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Photoacoustic spectroscopic imaging of intra-tumor heterogeneity and molecular identification

机译:肿瘤内非均其性和分子识别的光声光谱成像

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Purpose. To evaluate photoacoustic spectroscopy as a potential imaging modality capable of measuring intra-tumor heterogeneity and spectral features associated with hemoglobin and the molecular probe indocyanine green (ICG). Material and Methods. Immune deficient mice were injected with wildtype and VEGF enhanced MCF-7 breast cancer cells or SKOV3x ovarian cancer cells, which were allowed to grow to a size of 6-12 mm in diameter. Two mice were imaged alive and after euthanasia for (oxy/deoxy)-hemoglobin content. A 0.4 mL volume of 1 μg/mL concentration of ICG was injected into the tail veins of two mice prior to imaging using the photoacoustic computed tomography (PCT) spectrometer (Optosonics, Inc., Indianapolis, IN 46202) scanner. Mouse images were acquired for wavelengths spanning 700-920 nm, after which the major organs were excised, and similarly imaged. A histological study was performed by sectioning the organ and optically imaging the fluorescence distribution. Results. Calibration of PCT-spectroscopy with different samples of oxygenated blood reproduced a hemoglobin dissociation curve consistent with empirical formula with an average error of 5.6%. In vivo PCT determination of SaO2 levels within the tumor vascular was measurably tracked, and spatially correlated to the periphery of the tumor. Statistical and systematic errors associated with hypoxia were estimated to be 10 and 13%, respectively. Measured ICG concentrations determined by contrast-differential PCT images in excised organs (tumor, liver) were approximately 0.8 μg/mL, consistent with fluorescent histological results. Also, the difference in the ratio of ICG concentration in the gall bladder-to-vasculature between the mice was consistent with excretion times between the two mice. Conclusion. PCT spectroscopic imaging has shown to be a noninvasive modality capable of imaging intra-tumor heterogeneity of (oxy/deoxy)-hemoglobin and ICG in vivo, with an estimated error in SaO2 at 17% and in ICG at 0.8 μg/mL in excised tissue. Ongoing development of spectroscopic analysis techniques, probe development, and calibration techniques are being developed to improve sensitivity to both exogenous molecular probes and (oxy/deoxy)-hemoglobin fraction.
机译:目的。为了评估光声光谱作为能够测量肿瘤内血红蛋白和分子探针吲哚菁绿(ICG)相关的肿瘤内异质性和光谱特征的潜在成像模态。材料与方法。用野生型和VEGF增强的MCF-7乳腺癌细胞或SKOV3X卵巢癌细胞注射免疫缺陷小鼠,其允许长度为6-12mm的直径。两只小鼠在Euthanasia(氧/脱氧) - 血红蛋白含量上成熟和后成像。在使用光声计算机断层扫描(PCT)光谱仪(PCT)光谱仪(PCT)光谱仪之前,在成像之前将0.4ml体积为1μg/ ml浓度的Icg注入两只小鼠的尾静脉。(OptiSonics,Inc.,Indianapolis,46202)扫描仪。在跨越700-920nm的波长获取鼠标图像,之后切除主要器官并类似地成像。通过切割器官和光学成像荧光分布来进行组织学研究。结果。具有不同含氧血液样品的PCT光谱的校准再现与经验配方一致的血红蛋白离解曲线,其平均误差为5.6%。体内PCT测定肿瘤血管内的SaO2水平被测追踪,并在空间上与肿瘤的周边相关。估计与缺氧相关的统计和系统误差分别为10%和13%。测量通过在切除的器官(肿瘤,肝脏)中的对比差分PCT图像测定的ICG浓度约为0.8μg/ mL,与荧光组织学结果一致。而且,小鼠胆囊与脉管系统中的ICG浓度与小鼠之间的含量比的差异一致于两只小鼠之间的排泄时间。结论。 PCT光谱成像已经显示为能够在体内成像(氧/脱氧) - 半血红蛋白和ICG的肿瘤内非均质性的非侵入式模态,在切除的组织中在0.8μg/ ml下在17%和ICG中的SaO 2估计误差。正在开发持续发展光谱分析技术,探测器和校准技术,以提高对外源分子探针的敏感性和(氧/脱氧) - 半球蛋白级分。

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