Novel Biomarkers for Liver Imaging in the Monitoring of Cancer Therapy

肝细胞癌（HCC）每年导致约1500例英国死亡，发病率正在上升，主要是由于生活方式因素。最近开发的非侵入性定量磁共振成像（MRI）技术，如校正T1标测和MR弹性成像（分别以LiverMultiScan和Resoundant上市），已显示出表征肝纤维化的前景（Banerjee等人J Hep（2014），Huwart等人（2008））。然而，它们在监测下表征肝硬化的潜力，作为预测HCC发作的手段，尚未被探索，并且可以补充和增强常规成像，如超声（US），单相对比增强计算机断层扫描（CE-CT），弥散MRI或多相CE-MRI通常用于这类患者。这个学生项目旨在开发新的成像生物标志物来预测肝癌前病变（肝硬化）的监测下，使用一系列新的定量MRI技术与常规成像。影像学检查将在放射科进行，作为其标准治疗的一部分，并得到胃肠病学和肝病学团队的临床支持。该项目将需要开发专用计算工具，通过考虑成像衍生的患者和疾病特异性组织或组织灌注参数，可以补偿不同类型扫描之间的组织运动/变形，以及纵向采集的扫描，以便检测（并最终预测）组织特征从癌前状态到癌状态的变化。该项目包含一个非常强大的翻译组件，通过将开发的技术嵌入到软件产品中，以便快速部署到临床实践中。（建议嵌入/强烈调整这个学生与EPSRC中心博士培训（CDT）在医学影像，这是国王学院伦敦和帝国理工学院伦敦之间联合运行）：第一年交付：医学成像科学的MRes，包括图像采集和重建，成像化学和生物学，医学图像计算和计算建模的课程选项; Perspectum Diagnostics的MRes项目“T1映射中HCC检测的工具”。第二年交付：用于肝硬化患者常规成像的肝脏变形配准的开发。常规成像（US或CE-CT/MR）与T1和MR弹性成像的配准原型。关于方法学的会议/研讨会出版物。第3年交付：临床数据整理。对监测下肝硬化患者的不同T1标测技术进行全面比较和性能评价，并与MR弹性成像结果进行相关性分析。技术/临床会议/期刊出版物。第4年交付：完成软件集成，撰写论文和临床评价的其他出版物。

Hepatocellular carcinoma (HCC) causes approximately 1500 UK deaths per year and the incidence is rising, predominantly due to lifestyle factors. Recently developed non-invasive quantitative magnetic resonance imaging (MRI) techniques, such as corrected T1 mapping and MR elastography (commercialised as LiverMultiScan and Resoundant respectively) have shown promise in characterising liver fibrosis (Banerjee et al. J Hep (2014), Huwart et al. (2008)). However, their potential in characterising liver cirrhosis under surveillance, as a means to predict onset of HCC, has not yet been explored, and could complement and enhance routine imaging, such as ultrasound (US), single-phase contrast-enhanced computed tomography (CE-CT), diffusion MRI or multi-phasic CE-MRI commonly used for such patients.This studentship proposal aims at developing novel imaging biomarkers to characterise precancerous liver disease (cirrhosis) under surveillance, using a range of novel quantitative MRI techniques alongside routine imaging. Imaging will be conducted in the Department of Radiology, as part of their standard of care, with clinical support from the Gastroeneterology and Hepatology team. The project will require the development of dedicated computational tools that can compensate for tissue motion/deformation between different types of scans, and scans that are acquired longitudinally, by taking into account imaging-derived patient and disease-specific tissue or tissue perfusion parameters, in order to detect (and ultimately predict) changes in tissue characteristics from precancerous to cancerous states. This project contains a very strong translational component, by embedding the developed techniques into a software product for rapid deployment into clinical practice.PhD Roadmap (it is proposed to embed / strongly align this studentship with the EPSRC Centre for Doctoral Training (CDT) in Medical Imaging, which is run jointly between King's College London and Imperial College London): 1st year delivery: MRes in Medical Imaging Sciences, including course options on image acquisition & reconstruction, imaging chemistry & biology, and medical image computing & computational modelling; MRes project on "Tools for HCC detection in T1 mapping" at Perspectum Diagnostics.2nd year delivery: Development of deformable registration of the liver for routine imaging of patients with cirrhosis. Prototype for co-registration of routine imaging (US or CE-CT/MR) to T1 and MR elastography imaging. Conference/workshop publication on methodology.3rd year delivery: Collation of clinical data. Full comparison and performance evaluation of different T1 mapping techniques for patients with cirrhosis under surveillance, and correlation against MR elastography findings. Technical/clinical conference/journal publication(s).4th year delivery: Complete software integration, write up Thesis and additional publications with clinical evaluation.