Type of MRI contrast, tissue gadolinium, and fibrosis.

It has been presupposed that the thermodynamic stability (Ktherm) of gadolinium-based magnetic resonance imaging chelates relate to the risk of precipitating nephrogenic systemic fibrosis (NSF). This study compared low-Ktherm gadodiamide to a high-Ktherm gadoteridol in cultured fibroblasts and rats with uninephrectomies. Gadolinium content was assessed using scanning electron microscopy equipped with energy-dispersive x-ray spectroscopy in paraffin-embedded tissues. In vitro, fibroblasts demonstrated dose-dependent fibronectin generation, transforming growth factor β production, and expression of the activated myofibroblast stress fiber protein α smooth muscle actin. There were negligible differences with respect to toxicity or proliferation between the two contrast agents. In the rodent model, gadodiamide treatment led to greater skin fibrosis and dermal cellularity than gadoteridol. In the kidney, both contrast agents led to proximal tubule vacuolization and increased fibronectin accumulation. Despite large detectable gadolinium signals in spleen, skin, muscle, and liver from the gadodiamide-treated group, contrast-induced fibrosis appears to be limited to skin and kidney. These findings support the hypothesis that low thermodynamic stability chelates have a greater propensity to elicit NSF, and demonstrate that certain tissues are resistant to these effects.