SignificanceMany 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.AimWe aim to examine the reliability of PACT in the functional phenotyping of mouse models for vision research.ApproachA 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.ResultsQuantitative 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.ConclusionsPACT demonstrated sufficient sensitivity to detecting post-retinal functional deficits.
This study presents a novel method using Photoacoustic Computed Tomography (PACT) with a linear ultrasound (US) transducer array to observe visual-evoked hemodynamic responses in the deep mouse brain. By applying advanced data processing techniques, we successfully isolated hemodynamic responses within critical visual regions. The PACT system's high spatial resolution and deep tissue penetration enabled non-invasive examination of visual-evoked brain activity. Our findings demonstrate the potential of PACT for advancing optical neuroimaging and studying synaptic physiology, brain activities, and retinal diseases.
This study uses a label-free photoacoustic computed tomography (PACT) system with a linear ultrasound transducer array to monitor the visual-evoked hemodynamic responses in the mouse brain. Acoustic signals were collected during retinal photostimulation, utilizing flickering white light. The observed hemodynamic responses occurred in the primary visual cortex (V1), superior colliculus (SC), lateral geniculate nucleus (LGd), olivary pretectal nucleus (OPN), and suprachiasmatic nucleus (SCN). Response magnitudes and latencies were compared between wild-type, retinal degeneration (rd1), and melanopsin knock-out mice, illustrating the potential of our PACT system in studying brain activities related to retinal diseases.
In this study, we developed a label-free photoacoustic computed tomography system to monitor the visually-evoked hemodynamic changes in response to retinal photostimulation by flickering white light. The acoustic signals were collected by a 256-element linear ultrasound transducer array with a 10MHz central frequency, and a 750nm pulsed laser with a 10Hz repetition rate was used as the excitation source to avoid stimulating retinal photoreceptors. During the stimulation, the hemodynamic responses within the visual regions, such as the primary visual cortex, superior colliculus, and suprachiasmatic nucleus, have been observed. This demonstrates that our system can examine visually-evoked brain responses, and has the potential to study the brain activities in mouse models of retinal diseases.
The current functional brain mapping techniques such as fMRI and DOI suffer from limited spatial resolution. Photoacoustic (PA) imaging combines the sensitivity of optical imaging to hemodynamic variations, and spatial resolution of ultrasound detection. In this study, we built a label-free PA computed tomography (PACT) system with a ring-shaped ultrasound array to monitor the hemodynamic changes in the primary visual cortex (V1) of mice in response to retinal photostimulation. The responses of wild-type and retinal degenerate (rd1) mice were compared. A linear-array PACT system was also used to measure the visually-evoked subcortical responses. Therefore, PACT is potential tool to study the effect of retinal degeneration of mice on the visual pathway.
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