Impact of tracer uptake rate on quantification accuracy of myocardial blood flow in PET: A simulation study

Cardiac perfusion PET is commonly used to assess ischemia and cardiovascular risk, which enables quantitative measurements of myocardial blood flow (MBF) through kinetic modeling. However, the estimation of kinetic parameters is challenging due to the noisy nature of short dynamic frames and limited sample data points. This work aimed to investigate the errors in MBF estimation in PET through a simulation study and to evaluate different parameter estimation approaches, including a deep learning (DL) method. Simulated studies were generated using digital phantoms based on cardiac segmentations from 55 clinical CT images. We employed the irreversible 2-tissue compartmental model and simulated dynamic 13N-ammonia PET scans under both rest and stress conditions (220 cases each). The simulations covered a rest K1 range of 0.6 to 1.2 and a stress K1 range of 1.2 to 3.6 (unit: mL/min/g) in the myocardium. A transformer-based DL model was trained on the simulated dataset to predict parametric images (PIMs) from noisy PET image frames and was validated using 5-fold cross-validation. We compared the DL method with the voxel-wise nonlinear least squares (NLS) fitting applied to the dynamic images, using either Gaussian filter (GF) smoothing (GF-NLS) or a dynamic nonlocal means (DNLM) algorithm for denoising (DNLM-NLS). Two patients with coronary CT angiography (CTA) and fractional flow reserve (FFR) were enrolled to test the feasibility of applying DL models on clinical PET data. The DL method showed clearer image structures with reduced noise compared to the traditional NLS-based methods. In terms of mean absolute relative error (MARE), as the rest K1 values increased from 0.6 to 1.2 mL/min/g, the overall bias in myocardium K1 estimates decreased from approximately 58% to 45% for the NLS-based methods while the DL method showed a reduction in MARE from 42% to 18%. For stress data, as the stress K1 decreased from 3.6 to 1.2 mL/min/g, the MARE increased from 30% to 70% for the GF-NLS method. In contrast, both the DNLM-NLS (average: 42%) and the DL methods (average: 20%) demonstrated significantly smaller MARE changes as stress K1 varied. Regarding the regional mean bias (±standard deviation), the GF-NLS method had a bias of 6.30% (±8.35%) of rest K1, compared to 1.10% (±8.21%) for DNLM-NLS and 6.28% (±14.05%) for the DL method. For the stress K1, the GF-NLS showed a mean bias of 10.72% (±9.34%) compared to 1.69% (±8.82%) for DNLM-NLS and -10.55% (±9.81%) for the DL method. This study showed that an increase in the tracer uptake rate (K1) corresponded to improved accuracy and precision in MBF quantification, whereas lower tracer uptake resulted in higher noise in dynamic PET and poorer parameter estimates. Utilizing denoising techniques or DL approaches can mitigate noise-induced bias in PET parametric imaging.