4D-CT Attenuation Correction in Respiratory-Gated PET for Hypoxia Imaging: Is It Really Beneficial?

Previous literature has shown that 4D respiratory-gated positron emission tomography (PET) is beneficial for quantitative analysis and defining targets for boosting therapy. However the case for addition of a phase-matched 4D-computed tomography (CT) for attenuation correction (AC) is less clear. We seek to validate the use of 4D-CT for AC and investigate the impact of motion correction for low signal-to-background PET imaging of hypoxia using radiotracers such as FAZA and FMISO. A new insert for the Modus Medicals' QUASAR™ Programmable Respiratory Motion Phantom was developed in which a 3D-printed sphere was placed within the “lung” compartment while an additional compartment is added to simulate muscle/blood compartment required for hypoxia quantification. Experiments are performed at 4:1 or 2:1 signal-to-background ratio consistent with clinical FAZA and FMISO imaging. Motion blur was significant in terms of SUVmax, mean, and peak for motion ?1 cm and could be significantly reduced (from 20% to 8% at 2-cm motion) for all 4D-PET-gated reconstructions. The effect of attenuation method on precision was significant (?² hCT-AC = 5.5%/4.7%/2.7% vs ?² 4D-CT-AC = 0.5%/0.6%/0.7% [max%/peak%/mean% variance]). The simulated hypoxic fraction also significantly decreased under conditions of 2-cm amplitude motion from 55% to 20% and was almost fully recovered (HF = 0.52 for phase-matched 4D-CT) using gated PET. 4D-gated PET is valuable under conditions of low radiotracer uptake found in hypoxia imaging. This work demonstrates the importance of using 4D-CT for AC when performing gated PET based on its significantly improved precision over helical CT.