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

• 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
• 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

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。事实上，HCC 是美国所有癌症死亡中增长最快的原因，5年生存率为18%。 HCC的唯一治愈性疗法是肝移植或肝切除术（部分肝切除术）， 非手术候选人消融。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适应症。然而，许多HCC患者有潜在的 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是 肝切除术后肝功能衰竭，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。 手术性肝功能不全目前，通过确定未来的肝脏， 残余（FLR）体积。对于轻中度肝病的FLR体积没有明确的指南。是 已知门静脉血流量是驱动肝脏肥大的关键参数，但尚未得到很好的理解。 我们假设门静脉血流量、FLR生长轨迹和肝功能之间存在关系。 为了研究，我们将对7只健康猪进行部分肝切除，其中3只对照猪进行假手术 手术所有10只猪将在4个不同的时间点（术前， 术后第[POD] 0天、POD 6-8天和POD 26-30天）评价门静脉血流量 使用新的“4D流动”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-证明定量MR成像生物标志物在预测FLR功能中的实用性 和生长轨迹，并确定FLR函数与体积随时间的关系。 最后，我们的目的是通过餐后试验来确定门脉充血对门脉系统的影响 调节和顺应性作为预测参数。我们的目标是预测FLR的功能和生长， 通过一系列的三个目标，改善患者选择、术前手术计划和结果。 申请人Devashish Joshi，医学博士，是威斯康星大学麦迪逊分校的普外科住院医师 作为一名外科肿瘤学家和独立调查员。这笔奖学金将支持他的 第二年的专门研究时间与最小的临床责任。他的担保人放射科医生斯科特博士 里德和共同发起人、肝胆外科肿瘤学家莎朗·韦伯博士拥有以下方面的重要记录 指导外科实习生他们将指导和指导乔希博士完成拟议的项目， 改善肝癌患者的护理，并为成为外科医生科学家奠定基础。