IN VIVO MRI QUANTIFICATION OF TISSUE PERMEABILITY

含有钆螯合物的磁共振成像（MRI）造影剂继续在中枢神经系统疾病的评估中发挥关键作用，包括原发性和继发性肿瘤、感染（HIV）、血管疾病（动脉瘤）、脑梗死和白质疾病（多发性硬化症）。钆增强MR在肝脏和肝外腹部病变的特征方面也显示出一定的希望，也可能用于区分乳腺的良性和恶性病变。然而，对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，大量的研究工作都是针对使用MRI来定量评估生理参数，如血脑屏障通透性和细胞外空间（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。在这种模型中使用的一个常见假设是，gd -螯合物的体内松弛度与体外（生理盐水）测量的松弛度相似。本研究的第一个目的是通过在冷冻大鼠脑损伤中使用Gd螯合物前后的自旋-晶格和自旋-自旋弛豫率的MR测量来验证这一假设，并结合icp -原子发射光谱测量组织Gd水平。初步研究表明，体内损伤组织的Gd松弛度比生理盐水中测量的Gd松弛度高几倍。因此，基于临床核磁共振的血脑屏障通透性定量测量的推导将需要在体内确定体内松弛度。本提案的第二个目的是表明，对弛豫度的估计可能基于对ECS的独立测量（由脑病变中表观扩散系数的体内测量提供）。初步结果表明ADC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图像上看起来相似，但在通透性和弛豫度上有显着差异的病变。另一个重要的结果将是MRI测量受损组织的体内松弛度将允许确定最佳Gd剂量和MRI参数。

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.