IMPAKT Study: Imaging Modalities in Pediatric Assessments of Kidney Transplants

IMPAKT 研究：儿科肾移植评估中的成像方式

基本信息

批准号：
10662566
负责人：
Bernarda Viteri Baquerizo
金额：
$ 17.93万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-15 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10662566
关键词：
Acute Adult Advisory Committees Allografting Back Biological Markers Biopsy Blood Vessels Blood capillaries Blood flow Child Childhood Childhood Injury Chronic Chronic Kidney Failure Clinical Clinical Research Contrast Media Data Data Analyses Deterioration Development Plans Diagnosis Dialysis procedure Diffusion Doctor of Philosophy Early Diagnosis End stage renal failure Ensure Environment Extravasation Failure Fistula Foundations Freedom Functional disorder Future Glomerular Filtration Rate Goals Health Hemorrhage Hypoxia Image Image Enhancement Imaging technology Immunologics Immunotherapy Individual Infiltration Inflammation Inflammatory Injury Intervention Investigation Kidney Diseases Kidney Transplantation Leadership Longevity Magnetic Resonance Imaging Measures Mentors Mentorship Microbubbles Nephrology Non-Invasive Detection Oncogenic Operative Surgical Procedures Outcome Participant Pattern Pediatric Hospitals Pennsylvania Perfusion Philadelphia Positioning Attribute Process Prognosis Prognostic Marker Public Health Renal function Research Research Design Research Personnel Research Project Grants Research Training Risk Scientist Statistical Methods Structure Time Training Translational Research Transplant Recipients Transplantation Ultrasonography Universities allograft rejection arterial spin labeling biomedical imaging career career development cohort contrast enhanced cost data acquisition design diagnosis standard diagnostic biomarker experience follow-up graft failure imaging biomarker imaging modality improved indexing kidney allograft mortality multidisciplinary non-invasive imaging noninvasive diagnosis novel patient oriented patient oriented research personalized management personalized medicine post-transplant pre-clinical quantitative imaging rate of change research study skills success surveillance imaging tool treatment planning ultrasound vasoconstriction water diffusion

项目摘要

PROJECT SUMMARY/ ABSTRACT The overarching objectives of this proposal are to investigate whether novel quantitative MRI and ultrasound imaging parameters can reliably detect kidney transplant injury that indicates risk of allograft failure in children. Children with end-stage kidney disease (ESKD) have a mortality rate 30 times higher than children without it. As kidney transplantation provides a significant survival advantage over dialysis, children with ESKD often require multiple kidney allografts over their lifespan. Each transplant increases surgical, immunological, and oncogenic risk. Kidney allograft injury results from inflammatory, infectious, vascular, and fibrotic changes that can ultimately result in allograft failure. A major limitation to promoting long-term allograft survival is the lack of non- invasive diagnostic and prognostic biomarkers to reliably detect early injury in the allograft. This proposal seeks to develop magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) biomarkers to measure inflammation of kidney transplant in children. Currently, kidney allograft biopsy is the gold standard to diagnose such changes, but is invasive and not free of complications, which limits its use. Identifying such markers will allow us to implement individualized interventions to improve allograft survival and decrease unnecessary biopsies. Aim 1 will determine advanced MRI and CEUS parameters that associate with histopathological total inflammation Banff score and Chronic Allograft Damage Index (CADI) score. Aim 2 will identify novel MRI and CEUS parameters that predict change of eGFR in pediatric kidney transplant recipients at 6-24 months post-transplantation. The results will inform the field of novel non-invasive imaging biomarkers in pediatric kidney transplantation. Complementary to this investigation I plan to acquire further training in 1) conventional and CEUS research imaging acquisition and analysis, 2) MRI research data acquisition and analysis, 3) design and implementation of biomedical imaging based patient-oriented research studies, and 4) acquire leadership skills through a professional development plan in the rigorous research environment of Children’s Hospital of Philadelphia and University of Pennsylvania. To accomplish these goals, I have assembled a multi-disciplinary mentoring/advisory team of experts in clinical nephrology patient-oriented research (Primary mentor, Susan Furth, MD, PhD), MRI clinical and translational research studies (Timothy Roberts, MD, PhD; Suraj Serai, PhD), CEUS (Chandra Seghal, PhD; Susan Back, MD; Anush Sridharan, PhD), pediatric kidney transplantation biomarkers (Sandra Amaral, MD, MHS), multinational collaborative networks (Gregory Tasian, MD, MSCE), kidney disease statistical methods (Jarcy Zee, PhD), and patient-oriented imaging research (Kassa Darge, MD, PhD; Erum Hartung, MD, MSTR; Hansel Otero, MD). The proposed research, along with the structured mentoring, coursework, and training that comprise my career development plan, will provide me with the skills and experience necessary to ensure my success as an independent investigator with a unique skill set in developing imaging biomarkers for kidney transplantation.

项目摘要/摘要该提案的总体目标是研究新颖的定量MRI和超声是否成像参数可以可靠地检测到肾移植损伤，这表明儿童同种异体移植失败的风险。末期肾脏疾病（ESKD）的儿童的死亡率是没有该儿童的儿童的30倍。作为肾脏移植提供了比透析具有显着的生存优势，ESKD的儿童通常需要在其寿命中多个肾脏同类。每次移植都会增加手术，免疫学和致癌性风险。肾脏同种异体移植损伤是由炎症，传染性，血管和纤维化变化引起的，可以最终导致同种异体移植失败。促进长期同种异体移植存活的主要局限性是缺乏非 - 侵入性诊断和预后生物标志物可靠地检测出同种异体移植物的早期损伤。该建议寻求开发磁共振成像（MRI）和对比增强超声（CEU）生物标志物测量儿童肾脏移植的炎症。目前，肾脏同种异体移植活检是诊断出这种变化，但具有侵入性，并且不含并发症，这限制了其使用。确定这样的标记将使我们能够实施个性化的干预措施，以改善同种异体移植生存并减少不必要的活检。 AIM 1将确定与之相关的高级MRI和CEU参数组织病理学总炎症班夫评分和慢性同种异体移植损伤指数（CADI）得分。 AIM 2意志确定可预测小儿肾脏移植受者EGFR的变化的新型MRI和CEU参数移植后6-24个月。结果将为新型非侵入性成像生物标志物的领域提供信息在小儿肾脏移植中。补充这项投资，我计划在1中获得进一步的培训常规和CEU研究成像获取和分析，2）MRI研究数据获取和分析，3）基于生物医学成像的研究和实施，以患者为导向的研究，4）通过专业发展计划在严格的研究环境中获得领导技能费城儿童医院和宾夕法尼亚大学。为了实现这些目标，我已经组装了临床肾脏科专家的多学科心理/咨询团队患者研究（主要心理，医学博士Susan Fuurth），MRI临床和翻译研究（Timothy Roberts，MD，PhD； Suraj Serai，博士），CEUS（Chandra Seghal，PhD； Susan Back，医学博士； Anush Sridharan，PhD），儿科肾脏移植生物标志物（Sandra Amaral，MD，MHS），跨国协作网络（Gregory Tasian，Gregory Tasian， MD，MSCE），肾脏疾病统计方法（Jarcy Zee，PhD）和面向患者的成像研究（KASSA） Darge，医学博士；医学博士Erum Hartung； Hansel Otero，MD）。拟议的研究，以及结构化的心理，课程和培训完成了我的职业发展计划，将为我提供确保我作为独立技能的独立调查员成功所需的技能和经验在开发用于肾脏移植的成像生物标志物。