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

磁共振成像（MRI）是用于整个放射治疗由于良好的软组织对比度帮助delineationof肿瘤在各种治疗部位。MRI通常被认为是一种安全的技术，具有非常高的临床影响。它被认为是一种强有力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，全球已进行了2亿次MRI扫描，未报告受试者/患者的直接不良生物学效应。放射治疗是一种非常有效的治疗方法，可治疗多种疾病部位，在50%的癌症治疗中发挥着重要作用。最新的技术进步使得治疗方法能够更好地适应肿瘤，同时避免正常组织。这种改善的适形性通常需要改进的图像引导放射治疗（IGRT），通常使用直接在治疗前进行的锥形束CT（CBCT）扫描，以确保改善的输送准确性。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。MR目前也用于确定肿瘤内的局灶性肿瘤区域，如前列腺。关于这些联合暴露在临床相关条件下的影响，特别是在存在钆基造影剂的情况下，知之甚少。近年来的研究表明，钆可以作为一种潜在的治疗诊断剂。如果钆可以在IGRT期间用于增强肿瘤可视化，同时作为放射增敏剂，这可能是一个强有力的工具，以提高靶向和增加杀肿瘤剂量。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。它将在国家放射治疗标准定义的临床相关暴露条件下并在当前临床造影剂的存在下做到这一点，以模拟当前的临床方案以及未来验证纳米颗粒制剂的使用。它将访问目前仅在NPL可用的最先进的组合MR直线加速器设施。这将使一个更好的了解结合MRI辐射曝光的潜在好处，并预测其临床deliver.The项目的未来选择链接高级放射治疗集团在女王大学贝尔法斯特与商业合作伙伴，theDosimetry集团在国家物理实验室。它将为NPL在这一领域的工作做出重大贡献，以确定未来使用MRI-辐射联合暴露的国家标准，并使患者从这些治疗中获益最大化。它还将验证钆基纳米颗粒作为放射增敏剂的潜力。在这个项目中，学生将受益于一个独特的研究经验，通过与行业领先的公司，国家物理实验室互动，并积极促进MRI辐射研究项目的发展。该提案是跨生物学和物理学的多学科，为学生提供洞察力和机会，以获得临床前放射治疗研究，剂量学和辐射生物学领域的独特专业知识，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的皇家马斯登医院的研究培训访问这两家公司都将在明年投入临床使用MRI直线加速器，而Elekta是放射治疗设备的领先制造商，正在开发第一批商用MRI直线加速器。

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.