Potential novel diagnostic applications of laser ablation inductively coupled plasma mass spectrometry in trace metal imaging of hepatic metal disorders

The liver is the most central organ and largest gland of the body that controls the whole body metabolism. It produces inconceivable many essential proteins, is responsible for recovery of various food components, mediates the bile production, degrades toxins, and is involved in excretion of unwanted metabolites. Several of these metabolic or catabolic functions of the liver depend on trace elements that are either integral part of enzymes, cofactors, or directly serve as chemical catalysts. Therefore, a lack of trace elements can lead to organ failure or systemic illness. Conversely, excessive hepatic trace element deposition resulting from genetic disorders, intoxication, extensive dietary supply, or long-term parenteral nutrition may cause hepatic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Recently we established novel protocols that allow quantitative biometal imaging in human and murine tissues by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) [1, 2]. We here extended these studies and provide a multitude of novel examples demonstrating the applicability of LA-ICP-MS for quantification of metals with high accuracy in liver sections taken from clinical cases and experimental models of hepatic metal disorders. We further established a novel interactive software tool, i.e. "Ricarda", for handling, quantification and visualizing and displaying LA-ICP-MS data sets. Sample preparation, and quantification strategies were further optimized for application of LA-ICP-MS in daily routine use. We conclude that our findings provide strong evidence that the LA-ICP-MS methodologies provide novel, highly innovative diagnostic options for simultaneously imaging various metals in liver specimens with high sensitivity, spatial resolution, specificity, and quantification ability.