Object The intraoperative clear delineation between brain tumor and normal tissue in real time is required to ensure near-complete resection without damaging the nearby eloquent brain. Tumor Paint BLZ-100, a tumor ligand chlorotoxin (CTX) conjugated to indocyanine green (ICG), has shown potential to be a targeted contrast agent. There are many infrared imaging systems in use, but they are not optimized to the low concentration and amount of ICG. The authors present a novel proof-of-concept near-infrared (NIR) imaging system using a standard charge-coupled device (CCD) camera for visualizing low levels of ICG attached to the tumors. This system is small, inexpensive, and sensitive. The imaging system uses a narrow-band laser at 785 nm and a notch filter in front of the sensor at the band. The camera is a 2-CCD camera, which uses identical CCDs for both visible and NIR light. Methods The NIR system is tested with serial dilution of BLZ-100 from 1 μM to 50 pM in 5% Intralipid solution while the excitation energy is varied from 5 to 40 mW/cm2. The analog gain of the CCD was changed from 0, 6, and 12 dB to determine the signal-to-noise ratio. In addition to the Intralipid solution, BLZ-100 was injected 48 hours before euthanizing the mice that were implanted with the human glioma cell line. The brain was removed and imaged using the NIR imaging system. Results The authors' results show that the NIR imaging system using a standard CCD is able to visualize the ICG down to 50 nM of concentration with a high signal-to-noise ratio. The preliminary experiment on human glioma implanted in mouse brains demonstrated that BLZ-100 has a high affinity for glioma compared with normal brain tissue. Additionally, the results show that NIR excitation is able to penetrate deeply and has a potential to visualize metastatic lesions that are separate from the main tumor. Conclusions The authors have seen that BLZ-100 has a very high affinity toward human gliomas. They also describe a small, cost-effective, and sensitive NIR system for visualizing brain tumors tagged using BLZ-100. The authors hope that the use of BLZ-100 along with NIR imaging will be useful to delineate the brain tumors in real time and assist surgeons in near-complete tumor removal to increase survival and reduce neurological deficits.
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机译：对象需要实时脑肿瘤和正常组织之间的术中清晰描绘，以确保近乎完全切除，而不会损坏附近的雄性大脑。肿瘤涂料BLZ-100，与吲哚菁绿（ICG）缀合的肿瘤配体氯毒素（CTX），已示出潜在的靶向造影剂。使用许多红外成像系统，但它们没有优化到ICG的低浓度和数量。作者呈现了一种新颖的概念证据，使用标准电荷耦合器件（CCD）相机，用于可视化连接到肿瘤的低水平ICG。该系统很小，廉价，敏感。成像系统在785nm处使用窄带激光器和在带的传感器前面的凹口滤波器。相机是一个2-CCD摄像头，它使用相同的CCD来均可可见和NIR光。方法在5％intralipid溶液中通过1μm至50pm的Slz-100的连续稀释测试NIR系统，同时激发能量在5至40mW / cm 2 中。 CCD的模拟增益从0,6和12 dB变为确定信噪比。除了肠内溶液外，在使用人胶质瘤细胞系植入的小鼠安乐死之前，将BLZ-100注入48小时。使用NIR成像系统除去脑并成像。结果作者的结果表明，使用标准CCD的NIR成像系统能够以高信噪比可视化ICG降至50nm的浓度。植入于小鼠大脑中的人胶质瘤的初步实验表明，与正常脑组织相比，BLZ-100对胶质瘤具有很高的亲和力。另外，结果表明，NIR激发能够深入渗透并且具有可视化与主要肿瘤分离的转移性病变的潜力。结论作者已经看到BLZ-100对人胶质瘤具有非常高的亲和力。他们还描述了一种小型，经济效益和敏感的NIR系统，用于可视化使用BLZ-100标记的脑肿瘤。作者希望使用BLZ-100以及NIR成像的使用将是在实时描绘脑肿瘤的有用，并帮助外科医生在近乎完全的肿瘤去除以增加生存并减少神经缺陷。
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