Ultrasound modulated optical tomography for functional imaging of engineered tissue

组织工程是指培育用于临床的新组织或器官，这可能对未来的医学产生深远的影响。生物学家通常使用显微镜来了解细胞结合形成组织的方式。然而，随着实验室培养的组织变厚（2mm-1cm），传统的显微镜就不能使用了。造成这种情况的原因是，光线被组织严重散射（这就是为什么当你把手指放在灯泡前时，你看不到手指上的骨头）。因此，需要开发新的成像方法，以便利用光对厚组织进行成像。超声是医学上常用的厚组织成像方法，对测量组织的机械结构非常有用。然而，它无法获得与光相同的功能信息。例如，光可以用来检测细胞的荧光或血液中的氧含量。在这个项目中，我们将开发一种结合光和超声波对厚组织成像的新设备。该装置将以超声图像分辨率提供光的功能信息。该装置的原理是，当光通过超声波时，它会被调制成超声波的频率。这使得人们可以使用超声波在组织内的精确位置放置闪烁的灯塔，并提供一种计算光在组织内的位置的方法。将超声波的焦点移动到组织内的不同位置（就像在传统超声成像中所做的那样），可以在超声分辨率下建立组织内的光图像。由于组织内光与声的相互作用非常弱，因此从组织中发出的调制光信号非常弱，因此开发这种设备存在几个技术挑战。该小组在光与组织的相互作用、医疗仪器的设计和超声波方面拥有专业知识，我们将结合这些专业知识来增加从组织中出现的光信号的大小，并使光检测尽可能灵敏。一个例子是使用多个超声波源并干扰超声波以提供更大的光信号和更好的分辨率。此外，我们将使用计算机模拟来模拟光通过组织传播并与超声波相互作用的方式。这将有助于我们了解定位超声光源和光探测器的最佳方法，以实现最佳性能。在这个项目中，工程师和生物学家将密切合作，以确保我们正在建造一个有用的设备。在项目期间，将进行实验，以超声分辨率成像组织内的荧光信号。主要目标可以概括如下：1)开发光与超声相结合的系统，以超声分辨率获取组织内的光图像。2)利用新颖的超声方法，使从组织中出现的光信号尽可能大。3)获得厚组织内第一张高分辨率荧光图像4)同时测量原始光色和组织内荧光。这种新装置将为组织工程师提供一种重要的新工具。

Tissue engineering is the growth of new tissue or organs for clinical use, which could have a profound effect on medicine in the future. Biologists routinely use microscopes to understand the way that cells combine to form tissue. However, as the tissue being grown within the laboratory becomes thicker (2mm-1cm) then conventional microscopes cannot be used. The reason for this is that light is heavily scattered by tissue (this is the reason that you can't see the bone in your finger when you hold it up to a light bulb). New imaging methods therefore need to be developed to allow imaging of thick tissue using light. Ultrasound is a method that is routinely used in medicine for imaging thick tissue and is very useful for measuring the mechanical structure of tissue. However it cannot obtain the same functional information that can be obtained using light. For example, light can be used to detect the fluorescence of cells or the oxygen content of the blood. Within this project we will develop a new device that combines light and ultrasound to image thick tissue. This new device will provide the functional information of light at the image resolution of ultrasound. The device is based on the principle that when light passes through ultrasound it becomes modulated at the frequency of the ultrasound. This allows one to use ultrasound to place a flashing beacon of light within the tissue at a precise location and provides a method of working out where the light has been within the tissue. Moving the focus of the ultrasound to different locations within the tissue (as would be done in conventional ultrasound imaging) allows one to build up an image of light within the tissue at the resolution of ultrasound. There are several technical challenges to developing such a device as the interaction between light and sound within tissue is very weak and hence the modulated light signals emerging from the tissue are very weak. The group has expertise in light interaction with tissue, the design of medical instruments and ultrasound and we will combine this expertise to increase the size of the light signal emerging from tissue and make the light detection as sensitive as possible. One example is to use more than one source of ultrasound and interfere the ultrasound waves to provide larger light signals and better resolution. In addition we will use computer simulations to model the way light propagates through tissue and interacts with the ultrasound. This will help us understand the best way to position the ultrasound sources and light detectors to achieve the best performance. The engineers and biologists will work closely together during the project to ensure that we are constructing a useful device. Experiments will be performed to image fluorescent signals within tissue at the resolution of ultrasound during the project. The main aims can be summarised as follows; 1) Development a system combining light and ultrasound to obtain images of light within tissue at the resolution of ultrasound. 2) Use novel ultrasound methods to make the light signals emerging from the tissue as large as possible. 3) Obtain the first images of fluorescence at high resolution within thick tissue 4) Simultaneously measure the original light colour and the fluorescence within tissue. The new device will provide an important new tool for tissue engineers.