1. Standard Response Evaluation Criteria in Solid Tumors (RECIST) using 3D Slicer Slicer3 Training Compendium Jeffrey Yap, PhD Ron Kikinis, MD Wendy Plesniak, PhD

2. Materials This tutorial requires the following installation: 3D Slicer version 3.5 Software, which can be installed from http://www.na-mic.org/Slicer/Download/Snapshots/win32/Slicer3-3.5-RSNA-2009-11-06-win32.exe Tutorial data can be downloaded from: http://wiki.na-mic.org/Wiki/images/d/de/RECIST-Tutorial-Data.zip Disclaimer It is the responsibility of the user of 3DSlicer to comply with both the terms of the license and with the applicable laws, regulations and rules. Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -1-

3. Tutorial data Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -2- Unzip the tutorial dataset to find the following files: RECIST-TutorialScene-With-Snapshots.mrml (Scene file) RECIST-TutorialScene.mrml (Scene file) 2006-spgr.nrrd Axial 3D SPGR T1 post Gadolinium scan (Voxel dimension: 0.94mm x 0.94mm x 1.20mm, FOV: 240mm, Matrix: 256 x 256 2006-spgr-label.nrrd (pre-generated label map file) 2007-spgr.nrrd Axial 3D SPGR T1 post Gadolinium scan (Voxel dimension: 0.94mm x 0.94mm x 1.20mm, FOV: 240mm, Matrix: 256 x 256 2007-spgr-label.nrrd (pre-generated label map file) FiducialList.fcsv (fiducial list containing two fiducial markers) If all of these files are not present, please try downloading the tutorial dataset again.

4. Clinical context Baseline radiologist’s impression: a large falcine lesion is identified. present on both sides of the anterior falx adjacent to the frontal lobes. measures 3.1 cm anteroposteriorly, 3.05 cm from side-to-side, and almost 3.5 cm in height. minimal brain edema. enhances moderately on post gadolinium imaging. consistent with meningioma. ventricular system and subarachnoid spaces are within normal limits. Follow-up radiologist’s impression: left frontal lobe mass appears unchanged on all series. measures 3.3 x 3.2 cm in maximum dimension. no other intracranial masses, mass-effect, midline shift, edema, or extra-axial collections present. enhances moderately on post gadolinium imaging. consistent with meningioma. ventricular system and subarachnoid spaces are within normal limits. Has the tumor grown? Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -3- Baseline: June 2006 Follow-up: June 2007

5. Response Evaluation Criteria in Solid Tumors (RECIST) RECIST Methodology: All measurable lesions (up to a maximum of five lesions per organ and 10 lesions total, representative of all organs) are recorded and measured. Target lesions are selected on the basis of size (longest diameter) and their suitability for accurate repeated measurements. Measure the longest diameter. Also the orthogonal diameter(s). Assessment criteria: CR (complete response) = disappearance of all target lesions PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions SD (stable disease) = small changes that do not meet above criteria Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -4-

6. Learning objective Following this tutorial, you’ll be able to use 3D Slicer to: Load a MRML Scene file, Visually assess the response to therapy, Make quantitative linear measurements across tumor cross sections, and Make quantitative volume measurements of tumor anatomy Assess according to RECIST criteria. Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -5-

7. Workflow Overview 1.Load two post-treatment datasets 2.Adjust display of both studies in Slicer’s Volumes Module 3.Switch Layouts (to Axial (Red) Slice Layout) 4.Compare opposing diameters of largest tumor cross section using fiducial markers. 5.Compare volumetric measures of tumor using label map statistics. 6. Assess changes. Workflow for linear and volumetric measurements Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -6-

8. The Graphical User Interface (GUI) of Slicer3 integrates five components: the Menu Toolbar the Module GUI Panel the 3D Viewer the Slice Viewer the Slice and 3D View Controller Slice Viewer 3DViewer Module GUI Panel Slice and 3D View Controller Menu Toolbar Quick overview of Slicer3 GUI Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -7-

9. Loading data using a MRML scene file * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -8- Using File->Load Scene: Raises the Load Scene Interface select the RECIST- Tutorial-Scene-With- Snapshots.mrml file double click the file, or click “Open”

10. fyi: What is “MRML”? MRML (pronounced mur-muhl) stands for the "Medical Reality Markup Language"; and is an XML-based representation of a MRML Scene. MRML Scene description is the XML-based file (with extension.mrml) that contains the complete MRML Scene specification, and which references all datasets present in the MRML Scene. MRML Scene is the collection of datasets and their current state, viewing parameters, semantic descriptions, and algorithm parameterization. Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -9- * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

11. Loading data Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -10- Using Modules Menubutton: Expose the menu and select the “Volumes” module. * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

12. Displaying data Volumes Module GUI Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -11- Select 2006-spgr as the Active Volume Adjust Window/Level then… Select 2007-spgr as the Active Volume Adjust Window/Level These controls apply to the Active Volume. * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

13. Displaying data Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -12- Turn on a tracking crosshair: Using the Crosshair Icon, modify the crosshair to track the mouse: Navigator OFF Basic Crosshair ON * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

14. Displaying data Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -13- Zoom in/out by clicking the right mouse button inside the Slice Viewer and moving the mouse toward/away from you. Translate the volume by clicking and dragging the middle mouse button. * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

15. Exploring data Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -14- Scroll through the volume to identify the slice that shows the tumor cross section with largest area. For sake of example, we use the slice at S = 28.2mm * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

16. Exploring data Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -15- Note the annotations that report voxel (IJK) coordinates and spatial (RAS) coordinates. * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

17. Change layouts (shortcut using scene snapshot) Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -16- * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary Use the “Scene Snapshots” menubutton to select the “2006AxialOnly” snapshot. This changes the layout to display only the Axial slice.

18. Make linear measurements Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -17- Using Modules Menubutton: Expose the menu and select the “Fiducials Module”. In this scene, a Fiducial List containing two Fiducial points has already been created. * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary Side Note: The Fiducials Module is powerful and functionality-rich. Learn more about it here: http://www.slicer.org/slicerWiki/index.php/Modules:Fiducials-Documentation-3.4

19. Make linear measurements Select “FiducialList” from the Fiducial List menu. Turn on the Fiducials visibility with the List Visibility Toggle. Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -18- * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

20. Make linear measurements Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -19- Mouse over any fiducial point. When it turns “yellow”, it can be clicked and moved to a new (x,y) position. Record their linear distance along the largest diameter. D1 2006 = 33.246mm * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

21. Make linear measurements Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -20- Do the same for the opposing diameter. D2 2006 = 33.2318mm * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

22. Make volume measurements Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -21- Using Modules Menubutton: Expose the menu and select the “LabelStatistics” module under the “Statistics” group. * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

23. Make volume measurements Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -22- Specify 2006-spgr as the “Input Greyscale Volume” …and specify 2006spgr-label as the “Input Labelmap” Click “Apply”. Note the volumetric measure for the “green” tumor label (label 6). V 2006 = 17444.35 mm 3 * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

24. Change layouts (shortcut using scene snapshot) Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -23- Use the “Scene Snapshots” menubutton to select the “2007AxialOnly” snapshot. * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

25. Volume measurements… Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -24- Select “2007-spgr” as the Input Greyscale Volume. Select “2007-spgr- label” as they Input Labelmap. And click “Apply”. V = 17458.24mm 3 * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary While in the LabelStatistics module, compute volumetric measurement for this study.

26. Linear measurements… Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -25- Make fiducials visible using the toggle. Click and drag the fiducial markers and record orthogonal linear measurements for the tumor cross section. * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary Use the Fiducials Module shortcut in the toolbar...

27. Linear measurements… Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -26- D1 2007 =34.66mm and D2 2007 = 33.13mm * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

28. Comparing measurements Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -27- Compare corresponding measurements. Change in Tumor metrics: 2007-spgr 2006-spgr V mm 3 D2 (mm)D1 (mm) 17458.24 17444.35 31.70633.13 33.2318 33.246 % change: -0.34% -4.5% +0.08% * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

29. Assessment Using the RECIST assessment criteria: SD (stable disease) = small changes that do not meet above criteria Say something here about efficacy and limitations of RECIST. What can it capture, What does it not capture as well. Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -28- * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary (jeff – please discuss)

30. Assessment: Other tools to assess changes in tumor metrics Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -29- * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary Segue into Change Tracker tutorial. Provide a link to the tutorial and tutorial data.

31. Summary Summary of activity: Used interactive interface to load a scene Performed a workflow to make quantitative measures of tumor response to therapy including: --linear measurements --volume measurements Yap J, Kikinis R, Plesniak W: Harvard CTSC at RSNA2009 -30- * Load data & adjust display * Identify largest tumor cross section * Switch layouts & make linear measurements * Make volume measurements * Switch layouts & analyze follow-up * Assessment * Summary

32. Acknowledgments Harvard Clinical and Translational Science Center National Alliance for Medical Image Computing NIH U54EB005149 Neuroimage Analysis Center (NAC) National Center for Image-Guided Therapy (NCIGT) Surgical Planning Laboratory, Brigham and Women’s Hospital