核磁共振造影技術的應用在近代醫學上的進步與發展，現在已經成為在對於檢測腦部、脊椎、肌肉與骨骼等部位最具代表性也最受歡迎的影像處理方式，核磁共振造影主要是基於各組織中所含有的水中的氫原子在NMR 中所測量的訊號，而這樣的訊號可以根據座標軸而分解成兩個不同方向的分量，( I ) longitudinal relaxation ( T1 ) 與(Ⅱ)transverse relaxation ( T2 )，這兩個訊號的機制不同且不會互相影響。
　　一般使用以T1 機制為主的核磁共振造影顯影劑，以具高順磁性質的離子為主，最普遍的是以小分子的有機螯合劑與釓離子反應而能穩定存在的有機金屬錯合物。
　　粒徑在3 到10 奈米左右的磁性奈米粒子也可以將其發展應用在核磁共振造影顯影劑上，在大部分的情形中，這些磁性粒子是以T2的機制為主來影響影像的結果。
　　因此在本文中我們期望發展一種新的顯影劑能同時具有T1 與 T2 relaxation 的效果。使用四氧化三鐵奈米粒子為核，在其表面修飾TETA 的分子，TETA 在這裡是扮演螯合劑的角色與釓離子進行錯合，四氧化三鐵奈米粒子的表面存在有許多amino groups，而TETA具有carboxylic groups，我們利用EDC 進行amide bond 生成，用來連
結四氧化三鐵奈米粒子與TETA 分子，在實驗過程中我們根據不同莫耳比例的EDC、TETA 及四氧化三鐵奈米粒子依序配置共十五組的樣品，這樣不同比例的調控會造成TETA 在連結到四氧化三鐵奈米粒子表面時的結構會不同，而不同的結構會影響到TETA 與釓離子錯合的能力與數量，也會造成不同的T1 與T2 值。利用NMR 來對這十五組樣品進行T1 與T2 值的量測，根據測量出的結果，在T1 relaxation time的部分，排序第六組樣品(實驗中的比例Fe3O4 : TETA : EDC = 1 :500 : 500 ×2 )的結果與市售的顯影劑Gd-DPTA 相近，而在T2 relaxation time 的部分，排序第七組樣品( Fe3O4 : TETA : EDC = 1 :1000 : 1000 ×2 )的結果則優於市售的磁性粒子( USPIO )顯影劑，因此針對這兩組進行細胞毒性測試，而最後的結果細胞的存活百分率都可達百分之八十以上。

　　Magnetic resonance imaging ( MRI ) applications have steadily widened over the past decade.Currently, it is the preferred cross-sectional　imaging modality in most diseases of the brain,spine and musculoskeletal system. MRI is based on NMR signal of protons from water in tissues, membrane lipids, proteins, etc. These signals can be divided into two different, independent processes: ( I ) longitudinal relaxation ( T1 ) and (Ⅱ) transverse relaxation ( T2 ).
　　The generation of the MR contrast agents consists of T1-agents, high　spin paramagnetic ions, usually Gd3+ in very stable chelate form obtained through complexation by low molecular weight chelating molecules.
　　 Magnetic nanoparticles, with a size generally between 3 and 10 nm, have also been developed as contrast agents for both standard and functional MR imaging. In most situations, they are used for their significant capacity to produce predominantly T2-relaxation effects, which result in signal reduction on T2-weighted images.
　　 In the study, we have arranged to develop a contrast agent consisting of both T1 and T2 relaxation effects. Fe3O4 magnetic nanoparticles were chosen as core to modify with TETA. Herein, TETA serves as chelating　agent to complex with Gd3+. Due to the presence of the amino groups on the surface of the Fe3O4 nanoparticles and the carboxylic groups of the TETA, EDC was utilized to form amide bonds between Fe3O4 nanoparticles and TETA. Fifteen sample groups were classified by varying the molar ratios of EDC, TETA, and Fe3O4 particles. It is proposed that TETA could be attached on Fe3O4 surface with different　structural configuration. The different TETA conformation on Fe3O4 surface would couple with different amount of Gd3+ cations resulting in distinct T1 and T2 effects. Both T1 and T2 relaxation time were measured by NMR. Based on the resulting values, the T1 relaxation time of the sixth sample with molar ratio Fe3O4 : TETA : EDC = 1 : 500 : 500 ×2 is comparable to the available Gd-DPTA contrast agent and the seventh sample with molar ratio Fe3O4 : TETA : EDC = 1 : 1000 : 1000 ×2　surpasses commercial magnetic particles were USPIO in the T2 relaxation time. Furthermore, both sixth seventh performed cytotoxic and exhibited over 80% viability.

參考文獻
1. Lehn J. M. Supramolecular Ensembles；VCH：New York, 1995.
2. Turner P., History of Photography；Exeter：New York, 1987.
3. Faraday M., Philo. Trans. R. Soc.1875,147,145
4. 伊邦躍，奈米時代，五南出版社，2002.
5. 張立德，奈米時代，五南出版社，2002.
6. Zorman B., Ramakrishna M. V., and Friesner R. A.，J. Phys.
Chem. 1995,99, 7649.
7. Robert J. H., “ Introduction to Modern Colloid Science ” 1993.
8. Kruyt H. R., “ Colloid Science ” , Elsevier Science Publishing
Company INC , 1952.
9. Robert J. G., Robert R. and Stromberg “ Surface and Colloid Science
Vol.11 ” , published by Plenum Press , New York and London.
10. Schimid G., “ Clusters and Colloids ” : From Theory to Application ,
VCH：New York , 1994.
11. Weaver J. C. and Chizmadzhev Y. A., Bioelectrochemistry and
Bioenergetics, 1996, 41, 135.
12. Link S., Wang Z. L. and El-Sayed M. A., J. Phys. Chem. B, 1999,
13. Mulvaney P., Langmuir, 1996, 12, 788.
14. Giersig M. and Mulvaney P., Langmuir, 1993, 9, 3408.
15. Giersig M. and Mulvaney P., J. Phys. Chem., 1993, 97, 6334.
16. Kelly K. L., Coronado E., Zhao L. L. and Schatz G. C., J. Phys.
Chem. B, 2003, 107, 668.
17. Kittel C., “ Introduction to Solid State Physics ”, 7th edition, Wiley,
New York, 1996.
18. Kreibig U. and Vollmer M., “ Optical Properties of Metal Cluster ”,
Vol. 25, Springer, Berlin, 1995.
19. 奈米化裝置概要說明，S. G. Engineering Co.，Ltd.
20. Faraday M., Philo. Trans. R. Soc. London 1857，147，145-181
21. 張志焜，崔作林，納米技術與納米材料，北京國防工業出版社，2000
22. Schmid，G. “ Cluster and Colloids ”；VCH，Weinheim，1994
23. IEK 黃文魁博士研討會資料，2003.8.16
24. 微波電漿化學氣相沉積法成長奈米級類鑽膜尖狀結構/胡瑞凱/黃
振昌/國立清華大學材料科學工程研究所/碩士論文
25. 黃國政/國立清華大學/碩士論文，2001
26. Mendonca-Dias M. H., Gaggelli E. and Lauterbur P. C., Semin Nucl
Med, 1983, 13, 364.
27. Caille J. M., Lemanceau B. and Bonnemain B., AJNR Am J
Neuroradiol, 1983, 4, 1041.
28. Brasch R. C., A subject review. Radiology, 1983, 147, 781.
29. Brasch R. C. et al., Radiology, 1983, 147, 773.
30. Brasch R. C., Nitecki D. E. and Brant-Zawadzki M. et al., AJNR,
1983, 4, 1035.
31. Brasch R. C. et al., AJR Am J Roentgenol, 1983, 141, 1019.
32. Brasch R. C., Ehman and Wesbey G. E., Radiology, 1983, 149, 99.
33. Brasch R. C., Weinmann H. J. and Wesbey G. E., AJR Am J
Roentgenol, 1984, 142, 625.
34. Frank J. A., House W. V. and Lauterbur P. C., Clin. Res., 1976, 24,2174.
35. Zanelli G. D. and Kaelin A. C., Br J Radiol, 1981, 54, 403.
36. Edelstein W. A., Bottomley P. A., Hart H. R. and Smith L. S., J
Comput Assist Tomogr, 1983, 7, 391.
37. Schmiedl U., Ogan M. D., Moseley M. E. and Brasch R. C., AJR Am
J Roentgenol, 1986, 147, 1263.
38. Kornguth S. E. et al., J Neurosurg, 1987, 66, 898.
39. Unger E. C. et al., Invest Radiol, 1985, 20, 693.
40. Runge V. M. et al., AJR Am J Roentgenol, 1983, 141, 943.
41. Wesbey G. E. et al., Radiology, 1983, 149, 175.
42. Runge V. M. et al., Radiology, 1984, 152, 123.
43. Cory D. A., Schwartzentruber D. J. and Mock B. H., Magn Reson
Imaging, 1987, 5, 65.
44. Bucciolini M., Ciraolo L. and Renzi R., Med Phys, 1986, 13, 298.
45. Runge V. M. et al., Radiology, 1984, 153, 171.
46. Weinmann H. J., Brasch R. C., Press W. R. and Wesbey G. E., AJR
Am J Roentgenol, 1984, 142, 619.
47. Carr D. H., Brown J., Leung A. W. and Pennock J. M., J Comput
Assist Tomogr, 1984, 8, 385.
48. Carr D. H. et al., Lancet, 1984, 1, 484.
49. Lauffer R. B. et al., J Comput Assist Tomogr, 1985, 9, 431.
50. Unger E. C. et al., Invest Radiol, 1985, 20, 693.
51. Jackson L. S., Nelson J. A., Case T. A. and Burnham B. F., Invest
Radiol, 1985, 20, 226.
52. Fiel R. J. et al., Magn Reson Imaging, 1987, 5, 149.
53. Mattrey R. F., Long D. M., Multer F., Mitten R. and Higgins C. B.,
Radiology, 1982, 145, 755.
54. Mattrey R. F. et al., AJR Am J Roentgenol, 1987, 148, 1259.