorithm was tested on the publicly available Lung Image Database Consortium dataset, achieving high accuracy. By providing lung nodule characterization, this method can provide a robust alternative reference opinion for lung cancer diagnosis.

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Segmentation, denoising, and partial volume correction (PVC) are three major processes in the quantification of uptake regions in post-reconstruction PET images. These problems are conventionally addressed by independent steps. In this study, we hypothesize that these three processes are dependent; therefore, jointly solving them can provide optimal support for quantification of the PET images. To achieve this, we utilize interactions among these processes when designing solutions for each challenge. We also demonstrate that segmentation can help in denoising and PVC by locally constraining the smoothness and correction criteria. For denoising, we adapt generalized Anscombe transformation to Gaussianize the multiplicative noise followed by a new adaptive smoothing algorithm called regional mean denoising. For PVC, we propose a volume consistency-based iterative voxel-based correction algorithm in which denoised and delineated PET images guide the correction process during each iteration precisely. For PET image segmentation, we use affinity propagation (AP)-based iterative clustering method that helps the integration of PVC and denoising algorithms into the delineation process. Qualitative and quantitative results, obtained from phantoms, clinical, and pre-clinical data, show that the proposed framework provides an improved and joint solution for segmentation, denoising, and partial volume correction.