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Principal Investigator: Meng Yin
Organization: MAYO CLINIC ROCHESTER
Fiscal Year: 2024
Award: $331,603
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
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.
Terms: <3-D><3-Dimensional><3D><Accuracy of Diagnosis><Alcoholic Liver Diseases><Animals><Architecture><Assessment instrument><Assessment tool><Biological><Biological Markers><Bleeding><Blood><Blood Reticuloendothelial System><Body Tissues><Causality><Cause of Death><Cell-Extracellular Matrix><Choline Deficiency><Cirrhosis><Clinical><Clinical Research><Clinical Study><Closure by Ligation><Common Rat Strains><Data><Development><Diagnosis><Diagnostic><Diet><Disease Progression><Disease regression><ECM><Early Intervention><Effectiveness><Elasticity><Endoscopy><Engineering / Architecture><Esophageal Varix><Esophagogastroduodenoscopy><Esophagus><Etiology><Evaluation><Evolution><Extracellular Matrix><Fibrosis><Frequencies><Goals><Hemorrhage><Hepatic><Hepatic Disorder><High Fat Diet><Histologic><Histologically><Human><Hybrids><Image><Imaging Procedures><Imaging Technics><Imaging Techniques><Inferior Vena Cava><Inferior vena cava structure><Inflammation><Intercellular Fluid><Interstitial Fluids><Intervention><Intervention Strategies><Investigators><Knowledge><Laboratories><Life><Ligation><Liquid substance><Liver><Liver Fibrosis><Liver diseases><Liver lesion biopsy><Longitudinal Studies><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Elastography><Magnetic Resonance Imaging><Measurement><Measures><Mechanics><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Methods><Modeling><Modern Man><Monitor><Motion><NAFLD><NASH><NMR Imaging><NMR Tomography><Nuclear Magnetic Resonance Imaging><Operative Procedures><Operative Surgical Procedures><Outcome><Pathologic Processes><Pathological Processes><Patients><Phase><Portal Hypertension><Portal Pressure><Prevalence><Protocol><Protocols documentation><Radial><Radius><Rat><Rats Mammals><Rattus><Research><Research Personnel><Researchers><Risk><Role><Severities><Solid><Sorting><Spleen><Spleen Reticuloendothelial System><Steatohepatitis><Stress><Surgical><Surgical Interventions><Surgical Procedure><Techniques><Technology><Test Result><Testing><Therapeutic Intervention><Tissues><Training><Variant><Variation><Varices><Varicose Veins><Varicosity><Venous Blood Pressure><Venous Pressure><Venous Pressure level><Viscosity><Work><Zeugmatography><alcohol induced hepatic injury><alcohol induced liver disorder><alcohol induced liver injury><alcohol related liver disease><alcohol-associated liver disease><alcohol-induced hepatic dysfunction><alcohol-induced liver disease><alcohol-induced liver dysfunction><alcohol-mediated liver dysfunction><alcohol-mediated liver injury><alcohol-related liver disease><alcoholic liver injury><bile duct><bile ductule><bio-markers><biologic><biologic marker><biomarker><blood loss><causation><chronic hepatic disease><chronic hepatic disorder><chronic liver disease><chronic liver disorder><cirrhotic><clinical practice><clinical relevance><clinical significance><clinical translation><clinically relevant><clinically significant><clinically translatable><computer based prediction><developmental><diagnostic accuracy><diets><disease causation><elastic imaging><elasticity imaging><elastography><endoscopic imaging><esophageal varices><ethanol induced hepatic injury><ethanol induced liver disorder><ethanol induced liver injury><ethanol liver disease><ethanol-induced hepatic dysfunction><ethanol-induced liver disease><ethanol-induced liver dysfunction><ethanol-mediated liver dysfunction><ethanol-mediated liver injury><experience><fibrotic liver><fluid><hemodynamics><hepatic body system><hepatic disease><hepatic fibrosis><hepatic inflammation><hepatic organ system><hepatic stiffness><hepatocellular injury><hepatopathy><high risk><human subject><imaging><imaging biomarker><imaging in vivo><imaging marker><imaging-based biological marker><imaging-based biomarker><imaging-based marker><in vivo><in vivo imaging><inflamed liver><interstitial><intervention therapy><interventional strategy><liquid><liver biopsy><liver disorder><liver inflammation><liver stiffness><long-term study><longitudinal outcome studies><longterm study><mechanic><mechanical><mechanical properties><neural network><non-alcohol fatty liver disease><non-alcohol induced steatohepatitis><non-alcoholic fatty liver disease><non-alcoholic liver disease><non-alcoholic steato-hepatitis><non-alcoholic steatohepatitis><nonalcoholic fatty liver disease><nonalcoholic steato-hepatitis><nonalcoholic steatohepatitis><pre-clinical study><preclinical study><predictive modeling><pressure><primary end point><primary endpoint><reconstruction><response><screening><screenings><secondary end point><secondary endpoint><skills><social role><soft tissue><success><surgery><three dimensional><vector><viscoelasticity>