Preclinical photoacoustic neuroimaging using a reverberant cavity

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.

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 method.

If successful, the proposed research will set the experimental groundwork for developing an entirely new type of photoacoustic neuroimaging instrument that can acquire real-time 3D images of deep brain anatomy and function in small animals. By utilising just a single detector, it offers a major advantage in terms of cost and technical complexity over current multichannel photoacoustic scanners. Ultimately, it is anticipated that this will contribute to the translation of photoacoustic neuroimaging from laboratory based experimental technique to a powerful investigative tool that can be used routinely for preclinical neuroscience research. The impact of the technology could ultimately extend to improving our understanding of brain function, conditions such as stroke or traumatic brain injury and the biology of diseases such as epilepsy as well as contributing to the development of new therapies and interventions.