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

• 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
• 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

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的定量MRI和超声是否 影像学参数可以可靠地检测出儿童肾移植损伤，提示移植失败的风险。 患有终末期肾病（ESKD）的儿童的死亡率比没有它的儿童高30倍。 与透析相比，肾移植提供了显著的生存优势，ESKD儿童通常需要 多次肾脏移植每一次移植都会增加手术、免疫学和致癌性 风险移植肾损伤是由炎症、感染、血管和纤维化改变引起的， 最终导致同种异体移植失败。促进同种异体移植物长期存活的一个主要限制是缺乏非- 侵入性诊断和预后生物标志物，以可靠地检测移植物的早期损伤。该提案寻求 开发磁共振成像（MRI）和超声造影（CEUS）生物标志物， 测量儿童肾移植的炎症。目前，肾移植活检是诊断肾移植的金标准。 诊断这种变化，但侵入性和并发症，这限制了它的使用。识别此类 标记物将使我们能够实施个体化干预，以提高同种异体移植物的存活率， 不必要的活检目标1将确定与以下相关的高级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。目标2将 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。该结果将为新型非侵入性成像生物标志物领域提供信息 儿科肾脏移植作为这项研究的补充，我计划在1） 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面向患者的研究，以及4） 通过在严格的研究环境中的专业发展计划获得领导技能， 费城儿童医院和宾夕法尼亚大学。为了实现这些目标，我召集了 一个多学科的指导/咨询团队，由临床肾脏病学专家组成，以患者为导向的研究（初级 导师，Susan Furth，MD，PhD），MRI临床和转化研究（Timothy Roberts，MD，PhD; Suraj Serai，PhD）、CEUS（Chandra Seghal，PhD; Susan Back，MD; Anush Sridharan，PhD）、儿科肾脏 移植生物标志物（SandraAmaral，MD，MHS），多国合作网络（GregoryTasian， 医学博士、医学与临床工程师联合会）、肾脏疾病统计学方法（Jarcy Zee，博士）和以患者为导向的影像学研究（Kassa Darge，MD，PhD; Erum Hartung，MD，MSTR; Hansel Ostern，MD）。拟议的研究，沿着 我的职业发展计划包括结构化的指导、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 用于肾移植的成像生物标志物。