High spatial and temporal resolution imaging of gut structure and microcirculation in response to nutrition intake and to therapeutics

PHD项目的目标：开发先进的超声技术，用于在活体内对肠道结构和功能进行高空间和时间分辨率成像开发在存在脂肪层和组织运动的情况下的优化信号和图像处理和机器学习技术研究营养摄入、炎症和治疗剂在活体粘膜愈合过程中对肠道结构和微循环的影响项目描述：我们对肠道了解的最新进展表明，它不仅对营养吸收至关重要，而且是人体免疫系统不可或缺的一部分。健康的肠道几乎有益于人类健康的方方面面，保护我们免受营养缺乏、炎症、肥胖、糖尿病、免疫疾病、感染、心脏病和癌症的影响。现在也有压倒性的证据表明，健康的肠道可以预防许多精神健康疾病，包括抑郁、焦虑和自闭症。定量评估肠道健康状况、识别病理情况(例如炎症)、监测肠道修复(粘膜愈合)的能力以及对食物摄入和治疗药物的反应的能力，是加深我们对这一复杂系统的理解、新药开发以及肠道疾病患者的临床管理和药物开发的关键。最近的临床观察数据和现实世界的证据支持将粘膜愈合作为治疗炎症性肠病(IBD)的临床终点。然而，肠粘膜需要很长时间才能愈合，因此，在做出临床决定时，肠炎和粘膜愈合的纵向变化的客观证据是必要的。然而，目前我们在活体内测量肠道健康的能力非常有限，通常涉及间接或侵入性操作。肠道中的微血管血流反映了组织活动的变化。有令人信服的证据表明，肠道的特定区域精确地调节自己的血液流动，以满足局部吸收、代谢和修复过程的需求。有证据表明，特定的营养素和代谢物，以及一些治疗剂，会刺激血液流动发生更大的变化，这与减轻炎症和改善粘膜愈合有关。然而，到目前为止，这些血流变化的研究主要是在侵入性或体外组织中进行的。生物医学超声的几个最新进展，包括1)高达数万帧/秒的超高速数据采集，2)微气泡造影剂可以实现高对比度的血流成像，3)超分辨率超声获得亚衍射极限分辨率，使得在深部组织中以数十微米的分辨率非侵入性成像微血管形态和血流动力学成为可能。我们是最早在体外和体内展示超声超分辨率的公司之一。这些超声技术的进步为肠道结构和功能的非侵入性体内测量提供了令人兴奋的机会，提供了其他成像方式无法比拟的空间和时间分辨率。然而，使用超声波对肠道进行成像仍然存在重大挑战，包括显著的组织运动、脂肪的存在导致显著的声音失真和图像分辨率降低。在这个项目中，我们提议开发先进的超声成像、图像分析和机器学习技术来稳健地测量肠道微血管的结构和功能，并将这些技术应用于肠道炎症、粘膜愈合和肠道药物治疗反应的测量。

Aim of the PhD Project:Develop advanced ultrasound technology for high spatial and temporal resolution in vivo imaging of gut structure and functionDevelop optimised signal and image processing and machine learning technology in the presence of fat layers and tissue motionStudy the impact of nutrient intake, inflammation and therapeutic agents on gut structure and microcirculation during mucosal healing in vivoProject Description:Recent advances in our understanding of the gut demonstrated that it is not only crucial for nutrient absorption but is also an integral part of the body's immune system. A healthy gut benefits nearly every aspect of human health, protecting us from nutrient deficiencies, inflammation, obesity, diabetes, immune diseases, infections, heart disease and cancer. There is now also overwhelming evidence that a healthy gut protects against many mental health disorders including depression, anxiety and autism. The ability to quantitatively assess gut health, identify pathological conditions (e.g. inflammation), and monitor the gut's ability to repair (mucosal healing) and respond to food intake and therapeutic agents, is key to further our understanding of this complex system, to the development of new drugs, and to the clinical management of patients with gut disorders and drug development. Recent clinical observational data and real-world evidence support the use of mucosal healing as a clinical endpoint in treatment of Inflammatory Bowel Disease (IBD). However the gut mucosa takes a long time to heal and therefore objective evidence of inflammation of the bowel and longitudinal changes to mucosal healing are necessary when making clinical decisions. However, currently our ability to measure gut health in vivo is very limited, and often involves either indirect or invasive procedures.Microvascular blood flow in the gut reflects changes in tissue activity. There is compelling evidence that specific regions of the gut precisely regulate their own blood flow to meet the local demands of absorptive, metabolic and repair processes. There is evidence that particular nutrients and metabolites, as well as some therapeutic agents, stimulate greater changes in blood flow which are correlated with reduced inflammation and improved mucosal healing. However, to date these changes in blood flow have mainly been studied invasively or in ex-vivo tissues.Several recent advances in biomedical ultrasound, including 1) ultrafast data acquisition with up to tens of thousands of imaging frames per second, 2) microbubble contrast agents allowing high contrast imaging of blood flow, and 3) super-resolution ultrasound achieving sub-diffraction limited resolution, have made it possible to non-invasively image in deep tissue the microvascular morphology and flow dynamics with a resolution of tens of microns. We have been among the first to demonstrate ultrasound super-resolution in vitro and in vivo.These advances in ultrasound present exciting opportunities for non-invasive in vivo measurement of gut structure and function, offering spatial and temporal resolution unmatched by other imaging modalities. However, significant challenges exist in imaging the gut using ultrasound, including the significant tissue motion, the presence of fat causing significant sound aberration and decreased image resolution. More recently we have been the first to demonstrate real-time super-resolution using of phase change nanodroplets.In this project we propose to develop advanced ultrasound imaging, image analysis, and machine learning technologies for robust measurement of gut microvascular structure and function, and apply the technologies in the setting of gut inflammation, mucosal healing and measurement of gut response to drug treatment.