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Sodium NMR Relaxation Parameters in Cartilage: Implications for MR Imaging by Adil Bashir B.S., University of Engineering and Technology Lahore, Pakistan (1991)

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Sodium NMR Relaxation Parameters in Cartilage: Implications for MR Imaging by Adil Bashir B.S., University of Engineering and Technology Lahore, Pakistan (1991) Sodium NMR Relaxation Parameters in Cartilage: Implications for MR Imaging by Adil Bashir B.S., University of Engineering and Technology Lahore, Pakistan (1991) Submitted to the Department of Electrical Engineering and Computer Science in partial fulfillment of the require- ments for the degree of Master of Science in Electrical Engineering at the MASSACHUSETTS INSTITUTE OF TECHNOLOGY February 1995 © Massachusetts Institute of Technology, 1995. All Rights Reserved. Author ...... ................. Department of Electrical Engineering and Computer Science February 10, 1995 Certified by ..... ...................... .......................... Deborah Burstein Thesis Supervisor . - . I A I Certified ... .... .e. ee.......e.e.e.. ,~",~t'%.. %,.,' \J '"'Id' ' I Martha L. Gray Thesis Supervisor , .,,,\ . I Accepted by. ._- .... .......................... \) Frederic R. Morgenthaler Chairman, Departmental C\mmittee on Graduate Students Eng. MASSACHIJSETSINSTfTT oIr -r-, .... APR 13 1995 2 Sodium NMR Relaxation Parameters in Cartilage: Implications for MR Imaging by Adil Bashir Submitted to the Department of Electrical Engineering and Com- puter Science, in partial fulfillment of the requirements for the degree of Masters of Science. Cartilage is a dense connective tissue which covers the opposing ends of bones in a joint and acts as lubricating and resilient surface. Cartilage consists of hydrated extracellular matrix and relatively few cells. The extracellular matrix is a network of collagen fibers and large proteoglycan aggregates. Proteoglycans have a net negative charge under physi- ological conditions known as fixed charge density (FCD). These negatively charged mole- cules preferentially attract positive sodium ions and thus are a source of osmotic pressure which gives cartilage its resilience to compression. These extracellular sodium cations can be measured by nuclear magnetic resonance (NMR) and used as a nondestructive tech- nique to monitor the tissue glycosaminoglycan concentration. Arthritis is a degenerative disease of cartilage and is characterized by a decrease in proteoglycan concentration. Sodium MR imaging can be an early indicator of this degenerative process and may pro- vide non-invasive means of measuring cartilage degradation in vivo. The essential param- eters which effect the signal intensity in sodium MRI are sodium density, and sodium T1 and T2 relaxation times. Therefore the main goal of the present study was to determine these relaxation parameters. Calf epiphyseal (EP) cartilage was harvested from distal ulna joints. T1 determined for calf EP cartilage consisted of a single exponential time constant with mean of 18.2 ms and increased to 33.0 ms after trypsin degradation to remove carti- lage proteoglycans. Cartilage T2 consisted of two well defined exponential components, T2 fast = 0.96 ms and T2 slow = 21.1 ms. After treating cartilage with trypsin the T2 fast decreased considerably to 0.2 ms with slow component changing slightly to 24 ms. In summary, these data provide the fundamental tissue parameters necessary for designing magnetic resonance imaging protocols necessary for quantitative sodium density weighted images. These protocols will ultimately be useful in monitoring early degeneration of car- tilage and in evaluating in vivo therapies. Thesis Supervisors: Deborah Burstein, Ph.D. Associate Professor of Radiology Beth Israel Hospital Harvard Medical School Martha L. Gray, Ph.D. Associate Professor of Electrical and Medical Engineering Department of Electrical Engineering and Computer Science MIT and Harvard-MIT Division of Health Science and Technology 3 4 Acknowledgments I am truly indebted to my thesis supervisors, Deborah Burstein and Martha L. Gray for their guidance and support. Working with them and in their group has been an enriching experience. They also spent much time on reading the drafts of this thesis and giving com- ments. I would like to thank my whole family, especially my parents, for their never ending support without which my education to date would not have been possible. Their encour- agement and guidance was a constant source of motivation me during my stay at MIT. And last, but certainly not the least I would like to thank all of the friends that I have made at MIT. Thanks to all of you for making my time here fun, interesting, educational and sometimes difficult, but never boring. 5 6 Table of Contents 1 Introduction ................................................................................................................ 17 2 Theory ........................................................................................................................ 23 2.1 Basic Principles ................................................................................................ 23 2.1.1 Sodium NMR ......................................................................................... 28 2.2 NMR Relaxation .............................................................................................. 30 2.2.1 Spin-Lattice Relaxation (T1)..................................................................31 2.2.2 Spin-Spin Relaxation (T2 and T2*) ........................................................ 31 2.3 NMR Relaxation Mechanisms ......................................................................... 33 2.3.1 Dipole-Dipole Relaxation ...................................................................... 33 2.3.2 Quadrupolar Relaxation ......................................................................... 37 2.4 Relaxation of Biological Tissues ..................................................................... 40 2.5 Exchange .......................................................................................................... 41 2.6 Experimental Section ....................................................................................... 43 2.6.1 Experimental parameters ....................................................................... 43 2.6.2 T1 measurement ..................................................................................... 44 2.6.3 Measurement of T 2 ................................................................................. 45 3 Cartilage Physiology .................................................................................................. 49 3.1 Cartilage Composition ..................................................................................... 49 3.2 Articular Cartilage Structure ............................................................................ 52 3.3 Donnan Equilibrium ......................................................................................... 53 4 Previous work ............................................................................................................ 55 4.1 Musculoskeletal NMR ..................................................................................... 55 4.1.1 Knee MRI ............................................................................................... 55 4.1.2 Cartilage NMR ....................................................................................... 57 4.2 Sodium NMR ................................................................................................... 61 4.2.1 Spectroscopy .......................................................................................... 61 4.2.2 Sodium Relaxation Times ...................................................................... 63 4.2.3 Sodium Imaging ..................................................................................... 66 4.2.4 Multiple Quantum Spectroscopy ........................................................... 70 5 M ethods...................................................................................................................... 73 5.1 Physiological Preparations ............................................................................... 73 5.1.1 Epiphyseal Cartilage Explant ................................................................. 73 5.1.2 Articular Cartilage Explant .................................................................... 75 7 5.2 Sample Preparation .......................................................................................... 75 5.3 Pathologic Interventions .................................................................................. 76 5.3.1 Trypsin ................................................................................................... 76 5.3.2 Interleukin- 1 ........................................................................................ 77 5.4 NMR Methods ................................................................................................. 77 5.4.1 One Pulse ............................................................................................... 77 5.4.2 Sodium Concentration Calculations ...................................................... 78 5.4.3 Fixed charge density (FCD) calculations...............................................79 5.5 Relaxation time measurements ........................................................................ 79 5.5.1 T1 measurements - Inversion recovery ............................................... 79 5.5.2 T2 measurements - Hahn echo ............................................................ 80 5.5.3 T2fast by varying the dead time .............................................................. 81 5.5.4 T2fast from Linewidths ........................................................................... 82 5.6 Desorption
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