■在视觉研究中,有许多技术可以在小鼠模型中筛选视网膜表型,但是有效探测大脑的高级视觉中心仍然存在重大挑战。光声计算机断层扫描(PACT),具有对脑血流动力学反应(HR)的光学敏感性和超声分辨率,在全面评估小鼠大脑中更高的视觉功能方面提供了独特的优势。
■我们旨在检查PACT在用于视觉研究的小鼠模型的功能表型分析中的可靠性。
■建立了具有一维(1D)US换能器阵列和可调谐激光器的PACT-超声(US)并行成像系统。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,背侧外侧膝状核,视交叉上核,和橄榄前盖核。使用基于脉冲的数据处理协议将视觉诱发的HR与背景信号分离。具有杆/锥变性的rd1小鼠,黑视蛋白敲除(mel-KO)小鼠具有缺乏内在光敏性的感光神经节细胞,和作为对照的野生型小鼠成像。比较了视觉诱发HR的定量特征。
■HR的定量分析显示了三种小鼠品系之间的显着差异:(1)与野生型相比,rd1小鼠表现出更小和更慢的反应(n=10,10,p<0.01)和(2)mel-KO小鼠的振幅较低,但没有明显延迟的光反应比野生型小鼠(n=10,10,p<0.01)。这些结果与小鼠品系的已知视觉缺陷一致。
■PACT对检测视网膜后功能缺陷表现出足够的敏感性。
UNASSIGNED: 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.
UNASSIGNED: We aim to examine the reliability of PACT in the functional phenotyping of mouse models for vision research.
UNASSIGNED: 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. rd1 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.
UNASSIGNED: Quantitative analysis of the HRs shows significant differences among the three mouse strains: (1) rd1 mice showed both smaller and slower responses compared with wild type ( n = 10,10 , p < 0.01 ) and (2) mel-KO mice had lower amplitude but not significantly delayed photoresponses than wild-type mice ( n = 10,10 , p < 0.01 ). These results agree with the known visual deficits of the mouse strains.
UNASSIGNED: PACT demonstrated sufficient sensitivity to detecting post-retinal functional deficits.