Cancer Detection Using Diffuse Luminescence Imaging

描述(由申请人提供)：该提案的重点是使用氧敏感磷光标记和混合成像方式进行乳腺癌成像和肿瘤表征。我们提出使用同步漫反射光学层析成像(DOT)和磁共振成像(MRI)来获得高空间分辨率和定量的乳腺肿瘤功能图像。在注射造影剂的临床前模型中进行成像和对组织内的氧浓度进行成像具有重要的临床和科学意义。肿瘤中的低氧含量是肿瘤抗辐射区域的标志，也与不良的治疗结果相关。对于基础研究应用，了解肿瘤中缺氧是如何发展的，以及它与外源性和内源性低氧标志物是如何关联的，这也是非常重要的。在第一阶段，结合标准漫反射光学断层扫描(DOT)，我们使用长寿命氧气敏感造影剂和一个简单的雪崩光电二极管终身成像系统，获得了模拟体模的乳房组织缺氧区的高对比度图像。在第二阶段，将开发连续波和时间域寿命成像模块的原型，该模块将通过冷却的16元雪崩光电二极管(雪崩光电二极管)阵列进行并行采集，以实现高分辨率和高通量成像。这种低成本、紧凑的寿命成像仪模块将被设计成与混合成像系统中与MR单元相关的高磁场和RF场兼容。在我们的合作者位于NH的达特茅斯学院(Brian Pogue教授，塞耶工程学院)的设施中，在双模式成像设置中使用此APD模块，将执行模型和动物模型成像，以获得高分辨率和高对比度的功能光学图像。光学图像重建将利用从同时获得的高分辨率MR图像中获得的空间和解剖信息来辅助，以提高这些图像的精度。紧凑型基于雪崩光电二极管的探测器原型占地面积很小，将安装在磁共振成像单元的磁体内，大大降低了当前基于光电倍增管的探测系统的复杂性。与公众健康相关：混合成像与同时漫反射发光成像和磁共振成像可用于根据肿瘤的氧气浓度获得高分辨率的功能图。低氧乳腺癌的检测是主要的靶向应用，目的是利用外源性造影剂提高诊断的准确性和治疗预后。其他应用包括监测脑功能或脑出血的脑成像，以及监测组织和肌肉氧合、组织毒性等。

DESCRIPTION (provided by applicant): The focus of the proposal is in the area of breast cancer imaging and tumor characterization using oxygen sensitive phosphorescent labels and hybrid imaging modality. We propose to use simultaneous diffuse optical tomography (DOT) and magnetic resonance imaging (MRI) to obtain high spatial-resolution and quantitative functional images of breast tumors. Imaging in pre-clinical models with injected contrast agents and imaging the oxygen concentration within tissue are important for a number of clinical and scientific reasons. Low oxygen content in tumors is a marker of radiation-resistant tumor regions, and is also correlated with a poor treatment outcome. For basic research applications, it is also very important to understand how hypoxia develops in tumors and how it is correlated with exogenous and endogenous markers of low oxygen. During Phase I, in conjunction with standard diffuse optical tomography (DOT), we obtained high contrast images of hypoxic regions in breast tissue simulating phantoms using long-lived oxygen sensitive contrast agents and a simple lifetime imaging system with cooled avalanche photodiodes. In Phase II, a prototype of the CW and time domain lifetime imaging module will be developed which will have parallel acquisition across a cooled 16-element avalanche photodiode (APD) array for high resolution and high throughput imaging. The low-cost, compact lifetime imager module will be designed to be compatible with high magnetic and RF fields associated with MR units in hybrid imaging systems. Using this APD module in a dual-modality imaging setup at our collaborator's facility at Dartmouth College, NH (Prof. Brian Pogue, Thayer School of Engineering), phantom and animal model imaging will be performed to obtain functional optical images with high resolution and high contrast. The optical image reconstruction will be aided by the spatial and anatomical information obtained from simultaneously obtained high-resolution MR images in order to improve the accuracy of these images. The compact APD based detector prototype will have a small footprint and will be mounted inside the magnet of the MRI unit, dramatically decreasing the complexity of the current PMT based detection systems. PUBLIC HEALTH RELEVANCE: Hybrid imaging with simultaneous diffuse luminescence imaging and magnetic resonance imaging can be used to obtain high resolution functional maps of tumors based on their oxygen concentration. Hypoxic breast cancer detection is the primary target application, with the goal of improving diagnostic accuracy and treatment prognosis using exogenous contrast agents. Other applications could include brain imaging to monitor cerebral function or cerebral hemorrhage, and monitoring tissue and muscle oxygenation, histotoxicity, etc.