UCLA UCLA Electronic Theses and Dissertations Title Brain Imaging with Positron Emission Tomography: Quantification and Biomedical Applications in Alzheimer's Disease and Brain Tumors Permalink https://escholarship.org/uc/item/8bk5d65s Author Wardak, Mirwais Publication Date 2013 Supplemental Material https://escholarship.org/uc/item/8bk5d65s#supplemental Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA Los Angeles Brain Imaging with Positron Emission Tomography: Quantification and Biomedical Applications in Alzheimer’s Disease and Brain Tumors A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Biomedical Physics by Mirwais Wardak 2013 © Copyright by Mirwais Wardak 2013 ABSTRACT OF THE DISSERTATION Brain Imaging with Positron Emission Tomography: Quantification and Biomedical Applications in Alzheimer’s Disease and Brain Tumors by Mirwais Wardak Doctor of Philosophy in Biomedical Physics University of California, Los Angeles, 2013 Professor Sung-Cheng Huang, Chair Positron emission tomography (PET) is a unique and powerful imaging technique that is used to visualize and quantify various biological processes in living subjects in health and disease. PET imaging can also provide biological information for the assessment of therapies. In this dissertation, we will cover three projects that utilize the quantitative capability of PET for studying two neurological disorders: Alzheimer’s disease and brain tumors. One of the goals in PET imaging is to produce an image volume that accurately describes the true distribution of the injected radioactivity. The correction factor that has the most significant impact on the quantitative aspects of a PET image is attenuation correction. Without it, the reconstructed images will give a distorted view of the true activity distribution. Head ii movement during a PET scan (especially a dynamic scan) can also lead to a loss in the information content contained in a PET image. This is especially true when scanning patients with dementia or movement disorders. The transmission scan, which is typically acquired at the start of a PET study, corrects for photon attenuation in each of the serial emission scans that are acquired afterwards. In the first project of this dissertation, we developed a retrospective image-based movement correction (MC) method and evaluated its implementation on dynamic 18F-FDDNP PET images of cognitively intact control subjects and patients with Alzheimer’s disease (AD), each with varying degrees of head movement. 18F-FDDNP is a PET probe that binds to beta-amyloid plaques and neurofibrillary tangles, the neuropathological hallmarks of AD. The MC method corrected for transmission-emission misalignments as well as for emission-emission misalignments that might have been present in the dynamic PET scan. The image quality, tracer kinetics, and diagnostic accuracy of the 18F-FDDNP PET images were significantly improved after applying the MC method. In the second project of this dissertation, we investigated whether changes in 18F-FLT kinetic parameters, taken early after the start of therapy, could predict overall survival and progression-free survival in patients with recurrent malignant glioma undergoing treatment with bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). 18F-FLT is a radiotracer used in PET to measure cellular proliferation. We found that when a group of optimal kinetic parameter changes are incorporated into a linear discriminant function, one could accurately classify patients into their known survival groups. This method is advantageous because by reliably identifying short- and long-term survivors early during therapy, clinicians iii can discontinue ineffective treatment strategies and switch to more advanced treatment regimens that could improve patient outcome. Our third project expanded on what we did in our second project in that we acquired longitudinal 18F-FDOPA PET scans in addition to 18F-FLT PET scans. We also tried to predict overall survival as a continuous outcome variable using multiple linear regression (as opposed to a dichotomous categorical variable with discriminant analysis from before). In brain tumors, 18F-FDOPA is used to image amino acid transport. We found that in patients with recurrent malignant glioma, kinetic information from 18F-FLT alone was more predictive than using information from 18F-FDOPA alone. Using both probes combined provided comparable results to using 18F-FLT alone, suggesting that a single tracer may provide sufficient information for predicting OS with reasonable accuracy. The studies reported in this dissertation have demonstrated in three examples that the utility of kinetic quantification can significantly improve the value of PET for imaging biological functions in brain tissues in vivo. The developed methodologies in these examples are also expected to be useful in other quantitative brain PET imaging studies – for other applications or using other tracers. iv The dissertation of Mirwais Wardak is approved. Jorge R. Barrio Magnus Dahlbom Timothy Deming Christiaan Schiepers Sung-Cheng Huang, Committee Chair University of California, Los Angeles 2013 v DEDICATION I would like to dedicate this dissertation to my parents, Soorgul and Setara Wardak, for their love and continuous support throughout my life. I love you very much. My dad and mom. My dad at his doctoral commencement ceremony (Raleigh, North Carolina; May 1976) vi TABLE OF CONTENTS Page ABSTRACT OF THE DISSERTATION ...................................................................................... ii COMMITTEE PAGE ..................................................................................................................... v DEDICATION .............................................................................................................................. vi TABLE OF CONTENTS ............................................................................................................. vii LIST OF FIGURES ...................................................................................................................... xi LIST OF TABLES ........................................................................................................................ xv SUPPLEMENTARY MATERIALS .......................................................................................... xvi ACKNOWLEDGEMENTS ........................................................................................................ xix VITA ......................................................................................................................................... xxiii CHAPTER 1. INTRODUCTION .................................................................................................. 1 1.1 Special Aspects of Medical Imaging .................................................................................. 1 1.2 General Principles of Nuclear Medicine Imaging .............................................................. 2 1.2.1 Fundamental Concepts ................................................................................................. 2 1.2.2 The Power of Molecular Imaging ................................................................................ 2 1.3 Positron Emission Tomography (PET) ............................................................................... 3 1.3.1 Overview of PET .......................................................................................................... 4 1.4 Basic Physics of Positron Emission and Annihilation ........................................................ 6 1.4.1 Positron Emission ......................................................................................................... 6 1.4.2 Annihilation .................................................................................................................. 7 1.5 Photon Interactions ............................................................................................................. 8 1.6 Gamma Photon Detectors in PET ....................................................................................... 9 1.6.1 Detector Basics ............................................................................................................. 9 1.6.2 Block Detector ............................................................................................................ 10 1.7 Coincidence Detection ...................................................................................................... 11 1.7.1 Types of Coincidence Events ..................................................................................... 11 1.8 Attenuation Correction ...................................................................................................... 12 1.8.1 Attenuation ................................................................................................................. 13 1.8.2 Attenuation Correction in PET ................................................................................... 14 1.8.3 Attenuation Correction in PET/CT ............................................................................ 15 1.9 Image Reconstruction ....................................................................................................... 15 1.9.1 Filtered Backprojection .............................................................................................