Novel Biomarkers for Liver Imaging in the Monitoring of Cancer Therapy

肝细胞癌（HCC）每年在英国造成约1500人死亡，并且发病率正在上升，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映射和MR弹性成像（分别以LiverMultiScan和reoundant商业化）在表征肝纤维化方面显示出希望（Banerjee等人）。J Hep (2014), Huwart et al.（2008）。然而，它们在监测下表征肝硬化的潜力，作为预测HCC发病的一种手段，尚未被探索，并且可以补充和增强常规影像学，如超声（US），单相增强计算机断层扫描（CE-CT），弥散MRI或多期CE-MRI通常用于这类患者。该学生计划旨在开发新的成像生物标志物，利用一系列新的定量MRI技术和常规成像技术，在监测下表征癌前肝脏疾病（肝硬化）。影像学检查将在放射科进行，作为其标准护理的一部分，并由胃肠病学和肝病学团队提供临床支持。该项目将需要开发专用的计算工具，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，从而检测（并最终预测）从癌前到癌前状态的组织特征变化。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。博士路线图（建议将该奖学金与EPSRC医学成像博士培训中心（CDT）紧密结合，该中心由伦敦国王学院和伦敦帝国学院联合运营）：第一年交付：医学成像科学MRes，包括图像采集与重建，成像化学与生物学，医学图像计算与计算建模课程选择；透视诊断的MRes项目“T1制图中HCC检测工具”，第二年交付：肝硬化患者常规影像学中肝脏变形登记的发展。常规成像（US或CE-CT/MR）与T1和MR弹性成像共同配准的原型。关于方法论的会议/讲习班出版物。第三年交付：整理临床资料。对监测下肝硬化患者不同T1定位技术的全面比较和性能评估，以及与MR弹性成像结果的相关性。技术/临床会议/期刊出版物。第四年交付：完成软件集成，撰写论文和附加出版物，并进行临床评估。

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.