Abstract
Chronic liver inflammation progressively evokes fibrosis and cirrhosis resulting in compromised liver function, and often leading to cancer. Early diagnosis and staging of fibrosis is crucial because the five-year survival rate of early-stage liver cancer is high. This study investigates the progression of hepatic fibrosis induced in rats following ingestion of diethylnitrosamine (DEN). Changes in oxygen saturation and hemoglobin concentration resulting from chronic inflammation were assayed longitudinally during DEN ingestion by photoacoustic imaging (PAI). Accompanying liver tissue changes were monitored simultaneously by B-mode sonographic imaging. Oxygen saturation and hemoglobin levels in the liver increased over 5 weeks and peaked at 10 weeks before decreasing at 13 weeks of DEN ingestion. The oxygenation changes were accompanied by an increase in hepatic echogenicity and coarseness in the ultrasound image. Histology at 13 weeks confirmed the development of severe fibrosis and cirrhosis. The observed increase in PA signal representing enhanced blood oxygenation is likely an inflammatory physiological response to the dietary DEN insult that increases blood flow by the development of neovasculature to supply oxygen to a fibrotic liver during the progression of hepatic fibrosis. Assessment of oxygenation by PAI may play an important role in the future assessment of hepatic fibrosis.
Highlights
Chronic liver inflammation leading to liver fibrosis and cirrhosis is a major cause of mortality, accounting for 32,000 deaths in the USA alone and more than one million deaths each year worldwide [1].Pathologically, liver fibrosis is a consequence of a progressive accumulation of extracellular matrix proteins in the liver parenchyma that results from chronic liver tissue inflammation [2]
There was a noticeable increase in the PA signals in liver tissue at 5
It has been shown that as an adaptive molecular response to hypoxia, blood cells increase their HbO2 -carrying capacity and enhance capillary blood supply promoted by improved vascularization along with upregulation of key genes required for these responses, which are largely transcriptionally regulated by HIF-mediated gene expression [30]
Summary
Chronic liver inflammation leading to liver fibrosis and cirrhosis is a major cause of mortality, accounting for 32,000 deaths in the USA alone and more than one million deaths each year worldwide [1]. Liver fibrosis is a consequence of a progressive accumulation of extracellular matrix proteins in the liver parenchyma that results from chronic liver tissue inflammation [2]. A multitude of etiologies such as viral hepatitis (mostly from hepatitis B and C virus), alcoholic and non-alcoholic hepatic injuries, or toxin/drug-induced, metabolic, and autoimmune diseases that trigger reiterative damage to liver parenchyma have been implicated in liver fibrosis [3]. We have shown earlier that B-mode ultrasound can be used for accurate noninvasive fibrosis assessment [5]. Liver biopsy has Diagnostics 2020, 10, 705; doi:10.3390/diagnostics10090705 www.mdpi.com/journal/diagnostics
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