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Medicale Image Analysis Registration Validation Prof. Dr. Philippe Cattin MIAC, University of Basel Prof. Dr. Philippe Cattin: Registration Validation Contents 1 Validation 1.1 Validation of Registration Validation of Registration (2) Robustness Consistency Consistency (2) Consistency (3) Consistency (4) Visual Assessment Visual Assessment Visual Assessment (2) Visual Assessment (3) Visual Assessment (4) Visual Assessment (5) 1.2 Quantitative Validation for Rigid Registration Gold Standard for Rigid Registration Registration Error Measures FLE vs FRE vs TRE Point-Based Registration Error: Theory Point-Based Registration Error: Contents 4 5 6 7 8 9 10 11 12 13 14 15 16 18 19 20 21 1 of 35 22.09.2016 09:08 2 of 35 22.09.2016 09:08

Characteristics of TRE 1.3 Quantitative Validation for Non-Rigid Registration Validation of Non-Rigid Registration Validation of Non-Rigid Registration A possible solution for intra-subject registration A possible solution for intra-subject registration (2) A possible solution for intra-subject registration (3) A Better Solution for Multi-Modal Intra- Subject Registration Validation Discussion Conclusions The Holy Grail 22 24 25 26 27 28 29 30 31 32 Validation Validation of Registration(4) Before an image registration method can enter clinical practice, it must undergo thorough validation Technical validation Speed, robustness, accuracy, reliability,... Clinical validation usefulness, improved clinical diagnosis and patient management in health care FDA approval, incorporation into commercial system Liability The biggest problem to evaluate registration methods is the lack of ground truth (in particular for multi-modal methods) 3 of 35 22.09.2016 09:08 4 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Prof. Dr. Philippe Cattin: Registration Validation Validation of Registration (2) (5) Prior to deployment several important properties must be analysed: 1. Robustness Measurement precision 2. Consistency Circular (invertible) transformations 3. Visual assessment Subtraction images, overlays, landmarks, contours,... 4. Quantitative analysis Rigid registration: Implanted/attached markers, landmarks Non-rigid registration: Simulation of deformation followed by a motion recovery Robustness Robustness can be measured as the discrepancy of registration transformations if different starting estimates are given or the images are perturbed. 1. How is the registration affected by external factors (6) Misregistration of an image by a known amount, e.g. by upto or Adding noise, inhomogeneity, artefacts Adding error to landmark or feature estimates 2. Deviation from identity transformation which forms the ground truth Individual deviations of DOFs (, and the Euler angles) Target registration error (TRE) at landmarks or within volume overlap try to workout a range of working conditions. 5 of 35 22.09.2016 09:08 6 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Prof. Dr. Philippe Cattin: Registration Validation Consistency (7) Consistency (2) (8) Involves registration of an image triple, A to B, B to C, and C to A Ideally, the resulting transformations form a circular registration (6.1) Can be tested for robustness via individual transformation parameters or via TRE Consistency is not a measure for registration accuracy! Fig 6.1: Consistency test (1) Can individual registrations be composed? Fig 6.2: Consistency test (2) 7 of 35 22.09.2016 09:08 8 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Prof. Dr. Philippe Cattin: Registration Validation Consistency (3) (9) Consistency (4) (10) Scan/Rescan consistency Forward/reverse registration consistency. Fig 6.3: Consistency test (3) A true measure of reproducibility for a particular scanner/acquisition method. Fig 6.4: Consistency test (4) Some registration methods enforce this consistency property. 9 of 35 22.09.2016 09:08 10 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Prof. Dr. Philippe Cattin: Registration Validation Visual Assessment (11) Visual Assessment (12) The simplest validation can be performed by visually comparing the image pair before and after registration. Several approaches are used Image subtraction is a widely spread method for mono-modal images. Subtraction mode (only for mono-modal images) Overlay mode Iso-contours or colour coded (red/green) Checkerboard, morphing Horizontal or vertical shutters Reformating (interpolation) of the images might be required to show the same anatomical location. Visual assessment is only a qualitative validation method Fig 6.5: CT of a leg Fig 6.6: Pre-registration image subtraction Fig 6.7: Post-registration image subtraction 11 of 35 22.09.2016 09:08 12 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Prof. Dr. Philippe Cattin: Registration Validation Visual Assessment (2) (13) Visual Assessment (3) (14) Checkerboard visualisation Displaying contours of important structures in the other modality are not only applicable for mono-modal but also for multi-modal images. Fig 6.8: Registered retina fundus and fluo image shown in a checkerboard fashion Fig 6.9: CT, unregistered MR contour Fig 6.10: CT, registered MR contour 13 of 35 22.09.2016 09:08 14 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Visual Assessment (4) (15) Parts of the MR and CT image are displayed with a moveable shutter. Medicale Image Fig Analysis 6.11: Visual assessment using a shutter 15 of 35 22.09.2016 09:08 16 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Visual Assessment (5) (16) The MR (red) and CT (green) data set are displayed simultaneously. Their respective intensity can be adapted dynamically. Fig 6.12: Visual assessment using colour coding (red = MR, green = CT) 17 of 35 22.09.2016 09:08 18 of 35 22.09.2016 09:08

Quantitative Validation for Rigid Registration Gold Standard for Rigid Registration The theory behind accuracy establishment for rigid registration is well understood. (18) The gold standard method uses either physical markers or well-defined natural landmarks It allows to determine the registration accuracy It can be obtained from known marker positions from which ground truth transformation can be obtained Given a transformation of points from space of the first view to space of the second view Goal: make Target Registration Error ( ): The remaining might stem from registration mismatches or because the rigid body assumption is not accurate 19 of 35 22.09.2016 09:08 20 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Quantitative Validation for Rigid Registration Prof. Dr. Philippe Cattin: Registration Validation Quantitative Validation for Rigid Registration Registration Error Measures (19) FLE vs FRE vs TRE (20) Def: Fiducials are either attached or implanted markers (such as a gold sphere) used for rigid registration validation and targeting. Fiducial localisation error ( ) Error of localisation fiducials Fiducial registration error ( ) Distance between points (fiducials) used for registration Minimum value of cost function Target registration error ( ) Distance beetween points (targets) not used for registration This is the clinically relevant error Fig 6.13: Visualisation of,, and 21 of 35 22.09.2016 09:08 22 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Quantitative Validation for Rigid Registration Prof. Dr. Philippe Cattin: Registration Validation Quantitative Validation for Rigid Registration Point-Based (21) Registration Error: Theory The expected value of and can be estimated from using perturbation theory. The fiducial registration error is a function of, and given by (6.2) The target registration error is a function of,, fiducial configuration, and the target position. It is defined by Point-Based Registration Error: Characteristics of TRE proportional to inversely proportional to depends on target position has its minimum value at the fiducial configuration centroid (translational component) increases as the distance of the target point from the principal axis increases Iso-error contours are ellipsoidal (22) (6.3) where is the expected value, is the distance of the target from the principal axis, and is the RMS distance of the fiducials from the principal axis. 23 of 35 22.09.2016 09:08 24 of 35 22.09.2016 09:08

Quantitative Validation for Non-Rigid Registration Validation of Non-Rigid Registration (24) Robustness Difficult to find different valid initial starting estimates Consistency Non-rigid transformation must be invertible Visual assessment Small localised misregistrations difficult to see Gold standard Landmarks too sparse to give dense deformation map, markers need to be attached on/implanted to deformable tissue Simulation of a ground truth Deformation simulations are often not of a plausible nature, and often the same motion model is used for simulation and registration, introducing a bias 25 of 35 22.09.2016 09:08 26 of 35 22.09.2016 09:08

Prof. Dr. Philippe Quantitative Validation for Non-Rigid Registration Cattin: Registration Validation Prof. Dr. Philippe Quantitative Validation for Non-Rigid Registration Cattin: Registration Validation Validation of Non-Rigid Registration (25) A possible solution for (26) intra-subject registration Application dependent Non-rigid registration for motion compensation Non-rigid registration for segmentation Currently there is no standard methodology for the validation of non-rigid registration Application: Motion compensation in contrastenhanced MR mammography Objective: Assessment of with the region of suspected lesions Validation strategy: Simulation using FEMs Finite element methods (FEMs) Modelling of interrelation of different tissue types Applied forces or displacements can predict physically plausible motion Simulation of a range of typical, physically plausible motion 27 of 35 22.09.2016 09:08 28 of 35 22.09.2016 09:08

Prof. Dr. Philippe Quantitative Validation for Non-Rigid Registration Cattin: Registration Validation Prof. Dr. Philippe Quantitative Validation for Non-Rigid Registration Cattin: Registration Validation A possible solution for (27) intra-subject registration (2) A possible solution for (28) intra-subject registration (3) Registration of post-contrast volume to its FEM deformed version beware of correlated noise!!!! The gold standard transformation from the FEM model maps every point in to can be calculated over all voxels within the deformed breast volume Fig 6.14: Non-rigid registration validation scheme using FEM models Registration of the pre-contrast to the deformed post-contrast Calculating the from would be subject to a small residual, as the motion between and was neglected Solution: Estimate the transformation which maps to Subtract from and calculate the residual corrected called consistency registration error ( ) Fig 6.15: Non-rigid registration validation scheme using FEM models 29 of 35 22.09.2016 09:08 30 of 35 22.09.2016 09:08

Prof. Dr. Philippe Quantitative Validation for Non-Rigid Registration Cattin: Registration Validation A Better Solution for (29) Multi-Modal Intra-Subject Registration Validation Take simultaneously acquired T1- and T2-weighted breathhold MR images. Their contrast difference is very similar to real multi-modal images such as MR/CT. No problems with correlated noise Transformation is close to the identity, as the two images were captured at the same time can be easily calculated Fig 6.16: Optimal multi-modal validation scheme using T1/T2 MRI 31 of 35 22.09.2016 09:08 32 of 35 22.09.2016 09:08

Prof. Dr. Philippe Quantitative Validation for Non-Rigid Registration Cattin: Registration Validation Prof. Dr. Philippe Cattin: Registration Validation Validation Conclusions (30) Set-up of generic validation tool for non-rigid registration Applicable to other non-rigid registration methods and medical applications useful for improving the registration method Helps to compare the performance of different methods Discussion (31) Validation of image registration is essential, if not vital The ground truth is hardly ever available Rigid registration accuracy can be assessed using a gold standard (e.g. markers) Non-rigid registration accuracy can be only assessed using simulations of a gold standard (e.g. FEMs) However, the validation methodology should always be independent of registration methodology! 33 of 35 22.09.2016 09:08 34 of 35 22.09.2016 09:08

Prof. Dr. Philippe Cattin: Registration Validation Validation The Holy Grail (32) The Holy Grail of image registration would be an on line self-diagnosing registration method Fig 6.17: Holy Grail of the Monastery of Xenophontos 35 of 35 22.09.2016 09:08