Gamma Ray Imaging of Small Animals Using Position-Sensitive Photomultiplier Tubes A thesis submitted in partial fulfillment of the requirements for the degree of Bachelor of Science in Physics from the College of William and Mary in Virginia, By, Julie Cella Williamsburg, Virginia April 16th, 20042 Acknowledgments I would like to thank the generous support and guidance offered by my advisor Dr. Robert Welsh of the Physics Department and Dr. Eric Bradley and Dr. Margaret Saha of the Biology Department. I would also like to thank the kind advice and assistance offered by Jianguo Qian of Applied Science and Kevin Smith (William and Mary, ’03). In addition, I would like to acknowledge our collaborators at Jefferson Lab, Stan Majewski, Vladimir Popov, Mark F. Smith, Andrew G. Weisenberger, and Randy Wojcik. This research would not be possible without the support of NIH, Department of Energy, National Science Foundation, The Jeffress Trust, and in particular The HHMI Science Education Program for their support of my summer research, additional semester grants, and travel grant.3 Abstract This thesis is an interdisciplinary investigation of small animals consisting of two parts. First, a comparison of NaI(Tl) and CsI(Tl) pixilated scintillating crystals will be presented based on results of resolution tests performed using 5” diameter Hamamatsu 5800 PSPMTs. Second, application of the gamma ray detectors will be assessed using a biological model. The biological model chosen to analyze is the efficacy of potassium iodide as a blocking agent to the uptake of radioiodine by the thyroid. The blocking dose of potassium iodide is tested and the implications discussed.4 Table of Contents 1. Introduction……………………………………………………….5 2. SPECT Demands and Resolution Tests……………………….….7 2a. CsI (Tl) Crystal……………………………………………….8 2b. NaI (Tl) Crystal………………………………………………10 2c. Conclusion of Resolution Tests……………………………...12 3. Thyroid Blocking with Potassium Iodide as a Biological Model...12 3a. Reasons to Study KI blocking………………………………..13 3b. Summary of Previous Literature on Efficacy of KI Blocking..15 4. KI Blocking Study………………………………………………..18 4a. Data Analysis Method I: “Background Subtract”…………….20 4b. Data Analysis Method II: “Total Body ROI”…………………24 4c. Comparison of ROI data to Liquid Scintillation data…………26 4d. Percent of Injected Dose that the Thyroid Accumulates and Assessment…………………………………………….28 5. Conclusion………………………………………………………….32 Appendix A: Table III………………………………………………….33 Appendix B: Table XI…………………………………………………35 Appendix C: Computer Proficiency Requirement…………………….36 References……………………………………………………………...41 Bibliography……………………………………………………………435 1. Introduction This project is an interdisciplinary investigation of small animals. One goal is to study gene expression in a mouse using nuclear medicine imaging techniques. Study of the mechanisms and effects of gene expression from a molecular biology standpoint are limited by our ability to “see” into the animal. The techniques up until about ten years ago were almost always moment-in-time images that often required killing the animal in order to prepare it for imaging. The team working on this project has attempted to improve the process of small animal imaging by exploiting nuclear physics techniques. The detector design balances resolution and sensitivity demands so as to trace biologically relevant processes through the body of a mouse, in vivo, at the molecular level. The ability to do this allows for more comprehensive research that has both theoretical and therapeutic implications. The experimental set-up uses commercially available radioactive 125I labeled antibodies, ligands, and probes in its in vivo study. One of the challenges in designing this system was the spatial resolution demand due to the small body of a mouse. This was overcome by employing the techniques used in particle physics detection. The isotope of iodine chosen for this detector (125I) has a half-life of 60 days and emits both gamma rays and x-rays upon nuclear decay. The 125I captures an atomic electron becoming an excited state of 125Te with energy of 35 keV. That state decays mostly by internal conversion (~ 92%); it transfers its energy to another atomic electron, which gets ejected. So, both the electron capture and the internal conversion result in vacancies in the inner electron shells. The vacancies are filled as electrons fall down6energy levels emitting photons. Thus, the decay of each 125I nucleus results in the emission of mostly 28 keV atomic x-rays with a few 35 keV nuclear gamma rays. These photons are detected when they give up some or all of their energy to the detection material, in this case, the scintillators. Ideally, the radiation incident upon the scintillator will cause the emission of several visible photons. The scintillation photons are then detected using a light sensitive measuring device – a photomultiplier tube. The type of scintillation material chosen and the properties of the photomultiplier tube are specific to both the size of the small animal chosen and 125I. The current dual-modality system in use for imaging consists of two 5”-diameter round 3292 Hamamatsu Position Sensitive Photomultiplier Tubes (PSPMTs) and a Lixi X-Ray Machine. PSPMTs have the advantage over regular PMTs in that they can detect position, as well as energy and time of occurrence, of the incident photon. The pixilated scintillating material used preserves the position of the gamma ray because each pixel is optically isolated from the ones beside it. Therefore, the photons get channeled toward the surface of the detector. The incident photons then get converted to electrons at the photocathode where they are converted to electrons. The electrons are accelerated and the current multiplied using grids of dynodes at successively more positive voltages instead of cups