A hybrid optical and ultrasound system to measure localized oxygenation, blood flow and oxygen consumption in the human body

当患者长期缺乏氧气供应以满足组织的新陈代谢需求时，患者的健康就处于极大的危险之中。这最终会导致细胞死亡和器官衰竭。因此，对于临床医生来说，监测体内的氧合情况是非常重要的，特别是在危重患者或正在接受大手术的患者。例如，静脉系统中氧气水平的测量(静脉血氧饱和度)已被证明在降低全身感染(败血症)严重症状患者的死亡率方面非常有用。此外，静脉血氧饱和度的测量已被证明是术后并发症的一个很好的预测指标。目前，静脉血氧饱和度的临床监测包括将侵入性导管插入颈部附近的静脉，直接对血液进行测量。然而，进行这些测量所需的侵入性程序需要相当多的外科技能，并与感染和出血等风险相关。这些程序只在被认为病情足以证明危险是合理的患者中进行，例如重症监护病房的患者。这些实用性排除了许多患者可能受益于静脉血氧饱和度测量的诊断价值。本项工作的主要目的是开发一种新型的临床监护仪，将光学和超声技术相结合，可以无创地测量静脉血氧饱和度。新的临床监护仪有一个包含光学和超声波成分的探头，可以放置在测量部位上方的皮肤表面，并瞄准下面的局部区域。例如，它可以放在胸部，测量肺动脉中的静脉血氧饱和度，这包含了整个身体循环的血液。这种无创静脉血氧饱和度测量方法可以替代有创导管用于临床监测。这种新的监测器还可以用来瞄准从大脑中抽出血液的静脉(颈静脉)，这样就可以监控大脑的状况。其他应用包括监测血液循环不良的肢体、手术后的恢复和移植器官的功能。除了静脉血氧饱和度，新的监测仪还可以用来测量血液流量和氧气消耗，这分别表明组织的氧气输送和组织消耗的氧气量。这种新型监测器的原理是基于这样一种现象，即超声波可以在特定的组织区域内引起周期性运动，改变光线通过该区域的方式。当光穿过这个区域时，光的强度将会改变，并可以由表面安装的光学探测器检测到。换句话说，光由目标区域中最强的超声波标记。检测到的标记光被称为声光信号，可以用来获得局部氧合、血液流动和氧气消耗。在这项工作中，将系统地研究光学和超声技术相结合的不同方法，包括使用短脉冲高能超声和微泡(一种超声造影剂，经常用于现代超声扫描以提高图像质量)来增强声光信号。这项研究将通过实验室和人体实验进行。为了彻底理解，还将开发计算机模型来解释产生声光信号的不同机制。这些研究将允许设计一种可靠的混合监护仪，为在一系列不同的环境中的临床使用进行优化。

A patient's health is in great danger when there is a prolonged lack of oxygen delivery to meet the metabolic demand of the tissue. This will eventually lead to cell death and organ failure. Therefore, it is very important for clinicians to monitor oxygenation in the body especially in critically ill patients or those undergoing major surgery. For example a measure of the oxygen levels in the venous system (venous oxygen saturation) has been shown to be very useful in reducing the death rate of patients with severe symptoms of whole body infection (sepsis). Also, measurements of venous oxygen saturation have been shown to be a good predictor of post-operative complications. Currently, clinical monitoring of venous oxygen saturation involves inserting an invasive catheter into a vein near the neck to perform measurements directly on the blood. However, the invasive procedures required to make these measurements demand considerable surgical skill and are associated with risk such as infection and bleeding. These procedures are only carried out in patients deemed sick enough to justify the risk, e.g. patients in the intensive care unit. These practicalities preclude many patients who can potentially benefit from the diagnostic value of the venous oxygen saturation measurement. The main objective of this work is to develop a new clinical monitor which can measure venous oxygen saturation non-invasively by combining optical and ultrasound technologies. The new clinical monitor has a probe containing both optical and ultrasound components which can be placed on the skin surface over the measurement site and target a localised region beneath. For example, it can be placed over the chest and measure the venous oxygen saturation in the pulmonary artery which contains the blood that has circulated through the whole body. This non-invasive venous oxygen saturation measurement can replace its invasive catheter based counterpart for clinical monitoring. The new monitor can also be used to target a vein draining the blood from the brain (jugular vein) so that the condition of the brain can be monitored. Other applications include the monitoring of limbs with poor circulation, recovery after surgery and the functioning of transplanted organs. Apart from venous oxygen saturation, the new monitor can also be used to measure blood flow and oxygen consumption, which indicates oxygen delivery to the tissue and the amount of oxygen used up by the tissue respectively. The principle of the new monitor is based on the phenomenon that ultrasound waves can cause periodic movement within a specific tissue region changing the way light travels through it. When light passes through this region, the intensity of the light will be altered and can be detected by a surface mounted optical detector. In other words, the light is tagged by the ultrasound waves which are the strongest in the target region. The detected tagged light is known as the acousto-optic signal and can be used to derive localized oxygenation, blood flow and oxygen consumption.In this work, different ways of combining the optical and ultrasound techniques will be systematically investigated, including the enhancement of the acousto-optic signals using short bursts of high energy ultrasound and microbubbles (an ultrasound contrast agent often used in modern ultrasound scan to improve image quality). The investigation will be conducted by both laboratory based and human experiments. For a thorough understanding, computer models will also be developed to explain the different mechanisms that generate the acousto-optic signals. These investigations will allow the design of a reliable hybrid monitor optimized for clinical use in a range of different settings.