In vivo quantification of fluorescent molecular markers in real-time by ratio Imaging for diagnostic screening and image-guided surgery
In vivo quantification of fluorescent molecular markers in real-time by ratio Imaging for diagnostic screening and image-guided surgery
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DOI：
10.1002/lsm.20525
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发表时间：
2007-08-01
影响因子：
2.4
通讯作者：
Lilge, L.
中科院分区：
文献类型：
--
作者：
Bogaards, A.;Sterenborg, H. J. C. M.;Lilge, L.
“分子诊断筛选”和“分子图像引导手术”的未来应用将需要具有高分辨率和高通量（类似于>= 30帧/秒）的分子标记物图像。MRI、SPECT、PET、光学荧光断层扫描、超光谱荧光成像和生物发光成像不能提供如此高的帧速率。2D光学荧光成像可以提供具有高分辨率和高通量的表面图像。准确定量体内荧光的能力对于提取疾病状态的功能信息至关重要，然而可用的方法很少。在这里，引入比率2D量化方法。通过数学建模的性能进行了评估，使用类似的生物组织与荧光标记原卟啉IX的光学性质。在实验上的性能进行了评估，在不同的光学特性，采用一种新的原型临床成像系统的光学幻影。在接受乳房切除术的患者中证明了实时图像引导手术的临床可行性。讨论了引入的方法导致增加的定量性能的原因，随后进行修改，因此它可以应用于新型荧光分子标记物，如酞菁4和双荧光标记物。这些提供了额外的优点，因为这些可以提供对标记物浓度的线性响应，并进一步最小化对自发荧光和光学性质的依赖性，如通过建模所证明的。
Future applications of "molecular diagnostic screening" and "molecular image-guided surgery" will demand images of molecular markers with high resolution and high throughput (similar to >= 30 frames/second). MRI, SPECT, PET, optical fluorescence tomography, hyper-spectral fluorescence imaging, and bioluminescence imaging do not offer such high frame rates. 2D optical fluorescence imaging can provide surface images with high resolution and high throughput. The ability to accurately quantify the fluorescence in vivo is critical to extract functional information of the disease state, however few methods are available. Here, a ratiometric 2D quantification method is introduced. Through mathematical modeling the performance was evaluated using optical properties that resembled biological tissues with the fluorescent marker Protoporhyrin IX. Experimentally the performance was evaluated in optical phantoms with different optical properties employing a novel prototype clinical imaging system. The clinical feasibility of real-time, image-guided surgery was demonstrated in patients undergoing prostatectomy. Discussed are the reasons why the introduced method leads to an increased quantification performance followed by modifications so it can be applied to novel fluorescent molecular markers as phthalocyanine 4 and dual-fluorescent markers. These offer additional advantages as these can provide a linear response to marker concentration and further minimize the dependence on autofluorescence and optical properties, as demonstrated through modeling.