\ M355091 ,* 八、新型說明： 【新型所屬之技術領域】 本創作係關於一種用於小動物之造影系統。 …·. 【先前技術】 從臨床前研究到各類藥物研發、腦功能探索、基因表現、生醫及 分子影像等研究’皆大量使用動物進行實驗。因此如何觀察動物 • 活體内的資訊，是一個很重要的課題。現今的研究越來越需要活 體内的資訊，故採用非侵入式之活體造影是必要的。非侵入式之 活體造影不只能夠降低動物的犧牲及減少花費，亦可對同一組動 物進行研究以減少因不同活體所造成的變異性。 目前對於研究動物活體内生理代謝分布情形之核醫造影工具，包 括微型正子發射電腦斷層攝影系統（micr〇 p〇sitr〇n emissiQn • tom〇graI%，microPET)及微型單光子發射電腦斷層攝影系統 • ^micro single photon emission computed tomography, microSPECT) 兩種。針對單光子發射電腦斷層攝影系統而言，能夠提高解析度 應用於小動物造影最大的關鍵在於使用針孔準直儀，因此稱作針 - 孔單光子發射電腦斷層攝影系統(pinhole SPECT)。針孔單光子發 • 射電腦斷層攝影系統最大好處就是有高解析度，使用的針孔孔徑 越小解析度越好’但相對付出的代價是餘度會越低。為了改進 低靈敏度並降低劑量，於是多針孔準直儀的概念被提出來。多針 5 ' M355091 孔單光子贿電爾賴料、統(multi_pinMe spect)的特點是 • 針聽來增加錄度並域有高解析度，現今已經有不少 I動物專用的單光子發射電腦嶋攝财統被發展並商業化，例 & · NanQ—SPECF、U~SPECT等，然而價格十分昂貴，難以被一般 * \ 醫院、研究單位採用。 【新型内容】 馨她於專門開發的小動物多針孔單光子發射電腦斷層攝影系統， 本創作使用臨床的伽瑪攝影機搭配自行開發的多針孔準直儀之裝 置與步進馬達’可改裝運用醫院固有之臨床用單光子發射電腦斷 層攝影系統，將之進一步使用於小動物之活體研究。本創作所提 供之裝置具有降低成本、節省空間以及對既有之器材做更有效之 利用等多項優點，期望對臨床及學術研究帶來便利。 φ 疋以，本創作提供一種用於小動物之造影系統，包含： a.伽瑪攝影系統，包括一針孔準直儀及造影機； b· 一至多個針孔之鏡頭，其裝設於針孔準直儀之前端； c.步進馬達，用以承載小動物，並轉動該動物以利造影機 進行不同角度之造影。 於本系統中，該鏡頭具有南解析度之功能。在一較佳具體實施例， 該鏡頭具有3至9個針孔，更佳為具有7個針孔。 6 ' M355091 本創作之另外_實施射’針孔為鈍且不鋒料緣的針孔 (keel-edge pinhole) ’此設計可減少光子直接穿透而提高解析度。 ^ 於一更佳實施例中，針孔之孔徑為1mm，此小孔徑搭配多個針孔， 可同時兼顧靈敏度與解析度。 .本創作中步進馬達為一般市售步進馬達，較佳為可攜式之步進馬 達，便於使用者可隨身攜帶至不同醫院或場所造影。步進馬達旋 進時間視造影需求而定，例如該步進馬達速度可調整旋進時間快 慢，以因應接受麻藥注射多寡之小動物。在一較佳實施例中，該 旋進時間為照完一個平面後換至下一個平面之時間。 i 本創作可進一步包含用於影像重建軟體之演算法。較佳實施例 ® 中’影像重建軟體之演算法為用於解析式的演算法如Tent_FDK及 用於疊代式的演算法如 3D-maximum 1 ike 1 ihood-expeetation maximization (MLEM)或 3D- ordered subsets-expectation maximization (OSEM) ° 【實施方式】 實施例1:蒙地卡羅模擬 * 本創作使用的模擬軟體為GATE (Qeant4 △pplication for 7 M355091 I_gmPhie Smissi()n) ’ GATE是一套以蒙地卡羅軟體g_4為 核〜，專用於模擬核醫造影系统pET及SpECT的工具。gate的 特點為使用直譯式的程式語言，使用者能輕壯手。另一個特點 為GATE 了以模擬k間依賴(time_depen(|ent)的現象，讓時間依賴 的組成與取彳純程的描述—致，這是GATE關新的特色之一。 GATE可以提供簡單幾何模型及視覺化讓使用者有效的進行模 擬。本創作之系統模擬主要分成四個組件，偵檢器、準直儀、針 孔及假體。偵檢器晶體的材料為蛾化鈉_)，直徑為_咖厚 度5 mm。準直儀的材料為錯，長度285腿。針孔之建構為加入 材質是空氣之物件轉直儀上，真實祕巾較鈍且科利邊緣的 針孔(keel-edgepinhole)則利用2圓錐形及丨圓柱形物件來组成。執 仃模擬軟體的硬體設備為兩台桌上型電腦。電腦設鮮級一台為\ M355091 , * VIII, new description: [New technical field] This creation is about an imaging system for small animals. ..... [Prior Art] From preclinical research to various drug development, brain function exploration, gene expression, biomedical and molecular imaging studies, a large number of animals were used for experiments. Therefore, how to observe animals • Information in the living is an important issue. Today's research is increasingly requiring in vivo information, so non-invasive biopsy is necessary. Non-invasive bioimaging can not only reduce animal sacrifice and reduce costs, but also study the same group of animals to reduce variability caused by different living organisms. Currently, nuclear angiography tools for studying the physiological and metabolic distribution of animals in vivo include micro-positive emission computed tomography system (micr〇p〇sitr〇n emissiQn • tom〇graI%, microPET) and micro single photon emission computed tomography system. • ^micro single photon emission computed tomography, microSPECT) Two. For single-photon emission computed tomography systems, the ability to improve resolution is the key to the use of pinhole collimators, so it is called pinhole SPECT. Pinhole single photon emission • The biggest benefit of a computerized tomography system is the high resolution. The smaller the pinhole aperture used, the better the resolution. But the relative cost is the lower the margin. In order to improve the low sensitivity and reduce the dose, the concept of a multi-pinhole collimator was proposed. The multi-needle 5 ' M355091 hole single photon bribe is based on the multi-pin Me spect. The needle is used to increase the recording and the field has high resolution. Nowadays, there are many single-photon emission computers for I animals. The financial system was developed and commercialized, examples & · NanQ-SPECF, U~SPECT, etc., but the price is very expensive, it is difficult to be adopted by the general * \ hospitals, research units. [New Content] Xin She specializes in the development of small animal multi-pinhole single photon emission computed tomography system. This creation uses a clinical gamma camera with a self-developed multi-pinhole collimator device and stepper motor's refitable The hospital's intrinsic clinical single-photon emission computed tomography system is further used in the study of small animals. The devices provided by this creation have many advantages such as cost reduction, space saving and more efficient use of existing equipment, and are expected to facilitate clinical and academic research. φ 疋 ,, This creation provides an imaging system for small animals, comprising: a. gamma photography system, including a pinhole collimator and contrast machine; b· one or more pinhole lenses, which are mounted on the needle The front end of the hole collimator; c. Stepper motor for carrying small animals, and rotating the animal to facilitate contrast imaging at different angles. In this system, the lens has the function of south resolution. In a preferred embodiment, the lens has from 3 to 9 pinholes, more preferably seven pinholes. 6 ' M355091 Another _ implementation of this creation is a keel-edge pinhole that is blunt and has no edge. This design reduces the direct penetration of photons and improves resolution. ^ In a preferred embodiment, the pinhole has a hole diameter of 1 mm. This small aperture is matched with a plurality of pinholes, and both sensitivity and resolution can be considered. The stepping motor in this creation is a general-purpose stepping motor, preferably a portable stepping motor, which is convenient for the user to carry to the contrast of different hospitals or places. The stepping motor rotation time depends on the contrast demand. For example, the stepping motor speed can adjust the speed of the screwing in order to respond to the small animals that receive the anesthetic injection. In a preferred embodiment, the precession time is the time to switch to the next plane after photographing one plane. i This creation can further include algorithms for image reconstruction software. The algorithm for 'image reconstruction software' in the preferred embodiment® is an algorithm for analytic expressions such as Tent_FDK and an algorithm for iterative algorithms such as 3D-maximum 1 ike 1 ihood-expeetation maximization (MLEM) or 3D-order Subsets-expectation maximization (OSEM) ° [Embodiment] Example 1: Monte Carlo simulation * The simulation software used in this creation is GATE (Qeant4 △pplication for 7 M355091 I_gmPhie Smissi()n) ' GATE is a set of The Geo Carlo software g_4 is a core~, a tool dedicated to simulating the nuclear medicine imaging system pET and SpECT. The gate is characterized by the use of a literal translation of the programming language, and the user can be light and strong. Another feature is GATE to simulate the k-dependency (time_depen(|ent) phenomenon, let time-dependent composition and the description of the pure process, which is one of the features of GATE. GATE can provide simple geometry The model and visualization allow the user to effectively simulate. The system simulation of this creation is mainly divided into four components, the detector, the collimator, the pinhole and the prosthesis. The material of the detector crystal is moth sodium _), The diameter is _ coffee thickness 5 mm. The material of the collimator is wrong and the length is 285 legs. The pinhole is constructed by adding a material-type object that is made of air. The real secret towel is blunt and the kele-edge pinhole is composed of 2 conical and cylindrical objects. The hardware devices that implement the emulation software are two desktop computers. The computer has a fresh level
3.0 GHz 的 CPU 及 1G RAM，另一台為 1.8 GHz 的 CPU 及 768M 實施例2:系統機率矩陣之建立 多針孔單光子發射電腦斷層攝料統之影像重建法大多使用疊代 式次算法，本創作的模擬系統使用MLEM及0SEM，系統機率矩 陣的建構使用幾何估算的方法^ VGxel制彻。此方法將犯物體分 成65x65x65個，2D偵檢器分成129xl29個格子點；透過幾何關 係估算出每個物體上的體素(Voxel)投射到偵檢器上各個格子點的 機率，組成符合系統特性的機率矩陣。定義系統的座標空間，如 8 M355091 圖1 ’物體中心設定為座標原點(00,0)。偵檢平面的座標以μ平 =示其财向(簡τ絲；以ζ轴麵其行柯(edumn)， 1 首先假設針孔為無限小_，並將估算之座 為兩部份來考慮。T座標轉法如圖2為物體與針轉直儀之χ_γ 7剖面圖’ FL絲針轉絲的錢長、各健素的投影長度 2體素職檢平面中心的距離為d、垂線長L、針孔間離Pd並 1相似二角形原理求得Tt，最後依據三種情況求得T座標。Z 座標的算法與T座標相同，只需將投影長t改為各體素z軸高度Z。 t = X cos6> + 7sin6> L = 4d^~^p·3.0 GHz CPU and 1G RAM, another 1.8 GHz CPU and 768M Example 2: System probability matrix The multi-pinhole single photon emission computed tomography image reconstruction method mostly uses the iterative sub-algorithm. The simulation system of this creation uses MLEM and 0SEM, and the construction of the system probability matrix uses the method of geometric estimation ^ VGxel. This method divides the object into 65x65x65, and the 2D detector divides into 129xl29 grid points; through the geometric relationship, the probability that the voxel on each object is projected onto each grid point on the detector is estimated, and the composition conforms to the system characteristics. Probability matrix. Define the coordinate space of the system, such as 8 M355091 Figure 1 'The object center is set to the coordinate origin (00,0). The coordinate of the detection plane is μ flat = the direction of its wealth (simplified τ wire; the ζumn of the ζ axis, 1 first assume that the pinhole is infinitely small _, and consider the estimated seat as two parts) Figure 2 shows the relationship between the object and the needle-turning instrument. _γ 7 section view 'The length of the FL wire-needle wire, the projection length of each health factor 2 The distance between the voxel and the center of the voxel is d, and the vertical line is long. L, the pinhole is similar to Pd and 1 is similar to the digonal shape principle to obtain Tt. Finally, the T coordinate is obtained according to three cases. The algorithm of Z coordinate is the same as the T coordinate, and only the projection length t is changed to each voxel z-axis height Z. t = X cos6> + 7sin6> L = 4d^~^p·
Tt=^kzlil l~fl 1 ,t = Pd T = \T2={Tt-Pd)x{-\) ,t>Pd T3=Tt + Pd ,t<Pd ^著考慮實嶋大例3，_她三肖嫩，求縣健 到^嶋恤猶_顧。吻嶋實際投影 置’最後_幾何效率G來估算每個不同事件點 2機率鳴為射源通過針孔所形成的射束路_貞檢平面中心轴 間之夾角、ae騎效孔徑大小及D為體素到倾平面的距離。 G_ae2〇〇s3e M355091 實施例3 :模擬實驗 觀實驗使用雙圓柱假體如圖4 ’評估Z轴取樣、針孔間距及針孔 ： 數目對系統的影響。模擬假體S1:半徑2 mm、高18 mm; S2 : • - ·半徑5 mm、高18 mm。除了針孔間距實驗，假體高度更改為12 mm。注入活性皆為〇.8mCi，每筆投影模擬1秒共1〇〇筆。 影像品質分析 本創作各賴擬麟制MLEM進行讀錢，並漏％次的 疊代計算❶影像品質分析使用訊雜比⑼卿⑷肋以她撕取 變異係數(coefficient of variation，CV)2種方法進行評估。 訊雜比 * SNR2 = ^ 1^2/» - glm) • m=1 ^ [1〇] 此公式假設在帕松分佈下，M為所圈選R〇I (regi〇n 〇f恤咖) =象素總數。^為所圈選標幟物中單—像素的值，心為所圈選背 蹲像素的值，g2w-‘，表示影像中某一像素的訊號。匕為 所圈選標幟物中單一像素的平均值，在帕松分佈中平均值會等於 變異數(variance)。而變異數開平方等於標準差，在影像中標準差 ' 表示影像的雜訊。 ' M355091 * 變異係數 CF = -^_xl〇〇% mean • SD表標準差。變異係數可以用來分析雜訊對影像的影響，但會受 ' 到ROI圈選的影響，因此必須圈選同樣大小之ROI進行評估。 0 實施例4 : Z轴取樣 * Z軸取樣模擬之投影及使用重建影像如圖8，影像品質分析結果如 圖9。⑻及(b)顯示中央轴狀切面影像於疊代過程中cv及SNR的 變化，（c)及(d)顯示最佳收斂影像於不同z軸切面CV及SNR的變 化。系統取樣數尚會有較低的變異係數(Cv)及較好的訊雜比 (SNR)’且Z軸不同切面的變異係數(cv)及訊雜比(snr)變異較小。 • 針孔於系統的位置’主要取決於系統的取樣(sampling)。可以經由 轉動㈣—，R)不同角度，得到不同的Z轴取樣。額7針孔系 統進行評估’比較Z轴取樣3及轉動45度z袖取樣7之兩筆資料 如圖5並針對重建後衫像進行分析與評估。參數設定如下 :孔徑 2 mm、物體到針孔距離4G贿、針孔間距14 77咖、外圍針孔傾 斜角度2〇.27度及針孔張開角度25.7度。 實施例5 :針孔間距 、M355091 針孔間距對系統的影響，主要有疊影程度及入射角。使用7針孔 系統進行評估’比較不同針孔間距9.85、13.5及16 mm，外圍針 孔傾斜角度13.83、18.7及21.8度。其他參數設定如下：孔徑2 mm、 位置轉動45度、物體到針孔距離40 mm、及針孔張開角度25 7 度。 針孔間距模擬之投影及使用3D-MLEM重建影像如圖1〇，針孔間 距過大之影像邊緣會失真。疊影程度分別為〇、23.56及46.96%。 影像品質分析結果如圖11，顯示中央軸狀切面影像於疊代過程中 CV及SNR的變化。針孔間距大沒有疊影，有較佳的snr。cv在 最佳收斂前針孔間距小有較好表現’最佳收斂後針孔間距大有較好 表現。 實驗例6 :針孔數目 不同孔數對系統的影響，比較1、5、7及9針孔系統影像品質的 差異。各孔數使用最佳取樣頻率，5、7及9針孔系統位置轉動22.5、 45及11.25度。其他參數設定如下：孔徑2 mm、針孔間距14.77 mm、外圍針孔傾斜角度20.27度、物體到針孔距離40 mm、及針 孔張開角度25.7度。 實驗例7·系統效能評估 使用較複雜之4圓柱形假體如圖6進一步評估5、7及9針孔系統 12 'M355091 效能，P1及P2 :半徑1 mm、高18 mm、兩者中心相距4 ; p3 及P4 :半徑1.5 mm、高l8 mm、兩者中心相距6 mm。注入活性 皆為1.6 mCi ’每筆投影模擬丨秒共勘筆。參數設定：孔徑使用 .- 1 mm ’其他同針孔數目實驗。 評估結果之針孔數目與單針孔進行空間解析度及靈敏度比較，使用 假體為hot in warm假體如圖7。其hot spot為半徑〇.i5mm之點射 Φ 源’活性為〇·1 mCi; warm background為1000立方公厘之正方體， 整體活性為2 mCi。每筆投影模擬1秒共1〇〇筆’影像重建後，取 中央切面估算半高全寬(仙1 width at half miximum，FWHM)。 4圓柱形假體使用3D_mlEM重建影像如圖14，結果顯示5及7 孔系統較符合實際系統所需。1、5及7孔系統之靈敏度分別為 285、1126及1521cps/mCi/mL，與單孔系統比分別提高3.95及5.34 • 倍。7孔系統有較佳的靈敏度，因此最符合我們的實際系統所需。 Hot in warm假體重建結果如圖(15)，半高全寬分析單孔為1.13 mm 及七孔為1.41 mm。 【圖式簡單說明】 13Tt=^kzlil l~fl 1 , t = Pd T = \T2={Tt-Pd)x{-\) ,t>Pd T3=Tt + Pd ,t<Pd ^ Consider the actual case 3,_ She is three Xiao Nen, and she is looking forward to the county. The actual projection of the snout is set to 'final_geometry efficiency G to estimate each different event point. 2 probability is the beam path formed by the pinhole through the pinhole. The angle between the central axis of the inspection plane, the size of the ae riding effect aperture and D The distance from the voxel to the tilt plane. G_ae2〇〇s3e M355091 Example 3: Simulation experiment The observation experiment uses a double cylindrical prosthesis as shown in Fig. 4' to evaluate the Z-axis sampling, pinhole spacing and pinhole: the effect of the number on the system. Simulated prosthesis S1: radius 2 mm, height 18 mm; S2: • - · Radius 5 mm, height 18 mm. Except for the pinhole spacing experiment, the prosthesis height was changed to 12 mm. The injection activity is 〇8mCi, and each projection simulates 1 second for a total of 1 stroke. Image quality analysis This work relies on the MLEM to read money, and misses the generation of the iteration calculation. Image quality analysis uses the signal-to-noise ratio (9) Qing (4) rib to tear the coefficient of variation (CV) Method for evaluation. Signal to noise ratio * SNR2 = ^ 1^2/» - glm) • m=1 ^ [1〇] This formula assumes that under the Pason distribution, M is the circled R〇I (regi〇n 〇f-shirt) = total number of pixels. ^ is the value of the single-pixel in the circled flag, the heart is the value of the circled pixel, and g2w-', which represents the signal of a pixel in the image.匕 is the average of a single pixel in the circled marker, and the average value in the Pason distribution is equal to the variance. The square of the variance is equal to the standard deviation, and the standard deviation in the image represents the noise of the image. ' M355091 * Coefficient of variation CF = -^_xl〇〇% mean • SD table standard deviation. The coefficient of variation can be used to analyze the effect of noise on the image, but it will be affected by the ROI circle selection, so the same size ROI must be circled for evaluation. 0 Example 4: Z-axis sampling * The projection of the Z-axis sampling simulation and the use of reconstructed images are shown in Fig. 8, and the image quality analysis results are shown in Fig. 9. (8) and (b) show changes in cv and SNR during the iterative process of the central axial section image, and (c) and (d) show changes in the CV and SNR of the best convergence image in different z-axis planes. The system sampling number will have a lower coefficient of variation (Cv) and a better signal-to-noise ratio (SNR)', and the coefficient of variation (cv) and the ratio of the signal to noise (snr) of the Z-axis are smaller. • The position of the pinhole in the system' depends primarily on the sampling of the system. Different Z-axis samples can be obtained by rotating (four)-, R) different angles. The 7-pin system was evaluated. 'Compared with Z-axis sampling 3 and rotating 45 degrees z-sleeve sampling 7 of the two data. Figure 5 and analysis and evaluation of the reconstructed shirt image. The parameters are set as follows: aperture 2 mm, object to pinhole distance 4G bribe, pinhole spacing 14 77 coffee, peripheral pinhole tilt angle 2 〇.27 degrees and pinhole opening angle 25.7 degrees. Example 5: Pinhole spacing, M355091 The effect of pinhole spacing on the system is mainly the degree of overlap and the angle of incidence. Evaluation was performed using a 7-pin system. The different pinhole spacings were 9.85, 13.5, and 16 mm, and the peripheral pinhole tilt angles were 13.83, 18.7, and 21.8 degrees. Other parameters are set as follows: aperture 2 mm, position rotation 45 degrees, object to pinhole distance 40 mm, and pinhole opening angle 25 7 degrees. The projection of the pinhole spacing simulation and the reconstruction of the image using 3D-MLEM are shown in Fig. 1. The edge of the image with excessive pinhole distance is distorted. The degree of overlap is 〇, 23.56 and 46.96%. The image quality analysis results are shown in Figure 11, which shows the changes in CV and SNR during the iterative process of the central axial section image. There is no overlap between the pinholes and a better snr. Cv has a good pinhole spacing before the best convergence. The pinhole spacing is better after the best convergence. Experimental Example 6: Number of pinholes The effect of different number of holes on the system was compared with the image quality of the 1, 5, 7 and 9 pinhole systems. The optimum sampling frequency is used for each hole number, and the 5, 7 and 9 pinhole system positions are rotated 22.5, 45 and 11.25 degrees. Other parameters are set as follows: aperture 2 mm, pinhole spacing 14.77 mm, peripheral pinhole tilt angle 20.27 degrees, object to pinhole distance 40 mm, and pinhole opening angle 25.7 degrees. Experimental Example 7 System Performance Evaluation Using a more complex 4 cylindrical prosthesis, Figure 6 further evaluates the 5, 7 and 9 pinhole systems 12 'M355091 performance, P1 and P2: radius 1 mm, height 18 mm, center distance between the two 4 ; p3 and P4 : radius 1.5 mm, height l8 mm, center distance between the two is 6 mm. The injection activity is 1.6 mCi ’ each projection simulation of the leap second. Parameter setting: Aperture use .- 1 mm ’ other experiment with the same number of pinholes. The number of pinholes in the evaluation results was compared with the spatial resolution and sensitivity of the single pinhole, and the prosthesis was used as a hot in warm prosthesis as shown in Fig. 7. The hot spot is a radius 〇.i5mm point Φ source 'activity is 〇·1 mCi; warm background is 1000 cubic meters of cube, the overall activity is 2 mCi. After each projection is simulated for 1 second, the image is reconstructed, and the central section is used to estimate the full width at half maximum (FWHM). 4 Cylindrical prosthesis uses 3D_mlEM to reconstruct the image as shown in Figure 14. The results show that the 5 and 7-hole systems are more suitable for the actual system. The sensitivity of the 1, 5 and 7-well systems were 285, 1126 and 1521 cps/mCi/mL, respectively, which was 3.95 and 5.34 times higher than the single-hole system. The 7-well system has better sensitivity and therefore best meets our actual system requirements. The results of the hot in warm prosthesis reconstruction are shown in Fig. (15). The half-height full-width analysis single hole is 1.13 mm and the seven holes are 1.41 mm. [Simplified illustration] 13