通常於神經外科手術前會先拍攝病患腦部的醫學影像，並於手術前先透過醫學影像確立目標點與進行手術規劃，然而在手術的過程中，腦組織會因開顱或器械穿刺導致腦脊髓液流失進而產生形變，由於無法即時監測手術器械在腦內組織的位置，進而導致定位失準，因此發展術中磁振造影導引為目前神經外科的重要研究之一。本研究欲發展大腦假體以驗證術中磁振造影的精準度，目標為與豬腦機械性質相近的假體，且能在磁振造影中使腫瘤或病灶假體與正常腦質假體呈現不同顯像，以應用於磁振造影相容手術機器人檢驗及術中磁振造影手術訓練之用。
首先將大腦假體簡化為半球形，以洋菜膠體模擬腦質，並於表面覆蓋一層聚二甲基矽氧烷薄膜模擬腦膜。以3D列印製作大腦假體模具，並由靜態壓縮試驗與鬆弛試驗分別測試標準試件與有膜大腦假體與豬腦之彈性及黏彈性質。實驗結果顯示0.4%與0.6%洋菜濃度之有膜大腦假體與豬腦之生物力學性質最接近，然而0.4%洋菜濃度的大腦假體由於剛性較差，考慮到黏彈性質的相似性與加工性，發現0.6%洋菜濃度的有膜大腦假體為最適合假體材料。其次利用3D列印製作腫瘤定位模具，並以此製作含有腫瘤的大腦假體，再添加不同濃度的硫酸銅，改變其磁振造影的T1鬆弛時間。實驗結果顯示在磁振造影環境中可顯示不同顏色。結論，本研究發展之大腦假體，有可能應用於磁振造影相容立體定位手術機器人的檢驗以及大腦無框立體定位手術的術前規劃與教學。

During brain surgery, patient’s brain will undergo deformation due to craniotomy or cerebrospinal fluid leakage caused by puncture through meninges. Usually, the medical images used for surgical planning were taken before the surgery. Whereas the tumors or surgical targets will move away from its original position, lacking information of instantaneous position of needle tip in brain tissue will lead to low accuracy. Therefore, developing intraoperative MRI is one of the research goals for neurosurgeries nowadays. The main goal of this study is to develop phantoms for validating the accuracy and precision of intraoperative MRI. The requirements of the phantoms are twofold: the mechanical properties imitate those of the brain and with surgical target such as tumor that are distinguishable from healthy brain tissues when MR images are acquired.
The brain phantom was simplified to hemisphere and made from water-based agar gel doped with copper sulfate and covered by polydimethylsiloxane (PDMS). The molds of brain phantom were made by a 3D printer, and the elastic and viscoelastic properties of phantoms were tested by using quasistatic compression test and relaxation test. The results show that phantoms made from 0.4% and 0.6% agar and covered with PDMS are most similar to swine brain biomechanically. Considering the manufacturability, brain phantom made from 0.6% agar and covered with PDMS is suggested for the best design for brain phantom. Next, cerebrums phantoms embedded with tumor phantoms were made using this formula and with the aid of a 3D printed tumor positioning mold. MRI evaluation of the phantoms were performed. The results indicate T1 relaxation time of tumor phantoms can be changed by doping different concentrations of copper sulfate, leading to tumor phantoms with gray level different to the cerebrum phantoms. In conclusion, brain phantoms that have mechanical properties similar to swine brains and tumor phantoms distinguishable from cerebrum phantoms in MRI were developed. The phantom may be used to validate accuracy of MRI-guided surgical robots, preoperative planning, and surgical training related to intraoperative MRI.

[1] K. H. Yang, H. Mao, C. Wagner, F. Zhu, C. C. Chou, and A. I. King, "Modeling of the Brain for Injury Prevention," in Neural Tissue Biomechanics, L. E. Bilston Ed. Berlin, Heidelberg: Springer Berlin Heidelberg, pp. 69-120, 2011.
[2] K. Miller and K. Chinzei, "Constitutive Modelling of Brain Tissue: Experiment and Theory," Journal of Biomechanics, vol. 30, no. 11, pp. 1115-1121, 1997.
[3] K. Miller, "Constitutive Model of Brain Tissue Suitable for Finite Element Analysis of Surgical Procedures," Journal of Biomechanics, vol. 32, no. 5, pp. 531-537, 1999.
[4] K. Miller, K. Chinzei, G. Orssengo, and P. Bednarz, "Mechanical Properties of Brain Tissue in-vivo: Experiment and Computer Simulation," Journal of Biomechanics, vol. 33, no. 11, pp. 1369-1376, 2000.
[5] K. Miller and K. Chinzei, "Mechanical Properties of Brain Tissue in Tension," Journal of Biomechanics, vol. 35, no. 4, pp. 483-490, 2002.
[6] A. Gefen and S. S. Margulies, "Are in vivo and in situ Brain Tissues Mechanically Similar?," Journal of Biomechanics, vol. 37, no. 9, pp. 1339-1352, 2004.
[7] P. Aimedieu and R. Grebe, "Tensile Strength of Cranial Pia Mater: Preliminary Results," Journal of Neurosurgery, vol. 100, no. 1, pp. 111-114, 2004.
[8] X. Jin, J. B. Lee, L. Y. Leung, L. Zhang, K. H. Yang, and A. I. King, "Biomechanical Response of the Bovine Pia-arachnoid Complex to Tensile Loading at Varying Strain-rates," Stapp Car Crash Journal, vol. 50, pp. 637-649, 2006.
[9] X. Jin, C. Ma, L. Zhang, K. H. Yang, and A. I. King, "Biomechanical Response of the Bovine Pia-Arachnoid Complex to Normal Traction Loading at Varying Strain Rates," Stapp Car Crash Journal, vol. 51, pp. 115-126, 2007.
[10] X. Jin, K. H. Yang, and A. I. King, "Mechanical Properties of Bovine Pia–arachnoid Complex in Shear," Journal of Biomechanics, vol. 44, no. 3, pp. 467-474, 2011.
[11] X. Jin, H. Mao, K. H. Yang, and A. I. King, "Constitutive Modeling of Pia–Arachnoid Complex," Annals of Biomedical Engineering, vol. 42, no. 4, pp. 812-821, 2014.
[12] R. H. Hashemi, W. G. B. Jr., and C. J. Lisanti, MRI: the Basics, 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2010.
[13] 高材, 林康平, 林峰輝, 陳家進, 生物醫學工程導論. 臺中市: 滄海圖書, 2008.
[14] S. Pieper, M. Halle, and R. Kikinis, "3D Slicer," in 2004 2nd IEEE International Symposium on Biomedical Imaging: Nano to Macro (IEEE Cat No. 04EX821), vol. 1, Arlington, VA, USA, pp. 632-635, 2004.
[15] A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, "3D Slicer as an Image Computing Platform for the Quantitative Imaging Network," Magnetic Resonance Imaging, vol. 30, no. 9, pp. 1323-1341, 2012.
[16] J. R. Ryan, T. Chen, P. Nakaji, D. H. Frakes, and F. Gonzalez, "Ventriculostomy Simulation Using Patient-Specific Ventricular Anatomy, 3D Printing, and Hydrogel Casting," World Neurosurgery, vol. 84, no. 5, pp. 1333-1339, 2015.
[17] B. L. Tai, D. Rooney, F. Stephenson, P.-S. Liao, O. Sagher, A. J. Shih, and L. E. Savastano, "Development of a 3D-printed External Ventricular Drain Placement Simulator: Technical Note," vol. 123, no. 4, pp. 1070-1076, 2015.
[18] C. C. Ploch, C. S. S. A. Mansi, J. Jayamohan, and E. Kuhl, "Using 3D Printing to Create Personalized Brain Models for Neurosurgical Training and Preoperative Planning," World Neurosurgery, vol. 90, pp. 668-674, 2016.
[19] E. L. Madsen and G. D. Fullerton, "Prospective Tissue-mimicking Materials for Use in NMR Imaging Phantoms," Magnetic Resonance Imaging, vol. 1, no. 3, pp. 135-141, 1982.
[20] I. Mano, H. Goshima, M. Nambu, and M. Iio, "New Polyvinyl Alcohol Gel Material for MRI Phantoms," Magnetic Resonance in Medicine, vol. 3, no. 6, pp. 921-926, 1986.
[21] P. Brzozowski, K. I. Penev, F. M. Martinez, T. J. Scholl, and K. Mequanint, "Gellan Gum-based Gels with Tunable Relaxation Properties for MRI Phantoms," Magnetic Resonance Imaging, vol. 57, pp. 40-49, 2019.
[22] A. Hellerbach, V. Schuster, A. Jansen, and J. Sommer, "MRI Phantoms - Are There Alternatives to Agar?," PloS one, vol. 8, no. 8, p. e70343, 2013.
[23] M. D. Mitchell, H. L. Kundel, L. Axel, and P. M. Joseph, "Agarose as a Tissue Equivalent Phantom Material for NMR Imaging," Magnetic Resonance Imaging, vol. 4, no. 3, pp. 263-266, 1986.
[24] K. A. Kraft, P. P. Fatouros, G. D. Clarke, and P. R. S. Kishore, "An MRI Phantom Material for Quantitative Relaxometry," Magnetic Resonance in Medicine, vol. 5, no. 6, pp. 555-562, 1987.
[25] J. C. Blechinger, E. L. Madsen, and G. R. Frank, "Tissue-mimicking Gelatin–agar Gels for Use in Magnetic Resonance Imaging Phantoms," Medical Physics, vol. 15, no. 4, pp. 629-636, 1988.
[26] F. A. Howe, "Relaxation Times in Paramagnetically Doped Agarose Gels as a Function of Temperature and Ion Concentration," Magnetic Resonance Imaging, vol. 6, no. 3, pp. 263-270, 1988.
[27] M. Bucciolini, L. Ciraolo, and B. Lehmann, "Simulation of Biologic Tissues by Using Agar Gels at Magnetic Resonance Imaging," Acta Radiologica, vol. 30, no. 6, pp. 667-669, 1989.
[28] J. O. Christoffersson, L. E. Olsson, and S. Sjöberg, "Nickel-Doped Agarose Gel Phantoms in MR Imaging," Acta Radiologica, vol. 32, no. 5, pp. 426-431, 1991.
[29] V. Horsley and R. H. Clarke, "The Structure and Functions of the Cerebellum Examined by a New Method," Brain, vol. 31, no. 1, pp. 45-124, 1908.
[30] E. A. Spiegel, H. T. Wycis, M. Marks, and A. J. Lee, "Stereotaxic Apparatus for Operations on the Human Brain," Science, vol. 106, no. 2754, pp. 349-350, 1947.
[31] G. N. Hounsfield, "Computerized Transverse Axial Scanning (Tomography): Part 1. Description of System," The British Journal of Radiology, vol. 46, no. 552, pp. 1016-1022, 1973.
[32] R. Damadian, "Tumor Detection by Nuclear Magnetic Resonance," Science, vol. 171, no. 3976, pp. 1151-1153, 1971.
[33] L. Leksell and B. Jernberg, "Stereotaxis and Tomography a Technical Note," Acta Neurochirurgica, vol. 52, no. 1, pp. 1-7, 1980.
[34] G. Eggers, J. Mühling, and R. Marmulla, "Image-to-patient Registration Techniques in Head Surgery," International Journal of Oral and Maxillofacial Surgery, vol. 35, no. 12, pp. 1081-1095, 2006.
[35] Y. Lu, C. Yeung, A. Radmanesh, R. Wiemann, P. M. Black, and A. J. Golby, "Comparative Effectiveness of Frame-based, Frameless and Intraoperative MRI Guided Brain Biopsy Techniques," World Neurosurgery, vol. 83, no. 3, pp. 261-268, 2015.
[36] H. M. Shao, J. Y. Chen, T. K. Truong, I. S. Reed, and Y. S. Kwoh, "A New CT-Aided Robotic Stereotaxis System," Proc Annu Symp Comput Appl Med Care, pp. 668-672, 1985.
[37] D. Glauser, H. Fankhauser, M. Epitaux, J.-L. Hefti, and A. Jaccottet, "Neurosurgical Robot Minerva: First Results and Current Developments," Journal of Image Guided Surgery, vol. 1, no. 5, pp. 266-272, 1995.
[38] A. L. Goldson, "Preliminary Clinical Experience with Intraoperative Radiotherapy," J Natl Med Assoc, vol. 70, no. 7, pp. 493-495, 1978.
[39] G. R. Sutherland, P. B. McBeth, and D. F. Louw, "NeuroArm: an MR Compatible Robot for Microsurgery," International Congress Series, vol. 1256, pp. 504-508, 2003.
[40] A. E. Sloan, M. S. Ahluwalia, J. Valerio-Pascua, S. Manjila, M. G. Torchia, S. E. Jones, J. L. Sunshine, M. Phillips, M. A. Griswold, M. Clampitt, C. Brewer, J. Jochum, M. V. McGraw, D. Diorio, G. Ditz, and G. H. Barnett, "Results of the NeuroBlate System First-in-humans Phase I Clinical Trial for Recurrent Glioblastoma," Journal of Neurosurgery, vol. 118, no. 6, pp. 1202-1219, 2013.
[41] P. A. Starr, A. J. Martin, J. L. Ostrem, P. Talke, N. Levesque, and P. S. Larson, "Subthalamic Nucleus Deep Brain Stimulator Placement Using High-field Interventional Magnetic Resonance Imaging and a Skull-mounted Aiming Device: Technique and Application Accuracy," Journal of Neurosurgery, vol. 112, no. 3, pp. 479-490, 2010.
[42] P. A. Starr, L. C. Markun, P. S. Larson, M. M. Volz, A. J. Martin, and J. L. Ostrem, "Interventional MRI–guided Deep Brain Stimulation in Pediatric Dystonia: First Experience with the ClearPoint System," Journal of Neurosurgery, vol. 14, no. 4, pp. 400-408, 2014.
[43] 何炳林, "磁振造影相容之神經外科用立體定位手術機器人之發展," 碩士論文, 國立成功大學機械工程學系, 臺灣臺南市, 2016.
[44] 陳煌霖, "磁振造影相容之神經外科手術用五軸立體定位機器系統研究," 碩士論文, 國立成功大學機械工程學系, 臺灣臺南市, 2018.
[45] 彭郁濃, "術中核磁共振影像導引立體定位手術機器人," 碩士論文, 國立成功大學機械工程學系, 臺灣臺南市, 2019.
[46] A. Waltregny, V. Petrov, and J. Brotchi, "Serial Stereotaxic Biopsies," in Advances in Stereotactic and Functional Neurosurgery, vol. 21, pp. 221-226, Vienna: Springer, 1974.
[47] D. A. Bosch, "Indications for Stereotactic Biopsy in Brain Tumours," Acta Neurochirurgica, vol. 54, no. 3, pp. 167-179, 1980.
[48] M. Bernstein and A. G. Parrent, "Complications of CT-guided Stereotactic Biopsy of Intra-axial Brain Lesions," Journal of Neurosurgery, vol. 81, no. 2, pp. 165-168, 1994.
[49] F. Pervin and W. W. Chen, "Effect of Inter-species, Gender, and Breeding on the Mechanical Behavior of Brain Tissue," NeuroImage, vol. 54, pp. S98-S102, 2011.
[50] M. S. Conrad, R. N. Dilger, and R. W. Johnson, "Brain Growth of the Domestic Pig (Sus scrofa) from 2 to 24 Weeks of Age: a Longitudinal MRI Study," Developmental neuroscience, vol. 34, no. 4, pp. 291–298, 2012.
[51] Y. C. Fung, Biomechanics: Mechanical Properties of Living Tissues, 2nd ed. Springer, New York, 1993.
[52] E. Dintwa, E. Tijskens, and H. Ramon, "On the Accuracy of the Hertz Model to Describe the Normal Contact of Soft Elastic Spheres," Granular Matter, vol. 10, no. 3, pp. 209-221, 2008.
[53] H. K. P. Neubert, "A Simple Model Representing Internal Damping in Solid Materials," Aeronautical Quarterly, vol. 14, no. 2, pp. 187-210, 1963.
[54] 高御豪, "紫杉醇藥物動力學對背根神經節神經元形態與黏彈性力學之影響," 碩士論文, 國立成功大學機械工程學系, 臺灣臺南市, 2019.
[55] A. Altermatt, F. Santini, X. Deligianni, S. Magon, T. Sprenger, L. Kappos, P. Cattin, J. Wuerfel, and L. Gaetano, "Design and Construction of an Innovative Brain Phantom Prototype for MRI," Magnetic Resonance in Medicine, vol. 81, no. 2, pp. 1165-1171, 2019.
[56] A. Boschetto, L. Bottini, and F. Veniali, "Finishing of Fused Deposition Modeling Parts by CNC Machining," Robotics and Computer-Integrated Manufacturing, vol. 41, pp. 92-101, 2016.
[57] A. Lalehpour and A. Barari, "Post Processing for Fused Deposition Modeling Parts with Acetone Vapour Bath," IFAC-PapersOnLine, vol. 49, no. 31, pp. 42-48, 2016.
[58] A. P. Valerga, M. Batista, S. R. Fernandez-Vidal, and A. J. Gamez, "Impact of Chemical Post-Processing in Fused Deposition Modelling (FDM) on Polylactic Acid (PLA) Surface Quality and Structure," Polymers, vol. 11, no. 3, p. E566, 2019.
[59] I. G. Goryacheva, M. Z. Dosaev, Y. D. Selyutskiy, A. A. Yakovenko, C.-H. Hsiao, C.-Y. Huang, M.-S. Ju, and C.-H. Yeh, "Control of Insertion of Indenter into Viscoelastic Tissue Using a Piezoelectric Drive," Mekhatronika, Avtomatizatsiya, Upravlenie, vol. 21, no. 5, pp. 304-311, 2020.
[60] 劉冠廷, "大腦假體與註冊定位器於手術訓練之研究," 碩士論文, 國立臺灣大學機械工程學系, 臺灣臺北市, 2016.