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  • 學位論文

功能性核磁共振分子影像在肺外結核診斷之應用

Molecular imaging by functional MRI in detection of extrapulmonary tuberculosis

指導教授 : 賴文福

摘要


中文摘要 結核病是目前全世界非常重要的傳染疾病,每一年造成數百萬人感染,台灣每一年也有超過一萬三千個通報病例,是台灣最嚴重的傳染病。結核病和愛滋病的共同感染,更造成這個疾病在診斷和治療上面的困難。結核病可以發生在人體任何器官或組織,如淋巴結、腦膜、胸膜、腎臟、骨骼、皮膚、消化道等。在臺灣比較常見的肺外結核是淋巴結核及骨結核。雖然肺外結核的發生率比肺結核來得低(約佔4.3%,2009疾管局資料),但是肺外結核診斷難度較高。一方面是因為病變處的細菌較少,較難獲得細菌學證據;另一方面則因疾病部位難評估,常須手術獲取病灶標本,且目前並無適當之影像學檢查來輔助診斷。因此臨床上肺外結核,經常造成診斷上的困難,以至於延遲診斷而加速傳播。隨著分子影像在核磁共振上應用的日益發展,目前已發展出非常好的對比顯影劑,如超順磁氧化鐵奈米粒子。不僅可以被動的增強組織對比,更可以結合抗體等生物分子,形成分子影像探針,達到主動偵測疾病的目的。我們利用超順磁氧化鐵奈米粒子,和結核菌抗體形成一分子探針,從老鼠的靜脈注入以後,在核磁共振的T2影像下,有高倍的影像增強現象,可以清楚的診斷出老鼠皮下的結核感染組織。此種分子影像探針,可做為將來進一步應用在人體肺外結核的早期診斷。

並列摘要


Abstract Tuberculosis is an important infectious disease all over the world. Taiwan is also an endemic area with more than 13,000 patients newly diagnosed annually. Although the lungs are the most common organs infected by Mycobacterium tuberculosis, tuberculosis can involve any organ or tissue in the human body including the lymph nodes, meninges, pleura, kidney, bone, skin, and intestinal tracts. The incidence rate of extrapulmonary tuberculosis is lower than pulmonary tuberculosis (4.3% vs 95.7%, Taiwan CDC 2009 data). However, there are still some obstacles for early diagnosis in extrapulmonary tuberculosis such as fewer bacteria in infected sites, needing surgical biopsy for proof of MTB infection, and lack of effective diagnostic imaging tools. With the era of rapid development and progress in molecular imaging, an innovatively-designed probe consisting of super-paramagnetic iron oxide (SPIO) nanoparticles conjugated with Mycobacteria tuberculosis (MTB) surface antibody (TBsAb-nanoparticles) can be used to target Mycobacteria antigens, hence providing a new possibility for ultrasensitive detection of extrapulmonary tuberculosis in animal models. We used TBsAb-nanoparticles as a diagnostic probe, which was administered to mice bearing BCG infection in subcutaneous tissue by an intravenous injection. The infected site was detected in T2-weighted magnetic resonance images as a significant reduction in signal intensity compared to the opposite site of PBS injection. The results suggest that TBsAb-nanoparticles constitute a new non-invasive technology for the diagnosis of extrapulmonary tuberculosis.

參考文獻


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