Evaluation of the Effect of Multiple Linear Gadolinium-Based Contrast Agent Exposures on the Signal Intensity of the Dentate Nucleus in Multiple Sclerosis Patients

Abstract
Background: Magnetic resonance imaging (MRI) with gadolinium (GAD)-based contrast agents has been the imaging modality of choice for early detection and monitoring of multiple sclerosis (MS) patients. Objectives: This study aimed to assess the effect of multiple injections of linear GAD-based contrast agents on the signal intensity of the dentate nucleus (DN) in MS patients. Patients and Methods: A cohort of 122 MS patients with GAD-enhanced MRI scans and 61 healthy controls were enrolled in this study. The final standard GAD-enhanced MRI scans were acquired using 1.5T MRI systems. Non-enhanced T1-weighted MRI was performed to assess the DN hyperintensity. The signal intensity ratio (SIR) was also calculated by setting the regions of interest (ROIs) on the DN and pons and dividing the signal intensity of DN to that of pons. The patients were also divided into two subgroups, based on the total number of MRI exposures (> 4 times vs. others), and the subgroups were compared in terms of the mean SIR and hyperintensity. Results: Overall, 68% (n = 83) of the patients were exposed to a contrast agent more than four times. Of these patients, 31.3% (n = 26) showed DN hyperintensity, while no hyperintensity was found in other patients or healthy controls (P < 0.02 for both). The mean SIRs were 1.10 ± 0.07 and 1.04 ± 0.02 in the patients and healthy controls, respectively (P < 0.001). Besides, the mean SIR was 1.14 ± 0.04 in patients with DN hyperintensity and 1.09 ± 0.07 in other patients (P < 0.001). Based on the results, the mean SIR was 1.12 ± 0.7 in patients with > 4 contrast injections, while it was 1.06 ± 0.04 in patients with ≤ 4 contrast injections (P < 0.001). Conclusion: The SIR and visible DN hyperintensity increased by increasing the number of GAD injections, which could be due to the tissue deposition of GAD.

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