臺灣博碩士論文加值系統

前哨淋巴結(SLN)理論已是目前臨床上用於早期乳癌確認的標準程序之一。此程序需有術中造影系統的輔助，方可達預期結果。許多二維造影系統(2-D probe)與一提供三維(3-D)資訊的手持式單光子發射斷層掃描系統(freehand SPECT, fhSPECT)已被應用於提高術中前哨淋巴別定位的正確率。然2-D造影系統因缺乏深度資訊，易受前哨淋巴結附近的背景活度影響，而劣化其定位的表現；fhSPECT造影系統雖可提供良好的前哨淋巴結定位結果，但需使用複雜的統計重建法以產生影像。於此研究中，我們提出一新穎的術中3-D造影系統，雙光子斷層造影系統(DuPECT)，以連結術前透過先進儀器(PET、CT、SPECT、MRI…)得到的影像及術中得到的資訊，並提高SLN定位的準確度及降低偽陰性率(false negative rate)。此系統被設計來造影衰變(decay)過程中，會同時釋出兩個以上伽馬射線(cascaded gamma-ray)之放射性核種(如，Se-75與In-111)。DuPECT系統由一對以 LaBr3閃爍晶體構成的偵檢器(detector)、準值系統(collimation system)及符時線路(coincidence circuit)組成。此模擬研究中，平行孔(parallel hole)與平行板(slat)準值系統分別掛載於兩偵檢器前方，用以限制光子對進入偵檢器的方向與角度。藉由光子對被偵檢器記錄的位置和此二準直儀的幾何特性，分別可回推出直線與平面的光子飛行路徑。此直線與平面的交點即為射源所在位置。此研究中，Se-75(物理半衰期為 120天)被用於驗證DuPECT的概念、評估其表現以及最佳化此系統的設計；所有實驗均透過本實驗室發展的蒙地卡羅軟體完成。結果顯示，隨機事件之量與給予的活度呈正比；散射事件的數量在不同活度的實驗中均低於1.2 count/s (cps)。DuPECT系統僅可提供0.23±0.01 cps/MBq的靈敏度，此數值明顯低於多數2-D術中造影系統的表現(6.5–2,200 cps/MBq)。在影像模擬實驗中，此系統僅可勉強在由兩個鄰近於四個高活度注射點的前哨淋巴結與低背景活度構成的假體中，鑑別出前哨淋巴結的位置；當高活度注射點被排除在照野外時，兩個前哨淋巴結則可被清楚的鑑別。此結果指出，高活度注射點會嚴重的劣化影像品質。我們提出針孔-平行板(pinhole-slat) 的準直系統，以抑低注射點造成的影響。初步結果顯示，此準直系統可成功的排除高活度注射點帶來的影響。In-111與延遲時間窗校正技術 (delay-time-window technique, DTW) 的可行性亦於本研究中被評估。In-111因有合適的伽馬射線能量(171與245 keV)、較短的半衰期(2.8天)和較低的活度–劑量轉換因子，所以也是其中一有潛力應用於DuPECT系統上的放射性核種。初步結果顯示，In-111的245 keV伽馬射線因有85 ns的lifetime，會造成隨機事件數量明顯增加而不適用於目前的DuPECT系統。延遲時間窗校正技術(DTW)被廣泛應用於商用正子斷層掃描(PET)儀的隨機事件校正上；但在DuPECT系統上的表現卻不符預期。綜觀研究結果，DuPECT可成功偵測前哨淋巴結所在位置，為術中前哨淋巴結定位提供另一種選擇。系統的低靈敏度可能會限制此系統的應用，未來得在偵檢器材料及偵檢系統的幾何投入更多研究，以提升系統靈敏度。此外，DuPECT系統引入使用非單光子射源(cascaded isotope)之概念，我們期望此系統與概念能做為未來放射性藥品的發展的其中一個引子。

The sentinel lymph node (SLN) hypothesis is applied as part of the standard procedure for identifying early-stage breast cancer. Thus, an imaging system that can locate SLNs in operating rooms is desired. Several 2-D probe imaging systems and a freehand single-photon emission-computed tomography (fhSPECT) system have been proposed. However, 2-D probe imaging systems are affected by shine-through and shadowing effects. Here, we proposed an alternative to 3D imaging systems, i.e., a dual-photon emission computed tomography (DuPECT) system, which integrates both preoperative and intraoperative information to locate SLNs using cascade photons emitted isotopes such as Se-75 and In-111. The system consists of a LaBr3-based probe and planar head, a collimation system, and a coincidence circuit. When two photons from each disintegration were detected simultaneously, the slat and parallel-hole collimator define a plane and a line, respectively, which represent the possible flight paths of each photon. SLNs can be located using the line-plane intersection. In this study, Se-75 was used to evaluate the DuPECT concept, performance, and optimization of collimator configurations using Monte Carlo software developed in our laboratory. The result of the performance evaluation indicates that the randoms rate increases with increased initial activities, while the scatter rate is lower than 1.2 count/s for various activities. The sensitivity is 0.23±0.01 cps/MBq, which is significantly lower than that of most 2-D probe imaging systems (6.5–2,200 cps/MBq). In a simulated imaging study, four injection sites and two LNs placed at various depths are minimally distinguishable. However, the LNs are clearly identifiable in the absence of injection sites, indicating that photons emitted from the injection sites seriously deteriorate the image quality. To reduce the influence of injection sites, a pinhole-slat collimation system was proposed. Preliminary results show that the pinhole-slat collimation system succeeds in eliminating photons emitted from injection sites. In addition, a feasibility study of In-111 was conducted with a delay-time-window technique. In-111 was another potential cascade isotope for its appropriategamma energies (171 and 245 keV), short half-life (2.8 days), and relative low dose equivalent. Preliminary result indicates that In-111 is not appropriate for the DuPECT system due to its relative long half-time (85 ns) of the 245 keV gamma-ray. The number of random events increases significantly, leading to failed SLNs identification, as a wide coincidence time window is needed to accommodate the long life-lived 245 keV gamma. The proposed three-dimensional imaging system has the potential to identify injection sites and SLNs. However, difficulties with the low sensitivity for LN detection and in the choice of appropriate radioisotope must be overcome before its clinical usage.

ABSTRACT I
中文摘要 III
致謝 V
ABBREVIATIONS VII
TABLE OF CONTENTS VIII
LIST OF TABLES X
LIST OF FIGURES XI
PART I－INTRODUCTION 1
CHAPTER 1 1
GENERAL INTRODUCTION 1
CHAPTER 2 5
INTRAOPERATIVE PROBE SYSTEM 5
2.1. 1-D Probe System 5
2.2. 2-D Probe System 8
2.2.1. Scintillator-Based 2-D Probe System 10
2.2.1.1. Per-Operative Compact Imager (POCI) 10
2.2.1.2. Miniγ-Camera (CarolIRes) 11
2.2.2. Semiconductor-Based 2-D Probe System 12
2.2.2.1. Small Cadmium Telluride γ-Camera (SSGC) 12
2.2.2.2. MediPROBE 12
2.2.3. Routines and Challenges of 2-D Probe System 13
2.3. 3-D Probe System 15
PART II－PROOF-OF-CONCEPT STUDY 17
CHAPTER 3 17
3.1. Introduction 17
3.2. Materials and Method 20
3.2.1. Concept of DuPECT System 20
3.2.2. System Description 21
3.2.3. Validation 23
3.2.3.1. Probe Positioning 24
3.2.3.2. Resolution and Sensitivity Study 25
3.2.3.3. Measurements of True, Scatter, and Random Rates 26
3.2.3.4. Imaging Study 27
3.3. Results 30
3.3.1. Probe Positioning 30
3.3.2. Resolution and Sensitivity Study 31
3.3.3. Measurements of True, Scatter and Random Rates 33
3.3.4. Imaging Study 34
3.4 Discussion 36
PART III－OPTIMIZATION OF 40
COLLIMATOR CONFIGURATION 40
CHAPTER 4 40
4.1. Introduction 40
4.2. Materials and Methods 43
4.2.1. Feasibility Study of In-111 and Delay-Time-Window Method 43
4.2.2. Analytical Analyses of Collimators 45
4.2.2.1. Parallel-Hole Collimation 45
4.2.2.2. Slat Collimation 46
4.2.2.3. Pinhole Collimation 47
4.2.2.4. Fan-beam Collimation 47
4.2.2.5. Comparison of Various Collimations 49
4.2.3. Eliminate Injection–Site Detection 51
4.3. Results 53
4.3.1. Feasibility Study of In-111 and Delay-Time-Window Method 53
4.3.2. Analytical Analyses of Collimators 55
4.4. Discussion 58
PART IV－MAIN DISCUSSION 60
CHAPTER 5 60
PART V－CONCLUSIONS 65
CHAPTER 6 65
PART VI－BIBLIOGRAPHY 66

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