Caltech Optical Imaging Laboratory, Andrew and Peggy Cherng Department of Medical Engineering and Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Medicum, Faculty of Medicine, University of Helsinki, Helsinki, 00290, Finland.
Adv Sci (Weinh). 2021 Nov;8(21):e2102474. doi: 10.1002/advs.202102474. Epub 2021 Sep 17.
Photoacoustic tomography (PAT) with genetically encoded near-infrared probes enables visualization of specific cell populations in vivo at high resolution deeply in biological tissues. However, because of a lack of proper probes, PAT of cellular dynamics remains unexplored. Here, the authors report a near-infrared Forster resonance energy transfer (FRET) biosensor based on a miRFP670-iRFP720 pair of the near-infrared fluorescent proteins, which enables dynamic functional imaging of active biological processes in deep tissues. By photoacoustically detecting the changes in the optical absorption of the miRFP670 FRET-donor, they monitored cell apoptosis in deep tissue at high spatiotemporal resolution using PAT. Specifically, they detected apoptosis in single cells at a resolution of ≈3 µm in a mouse ear tumor, and in deep brain tumors (>3 mm beneath the scalp) of living mice at a spatial resolution of ≈150 µm with a 20 Hz frame rate. These results open the way for high-resolution photoacoustic imaging of dynamic biological processes in deep tissues using NIR biosensors and PAT.
光声断层扫描（PAT）结合基因编码的近红外探针，可以在高分辨率下对生物组织深处的特定细胞群体进行体内可视化。然而，由于缺乏合适的探针，细胞动力学的 PAT 仍然未被探索。在这里，作者报道了一种基于近红外荧光蛋白 miRFP670-iRFP720 对的近红外荧光共振能量转移（FRET）生物传感器，它能够对深部组织中活跃的生物过程进行动态功能成像。通过光声检测 miRFP670 FRET 供体的光吸收变化，他们使用 PAT 以高时空分辨率监测深部组织中的细胞凋亡。具体来说，他们以 ≈3 µm 的分辨率在小鼠耳部肿瘤中的单个细胞中检测到了凋亡，并且在活鼠的深部脑肿瘤（头皮下 >3 mm）中以 ≈150 µm 的空间分辨率和 20 Hz 的帧率进行了检测。这些结果为使用近红外生物传感器和 PAT 对深部组织中的动态生物过程进行高分辨率光声成像开辟了道路。
