Quantitative Hemodynamics of the Liver with 4D Flow MRI

描述（由申请方提供）：本研究的总体目标是开发一种基于MRI的全面、无创方法，以量化门静脉高压患者肝血管系统中的血流量。门脉高压是慢性肝病终末期最常见和致命的并发症，会导致门体侧支循环（静脉曲张）的发展，使血液从肝脏分流，肾功能障碍（肝肾功能） 综合征），腹水积聚，以及其他并发症。门静脉高压症目前是通过有创导管测量肝静脉压力梯度（HVPG）来评估的。HVPG是门静脉高压症最有效的生物标志物，但仅提供了疾病的总体测量。大多数疗法通过减少流向肝脏的流量来降低门静脉压力（例如，β-受体阻滞剂）或从门静脉循环分流（TIPS手术）。需要准确的肝血流生物标志物，以补充和增强HVPG测量。然而，目前没有可用的方法来提供这样的血液动力学信息。 该提案旨在开发一种速度敏感的“4D流”MRI方法，该方法同时对肝血管解剖结构进行成像并量化肝的所有血管区域内的血流。该方法基于已建立和验证的径向欠采样k空间轨迹（PC VIPR），并将提供具有高级速度编码的快速图像采集，以提高速度灵敏度，匹配肝脏中遇到的流速范围。该采集将与非笛卡尔平行成像相结合，以进一步将扫描时间减少到约10分钟的自由呼吸，同时在大成像体积上保持高空间（<1.3 mm各向同性）和高时间分辨率（<50 ms），具有良好的图像质量和准确的流量量化。将使用血管周围超声流量探头作为参考标准，在猪的肝血管系统中评价该方法的准确性。将在门静脉高压患者和正常受试者中确定流量测量的精确度（可重复性），同时还将量化影响精确度的因素（膳食、昼夜变化）。最后，将通过肝脏中的无创流量测量来确定该方法的临床效用，作为在门静脉高压患者中使用经充分验证的β受体阻滞剂测试剂量范例的初步研究的一部分。肝静脉压力梯度（HVPG）的降低与使用试验剂量普萘洛尔（一种非选择性β受体阻滞剂）实现的门静脉血流量降低相关。本研究将证明4D flow MRI作为HVPG的无创替代生物标志物的潜在临床实用性。 如果成功，4D flow MRI将提供一种全面的工具来量化和表征门静脉高压症的血流，改善静脉曲张出血的风险分层，并提供非侵入性替代生物标志物来评价门静脉血流对药理学挑战的反应。

DESCRIPTION (provided by applicant): The overall goal of this research is the development of a comprehensive, non-invasive MRI based method to quantify blood flow in the hepatic vasculature of patients with portal hypertension. Portal hypertension is the most common and lethal complication of end-stage chronic liver disease and leads to the development of portosystemic collaterals (varices) that shunt blood from the liver, renal dysfunction (hepatorenal syndrome), accumulation of ascites, among other complications. Portal hypertension is currently assessed using invasive catheter-based measurements of hepatic venous pressure gradient (HVPG). HVPG is the best-validated biomarker of portal hypertension, but only provides a global measure of disease. Most therapies reduce portal pressure through reductions in the flow to the liver (eg. beta-blockers) or shunting flow from the portal circulation (TIPS procedure). There is need for accurate biomarkers of blood flow to the liver that would complement and augment HVPG measurements. However, there are currently no available methods to provide such hemodynamic information. This proposal seeks to develop a velocity sensitive "4D flow" MRI method that simultaneously images the hepatic vascular anatomy and quantifies blood flow within all vascular territories of the liver. This approach is based on established and validated radially undersampled k-space trajectories (PC VIPR) and will provide a rapid image acquisition with advanced velocity encoding to improve velocity sensitivity, matching the range of flow velocities encountered in the liver. This acquisition will be coupled with non-Cartesian parallel imaging to further reduce scan time to approximately 10 min of free breathing while maintaining high spatial (<1.3 mm isotropic), and high temporal resolution (<50 ms) over a large imaging volume with good image quality and accurate flow quantification. The accuracy of this approach will be evaluated in the hepatic vasculature of swine using perivascular ultrasonic flow probes as the reference standard. The precision (repeatability) of the flow measurements will be determined in patients with portal hypertension and in normal subjects while also quantifying factors that impact precision (meals, diurnal variation). Finally, the clinical utility of the apprach will be determined with non-invasive flow measurements in the liver as part of a pilot study that uses a well- validated beta-blocker test-dose paradigm in patients with portal hypertension. The decrease in hepatic venous pressure gradient (HVPG) will be correlated with decreases in portal blood flow achieved using test dose of propranolol, a non-selective beta-blocker. This study will demonstrate the potential clinical utility of 4D flow MRI as a non-invasive surrogate biomarker of HVPG. If successful, 4D flow MRI would provide a comprehensive tool to quantify and characterize blood flow in portal hypertension, improving risk stratification for variceal hemorrhage and providing non- invasive surrogate biomarkers to evaluate the response of portal flow to pharmacological challenges.