A contrast agent for MRI of calcifications in breast cancer

Thesis (S.M.)--Harvard-MIT Program in Health Sciences and Technology, 2013.

Bibliographic Details
Main Author: Marmurek, Jonathan
Other Authors: Robert E. Lenkinski and Bruce R. Rosen.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2014
Subjects:
Online Access:http://hdl.handle.net/1721.1/83969
_version_ 1811082383357640704
author Marmurek, Jonathan
author2 Robert E. Lenkinski and Bruce R. Rosen.
author_facet Robert E. Lenkinski and Bruce R. Rosen.
Marmurek, Jonathan
author_sort Marmurek, Jonathan
collection MIT
description Thesis (S.M.)--Harvard-MIT Program in Health Sciences and Technology, 2013.
first_indexed 2024-09-23T12:02:13Z
format Thesis
id mit-1721.1/83969
institution Massachusetts Institute of Technology
language eng
last_indexed 2024-09-23T12:02:13Z
publishDate 2014
publisher Massachusetts Institute of Technology
record_format dspace
spelling mit-1721.1/839692019-04-11T10:38:56Z A contrast agent for MRI of calcifications in breast cancer Contrast agent for magnetic resonance imaging of calcifications in breast cancer Marmurek, Jonathan Robert E. Lenkinski and Bruce R. Rosen. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Thesis (S.M.)--Harvard-MIT Program in Health Sciences and Technology, 2013. Vita. Cataloged from PDF version of thesis. Includes bibliographical references (pages 37-39). Clinical x-ray mammography cannot delineate between hydroxyapatite and calcium oxalate, the respective forms of calcification in malignant and benign breast tumors. The water-poor nature of solid calcifications makes them difficult to image by conventional MRI. Recently, ultra-short echo time (UTE) MRI has enabled detection of solid calcified structures, but it is not specific to the underlying chemical composition. This thesis presents a hydroxyapatite-targeted gadolinium contrast agent for UTE MRI of calcification in malignant breast cancer. The hydroxyapatite-targeted contrast agent was synthesized by conjugating a bisphosphonate, pamidronate, to a gadolinium chelate. Binding specificity was tested by UTE MRI of the contrast agent reacted with hydroxyapatite, calcium oxalate, and other calcium-based crystals. The sensitivity of the contrast agent for hydroxyapatite was evaluated by UTE MRI: the lowest detectable concentration of hydroxyapatite-adsorbed contrast was 1 pM. Longitudinal relaxation time measurements were used to estimate the apparent relaxivity of the hydroxyapatite contrast agent to be >1000 s-I/mM. The targeted agent relaxivity is enhanced more than a 100-fold compared to conventional untargeted gadolinium contrast agents due to the restricted rotational motion of the contrast agent upon binding to a solid surface. In-vivo MRI of systemic delivery of the contrast agent was demonstrated in an animal model for breast cancer with hydroxyapatite calcifications. Pre- and post-contrast UTE MRI were acquired with systemic contrast agent injections. Dual-echo UTE subtraction images between short and long echoes showed specific uptake of the contrast agent to the calcifications. The mean signal intensity of the calcified regions enhanced by 200% between pre- and post-contrast images, posing the hydroxyapatite-targeted contrast agent as a clinical diagnostic for distinguishing benign and malignant calcification forms in breast cancer. by Jonathan Marmurek. S.M. 2014-01-14T15:25:45Z 2014-01-14T15:25:45Z 2013 Thesis http://hdl.handle.net/1721.1/83969 863155258 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 45 pages application/pdf Massachusetts Institute of Technology
spellingShingle Harvard--MIT Program in Health Sciences and Technology.
Marmurek, Jonathan
A contrast agent for MRI of calcifications in breast cancer
title A contrast agent for MRI of calcifications in breast cancer
title_full A contrast agent for MRI of calcifications in breast cancer
title_fullStr A contrast agent for MRI of calcifications in breast cancer
title_full_unstemmed A contrast agent for MRI of calcifications in breast cancer
title_short A contrast agent for MRI of calcifications in breast cancer
title_sort contrast agent for mri of calcifications in breast cancer
topic Harvard--MIT Program in Health Sciences and Technology.
url http://hdl.handle.net/1721.1/83969
work_keys_str_mv AT marmurekjonathan acontrastagentformriofcalcificationsinbreastcancer
AT marmurekjonathan contrastagentformagneticresonanceimagingofcalcificationsinbreastcancer
AT marmurekjonathan contrastagentformriofcalcificationsinbreastcancer