Title: End-to-End Abnormality Detection in Medical Imaging. Abstract: Deep neural networks (DNN) have shown promising performance in computer vision. In medical imaging, encouraging results have been achieved with deep learning for applications such as segmentation, lesion detection and classification. Nearly all of the deep learning based image analysis methods work on reconstructed images, which are obtained from original acquisitions via solving inverse problems (reconstruction). The reconstruction algorithms are designed for human observers, but not necessarily optimized for DNNs which can often observe features that are incomprehensible for human eyes. Hence, it is desirable to train the DNNs directly from the original data which lie in a different domain with the images. In this paper, we proposed an end-to-end DNN for abnormality detection in medical imaging. To align the acquisition with the annotations made by radiologists in the image domain, a DNN was built as the unrolled version of iterative reconstruction algorithms to map the acquisitions to images, and followed by a 3D convolutional neural network (CNN) to detect the abnormality in the reconstructed images. The two networks were trained jointly in order to optimize the entire DNN for the detection task from the original acquisitions. The DNN was implemented for lung nodule detection in low-dose chest computed tomography (CT), where a numerical simulation was done to generate acquisitions from 1,018 chest CT images with radiologists' annotations. The proposed end-to-end DNN demonstrated better sensitivity and accuracy for the task compared to a two-step approach, in which the reconstruction and detection DNNs were trained separately. A significant reduction of false positive rate on suspicious lesions were observed, which is crucial for the known over-diagnosis in low-dose lung CT imaging. The images reconstructed by the proposed end-to-end network also presented enhanced details in the region of interest. 