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: 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
• 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

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。作为 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 在其一生中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 风险。同种异体肾损伤是由炎症、感染、血管和纤维化变化引起的，这些变化可以 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可可靠地检测同种异体移植物的早期损伤。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，同种异体肾移植活检是诊断肾病的金标准。 诊断此类变化，但具有侵入性且会出现并发症，这限制了其使用。识别此类 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 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 组织病理学总炎症班夫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。结果将为新型非侵入性成像生物标志物领域提供信息 在小儿肾移植中。作为本次调查的补充，我计划接受以下方面的进一步培训：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) 基于生物医学成像的以患者为导向的研究的设计和实施，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 费城儿童医院和宾夕法尼亚大学。为了实现这些目标，我集合了 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 达格，医学博士、哲学博士； Erum Hartung，医学博士，MSTR；汉塞尔·奥特罗，医学博士）。拟议的研究以及 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。