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171
60. Esposito BP, Breuer W, Sirankapracha P, Pootrakul P, Hershko C, Cabantchik ZI.
Labile plasma iron in iron overload: redox activity and susceptibility to chelation.
Blood 102 (7): 2670-7, 2003.
61. Faa G, Sciot R, Farci AM, Callea F, Ambu R, Congiu T, van Eyken P, Cappai G,
Marras A, Costa V, et al. Iron concentration and distribution in the newborn liver.
Liver 14 (4): 193-9, 1994.
62. Faa G, Terlizzo M, Gerosa C, Congiu T, Angelucci E. Patterns of iron distribution
in liver cells in beta-thalassemia studied by X-ray microanalysis. Haematologica
87 (5): 479-84, 2002.
63. Fischer R, Engelhardt R. Deferiprone versus desferrioxamine in thalassaemia, and
T2* validation and utility. Lancet 361 (9352): 182-3; author reply 183-4, 2003.
64. Fischer R, Piga A, Harmatz P, Nielsen P. Monitoring long-term efficacy of iron
chelation treatment with biomagnetic liver susceptometry. Ann N Y Acad Sci
1054: 350-7, 2005.
65. Fitchett DH, Coltart DJ, Littler WA, Leyland MJ, Trueman T, Gozzard DI, Peters
TJ. Cardiac involvement in secondary haemochromatosis: a catheter biopsy study
and analysis of myocardium. Cardiovasc Res 14 (12): 719-24, 1980.
66. Ford JC, Wehrli FW. In vivo quantitative characterization of trabecular bone by
NMR interferometry and localized proton spectroscopy. Magn Reson Med 17 (2):
543-51, 1991.
67. Fung EB, Harmatz PR, Lee PD, Milet M, Bellevue R, Jeng MR, Kalinyak KA,
Hudes M, Bhatia S, Vichinsky EP. Increased prevalence of iron-overload
associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J
Haematol 135 (4): 574-82, 2006.
68. Galanello R, Kattamis A, Piga A, Fischer R, Leoni G, Ladis V, Voi V, Lund U,
Tricta F. A prospective randomized controlled trial on the safety and efficacy of
alternating deferoxamine and deferiprone in the treatment of iron overload in
patients with thalassemia. Haematologica 91 (9): 1241-3, 2006.
69. Gandon Y, Olivie D, Guyader D, Aube C, Oberti F, Sebille V, Deugnier Y. Non-invasive
assessment of hepatic iron stores by MRI. Lancet 363 (9406): 357-62,
2004.
70. Ganz T. Hepcidin and its role in regulating systemic iron metabolism.
Hematology Am Soc Hematol Educ Program: 29-35, 507, 2006.
71. Ganz T. Hepcidin in iron metabolism. Curr Opin Hematol 11 (4): 251-4, 2004.
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 C.K. |
| Advisor (committee member) |
Singh, Manbir Prakash, Surya Coates, Thomas Nayak, Krishna S. |
| 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 | cisadmin@dots.usc.edu |
| Filename | etd-Ghugre-20080415 |
| Archival file | uscthesesreloadpub_Volume17/etd-Ghugre-20080415.pdf |
Description
| Title | Page 187 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | 171 60. Esposito BP, Breuer W, Sirankapracha P, Pootrakul P, Hershko C, Cabantchik ZI. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood 102 (7): 2670-7, 2003. 61. Faa G, Sciot R, Farci AM, Callea F, Ambu R, Congiu T, van Eyken P, Cappai G, Marras A, Costa V, et al. Iron concentration and distribution in the newborn liver. Liver 14 (4): 193-9, 1994. 62. Faa G, Terlizzo M, Gerosa C, Congiu T, Angelucci E. Patterns of iron distribution in liver cells in beta-thalassemia studied by X-ray microanalysis. Haematologica 87 (5): 479-84, 2002. 63. Fischer R, Engelhardt R. Deferiprone versus desferrioxamine in thalassaemia, and T2* validation and utility. Lancet 361 (9352): 182-3; author reply 183-4, 2003. 64. Fischer R, Piga A, Harmatz P, Nielsen P. Monitoring long-term efficacy of iron chelation treatment with biomagnetic liver susceptometry. Ann N Y Acad Sci 1054: 350-7, 2005. 65. Fitchett DH, Coltart DJ, Littler WA, Leyland MJ, Trueman T, Gozzard DI, Peters TJ. Cardiac involvement in secondary haemochromatosis: a catheter biopsy study and analysis of myocardium. Cardiovasc Res 14 (12): 719-24, 1980. 66. Ford JC, Wehrli FW. In vivo quantitative characterization of trabecular bone by NMR interferometry and localized proton spectroscopy. Magn Reson Med 17 (2): 543-51, 1991. 67. Fung EB, Harmatz PR, Lee PD, Milet M, Bellevue R, Jeng MR, Kalinyak KA, Hudes M, Bhatia S, Vichinsky EP. Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J Haematol 135 (4): 574-82, 2006. 68. Galanello R, Kattamis A, Piga A, Fischer R, Leoni G, Ladis V, Voi V, Lund U, Tricta F. A prospective randomized controlled trial on the safety and efficacy of alternating deferoxamine and deferiprone in the treatment of iron overload in patients with thalassemia. Haematologica 91 (9): 1241-3, 2006. 69. Gandon Y, Olivie D, Guyader D, Aube C, Oberti F, Sebille V, Deugnier Y. Non-invasive assessment of hepatic iron stores by MRI. Lancet 363 (9406): 357-62, 2004. 70. Ganz T. Hepcidin and its role in regulating systemic iron metabolism. Hematology Am Soc Hematol Educ Program: 29-35, 507, 2006. 71. Ganz T. Hepcidin in iron metabolism. Curr Opin Hematol 11 (4): 251-4, 2004. |
