Preclinical photoacoustic neuroimaging using a reverberant cavity

光声成像是一种新兴的基于激光产生的超声的小型动物成像方式，它提供了分辨率为几百微米的厘米级深度的神经血管解剖和功能的实时3D图像。因此，它提供了大量的机会来可视化血液动力学的变化，以研究大脑功能和神经状况，如中风或癫痫的小鼠模型。然而，要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，通常需要由数千个探测器组成的超声阵列。实现这种阵列的成本和技术复杂性令人望而却步，并限制了该技术在临床前的实际应用。为了解决这一问题，我们建议开发一种全新的光声成像仪，在该仪器中，鼠头被封闭在一个声学混响腔中，并且只用一个固定的探测器记录光声波。我们已经从理论上证明了用这种方法可以从单个激光脉冲重建出完整的3D图像。因此，与传统的多通道光声扫描仪相比，它在降低成本和提高采集速度/分辨率方面提供了重大好处。该项目的目的是进行一项为期12个月的概念验证研究，从实验上证明这一方法。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的脑功能研究方面具有重要的互补专业知识。其目的将是通过开发一个原型混响腔并获取组织幻影和小鼠大脑的体内外图像来说明基本的概念验证。预计这项工作将为寻求进一步开发这项技术的后续资金奠定基础，并确立其作为神经科学研究的临床前工具的应用。

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.