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血液活度動態在線分析系統（二代）
一、產品介紹:
該系統適用于藥物動力學血液放射活度實時測量研究（可配合于PET、SPECT、PET/MRI系統）
Twilite 是由 Swisstrace 公司所研發設計的高靈敏度自動血液取樣系統。此系統可與 PET 、SPECT、或 PET/MR 影像系統結合使用，無論是小至實驗動物、大至其他更大的個體，均能夠在線高分辨率采集血液活度實時變化數據。
Twilite 系統的核心是一個設計精巧的偵測頭（探測器），由 LYSO 晶體與屏蔽外來輻射用的醫療級鎢加工製成，因此完全與 MR 影像系統相容。閃爍信號透過兩條可自訂長度的高效率光導管傳輸至光子偵測單元。此設計的偵測頭端完全沒有任何電子零件，所以能夠避免來自其他設備所造成的電磁干擾問題。此外，這樣的設計也能夠將人體研究實驗的潛在風險*小化。
數據采集是使用 PMOD 公司所開發的 PSAMPLE 軟件，藉由 TCP/IP 介面傳輸，允許同時記錄多套 Swisstrace 系統的訊號，例如可同時使用 Twilite 系統與 Twin beta probe 系統。此外，尚有兩個類比訊號輸入孔可同時記錄來自其他儀器的訊號，例如Laser Doppler Flowprobes、ECG 或來自輔助設備的觸發訊號。 PMOD 軟件的功能模塊可對取得的放射活度信號進行離線處理分析。
此系統也脫離計算機獨立工作。儀器前方的觸摸式面板可直接進行操作，并即時顯示測量數據。
Twilite 系統性能優越。除了擁有**的靈敏度外，即使在高輻射值的環境下，仍然呈現出穩定的線性度與信噪比。
Swisstrace 公司的開發人員在放射定量實驗方面具有相當深厚的經驗。系統設計乃針對 PET 系統（包含小動物與人）**化。偵測頭精巧的尺寸尤其適合使用于小動物正子造影系統中，搭配動、靜脈分流管（arterio-venous shunt）， Twilite 系統可測得全血的動脈輸入函數（arterial input function， AIF）而不必將血液抽離體外。
二、實驗結
圖1 圖2 圖3
儀器結構組成（1-9項為產品標配）：
1、連接股動脈與股靜脈的分流管 （自購）
2、蠕動幫浦（Peristaltic Pump）（自購）
3、Twilite 鎢制探測器
4、LYSO 晶體1
5、LYSO 晶體2
6、光導管：傳輸光子訊號至PMT。標準長度2 m，若需使用于MR 系統可延長至10 m
7、光子偵測單元
8、兩個模擬訊號輸入孔（可與其他品牌儀器配合使用，監控呼吸、ECG 或血壓等）
9、TCP/IP 傳輸接口：可透過因特網傳輸或直接與計算機連接，使用PMOD 軟件PSAMPLE 模塊進行數據采集
10、安裝PMOD 軟件的計算機，進行數據采集與分析（自購）
結構說明：動靜脈分流管（小鼠用PE10，大鼠用PE50）可同時用于血壓量測、藥物注射及血液樣本采集等其他功能，如圖3所示。血液樣本采集可用解剖刀在導管上劃一個小口，在采集時間點將導管往缺口方向推，即可取得血液樣本。
●結構與曲線函數（如下圖）
左圖為實驗架構。血流以蠕動泵驅動，從股動脈流出體外，經過耦合訊號偵測頭后，再由股靜脈回到體內。t1與t2兩個三向閥分別用來進行血液取樣與藥物注射。右圖為Twilite 系統所測得的小鼠動脈輸入曲線。
三、系統規格
| 序號 | |||
| 1 | 偵測頭 | 尺寸 | 80 × 62 × 56 mm (L ×W × H). 約5 kg |
| 材質 | 由醫療級鎢加工制成 | ||
| 閃爍晶體 | LYSO | ||
| 聯機 | 兩條高效率光導管，長度2 -- 10 m | ||
| 2 | 性能 | 靈敏度 | 導管內徑0.28 mm: 0.2 cps/kBq/ml（小鼠） |
| 導管內徑0.58 mm: 0.8 cps/kBq/ml（大鼠） | |||
| 導管內徑1.00 mm: 2.4 cps/kBq/ml（更大個體） | |||
| 3 | 線性度 | 6000 cps 以下完全線性（無誤差），在10000 cps以上，誤差小于1% | |
| 4 | 光子偵測單元 | 光子檢測裝置 | 19英寸光子計數裝置與采集系統 |
| 操作 | 可單獨操作，執行系統檢查與校正等功能，觸摸屏實時數據顯[cps] | ||
| 5 | 輸入 | 輔助模擬輸入 | 面板前方提供兩個BNC 規格模擬訊號輸入孔（0 -- 3.3 V） |
| 6 | 數據擷取 | 軟件 | 軟件PMOD 軟件PSAMPLE 模塊 |
| 操作系統 | Windows 7， XP， vista， MacOSX， Linux | ||
| 傳輸接口 | TCP/IP （可選配無線傳輸） |
四、用戶名單
| 序號 | 客戶 | 儀器數量 |
| 1 | University of Zurich | 1 |
| 2 | Federal Institute of Technology， Zurich | 1 |
| 3 | Research Institution Juelich Germany | 1 |
| 4 | University of Antwerp， Belgium | 1 |
| 5 | Research Institute， Paris | 1 |
| 6 | University of Hannover | 1 |
| 7 | University of Oslo | 1 |
| 8 | Genentech， San Francisco | 2 |
| 9 | Amgen Biotechnology | 1 |
五、合作伙伴
PMOD Technologies Ltd. Unitectra
Zurich， Switzerland Zurich， Switzerland
University of Zurich CSEM
Zurich， Switzerland Neuchatel， Switzerland
六、藥物動力學實驗論文(部分摘要)
Quantification of Brain Glucose Metabolism by 18F-FDG PET
with Real-Time Arterial and Image-Derived Input Function in Mice
Malte F. Alf1，2， Matthias T. Wyss3，4， Alfred Buck3， Bruno Weber4， Roger Schibli1，5， and Stefanie D. Kr?mer11Center for
Radiopharmaceutical Sciences of ETH， PSI， and USZ， Institute of Pharmaceutical Sciences， Department of Chemistry and
Applied Biosciences， ETH Zurich， Zurich， Switzerland; 2Laboratory of Functional and Metabolic Imaging， Institute of Physics of
Biological Systems， Ecole Polytechnique Fédérale de Lausanne， Lausanne， Switzerland; 3Department of Nuclear Medicine，
University Hospital Zurich， Zurich， Switzerland; 4Institute of Pharmacology and Toxicology， University of Zurich， Zurich，Switzerland;
and 5Center for Radiopharmaceutical Sciences of ETH， PSI， and USZ， Paul Scherrer Institute PSI， Villigen， Switzerla
Kinetic modeling of PET data derived from mouse modelsremains hampered by thetechnical inaccessibility of an accurateinput function (IF).
In this work， we tested the feasibility of IF measurement with an arteriovenous shunt and a coincidencecounter in mice and compared the method
with an imagederived IF (IDIF) obtained by ensemble-learning independent component analysis of the heart region. Methods: 18F-FDG brain kinetics were quantified in 2 mouse strains， CD1 and C57BL/6， using the standard 2-tissue-compartment model. Fits obtained with the 2 IFs were compared regarding their goodness of fit as assessed by the residuals， fit parameter SD， and Bland–Altman analysis. Results: On average， cerebral glucose metabolic rate was 10% higher for IDIF-based quantification.The precision of model parameter fitting was significantly higher using the shunt-based IF， rendering the quantification of single process rate constants feasible. Conclusion: We demonstrated that the arterial IF can be measured in mice with a femoral arteriovenous shunt. This technique resulted in higher precision for kinetic modeling parameters than did use of the IDIF. However，for longitudinal or high-throughput studies， the use of a minimally invasive IDIF based on ensemble-learning independent component analysis represents a suitable alternative.
Key Words: energy metabolism; PET; molecular imaging; glucose; kinetic modeling
J Nucl Med 2013; 54:1–7 DOI: 10.2967/jnumed.112.107474
PET with 18F-FDG is a commonly used method to determine glucose metabolism in animal and human tissues (1). Full quantification of 18F-FDG kinetics can be achieved by applying a 2-tissue-compartment model (2). The model requires the time course of the 18F-FDG concentration in the target organ(tissue time–activity curve) and in arterial plasma (input function， IF). In human brain PET， the IF is commonly measured from a catheter placed in the radial artery. An alternative is derivation of the IF from PET images via values measured in a volume of interest placed over the cardiac ventricles or a large vessel. A prerequisite of image-derived IFs (IDIFs) is the location of the blood pool and the organ of interest in the same field of view. In general， one or more arterial blood samples are measured to calibrate the IDIF. In a recent review article for human PET(3)， the authors concluded that arterial blood sampling remains the preferred method to define the IF， because invasiveness is hardly reduced by the use of an IDIF.
In small animals， the small blood volume is the major constraint for manual blood sampling. This constraint prompted the development of several alternative methods， such as the sampling of very small volumes via a microfluidic chip (4) or the use of b-probes for measuring the blood radioactivity (5，6). Despite these new physical methods， the main research focus has been on developing the use of IDIFs， where blood radioactivity is estimated directly from the dynamic PET images. IDIF generation from simple analysis of blood pool volumes such as the liver or the heart ventricles is flawed by 18F-FDG uptake by the liver or spillover from surrounding myocardium， cardiac motion， and partial-volume effects. Compensation can be achieved to varying degrees by image processing methods such as factor analysis (7)， modelbased techniques (8)， independent component analysis (9)， so-called hybrid IDIFs (e.g.， 10，11)， and cardiac gating combined with improved image reconstruction algorithms (12). Most of these methods rely on at least 1 measure from a blood sample for scaling of the IDIF.Hence， blood sampling is not entirely obviated.
To our knowledge， there is currently no gold standard to define the real-time 18F-FDG arterial IF in mice in a reliable and easily accessible manner. In this study， we adapted a method for direct blood radioactivity measurements and an approach for the generation of IDIFs for use in mice. We acquired real-time blood radioactivity curves by means of a new coincidence counter in combination with an arteriovenous shunt and compared the findings to IDIFs generated from PET data of the cardiac region with an ensemblelearning independent component analysis (EL-ICA) algorithm (13).We used 2 different mouse strains to explore the possible strain dependency of our methods: C57BL/6 mice， because they are relevant for studies of genetically modified animals， and CD1 mice， because they are valuable as disease models，such as cerebral ischemia (14). The purpose of this work was 2-fold. First， we evaluated whether the arteriovenous-shunt/ counter technique， which was previously demonstrated in rats (15)， is also feasible in mice. Second， we compared 18F-FDG kinetic parameters and fit precisions obtained with the experimental shunt IF and the IDIF.
