Acute susceptibility changes of deep gray matter nuclei to gadobutrol: a prospective longitudinal study using...

Gadolinium-based contrast agents (GBCAs) are associated with gadolinium deposition in the brain. Quantitative susceptibility mapping (QSM) enables sensitive quantification of paramagnetic substances. However, the acute and cumulative effects of macrocyclic GBCAs on deep gray matter nuclei remain incompletely understood, with prior evidence largely based on cross-sectional studies lacking robust longitudinal data within the same individuals. Therefore, this prospective longitudinal study aimed to investigate acute susceptibility changes in deep gray matter nuclei following gadobutrol administration and to evaluate the sensitivity of QSM in detecting subtle susceptibility changes in these regions associated with cumulative use.

In this prospective longitudinal study, 72 patients (mean age 59±10 years, 39 males/33 females) underwent multi-parametric magnetic resonance imaging (MRI) at 3-Tesla, including QSM, T1 mapping, and T2* mapping, both before and after gadobutrol administration. QSM values were measured across 14 deep gray matter nuclei. The number of prior GBCA administrations and clinical variables (age, sex, tumor type, radiotherapy/chemotherapy history) were recorded. Statistical analyses included paired t-tests (pre- vs. post-contrast QSM, Bonferroni-corrected), Spearman correlation (ΔQSM vs. ΔT1/ΔT2*), and linear mixed-effects models (associations between GBCA exposure and susceptibility changes, adjusted for clinical covariates).

Significant post-injection susceptibility changes were observed in specific deep gray matter nuclei: increases in the left amygdala (pre: -15.61 ppb, post: -14.42 ppb, Cohen's d =0.20) and right hippocampus (pre: 2.44 ppb, post: 4.41 ppm, Cohen's d =0.48), and decreases in the left hippocampus (pre: 1.64 ppb, post: 0.87 ppb, Cohen's d =-0.19), bilateral putamen (left: pre: 48.55 ppb, post: 47.13 ppb, Cohen's d =-0.12; right: pre: 22.45 ppb, post: 21.56 ppb, Cohen'd =-0.09), and bilateral globus pallidus (pallidum) (left: pre: 35.04 ppb, post: 30.71 ppb, Cohen's d =-0.21; right: pre: 98.99 ppb, post: 93.05 ppb, Cohen's d =-0.20) (all P<0.05). A negative correlation was found between ΔQSM and ΔT2* in the left pallidum (R=-0.35, P<0.001) and the right pallidum (R=-0.27, P=0.003); in the right putamen, ΔQSM and ΔT2* exhibited a significant negative correlation (R=-0.25, P=0.005). However, in the right hippocampus, ΔQSM and ΔT2* exhibited a significant positive correlation (R=0.21, P=0.021). A significant difference was found in the right hippocampus based on lesion presence (P<0.001), but there was no significant effect on the left hippocampus (P=0.51). The number of prior gadobutrol injections was positively associated with susceptibility in the left amygdala [β =0.88; 95% confidence interval (CI): 0.06, 1.73; P=0.04].

Gadobutrol administration induces spatially heterogeneous susceptibility changes in deep gray matter nuclei, demonstrating acute susceptibility changes. QSM detected changes not significantly correlated with ΔT1, supporting its potential advantage over traditional T1-weighted imaging (T1WI) for detecting gadolinium deposition.