{Reference Type}: Journal Article {Title}: Self-normalization for a 1 mm3resolution clinical PET system using deep learning. {Author}: Chin M;Jafaritadi M;Franco AB;Nasir Ullah M;Chinn G;Innes D;Levin CS; {Journal}: Phys Med Biol {Volume}: 69 {Issue}: 17 {Year}: 2024 Aug 14 {Factor}: 4.174 {DOI}: 10.1088/1361-6560/ad69fb {Abstract}: Objective.This work proposes, for the first time, an image-based end-to-end self-normalization framework for positron emission tomography (PET) using conditional generative adversarial networks (cGANs).Approach.We evaluated different approaches by exploring each of the following three methodologies. First, we used images that were either unnormalized or corrected for geometric factors, which encompass all time-invariant factors, as input data types. Second, we set the input tensor shape as either a single axial slice (2D) or three contiguous axial slices (2.5D). Third, we chose either Pix2Pix or polarized self-attention (PSA) Pix2Pix, which we developed for this work, as a deep learning network. The targets for all approaches were the axial slices of images normalized using the direct normalization method. We performed Monte Carlo simulations of ten voxelized phantoms with the SimSET simulation tool and produced 26,000 pairs of axial image slices for training and testing.Main results.The results showed that 2.5D PSA Pix2Pix trained with geometric-factors-corrected input images achieved the best performance among all the methods we tested. All approaches improved general image quality figures of merit peak signal to noise ratio (PSNR) and structural similarity index (SSIM) from ∼15 % to ∼55 %, and 2.5D PSA Pix2Pix showed the highest PSNR (28.074) and SSIM (0.921). Lesion detectability, measured with region of interest (ROI) PSNR, SSIM, normalized contrast recovery coefficient, and contrast-to-noise ratio, was generally improved for all approaches, and 2.5D PSA Pix2Pix trained with geometric-factors-corrected input images achieved the highest ROI PSNR (28.920) and SSIM (0.973).Significance.This study demonstrates the potential of an image-based end-to-end self-normalization framework using cGANs for improving PET image quality and lesion detectability without the need for separate normalization scans.