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

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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.