Laparoscopic contrast enhanced ultrasound for cancer detection

胰腺癌是英国第十大常见癌症，其发病率在过去40年中增加了30%，但5年生存率一直很低，约为8%，在同一时期没有改善。目前只有大约10%的病人适合做手术。早期发现疾病可以通过增加癌症仍然适合手术切除的患者数量，在患者预后中发挥重要作用。那些肿瘤无法触及或进展到不能手术的患者依赖于化疗或免疫疗法。然而，胰腺导管癌的特征是致密的纤维化基质和富含胶原的细胞外基质的演变，这严重限制了治疗药物的渗透。这引起了人们对开发针对这种致密基质的治疗方法的极大兴趣。我们的团队正致力于开发能够更好地成像基质的工具，以支持早期诊断和微创治疗。这集中在新的造影剂，以提高成像灵敏度，但这些新的成像增强和功能的全部潜力只能有效地实现与新的超声硬件和换能器的出现，以利用他们。为了改善患者的治疗效果，迫切需要新的超声换能器，这种换能器可以通过内窥镜或腹腔镜进入组织，从而提供更灵敏的成像，以检测癌症中微观组织的变化。光声成像（PA）是一种基于激光成像的新兴生物医学成像方式。与常规超声相比，PA成像能够提供软组织的功能信息，用于治疗监测和肿瘤检测。研究了US/PA双模成像技术，并将其应用于PA显微镜。近年来，在导管设计、换能器配置和扩展功能方面，这种双模成像已经在血管内和内窥镜应用的微型换能器和导管中实现。腹腔镜下PA成像装置的发展是一个新的课题，其中只有少数原型设计被报道。还有相当大的机会进一步提高设备规格，包括尺寸和性能。本项目将使用理论和实验方法研究先进腹腔镜PA设备的发展。通过与US4US的合作，将进一步支持这种多模态成像的实现，US4US专门从事新产品开发，提供能够操作我们的设备以提供新型超声成像应用的驱动系统。该项目将受益于与另一个FUSE项目和包括胰腺癌专家在内的学术界研究小组的合作。结果将是新的腹腔镜设备，优化了胰腺的对比度增强成像，为治疗提供更好和更早的疾病检测，并改善患者的预后。关键Objectives1。确定腹腔镜下PA装置的成像机制、设备配置和材料2。模拟美国换能器和光学装置，从理论上估计和辅助器件性能的设计。为所提出的腹腔镜PA装置制造和表征US换能器4。为了评估基本的PA成像性能，如分辨率，光影响和信噪比，开发的设备通过幻影5。通过离体和体内研究评估所开发设备的成像性能。

Pancreatic cancer is the tenth most common cancer in the UK, with an incidence that has increased by 30% over the last 40 years but persistently low 5-year survival of approximately 8% that has not improved over the same time period. Currently only around 10% of patients are suited to surgery. Earlier detection of disease could play a significant role in patient outcomes by increasing the number of patients whose cancer remains suited to surgical resection. Those patients whose tumour is not accessible or too advanced for surgery are reliant on chemotherapy or immune-therapy treatments. However, pancreatic ductal carcinoma is characterised by the evolution of a dense fibrotic stroma and collagen-rich extra-cellular matrix that can severely limit the penetration of drugs available to treat it. This has led to considerable interest in the development of therapeutics that can target this dense stroma to enable treatment. Our group is working on developing tools that can allow better imaging of stroma to support earlier diagnosis and minimally invasive treatments. This has focussed on new contrast agents to improve imaging sensitivity, but the full potential of these new imaging enhancement and functionality can only be effectively realised with the advent of new ultrasound hardware and transducers to exploit them. New ultrasound transducers that can access tissues endo- or laparoscopically to deliver imaging more sensitive to the detection of microscale tissue alterations in cancer are urgently required to improve patient outcomes. Photoacoustic (PA) imaging is an emerging biomedical imaging modality based on laser-generated US. Compared to conventional US, PA imaging is capable of providing functional information of soft tissue for treatment monitoring and tumor detection. The US/PA dual-modality imaging has been studied and employed for PA microscopy. In recent years, such dual-modality imaging has been implemented with miniature transducers and catheters for intravascular and endoscopic applications in terms of catheter design, transducer configuration, and extended functions. The topic of laparoscopic PA imaging device development is further new, in which only a few prototype designs have been reported. There remains considerable opportunity to further enhance the device specifications including size and performance. This project will investigate the development of advanced laparoscopic PA devices using both theoretical and experimental approaches. Realization of such multi-modal imaging will be further supported through collaboration with US4US, who specialize in new product development providing the drive systems that capable of operating our devices to deliver novel ultrasound imaging applications. This project will benefit from association with another FUSE project and the research groups of the academics, including pancreatic cancer experts, involved across each of these. The outcome will be new laparoscopic devices optimised for contrast enhanced imaging of the pancreas to deliver better and earlier detection of disease for treatment and improved patient outcomes.Key Objectives1. To identify the imaging mechanisms, device configuration, and materials for the design of a laparoscopic PA device2. To simulate the US transducers and optical setup to theoretically estimate and aid design of device properties3. To fabricate and characterize US transducers for the proposed laparoscopic PA device4. To evaluate the basic PA imaging performance, say resolution, optical fluence and signal-to-noise ratio, of developed devices via phantoms5. To evaluate the imaging performance of developed devices via ex vivo and in vivo studies.