Imaging the stars from within: Super-resolution contrast ultrasound imaging

使用自适应光学，首先应用于天文学，然后（在STFC的资助下）成功地适用于光学显微镜，我们的目标是产生微米分辨率的超声成像。具体而言，目标是跟踪循环中的微泡造影剂，从而生成血管网络的详细图像。这是为了满足与异常微血管网络相关的常见疾病（如癌症、缺血、炎性疾病、移植排斥和组织再生）中微血管评估的未满足的临床需求。一个例子是持续需要快速和低风险的生物标志物的治疗结果及其预测癌症。实体瘤的当前缓解评价标准（RECIST）利用计算机断层扫描（CT）来评估肿瘤体积变化，通常在治疗后3个月进行。这种间接评估显著限制了基于治疗反应的早期个性化，并可能导致次优的发病率和死亡率。每年，英格兰有超过25万人被诊断患有癌症，大约13万人因癌症而无法生存。每年NHS相关费用约为45亿英镑，整个社会的费用约为183亿英镑。尽管这些统计数据正在改善，但英国卫生部的目标是实现与欧盟其他国家相同的平均癌症存活率，以试图每年多挽救5,000人的生命。我们提出的产品将用于为每位患者的护理提供额外的益处，可用于：-早期诊断，有可能成为筛查测试，-早期和快速的疾病监测，使早期患者分层。超声以低成本和低风险为患者提供真实的时间图像，对于组织的重复成像非常有吸引力。根据卫生部的建议，我们将评估我们在测量已建立的生物标志物（如微血管密度（这是许多癌症的已建立的生物标志物））方面的技术，并考虑产生新的生物标志物，如毛细血管血流速度、血管结构和迂曲度，这些生物标志物可能提供血管相关疾病的强大区分。这是对所有当前宏观成像模态的显著改进。有一个真实的机会，建立CEUS作为灌注评估的领先模式，通过转换现有的技术，提供超分辨率图像的点源在光学（显微镜，天文学），毫米波和雷达。该建议将部署从单个微泡的散射作为先验知识，用于实施类似于光学显微镜中使用的可用的最大锐度似然技术。我们将在超声场仿真环境中实现现有的算法，以定义将用于在体外测试这些算法的实验，并最终确定波束形成方法的设计。通过利用现有的图像分析算法用于粒子跟踪，我们将产生在体外微血管幻影的可视化。我们的工业合作伙伴BK Medical将提供一个可以在现有超声成像产品中实施的原型工具。最后，我们将使用现有的商业设备来收集癌症患者数据，以识别具有有希望的图像数据的患者组（与金标准相比）。这将为我们原型的增强成像能力的商业化提供一个后续项目的焦点。

Using adaptive optics, first applied in astronomy and then (under STFC funding) successfully adapted for use in optical microscopy, we aim to to produce micrometric resolution ultrasound imaging. Specifically, the goal is to track microbubble contrast agents in circulation thus generating detailed images of the vascular network. This is to meet the unmet clinical need for microvascular assessment in common diseases associated with abnormal microvascular networks such as cancer, ischaemia, inflammatory disease, transplant rejection and tissue regeneration. An example is the ongoing need for rapid and low-risk biomarkers of treatment outcome and its prediction in cancer. The current response evaluation criteria for solid tumours (RECIST) utilises Computerised Tomography (CT) to assess tumour volume changes which typically is done three (3) months after the treatment. Such indirect assessment significantly limits early personalisation based on treatment response and may contribute to suboptimal morbidity and mortality rates. Every year, over 250,000 people in England are diagnosed with cancer, and around 130,000 do not survived as a result of the disease. The annual NHS related costs are in the order of £4.5 billion, and the cost to society as a whole about £18.3 billion. Although these statistics are improving the UK Department of Health aims to achieve the average cancer survival rate on par with the rest of the European Union in an attempt to save an extra 5,000 lives every year. Our proposed product will be used to provide additional benefits to the care of each patient that can be used for: -Early diagnosis with the potential of becoming a screening test, -Early and fast disease monitoring that enables early patient stratification. Ultrasound provides real time images at low cost and low risk to patients, which is very attractive for repeated imaging of tissues. As recommended by the Department of Health we will assess our technique in the measurement of an established biomarker such as microvascular density (which is an established biomarker for many cancers), and consider the generation of new biomarkers such as capillary blood velocity, vessel structure and tortuosity that may provide a robust differentiation of vascular related disease. This is a significant improvement to all current imaging modalities that are macroscopic. There is a real opportunity to establish CEUS as the leading modality for perfusion assessment by translating existing technology that provides super-resolution images of point sources in optics (microscopy, astronomy), mm-wave and radar. This proposal will deploy the scatter from single microbubbles as a priori knowledge for implementing an available maximum sharpness likelihood technique similar to that used in optical microscopy. We will implement existing algorithms in an ultrasound field simulation environment to define the experiments that will be used to test these algorithms in vitro and finalize the design of the beamforming method. By utilizing existing image analysis algorithms used for particle tracking we will generate the visualization of in vitro microvascular phantoms. A prototype tool that can be implemented in existing ultrasound imaging product provided by BK Medical, our industrial partner, will be delivered. Finally, we will use existing commercial equipment to collect cancer patient data in order to identify a patient group with promising image data (in comparison with a gold standard). This will provide a focal point in a follow up project for the commercialization of the enhanced imaging capability of our prototype.