Multiparametric Magnetic Resonance Imaging of Pancreas Disease

本项目属于EPSRC Healthcare Technologies(医学成像)研究领域合作与监督本项目将与透视诊断有限公司合作进行。该项目将由牛津大学的Daniel Bulte教授、Perspectom Diagnostics有限公司的Michael Brady爵士教授和Ged Ridgway博士监督。项目细节与慢性肝病一样，慢性胰腺疾病也在增加，肥胖及其相关疾病，如代谢综合征、心血管疾病和癌症的发病率也在上升。肥胖导致肝脏、心脏或胰腺等器官异位脂肪堆积，并触发一系列炎症反应，最终导致纤维化和原发癌症风险增加。肝脏或胰腺等器官的脂肪渗透最初是无症状的，通常作为腹部成像程序的一部分附带报告。定量成像对于早期发现和诊断这些疾病是必不可少的，以便更密切地监测这些受试者。与计算机断层扫描(CT)或超声等其他成像技术相比，磁共振成像提供了安全、准确和精确的工具。透视诊断有限公司开发了一套用于评估肝脏疾病的非对比、定量磁共振成像方案。肝脏的多参数成像能够可靠地量化实质组织中的脂肪、铁和纤维炎症；这些参数可以预测非酒精性脂肪肝、血色素沉着症、脂肪性肝炎或自身免疫性肝炎等患者的临床结果，以及与酒精相关的肝病。虽然这些MRI方案并不容易适用于胰腺疾病，但它们是很好的首选方案。我们相信这一点主要有两个原因，(1)事实是，当暴露在脂肪渗透中时，胰腺表现出与肝脏相似的疾病进展--类似的术语非酒精性脂肪性胰腺疾病(NAFPD)已经被创造出来--以及(2)类似的情况在胰腺中被描述，包括胰腺脂肪变性、铁负荷过重、胰腺纤维化、慢性胰腺炎、胰腺癌、胰腺囊肿或胰管阻塞。更大胆的研究试图确定某些胰腺疾病，如NAFPD和β细胞功能障碍，以及II型糖尿病(T2 DM)的发病之间的联系，但结果尚不确定。在胰腺移植中，脂肪变性目前是通过器官取出时的肉眼检查来主观评估的，是器官被丢弃的常见原因。这项研究项目的第一年将集中在MRI获取的技术挑战和用于胰腺脂肪量化的质子密度脂肪分数(PDFF)度量的验证上。对于这个问题，肝脏脂肪评估中的某些建模假设不成立；此外，胰腺的不同几何形状和位置使其在没有伪影的情况下成像具有挑战性，影响了脂肪的量化。DPHIL的第二年将致力于研究胰腺分割的方案，以评估胰腺脂肪变性的空间异质性。分割将有助于评估胰腺体积和表面不规则性，这与某些情况如T1 DM有关，本身可能构成与胰腺健康状况相关的有用的成像生物标记物。该项目的第三年计划开发用于量化纤维炎症及其与发生胰腺癌风险的松弛计量学方案。我们已经获得了近20,000份英国生物库志愿者样本，每个样本都有多个胰腺磁共振成像方案。我们的目标也是通过研究合作在项目过程中获取患者数据。

This project falls within the EPSRC Healthcare Technologies (Medical Imaging) research areaCollaboration and SupervisionThis project will be carried out in collaboration with Perspectum Diagnostics Ltd. The project will be supervised by Prof. Daniel Bulte at the University of Oxford and Prof. Sir Michael Brady and Dr. Ged Ridgway at Perspectum Diagnostics Ltd.Project DetailsMuch like chronic liver disease, chronic pancreas disease is on the rise together with the increasing prevalence of obesity and its associated conditions, such as the metabolic syndrome, cardiovascular disease and cancer. Obesity causes ectopic fat accumulation in organs such as the liver, heart or pancreas, and triggers a set of inflammatory responses that ultimately lead to fibrosis and increased risk of primary cancer. Fatty infiltration of organs such as the liver or the pancreas is initially asymptomatic and is usually reported incidentally as part of an abdominal imaging routine. Quantitative imaging becomes essential to the early detection and diagnosis of these conditions in order to monitor these subjects more closely. MRI provides safe, accurate and precise tools compared to other imaging techniques such as Computed Tomography (CT) or ultrasound.Perspectum Diagnostics Ltd have developed a set of non-contrast, quantitative MRI protocols for the assessment of liver disease. Multiparametric imaging of the liver allows for the reliable quantification of fat, iron and fibro-inflammation in parenchymal tissue; these parameters predict clinical outcomes in patients with NAFLD, hemochromatosis, steatohepatitis or autoimmune hepatitis, to name a few, as well as alcohol-related liver disease. While these MRI protocols are not readily applicable to pancreas disease, they constitute excellent first candidates. We believe this for two main reasons, (1) the fact that the pancreas shows similar disease progression to the liver when exposed to fatty infiltration -the analogous term Non-Alcoholic Fatty Pancreas Disease (NAFPD) has been coined- and (2) similar conditions have been described in the pancreas, including pancreatic steatosis, iron overload, pancreatic fibrosis, chronic pancreatitis, pancreatic cancer, pancreatic cysts or pancreatic duct obstruction. More adventurous research has attempted to establish a link between certain pancreas conditions such as NAFPD and beta-cell dysfunction and the onset of type II diabetes mellitus (T2DM), with inconclusive results. In pancreatic transplantation, steatosis is currently assessed subjectively through visual inspection upon organ retrieval and is a frequent cause of organ discard.The first year of this research project will focus on the technical MRI acquisition challenges and the validation of the Proton Density Fat Fraction (PDFF) metric for fat quantification in the pancreas. For this problem, certain modelling assumptions in liver fat assessment do not hold; also, the variable geometry and location of the pancreas make it a challenging organ to image without artefacts, compromising fat quantification. The second year of the DPhil will aim to investigate protocols for the segmentation of the pancreas in order to assess the spatial heterogeneity of pancreatic steatosis. Segmentation will help towards the assessment of pancreatic volume and surface irregularity, which have been linked to certain conditions such as T1DM and may themselves constitute useful imaging biomarkers tied with pancreas health state. The third year of the project is planned for the development of relaxometry protocols for the quantification of fibro-inflammation and its association with the risk of developing pancreatic cancer. Nearly 20,000 UK Biobank volunteer acquisitions have become available to us, each with multiple pancreas MRI protocols. We are also aiming to acquire patient data within the course of the project through research collaborations.