-1- CTSA at RSNA 2009 Measuring Volume Change in Tumors Jeffrey Yap, PhD Ron Kikinis, MD Wendy Plesniak PhD Kilian M Pohl, PhD Ender Konugolu, PhD Andriy Fedorov, PhD Slicer3 Training Compendium

-2- CTSA at RSNA 2009 Data This course is built upon two scans of a patient with meningioma: MR Scan 1MR Scan 2 Please note: we have pre-adjusted the window and level settings for these volumes so that they are appropriate for display on most laptops. If display is not satisfactory on your machine or projector, the Volumes Module may be used to refine these settings.

-3- CTSA at RSNA 2009 Data Clinical context Baseline radiologist’s impression: large falcine lesion is identified. measures 3.1 cm anteroposteriorly, 3.05 cm from side-to-side, 3.5 cm in height. enhances moderately on post gadolinium imaging. Follow-up radiologist’s impression: left frontal lobe mass appears unchanged on all series. measures 3.3 x 3.2 cm in maximum dimension. enhances moderately on post gadolinium imaging. How has the tumor changed? Baseline: June 2006 Follow-up: June 2007

-4- CTSA at RSNA 2009 Overview Part I: Applying RECIST methodology Part II: Measuring volume change in tumors using ChangeTracker

-5- CTSA at RSNA 2009 Part I Standard Response Evaluation Criteria in Solid Tumors (RECIST) using 3D Slicer Jeffrey Yap, PhD Ron Kikinis, MD Wendy Plesniak, PhD

-6- CTSA at RSNA 2009 Response Evaluation Criteria in Solid Tumors (RECIST) Methodologies: WHO: Largest diameter and its perpendicular RECIST: Largest diameter (LD) only. 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

-7- CTSA at RSNA 2009 Learning objective Following Part I of 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.

-8- CTSA at RSNA 2009 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

-9- CTSA at RSNA 2009 Select File->Close Scene: Close any previous scene This removes any datasets previously loaded into Slicer.

-10- CTSA at RSNA 2009 Loading data using a MRML scene file Using File->Load Scene: This raises the Load Scene Interface select the file RECIST-Simple.mrml double click the file, or click Open

-11- CTSA at RSNA 2009 Loading data: quick look at both image volumes The image volume 2006-spgr should be displayed in the background BG layer. The image volume 2007-spgr should be displayed in the foreground FG layer. Use the FG/BG toggle button and the Fade Slider to see both volumes. Toggle BGonly Fade FGonly

-12- CTSA at RSNA 2009 Explore the datasets Scroll in any Slice Viewer to look for large tumor cross sections Zoom in the Slice Viewers by Right-Clicking and dragging forward or back with the mouse. Pan in the Slice Viewers by Middle-Clicking and dragging with the mouse. Left-Click-and-drag in the 3D Viewer will rotate the view

-13- CTSA at RSNA 2009 Using Modules Menubutton: Expose the menu and select the Fiducials Module. Side Note: The Fiducials Module is powerful and functionality-rich. Learn more about it here: Loading data: quick look at both image volumes

-14- CTSA at RSNA 2009 Using Fiducials for linear measurement Pick Place Transform Notice the Mouse Mode Toolbar for specifying the Mode of Interation Slicer is currently in “Transform Mode”

-15- CTSA at RSNA 2009 Using Fiducials for linear measurement Select Place Mode, to Place Fiducial Points NOTE: In Place Mode any Left-mouse- button click in a viewer will create a new fiducial point at the spatial location within the volumetric frame of reference.

-16- CTSA at RSNA 2009 Using Fiducials for linear measurement Scroll to the – mm position in the Sagittal Slice Viewer Click and Drag the Right Mouse Button to zoom in. Click and Drag the Middle Mouse button to center the tumor.

-17- CTSA at RSNA 2009 Using Fiducials for linear measurement Click with the left mouse button to place two fiducial points along the long diameter. THEN Change back to Transform Mode

-18- CTSA at RSNA 2009 Using Fiducials for linear measurement Note the magnified region around the cursor in the bottom-most GUI panel. Move the mouse over either fiducial point. When it turns yellow, you can move it by clicking and dragging with the left mouse button.

-19- CTSA at RSNA 2009 The distance measurement (mm) will be updated in the Fiducial’s GUI panel. Using Fiducials for linear measurement

-20- CTSA at RSNA 2009 Toggle between foreground and background to observe the corresponding slice and adjust the measurement for the follow-up study. Using Fiducials for linear measurement

-21- CTSA at RSNA 2009 Compute tumor volume using segmentation Link all Slice Viewers using the Link Toggle if they are unlinked linked Unlinked Select the 2006-spgr- label Tumor Mask in the LB layer Select the None volume in the FG layer The tumor segmentation for the baseline volume is displayed

-22- CTSA at RSNA 2009 Using Modules Menubutton: Expose the menu and select the LabelStatistics module under the Statistics group. Compute tumor volume

-23- CTSA at RSNA 2009 Compute tumor volume Specify 2006-spgr as the Input Greyscale Volume Specify 2006-spgr- label as the Input Labelmap Click Apply. The tumor volume for label 6 (green) is shown in mm 3

-24- CTSA at RSNA 2009 Assessment The same analysis may be done for the follow-up study: Specify 2007-spgr as the Input Greyscale Volume Specify 2007-spgr-label as the Input Labelmap And click Apply. Final RECIST tumor metrics: 2007-spgr 2006-spgr V mm 3 CD (mm)LD (mm) % change: -2.78% -0.84% 0.15%

-25- CTSA at RSNA 2009 RECIST methodology: Is an effective approach for measuring sizeable changes in tumor size and assessing tumor response to therapy. We are developing new analysis tools in 3D Slicer for assessing change over time, including when the changes are small. Summary

-26- CTSA at RSNA D Slicer’s LabelDiameterEstimation module (available currently only in the Slicer nightly builds), will automatically compute the largest tumor diameter given an initial segmentation. Baseline: June 2006 Follow-up: June 2007 New tools

-27- CTSA at RSNA D Slicer’s Measurements module, is developing a measurement widget that operates in the 3D Viewer and the Slice Viewers. (the prototype version is available in Slicer’s nightly builds). New tools

-28- CTSA at RSNA D Slicer’s ChangeTracker module can assess volumetric changes at the voxel-level. New tools

-29- CTSA at RSNA 2009 Part II The module described in this tutorial was tested on Axial 3D SPGR T1 post Gadolinium scans (Voxel dimension: 0.94mm x 0.94mm x 1.20mm, FOV: 240mm, Matrix: 256 x 256) Analyzing Small Volumetric Changes using the ChangeTracker Module Kilian M Pohl, PhD Ender Konugolu, PhD Andriy Fedorov, PhD

-30- CTSA at RSNA 2009 Select File->Close Scene: Close any previous scene This removes any datasets previously loaded into Slicer.

-31- CTSA at RSNA 2009 Loading training dataset Select File->Load Scene: This raises the Load Scene Interface select the file: ChangetrackerTutorial2009.mrml double click the file, or click Open

-32- CTSA at RSNA 2009 Using the Layout MenuButton Change Layout to Four-up Select Four-up layout.

-33- CTSA at RSNA 2009 Select ChangeTracker Module Using the Modules Menubutton, Select the ChangeTracker Module from the Wizards category.

-34- CTSA at RSNA 2009 Workflow Wizard The Workflow Wizard guides the user through a sequence of steps and has the following components: the Step Panel the User Panel the Navigation Panel Step Panel User Panel Navigation Panel

-35- CTSA at RSNA 2009 Select Scans Select: Scan 1 = 2006-spgr Scan 2 = 2007-spgr

-36- CTSA at RSNA 2009 Zoom in Move sliders to see tumor Zoom in (Right mouse down and push/pull) Press Next

-37- CTSA at RSNA 2009 Identify Volume of Interest A VOI Box Widget is positioned within the volume, and its blue extent is displayed in each Slice Viewer Press Display volume rendering and VOI label Right mouse click in the tumor center.

-38- CTSA at RSNA 2009 VOI box widget and volume rendering of tumor in yellow Identify Volume of Interest Right mouse click in any Slice Viewer to adjust VOI center Left mouse click in any Slice Viewer to change the VOI extent

-39- CTSA at RSNA 2009 VOI Widget range sliders are color-coded to match VOI box Widget handles in 3D Viewer Fine-tune the VOI using the VOI Widget range sliders or by moving the VOI Widget handles in 3D view Identify Volume of Interest

-40- CTSA at RSNA 2009 Identify Volume of Interest Scroll through slices to ensure that tumor boundaries are included in the VOI Click Next

-41- CTSA at RSNA 2009 Segment Tumor Slice Viewers show VOI with current segmentation overlay in light yellow 3D Viewer shows model of tumor Change Segmentation by moving range slider

-42- CTSA at RSNA 2009 Press Grid to view grid with original voxel size (You may need to pan/zoom in slice viewers to refresh their display) Segment Tumor

-43- CTSA at RSNA 2009 Press Slice to see the first scan in the 3D Viewer Note: The 3D View can be reset using the Axis Navigator Widget Segment Tumor

-44- CTSA at RSNA 2009 Press Next Segment Tumor

-45- CTSA at RSNA 2009 Choose Metric Type Choice of Metric: Detect change by analyzing intensity pattern (fast) Measure change by analyzing deformation map (slow) Select fast and press Analyze

-46- CTSA at RSNA 2009 Analysis I: Volume Preserving Registration BeforeAfterwards Konukoglu et al.,“Monitoring Slowly Evolving Tumors”, ISBI, 2008

-47- CTSA at RSNA 2009 Analysis II: Normalize Intensities Scan 1Scan 2Scan 2 - Norm Konukoglu et al.,“Monitoring Slowly Evolving Tumors”, ISBI, 2008

-48- CTSA at RSNA 2009 PDF of Dormant Tissue Determine probability density function Analysis III: Detect Change – Intensity Based - = Compute statistics of static tissue: Subtract Scan2 from Scan1 Define region of static tissue

-49- CTSA at RSNA 2009 Analysis III: Detect Change – Intensity Based Mode : Sensitive Moderate Robust False Positive Risk: High Medium Low Growth (mm 3 ) : Growth (voxel): Analysis Data Konukoglu et al.,“Monitoring Slowly Evolving Tumors”, ISBI, 2008

-50- CTSA at RSNA 2009 Analysis III: Detect Change–Deformation Map = Determine change via mapping: Compute diffeomorphic mapping between scans Compute Jacobian Apply mapping to segmentation or Mode : Jaccobian Growth (mm 3 ) : 1291 Growth (voxels): 1049 Mode : Segmentation Growth (mm 3 ) : 1386 Growth (voxels): 1126

-51- CTSA at RSNA 2009 Show Change in Pathology Change in volume is shown: magenta = growth green = shrinkage Select visibility icon to show slice in the 3D Viewer

-52- CTSA at RSNA 2009 Show Change in Pathology Lightbox View shows five consecutive slices for the VOI in the first scan (top), and in the second scan (bottom)

-53- CTSA at RSNA 2009 Show Change in Pathology Define sensitivity of analysis

-54- CTSA at RSNA 2009 Show Change in Pathology Click on the colored bar at the top of any Slice Viewer to show or hide the controls. This allows more display space for viewing the image data.

-55- CTSA at RSNA 2009 Appropriate use Tested on Axial 3D SPGR T1 post Gadolinium scans (Voxel dimension: 0.94mm x 0.94mm x 1.20mm, FOV: 240mm, Matrix: 256 x 256) Tumor boundary should be clear Only for contrast enhanced images Need homogenous enhancement across timepoints Not tested for tumors with necrosis in one timepoint

-56- CTSA at RSNA 2009 Acknowledgments Harvard Clinical and Translational Science Center National Alliance for Medical Image Computing NIH U54EB Brain Science Foundation INRIA, France Neuroimage Analysis Center (NAC) National Center for Image-Guided Therapy (NCIGT) Surgical Planning Laboratory, Brigham and Women’s Hospital