IN VIVO MRI QUANTIFICATION OF TISSUE PERMEABILITY

含有Gd络合物的磁共振成像(MRI)造影剂继续在评估中枢神经系统疾病方面发挥关键作用，包括原发和继发性肿瘤、感染(HIV)、血管疾病(动脉瘤)、脑梗塞和白质疾病(多发性硬化症)。Gd增强磁共振在确定肝脏和肝外腹部病变方面也显示出一些希望，也可能在鉴别乳腺良恶性病变方面有所作为。然而，对MRI增强模式的定性评估只能提供有限的病理生理学见解。近年来，MRI被用于定量评估血脑屏障通透性和细胞外间隙相对体积等生理参数。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。这类模型中使用的一个常见假设是，Gd-螯合物的体内弛豫度与体外(在生理盐水中)测量的结果相似。这项提议的第一个目的是通过在冰冻的大鼠脑损伤中注射Gd-螯合物前后的自旋-晶格和自旋-自旋弛豫速率的MR测量，以及对组织Gd水平的电感耦合等离子体原子发射光谱测量来验证这一假设。初步工作表明，体内受损组织中的Gd驰豫率比在生理盐水中测量的Gd驰豫率高出数倍。因此，临床上基于磁共振的血脑屏障通透性定量测量的推导将需要活体测定体内的松弛率。这项建议的第二个目的是表明，松弛能力的估计可能基于ECS的独立测量(通过在体内测量大脑病变中的表观扩散系数来提供)。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将是能够区分在磁共振图像中看起来相似，但在渗透性和松弛性方面明显不同的病变。另一个重要的结果是，MRI测量受损组织的体内弛豫度将使确定最佳Gd剂量和MRI参数成为可能。

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.