Development of electro-optically tuneable Fabry-Pérot ultrasound sensors for high speed biomedical photoacoustic imaging

光声（PA）成像是一种新兴的生物医学成像模式，它依赖于吸收短光脉冲来在组织内产生超声波。这些波传播到皮肤，在皮肤处，换能器阵列检测到时间分辨的PA信号。然后使用图像重建算法获得高分辨率（数十微米）3-D图像。PA成像结合了许多强大的属性，例如多尺度成像能力，范围从单细胞分辨率（使用PA显微镜）到使用PA断层扫描的微米分辨率（mm深度处的数十微米到cm深度处的数百微米），以及在血管化软组织中的强对比度，其中其他模态，如MRI，X射线CT和超声缺乏灵敏度。它是非侵入性的，并结合了纯光学成像模式的优点，即光谱特异性，与传统的超声成像的优点，即高空间分辨率。虽然压电超声检测器是最广泛使用的，但当应用于表面的高分辨率PA成像时，它们具有明显的缺点，因为所需的小有源元件尺寸导致低的声学灵敏度。相比之下，光学超声探测器，如法布里-珀罗干涉仪（FPI）传感器已被证明提供非常小的，衍射限制的元件尺寸，高声学灵敏度，近均匀的频率响应（直流-100 MHz），和光学透明的有效的后向模式PA成像。基于FPI传感器的全光学PA扫描仪可以说为厘米深度的高分辨率3D成像设定了标准。它的成像性能使得能够在临床前研究中获得引人注目的大脑、皮肤和肿瘤血管图像。然而，扫描仪的当前设计具有一个显著的限制：与基于压电检测器阵列的最先进的扫描仪相比，成像速度低。该项目旨在通过开发用于快速生物医学PA成像的电光可调FPI传感器来克服这一限制，并满足以下目标：1）电光（EO）可调聚合物间隔物的开发和合成，2）EOFPI传感器制造方法的开发，3）EOFPI控制和并行读出的仪器开发，以及4）使用并行检测的高帧速率PA成像的演示。预期这将提供利用FPI感测概念可实现的成像速度的阶跃变化。最终，该技术可以提供真实的时间体积、高分辨率PA成像，这将为广泛的临床前和临床应用打开大门，例如神经功能成像和血流成像。在这个项目中，目的是证明基于EOFPI的PA成像的原理证明及其随之而来的成像速度的提高。

Photoacoustic (PA) imaging is an emerging biomedical imaging modality that relies on the absorption of short optical pulses to generate ultrasound waves within the tissue. These waves propagate to the skin where time-resolved PA signals are detected by transducer arrays. High resolution (tens of microns) 3-D images are then obtained using image reconstruction algorithms. PA imaging combines a number of powerful attributes, such as multiscale imaging capabilities ranging from single cell resolution (using PA microscopy) to micron resolution using PA tomography (tens of microns at mm depths to hundreds of microns at cm depths) and strong contrast in vascularised soft tissues where other modalities such as MRI, x-ray CT, and ultrasound lack sensitivity. It is non-invasive and combines the advantages of purely optical imaging modalities, i.e. spectral specificity, with those of conventional ultrasound imaging, i.e. high spatial resolution. While piezoelectric ultrasound detectors are the most widely used, they have distinct drawbacks when applied to superficial, high resolution PA imaging since the required small active element size results in low acoustic sensitivity. By contrast, optical ultrasound detectors such as Fabry-Pérot interferometer (FPI) sensors have been shown to provide very small, diffraction-limited element sizes, high acoustic sensitivity, near-uniform frequency response (dc-100MHz), and optical transparency for efficient backward mode PA imaging. The all-optical PA scanner based on the FPI sensor has arguably set the standard for high resolution, 3-D imaging to cm depths. Its imaging performance has enabled the acquisition of compelling images of the vasculature in the brain, the skin, and tumours in preclinical studies. However, the current design of the scanner has one significant limitation: low imaging speed compared to state-of-the-art scanners based on piezoelectric detector arrays. This project aims to overcome this limitation by developing electro-optically tuneable FPI sensors for fast biomedical PA imaging by meeting the following objectives: 1) development and synthesis of electro-optically (EO) tuneable polymer spacers, 2) development of methods for the fabrication of EOFPI sensors, 3) instrumentation development for EOFPI control and parallelised readout, and 4) demonstration of high frame rate PA imaging using parallelised detection. This is expected to provide a step change in imaging speed achievable with the FPI sensing concept. Ultimately, this technology could provide real time volumetric, high resolution PA imaging, which would open the door to a broad range of preclinical and clinical applications, such as neuro-functional imaging and blood flow imaging. In this project, the aim is to demonstrate the proof-of-principle of EOFPI-based PA imaging and its attendant increase in imaging speed.