QUANTIFYING KIDNEY INJURY AND INFLAMMATION WITH FLUORINE (19F) MRI

使用氟 (19F) MRI 量化肾脏损伤和炎症

基本信息

批准号：
8385326
负责人：
SAMUEL A WICKLINE
金额：
$ 22.8万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-17 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8385326
关键词：
Acute Acute Disease Acute Renal Failure with Renal Papillary Necrosis Adoption Aging Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Anticoagulation Arthritis Behavior Biological Markers Blood Vessels Blood Volume Cardiovascular Diseases Carotid Artery Plaques Cells Chronic Chronic Disease Chronic Kidney Failure Classification Clinical Clinical Trials Coagulation Process Consumption Contrast Media Creatinine Development Diagnosis Diagnostic Imaging Dialysis procedure Disease Drug Delivery Systems Drug Formulations Elderly Extravasation FDA approved Fluorine Fluorocarbons Functional Imaging Functional disorder Goals Healthcare Hypoxia Image Imaging Device Incidence Individual Industry Collaborators Inflammation Inflammatory Injury Integrins Intervention Kidney Kidney Diseases Kidney Failure Lead Ligands Magnetic Resonance Imaging Malignant Neoplasms Manufacturer Name Maps Measures Medical Imaging Methods Metric Molecular Molecular Target Morbidity - disease rate Natural regeneration Output Oxygen Pathway interactions Patients Perfusion Play Protons Recovery Regional Perfusion Relaxation Renal Blood Flow Renal clearance function Renal function Reperfusion Injury Research Personnel Resources Risk Risk Factors Role Safety Sensitivity and Specificity Signal Transduction Staging Stratification Syndrome System Time Toxic effect Transplantation Tubular formation Urine Work Workload angiogenesis base clinical application flexibility glomerular filtration imaging modality improved in vivo inflammatory marker interest kidney vascular structure molecular imaging mortality mouse model nanoparticle patient population prognostic prolylarginine renal ischemia research clinical testing response tool urinary

项目摘要

DESCRIPTION (provided by applicant): Acute kidney injury in the face of chronic kidney disease is a frequent clinical problem with an increasing incidence, an unacceptably high mortality rate that has not improved in more than 50 years, and no specific treatment. Interest is keen for the pursuit of methods for quantifying structural and functional disruption in progressive chronic disease and acute injury that might improve the sensitivity, specificity, and time in which renal injury is diagnosed, and facilitate risk stratification and/or provide prognostic information including prediction of recovery of renal function. We contend that the combination of adjunctive image-based functional and molecular readouts of regional blood volume, oxygenation, and inflammation could enhance these new urinary biomarkers to fully quantify the renal risk state and evaluate therapy in both chronic and acute diseases. We propose to explore and compare an alternative approach to existing methods with the use of native and molecularly targeted perfluorocarbon nanoparticles (PFC NPs) that could offer numerous advantages for diagnostic imaging and drug delivery to chronic and acute kidney diseases. Our preliminary results showed intrarenal oxygenation could be non-invasively mapped by 19F MRI. Renal ischemia-reperfusion (I/R) injury induced outer medullary vascular non-perfusion was directly detected by regional reduction of 19F signal intensity from circulating PFC NPs. Such regional non-perfusion of renal vasculature was effectively inhibited by PFC NPs facilitated anticoagulation therapy. The proposal is highly translational and the methods to be developed have a direct path to clinical testing and implementation because the targeted PFC NPs contrast platform already is in FDA-approved clinical trials for molecular imaging of angiogenesis with fluorine (19F) MRI/MRS. Furthermore, the dual, simultaneous proton and fluorine imaging methods are fundamentally developed and implemented on a clinical 3T scanner, and ready for adoption by any manufacturer. Accordingly our aims are to: AIM 1. Validate 19F MRI of PFC NPs is a quantitative measure for mapping intrarenal blood volume, PO2, and inflammation using a mouse model of renal ischemia/reperfusion (I/R) injury AIM 2. Evaluate the effect of PPACK NPs on inhibiting intrarenal nonperfusion using 19F MRI in vivo PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page PUBLIC HEALTH RELEVANCE: Chronic renal disease combined with acute kidney injury is a frequent clinical problem with an increasing incidence, an unacceptably high mortality rate that has not improved in more than 50 years, and no specific treatment. We propose to implement adjunctive noninvasive functional and molecular imaging readouts of intrarenal blood volume, oxygenation, and inflammation and to develop a nanoparticle facilitated anticoagulation therapy that should enhance diagnosis and treatment of chronic and acute kidney diseases. The proposal is highly translational and the methods to be developed have a direct path to clinical testing and implementation.

描述（由申请人提供）：面对慢性肾脏疾病的急性肾脏损伤是一个常见的临床问题，发生率越来越高，高死亡率不高，在50多年的时间内没有改善，没有特定的治疗方法。兴趣渴望追求量化结构和功能破坏的方法慢性疾病和急性损伤可能会提高敏感性，特异性和时间诊断出肾脏伤害并促进风险分层和/或提供预后信息包括预测肾功能的恢复。我们认为，辅助性基于图像的功能和分子读数的区域血容量，氧合和炎症的结合可以增强这些新的尿生物标志物，以充分量化肾脏风险状态并评估慢性疾病和急性疾病的治疗。我们建议探索和比较现有方法的替代方法与使用天然和分子靶向的全氟纳米颗粒（PFC NPS）的使用，该方法可以为诊断成像和药物提供慢性和急性肾脏疾病提供许多优势。我们的初步结果表明，19f MRI可以无创局内氧合作用。肾脏缺血再灌注（I/R）损伤诱导的髓外血管非灌注直接通过循环PFC NP的区域降低19F信号强度直接检测到。 PFC NPS促进抗凝治疗有效抑制了这种区域性肾血管的不良渗透。该提案是高度转化的，要开发的方法具有临床测试和实施的直接途径，因为靶向的PFC NPS对比平台已经在FDA批准的临床试验中，用于用氟（19F）MRI/MRI/MRS进行血管生成的分子成像。此外，双重的，同时的质子和氟成像方法从根本上是在临床3T扫描仪上开发和实施的，并准备好被任何制造商采用。因此，我们的目的是：目标1。验证PFC NP的19F MRI是使用肾脏缺血/再灌注（I/R）损伤的鼠标模型来映射血液内血容量，PO2和炎症的定量措施。 09/04，重新发行4/2006）页面延续格式页面公共卫生相关性：慢性肾脏疾病与急性肾脏损伤是一个经常出现的临床问题，发病率不断增加，高死亡率高50年以上没有提高，没有具体的治疗方法。我们建议实施辅助性非侵入性功能和分子成像读数，对肾内血容量，氧合和炎症进行辅助，并发展纳米颗粒促进抗凝治疗，以增强慢性和急性肾脏疾病的诊断和治疗。该提案是高度转化的，要开发的方法具有临床测试和实施的直接途径。