Dual-Tracer PET Using Generalized Factor Analysis of Dynamic Sequences

Abstract

Purpose With single-photon emission computed tomography, simultaneous imaging of two physiological processes relies on discrimination of the energy of the emitted gamma rays, whereas the application of dual-tracer imaging to positron emission tomography (PET) imaging has been limited by the characteristic 511-keV emissions. Procedures To address this limitation, we developed a novel approach based on generalized factor analysis of dynamic sequences (GFADS) that exploits spatio-temporal differences between radiotracers and applied it to near-simultaneous imaging of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) (brain metabolism) and 11C-raclopride (D2) with simulated human data and experimental rhesus monkey data. We show theoretically and verify by simulation and measurement that GFADS can separate FDG and raclopride measurements that are made nearly simultaneously. Results The theoretical development shows that GFADS can decompose the studies at several levels: (1) It decomposes the FDG and raclopride study so that they can be analyzed as though they were obtained separately. (2) If additional physiologic/anatomic constraints can be imposed, further decomposition is possible. (3) For the example of raclopride, specific and nonspecific binding can be determined on a pixel-by-pixel basis. We found good agreement between the estimated GFADS factors and the simulated ground truth time activity curves (TACs), and between the GFADS factor images and the corresponding ground truth activity distributions with errors less than 7.3±1.3 %. Biases in estimation of specific D2 binding and relative metabolism activity were within 5.9±3.6 % compared to the ground truth values. We also evaluated our approach in simultaneous dual-isotope brain PET studies in a rhesus monkey and obtained accuracy of better than 6 % in a mid-striatal volume, for striatal activity estimation. Conclusions Dynamic image sequences acquired following near-simultaneous injection of two PET radiopharmaceuticals can be separated into components based on the differences in the kinetics, provided their kinetic behaviors are distinct.

Dynamic whole-body PET imaging: principles, potentials and applications

“…However, one must be cautious that in some studies, components may not be fully separated, leading to problems especially for quantitative applications. Alternatively, it is possible to apply other non-compartmental methods to dynamic images and TACs such as independent component analysis (ICA) [141,142], factor analysis [143][144][145][146], spectral analysis [147,148], cluster analysis [149] or heterogeneity analysis (e.g., fractal dimension) [38]. It remains to be demonstrated whether these methods, given their subtleties and challenges (such as the challenge of accurately mapping their derived images to specific physiological processes) will translate to clinical applications.…”

Positron Emission Tomography: Current Challenges and Opportunities for Technological Advances in Clinical and Preclinical Imaging Systems

“…However, this technique is based on distinguishing between different photon energies and will not work in standard PET imaging because all annihilation photons resulting from positron annihilation have the same energy (Figure 1). To overcome this limitation, alternative techniques have been proposed, including the following: simultaneous injection of or sequential close-in-time injections of two radiotracers that do not interfere with each other (92);dynamic imaging of timed injections followed by constrained kinetic modeling to separate the particular dynamics of each radiotracer (93) using generalized factor analysis of the dynamic sequences (94); orthe use of a combination of radiotracers, one of which emits an additional photon simultaneously with the annihilation photons. The two radiotracers can be differentiated by measuring the energy of the third photon (which has to be different from 511 keV) (95).…”

“…dynamic imaging of timed injections followed by constrained kinetic modeling to separate the particular dynamics of each radiotracer (93) using generalized factor analysis of the dynamic sequences (94); or…”

Impact of contamination with long-lived radionuclides on PET kinetics modelling in multitracer studies

“…If the photon energies cannot be separated, separation must typically be performed in time, applying and imaging the tracers in sequence rather than simultaneously (although some research papers have explored other ways of signal separation [6]). The waiting time between the imaging of two tracers should preferably be long enough so that the first tracer has decayed to an insignificant level by the time the second tracer is imaged.…”