Liver fibrosis/cirrhosis is one of the most common outcomes of chronic liver disease. Chronic liver disease is assessed by progressive fibrosis caused by repeated injury due to metabolic dysfunction, alcohol abuse, viral hepatitis, or autoimmune disease. If it is left unchecked, liver fibrosis will progress to cirrhosis, an advanced stage of the disease estimated to affect 1?2% of the world?s population. The major clinical consequences of cirrhosis are impaired liver function and development of hepatocellular carcinoma (HCC), both of which increase the risk of death. The current gold diagnostic method of biopsy has many limitations such as sampling errors, high inter-observer variability with 33% error rate even for diagnosis of advanced stages of liver fibrosis such as cirrhosis. Currently, there is NO non-invasive way to detect liver fibrosis at an early stage with desired sensitivity and accuracy. There is a major unmet medical need to develop noninvasive imaging methodologies and MRI contrast agents to detect early stage of liver fibrosis and stage the progression of liver fibrosis. The goal of STTR Phase I research is to obtain proof-of-principle evidence to achieve early detection of liver fibrosis with significantly improved sensitivity and selectivity by optimizing and characterizing our designed protein-based contrast agents (ProCAs) with liver preference and disease specificity.
Aim 1 is to develop MRI molecular imaging contrast agents for non-invasive detection of liver fibrosis.
Aim 2 is to evaluate in vivo imaging capability of liver fibrosis for early stage detection using mouse.
Aim 3 is to perform acute toxicity studies.
s Our study will open a new avenue for liver fibrosis/cirrhosis diagnosis/prognosis by protein design. The proposed studies are expected to fill in the major medical gaps and to facilitate to devise treatment strategy to reverse fibrosis and follow high risk patients.
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