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博碩士論文 etd-0526114-015528 詳細資訊
Title page for etd-0526114-015528
論文名稱
Title
Ficoll 70對磁共振造影劑Dotarem的擁擠效應及與其他高分子擁擠劑之比較
The Crowding Effect of Ficoll 70 on Magnetic Resonance Imaging Contrast Agent Dotarem and Comparison with Other Macromolecular Crowders
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
82
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2014-06-17
繳交日期
Date of Submission
2014-06-27
關鍵字
Keywords
MRI、高分子、擁擠效應、造影劑、Ficoll 70
MRI, macromolecular, crowding effect, contrast agent, Ficoll 70
統計
Statistics
本論文已被瀏覽 5664 次,被下載 461
The thesis/dissertation has been browsed 5664 times, has been downloaded 461 times.
中文摘要
由於核磁共振成像(Magnetic Resonance Imaging, MRI)的非侵入性和能提供多方面結構及動態資訊,使其成為臨床醫學診斷、材料科學、心理學及語言學等領域的重要工具。數十年來科學家致力於研究開發多樣化的造影劑,各式造影劑的研究發展使MRI技術更具有選擇性和應用性,促使MRI也成為分子影像學的重要技術。造影劑的效能取決於造影劑分子的化學結構和其與周圍環境分子的交互作用。在一個典型的生物環境系統裡,有許多大型高分子,例如:蛋白質、醣類、核酸、脂質等。這些高分子的存在使細胞呈現一個高度擁擠的環境。本工作以Ficoll 70作為擁擠劑,研究擁擠效應對造影劑鬆弛效能的影響,並與其他擁擠劑(polyethylene glycol-PEG, sodium polyacrylate-NaPA)進行比較。Ficoll 70 是具有網狀結構的聚蔗糖,而PEG 和NaPA則是線性的結構。藉由比較Ficoll 70與PEG以及NaPA的實驗結果有助於了解擁擠劑之分子結構與特性對擁擠效應之影響。
我們採用的MRI造影劑Dotarem是常見的造影劑,具有顺磁性質,可加強MRI的對比度。透過改變擁擠劑及造影劑的濃度,測量NMR光譜、鬆弛及擴散參數來研究高分子擁擠效應對MRI造影劑鬆弛效能產生的影響。
本工作使用液態200 MHz NMR光譜儀測量1H化學位移並比較縱向和橫向的鬆弛速率,研究Dotarem水溶液結構與動態上的資訊。利用固態500 MHz NMR 光譜儀測量擴散係數,了解水分子在擁擠環境中的平移擴散。我們也透過變場變溫鬆弛分散(NMRD)的實驗測量了解水分子在各種磁場下的動態資訊。比較Ficoll 70以及PEG和NaPA,我們發現擁擠劑分子結構對造影劑之鬆弛效能有明顯影響。這些結果也表明,藉由擁擠環境下研究造影劑分子的鬆弛機制,可以增加對MRI影像對比度的微觀機制之確認,避免核磁共振成像解讀上的誤判。
Abstract
Owing to its many advantages such as noninvasiveness and its ability for providing multiple layers of information on structure and dynamics, magnetic resonance imaging (MRI) has become an essential clinical equipment but also a powerful tool for basic research in various fields. By using MRI contrast agents, more specificity and selectivity can be achieved with MRI, which has prompted the development of thousands of MRI contrast agents over the past decades. The performance of the MRI contrast agent depends on their chemical structure and the interaction with the other molecules around them such as water. The basic principle of MRI contrast agents is to increase water relaxation with paramagnetic ions. The performance of an MRI contrast agent depends not only on the structure and dynamics of the compound, but also on the environment it is located. In a typical living system, there are lots of macromolecules such as proteins, lipids, sugars, nucleic acids, ribosomes etc, making cell a highly crowded environment. To obtain insight into the influence of water motions by Dotarem under the crowded conditions, we use three types of crowding agent (Ficoll 70、NaPA、PEG6000). Ficoll 70 (70 kDa) is a synthetic crowding agent and a cross-linked sucrose polymer. NaPA and PEG6000 are linear structural polymers.
We used nuclear magnetic resonance spectroscopy (NMR) to measure the longitudinal relaxation rate (R1), transverse relaxation rate (R2), translational diffusion, MRI and NMRD (Nuclear Magnetic Relaxation Dispersion) under different concentrations of crowders and contrast agent. We have found that macromolecular crowding effect is an important contributing factor that affects the performance of MRI contrast agents. The details of the crowding effect of different crowding agents are compared and discussed. The results demonstrate the significant effect of crowders on the relaxivity of MRI contrast agent and indicate that a molecular level understanding of the relaxtion mechanism of MRI contrast agent in a crowded environment helps establishment of a microscopic picture of MRI contrast generation and prevents mistakes in diagnosis in medical MRI.
目次 Table of Contents
目錄 vi
圖目錄 ix
表目錄 xii
第一章 緒論 1
1.1 前言 1
1.2文獻回顧 3
1.3 研究動機 5
第二章 擁擠與侷限效應 6
2.1擁擠與侷限效應介紹 6
2.2熱力學觀點解釋擁擠和侷限 7
第三章 核磁共振簡介 11
3.1核磁共振基本理論25, 26 11
3.2 NMR鬆弛(Relaxation) 13
3.2.1 T1縱向鬆弛速率(longitudinal relaxation) 14
3.2.2 T2橫向鬆弛(transverse relaxation) 16
3.3擴散實驗 18
3.4 MRI微影像實驗 20
第四章 商用造影劑簡介 24
4.1造影劑分子開發 24
4.2 商用造影劑 24
4.3 順磁分子鬆弛理論38,39 25
4.3.1 內層質子鬆弛機制 40, 41 27
4.3.2 外層質子鬆弛機制 28
4.3.3 內外層水分子間的交換機制 29
4.3.4造影劑影響水鬆弛效能的主要因素 30
4.4 NMRD實驗44 31
第五章 實驗部分 33
5.1 實驗藥品 33
5.1.1 Ficoll 70 33
5.1.2 NaPA ( Polyacrylic acid, sodium salt) 33
5.1.3 PEG (Polyethylene glycol) 34
5.1.4 Dotarem (Gd-DOTA) 34
5.1.5 擁擠劑之選擇 35
5.2 樣品製備 35
5.2.1 擁擠試劑製備 35
5.2.2 Dotarem製備 35
5.2.3 溶劑製備 35
5.3儀器實驗配製 36
5.3.1 鬆弛實驗 36
5.3.2 擴散實驗 36
5.3.3 影像實驗 37
5.3.4 NMRD實驗 37
5.4儀器設備 37
5.5儀器條件 38
第六章 結果與討論 40
6.1不同濃度高分子水溶液1H 一維光譜 40
6.2不同造影劑濃度隨高分子濃度變化水溶液R1測量 45
6.3不同高分子濃度隨造影劑濃度變化水溶液R1測量 47
6.4不同類型高分子水溶液R1測量與比較 50
6.5不同類型高分子水溶液R2測量與比較 51
6.7微影像實驗 56
6.8 NMRD實驗 59
6.9依數性質與擁擠效應 63
第七章 結論 65
參考文獻 66
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