2 Muhammad Muneeb Saad. et al.
discriminator model classifies the generated images from the real images and
provides gradient feedback to the generator. The generator model updates its
learning of the feature distribution of real images through feedback provided
by the discriminator. GANs work with adversarial training where the generator
and the discriminator try to improve their performance based on each other’s
feedback [2].
GANs face difficulty in synthesizing images with complex and diverse fea-
tures. This problem arises due to technical challenges that occur during the train-
ing of GANs. Training challenges include mode collapse, non-convergence, and
instability [3]. Mode collapse refers to the generation of identical synthetic im-
ages by the generator regardless of diverse real images while the non-convergence
and instability problem imbalanced the training due to the vanishing gradient
problem. These problems limit the utility of GANs for image datasets with a
diverse range of salient image features [4]. In general, GANs are designed with
convolutional neural networks (CNNs) that fail to capture image features such
as texture, geometry, position, and color of the objects. One of the reasons could
be that the CNNs mostly utilize convolutional features in modeling the depen-
dencies over diverse image regions [5].
In the domain of biomedical imaging, the diverse features of biomedical im-
ages are important to consider in disease recognition or computer-based diagnosis
tasks [6]. These diverse features contain significant information about the disease
being diagnosed and analyzed. GANs have been utilized for biomedical image
synthesis. Several imaging modalities such as X-rays, Computed Tomography
(CT), Magnetic Resonance (MR), Ultrasound, and Positron Emission Tomogra-
phy (PET) have utilized GANs to generate synthetic samples [7]. The generation
of diversified synthetic images is a significant barrier for GANs that limits their
utility in the biomedical imaging domain.
X-ray images are widely utilized to diagnose diseases in the human body. X-
ray images contain a wide spectrum of disease features that help physicians to
monitor diseases more accurately [8]. Publicly available X-ray image datasets are
limited and imbalanced [9]. Image synthesis is a potential means of augmenting
and balancing these X-ray images. In image synthesis, synthetic images are pro-
duced by replicating the actual distributions of image features. Therefore, this
method is significant as compared to the traditional augmentation approaches
such as geometrical transformations [10]. GANs have demonstrated remarkable
advancements in image synthesis in the biomedical imaging domain [11].
State-of-the-art GANs such as ProGAN [12], StyleGAN [13], and MSG-GAN
[14] have been used for biomedical image synthesis. These GAN architectures
have demonstrated significant performance in generating diverse images [15].
Minibatch discrimination, PixNorm, progressive growth of GAN layers, and
Spectral normalization techniques have also been utilized to enhance the di-
versity of synthetic images. The multi-scale gradient technique enables the dis-
criminator learning more robust for the classification of real and synthetic images
[16]. Biomedical images contain salient disease features such as the location, size,
color, and structure of the disease region of interest. These features are suscep-