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CALIBRATION OF IRON-MEDIATED MRI RELAXATION BY
MONTE CARLO MODELING
by
Nilesh Ramesh Ghugre
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOMEDICAL ENGINEERING)
May 2008
Copyright 2008 Nilesh Ramesh Ghugre
Object Description
| Title | Calibration of iron-mediated MRI relaxation by Monte Carlo modeling |
| Author | Ghugre, Nilesh Ramesh |
| Author email | nileshghugre@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biomedical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2008-03-13 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-04-15 |
| Advisor (committee chair) |
Wood, John Khoo, Michael |
| Advisor (committee member) |
Singh, Manbir Prakash, Surya Coates, Thomas Nayak, Krishna |
| Abstract | Iron overload is a serious condition for patients with thalassemia major, transfusion-dependent sickle cell anemia and inherited disorders of iron metabolism. Liver biopsy is the prevailing clinical standard for estimation of hepatic iron content; however, it is invasive, painful, expensive, prone to sampling error and provides only indirect information regarding other inaccessible organs (heart, pancreas). As an alternative, MRI is becoming increasingly important in non-invasive quantification of tissue iron, overcoming the drawbacks of traditional techniques. Super-paramagnetic substances such as iron-oxide particles produce magnetic field disturbances that increase MRI relaxivities R1 (1/T1), R2 (1/T2) and R2* (1/T2*), indirectly reflecting tissue iron loading. These relationships vary with iron species and with organ, requiring tissue biopsy for calibration, a critical limitation for inaccessible organs. Although recent work has demonstrated clinically-valid estimates of iron for human liver, the calibration varies with MRI acquisition method forcing recalibration for new MRI methods. There is indication that calibration curves vary with iron chelation history as well. To understand and correct these limitations, a thorough understanding of the underlying biophysics will be of critical importance. Toward this end, a Monte Carlo model-based approach was employed to simulate iron-proton interactions and hence determine iron-induced MRI signal relaxation in tissues.; Liver represented an ideal organ for this purpose since liver biopsy is routinely available, clinically relevant and simple in architecture. Histological analysis was performed on the liver biopsies which formed the basis for generating a realistic 'virtual' iron loaded environment. Predicted relaxivities were well within confidence bounds of published in vivo calibration curves. R2*- iron calibration was primarily governed by magnetic susceptibility of iron deposits. R2- iron calibration was driven by local magnetic landscape generated by the scale and distribution of iron deposits. The study suggested that diffusion-based losses dominate the underlying basis for relaxivity- iron behavior and that inter-molecular exchange mechanisms can be safely neglected. The real power of the model lies in extrapolating relaxivity- iron relationships for new conditions such as higher field strength, different disease type, change in chelation therapy and new MRI sequence without having to recalibrate in large patient populations. A bridge between pathophysiology and intrinsic biophysics will help explain variability seen across the parameter-dependent calibrations, improving accuracy of diagnosis, management and care of patients with iron overload syndromes. |
| Keyword | MRI; thalassemia; iron overload; relaxation; relaxivity; iron; microscopy; liver |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1115 |
| Contributing entity | University of Southern California |
| Rights | Ghugre, Nilesh Ramesh |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Ghugre-20080415 |
| Archival file | uscthesesreloadpub_Volume17/etd-Ghugre-20080415.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Full text | CALIBRATION OF IRON-MEDIATED MRI RELAXATION BY MONTE CARLO MODELING by Nilesh Ramesh Ghugre A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOMEDICAL ENGINEERING) May 2008 Copyright 2008 Nilesh Ramesh Ghugre |
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