CT-PET IMAGE FUSION AND PET IMAGE SEGMENTATION FOR RADIATION THERAPY by Yiran Zheng Submitted in partial fulfillment of the requirements For the degree of Doctor of Philosophy Dissertation Adviser: Barry W. Wessels, Ph.D. Department of Biomedical Engineering CASE WESTERN RESERVE UNIVERSITY January, 2011 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF GRADUATE STUDIES We hereby approve the thesis/dissertation of Yiran Zheng candidate for the Ph.D. degree *. (signed) Andrew M. Rollins, Ph.D. (chair of the committee) Xin Yu, Ph.D. Barry W. Wessels, Ph.D. Syed F. Akber, Ph.D. ________________________________________________ ________________________________________________ (date) July 12th, 2010 *We also certify that written approval has been obtained for any proprietary material contained therein. Dedication To my parents and my wife Table of Contents Table of Contents ............................................................................................... 1 List of Tables ...................................................................................................... 4 List of Figures .................................................................................................... 6 Acknowledgements ............................................................................................ 8 List of Abbreviations ........................................................................................ 10 Abstract ............................................................................................................ 12 Chapter 1 An Introduction to PET and Radiation Therapy Treatment Planning ......................................................................................... 14 1.1 Physics of positron emission tomography (PET) .......................... 14 1.1.1 The spatial resolution of PET imaging system ............. 21 1.1.2 18F-FDG - the radiotracer used in PET ......................... 24 1.2 Radiation therapy treatment planning ............................ 27 1.2.1 Radiation therapy and External Beam Radiation Therapy ................................................................................... 27 1.2.2 Treatment planning for radiation therapy.................... 32 1.3 The role of PET in radiation therapy treatment planning and the significance of this research .................................................. 35 1.4 Overview of dissertation organization .......................................... 38 Chapter 2 A Machine Based CT-PET Image Fusion System .......................... 41 - 1 - 2.1 Abstract ......................................................................................... 41 2.2 Introduction ................................................................................... 43 2.3 Methods and materials ................................................................. 46 2.3.1 Patients .......................................................................... 46 2.3.2 Image Acquisition .......................................................... 46 2.3.3 Image Fusion ................................................................. 49 2.3.4 Data Analysis ................................................................. 49 2.4 Results ........................................................................................... 51 2.5 Discussion ...................................................................................... 56 2.6 Conclusion ..................................................................................... 59 Chapter 3 An Automatic Method for PET Target Segmentation Using a Lookup Table Based on Volume and Concentration Ratio ........................... 61 3.1 Abstract ......................................................................................... 61 3.2 Introduction ................................................................................... 63 3.3 Methods and materials ................................................................. 66 3.4 Results ........................................................................................... 73 3.5 Discussion ...................................................................................... 86 3.6 Conclusion ..................................................................................... 94 Chapter 4 Conclusions and Suggestions of Future Work ............................... 96 4.1 Conclusions .................................................................................... 96 4.2 Future work ................................................................................... 97 - 2 - 4.2.1 Validation of CT-PET image fusion ............................... 98 4.2.2 Extensive application of the fiducial device .................. 99 4.2.3 Validation of the machine independence of the new PET image segmentation method ................................ 100 4.2.4 Application of the automatic PET segmentation results for clinical outcome improvement ............................ 101 4.3 Summary ..................................................................................... 102 Bibliography ................................................................................................... 104 - 3 - List of Tables Table 1.1 The physical properties of selected radionuclides used in PET imaging system (17) ....................................................... 25 Table 2.1 Fiducial registration error of fiducial based CT-PET image fusion for each patient. .................................................... 52 Table 2.2 Average target registration error ± STD (mm) of anatomical landmarks vs. fusion methods................................. 53 Table 2.3 The results of one-way ANOVA F-test for the target registration errors using manual, fiducial, and automatic image fusion methods for each anatomical landmark. .................................................................................... 55 Table 3.1 Threshold lookup table consists of target volume and radioactivity concentration ratio. A desired threshold for target segmentation is chosen from this table based on the initial estimate of target volume and concentration ratio. ..................................................................... 76 Table 3.2 Recovery coefficient table. Concentration ratio (C) was corrected and recovered for partial volume effect based on initial estimate of target volume and measured source/background (S/B) ratio. .................................. 79 - 4 - Table 3.3 Volume calculation results using current method for spheres were imaged in Philips Allegro PET scanner. Each sphere was scanned with 4 different concentration ratios ranging from 3:1 to 12:1 in two-fold redundancy. ................................................................... 81 Table 3.4 Volume calculation results using current method for spheres were imaged in Philips Gemini TF PET/CT scanner. Each sphere was scanned with 3 different concentration ratios ranging from 3:1 to 12:1. ........................... 82 Table 3.5 Volume estimation uncertainty (% error) comparison of the current method with other published methods (88, 90)................................................................................................ 83 Table 3.6 Target volume calculation for clinical patient images compared with the CT-defined GTV. .......................................... 85 - 5 - List of Figures Figure 1.1 Positron emission and annihilation ............................................ 15 Figure 1.2 Types of false coincidence event. ................................................. 18 Figure 1.3 The physical limitation of the spatial limitation in PET imaging system due to positron range and non-collinearity effect. ................................................................ 22 Figure 2.1 The design of the fiducial board. ................................................. 47 Figure 2.2 The set up of fiducial board on couch .......................................... 48 Figure 3.1 Workflow of the current PET target segmentation method. First, a mean intensity method was used to obtain the initial volume and S/B ratio (steps 1, 2, 3a, and 3b). Next (steps 3c and 3d), the concentration ratio was obtained by applying the recovery coefficient table (Table 3.2). Based on the initial volume and the recovered concentration ratio, a desired threshold was then selected from the threshold lookup table (step 4). Lastly, this threshold was used to perform a standard level set method to delineate and estimate the final target volume (steps 5 and 6). .................................................... 70 Figure 3.2 Optimal thresholds yielding correct target volume for - 6 - each sphere target with different volume and radioactivity concentration ratio in Allegro scanner (a) and Gemini TF scanner (b). ........................................................ 74 Figure 3.3 Plots of S/B ratio versus measured sphere volume for the phantom scanned in Allegro (a) and Gemini TF scanner (b)................................................................................... 78 Figure 3.4 Comparison of CT volume and the segmented PET volume for lesion No. 2. The left panel is the axial CT slice with the manually defined GTV (green). The right panel is the co-registered PET slice with the automatically delineated contour as applied by the current method (pink)................................................................. 84 - 7 - Acknowledgements First of all, I would like to specially thank Dr. Barry W. Wessels, my research advisor, for his support, help