Assessment of Age-related Oxygenation Changes in Calf Skeletal Muscle by Photoacoustic Imaging: A Potential Tool for Peripheral Arterial Disease.

Peripheral artery disease is often asymptomatic, and various imaging and nonimaging techniques have been used for assessment and monitoring treatments. This study is designed to demonstrate the ability of photoacoustic imaging to noninvasively determine changes in tissue oxygenation that occur in mice's hind limb skeletal muscle as they age. Mice from two age cohorts were scanned bilaterally with a pulsed laser. The photoacoustic signal was unmixed to generate a parametric map of estimated oxygen saturation and then overlaid on grayscale ultrasound images. Tissue oxygenation measured in young and old mice was compared. Photoacoustic imaging visually and quantitatively showed the decrease in skeletal muscle oxygenation that occurs with age. Percent tissue oxygenation decreased from 30.2% to 3.5% (p < 0.05). This reduction corresponded to reduced fractional area of oxygenation, which decreased from 60.6% to 6.0% (p < 0.05). The change in oxygenation capacity of the still active vascular regions was insignificant (p > 0.05). Intrasubject, intra-, and interobserver comparisons showed low variability in measurements, exhibited by high regression and intraclass correlations exceeding 0.81 for all ages. The decrease in oxygenation detected by photoacoustic imaging paralleled the known oxygenation decrease observed in aging tissues, demonstrating that photoacoustic imaging can assess age-related changes in a mouse calf muscle. These intramuscular changes could potentially act as a strong diagnostic marker for peripheral artery disease. This study thus opens the doors for a novel, affordable, noninvasive method of evaluation free of radiation or exogenous material.

Photoacoustic Imaging for Assessing Tissue Oxygenation Changes in Rat Hepatic Fibrosis.

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.