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

利用自适应光学，首先应用于天文学，然后(在STFC资助下)成功地用于光学显微镜，我们的目标是产生微米分辨率的超声成像。具体地说，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。这是为了满足与癌症、缺血、炎症性疾病、移植排斥反应和组织再生等与异常微血管网络相关的常见疾病的微血管评估的临床需求。一个例子是对治疗结果及其在癌症中的预测的快速和低风险生物标志物的持续需求。目前的实体肿瘤反应评估标准(RECIST)利用计算机断层扫描(CT)来评估肿瘤体积的变化，通常在治疗三(3)个月后进行。这种间接评估大大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。在英国，每年有超过25万人被诊断出患有癌症，大约13万人死于这种疾病。每年NHS的相关成本约为45亿GB，对整个社会的成本约为183亿GB。尽管这些统计数据正在改善，但英国卫生部的目标是达到与欧盟其他国家相同的平均癌症存活率，试图每年额外挽救5000人的生命。我们建议的产品将用于为每个患者的护理提供额外的好处，这些好处可以用于：-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。超声为患者提供低成本、低风险的实时图像，对于组织的重复成像非常有吸引力。根据卫生部的建议，我们将评估我们的技术在测量已建立的生物标记物如微血管密度(这是许多癌症的已建立的生物标记物)中的作用，并考虑产生新的生物标记物，如毛细血管血流速度、血管结构和弯曲度，这些可能提供血管相关疾病的强有力的鉴别。这是对目前所有宏观成像方式的重大改进。有一个真正的机会，通过转化现有的技术，将CEU确立为灌注评估的领先方式，这些技术提供光学(显微镜、天文学)、毫米波和雷达点源的超分辨率图像。这一建议将利用单个微泡的散射作为先验知识，以实现与光学显微镜中使用的类似的可用的最大锐度似然技术。我们将在超声场模拟环境中实现现有算法，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。通过利用现有的用于粒子跟踪的图像分析算法，我们将生成体外微血管模型的可视化。我们将交付一个可以在我们的工业合作伙伴BK Medical提供的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的数据，以便识别具有有前景的图像数据的患者组(与黄金标准相比)。这将为我们的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.