Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based analysis of longitudinal ¹⁸F-FDG PET/CT data from patients with non-small cell lung cancer (NSCLC)

Deformable image registration allows volume of interest (VOI)- and voxel-based analysis of longitudinal changes in fluorodeoxyglucose (FDG) tumor uptake in patients with non-small cell lung cancer (NSCLC). This study evaluates the performance of the elastix toolbox deformable image registration algorithm for VOI and voxel-wise assessment of longitudinal variations in FDG tumor uptake in NSCLC patients.

Evaluation of the elastix toolbox was performed using ¹⁸F-FDG PET/CT at baseline and after 2 cycles of therapy (follow-up) data in advanced NSCLC patients. The elastix toolbox, an integrated part of the IMALYTICS workstation, was used to apply a CT-based non-linear image registration of follow-up PET/CT data using the baseline PET/CT data as reference. Lesion statistics were compared to assess the impact on therapy response assessment. Next, CT-based deformable image registration was performed anew on the deformed follow-up PET/CT data using the original follow-up PET/CT data as reference, yielding a realigned follow-up PET dataset. Performance was evaluated by determining the correlation coefficient between original and realigned follow-up PET datasets. The intra- and extra-thoracic tumors were automatically delineated on the original PET using a 41% of maximum standardized uptake value (SUV_max) adaptive threshold. Equivalence between reference and realigned images was tested (determining 95% range of the difference) and estimating the percentage of voxel values that fell within that range.

Thirty-nine patients with 191 tumor lesions were included. In 37/39 and 12/39 patients, respectively, thoracic and non-thoracic lesions were evaluable for response assessment. Using the EORTC/SUV_max-based criteria, 5/37 patients had a discordant response of thoracic, and 2/12 a discordant response of non-thoracic lesions between the reference and the realigned image. FDG uptake values of corresponding tumor voxels in the original and realigned reference PET correlated well (R ²=0.98). Using equivalence testing, 94% of all the voxel values fell within the 95% range of the difference between original and realigned reference PET.

The elastix toolbox impacts lesion statistics and therefore therapy response assessment in a clinically significant way. The elastix toolbox is therefore not applicable in its current form and/or standard settings for PET response evaluation. Further optimization and validation of this technique is necessary prior to clinical implementation.