IN VIVO MRI QUANTIFICATION OF TISSUE PERMEABILITY

组织渗透性的体内 MRI 量化

• 批准号: 2842881
• 负责人: HAROLD L. KUNDEL
• 金额: $ 12.67万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2002-07-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2842881
• 关键词: bioimaging /biomedical imaging; blood brain barrier; brain imaging /visualization /scanning; brain injury; cell morphology; chelating agents; chemical kinetics; chemical models; contrast media; cryopreservation; diffusion; dosage; emission spectrometry; gadolinium; intravenous administration; laboratory rat; magnetic resonance imaging; membrane permeability; plasma

Magnetic resonance imaging (MRI) contrast agents that contain gadolinium chelates continue to play a critical role in the evaluation of diseases of the central nervous system including primary and secondary neoplasia, infection (HIV), vascular disorders (aneurysms), cerebral infarction and white matter disease (multiple sclerosis). Gadolinium-enhanced MR has also shown some promise in characterizing hepatic and extrahepatic abdominal lesions, and possibly also for discriminating benign from malignant lesions in the breast. Qualitative assessments of MRI enhancement patterns have, however, provided only limited pathophysiological insights. Recently, considerable research efforts have been directed at the use of MRI for the quantitative assessment of physiologic parameters such as the blood-brain barrier permeability and the relative volume of the extracellular space (ECS). Kinetic models of tissue and plasma Gd concentration allow these physiologic parameters to be extracted from dynamic MR signal data. One common assumption used in such models is that the in vivo relaxivity of Gd-chelates is similar to that measured in vitro (in saline). The first aim of this proposal is to test this assumption using MR measurements of spin-lattice and spin-spin relaxation rates before and after administration of Gd-chelate in a freezing rat brain lesion, in conjunction with ICP-atomic emission spectroscopic measurements of tissue Gd levels. Preliminary work indicates that the in vivo Gd relaxivity in damaged tissue is several times higher than the Gd relaxivity measured in saline. Derivation of clinical MR-based quantitative measures of blood-brain barrier permeability will therefore require an in vivo determination of in vivo relaxivity. The second aim of this proposal is to show that estimates of relaxivity may be based on an independent measure of ECS (provided by an in vivo measurement of the apparent diffusion coefficient in the brain lesion). Preliminary results suggest that ADC is highly correlated with the ECS volume. An important consequence of this work will be the ability to differentiate between lesions that appear similar in the MR image, but differ significantly in their permeability and relaxivity. Another significant outcome will be that MRI measurements of in vivo relaxivity in the damaged tissues will permit determination of the optimum Gd dose and MRI parameters.

含有钆螯合物的磁共振成像（MRI）造影剂在评价中枢神经系统疾病（包括原发性和继发性肿瘤、感染（HIV）、血管疾病（动脉瘤）、脑梗死和白色疾病（多发性硬化））中继续发挥关键作用。 钆增强磁共振在肝脏和肝外腹部病变的特征方面也显示出一定的前景，也可能用于区分乳腺良恶性病变。 然而，MRI增强模式的定性评估仅提供了有限的病理生理学见解。最近，相当多的研究工作已经针对使用MRI的定量评估的生理参数，如血脑屏障的渗透性和细胞外空间（ECS）的相对体积。 组织和血浆Gd浓度的动力学模型允许从动态MR信号数据中提取这些生理参数。 在这样的模型中使用的一个常见的假设是，在体内的Gd-螯合物的弛豫率是类似于在体外测量（在盐水中）。 本建议的第一个目的是测试这一假设，使用MR测量自旋晶格和自旋自旋弛豫率之前和之后的Gd-螯合物在冷冻大鼠脑病变，结合ICP-原子发射光谱测量组织Gd水平。初步工作表明，在体内Gd弛豫在受损组织是几倍高于Gd弛豫在盐水中测量。因此，血脑屏障通透性的基于临床MR的定量测量的推导将需要体内弛豫率的体内测定。 该建议的第二个目的是表明弛豫率的估计可以基于ECS的独立测量（由脑病变中的表观扩散系数的体内测量提供）。初步结果表明，ADC值与ECS体积高度相关。这项工作的一个重要结果是能够区分在MR图像中看起来相似，但在渗透性和弛豫性方面有显著差异的病变。 另一个重要的结果将是，MRI测量体内弛豫率在受损组织将允许确定最佳Gd剂量和MRI参数。