Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
College of Chemistry and Chemical Engineering, Qingdao University, Qingdao, Shandong 266071, China.
ACS Nano. 2023 Sep 12;17(17):17082-17094. doi: 10.1021/acsnano.3c04690. Epub 2023 Aug 17.
Fluorescence imaging in the second near-infrared (NIR-II) window has attracted considerable interest in investigations of vascular structure and angiogenesis, providing valuable information for the precise diagnosis of early stage diseases. However, it remains challenging to image small blood vessels in deep tissues because of the strong photon scattering and low fluorescence brightness of the fluorophores. Here, we describe our combined efforts in both fluorescent probe design and image algorithm development for high-contrast vascular imaging in deep turbid tissues such as mouse and rat brains with intact skull. First, we use a polymer blending strategy to modulate the chain packing behavior of the large, rigid, NIR-II semiconducting polymers to produce compact and bright polymer dots (Pdots), a prerequisite for fluorescence imaging of small blood vessels. We further developed a robust Hessian matrix method to enhance the image contrast of vascular structures, particularly the small and weakly fluorescent vessels. The enhanced vascular images obtained in whole-body mouse imaging exhibit more than an order of magnitude improvement in the signal-to-background ratio (SBR) as compared to the original images. Taking advantage of the bright Pdots and Hessian matrix method, we finally performed through-skull NIR-II fluorescence imaging and obtained a high-contrast cerebral vasculature in both mouse and rat models bearing brain tumors. This study in Pdot probe development and imaging algorithm enhancement provides a promising approach for NIR-II fluorescence vascular imaging of deep turbid tissues.
近红外二区（NIR-II）荧光成像是研究血管结构和血管生成的热点，为早期疾病的精确诊断提供了有价值的信息。然而，由于荧光团的强光子散射和低荧光亮度，在深部组织中对小血管进行成像仍然具有挑战性。在这里，我们描述了我们在荧光探针设计和图像算法开发方面的共同努力，以实现具有完整颅骨的小鼠和大鼠脑等深部混浊组织中的高对比度血管成像。首先，我们使用聚合物共混策略来调节大的、刚性的 NIR-II 半导体聚合物的链堆积行为，以产生紧凑且明亮的聚合物点（Pdots），这是小血管荧光成像的前提。我们进一步开发了一种稳健的Hessian 矩阵方法来增强血管结构的图像对比度，特别是小而弱荧光的血管。与原始图像相比，全身成像的小鼠获得的增强血管图像的信号与背景比（SBR）提高了一个数量级以上。利用明亮的 Pdots 和 Hessian 矩阵方法，我们最终进行了穿透颅骨的 NIR-II 荧光成像，并在患有脑肿瘤的小鼠和大鼠模型中获得了高对比度的脑血管。这项关于 Pdots 探针开发和图像算法增强的研究为深部混浊组织的 NIR-II 荧光血管成像提供了一种有前途的方法。
