Quantifying Liver Fibrosis with Acoustic Radiation Force

用声辐射力量化肝纤维化

• 批准号: 7934296
• 负责人: Kathryn Radabaugh Nightingale
• 金额: $ 4.79万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-10 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934296
• 关键词: Ablation; Acoustics; Affect; Aftercare; Algorithms; American; Animals; Biopsy; Biopsy Specimen; Blood Vessels; Breast; Cause of Death; Chronic; Chronic Hepatitis; Cicatrix; Cirrhosis; Clinical; Clinical Research; Core Biopsy; Country; Coupled; Custom; Data; Deposition; Development; Diagnosis; Diffuse; Disease; Disease Progression; Dyslipidemias; Enzymes; Epidemic; Etiology; Evaluation; Fatty Liver; Fibrosis; Frequencies; Functional disorder; Funding; Goals; Heating; Hepatic; Hepatocyte; Histologic; Histology; Hospitalization; Human; Human Volunteers; Hyperinsulinism; Hypertension; Image; Inflammation; Inflammatory; Institutes; Lateral; Length; Lipids; Liver; Liver Failure; Liver Fibrosis; Liver diseases; Location; Measurement; Measures; Mechanics; Medical; Metabolic; Metabolic syndrome; Methods; Metric; Modeling; Monitor; Morphologic artifacts; Motion; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Needles; Neoplastic liver; Obesity; Outpatients; Patient Care; Patients; Penetration; Physicians; Physiologic pulse; Positioning Attribute; Procedures; Process; Property; Radiation; Rattus; Rectal Tumors; Relative (related person); Research; Research Personnel; Resolution; Risk; Sampling; Secondary to; Serum; Serum Markers; Speed; Staging; Structure; System; Technology; Tissues; Transducers; Treatment Protocols; Ultrasonics; Ultrasonography; United States; United States National Institutes of Health; Western World; base; breast lesion; clinically relevant; computerized data processing; cost; egg; experience; healthy volunteer; human study; image processing; imaging modality; in vivo; liver biopsy; liver function; liver imaging; non-alcoholic fatty liver; nonalcoholic steatohepatitis; parallel processing; reconstruction; response; simulation; soft tissue; tool; tumor; Ablation; Acoustics; Affect; Aftercare; Algorithms; American; Animals; Biopsy; Biopsy Specimen; Blood Vessels; Breast; Cause of Death; Chronic; Chronic Hepatitis; Cicatrix; Cirrhosis; Clinical; Clinical Research; Core Biopsy; Country; Coupled; Custom; Data; Deposition; Development; Diagnosis; Diffuse; Disease; Disease Progression; Dyslipidemias; Enzymes; Epidemic; Etiology; Evaluation; Fatty Liver; Fibrosis; Frequencies; Functional disorder; Funding; Goals; Heating; Hepatic; Hepatocyte; Histologic; Histology; Hospitalization; Human; Human Volunteers; Hyperinsulinism; Hypertension; Image; Inflammation; Inflammatory; Institutes; Lateral; Length; Lipids; Liver; Liver Failure; Liver Fibrosis; Liver diseases; Location; Measurement; Measures; Mechanics; Medical; Metabolic; Metabolic syndrome; Methods; Metric; Modeling; Monitor; Morphologic artifacts; Motion; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Needles; Neoplastic liver; Obesity; Outpatients; Patient Care; Patients; Penetration; Physicians; Physiologic pulse; Positioning Attribute; Procedures; Process; Property; Radiation; Rattus; Rectal Tumors; Relative (related person); Research; Research Personnel; Resolution; Risk; Sampling; Secondary to; Serum; Serum Markers; Speed; Staging; Structure; System; Technology; Tissues; Transducers; Treatment Protocols; Ultrasonics; Ultrasonography; United States; United States National Institutes of Health; Western World; base; breast lesion; clinically relevant; computerized data processing; cost; egg; experience; healthy volunteer; human study; image processing; imaging modality; in vivo; liver biopsy; liver function; liver imaging; non-alcoholic fatty liver; nonalcoholic steatohepatitis; parallel processing; reconstruction; response; simulation; soft tissue; tool; tumor

DESCRIPTION (provided by applicant): The objective of the proposed research is to develop an ultrasonic, radiation-force based imaging system capable of locally quantifying the shear modulus of soft tissues throughout a 2D Field of View (FOV), and to investigate its utility in the context of staging liver fibrosis. This system will build upon technology that has been developed during the first funding cycle (Acoustic Radiation Force Impulse (2D-ARFI) imaging), and will provide co-registered B-mode and quantitative stiffness images over a large FOV. We have developed robust, quantitative shear modulus reconstruction methods based upon ultrasonically monitoring tissues' responses to localized radiation force excitations. We have validated these methods in calibrated tissue mimicking phantoms and have performed initial clinical studies using these reconstruction methods to quantify the shear modulus of the livers of healthy volunteers. In this proposal, we will optimize these methods and investigate their ability to stage and quantify liver fibrosis. Over 25,000,000 Americans have experienced liver disease. Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common liver disease in the western world and is approaching epidemic proportions as obesity becomes a significant medical dilemma. NAFLD is the hepatic manifestation of metabolic syndrome (obesity, hyperinsulinemia, dyslipidemia, hypertension) in which lipid accumulates in hepatocytes. NAFLD patients can progress to Non-Alcoholic Steatohepatitis (NASH, i.e. inflammatory hepatic steatosis), progressive fibrosis, cirrhosis (i.e. extensive fibrotic scarring throughout the liver), and end-stage liver disease (decompensated cirrhosis). Treatment of the majority of liver diseases, including NAFLD and chronic hepatitis, is dictated by the extent of fibrosis throughout the liver, as determined by liver biopsy and liver function using blood serum markers. Unfortunately, blood serum markers are not specific for liver decompensation, and liver biopsy samples are associated with inaccurate fibrosis evaluation since they are typically limited to a single needle core (18-25 mm in length, 14-18 gauge needle). We hypothesize that: 1) our proposed imaging system will be capable of quantifying changes in liver stiffness (i.e. shear modulus), 2) these stiffness changes will be correlated with histologically determined fibrosis stage, and 3) the 2D nature of our method will increase the accuracy of fibrosis staging as compared to the clinical standard of a single core needle biopsy. Due to its noninvasive and inexpensive nature, this system will provide the currently unavailable ability to longitudinally track fibrotic hepatic disease progression and monitor the liver's response to treatment protocols. We have initiated development of and propose to expand custom beam sequences and robust data processing algorithms to provide shear modulus estimates throughout a 2D FOV, with resolution approaching 3x3 mm, to be overlaid on co-registered B-mode images. We have obtained initial data in rat liver in vivo, and propose studies in a known chronic liver disease/fibrosis rat model to investigate the correlation between fibrosis score, histology, and our stiffness metric. We have also obtained preliminary data in human volunteers in vivo, and we propose an in vivo human study in which our stiffness metric will be correlated with biopsy findings. Upon completion of these studies, we will have 1) developed a noninvasive method of hepatic fibrosis stiffness scoring and monitoring over a large region of the liver for both human and small animal imaging, 2) determined the correlation between the fibrosis stiffness metric and histologic fibrosis stage, 3) demonstrated the system's feasibility in a small human clinical study, and 4) be in position to perform a large follow-on clinical study of the method's utility for liver disease staging and treatment monitoring.

描述（由申请人提供）：拟议的研究的目的是开发一个超声波，辐射力的成像系统，能够在2D视野（FOV）（FOV）中局部量化软组织的剪切模量（FOV），并在分期肝纤维化的背景下研究其效用。该系统将建立在第一个融资周期（声学辐射力冲动（2D-ARFI）成像）中开发的技术，并将在大型FOV上提供共同注册的B模式和定量刚度图像。我们已经建立了基于超声监测组织对局部辐射力激发的反应的强大定量剪切模量重建方法。我们已经验证了模仿幻影的校准组织中的这些方法，并使用这些重建方法进行了初步临床研究，以量化健康志愿者肝脏的剪切模量。在此提案中，我们将优化这些方法，并研究它们分阶段和量化肝纤维化的能力。超过2500万美国人患有肝病。非酒精性脂肪肝疾病（NAFLD）是西方世界上最常见的肝病，并且随着肥胖症成为严重的医学困境，正接近流行比例。 NAFLD是代谢综合征（肥胖，高胰岛素血症，血脂异常，高血压）的肝表现，其中脂质在肝细胞中积聚。 NAFLD患者可以发展为非酒精性脂肪性肝炎（NASH，即炎症性肝脂肪变性），进行性纤维化，肝硬化（即在整个肝脏中广泛的纤维化疤痕）和终阶段的肝病（肝硬化代理）。通过肝活检和肝功能，使用血清标记物确定，大多数肝病的治疗，包括NAFLD和慢性肝炎在内。不幸的是，血清标记并非特定于肝脏代偿性，并且肝活检样品与不准确的纤维化评估有关，因为它们通常仅限于单针核（长度为18-25 mm，14-18仪表针）。我们假设：1）我们提出的成像系统将能够量化肝脏刚度的变化（即剪切模量），2）这些刚度变化将与组织学确定的纤维化阶段相关，而3）我们方法的2D性质将增加纤维化分期的准确性，而纤维化的准确性将与单核核心核心针对单核针对临床标准的纤维化标准相比。由于其无创和廉价的性质，该系统将提供当前不可用的能力，以纵向跟踪纤维化的肝病进展并监测肝脏对治疗方案的反应。我们启动了开发并提议扩展自定义梁序列和鲁棒数据处理算法，以在2D FOV中提供剪切模量估计值，分辨率接近3x3 mm，并在共同注册的B模式图像上覆盖。我们已经在体内获得了大鼠肝脏中的初始数据，并提出了在已知的慢性肝病/纤维化大鼠模型中进行研究，以研究纤维化评分，组织学和我们的僵硬度量的相关性。我们还在体内获得了人类志愿者的初步数据，我们提出了一项体内人类研究，其中我们的僵硬度量与活检结果相关。这些研究完成后，我们将有1）开发了一种无创的肝纤维化刚度评分和监测的肝脏和小动物成像的监测方法，2）确定纤维化僵硬度量和组织学纤维化阶段之间的相关性，3）在小人类的临床研究中表现出了该系统的可行性，并表现出4）的可行性，并表现出4）的位置，以表现出一个位置，以实现一项位置，以表现出一定的位置。肝病分期和治疗监测。