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Introduction Multi-series CT (MSCT) scans, including non-contrast CT (NCCT), CT Perfusion (CTP), and CT Angiography (CTA), are widely used in acute stroke imaging. While each scan has its advantage in disease diagnosis, the varying image resolution of different series hinders the ability of the radiologist to discern subtle suspicious findings. Besides, higher image quality requires high radiation doses, leading to increases in health risks such as cataract formation and cancer induction. Thus, it is highly crucial to develop an approach to improve MSCT resolution and to lower radiation exposure. Hypothesis MSCT imaging of the same patient is highly correlated in structural features, the transferring and integration of the shared and complementary information from different series are beneficial for achieving high image quality. Methods We propose TL-GAN, a learning-based method by using Transfer Learning (TL) and Generative Adversarial Network (GAN) to reconstruct high-quality diagnostic images. Our TL-GAN method is evaluated on 4,382 images collected from nine patients’ MSCT scans, including 415 NCCT slices, 3,696 CTP slices, and 271 CTA slices. We randomly split the nine patients into a training set (4 patients), a validation set (2 patients), and a testing set (3 patients). In preprocessing, we remove the background and skull and visualize in brain window. The low-resolution images (1/4 of the original spatial size) are simulated by bicubic down-sampling. For training without TL, we train different series individually, and for with TL, we follow the scanning sequence (NCCT, CTP, and CTA) by finetuning. Results The performance of TL-GAN is evaluated by the peak-signal-to-noise ratio (PSNR) and structural similarity (SSIM) index on 184 NCCT, 882 CTP, and 107 CTA test images. Figure 1 provides both visual (a-c) and quantity (d-f) comparisons. Through TL-GAN, there is a significant improvement with TL than without TL (training from scratch) for NCCT, CTP, and CTA images, respectively. These significances of performance improvement are evaluated by one-tailed paired t-tests (p < 0.05). We enlarge the regions of interest for detail visual comparisons. Further, we evaluate the CTP performance by calculating the perfusion maps, including cerebral blood flow (CBF) and cerebral blood volume (CBV). The visual comparison of the perfusion maps in Figure 2 demonstrate that TL-GAN is beneficial for achieving high diagnostic image quality, which are comparable to the ground truth images for both CBF and CBV maps. Conclusion Utilizing TL-GAN can effectively improve the image resolution for MSCT, provides radiologists more image details for suspicious findings, which is a practical solution for MSCT image quality enhancement.