Ultrasound mediated bioluminescence tomography for high sensitivity, high spatial resolution 3D imaging

用于高灵敏度、高空间分辨率 3D 成像的超声介导生物发光断层扫描

• 批准号: NC/L00187X/1
• 负责人: Stephen Morgan
• 金额: $ 44.55万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FL00187X%2F1
• 关键词: Ultrasound; mediated; bioluminescence; tomography; sensitivity

Optical imaging is a unique and powerful technique for implementation of 'refinement' and 'reduction' within the Principles of Humane Experimental Techniques. Using traditional disease models, infected animals (ranging between 3-10) are sacrificed at defined time points and tissues are excised for determination of pathogen numbers and localization. For example, a six time point experiment would result in the use of 18-60 animals. In contrast, the non-invasive nature of optical imaging allows the course of an infection to be monitored simply by imaging the visible or near infrared signal detected from within the same group of animals, typically six to eight in total. Importantly, multiple imaging of the same animal throughout an experiment allows disease progression to be followed with extreme accuracy and consistency, while allowing each animal to act as its own control. There is a major drawback in using optical imaging as light is heavily scattered by tissue which results in poor quality images. For example in tracking stem cells in tissue, optical scattering means that we cannot tell where precisely where the cells go in the body, how many are at a particular and what their action is. This severely hampers research into understanding the use of stem cells in aiding the body's immune response. We propose to develop an imaging system that combines ultrasound and optical techniques to significantly improve the spatial resolution and sensitivity of bioluminescence imaging. Information from the ultrasound will be used in two ways to address this problem. Firstly, as ultrasound makes a small change to the mechanical properties of the tissue, this can be used to modulate the bioluminescent light produced within the tissue. This provides a modulated light 'beacon' which can be used to precisely probe different regions of the tissue, thus overcoming the effects of light scattering and improving spatial resolution. Secondly we will use the ultrasound image to provide 3D maps of tissue structure. Both modulated light beacons and structural information will be used to inform an image reconstruction algorithm based on our widely used NIRFAST software (www.nirfast.org). The system will be demonstrated in studies of nude mice during the course of the project. Based on our proof of concept data, we anticipate that the spatial resolution will be a maximum of 0.5mm, compared to the current state of the art of 2.5mm. This will contribute to a significant impact on the 3Rs. Replacement: better imaging will inform more accurate computational models; Reduction: imaging enables the same animals to used over time and more accurate quantitative imaging allows fewer animals to be used in a single study; Refinement: through the improved quality of research findings.

光学成像是在人道实验技术原理中实施“改进”和“还原”的独特而有力的技术。使用传统疾病模型，在定义的时间点处以感染的动物（在3-10之间），并切除组织以确定病原体数量和定位。例如，六个时间点实验将导致使用18-60只动物。相反，光学成像的非侵入性质可以通过从同一组动物内检测到可见的或接近红外信号来监测感染的过程，通常总共六到八个。重要的是，整个实验中对同一动物的多次成像允许疾病进展，以极高的准确性和一致性，同时允许每只动物充当自身的控制。使用光学成像是一个主要的缺点，因为光线大量散布着组织，从而导致质量差的图像。例如，在跟踪组织中的干细胞时，光学散射意味着我们无法确切地分辨细胞在体内的何处，特定在某个特定的作用以及它们的作用是什么。这严重阻碍了理解干细胞在帮助人体免疫反应中使用的研究。我们建议开发一个结合超声和光学技术的成像系统，以显着提高生物发光成像的空间分辨率和灵敏度。超声波的信息将以两种方式来解决此问题。首先，由于超声对组织的机械性能做出了很小的变化，因此可以用于调节组织内产生的生物发光光。这提供了一个调制的光“信标”，可用于精确探测组织的不同区域，从而克服了光散射和改善空间分辨率的影响。其次，我们将使用超声图像提供组织结构的3D图。调制的轻型信标和结构信息都将用于基于我们广泛使用的Nirfast软件（www.nirfast.org）的图像重建算法为图像重建算法提供信息。该系统将在项目过程中对裸鼠的研究中进行证明。根据我们的概念数据证明，我们预计与当前的2.5mm的技术状态相比，空间分辨率最高为0.5mm。这将对3RS产生重大影响。替换：更好的成像将为更准确的计算模型提供信息；还原：成像使相同的动物随着时间的流逝而使用，并且更准确的定量成像可以使一项研究中使用更少的动物。改进：通过改善研究结果的质量。