Ultrasound modulated optical tomography for functional imaging of engineered tissue

组织工程是用于临床的新组织或器官的生长，这可能对未来的医学产生深远的影响。生物学家经常使用显微镜来了解细胞结合形成组织的方式。然而，随着实验室内生长的组织变得更厚(2毫米-1厘米)，常规显微镜就不能使用了。这样做的原因是光线被组织严重散射(这就是当你拿着灯泡时看不到手指上的骨头的原因)。因此，需要开发新的成像方法，以允许使用光对厚组织进行成像。超声是医学上常规用于成像厚组织的方法，对于测量组织的机械结构非常有用。然而，它不能获得使用光可以获得的相同功能信息。例如，光可以用来检测细胞的荧光或血液的含氧量。在这个项目中，我们将开发一种新的设备，将光和超声波结合在一起，对厚组织进行成像。这种新的装置将以超声的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，它会以超声波的频率进行调制。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光的信标，并提供了一种计算光在组织内的位置的方法。将超声的焦点移动到组织内的不同位置(如在常规超声成像中所做的那样)允许人们以超声的分辨率在组织内建立光的图像。开发这样的装置有几个技术挑战，因为组织内的光和声之间的相互作用非常弱，因此从组织中出现的调制光信号非常弱。该团队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组织发出的光信号的大小，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在组织中传播并与超声波相互作用的方式。这将帮助我们了解放置超声源和光探测器以实现最佳性能的最佳方式。工程师和生物学家将在项目期间密切合作，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，以超声波的分辨率对组织内的荧光信号进行成像。其主要目的可概括如下：1)开发一种结合光和超声的系统，以获得组织内超声分辨率的光图像。2)使用新的超声方法，使从组织中发出的光信号尽可能大。3)获得厚组织内高分辨率的第一批荧光图像4)同时测量原始光色和组织内的荧光。这一新设备将为组织工程师提供一个重要的新工具。

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.