Predicting Future Liver Remnant Function and Growth Trajectory Using Novel MR Imaging Biomarkers

使用新型 MR 成像生物标志物预测未来的肝脏残余功能和生长轨迹

基本信息

批准号：
10749468
负责人：
Devashish Joshi
金额：
$ 7.54万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-26 至 2024-07-25
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10749468
关键词：
4D MRI Ablation Animals Automobile Driving Blood flow Cancer Etiology Cancer Patient Caring Cessation of life Child Cirrhosis Clinical Complication Dedications Excision Exclusion Family suidae Fellowship Foundations Future Goals Growth Guidelines Hepatectomy Hepatic Hepatic Insufficiency Hepatobiliary Hyperemia Hypertrophy Image Liver Liver Dysfunction Liver Failure Liver Regeneration Liver diseases Magnetic Resonance Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of liver Mentors Methods Operative Surgical Procedures Outcome Partial Hepatectomy Patient Care Patient Selection Patients Phase Portal System Portal Venous System Postoperative Period Primary Malignant Neoplasm of Liver Primary carcinoma of the liver cells Records Research Research Personnel Research Project Grants Research Training Risk Scientist Series Surgeon Surgical Oncologist Surgical complication Survival Rate Time Training United States Universities Unresectable Wisconsin cancer care candidate identification career career development curative treatments experimental study improved liver function liver transplantation magnetic resonance imaging biomarker mortality multidisciplinary nonalcoholic steatohepatitis novel radiologist reconstruction sham surgery translational scientist

项目摘要

PROJECT ABSTRACT Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths in the world. In fact, HCC is the fastest growing cause of all cancer deaths in the United States with a poor 5-year survival rate of 18%. The only curative therapies for HCC are liver transplantation or liver resection (partial hepatectomy) and for non-surgical candidates ablation. Malignant tumors within the liver, whether primary or secondary, are the most common indication for curative partial hepatectomies. However, many patients with HCC have underlying cirrhosis or some degree of liver dysfunction. As a result, the most severe complication after surgery remains post-hepatectomy liver failure with a mortality rate between 1.2 to 33.8%. Successful curative partial hepatectomy requires sufficient liver regeneration and function to avoid post- operative hepatic insufficiency. Currently, potential surgical candidates are identified by determining future liver remnant (FLR) volume. There are no clear guidelines for FLR volume in mild-moderate liver disease. It is known that portal blood flow is a key parameter driving liver hypertrophy but is not well understood. We hypothesize that there is a relationship between portal blood flow, FLR growth trajectory, and liver function. To investigate, we will perform partial hepatectomies in 7 healthy pigs with 3 controls undergoing a sham surgery. All 10 pigs will undergo magnetic resonance (MR) Imaging at 4 separate time points (pre-operative, post-operative day [POD] 0, between POD 6-8, and between POD 26-30) to evaluate for portal blood flow using a novel “4D flow” MR method, liver volume, and liver function. Our imaging time points will help assess the first two aims – demonstrating the utility of quantitative MR imaging biomarkers in predicting FLR function and growth trajectory, and also determining the relationship between FLR function and volume over time. Finally, we aim to determine the effects of portal hyperemia via a meal challenge to assess portal system accommodation and compliance as a predictive parameter. Our goal is to predict FLR function and growth to improve patient selection, pre-operative surgical planning, and outcomes through a series of three aims. The applicant, Devashish Joshi, MD, is a general surgery resident at the University of Wisconsin-Madison pursuing a career as a surgical oncologist and independent investigator. This fellowship would support his second year of dedicated research time with minimal clinical responsibilities. His sponsor, radiologist Dr. Scott Reeder, and co-sponsor, hepatobiliary surgical oncologist Dr. Sharon Weber, have significant track records of mentoring surgical trainees. They will guide and mentor Dr. Joshi in completing the proposed project to improve care in patients with liver cancer and build his foundations towards becoming a surgeon-scientist.

项目摘要肝细胞癌 (HCC) 是世界上第四大癌症相关死亡原因。是美国所有癌症死亡中增长最快的原因，其 5 年生存率仅为 18%。 HCC 的唯一治疗方法是肝移植或肝切除术（部分肝切除术）非手术消融的候选者是肝脏内的恶性肿瘤，无论是原发性还是继发性。治愈性部分肝切除术的常见指征然而，许多 HCC 患者有潜在的症状。肝硬化或某种程度的肝功能障碍因此，手术后最严重的并发症仍然存在。肝切除术后肝功能衰竭的死亡率在 1.2% 至 33.8% 之间。成功的治愈性部分肝切除术需要足够的肝再生和功能，以避免术后并发症。目前，通过确定未来的肝脏来确定潜在的手术候选者。残余 (FLR) 体积对于轻中度肝病的 FLR 体积没有明确的指南。众所周知，门静脉血流量是驱动肝脏肥大的关键参数，但目前尚不清楚。我们探索了门静脉血流、FLR 生长轨迹和肝功能之间的关系。为了进行调查，我们将对 7 头健康猪进行部分肝切除术，其中 3 头对照猪进行假手术所有 10 头猪将在 4 个不同的时间点（手术前、手术前、手术后）接受磁共振 (MR) 成像。术后第 [POD] 0 天、POD 6-8 之间以及 POD 26-30 之间）评估门静脉血流使用新颖的“4D 血流”MR 方法、肝脏体积和肝功能，我们的成像时间点将有助于评估。前两个目标 – 展示定量 MR 成像生物标志物在预测 FLR 功能中的效用和增长轨迹，并确定 FLR 功能和体积随时间变化的关系。最后，我们的目标是通过膳食挑战来评估门静脉系统，以确定门静脉充血的影响我们的目标是预测 FLR 功能和增长。通过一系列三个目标来改善患者选择、术前手术计划和结果。申请人德瓦什什·乔希（Devashish Joshi）医学博士是威斯康星大学麦迪逊分校的普通外科住院医师。这份奖学金将支持他从事外科肿瘤学家和独立研究者的职业生涯。他的资助者、放射科医生斯科特博士在第二年投入了最少的临床责任。 Reeder 和共同发起人肝胆外科肿瘤学家 Sharon Weber 博士拥有重要的跟踪记录他们将指导乔希博士完成拟议的项目改善肝癌患者的护理，并为成为一名外科医生科学家奠定基础。