Neural network-aided unsupervised input function estimation for dual-time-window PET Patlak analysis

This study aims to develop and validate a dual-time-window (DTW) Patlak plot method that eliminates the need for invasive blood sampling and reduces scan duration. We seek to improve the accuracy of the net influx constant ([Formula: see text]) estimation, addressing the inaccuracies inherent in traditional DTW and single-time-window methods, which often introduce bias and hinder comparability across different cohorts.

We developed an unsupervised, multi-branch neural network (NN) to assist in estimating missing data intervals within the DTW protocol, thereby facilitating accurate Patlak analysis. The model fits the mapping from time to the time-activity curve (TAC), generating multiple pseudo input functions (IFs). A correlation coefficient is then computed between each pseudo IF and the voxel-level measured data, extracting statistical information guided by the kinetic process. These correlation scores were used to construct a weighted statistic, serving as the final IF (NNIF). Our approach was validated using both simulation and clinical data, including [Formula: see text]-FDG PET scans from 67 lung cancer subjects. Additionally, we compared the performance of our method with other simplified quantification techniques to demonstrate its efficacy in achieving high-quality parametric imaging and reliable quantitative analysis within abbreviated scanning protocols.

Our proposed method achieved high accuracy in the estimation of IF, with a maximum mean absolute deviation (MAD) of 0.04 in a real patient study. The regressed [Formula: see text] derived from different DTW scan protocols exhibited good consistency. In simulation studies , the best relative absolute error (RAE) was 0.0302. In real patient study, the optimal average peak signal-to-noise ratio (PSNR) of parametric imaging reached 97.40 dB, while the best average R-squared ([Formula: see text]) in ROI-based quantitative analysis reached 0.991.

We demonstrate the feasibility of using a weighted statistic, constructed from a multi-branch neural network, to accurately estimate the complete IF. This approach enables the generation of high-quality parametric images with shortened scan protocols, effectively reducing scanning time while ensuring accurate Patlak analysis.