Noninvasive assessment of portal hypertension and hepatic interstitial pressure with advanced magnetic resonance elastography

慢性肝病（CLD）是一种非常常见的死亡原因，由于肝硬化的发展和随之而来的危及生命的门脉高压（PHTN）。肝静脉压梯度（HVPG）测量是评估PHTN的金标准，但由于其侵入性和对操作人员技能和经验的要求，在常规临床环境中不易获得。因此，迫切需要一种安全、可靠、独立于操作人员的非侵入性方法来诊断和监测PHTN，以便进行早期有针对性的干预。生物软组织通常具有双相结构，包括饱和液体（间质液和血液）的固体基质（细胞、细胞外基质）。磁共振弹性成像（MRE）可以定量评估多种组织的力学性能。其中，肝脏硬度包括固体应力和流体压力，在临床上广泛用于评估肝纤维化，作为肝活检的替代方法。

Chronic liver disease (CLD) is a highly common cause of death due to the development of cirrhosis and consequential life-threatening portal hypertension (PHTN). Hepatic venous pressure gradient (HVPG) measurement is the gold standard to evaluate PHTN but not readily available in routine clinical settings due to its invasiveness and requirement of adequate operator skill and experience. Thus, an urgent need for a safe, reliable, operator-independent noninvasive method exists for diagnosing and monitoring PHTN to allow early targeted interventions. Biological soft tissues usually have a biphasic architecture, including a solid matrix (cells, extracellular matrix) saturated with fluid (interstitial fluid and blood). MR elastography (MRE) can quantitatively assess multiple tissue mechanical properties. Within them, liver stiffness, which comprises solid stress and fluid pressure, is widely used clinically to assess hepatic fibrosis as a liver biopsy alternative. Our prior studies show that MRE-assessed viscoelasticity can distinguish solid-related fibrosis and fluid-related inflammation in early-stage CLD. Other hepatosplenic MRE parameters (compressibility and nonlinearity) are promising biomarkers for hemodynamics-associated fluid pressure but require systematic evaluation. The overall goal of this work is to develop an advanced multiparametric 3D vector MRE (3DV MRE) technique of the liver and spleen for fully characterizing PHTN in advanced CLD. • In Aim 1, a dual-frequency, self-navigating, and hybrid radial-Cartesian 3DV MRE method will be developed for characterizing multiple mechanical properties in both small animals and human subjects. We will develop a model-based iterative reconstruction and a 3D neural network inversion to calculate viscoelasticity, compressibility, and nonlinearity in the liver and spleen from the hybrid 3DV MRE data. • In Aim 2, we will use 3DV MRE imaging on three PHTN rat models (diet-induced nonalcoholic steatohepatitis (N=22), cirrhosis-induced PHTN after bile duct ligation surgery (N=22), and congestion-induced PHTN after partial inferior vena cava ligation surgery (N=22)). Technical integrity, scientific rigor, and diagnostic accuracy will be assessed by comparing multiple imaging biomarkers with in vivo interstitial fluid and portal pressure measurements, ex vivo dynamic mechanical analysis testing results, and histologic features. • Before the clinical translation, we will evaluate the repeatability of MRE biomarkers in 5 controls and 5 clinical patients using a test-retest strategy. Finally, a pilot clinical study in 10 controls and 50 clinical patients with endoscopy or HVPG will rigorously cross-validate the diagnostic accuracy of the PHTN predictors. Advanced 3DV MRE development enables other investigators and us to explore this promising technology for many other etiologies related to fluid pressure. This project’s success will also provide a valuable noninvasive assessment tool for emerging therapeutic interventions.