Nanobubbles for earlier pancreatic cancer detection

胰腺癌是英国第十大最常见的癌症，其发病率在过去40年中增加了30%，但五年生存率一直很低，约为8%，在同一时期没有改善。目前，只有大约10%的患者适合手术。更早发现疾病可以增加癌症仍然适合手术切除的患者数量，从而对患者的预后起到重要作用。那些肿瘤无法触及或太过晚期而无法手术的患者依赖于化疗或免疫治疗。然而，胰腺导管癌的特点是形成致密的纤维间质和富含胶原的细胞外基质，这严重限制了可用于治疗它的药物的渗透。这导致了人们对能够针对这种致密的间质进行治疗的治疗方法的开发产生了相当大的兴趣。迫切需要改进成像基质密度和对药物渗透的敏感性的方法，以更好地优化和监测治疗，以改善患者的结果。我们先前演示了超声造影(CEUS)如何有效地识别转移[1]，其中微泡可以改善图像质量并提供生理信息。然而，通常使用的造影剂微泡仅限于循环，限制了它们突出疾病的能力，直到供应肿瘤的血管开始受到影响，无法成像肿瘤组织本身。在这个项目中，我们将研究纳米气泡作为一种更适合早期癌症检测的造影剂。它们足够小，可以逃脱血管，并自然地保留在肿瘤组织中。它们有可能提供不同大小的颗粒渗透到肿瘤间质的信息，但要实现这一新的超声成像领域的潜力，需要新的成像方法。虽然定量超声成像，特别是在乳腺成像的背景下，自20世纪70年代以来一直在研究，但直到最近十年，固态电子学和阵列技术的发展才促进了足够的灵敏度和特异度，以与替代医学成像模式竞争[2]。与核磁共振扫描相反，超声成像可以提供定量信息(如波速的空间分布)，从而便于对被检查的不均匀结构的材料特性进行表征。此外，在非破坏性评估(NDE)领域，最近使用超声波旅行时间层析成像来绘制多晶金属的各向异性的颗粒结构和取向的情况也出现了激增[3]。然而，在医学和无损检测应用中，这些方法的成功高度依赖于检查孔径的范围以及关于被检查对象的全局结构和属性的先验知识的可用性。为了在肿瘤特征化的背景下避开这些挑战，这个项目将研究使用CEUS构建癌症组织的定量图像的潜力。

Pancreatic cancer is the tenth most common cancer in the UK, with an incidence that has increased by 30% increase 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. Improved methods of imaging stroma density and susceptibility to drug penetration are urgently required to better optimise and monitor treatments to improve patient outcomes. We previously demonstrated how contrast enhanced ultrasound (CEUS), where microbubbles can improve image quality and provide physiological information, are effective in the identification of metastasis [1]. However, the contrast agent microbubbles commonly used are confined to the circulation, limiting their ability to highlight disease until the blood vessels supplying the tumour begin to be affected and unable to image tumour tissue itself. In this project we will investigate nanobubbles as a more suitable contrast agent for early stage cancer detection. They are small enough to escape the blood vessels and are naturally retained in tumour tissues. They have the potential to provide information on the penetration of different sized particles into the tumour stroma, but to realise the potential of this new area of ultrasound imaging novel imaging approaches are needed. Although quantitative ultrasound imaging, particularly in the context of breast imaging, has been investigated since the 1970s, it is only in the last decade that developments in solid state electronics and array technology have facilitated sufficient sensitivity and specificity to compete with alternative medical imaging modalities [2]. Contrary to MRI scans, ultrasound imaging can provide quantitative information (such as the spatial distribution of wave speed) and thus facilitate material characterisation of the heterogeneous structures under inspection. Furthermore, in the field of non-destructive evaluation (NDE), there has been a recent surge in using ultrasonic travel time tomography to map the anisotropic grain structures and orientations of polycrystalline metals [3]. However, in both medical and NDE applications, the success of these methods is highly dependent on the extent of the inspection aperture and the availability of prior knowledge about the global structure and properties of the inspected object. To circumvent these challenges in the context of tumour characterisation, this project will examine the potential of using CEUS to construct quantitative images of cancerous tissues.