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：
10524906
负责人：
Bernarda Viteri Baquerizo
金额：
$ 18.1万
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/10524906
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 End stage renal failure Ensure Environment Extravasation Failure Fistula Foundations Freedom Functional disorder Future Glomerular Filtration Rate Goals Gold Health Hemorrhage Hypoxia Image Image Enhancement Imaging technology Immunologics Immunotherapy Individual Inflammation Inflammatory Injury Intervention Investigation Kidney Diseases Kidney Transplantation Leadership Leucocytic infiltrate Longevity Magnetic Resonance Imaging Measures Mentors Mentorship Nephrology 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 base 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 imaging study 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.

项目概要/摘要该提案的首要目标是研究新型定量 MRI 和超声检查是否成像参数可以可靠地检测肾移植损伤，从而表明儿童同种异体移植失败的风险。患有终末期肾病 (ESKD) 的儿童的死亡率比未患终末期肾病的儿童高 30 倍。肾移植比透析具有显着的生存优势，患有 ESKD 的儿童通常需要在其生命周期内进行多次同种异体肾移植，每次移植都会增加手术、免疫和致癌性。肾脏同种异体移植物损伤是由炎症、感染、血管和纤维化变化引起的。最终导致同种异体移植失败的一个主要限制是缺乏非同种异体移植物的长期存活。该提案寻求侵入性诊断和预后生物标志物，以可靠地检测同种异体移植物的早期损伤。开发磁共振成像（MRI）和超声造影（CEUS）生物标志物目前，同种异体肾移植活检是儿童肾移植炎症指标的金标准。诊断此类变化，但具有侵入性且不会避免并发症，这限制了其识别的使用。标记将使我们能够实施个体化干预措施，以提高同种异体移植物的存活率并减少目标 1 将确定与相关的高级 MRI 和 CEUS 参数。组织病理学总炎症 Banff 评分和慢性同种异体移植物损伤指数 (CADI) 评分将进行。确定预测儿童肾移植受者 eGFR 变化的新 MRI 和 CEUS 参数移植后 6-24 个月的结果将为新型非侵入性成像生物标志物领域提供信息。作为这项研究的补充，我计划在 1) 方面获得进一步的培训。常规和 CEUS 研究成像采集和分析，2) MRI 研究数据采集和分析，3) 设计和实施基于生物医学成像的以患者为导向的研究，以及 4) 在严谨的研究环境中通过专业发展计划获得领导技能为了实现这些目标，我召集了费城儿童医院和宾夕法尼亚大学。临床肾病学以患者为导向的研究专家组成的多学科指导/咨询团队（初级导师，Susan Furth，医学博士、哲学博士），MRI 临床和转化研究（Timothy Roberts，医学博士、哲学博士； Suraj Serai 博士），CEUS（Chandra Seghal 博士；Susan Back 医学博士；Anush Sridharan 博士），儿科肾脏移植生物标志物（Sandra Amaral，MD，MHS），跨国合作网络（Gregory Tasian， MD、MSCE）、肾脏疾病统计方法（Jarcy Zee 博士）和以患者为中心的影像研究（Kassa Darge，医学博士、哲学博士；Erum Hartung，医学博士、MSTR；Hansel Otero，医学博士）。构成我职业发展计划的结构化指导、课程和培训将为我提供确保我作为一名具有独特技能的独立调查员取得成功所需的技能和经验开发用于肾移植的成像生物标志物。