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.
Our research utilizes capacitive micromachined ultrasonic transducers (CMUTs) for advanced photoacoustic (PA) and ultrasound (US) imaging in mice, focusing on visual-evoked hemodynamic responses. CMUTs exhibit superior sensitivity and wider bandwidth than traditional PZT arrays, enabling improved spatial resolution and image quality. Preliminary tests of a 1-D CMUT array demonstrated its potential in capturing hemodynamic responses in the primary visual cortex (V1) and superior colliculus (SC) during retinal photostimulation. With its impressive performance and miniaturization potential, CMUTs show promise for future applications in studying visual responses in transgenic mice and disease models without the need for anesthesia or restraint.
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.
Accurate dose definition is vital for ensuring optimal radiation therapy (RT) outcomes. The combination of ionizing radiation acoustic imaging (iRAI) and volumetric ultrasound imaging (US) holds the potential for real-time and precise determination of the radiation dose on anatomical structures. We developed an iRAI-US dual-modality system, utilizing a custom 2D matrix array transducer for iRAI and a commercial 2D MAT for US. The studies on phantoms quantified the system performance, and then the experiments using a rabbit liver model in vivo achieved online monitoring of dose on anatomy during RT in real time. These findings demonstrated the potential of iRAI-US combined imaging for personalized RT with improved efficacy and safety.
This study illustrates the potential of non-invasive Photoacoustic Microscopy (PAM) to monitor functional changes in a squirrel monkey brain due to peripheral mechanical stimulation. Our unique approach employs a deep Fully Convolutional Neural Network (FCNN) to significantly enhance PAM image quality, improving signal-to-noise ratio and structural similarity index. Notably, functional changes induced by peripheral mechanical stimulation were effectively observed. The study showcases the potential of PAM in neurological applications, advancing our understanding of brain hemodynamics, and the transformative effect of machine learning techniques on PAM image quality, opening new possibilities for future neuroscientific research.
Ionizing radiation acoustic imaging (iRAI) provides the potential to map the radiation dose during radiotherapy in real time. Described here is the development of iRAI volumetric imaging system in mapping the three-dimensional (3D) radiation dose deposition of clinical radiotherapy treatment plan with patient receiving radiation to liver tumor. The real-time visualizations of radiation dose delivered have been archived in patients with liver tumor under a clinical linear accelerator. This proof-of-concept study demonstrated the potential of iRAI to map the dose distribution in deep body during radiotherapy, potentially leading to personalized radiotherapy with optimal efficacy and safety.
Ionizing radiation acoustic imaging (iRAI) provides the potential to map the radiation dose during radiotherapy in real time. Described here is our recent development of an iRAI volumetric imaging system in mapping the three-dimensional (3D) radiation dose deposition of a complex clinical radiotherapy treatment plan. Temporal 3D dose accumulation of a treatment plan was first imaged in a phantom. Then, semi-quantitative iRAI measurements were verified with rabbit liver model in vivo. Finally, for the first time, real-time visualization of radiation dose delivered deep in a patient with liver metastases was successfully performed. These studies demonstrate the potential of iRAI to map the dose distribution in deep body during radiotherapy, potentially leading to personalized radiotherapy with optimal efficacy and safety.
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 feasibility of using photoacoustic imaging (PAI) to measure electrically-evoked hemodynamic responses in a squirrel monkey brain in vivo was examined. A linear-array photoacoustic computed tomography (PACT) system and a high-resolution photoacoustic microscopy (PAM) system were built for imaging subcortical and cortical brain regions, respectively. The hemodynamic responses at multiple cortices, including premotor, primary motor, and primary somatosensory cortices, were monitored. The variations could be observed in all cortices and their underlying cortical and subcortical brain regions. The results from this study validated the potential of PAI technique for multiscale and multi-resolution functional brain mapping for non-human primates.
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.
A new concept to achieve ultrasound-mediated hyperthermia (USHT) with the guidance of X-ray-induced radiation acoustic imaging (xRAI) is proposed. During radiation therapy of cancer patients, the received acoustic signals for xRAI can be used to correct the aberration caused by inhomogeneous acoustic property of human skull and provide guidance for focused ultrasound to achieve USHT with the same ultrasound array at the X-ray dose deposition area. To prove this concept, simulations with a human head model were made for both point targets and a tumor volume. The focused acoustic patterns with and without xRAI-based aberration correction were compared. The feasibility of this xRAI-guided USHT concept was further demonstrated by experimental studies using a human skull.
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