Chen Si, Chen Hao, Li Xinxin, He Shuqing, Shou Kangquan, Qian Kun, Fang Zhao, Gu Feng, Chang Baisong, Cheng Zhen
Department of Neurology, Xiangya Hospital, Central South University, Xiangya Road 88, Changsha, 410008, China.
Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Canary Center at Stanford for Cancer Early Detection, Stanford University, California, 94305-5344, USA.
Adv Sci (Weinh). 2025 Apr;12(16):e2416390. doi: 10.1002/advs.202416390. Epub 2025 Mar 5.
Cerebral collateral circulation and blood-brain barrier (BBB) are critically required to maintain the normal brain functions, a fact stressing the need for accurate and in vivo diagnostic tools that can afford valuable pathophysiological insight into the functioning of neurovascular unit in space and time. Currently, understanding of collateral perfusion and BBB evolution under both physiological and pathological conditions remains sparse, largely owing to limitations in methods for recording diminutive route of cerebral blood flow. Here, it is reported that highly crystalline semiconducting organic nanoprobes (named 4T-BSA) composed of small-molecule dye and bovine serum albumin showed vast potential for live-brain vascular imaging in the second near-infrared window (NIR-II, 1000-1700 nm). The 4T-BSA nanoprobes had superior imaging penetration depth in intact mouse brain with high signal-to-background ratio (SBR) of 6.0 and down to sub-50-µm spatial resolution of cerebral vasculature in three typical models of neurological pathophysiology. By visualizing the vascular collateral perfusion and albumin leakage, 4T-BSA nanoprobes identified the pathological activities of brain associated with the arterial/venous collateral flow network and BBB disruption. It is anticipated that NIR-II imaging of cerebral collateral circulation and BBB disruption will bring broad opportunities to address major medical challenges across timely, protective, and restorative interventions for neurological diseases.
脑侧支循环和血脑屏障（BBB）对于维持正常脑功能至关重要，这一事实凸显了对准确的体内诊断工具的需求，这些工具能够在空间和时间上为神经血管单元的功能提供有价值的病理生理学见解。目前，对于生理和病理条件下侧支灌注和血脑屏障演变的理解仍然匮乏，这主要归因于记录脑血流微小路径方法的局限性。在此，据报道，由小分子染料和牛血清白蛋白组成的高度结晶的半导体有机纳米探针（命名为4T-BSA）在第二近红外窗口（NIR-II，1000 - 1700 nm）显示出在活体脑血管成像方面的巨大潜力。4T-BSA纳米探针在完整小鼠脑中具有卓越的成像穿透深度，在三种典型的神经病理生理学模型中，其信号背景比（SBR）高达6.0，并且脑脉管系统的空间分辨率低至50 µm以下。通过可视化血管侧支灌注和白蛋白渗漏，4T-BSA纳米探针识别出与动/静脉侧支血流网络和血脑屏障破坏相关的脑部病理活动。预计脑侧支循环和血脑屏障破坏的NIR-II成像将为应对神经疾病的及时、保护性和恢复性干预中的重大医学挑战带来广泛机遇。
