臨床上都是利用99mTc核醫藥物聚集在前哨淋巴結的特性來偵測乳癌細胞的轉移，一般都是醫生於手術中，手持加馬探頭(Gamma probe)偵測核種聚集區域，即前哨淋巴結位置，並據以切除。但此技術易受雜訊影響、且無提供即時影像與深度資訊，因此近年來許多團隊致力於開發一套適用於手術中的影像探頭，希望能克服加馬探頭的缺點。然而傳統SPECT影像使用單光子射源如99mTc，需要旋轉偵檢器180度，才能重建三維影像，不可能在短時間內完成，提供即時影像，因此我們實驗室提出DuPECT方法，使用能同時發出兩個光子的雙光子射源，利用成對的準直儀限制光子路徑，與同符線路判斷收到的兩顆光子為同一衰變時發出，再由兩光子飛行軌跡的交點進行影像重建。因此DuPECT系統不需全角度的投影資訊可即時成像，並提供三維空間資訊。
然而DuPECT系統最大限制即靈敏度不高，因此我們嘗試以聚焦式準直儀的扇形準直儀(Fan-beam collimator)與錐狀射束準直儀(Cone-beam collimator)增加靈敏度。為了探討系統可行性，我們以蒙地卡羅軟體-GATE進行驗證，卻發現模擬時間耗時，且無法模擬焦距太小的幾何，因此建立一套更有效率、兼具彈性的幾何設計系統有其必要性。而GATE模擬時間中，光子與物理模組作用占了很大的比例，因此我們自行設計一套物理模組並結合能快速模擬光子在像素化假體遷移(transport)與作用的SimSET組成一套系統稱之 Virtual collimator System。
為了驗證Virtual Collimator System的準確度，我們與GATE比較，分別使用99mTc與75Se模擬隙縫式準直儀(Slat collimator)與扇形準直儀。確定Virtual Collimator System可行性後，我們即以此系統模擬DuPECT系統，先決定理想的聚焦式準直儀焦距，再分別測試使用扇形與錐狀射束準直儀搭配隙縫式準直儀時的系統靈敏度與解析度。
實驗結果顯示Virtual Collimator System與GATE在模擬隙縫式準直儀與扇形準直儀上，系統解析度與系統靈敏度有很高的一致性。而在模擬隙縫式準直儀時，可以增高2~3倍的模擬效率; 模擬扇形準直儀時，更可以增高20~60倍的模擬效率，因此Virtual Collimator System對於模擬複雜幾何構造時，能大大增進模擬效率，並提供準確結果。
而在DuPECT系統探討中，發現錐狀射束準直儀有較扇形準直儀更佳的系統解析度與系統靈敏度，使用錐狀射束準直儀時，當射源在焦點，靈敏度為5.42 cps/kBq，解析度在xyz方向分別為2.12×2.12×4.38毫米。研究證實，DuPECT系統應用於手術中前哨淋巴結偵測是可行的，儘管系統最大限制為系統表現深受物體所在位置影響，但相信未來非常有機會進入臨床測試階段。

In clinic, the detection of breast metastasis utilizes the aggregating effect of 99mTc labeled pharmaceuticals in sentinel lymph node (SLN). The doctor hold the gamma counting probe to locate the most radioactive (“hottest”) node (i.e. SLN) during operation and perform the resection. But the gamma counting probe technique is susceptible to noise and lack of depth information. In recent years, many groups devoted to develop an imaging probe suitable for the use in the operating room, hoping to overcome the drawbacks of the gamma counting probe.
However, traditional single photon emission computed tomography (SPECT) needs to scan 180 degrees to enable the reconstruction of the three dimensional image. As a result, it is impossible to perform real-time imaging for operation purpose. Our laboratory proposes the DuPECT (dual photons emission computed tomography) system employing the radioisotopes that emit two photons simultaneously. The DuPECT system uses the collimator pairs to restrict the direction of incoming photons and the coincidence circuit to determine whether the detected two photons are emitted in the same decay. The source position is simply the intersecting of the trajectory of the detected photons. The DuPECT system provides three-dimensional spatial information without requiring the rotation of the system.
Since the biggest limitation of the DuPECT is its low sensitivity, we try to take advantage of the converging collimators (including the fan-beam collimator and cone-beam collimator) to improve the sensitivity. We utilized the GATE Monte-Carlo simulation (MCS) to validate the feasibility of the DuPECT. However, GATE is time-consuming and can’t simulate the geometry with small focal length. So it is essential to develop a more efficient and flexible geometry-based simulation system. In GATE, the interaction between the photons and collimator takes a large portion of the simulation time. Therefore in this study, we design a new Virtual collimator combined with the SimSET to speed up the simulation.
The projection data of the Virtual collimator are compared with GATE to validate the accuracy of the proposed system. Both 99mTc and 75Se are used in the slat collimator and the fan-beam collimator simulation. After demonstrating the feasibility of the Virtual collimator, it was used to construct the DuPECT system. In the study, the optimal focal length of the converging collimator was determined first, and then testing the sensitivity and resolution of fan-beam collimator and cone-beam collimator separately to pair with the slat collimator.
According to both slat and fan-beam collimator experimental results, we demonstrate that Virtual collimators are in good agreement with GATE simulation in terms of resolution and sensitivity. In Comparison to GATE, the Virtual collimator improve 2~3 and 20~60 times simulating efficiency for slat collimator and fan-beam collimator, respectively. We conclude that the Virtual collimator boost simulating efficiency and produce the accurate results even on complex geometry.
The preliminary results suggest the use of Cone-beam collimator for the DuPECT system as it show better resolution and sensitivity than fan-beam collimator. The system sensitivity is 5.42 cps/kBq with resolution of 2.12*2.12*4.38 mm at x, y, and z direction when the source is placed at the focal point. The results demonstrate that the DuPECT system is feasible for intraoperative detection of the SLN. Although the system is strongly position dependent, we believe that the DuPECT-SLN Probe System will come into clinical trial stage in the future.

Aarsvold, J. N. and Alazraki, N. P. (2005). "Update on detection of sentinel lymph nodes in patients with breast cancer." Semin Nucl Med 35: 116-128.
Albertini, J., Lyman, G., Cox, C., et al. (1996). " Lymphatic mapping and sentinel node biopsy in the patient with breast cancer." JAMA 276: 1818-1822.
Atkins, H., Hayward, J., Klugman, D., et al. (1972). "Treatment of early breast cancer: a report after ten years of a clinical trial." British medical journal 2: 423-432.
Beekman, F. and van der Have, F. (2007). "The pinhole: gateway to ultra-high-resolution three-dimensional radionuclide imaging." Eur J Nucl Med Mol Imaging 34: 151-161.
Boisson, F., Bekaert, V., El Bitar, Z., et al. (2011). "Characterization of a rotating slat collimator system dedicated to small animal imaging." Phys Med Biol 56: 1471-1485.
Borgstein, P., Pijpers, R., Comans, E., et al. (1998). "Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection." Journal of the American College of Surgeons 186: 275-358.
Cabanas, R. (1977). "An approach for the treatment of penile carcinoma." Cancer 39: 456-522.
Cao, Z., Bal, G., Accorsi, R., et al. (2005). "Optimal number of pinholes in multi-pinhole SPECT for mouse brain imaging—a simulation study." Phys Med Biol 50: 4609-4624.
Capote, R. M. and Almeida, P. (2011). "Optimal Design of Fan Beam Collimationfor Pixelated Breast Imaging Systems." IEEE Nuclear Science Symposium Conference Record: 3260-3262.
Carter, C., Allen, C. and Henson, D. (1989). "Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases." Cancer 63: 181-188.
CAUSER, D. A. and TAYLOR, C. G. (1974). "A high-sensitivity, high-resolution, diverging, collimator for use with low energy isotopes." Phys Med Biol 20: 318-320.
Chen, C.-L., Wang, Y., Lee, J. J. S., et al. (2008). "Integration of SimSET photon history generator in GATE for efficient Monte Carlo simulations of pinhole SPECT." Medical Physics 35: 3278.
Chia-Lin, C., Yuchuan, W., Jason, J. S. L., et al. (2008). "Integration of SimSET photon history generator in GATE for efficient Monte Carlo simulations of pinhole SPECT." Medical Physics 35.

Cserni, G., Amendoeira, I., Apostolikas, N., et al. (2003). "Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines." European Journal of Cancer 39: 1654-3321.
Daube-Witherspoon, M., Surti, S., Perkins, A., et al. (2010). "The imaging performance of a LaBr3-based PET scanner." Phys Med Biol 55: 45-109.
Daube-Witherspoon, M. E., Surti, S., Perkins, A., et al. (2010). "The imaging performance of a LaBr3-based PET scanner." Phys Med Biol 55: 45-64.
Fisher, B., Montague, E., Redmond, C., et al. (1977). "Comparison of radical mastectomy with alternative treatments for primary breast cancer. A first report of results from a prospective randomized clinical trial." Cancer 39: 2827-2866.
Formiconi, A. (1998). "Geometrical response of multihole collimators." Phys Med Biol 43: 3359-3438.
Freed, M., Kupinski, M. A., Furenlid, L. R., et al. (2008). "A prototype instrument for single pinhole small animal adaptive SPECT imaging." Medical Physics 35: 1912.
Gentilini, O., Cremonesi, M., Toesca, A., et al. (2010). "Sentinel lymph node biopsy in pregnant patients with breast cancer." Eur J Nucl Med Mol Imaging 37: 78-83.
Giuliano, A., Kirgan, D., Guenther, J., et al. (1994). "Lymphatic mapping and sentinel lymphadenectomy for breast cancer." Annals of surgery 220: 391.
Helmers, H., von Boetticher, H., Schreiber, P., et al. (1982). "Advances in gamma-gamma-coincidence scintigraphy with the scintillation camera." Phys Med Biol 27: 1495-2001.
Holen, R. V., Vandenberghe, S., Staelens, S., et al. (2009). "Fast 3D iterative image reconstruction for SPECT with rotating slat collimators." Phys Med Biol 54: 715-729.
Jaszaak, R., Li, J. and Wang, H. (1994). "Pinhole collimation for ultra-high-resolution, small-field-of-view SPECT." Phys Med Biol 39: 425-437.
Jaszczak., R. J., Chang., L. T. and Murphy., P. H. (1979). "Single photon-emission computer-tomography using multi-slice fan beam collimators." IEEE Trans. Nucl. Sci. 26: 610-618
Kang, T., Yi, M., Hunt, K. K., et al. (2010). "Does blue dye contribute to success of sentinel node mapping for breast cancer?" Ann Surg Oncol 17 Suppl 3: 280-285.
Kennedy, J., Israel, O., Frenkel, A., et al. (2006). "Super-resolution in PET imaging." IEEE Trans. Med. Imaging 25: 137-184.

Kern, K. (1999). "Sentinel lymph node mapping in breast cancer using subareolar injection of blue dye." Journal of the American College of Surgeons 189: 539-584.
Kerrou, K., Pitre, S., Coutant, C., et al. (2011). "The usefulness of a preoperative compact imager, a hand-held gamma-camera for breast cancer sentinel node biopsy: final results of a prospective double-blind, clinical study." J Nucl Med 52: 1346-1353.
Khalil, M. M., Tremoleda, J. L., Bayomy, T. B., et al. (2011). "Molecular SPECT Imaging: An Overview." Int J Mol Imaging 2011: 796025.
Kim, T., Giuliano, A. E. and Lyman, G. H. (2006). "Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis." Cancer 106: 4-16.
Krag, D. N., Weaver, D. L., Alex, J. C., et al. (1993). "Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe." Surg. Oncol. 2-335.
Lerman, H., Metser, U., Lievshitz, G., et al. (2006). "Lymphoscintigraphic sentinel node identification in patients with breast cancer: the role of SPECT-CT." Eur J Nucl Med Mol Imaging 33: 329-337.
Lim, C. B., Chang, L. T. and Jaszczak, R. J. (1980). "Performance analysis of three camera configurations for single photon emission computedtomography." IEEE Trans. Nucl. Sci. 27: 559-566.
Linehan, D., Hill, A., Akhurst, T., et al. (1999). "Intradermal radiocolloid and intraparenchymal blue dye injection optimize sentinel node identification in breast cancer patients." Ann Surg Oncol 6: 450-454.
Lyman, G. H., Giuliano, A. E., Somerfield, M. R., et al. (2005). "American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer." J Clin Oncol 23: 7703-7720.
MacDonald, L. R., Patt, B. E., Iwanczyk, J. S., et al. (2000). "High-resolution hand-held gamma camera." Proceedings of SPIE 4142: 242.
Mah, E. and Spicer, K. M. (2007). "Comparison of medium- and high-energy collimators for 131I-tositumomab dosimetry." J Nucl Med Technol 35: 148-153.
Mahmood, S., Erlandsson, K., Cullum, I., et al. (2011). "Experimental results from a prototype slit-slat collimator with mixed multiplexed and non-multiplexed data." Phys Med Biol 56: 4311-4331.
Mahmood, S. T., Erlandsson, K., Cullum, I., et al. (2009). "Design of a novel slit-slat collimator system for SPECT imaging of the human brain." Phys Med Biol 54: 3433-3449.
Mahmood, S. T., Erlandsson, K., Cullum, I., et al. (2010). "The potential for mixed multiplexed and non-multiplexed data to improve the reconstruction quality of a multi-slit-slat collimator SPECT system." Phys Med Biol 55: 2247-2268.
Martin, R. (2000). "Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: Results of a multi-institutional study." Surgery 128: 139-144.
Martin, R., Edwards, M., Wong, S., et al. (2000). "Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group." Surgery 128: 139-183.
Mathelin, C., Salvador, S., Huss, D., et al. (2007). "Precise Localization of Sentinel Lymph Nodes and Estimation of Their Depth Using a Prototype Intraoperative Mini -Camera in Patients with Breast Cancer." J Nucl Med 48: 623-629.
Melcher, C. (2000). "Scintillation crystals for PET." J Nucl Med : official publication, Society of Nuclear Medicine 41: 1051-1056.
Moses, W. W. (2007). "Recent Advances and Future Advances in Time-of-Flight PET." Nucl Instrum Methods Phys Res A 580: 919-924.
Nemoto, T., Vana, J., Bedwani, R., et al. (1980). "Management and survival of female breast cancer: results of a national survey by the American College of Surgeons." Cancer 45: 2917-2941.
Novak, J. R., Ayan, A. S., Accorsi, R., et al. (2008). "Verification of the sensitivity and resolution dependence on the incidence angle for slit-slat collimation." Phys Med Biol 53: 953-966.
Pareto, D., Pav, x000Ed, et al. (2001). "Characterisation of fan-beam collimators." Eur J Nucl Med Mol Imaging 28: 144-149.
Park, M.-A., Moore, S. C. and Kijewski, M. F. (2005). "Brain SPECT with short focal-length cone-beam collimation." Medical Physics 32: 2236.
Pitre, S., Ménard, L., Ricard, M., et al. (2003). "A hand-held imaging probe for radio-guided surgery: physical performance and preliminary clinical experience." Eur J Nucl Med Mol Imaging 30: 339-682.
Raylman, R. (2001). "Performance of a dual, solid-state intraoperative probe system with 18F, 99mTc, and (111)In." Journal of nuclear medicine : official publication, Society of Nuclear Medicine 42: 352-412.
Reschini, E. and Peracchi, M. (1984). "Uptake of 75Se-selenocholesterol by an adrenal cortical carcinoma and its metastases." Eur J Nucl Med 9: 291-294.
Russo, P., Curion, A. S., Mettivier, G., et al. (2011). "Evaluation of a CdTe semiconductor based compact gamma camera for sentinel lymph node imaging." Medical Physics 38: 1547.
Sabbir, A., Kramer, G. H., Semmler, W., et al. (2011). "Performance study of a fan beam collimator designed for a multi-modality small animal imaging device." Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment 629: 368-376.
Saffer, J., Barrett, H. H., Barber, H., et al. (1992). "Surgical probe design for a coincidence imaging system without a collimator." Image and vision computing 10: 333-674.
Schneebaum, S., Even-Sapir, E., Cohen, M., et al. (1999). "Clinical applications of gamma-detection probes - radioguided surgery." Eur J Nucl Med 26: 35.
Shilo, S., Krausz, Y., Reinus, C., et al. (2001). "The Use Of 75Se-Selenocholestrol SPECT in the Localization of Steroid-Secreting Tumor." Israel Medical Association journal 3: 455-456.
Simon, R. C., James, A. S. and Michael, E. P. (2003). "Physics in Nuclear Medicine the third edition." 239-241.
Surti, S., Karp, J. and Muehllehner, G. (2004). "Image quality assessment of LaBr3-based whole-body 3D PET scanners: a Monte Carlo evaluation." Phys Med Biol 49: 4593-5203.
Surti, S., Karp, J., Muehllehner, G., et al. (2002). "Investigation of lanthanum scintillators for 3D PET." Nuclear Science Symposium Conference Record, 2002 IEEE 2: 1177.
Tanis, P., Lont, A., Meinhardt, W., et al. (2002). "Dynamic sentinel node biopsy for penile cancer: reliability of a staging technique." The Journal of urology 168: 76-156.
Tsui, B. and Gullberg, G. (1990). "The geometric transfer function for cone and fan beam collimators." Physics in Medicine and Biology 35: 81.
Tsui, B. M. W., Gullberg*, G. T., Edgerton, E. R., et al. (1986). "Design and Clinical Utilityof a Fan Beam Collimator for SPECTImaging of the Head." J Nucl Med 27: 810-819.
Van Holen, R., Staelens, S. and Vandenberghe, S. (2011). "Tomographic image quality of rotating slat versus parallel hole-collimated SPECT." Phys Med Biol 56: 7205-7222.
Vanhove, C., Defrise, M., Bossuyt, A., et al. (2009). "Improved quantification in single-pinhole and multiple-pinhole SPECT using micro-CT information." Eur J Nucl Med Mol Imaging 36: 1049-1063.
Veronesi, U., Paganelli, G., Galimberti, V., et al. (1997). "Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes." Lancet 349: 1864-1871.

Wawroschek, F., Vogt, H., Weckermann, D., et al. (2001). "Radioisotope guided pelvic lymph node dissection for prostate cancer." The Journal of urology 166: 1715-1724.
Wendler, T., Herrmann, K., Schnelzer, A., et al. (2010). "First demonstration of 3-D lymphatic mapping in breast cancer using freehand SPECT." Eur J Nucl Med Mol Imaging 37: 1452-1461.