The present study focuses on the elemental and molecular analysis of contrast agents in tissue thin sections to assess the deposition and distribution of gadolinium from gadolinium-containing contrast agents (GBCAs) in the body. The discovery of gadolinium deposition in the brain following the use of GBCAs has raised significant concerns about neurotoxic risks, necessitating further research on the peripheral nervous system to fully investigate neurological effects and their causes. Indications for neurotoxicity include findings from rat studies, which show a decreased startle response and pain hypersensitivity, as well as reported patient symptoms such as brain fog, headaches, and pain in the extremities. For this purpose, a 266 nm laser ablation (LA) coupled with an inductively coupled plasma mass spectrometry (ICP-MS) system and a quantum cascade laser (QCL) -based infrared (IR) microscope are used. The investigated tissue sections originate from samples of the sciatic nerve.

The gadolinium distribution was quantified in axial and longitudinal sections of the sciatic nerve. In addition to the element gadolinium, the endogenous elements phosphorus and iron as well as copper and zinc were analyzed to obtain information on the microscopic structure of the samples and to correlate this with the gadolinium concentration. Matrix-matched gelatin standards were used for quantification. The detection limit was improved by optimizing various parameters such as LA transport gas flow and laser spot size. In the tissue sections of patients injected with GCBAs for medical applications, 0.05 μg/g to 3.1 μg/g gadolinium was detected at the perineurium of the nerve fascicles, indicating a accumulation of the metal in this area.

QCL-based IR microspectroscopy of the samples revealed a correlation between the distribution of gadolinium and the distributions of lipid and collagen signatures in the perineurium and blood vessels of the sciatic nerve. Furthermore, image segmentation based on uniform manifold approximation and projection for dimension reduction (UMAP) to visualize different tissue types in nerve thin sections was investigated and showed potential to visualize and distinguish between different structures in the tissue.