Positron emission tomography (PET) image quality can be improved by higher injected activity and/or longer acquisition time, but both may often not be practical in preclinical imaging. Common preclinical radioactive doses (10MBq) have been shown to cause deterministic changes in biological pathways. Reducing the injected tracer activity and/or shortening the scan time inevitably results in low-count acquisitions which poses a challenge because of the inherent noise introduction. We present an image-based deep learning (DL) framework for denoising lower count micro-PET images. For 36 mice, a 15-min [18F]FDG (8.15 ± 1.34MBq) PET scan was acquired at 40min post-injection on the Molecubes β-CUBE (in list mode). The 15-min acquisition (high-count) was parsed into smaller time fractions of 7.50, 3.75, 1.50, and 0.75min to emulate images reconstructed at 50, 25, 10, and 5% of the full counts, respectively. A 2D U-Net was trained with mean-squared-error loss on 28 high-low count image pairs. The DL algorithms were visually and quantitatively compared to spatial and edge-preserving denoising filters; the DL-based methods effectively removed image noise and recovered image details much better while keeping quantitative (SUV) accuracy. The largest improvement in image quality was seen in the images reconstructed with 10 and 5% of the counts (equivalent to sub-1MBq or sub-1min mouse imaging). The DL-based denoising framework was also successfully applied on the NEMA-NU4 phantom and different tracer studies ([18F]PSMA, [18F]FAPI, and [68Ga]FAPI). Visual and quantitative results support the superior performance and robustness in image denoising of the implemented DL models for low statistics micro-PET. This offers much more flexibility in optimizing preclinical, longitudinal imaging protocols with reduced tracer doses or shorter durations.
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