Chang Kai-Wei, Wang Xueding, Wong Kwoon Y, Xu Guan
University of Michigan, Department of Biomedical Engineering, Ann Arbor, Michigan, United States.
University of Michigan, Department of Radiology, Ann Arbor, Michigan, United States.
Neurophotonics. 2024 Jul;11(3):035005. doi: 10.1117/1.NPh.11.3.035005. Epub 2024 Jul 30.
Many techniques exist for screening retinal phenotypes in mouse models in vision research, but significant challenges remain for efficiently probing higher visual centers of the brain. Photoacoustic computed tomography (PACT), with optical sensitivity to hemodynamic response (HR) in brain and ultrasound resolution, provides unique advantages in comprehensively assessing higher visual function in the mouse brain.
We aim to examine the reliability of PACT in the functional phenotyping of mouse models for vision research.
A PACT-ultrasound (US) parallel imaging system was established with a one-dimensional (1D) US transducer array and a tunable laser. Imaging was performed at three coronal planes of the brain, covering the primary visual cortex and the four subcortical nuclei, including the superior colliculus, the dorsal lateral geniculate nucleus, the suprachiasmatic nucleus, and the olivary pretectal nucleus. The visual-evoked HR was isolated from background signals using an impulse-based data processing protocol. mice with rod/cone degeneration, melanopsin-knockout (mel-KO) mice with photoreceptive ganglion cells that lack intrinsic photosensitivity, and wild-type mice as controls were imaged. The quantitative characteristics of the visual-evoked HR were compared.
Quantitative analysis of the HRs shows significant differences among the three mouse strains: (1) mice showed both smaller and slower responses compared with wild type ( , ) and (2) mel-KO mice had lower amplitude but not significantly delayed photoresponses than wild-type mice ( , ). These results agree with the known visual deficits of the mouse strains.
PACT demonstrated sufficient sensitivity to detecting post-retinal functional deficits.
在视觉研究中，存在多种用于筛选小鼠模型视网膜表型的技术，但在有效探测大脑更高视觉中枢方面仍存在重大挑战。光声计算机断层扫描（PACT）对大脑中的血流动力学反应（HR）具有光学敏感性且具备超声分辨率，在全面评估小鼠大脑的更高视觉功能方面具有独特优势。
我们旨在检验PACT在视觉研究小鼠模型功能表型分析中的可靠性。
建立了一个PACT-超声（US）并行成像系统，该系统配备一维（1D）超声换能器阵列和可调谐激光器。在大脑的三个冠状平面进行成像，覆盖初级视觉皮层和四个皮层下核，包括上丘、背外侧膝状核、视交叉上核和橄榄前顶盖核。使用基于脉冲的数据处理协议从背景信号中分离出视觉诱发的HR。对患有视杆/视锥细胞退化的小鼠、缺乏内在光敏性的光感受性神经节细胞的黑视蛋白敲除（mel-KO）小鼠以及作为对照的野生型小鼠进行成像。比较视觉诱发HR的定量特征。
对HR的定量分析显示三种小鼠品系之间存在显著差异：（1）与野生型相比，患有视杆/视锥细胞退化的小鼠显示出更小且更慢的反应（ ， ），以及（2）mel-KO小鼠的光反应幅度较低，但与野生型小鼠相比光反应延迟不显著（ ， ）。这些结果与小鼠品系已知的视觉缺陷一致。
PACT在检测视网膜后功能缺陷方面表现出足够的敏感性。
