Establishment of novel innovative bioimaging techniques of metals by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for diagnosis of liver damage

Objective: Hereditary disorders associated with metal overload or unwanted toxic accumulation of heavy metals can lead to high morbidity and mortality. Patients with hereditary hemochromatosis or Wilson disease for example may develop severe hepatic pathology including fibrosis, cirrhosis or even heptocellular carcinoma [1, 2]. While relevant disease genes are identified and genetic testing is applicable, liver biopsy in combination with energy-dispersive X-ray spectroscopy (EDX) is still applied for accurate diagnostic assessment of metal deposits and storage disorders in liver. Conversely, several metals are needed in trace amounts for carrying out vital functions and their deficiency due to rapid growth, pregnancy, excessive blood loss, and insufficient nutritional or digestive uptake results in organic and systemic shortcomings. Actually, genetic screening and definitive measurements are used in diagnosis of metal overload or deficiency. However, EDX-ray spectroscopy alone is not sensitive enough to analyze trace metal distribution in liver tissue and the quantification of metal images is difficult. Design: In this study, we performed elemental imaging of human liver tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and monitored the distribution of carbon, sodium, magnesium, phosphorus, potassium, calcium, chromium, manganese, iron, cobalt, copper, zinc, molybdenum, zinc, cadmium, tin, mercury, and lead in thin cryo-sections of healthy and diseased livers. Results: We demonstrate that most of the metals are rather homogeneous distributed within the normal tissue, while they are redirected within fibrotic and cirrhotic livers resulting in significant metal deposits. Moreover, total Iron and copper concentrations in disease liver were found about 3 and 5 times higher than in normal liver samples. Conclusions: We conclude that biometal imaging techniques via LA-ICP-MS are novel innovative diagnostic devices that will revolutionize clinical practice in identification and evaluation of various metal disorders in liver.