Measuring Bladder Permeability with MRI Using a Novel Contrast Agent Formulation

摘要 该第二阶段SBIR提案利用了第一阶段在开发新型控制器方面取得的进展， trast mixture增强T1加权MRI技术是一种安全、敏感和客观的诊断试验， 间质性膀胱炎/膀胱疼痛综合征中膀胱腔表面通透性增加 IC/BPS患者。进行这种测试的目的最终是让临床医生，在某些情况下， 在某些情况下，鉴别诊断慢性非感染性膀胱炎症与慢性非感染性膀胱炎， 骨盆底缺损利用阶段I支持物来证明新的对比混合物上级 单独滴注FDA批准的钆螯合物（Gadovist）或超顺磁性氧化铁 纳米颗粒（Feraheme）在从管腔分割大鼠膀胱壁中的作用。对比度混合依赖于 用于改善图像对比度的两种造影剂的颗粒尺寸和对比机制的差异 膀胱壁。Gadovist缩短局部T1，Feraheme缩短局部T2，其中 可以独立地跟踪这两个分量。因此，定量T1测量可以成为一个双- Gd对比渗透率的标志物，尽管定量关系必须仔细确定， 地雷。在7 T的高场强下进行I期大鼠研究。当转换为图像时- 在3 T临床场强扫描仪中对人类受试者进行的研究表明，新型造影剂混合物安全耐受， 艾德，其3 mm厚的膀胱壁可通过一系列单次屏气成像 在临床上可接受的成像时间内（总共<1小时）使用FLASH序列。对于阶段1，新的对比度混合- 因此，我们需要开发一种新的单位剂型， 适合FDA备案的造影剂混合物，并优化其在临床强度磁体使用中的成像性能， 我们还将验证钆在膀胱和膀胱周围器官中的组织信号增强 通过电感耦合等离子体质谱法（ICP-MS）测量。我们的长期目标是发展 通过优化、验证和扩展定量的用于改善IC患者护理的造影剂 MRI方法用于识别膀胱渗透性与骨盆底张力的IC患者。

ABSTRACT This Phase II SBIR proposal leverages the progress made in Phase I on the development of a novel con- trast mixture enhanced T1-weighted MRI technique as a safe, sensitive, and objective diagnostic test for the increased permeability in the luminal surface of the urinary bladder in Interstitial Cystitis/Bladder Pain Syn- drome (IC/BPS) patients. The purpose of having such a test is ultimately to allow clinicians, in certain cir- cumstances, to differentially diagnose a chronic, non-infectious inflammation of the urinary bladder from a pelvic floor defect. Phase I support was utilized to demonstrate that the novel contrast mixture is superior to individual instillation of either FDA approved gadolinium chelate (Gadovist) or superparamagnetic iron oxide nanoparticles (Feraheme) in segmenting the rat bladder wall from lumen. The contrast mixture relies on the differences in particle size and contrast mechanisms of the two contrast agents for improved image contrast of the bladder wall. Gadovist shortens the local T1 and Feraheme shortens the local T2, wherein each of the two components can be tracked independently. Quantitative T1 measurements can thus become a bi- omarker for Gd contrast permeability, albeit the quantitative relationship would have to be carefully deter- mined. The rat studies in Phase I were performed at a high field strength of 7T. When transitioning to imag- ing of human subjects in clinical field strength scanners at 3T, the novel contrast mixture was safely tolerat- ed by human subjects, whose 3 mm thick bladder wall could be imaged by a series of single-breath-hold FLASH sequences in a clinically acceptable imaging time (<1 h total). For Phase 1, the novel contrast mix- ture was extemporaneously compounded, and therefore, we need to develop a unit dosage form of novel contrast mixture suitable for an FDA filing and optimize its imaging properties in clinical strength magnet us- ing cat. We will also validate the tissue signal enhancement in bladder and perivesical organs by gadolinium measurement by inductively coupled plasma mass spectrometry (ICP-MS). Our long-term goal is to develop contrast agents for improved patient care of IC patients by optimizing, validating, and extending quantitative MRI methods for identifying IC patients with bladder permeability versus pelvic floor tonicity.