Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy

Abstract

Background: Gadolinium (Gd)-containing MRI contrast agents (GdCA) are widely used in studies of brain tumors, and a number of reports suggest that under certain conditions, such as renal failure, Gd may be released from GdCA into patient's tissues. Whether this may happen in abnormal tissues in the absence of renal failure has not been studied. Purpose: To test the hypothesis that the local retention of GdCA resulting from brain tumor-associated alterations in the blood–brain barrier (BBB) may result in the deposition of Gd released from the GdCA, depending on stability. Material and Methods: In this retrospective study, 30 selected brain tumor biopsies from 28 patients (taken before and after an institutional switch from a less stable to an intermediate stable GdCA) were searched for Gd-containing deposits using scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDS). Relevant histories and laboratory results were obtained through institutional electronic records. Associations between the presence of deposits and other variables were tested for statistical significance using the two-tailed Fisher's exact test. Results: Insoluble deposits containing Gd associated with phosphorus and calcium were found in seven biopsies from five patients. These deposits were found in patients with estimated GFRs above 53 ml/min, and were detected more often in those receiving GdCA before the switch from a less stable to an intermediate stable GdCA ( P = 0.04), and may be more frequent in patients receiving more than one contrast-enhanced MR scan ( P = 0.15). Conclusion: Gd-containing deposits are present in brain tumors following contrast-enhanced MR scans in patients without severe renal disease. Further studies are needed to assess the clinical importance of the deposits we observed and to determine whether they are also found in other conditions that alter the integrity of the BBB.