A Generalized Linear modeling approach to bootstrapping multi-frame PET image data

PET imaging is an important diagnostic tool for management of patients with cancer and other diseases. Medical decisions based on quantitative PET information could potentially benefit from the availability of tools for evaluation of associated uncertainties. Raw PET data can be viewed as a sample from an inhomogeneous Poisson process so there is the possibility to directly apply bootstrapping to raw projection-domain list-mode data. Unfortunately this is computationally impractical, particularly if data reconstruction is iterative or the acquisition protocol is dynamic. We develop a flexible statistical linear model analysis to be used with multi-frame PET image data to create valid bootstrap samples. The technique is illustrated using data from dynamic PET studies with fluoro-deoxyglucose (FDG) and fluoro-thymidine (FLT) in brain and breast cancer patients. As is often the case with dynamic PET studies, data have been archived without raw list-mode information. Using the bootstrapping technique maps of kinetic parameters and associated uncertainties are obtained. The quantitative performance of the approach is assessed by simulation. The proposed image-domain bootstrap is found to substantially match the projection-domain alternative. Analysis of results points to a close relation between relative uncertainty in voxel-level kinetic parameters and local reconstruction error. This is consistent with statistical theory.