Evaluation of HCC Response to Systemic Therapy With Quantitative MRI
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- SubStudy 1: Apparent Diffusion Coefficient (ADC)
研究概览
简要总结
The incidence of hepatocellular carcinoma (HCC) has recently increased in the United States. Although imaging plays a major role in HCC screening and staging, the possibility of predicting HCC tumor grade, aggressiveness, angiogenesis and hypoxia with imaging are unmet needs. In addition, new antiangiogenic drugs now available to treat advanced HCC necessitate the use of new imaging criteria beyond size. The investigators would like to develop and validate non-invasive magnetic resonance imaging (MRI) methods based on advanced diffusion-weighted imaging (DWI), MR Elastography, BOLD (blood oxygen level dependent) MRI and perfusion-weighted imaging (PWI, using gadolinium contrast) to be used as non-invasive markers of major histopathologic features of HCC, and to predict and assess early response of HCC to systemic therapy. The investigators also would like to develop quality control tools to improve the quality and decrease variability of quantitative MRI metrics. These techniques combined could represent non-invasive correlates of histologic findings in HCC, could enable individualized therapy, and provide prognosis in patients with HCC.
详细描述
The incidence of hepatocellular carcinoma (HCC) has recently increased in the US mostly due to an increase in chronic hepatitis C infection. Angiogenesis is critical for the growth and metastatic progression of HCC. With the development of new antiangiogenic drugs such as sorafenib, imaging methods to predict and assess therapeutic response beyond changes in size become critical. However, validated imaging methods to predict and assess early HCC response to targeted agents are lacking.
In this study, the investigators would like to develop quantitative MRI methods interrogating different features of HCC tumor biology and pathology, including tumor cellularity, grade, angiogenesis and hypoxia. The investigators propose a multiparametric approach combining advanced DWI (IVIM: intravoxel incoherent motion diffusion measuring perfusion fraction and true diffusion coefficient), DCE-MRI (dynamic contrast-enhanced MRI, which measures arterial and portal flow, mean transit time, blood volume and distribution volume), and BOLD MRI using oxygen or carbogen challenge. This protocol will be performed in patients with HCC undergoing hepatic resection. Routine and advanced histopathologic methods will be performed (tumor grade, CK19 expression, presence of microvascular invasion, VEGF expression, microvessel density, HIF 1-alpha expression). MRI metrics will be correlated with histopathologic metrics.
The first portion of the proposal involves the development of a QC algorithm assessing MR data quality and test-retest. The investigators will propose solutions to improve data acquisition and processing. The last 2 years of the study will be dedicated to a prospective randomized study comparing Yttrium 90 radioembolization to sorafenib, assessing the role of baseline MRI metrics and early changes (at 2 weeks) in these metrics as markers of tumor response and time to progression in patients with unresectable HCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Study group
- •Patients diagnosed with HCC, who will undergo resection or transplantation within 6 months, as part of routine clinical care and patients diagnosed with unresectable HCC
- •18 years of age and older
- •Patient is able to give informed consent for this study
- •Control group
- •Healthy volunteers 18 years of age and older
- •Subject is able to give informed consent for this study
排除标准
- •Age less than 18 years
- •Unable or unwilling to give informed consent
- •Contra-indications to MRI:
- •Electrical implants such as cardiac pacemakers or perfusion pumps
- •Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants
- •Ferromagnetic objects such as jewelry or metal clips in clothing
- •Pregnant subjects
- •Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions
研究组 & 干预措施
Magnetic Resonance Imaging
dynamic contrast-enhanced MRI measuring arterial and portal flow
干预措施: Magnetic Resonance Imaging (Device)
Healthy Controls
结局指标
主要结局
SubStudy 1: Apparent Diffusion Coefficient (ADC)
时间窗: Day 1
Tumor diffusion (apparent diffusion coefficient) measured with diffusion-weighted imaging sequence
SubStudy 1: Total Tumor Perfusion (Ft)
时间窗: Day 1
Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast
SubStudy 1: Tumor Arterial Perfusion Fraction (ART)
时间窗: Day 1
Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast
SubStudy 1: Tumor Mean Transit Time (MTT)
时间窗: Day 1
Tumor mean transit time (MTT) of contrast agent. Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast
SubStudy 1: Tumor Distribution Volume (DV)
时间窗: Day 1
Tumor distribution volume (DV) of contrast agent. Perfusion/flow measured with dynamic contrast-enhanced imaging using gadolinium contrast
SubStudy 1: Oxygen Uptake
时间窗: Day 1
Oxygen uptake measured with T2\* and T1-weighted imaging
SubStudy 2: ADC
时间窗: baseline and 6 weeks after Y90
Tumor diffusion measured with diffusion-weighted imaging sequence. In diffusion weighted MR imaging (DWI), the signal is proportional to the Brownian motion diffusion of free water protons in tissues. Deposition of collagen in tissue (as in fibrotic disease), or cellularity in tumors act as impediments to free water diffusion. Using different mathematical models, the degree of diffusion can be quantified from the MRI signal, to provide information on diffusion restriction due to disease. From mono exponential fit of diffusion signal, one can obtain the apparent diffusion coefficient (ADC). However, this coefficient reflects free water proton diffusion, as well as transport of water protons in the capillary vessels (capillary perfusion).
SubStudy 1: Percent Change in Oxygen Uptake
时间窗: Day 1, pre-oxygen administration and 10 min. post-oxygen administration
Oxygen uptake measured with T2\* and T1-weighted imaging. Oxygen uptake (% change pre and post O2 administration) calculated by Liver ΔR2\*=100 x (R2\* post O2-R2\* pre O2)/R2\* pre O2. The healthy participants breathed 100% medical O2 through a mask for 10 min., and were imaged before and after O2 administration with the MRI methods that are sensitive to oxygen uptake in tumors.
SubStudy 2: Diffusion Coefficient D
时间窗: baseline and 6 weeks after Y90
Tumor diffusion measured with diffusion-weighted imaging sequence. To separate the diffusion effect from capillary perfusion, a bi-exponential model is used, which provides 3 coefficients: one is the true diffusion coefficient D, reflecting free water proton diffusion.
SubStudy 2: Pseudodiffusion Coefficient D*
时间窗: baseline and 6 weeks after Y90
Tumor diffusion measured with diffusion-weighted imaging sequence. To separate the diffusion effect from capillary perfusion, a bi-exponential model is used, which provides 3 coefficients: one is the pseudo-diffusion coefficient D\*, affected by free diffusion and capillary perfusion.
SubStudy 2: Perfusion Fraction (PF)
时间窗: baseline and 6 weeks after Y90
Tumor diffusion measured with diffusion-weighted imaging sequence. To separate the diffusion effect from capillary perfusion, a bi-exponential model is used, which provides 3 coefficients: one is the perfusion fraction PF, which reflects how much the diffusion-weighted signal is affected by capillary perfusion. PF is a measure of vascularity in the tissue.
次要结局
- SubStudy 2: Extravascular Extracellular Volume ve(baseline and 6 weeks after Y90)
- SubStudy 2: Total Tumor Perfusion (Ft)(baseline and 6 weeks after Y90)
- SubStudy 2: Tumor Arterial Perfusion Fraction (ART)(baseline and 6 weeks after Y90)
- SubStudy 2: Tumor Mean Transit Time (MTT) of Contrast Agent(baseline and 6 weeks after Y90)
- Substudy 2: Tumor Stiffness(baseline and 6 weeks after Y90)
- Tumor Response(6 weeks and 6-12 months)
研究者
Bachir Taouli
Professor, Radiology and Medicine
Icahn School of Medicine at Mount Sinai