Physical and biological characterisation of clinically relevant combined MRI-radiation exposures with conventional and nanoparticle contrast agents

磁共振成像（MRI）在整个放疗过程中使用，因为它具有优异的软组织造影剂，有助于在各种治疗部位描绘肿瘤。MRI通常被认为是一种安全的技术，具有很高的临床影响。它被认为是一种强大的非侵入性诊断工具，用于研究身体的解剖结构和功能，无论是健康还是疾病。据估计，全世界已进行了2亿次核磁共振扫描，在受试者/患者中未报告直接的不良生物学效应。放射治疗是一种对许多疾病部位非常有效的治疗方法，在所有癌症治疗中占50%的主要作用。最近的技术进步使得治疗更符合肿瘤，同时避免正常组织。为了提高一致性，通常需要改进图像引导放疗（IGRT），通常使用锥形束CT （CBCT）扫描直接进行预处理，以确保提高输送精度。MR-Linacs正在成为一种潜在的解决方案，可以更好地可视化软组织预处理，作为图像引导放射治疗（IGRT）解决方案的一部分。磁共振成像目前也用于确定肿瘤内的病灶肿瘤区域，如前列腺。在临床相关条件下，特别是在钆基造影剂存在的情况下，对这些联合暴露的影响知之甚少。最近的研究表明，钆可以作为一种潜在的治疗剂。如果钆能在IGRT期间增强肿瘤显像，同时作为放射增敏剂，这可能是提高靶向性和增加杀瘤剂量的有力工具。该项目将评估这些组合暴露在一系列正常和肿瘤细胞模型中的生物学影响，量化DNA损伤和细胞存活终点。它将在临床相关的暴露条件下进行，由国家放射治疗标准定义，并在当前临床对比剂的存在下模拟当前临床方案，以及未来使用纳米颗粒配方的证明。它将使用目前只有国家物理实验室才能使用的最先进的mr - linfacilities。这将有助于更好地了解联合mri辐射暴露的潜在益处，并对其临床交付的未来选择做出预测。该项目将贝尔法斯特女王大学的高级放射治疗小组与商业伙伴国家物理实验室的剂量测定小组联系起来。它将为NPLs在这一领域的工作做出重大贡献，旨在确定未来使用联合核磁共振辐射暴露的国家标准，并最大限度地提高患者从这些治疗中获益。它还将验证钆基纳米颗粒作为放射性增敏剂的潜力。在这个项目中，学生将受益于独特的研究经验，通过与行业领先的公司，国家物理实验室的互动，并积极为核磁共振辐射研究项目的发展做出贡献。该建议是跨生物学和物理学的多学科，使学生有机会在临床前放疗研究，剂量学和辐射生物学领域获得独特的专业知识，重点是脑和前列腺肿瘤。此外，与商业合作伙伴的互动将导致与其他工业和学术机构的互动，其中可能包括对曼彻斯特克里斯蒂医院和伦敦皇家马斯登医院的研究培训访问，这两家医院将于明年投入临床MRI-Linac，以及领先的放射治疗设备制造商Elekta，他们正在开发第一台商用MRI-Linac设备。

Magnetic resonance imaging (MRI) is used throughout radiotherapy due to excellent soft tissue contrast aiding delineationof the tumour in a variety of treatment sites. MRI is generally considered a safe technology with very high clinical impact. Itis accepted as a powerful non-invasive diagnostic tool to investigate the anatomical structures and functions in the body, inboth health and disease. It is estimated that 200 million MRI scans have been performed worldwide and no direct adversebiological effects have been reported in subjects/patients. Radiotherapy is a highly effective treatment for a wide number ofdisease sites and plays a major role in 50% of all cancer treatments. Recent technological advances have allowedtreatments which conform better to the tumour while avoiding normal tissue. This improved conformity often requiresimproved image guided radiotherapy (IGRT) generally performed using cone beam CT (CBCT) scans taken directly pretreatmentto ensure improved delivery accuracy. MR-Linacs are emerging as a potential solution to better visualize the softtissue pre-treatment as part of an image guided radiation therapy (IGRT) solution. MR is currently also used to define focaltumour regions within tumours such as the prostate. Little is known about the impact of these combined exposures underclinically relevant conditions, particularly in the presence of gadolinium-based contrast agents. Recent studies have shownthat gadolinium can act as a potential theranostic agent. If gadolinium could be used to enhance tumour visualizationduring IGRT and act as a radio-sensitizer at the same time, this could be a powerful tool to improve targeting and increasetumouricidal dose.This project will assess the biological impact of these combined exposures in a range of normal and tumour cell modelsquantifying DNA damage and cell survival endpoints. It will do this under clinically relevant exposure conditions, defined byNational Radiotherapy Standards and in the presence of the current clinical contrast agent to mimic current clinicalprotocols as well as future proofing the use of a nanoparticle formulation. It will access state-of-the-art combined MR-linacfacilities currently only available at NPL. This will allow a greater understanding of the potential benefits of combined-MRIradiation exposures and make prediction for future options for their clinical delivery.The project links the Advanced Radiotherapy Group at Queen's University Belfast with the commercial partner, theDosimetry Group at the National Physical Laboratory. It will make a significant contribution to NPLs work in this spaceaiming to define future National Standards for the use of combined MRI-radiation exposures and to maximise patientbenefit from these treatments. It will also validate the potential of gadolinium-based nanoparticles as radiosensitisers. Inthis project the student will benefit from a unique research experience by interacting with an industry leading company, theNational Physical Laboratory and actively contributing to the development of the MRI-Radiation Research Project. Theproposal is multidisciplinary across biology and physics giving the student insight and opportunity to gain unque expertisein the areas of preclinical radiotherapy research, dosimetry and radiation biology focussed on brain and prostate tumours.In addition, interaction with commercial partner will lead to interaction with other industrial and academic institutes whichmay include a research training visit to Christie Hospital Manchester and the Royal Marsden Hospital in London which willboth be commissioning clinical MRI-Linacs next year and Elekta, leading manufacturer in radiotherapy facilities who isdeveloping the first commercial MRI-Linac units.