Deep learning-based triple-tracer brain PET scanning in a single session: A simulation study using clinical data

Objectives: Multiplexed Positron Emission Tomography (PET) imaging allows simultaneous acquisition of multiple radiotracer signals, thus enhancing diagnostic capabilities, reducing scan times, and improving patient comfort. Traditional methods often require significant delays between tracer injections, leading to physiological changes and noise interference. Recent advancements, including multi-tracer compartment modeling and machine learning, provide promising solutions. This study explores the deep learning (DL)-based single-session triple-tracer brain PET imaging protocol, aiming at simplifying multi-tracer PET imaging, while reducing radiation exposure. Methods: The study uses the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, which includes cognitively normal (CN) patients, as well as patients with mild cognitive impairment (MCI) and dementia. The dataset also includes PET scans acquired with amyloid (¹⁸F-florbetaben [FBB] or ¹⁸F-florbetapir [FBP]), ¹⁸F-Fluorodeoxyglucose (FDG), and tau ¹⁸F-flortaucipir (FTP). To mimic the effect of simultaneous acquisition of multiple PET tracers, we generated synthetic dual- and triple-tracer images by summing FBP/FBB, FTP, and FDG scans. A DL model based on Swin Transformer architecture was developed to separate these signals, using five-fold cross-validation and mean squared error (MSE) loss. The synthetic PET images were evaluated using established image quality metrics, including MSE, structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR). In addition, clinical evaluation was conducted by two nuclear medicine specialists to assess the amyloid and tau status in the synthetic and reference images. Results: The proposed DL model effectively synthesized realistic FBB/FBP and FDG images from dual- and triple-tracer PET images. Although the proposed DL model's performance in generating FTP images was less successful, it remains promising. The clinical evaluation revealed that the amyloid status estimated from the synthetic images led to a sensitivity of 92% and specificity of 86% for FBB, while it showed a sensitivity of 93% and specificity of 67% for tau status using FBP extracted from the triple-tracer images. The calculated quantitative metrics showed that the mean error for synthetic amyloid images (FBB: 0.03 SUV, FBP: 0.00 SUV) was higher than FDG for FBB (0.02 SUV) but lower than FDG for FBP (-0.01 SUV), and comparable to FTP (FBB: 0.03 SUV, FBP: 0.00 SUV). Voxel-wise correlation analysis demonstrated strong correlation between synthetic and reference images, particularly for amyloid images (FBB: y = 0.98x + 0.00, R² = 0.85; FBP: y = 1.11x + 0.04, R² = 0.73), while FTP (FBB: y = 0.87x + 0.14, R² = 0.51; FBP: y = 0.98x + 0.09, R² = 0.59) and FDG images (FBB: y = 1.01x + 0.18, R² = 0.85; FBP: y = 0.96x + 1.37, R² = 0.77) showed moderate correlations. Conclusion: Our study demonstrates that the suggested DL model can separate the signals belonging to three different radiotracers from simultaneous triple-tracer PET scans. This method may make multiplex scanning feasible in the clinic, hence reducing the scanning time, radiation hazard and improving patient comfort.