title: Sensitivity study of voxel-based PET image comparison to image registration algorithms.
abstract: OBJECTIVE
  Accurate deformable registration is essential for voxel-based comparison of sequential positron emission tomography (PET) images for proper adaptation of treatment plan and treatment response assessment. The comparison may be sensitive to the method of deformable registration as the optimal algorithm is unknown. This study investigated the impact of registration algorithm choice on therapy response evaluation.
  
  
  METHODS
  Sixteen patients with 20 lung tumors underwent a pre- and post-treatment computed tomography (CT) and 4D FDG-PET scans before and after chemoradiotherapy. All CT images were coregistered using a rigid and ten deformable registration algorithms. The resulting transformations were then applied to the respective PET images. Moreover, the tumor region defined by a physician on the registered PET images was classified into progressor, stable-disease, and responder subvolumes. Particularly, voxels with standardized uptake value (SUV) decreases >30% were classified as responder, while voxels with SUV increases >30% were progressor. All other voxels were considered stable-disease. The agreement of the subvolumes resulting from difference registration algorithms was assessed by Dice similarity index (DSI). Coefficient of variation (CV) was computed to assess variability of DSI between individual tumors. Root mean square difference (RMSrigid) of the rigidly registered CT images was used to measure the degree of tumor deformation. RMSrigid and DSI were correlated by Spearman correlation coefficient (R) to investigate the effect of tumor deformation on DSI.
  
  
  RESULTS
  Median DSIrigid was found to be 72%, 66%, and 80%, for progressor, stable-disease, and responder, respectively. Median DSIdeformable was 63%-84%, 65%-81%, and 82%-89%. Variability of DSI was substantial and similar for both rigid and deformable algorithms with CV > 10% for all subvolumes. Tumor deformation had moderate to significant impact on DSI for progressor subvolume with Rrigid = - 0.60 (p = 0.01) and Rdeformable = - 0.46 (p = 0.01-0.20) averaging over all deformable algorithms. For stable-disease subvolumes, the correlations were significant (p < 0.001) for all registration algorithms with Rrigid = - 0.71 and Rdeformable = - 0.72. Progressor and stable-disease subvolumes resulting from rigid registration were in excellent agreement (DSI > 70%) for RMSrigid < 150 HU. However, tumor deformation was observed to have negligible effect on DSI for responder subvolumes with insignificant |R| < 0.26, p > 0.27.
  
  
  CONCLUSIONS
  This study demonstrated that deformable algorithms cannot be arbitrarily chosen; different deformable algorithms can result in large differences of voxel-based PET image comparison. For low tumor deformation (RMSrigid < 150 HU), rigid and deformable algorithms yield similar results, suggesting deformable registration is not required for these cases.
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Stephen
authors.initials: S
authors.lastname: Yip
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Aileen B
authors.initials: AB
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 and Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Hugo J W L
authors.initials: HJ
authors.lastname: Aerts
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Ross
authors.initials: R
authors.lastname: Berbeco
mesh_terms: D000368:Aged; D000465:Algorithms; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging*; D005260:Female; D056973:Four-Dimensional Computed Tomography / Q000379:methods*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed / Q000379:methods*