Measuring Bladder Permeability with MRI Using a Novel Contrast Agent Formulation

使用新型造影剂配方通过 MRI 测量膀胱渗透性

• 批准号: 9788421
• 负责人: JONATHAN H KAUFMAN
• 金额: $ 58.5万
• 依托单位: LIPELLA PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-20 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788421
• 关键词: Acetic Acids; Bladder; Chelating Agents; Chemicals; Chronic; Clinical; Clinical Research; Clinical Trials; Contrast Media; Defect; Development; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Dimensions; Disease; Dosage Forms; Drug or chemical Tissue Distribution; Epidemiology; Exclusion; FDA approved; Felis catus; Female; Formulation; Frequencies; Gadolinium; Gadovist; General Population; Goals; Image; Imaging Techniques; Individual; Inductively Coupled Plasma Mass Spectrometry; Inflammation; Injections; Institutional Review Boards; Interstitial Cystitis; Intravenous; Label; Magnetic Resonance Imaging; Market Research; Measurement; Measures; Medical; Methods; Morphologic artifacts; Motion; Noise; Organ; Particle Size; Pathology; Patient Care; Patients; Pelvic floor structure; Permeability; Persons; Pharmacologic Substance; Phase; Physiologic pulse; Prevalence; Protocols documentation; Rattus; Resolution; Saline; Series; Signal Transduction; Small Business Innovation Research Grant; Sterility; Surface; Symptoms; Techniques; Testing; Thick; Three-Dimensional Imaging; Time; Tissues; Urination; Urine; Vial device; Water; base; chronic pelvic pain; clinical development; cohort; contrast imaging; dosage; ferumoxytol; gadobutrol; human imaging; human subject; imaging modality; imaging properties; improved; intravesical; iron oxide nanoparticle; man; micturition urgency; molecular size; novel; phase 1 study; spatiotemporal; superparamagnetism; tool; translation to humans

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.

摘要