Nanobubbles for earlier pancreatic cancer detection

用于早期胰腺癌检测的纳米气泡

• 批准号: 2886053
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2886053
• 关键词: Nanobubbles; earlier; pancreatic; cancer; detection

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.

胰腺癌是英国第十大最常见癌症，其发病率在过去40年中增加了30%，但5年生存率持续较低，约为8%，并且在同一时期没有改善。目前，只有10%的患者适合手术。疾病的早期检测可以通过增加癌症仍然适合手术切除的患者数量来对患者的预后发挥重要作用。那些肿瘤无法接近或太晚期而无法手术的患者依赖化疗或免疫治疗。然而，胰腺导管癌的特征在于致密纤维化间质和富含胶原蛋白的细胞外基质的演变，这严重限制了可用于治疗它的药物的渗透，这导致了对可以靶向这种致密间质以实现治疗的治疗方法的开发的相当大的兴趣。迫切需要改善基质密度和药物渗透敏感性的成像方法，以更好地优化和监测治疗，改善患者的预后。我们之前证明了造影剂增强超声（CEUS），其中微泡可以提高图像质量并提供生理信息，如何有效地识别转移[1]。然而，通常使用的造影剂微泡局限于循环，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并且不能对肿瘤组织本身成像。在这个项目中，我们将研究纳米气泡作为更合适的造影剂用于早期癌症检测。它们小到足以逃离血管，并自然保留在肿瘤组织中。它们有可能提供关于不同大小的颗粒渗透到肿瘤基质中的信息，但要实现超声成像这一新领域的潜力，需要新的成像方法。尽管自20世纪70年代以来一直在研究定量超声成像，特别是在乳腺成像的背景下，但直到最近十年，固态电子和阵列技术的发展才促进了足够的灵敏度和特异性，以与替代医学成像模式竞争[2]。与MRI扫描相反，超声成像可以提供定量信息（例如波速的空间分布），从而有助于对检查中的异质结构进行材料表征。此外，在无损评价（NDE）领域，最近出现了使用超声走时层析成像来绘制多晶金属的各向异性晶粒结构和取向的热潮[3]。然而，在医学和无损检测应用中，这些方法的成功在很大程度上取决于检查孔径的范围和关于被检查对象的全局结构和属性的先验知识的可用性。为了在肿瘤表征的背景下规避这些挑战，该项目将研究使用CEUS构建癌组织定量图像的潜力。