MULTISPECTRAL QUANTITATIVE IMAGE RECONSTRUCTION METHODS FOR PHOTOACOUSTIC MOLECULAR IMAGING

光声分子成像多光谱定量图像重建方法

• 批准号: EP/D069181/1
• 负责人: Paul Beard
• 金额: $ 41.71万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FD069181%2F1
• 关键词: MULTISPECTRAL; QUANTITATIVE; IMAGE; RECONSTRUCTION; METHODS

Following the sequencing of the mouse genome, and the ability to genetically engineer small animal models for the purpose of studying disease processes, there is enormous interest in the life sciences, pre-clinical medicine and the pharmaceutical industry in developing new imaging tools that can characterise these models with high spatial resolution at a cellular or molecular level. Photoacoustic imaging, a new technique based upon the laser excitation of ultrasound, is rapidly becoming recognised as one of a new generation of optical molecular imaging modalities that is set to make a major impact on this field. Its promise is underscored by two factors: firstly, its demonstrated ability to provide high resolution anatomical images based on optical absorption in small animals such as mice and secondly, the availability of a wide range of targeted contrast agents developed for other optical molecular imaging modalities that can potentially be used to provide information at a cellular or molecular level. Termed molecular imaging, the latter can be achieved by introducing an optical absorbing contrast agent that selectively binds to a cellular or molecular receptor known to be associated with a specific disease process - eg tumour growth. By obtaining photoacoustic measurements at multiple wavelengths and, knowing the spectral signature of the contrast agent, it should be possible to identify where, and in what quantity, the contrast agent has accumulated. In this way, the location and expression levels of specific genes or proteins known to be involved in the disease process can be imaged thus providing an insight into the underlying biological processes. To achieve this, a major advance in the way photoacoustic images are reconstructed is required. Current methods provide an image of the internally absorbed optical energy distribution. It is commonly assumed that by obtaining a set of these images at different wavelengths, and matching the spectral characteristics of the contrast agent to those of the absorbed energy at each image pixel, it will be possible to detect and quantify the accumulation of the contrast agent. However, this hypothesis is highly questionable on account of the spatial-spectroscopic crosstalk in an absorbed energy map - in essence the significant spectral characteristics of tissue constituents such as haemoglobin corrupts those of the contrast agent compromising the ability to detect and quantify its presence. The aim of the proposed research is to overcome this by taking the image reconstruction process a stage further than has been previously attempted. This involves accounting for the light transport in the tissue and the known spectral characteristics of the contrast agent and tissue absorbers and scatterers. To achieve this, it is proposed to employ a mathematical model that describes the absorbed optical energy distribution, and its wavelength dependence, within the tissue. By repeatedly adjusting the input parameters of the model until its output matches that of the conventionally reconstructed absorbed energy images, a map of the absolute concentration of the contrast agent can be obtained. The project will require the development of novel computational methods to solve what is an inverse problem of significant scale, analysis of the accuracy and resolution with which the contrast agent concentration can be determined and evaluation using simulated and experimentally obtained phantom and in vivo data / the latter being obtained using a 3D photoacoustic small animal scanner which we are currently developing under a recently awarded EPSRC project. This related project, along with the proposed research and our existing expertise in photoacoustic imaging, modelling light transport and inverse problems provides a timely opportunity to make a significant contribution to the development of photoacoustic imaging as a sensitive, specific and quantitative molecular imaging tool.

继小鼠基因组测序和为研究疾病过程而对小动物模型进行遗传工程改造的能力之后，生命科学、临床前医学和制药工业对开发新的成像工具产生了巨大的兴趣，这些成像工具可以在细胞或分子水平上以高空间分辨率对这些模型进行成像。光声成像是一种基于激光激发超声波的新技术，正迅速成为公认的新一代光学分子成像模式之一，将对这一领域产生重大影响。它的前景是强调了两个因素：首先，它的证明能力，提供高分辨率的解剖图像的基础上，在小动物，如小鼠的光学吸收，其次，广泛的目标造影剂的可用性开发的其他光学分子成像模式，可以潜在地用于提供信息，在细胞或分子水平。后者称为分子成像，可以通过引入光学吸收造影剂来实现，该造影剂选择性地结合已知与特定疾病过程（例如肿瘤生长）相关的细胞或分子受体。通过在多个波长处获得光声测量，并且知道造影剂的光谱特征，应当能够识别造影剂在何处以及以何种量累积。通过这种方式，可以对已知参与疾病过程的特定基因或蛋白质的位置和表达水平进行成像，从而提供对潜在生物过程的深入了解。为了实现这一点，需要在光声图像重建的方式上取得重大进展。目前的方法提供了内部吸收的光能分布的图像。通常假设，通过在不同波长下获得一组这些图像，并且将造影剂的光谱特性与每个图像像素处的吸收能量的光谱特性相匹配，将有可能检测和量化造影剂的累积。然而，由于吸收能量图中的空间光谱串扰，这种假设是非常有问题的-本质上，组织成分（例如血红蛋白）的显著光谱特性破坏了造影剂的光谱特性，从而损害了检测和量化其存在的能力。所提出的研究的目的是克服这一点，采取的图像重建过程的一个阶段比以前尝试。这涉及考虑组织中的光传输以及造影剂和组织吸收体和散射体的已知光谱特性。为了实现这一点，建议采用描述组织内吸收的光能分布及其波长依赖性的数学模型。通过重复调整模型的输入参数直到其输出与常规重建的吸收能量图像的输出相匹配，可以获得造影剂的绝对浓度的图。该项目将需要开发新的计算方法来解决显着规模的逆问题，分析造影剂浓度的准确性和分辨率，并使用模拟和实验获得的体模和体内数据进行评估/后者使用3D光声小动物扫描仪获得，我们目前正在根据最近授予的EPSRC项目进行开发。这个相关的项目，沿着拟议的研究和我们现有的专业知识，在光声成像，建模光传输和逆问题提供了一个及时的机会，使一个显着的贡献，光声成像作为一个敏感的，具体的和定量的分子成像工具的发展。