Preclinical photoacoustic neuroimaging using a reverberant cavity

光声成像是一种新兴的基于激光超声的小动物成像模式，其提供了以几百微米的分辨率提供厘米级深度的神经血管解剖和功能的实时3D图像的前景。因此，它提供了大量的机会来可视化血液动力学变化，用于研究脑功能和神经系统疾病，如小鼠模型中的中风或癫痫。然而，以足够高的帧速率获取高分辨率3D图像以可视化小鼠大脑中的动态神经生理事件通常需要由数千个检测器组成的超声阵列。实现这种阵列的成本和技术复杂性是令人望而却步的，并且限制了该技术的实际临床前应用。我们建议通过开发一种全新的光声成像仪器来解决这一问题，在该仪器中，鼠标头被封闭在声学混响腔中，并且仅用单个固定检测器记录光声波。我们已经从理论上证明，一个完整的3D图像可以用这种方法从一个单一的激光脉冲重建。因此，它提供了主要的好处，在成本降低和提高采集速度/分辨率方面超过传统的多通道光声扫描仪。该项目的目的是进行为期12个月的概念验证研究，以实验方式证明这种方法。该项目将涉及两个研究小组之间的新合作，这两个研究小组在光声仪器和图像重建方法以及小动物模型中的脑功能研究方面具有重要的互补专业知识。我们的目标将是说明基本的概念验证，通过开发一个原型混响腔，并获取组织幻影和小鼠大脑离体和体内的图像。预计这项工作将为寻求后续资金奠定基础，以进一步开发该技术并将其应用于神经科学研究的临床前工具。

Photoacoustic imaging is an emerging small animal imaging modality based on laser generated ultrasound that offers the prospect of providing real-time 3D images of neurovascular anatomy and function to cm scale depths with a resolution of a few hundred microns. As it consequence, it offers a wealth of opportunities to visualise haemodynamic changes for studying brain function and neurological conditions such as stroke or epilepsy in mouse models. However, acquiring a high resolution 3D image at sufficiently high frame rates to visualise dynamic neurophysiological events in the mouse brain typically requires an ultrasound array composed of several thousand detectors. The cost and technical complexity of realising such an array is prohibitive and limits the practical preclinical application of the technique. We propose to address this by developing an entirely novel photoacoustic imaging instrument in which the mouse head is enclosed in an acoustically reverberant cavity and the photoacoustic waves are recorded with just a single stationary detector. We have shown theoretically that a complete 3D image can be reconstructed with this approach from just a single laser pulse. It thus offers major benefits in terms of cost reduction and improved acquisition speed/resolution over conventional multichannel photoacoustic scanners. The aim of the project is to undertake a 12 month proof-of-concept study to demonstrate this approach experimentally. The project will involve a new collaboration between two research groups who have significant complementary expertise in photoacoustic instrumentation and image reconstruction methods and the study of brain function in small animal models. The objective will be to illustrate basic proof-of-concept by developing a prototype reverberant cavity and acquiring images of tissue phantoms and the mouse brain ex vivo and in vivo. It is anticipated that this work will set the scene for seeking follow-on funding to further develop the technology and establish its application as a preclinical tool in neuroscience research.