In the October 2014 issue of Investigative Radiology, Errante et al report study findings that confirm the association between the increase in the unenhanced T1-weighted signal intensity of the dentate nucleus and the number of gadolinium-enhanced MRI scans. (The dentate nucleus is located within the deep white matter of the brain.)
The study included 38 patients with Multiple Sclerosis (MS) and 37 patients with brain metastases (BMs) who had undergone at least 2 consecutive enhanced MRIs. After calculating the dentate nuclei-to-pons (DNP) signal intensity ratio, these values were compared between patients with less than 6 and those with 6 or more contrast-enhanced MRI. A progressive increase in the T1 signal intensity of the DNP ratio was observed in both the MS group and the BM group. All patients had normal kidney function.
The findings support the data presented by Kanda et al in late 2013 which found that multiple administrations of Gadolinium-Based Contrast Agents, particularly gadodiamide (Omniscan), are associated with increased signal intensity of the dentate nucleus on unenhanced T1-weighted images in patients with brain metastases as well as in patients with MS.
Unlike the study by Kanda et al, the Errante study excluded patients with kidney and/or liver dysfunction. Errante and colleagues noted that their results, “in fact, support the idea that gadolinium may accumulate in tissues of patients with normal kidney function, as opposed to the known deposits rarely reported in the skin of patients with severe kidney failure who have Nephrogenic Systemic Fibrosis”.
Interestingly, the product labeling of all Gadolinium-Based Contrast Agents (GBCAs) note that Gadolinium-Based Contrast Agents “do not cross an intact blood-brain barrier”; however, “disruption of the blood-brain barrier” or “abnormal vascularity” allows accumulation in lesions such as neoplasms (tumors), abscesses, and subacute infarcts. Disruption of the blood-brain barrier is why Gadolinium is deposited in brain tumors, and brain lesions like those seen in MS patients. The abnormal brain tissue then becomes more clearly defined or enhanced on magnetic resonance (MR) images. Gadolinium is neurotoxic and should not remain in the brain; however, the Errante et al study and others in the literature indicate that Gadolinium retention in the brain does occur.
Errante et al concluded that their “study shows that the increase in the unenhanced T1 signal intensity has a linear relationship with the number of gadolinium-enhanced MRI scans in patients with MS and BM”. They noted that “this finding suggests substantial dechelation of gadodiamide in patients with normal renal function”. They strongly recommended further comparative studies with other GBCAs, both linear and macrocyclic.
Based on GBCA product labeling, it might not be the result of “dechelation”, but instead a predicted outcome when the blood-brain barrier is crossed, especially after multiple doses of a Gadolinium-Based Contrast Agent. It would seem that additional studies are urgently needed to make that determination since many patients receive multiple doses of contrast.
Errante, Y., Cirimele, V., Mallio, C. A., Di Lazzaro, V., Zobel, B. B., & Quattrocchi, C. C. (2014). Progressive Increase of T1 Signal Intensity of the Dentate Nucleus on Unenhanced Magnetic Resonance Images Is Associated With Cumulative Doses of Intravenously Administered Gadodiamide in Patients With Normal Renal Function, Suggesting Dechelation. Investigative Radiology, 49(10), 685–690. doi:10.1097/RLI.0000000000000072. Retrieved from http://journals.lww.com/investigativeradiology/Abstract/2014/10000/Progressive_Increase_of_T1_Signal_Intensity_of_the.8.aspx
Kanda, T., Ishii, K., Kawaguchi, H., Kitajima, K., & Takenaka, D. (2013). High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-weighted MR Images: Relationship with Increasing Cumulative Dose of a Gadolinium-based Contrast Material. Radiology, 131669. doi:10.1148/radiol.13131669. Retrieved from http://pubs.rsna.org/doi/abs/10.1148/radiol.13131669