Wayne State University Wayne State University Dissertations 1-1-2013 Imaging Iron Content In Patients With Multiple Sclerosis Using Magnetic Resonance Imaging Charbel Abdo Habib Wayne State University, Follow this and additional works at: http://digitalcommons.wayne.edu/oa_dissertations Recommended Citation Habib, Charbel Abdo, "Imaging Iron Content In Patients With Multiple Sclerosis Using Magnetic Resonance Imaging" (2013). Wayne State University Dissertations. Paper 841. This Open Access Dissertation is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Dissertations by an authorized administrator of DigitalCommons@WayneState. IMAGING IRON CONTENT IN PATIENTS WITH MULTIPLE SCLEROSIS USING MAGNETIC RESONANCE IMAGING by CHARBEL A. HABIB DISSERTATION Submitted to the Graduate School of Wayne State University, Detroit, Michigan in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY 2013 MAJOR: BIOMEDICAL ENGINEERING Approved by: _________________________________________ Advisor Date _________________________________________ _________________________________________ _________________________________________ _________________________________________ DEDICATION I dedicate my work to my family ii ACKNOWLEDGMENTS First and foremost, I would like to thank God for his blessing and for giving me the strength and the opportunity to expand my knowledge in two of the most interesting research areas combined: Engineering and Medicine. The PhD journey is never easy and therefore, it is indeed God’s blessings to have the great people around you to support you along this path. Therefore, I would like to thank my family for their encouragement, for their prayers and for their everlasting support. I would like to thank my mother, Mrs. Yolla Abdo Habib, for her prayers and constant support. She always taught us to seek the best and never stop! She was always ready to give everything so we can excel and succeed, even though this meaning that we will be far from her! Thank you Mother for this selfless love; you are such a blessing in my life; I hope I can be in my life half of what you have been for us. I would like to thank my dear wife, Mrs. Rana El Hachem-Habib, for her love, her patience, and her “silent wisdom”. Thank you my love for your support even from thousands and thousands of miles away, and for your understanding of how tough this route is and yet…, you honored me by sharing it with me... I love you dearly and looking forward for more and more great challenges and successes to share. I would like to thank my sister, Dr. Zeina Habib-Adel, for being such an inspiration over the years and for her support and guidance since day one. You are truly the amazing sister and you definitely deserve the best, because you are the best. I would like to thank my uncles, Fr. Fadi Bou Chebel and Mr. Antoine Bou Chebel, who enlightened me over the years and advised me on making the right steps which led me to this day. I will be in a lifetime debt for everything you have done for me. Thank you! iii I would like to thank Dr. E. Mark Haacke, my mentor and my advisor, for giving me the opportunity to train in his lab. Dr. Haacke doesn’t only teach his students about Magnetic Resonance Imaging, but he also teaches us how to always make our work “perfect” and never settle for “good”! Thank you for being such a great mentor and advisor, and for all the support you provided during my graduate studies. I would like to thank my dissertation committee members: Dr. Monte Harvill, Dr. Jiani Hu and Dr. Weiping Ren for their guidance and their constructive critique to make my research more complete and sharp. I would like to thank all the co-authors of my papers, for their contribution to the work. Special thanks go to Dr. Jean Peduzzi, Dr. Kenneth Casey and Dr. Elizabeth Dawe. I would like to thank the MR Research Facility group, faculty, post docs, graduate students and staff for all their help and advices. I would especially like to thank Mrs. Lisa Brownshidle, Mrs. Rachel Martis-Laze and Mr. Zahid Latif for all their help. I would also like to thank Dr. Jessy Mouannes-Srour and Uday Bhaskar Krishnamurthy for proof reading my dissertation. Last but not least, I would like to thank all my friends, who, when I was many miles away from home, made me feel I’m home. I would like to thank Mr. Richard Chaaya, Dr. Areen Al Bashir, Mr. Maurice Farah, Ms. Judith Farah, Mr. Emil Pacurar and Dr. Gabriela Trifan. Thank you for all the moments we shared, thank you for all the advices you gave and all the support you provided. iv PREFACE Magnetic resonance imaging is widely used as a diagnostic tool in clinical settings. Being non-invasive and non-ionizing makes it an ideal method to image human subjects in both cross- sectional and longitudinal studies. In the past decade, susceptibility weighted imaging (SWI) has received a great deal of attention in both the research and clinical realms. Due to its new source of contrast compared to conventional MRI, SWI offers new directions in studying the brain and its vasculature as well as imaging magnetic material (such as iron). Imaging iron is important because it is thought to be associated with normal aging and some neurodegenerative disease. For example, in multiple sclerosis (MS), a complex autoimmune neurodegenerative disease, iron involvement has been reported in patients both in vivo and post mortem. This iron deposition is believed to be not only associated with the inflammatory process in MS but also with vascular abnormalities in the brain and neck. In this work, we will first validate the ability of SWI to create contrast based on local iron content and we will use this technique to evaluate iron content in MS patients compared to normal (healthy) subjects. We will present a new means to extract iron content in large areas, which eliminates the effect of averaging (previously used) on data assessment. Finally, in order to study the relation between increased iron content, lesion load and the new theory of vascular involvement in MS (mentioned above), we will introduce the possibility of developing a vascular animal model of MS, by emphasizing the similarities and differences in the human and swine venous drainage system and presenting some preliminary data toward that direction. v TABLE OF CONTENTS Dedication --------------------------------------------------------------------------------------------------- ii Acknowledgments ------------------------------------------------------------------------------------------ iii Preface ------------------------------------------------------------------------------------------------------- v List of Tables ---------------------------------------------------------------------------------------------- viii List of Figures ---------------------------------------------------------------------------------------------- ix Abbreviation List ------------------------------------------------------------------------------------------- xi Chapter 1 – Introduction 1.1 – Background and Project Motivation -------------------------------------------- 1 1.2 – Project Aims ----------------------------------------------------------------------- 4 Chapter 2 – Iron in the Brain ----------------------------------------------------------------------------- 5 2.1 – Iron Types -------------------------------------------------------------------------- 7 2.2 – Iron Distribution in the Brain ---------------------------------------------------- 8 2.3 – Iron and Age ----------------------------------------------------------------------- 9 2.4 – Iron and Neurodegenerative Disease ------------------------------------------- 10 2.5 – Iron as Seen with MRI ------------------------------------------------------------ 13 Chapter 3 – Susceptibility Weighted Imaging --------------------------------------------------------- 17 3.1 – Magnetic Susceptibility ---------------------------------------------------------- 19 3.2 – Gradient Echo ---------------------------------------------------------------------- 21 3.3 – Susceptibility Weighted Imaging ----------------------------------------------- 26 3.4 – SWI filtered Phase Images ------------------------------------------------------- 28 Chapter 4 – Characterizing the Mesencephalon Using Susceptibility Weighted Imaging ------- 32 vi Chapter 5 – Multiple Sclerosis --------------------------------------------------------------------------- 45 5.1 – Different Types of MS ------------------------------------------------------------ 46 5.2 – MS Patients ------------------------------------------------------------------------- 49 5.3 – Immunological Approach -------------------------------------------------------- 52 5.4 – Cellular Approach ----------------------------------------------------------------- 56 5.5 – Molecular Approach -------------------------------------------------------------- 58 5.6 – Vascular Involvement in MS ---------------------------------------------------- 60 5.7 – Neuronal Involvement in MS ---------------------------------------------------- 61 5.8 – Correlational Interpretations ----------------------------------------------------- 68 Chapter 6 – Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains ------------------ 72 Chapter 7 – Assessing Iron Content in the Deep Gray Matter of MS Patients and Healthy Controls ------------------------------------------------------------------------- 80 Chapter 8 – Cerebral Vasculature of