Longitudinal optical imaging of tumor metabolism and hemodynamics
Longitudinal optical imaging of tumor metabolism and hemodynamics
复制标题
DOI：
10.1117/1.3285584
复制
发表时间：
2010-01-01
影响因子：
3.5
通讯作者：
Dewhirst, Mark W.
中科院分区：
文献类型：
--
作者：
Skala, Melissa C.;Fontanella, Andrew;Dewhirst, Mark W.
肿瘤缺氧的一个重要特征是其时间不稳定性，或称为“循环缺氧”。“循环缺氧的主要后果是增加肿瘤的侵袭性和治疗抵抗力，超过慢性缺氧。肿瘤代谢需求、血红蛋白氧饱和度和血流的纵向成像将为了解肿瘤中循环缺氧的机制和分布提供有价值的见解。通过光学氧化还原比（FAD/NADH的荧光强度）的代谢需求的荧光成像、血红蛋白氧饱和度的吸收显微镜检查以及血管形态和血流的多普勒光学相干断层扫描被组合以每6小时非侵入性地监测小鼠背部皮肤褶皱窗口室肿瘤模型（人鳞状细胞癌）中的氧供应和需求的变化，持续36小时。发现代谢需求、血氧和血流量的生物标志物均随时间显著变化（p < 0.05）。氧供应和需求的这些变化叠加在肿瘤中代谢需求随着与最近血管的距离而显著（p < 0.05）下降（在正常组织中未观察到这种梯度）。显著（p < 0.05），但弱（r
An important feature of tumor hypoxia is its temporal instability, or "cycling hypoxia." The primary consequence of cycling hypoxia is increased tumor aggressiveness and treatment resistance beyond that of chronic hypoxia. Longitudinal imaging of tumor metabolic demand, hemoglobin oxygen saturation, and blood flow would provide valuable insight into the mechanisms and distribution of cycling hypoxia in tumors. Fluorescence imaging of metabolic demand via the optical redox ratio (fluorescence intensity of FAD/NADH), absorption microscopy of hemoglobin oxygen saturation, and Doppler optical coherence tomography of vessel morphology and blood flow are combined to noninvasively monitor changes in oxygen supply and demand in the mouse dorsal skin fold window chamber tumor model (human squamous cell carcinoma) every 6 h for 36 h. Biomarkers for metabolic demand, blood oxygenation, and blood flow are all found to significantly change with time (p < 0.05). These variations in oxygen supply and demand are superimposed on a significant (p < 0.05) decline in metabolic demand with distance from the nearest vessel in tumors (this gradient was not observed in normal tissues). Significant (p < 0.05), but weak (r