聚焦式超音波應用於帕金森氏症動物模式之診斷治療整合前瞻研究---子計畫四：帕金森氏症動物模型之核磁共振影像對比劑/藥物模型開發

Abstract

本子計畫將發展具有提供清晰影像對比與藥物釋放功能之新型磁共振顯影劑(Contrast agent)。該新型磁振顯影劑的設計需考慮生物相容性(Biocompatibility)並造成組織較強的 T2 弛緩(Relaxation)，因此選擇超順磁奈米氧化鐵(Iron oxide nanoparticles)符合本研究的 需求。首先，以高分子材料聚乙烯乙二醇 (Polyethylene glycol, PEG) 包覆超順磁奈米氧 化鐵以增加生物相容性；此外，超順磁奈米氧化鐵 (Ultra-small paramagnetic iron oxide ,USPIO)外包覆PEG 可進行表面修飾以便攜帶帕金森氏症或是其他腦病變之治療 性藥物，最後由血液循環運送至特定腦區給予投藥。在本次整合型總計畫中，預計開發 造影定位導引之聚焦式超音波腦部治療系統 (Image-guided focused ultrasound brain therapy system)用於帕金森氏症動物模型之熱燒灼治療。透過本子計畫所開發超順磁奈 米氧化鐵將有助於提高磁振灌流造影訊號雜訊比(Contrast to noise ratios, CNRs)以輔助 聚焦式超音波熱燒灼治療時磁共振造影定位病灶；聚焦式超音波腦部治療系統可暫時提 高特定腦區之血腦屏障(Blood-brain barrier, BBB)對大分子的通透性，有利於子計畫所設 計攜帶型藥物之超順磁奈米氧化鐵通過血腦屏障到達病灶，進而提供治療與定位追蹤。 本子研究所提出的構想為極具潛力用以評估帕金森氏症或其他腦病變病程與治療的方 法極具研究與臨床上的價值。

The aim of this sub-project is to develop a novel magnetic resonance (MR) contrast agent with creating significant image contrast and drug delivery in vivo. Due to its biocompatibility and strong effects on T2(*) relaxation, iron oxide nanoparticles appear to be the contrast agent of choice, and self-assembled monolayer ultra-small paramagnetic iron oxide (USPIO) nanoparticles are coated with polyethylene glycol (PEG). Furthermore the USPIO provide an active functional group capable of conjugating with therapeutic agent. In the main project, the image-guided focused ultrasound brain therapy system for Parkinson』s disease in animal model will be established. It can conduct localized neural tissue thermal ablation. USPIO can increase contrast-to-noise ratios (CNRs) over the perfusion MR imaging that leads to the evaluation of location and distribution of thermal ablation in the brain. The focused ultrasound brain therapy system also can be used to increase the permeability of blood-brain barrier (BBB) and USPIO labeled drug can have the better penetration across the BBB. It is a potential method of in vivo evaluating the progress of Parkinson』s disease and treatment strategies.