Background: Diagnostic I-131 whole-body planar imaging in differentiated thyroid cancer (DTC) is count-limited by low administered activity, and quality worsens under rapid acquisition. Models trained on such data struggle because their targets lack photon statistics.

Purpose: To test whether high-quality post-therapeutic (PT) I-131 scans can serve as superior training references for enhancing sparse diagnostic planar images, using transfer learning and input-image addition. Methods: In this single-center prospective study, 111 patients were enrolled in PT training (n = 19), diagnostic follow-up (FU) training (n = 58), and FU paired test (n = 34) cohorts.

Five Restormer-based models were trained: FU_DLx2 on FU labels; PT_DLx2 transfer-learned on PT data; PT_DLx1+ and PT_DLx2+ with input-image addition; PT_DLx6 as a PT-only reference. Test-time processing used two-step denormalization and Poisson re-scaling to preserve noise statistics.

Quality was assessed by PSNR, SSIM, and a blinded dual-reader evaluation of all 34 test-cohort patients. Results: PT_DLx2 achieved the highest PSNR (34.4 +/- 3.6 dB) and SSIM (0.81 +/- 0.07).

PT_DLx1+ and PT_DLx2+ were comparable (33.8 and 33.3 dB; SSIM 0.80). FU_DLx2 ranked below the unprocessed fast scan (30.3 vs.

32.0 dB; 0.76 vs. 0.79).

Subjectively, PT_DLx2+ scored highest in image quality (4.54 +/- 0.60) and diagnostic confidence (4.54 +/- 0.60), surpassing the reference standard (4.19 +/- 0.83 and 4.31 +/- 0.81; P = 0.005 and P = 0.008). FU_DLx2 and PT_DLx6 scored lowest.

Conclusion: Count-rich PT scans provide effective training priors for reconstructing extremely sparse images. Input-image addition and cross-domain transfer learning from PT data outperformed direct training on count-limited diagnostic data, supporting 2x scan acceleration with quality matching or exceeding the unaccelerated standard scan for selected PT-derived configurations.