Deep learning approaches are playing an ever-increasing role throughout diagnostic medicine, especially in neuroradiology, to solve a wide range of problems such as segmentation, synthesis of missing sequences, and image quality improvement. Of particular interest is their application in the reduction of gadolinium-based contrast agents, the administration of which has been under cautious reevaluation in recent years because of concerns about gadolinium deposition and its unclear long-term consequences. A growing number of studies are investigating the reduction (low-dose approach) or even complete substitution (zero-dose approach) of gadolinium-based contrast agents in diverse patient populations using a variety of deep learning methods. This work aims to highlight selected research and discusses the advantages and limitations of recent deep learning approaches, the challenges of assessing its output, and the progress toward clinical applicability distinguishing between the low-dose and zero-dose approach.

Generative Adversarial Networks (GANs) have been used to model the underlying probability distribution of sample based datasets. GANs are notoriuos for training difficulties and their dependence on arbitrary hyperparameters. One recent improvement in GAN literature is to use the Wasserstein distance as loss function leading to Wasserstein Generative Adversarial Networks (WGANs). Using this as a basis, we show various ways in which the Wasserstein distance is estimated for the task of generative modelling. Additionally, the secrets in training such models are shown and summarized at the end of this work. Where applicable, we extend current works to different algorithms, different cost functions, and different regularization schemes to improve generative models.

Objectives The purpose of this study was to implement a state-of-the-art convolutional neural network used to synthesize artificial T1-weighted (T1w) full-dose images from corresponding noncontrast and low-dose images (using various settings of input sequences) and test its performance on a patient population acquired prospectively. Materials and Methods In this monocentric, institutional review board–approved study, a total of 138 participants were included who received an adapted imaging protocol with acquisition of a T1w low dose after administration of 10% of the standard dose and acquisition of a T1w full dose after administration of the remaining 90% of the standard dose of a gadolinium-containing contrast agent. A total of 83 participants formed the training sample (51.7 ± 16.5 years, 36 women), 25 the validation sample (55.3 ± 16.4 years, 11 women), and 30 the test sample (55.0 ± 15.0 years, 9 women). Four input settings were differentiated: only the T1w noncontrast and T1w low-dose images (standard setting), only the T1w noncontrast and T1w low-dose images with a prolonged postinjection time of 5 minutes (5-minute setting), multiple noncontrast sequences (T1w, T2w, diffusion) and the T1w low-dose images (extended setting), and only noncontrast sequences (T1w, T2w, diffusion) were used (zero-dose setting). For each setting, a deep neural network was trained to synthesize artificial T1w full-dose images, which were assessed on the test sample using an objective evaluation based on quantitative metrics and a subjective evaluation through a reader-based study. Three readers scored the overall image quality, the interchangeability in regard to the clinical conclusion compared with the true T1w full-dose sequence, the contrast enhancement of lesions, and their conformity to the respective references in the true T1w full dose. Results Quantitative analysis of the artificial T1w full-dose images of the standard setting provided a peak signal-to-noise ratio of 33.39 ± 0.62 (corresponding to an average improvement of the low-dose sequences of 5.2 dB) and a structural similarity index measure of 0.938 ± 0.005. In the 4-fold cross-validation, the extended setting yielded similar performance to the standard setting in terms of peak signal-to-noise ratio (P = 0.20), but a slight improvement in structural similarity index measure (P < 0.0001). For all settings, the reader study found comparable overall image quality between the original and artificial T1w full-dose images. The proportion of scans scored as fully or mostly interchangeable was 55%, 58%, 43%, and 3% and the average counts of false positives per case were 0.42 ± 0.83, 0.34 ± 0.71, 0.82 ± 1.15, and 2.00 ± 1.07 for the standard, 5-minute, extended, and zero-dose setting, respectively. Using a 5-point Likert scale (0 to 4, 0 being the worst), all settings of synthesized full-dose images showed significantly poorer contrast enhancement of lesions compared with the original full-dose sequence (difference of average degree of contrast enhancement—standard: −0.97 ± 0.83, P = <0.001; 5-minute: −0.93 ± 0.91, P = <0.001; extended: −0.96 ± 0.97, P = <0.001; zero-dose: −2.39 ± 1.14, P = <0.001). The average scores of conformity of the lesions compared with the original full-dose sequence were 2.25 ± 1.21, 2.22 ± 1.27, 2.24 ± 1.25, and 0.73 ± 0.93 for the standard, 5-minute, extended, and zero-dose setting, respectively. Conclusions The tested deep learning algorithm for synthesis of artificial T1w full-dose sequences based on images after administration of only 10% of the standard dose of a gadolinium-based contrast agent showed very good quantitative performance. Despite good image quality in all settings, both false-negative and false-positive signals resulted in significantly limited interchangeability of the synthesized sequences with the original full-dose sequences.

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We propose a novel learning-based framework for image reconstruction particularly designed for training without ground truth data, which has three major building blocks: energy-based learning, a patchbased Wasserstein loss functional, and shared prior learning. In energy-based learning, the parameters of an energy functional composed of a learned data fidelity term and a data-driven regularizer are computed in a mean-field optimal control problem. In the absence of ground truth data, we change the loss functional to a patch-based Wasserstein functional, in which local statistics of the output images are compared to uncorrupted reference patches. Finally, in shared prior learning, both aforementioned optimal control problems are optimized simultaneously with shared learned parameters of the regularizer to further enhance unsupervised image reconstruction. We derive several time discretization schemes of the gradient flow and verify their consistency in terms of Mosco convergence. In numerous numerical experiments, we demonstrate that the proposed method generates state-of-the-art results for various image reconstruction applications-even if no ground truth images are available for training.