MRI Contrast Deposition in Neuronal Tissue in Subjects with Normal Renal Function

Gadolinium-based contrast agents (GBCA) are intravenous drugs used to enhance the quality of MRI. They permit the detection and diagnosis of a host of pathologic conditions more so than non-contrast MRI scans. Of those diseases and conditions, one can detect visible inflammation, vessel occlusion and anomalies, cardiac muscle scarring, tumors, and acute MS lesions.

Although elemental Gadolinium is cytotoxic, it can be chelated because of its organic ligand to allow safe administration. The human body can generally clear GBCAs via the renal system to a high degree, but it has been discovered that patients with impaired kidney function are at risk for developing nephrogenic systemic fibrosis (NSF), and deposition within the skin. Judicious and cautious usage of these agents, which involve testing a subject’s kidney function before every MRI which includes GBCAs, has led to the practical usage and eradication of NSF. 

This week’s paper discusses recent news about GBCAs out of Radiology. 

Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging. McDonald RJ, et al. Radiology. 2015 Jun;275(3):772-82.

In this paper, deposition of Gadolinium (III) was assessed using the signal from MR images, as well as from mass spectrometry and transmission electron microscopy using neural tissue samples.

Two groups of deceased patients were studied: one control group (n=10), who have had an MR-scan without contrast; And the contrast group (n=13), who have had at least 4 Gadodiamide contrast-enhanced scans (Omniscan, GE Healthcare). All patients in the contrast group had relatively normal renal function at the time of MR examination. Magnetic field strenghs used were 1.5 and 3-Tesla. MR images were extracted and analyzed. The regions in focus are the dentate nucleus and pons in the posterior fossa, as well as the globus palldius and pulvinar thalamus in the basal ganglia.

Mean T1-weighted signal intensities were computed by user-defined regions of interest and normalized to the CSF signal.  This important step can help account for intra and inter-sequence signal intensity differences, differences in MR units, and magnetic field inhomogeneity along the primary magnetic field axis; as well as inherent scanner differences. Percentage change in signal intensity from first to last unenhanced T1-weighted scans were computed for the contrast group.

Figure 1: Axial T1-weighted MR images through, A, C, E, basal ganglia and, B, D, F, posterior fossa at level of dentate nucleus. Images are shown for, A, B, control group patient 4, and the, C, D, first and, E, F, last examinations performed in contrast group patient 13. Regions of interest used in quantification of signal intensity are shown as dashed lines for globus pallidus (green), thalamus (blue), dentate nucleus (yellow), and pons (red).

As a standard of comparison to assess Gadolinium deposition, tissue samples were extracted and analyzed for both groups using mass spectrometry, transmission electron microscopy, and light microscopy to quantify, localize, and assess the effects of Gadolinium deposition. 

Qualitative changes in T1-weighted signal intensity in the basal ganglia and posterior fossa after multiple injections were observed. This was not observed in unenhanced T1-weighted images from the non-contrast group.

For all measured regions, correlations were seen comparing the cumulative intravenous dose vs. % change in pre-contrast T1 signal, as well as cumulative intravenous dose vs. the Gadolinium (III) in µg / g of tissue, Thus, the mass spectrometry validated the results from the findings seen in the T1-weighted images. No Gadolinium deposition (III) was observed in the control group with mass spectrometry.

Figure 2: Gadolinium detection with mass spectrometry of cadaveric tissues and quantification of MR signal intensity changes. A–D, Changes in T1-weighted signal intensities in globus pallidus, thalamus, dentate, and pons are plotted against cumulative intravenous gadolinium exposure. E–H, Changes in gadolinium ion signal detected with mass spectrometry are plotted against cumulative intravenous gadolinium exposure.

What these findings suggest is that:

Neuronal Gadolinium deposition is present in subjects who have been injected with Gadolinium-based contrast agents, who also have normal renal function.

Although the results may be alarming, it is still unknown whether the Gadolinum detected in these neuronal tissues is in chelated or free ionic form—the latter being more toxic. Additionally, it is also unclear what effect this Gadolinium may have on the human physiology.

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References:

1.   McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, et al. Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging. Radiology. 2015 Jun;275(3):772-82.