title: Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based analysis of longitudinal (18)F-FDG PET/CT data from patients with non-small cell lung cancer (NSCLC).
abstract: BACKGROUND
  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.
  
  
  METHODS
  Evaluation of the elastix toolbox was performed using (18)F-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 (SUVmax) 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.
  
  
  RESULTS
  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/SUVmax-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.
  
  
  CONCLUSIONS
  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.
authors: University of Groningen and Department of Pulmonary Diseases, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, , 9700 RB Groningen, The Netherlands.
authors: Gerald Sma
authors: GS
authors: Kerner
authors: Philips Technologie GmbH Innovative Technologies, Postfach 40, Philipstr. 8, Aachen, 52068 Germany.
authors: Alexander
authors: A
authors: Fischer
authors: University of Groningen and Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, , 9700 RB Groningen, The Netherlands.
authors: Michel Jb
authors: MJ
authors: Koole
authors: University of Groningen and Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, , 9700 RB Groningen, The Netherlands ; Department of Nuclear Medicine, Faculty of Medicine & Health Sciences, Tygerberg Hospital, Stellenbosch University, Francie van Zijl drive, Cape Town, 7505 South-Africa.
authors: Jan
authors: J
authors: Pruim
authors: University of Groningen and Department of Pulmonary Diseases, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, , 9700 RB Groningen, The Netherlands.
authors: Harry Jm
authors: HJ
authors: Groen
keywords: Elastix; Image deformation; NSCLC; PET/CT