Functional Magnetic Resonance Imaging for Tumors

肿瘤功能磁共振成像

• 批准号: 6558386
• 负责人: MURALI CHERUKURI
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6558386
• 关键词: bioimaging /biomedical imaging; biomedical equipment development; contrast media; electron spin resonance spectroscopy; free radicals; functional magnetic resonance imaging; hypoxia; image processing; laboratory mouse; metastasis; neoplastic process; oximetry; pathologic process; phantom model; respiratory oxygenation; technology /technique development

Understanding tumor physiology is useful in the diagnosis and treatment of solid tumors. More than 30% of tumors are known to contain hypoxic regions (< 10 mm Hg). Tumors with hypoxic regions are usually associated with higher metastatic potential as well as being resistant to chemotherapy and radiotherapy as well. While currently used pO2 measuring techniques are invasive and used only in tumors, which are accessible, the data obtained from these studies suggest the valuable prognostic information, which they have provided suggest the importance of these measurements. Some of the desirable features in a clinically useful pO2 measuring technique are: 1) non-invasive; 2) quantitative; 3) repeatable; and 4) sensitive to hypoxia/ischemia. Based on these considerations, we have been developing imaging techniques based on spectroscopic technique called Electron Paramagnetic Resonance (EPR), which is similar to Nuclear Magnetic Resonance (NMR), but probes species with unpaired electrons such as free radicals. The intrinsic EPR property of the paramagnetic probes used to extract oxygen is the oxygen dependent line width. Extraction of this parameter on a pixel-by-pixel basis thereby makes it possible to image oxygen in a given object. Based on this principle three independent approaches were considered for small animal imaging applications, which have the potential to be translated to human use as well. Project 1: We have developed, validated and tested the capability of non-invasive pO2 imaging in tumor bearing mice using Time-domain EPR Imaging.. We have optimized the imaging time, contrast agent dosing, gradients etc. The imaging modality is validated with standard pO2 measuring techniques. Feasibility of providing non-invasive and quantitative images of tissue oxygen status was demonstrated in tumor bearing mice. Data acquisition strategies: Integration of a low cost data acquisition system has been accomplished using commercially available high-speed digitizers. Additionally, novel data acquisition strategies such as time-locked sub-sampling are being developed. Project 2: Continuous Wave EPR Imaging unit capable of small animal imaging has been developed. This technique can monitor tissue redox status by following the levels of a redox-sensitive contrast agent. Additionally, endogenous free radicals can be detected using spin traps in pathological conditions. Recent efforts focus on improving the detection sensitivity, imaging speed, and image processing. Resolution recovery in EPR imaging has been attempted with some degree of success with iterative algorithms. Proof-in-principle of redox status imaging has been demonstrated using simple in vivo models. Project 3: Overhauser enhanced MRI is a combination of EPR amd MRI. The MRI aspect of this technique provides anatomical information and the EPR aspect information pertaining to pO2. The MRI is implemented at 15 mT. The loss in resolution inherent at such low fields is recovered using a paramagnetic contrast agent. This method has been tested and validated in phantom objects as well as in in vivo studies. The quantitative pO2 imaging capabilities of OMRI have been also validated using standard techniques such as Polarography. Preliminary studies on tumor perfusion and oxygenation and the changes in response to radiotherapy or

了解肿瘤生理学有助于实体瘤的诊断和治疗。超过30%的肿瘤已知含有缺氧区(&lt；10毫米汞)。有缺氧区的肿瘤通常与较高的转移潜力以及对化疗和放射治疗的耐药有关。虽然目前使用的PO2测量技术是侵入性的，仅用于可接触到的肿瘤，但从这些研究获得的数据表明了有价值的预后信息，他们提供的信息表明了这些测量的重要性。临床上有用的PO2测量技术的一些理想特征是：1)无创；2)定量；3)可重复；4)对缺氧/缺血敏感。基于这些考虑，我们一直在开发基于光谱技术的成像技术，称为电子顺磁共振(EPR)，类似于核磁共振(NMR)，但探测物种具有未配对的电子，如自由基。用于提取氧的顺磁探针的固有EPR特性是氧相关线宽。因此，在逐个像素的基础上提取该参数使得能够对给定物体中的氧气进行成像。基于这一原则，考虑了三种独立的方法用于小动物成像应用，这三种方法也有可能转化为人类使用。项目1： 我们已经开发、验证和测试了使用时域EPR成像在荷瘤小鼠身上进行非侵入性PO2成像的能力。我们对成像时间、造影剂剂量、梯度等进行了优化。通过标准的PO2测量技术验证了成像方式。在荷瘤小鼠中，提供组织氧状态的非侵入性和定量图像的可行性被证明。数据采集策略：低成本数据采集系统的集成已经使用商业上可获得的高速数字转换器完成。此外，正在开发新的数据采集策略，如时锁子采样。项目2：研制了可用于小动物成像的连续波电子顺磁共振成像装置。这项技术可以通过跟踪氧化还原敏感型造影剂的水平来监测组织的氧化还原状态。此外，在病理条件下，可以使用自旋陷阱来检测内源性自由基。最近的努力集中在提高检测灵敏度、成像速度和图像处理上。EPR成像中的分辨率恢复已经尝试了迭代算法，并取得了一定程度的成功。氧化还原状态成像的原理证明已经使用简单的活体模型进行了演示。项目3：Overhauser增强MRI是EPR和MRI的结合。该技术的MRI方面提供了与pO2有关的解剖信息和EPR方面的信息。磁共振成像是在15MT实施的。在如此低的磁场下固有的分辨率损失可以使用顺磁造影剂来恢复。这种方法已经在幻影对象和活体研究中进行了测试和验证。OMRI的定量pO2成像能力也已使用极谱等标准技术进行了验证。肿瘤的血流灌注和氧合功能及其对放射治疗反应的初步研究