组织鬼怪模拟，以评估乳癌手术潜在的近红外荧光成像中的应用
Summary
Near-infrared fluorescence (NIRF) imaging may improve therapeutic outcome of breast cancer surgery by enabling intraoperative tumor localization and evaluation of surgical margin status. Using tissue-simulating breast phantoms containing fluorescent tumor-simulating inclusions, potential clinical applications of NIRF imaging in breast cancer patients can be assessed for standardization and training purposes.
Abstract
不准确的术中肿瘤的定位及手术切缘状态结果在保乳手术（BCS）的次优结果的评价。光学成像，特别是近红外荧光（NIRF）成像，可以通过提供的外科医生用在实时前和术中肿瘤的定位工具降低阳性手术切缘的下面BCS的频率。在目前的研究中，NIRF引导BCS的潜在利用组织模拟乳房假体的标准化和培训的原因进行了评价。
乳房假体与媲美正常乳腺组织的光学特性来模拟乳腺癌保乳手术。肿瘤模拟含有荧光染料吲哚菁绿（ICG）的夹杂物被结合在体模在预定的位置和成像前和术中肿瘤的定位，实时NIRF引导肿瘤切除术，NIRF制导评估手术的程度，以及手术切缘术后评估。定制的NIRF相机作为一种临床原型成像的目的。
含肿瘤模拟夹杂物的乳房假体提供了一个简单，价格低廉，用途广泛的工具来模拟并评估术中肿瘤成像。凝胶状幻影具有类似于人体组织的弹性属性，并且可以使用常规的外科手术器械进行切割。此外，该模体含有血红蛋白和脂肪乳用于模仿吸收的光子和散射，分别建立类似于人类乳腺组织均匀的光学特性。 NIRF成像的主要缺点是有限的穿透深度的光子穿过组织，从而阻碍深层肿瘤（非侵袭性）成像反射照明策略传播时。
Introduction
保乳手术（BCS），其次是放射治疗是乳腺癌患者的标准治疗为T 1-T 2乳腺癌1,2。不准确的手术结果的阳性手术切缘在20至40％的谁接受BCS，因此需要附加的外科手术或放射治疗3,4,5病人的程度术评估。虽然广泛切除邻近健康乳房组织可能会降低手术切缘阳性的频率，这也将阻碍美容效果，并增加合并症6,7。因此，需要新的技术，提供了对原发肿瘤的位置和手术的程度术的反馈。光学成像，特别是近红外荧光（NIRF）成像，可以通过提供的外科医生用的r中前和术中肿瘤的定位工具减少以下BCS阳性手术切缘的频率EAL时间。最近，我们小组汇报了卵巢癌患者先在人类试验的肿瘤靶向荧光成像，显示出这项技术来检测原发肿瘤及腹腔转移癌具有较高的敏感性8的可行性。在继续到临床研究中的乳腺癌患者，但是，各种肿瘤靶向NIRF成像应用中的BCS的可行性已经可以使用临床前体模进行评价。
下面的研究方案介绍含有荧光肿瘤模拟夹杂9组织模拟乳房假体的使用NIRF成像。幽灵提供了一个廉价和灵活的工具来模拟前和术中肿瘤定位，实时NIRF引导肿瘤切除术，对手术切缘状况进行评估，并检测残留病灶。凝胶状幻影具有类似于人体组织的弹性属性，并且可以使用常规s中被切urgical仪器。在模拟的手术过程中，外科医生通过触觉信息（在可触知的夹杂物的情况下）和手术区域的视觉检查指导。此外，NIRF成像应用，以提供对手术的程度实时术中反馈的外科医生。
但是应当强调的是，NIRF成像需要使用的荧光染料。理想地，荧光染料，应使用能发出在近红外光谱范围内的光子（650 – 900纳米），以尽量减少由分子在组织生理学上丰富的吸收的光子和散射（ 例如 ，血红蛋白，脂质，弹性蛋白，胶原，和水） 10,11。而且，自体荧光（ 即，在由于在活细胞中的生化反应组织中的固有荧光活性）被最小化，在近红外光谱范围内，产生最佳的肿瘤-背景比11。由共轭NIRF染料肿瘤精华素泰德部分（ 例如，单克隆抗体），可用于术中成像应用而获得的靶向递送的荧光染料。
由于人的眼睛是不敏感的，在近红外光谱范围内点亮，高灵敏度的摄像机装置所需的NIRF成像。已经开发了几个NIRF成像系统，术中使用迄今12。在当前的研究中，我们使用一个自定义的构建是在术中的合作与应用慕尼黑工业大学开发NIRF成像系统。该系统允许同时获取彩色图像和荧光图像。以提高荧光图像的精度，校正方案为光强变化的组织实施。详细描述通过Themelis 等人提供的。13
Protocol
Representative Results
Discussion
我们通过使用乳房形幻影集成肿瘤模拟夹杂模拟NIRF制导BCS的潜在的临床应用。术中肿瘤的定位，NIRF引导下肿瘤切除术，手术的程度的评估，以及手术切缘术后评估中使用自定义构建NIRF摄像系统中的所有可行的。非侵入性的检测荧光肿瘤模拟夹杂物仅是为夹杂物定位在虚线组织在2厘米或更小的深度是可行的。术，但是，在有限的信号的穿透深度在很大程度上解决了由BCS手术的性质，其中，所述外…
Disclosures
The authors have nothing to disclose.
Acknowledgements
This work was supported by a grant from the Jan Kornelis de Cock foundation.
Materials
| Bovine hemoglobin | Sigma-Aldrich, Zwijndrecht, The Netherlands | H2500 | Simulates absorption of photons in tissue |
| Intralipid 20% | Sigma-Aldrich, Zwijndrecht, The Netherlands | I141 | Simulates scattering of photons in tissue |
| Silicone A translucent 40 (2-components poly-addition silicone) | NedForm, Geleen, The Netherlands | N/A | Package consists of components A and B, that should be mixed one on one (A:B=10:1). Link to manufacturers page: http://tinyurl.com/ncjq7jx |
| Gelatine 250 Bloom | Sigma-Aldrich, Zwijndrecht, The Netherlands | 48724 | Construction of breast-shaped phantoms |
| Agarose | Hispanagar, Burgos, Spain | N/A | Construction of tumor-simulating inclusions |
| Tris | Sigma-Aldrich, Zwijndrecht, The Netherlands | T1503 | |
| Hcl | Sigma-Aldrich, Zwijndrecht, The Netherlands | 258148 | |
| NaCl | Sigma-Aldrich, Zwijndrecht, The Netherlands | S9888 | |
| NaH3 | Merck, Darmstadt, Germany | 822335 | CAUTION: severe poison. The toxicity of this compound is comparable to that of soluble alkali cyanides and the lethal dose for an adult human is about 0.7 grams. |
| Examples of NIRF imaging devices for intraoperative application: | |||
| T2 NIRF imaging platform | SurgVision BV, Heerenveen, The Netherlands | N/A | Customized NIRF imaging system used in the current study. More details available at www.surgvision.com |
| Photodynamic Eye | Hamamatsu Photonics Deutschland GmbH, Herrsching am Ammersee, Germany | PC6100 | www.iht-ltd.com |
| FLARE imaging system kit | The FLARE Foundation Inc, Wayland, MA, USA | N/A | www.theflarefoundation.org |
| Fluobeam | Fluoptics, Grenoble, France | N/A | www.fluoptics.com |
| Artemis handheld camera | Quest Medical Imaging BV, Middenmeer, the Netherlands | N/A | www.quest-mi.com |
| Examples of NIRF fluorescent dyes for intraoperative application: | |||
| Indocyanine green | ICG-PULSION, Feldkirchen, Germany | PICG0025DE | Clinical grade fluorescent dye for NIRF imaging used in the current study. More details available at www.pulsion.com |
| IRDye 800CW NHS Ester | LI-COR Biosciences, Lincoln, NE, USA | 929-70021 | www.licor.com |
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