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

博士项目目标：开发先进的超声技术，用于高空间和时间分辨率的肠道结构和功能的体内成像。在脂肪层和组织运动的情况下，开发优化的信号和图像处理以及机器学习技术。研究营养摄入的影响。项目描述：我们对肠道的理解的最新进展表明，它不仅对营养吸收至关重要，而且是人体免疫系统的一个组成部分。健康的肠道几乎对人体健康的各个方面都有好处，保护我们免受营养缺乏、炎症、肥胖、糖尿病、免疫疾病、感染、心脏病和癌症的侵害。现在也有大量证据表明，健康的肠道可以预防许多精神疾病，包括抑郁症、焦虑症和自闭症。定量评估肠道健康，识别病理状况（如炎症），监测肠道修复能力（粘膜愈合）以及对食物摄入和治疗药物的反应，是进一步了解这一复杂系统，开发新药，以及肠道疾病患者临床管理和药物开发的关键。最近的临床观察数据和真实世界的证据支持使用粘膜愈合作为治疗炎症性肠病（IBD）的临床终点。然而，肠道黏膜需要很长时间才能愈合，因此在做出临床决定时，需要肠道炎症和粘膜愈合纵向变化的客观证据。然而，目前我们在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手术。肠道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身的血流量，以满足局部吸收、代谢和修复过程的需要。有证据表明，特定的营养物质和代谢物，以及一些治疗药物，会刺激血流发生更大的变化，这与减少炎症和改善粘膜愈合有关。然而，到目前为止，这些血流变化主要是在侵入性或离体组织中研究的。生物医学超声的一些最新进展，包括1)每秒高达数万帧成像的超快数据采集，2)允许高对比度血流成像的微泡造影剂，以及3)实现亚衍射极限分辨率的超分辨率超声，使得以数十微米的分辨率对深层组织微血管形态和血流动力学进行非侵入性成像成为可能。我们是第一个在体外和体内证明超声超分辨率的人。超声技术的这些进步为非侵入性体内肠道结构和功能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，使用超声对肠道进行成像存在重大挑战，包括明显的组织运动，脂肪的存在导致明显的声音畸变和图像分辨率降低。最近，我们首次展示了使用相变纳米液滴的实时超分辨率。在本项目中，我们建议开发先进的超声成像，图像分析和机器学习技术，用于肠道微血管结构和功能的稳健测量，并将这些技术应用于肠道炎症，粘膜愈合和肠道对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.