Synopsis
To assess potential regional and global
correlations between brain relaxation times and the number of prior
administrations of linear gadolinium-based contrast agents (GBCA) using
quantitative MRI. The subjects consisted of 40 patients (7 patients with multiple
prior linear GBCA exposures and 33 patients with no prior GBCA exposures) with
brain MRI using the mixed turbo spin-echo pulse sequence. T1 and T2 relaxation
times were assessed in selected regions of brain parenchyma (GP, DN, thalamus,
and pons) and the whole brain, and were demonstrated to be associated with the
number of gadolinium administrations. A stronger relationship was demonstrated
in gray matter.Purpose
Recently it has
become apparent that patients with normal renal function may exhibit
progressively increased signal intensity in selected regions of the brain on
T1-weighted images obtained in the setting of repeated MR studies using gadolinium-based
contrast agents (GBCA), especially linear GBCAs (1-5). Prior studies used only qualitative measures
based on weighted signal intensities in selected regions of interest without a
quantitative assessment of the true relaxation times. The purpose of this work
was to assess potential regional and global correlations between brain
relaxation times, using T1 and T2 quantitative MRI sequences, and the number of
prior administrations of linear GBCA.
Methods
This IRB approved, HIPAA compliant retrospective study conducted
in 2008-2014 evaluated 40 patients (17 men, 23 women; 3.8–87 years; median age,
27 years) with brain MRI acquired using the mixed turbo spin-echo pulse
sequence at a 1.5T unit. For regional assessment, regions-of-interest (ROIs)
were placed on a T1 map by a single blinded neuroradiologist in the globus
pallidus (GP), thalamus, dentate nucleus (DN), and centrally within the pons.
Using an in-house developed Mathcad (PTC, Needham, MA) program, the T1 and T2
relaxation times within each of these structures were calculated using the same
ROIs. For global measurement, the whole brain, including white (WM) and gray
matter (GM), was segmented using a 3-channel dual-clustering algorithm
programmed in Mathcad (6). T1 and T2 relaxation time
histograms of all segments were generated and modeled with Gaussian functions.
The mean T1 of WM/GM and T2 of the whole brain were measured. Regression
analysis was performed (Stata ver. 12.1, Stata Corp LP, College Station, TX,
USA) to assess whether an association exists between the regional and global T1
and T2 relaxation times and the number of prior GBCA administrations.
Results
Of 40 subjects, 7 patients (4 men, 3 women; 7–77 years; median
age, 47) received linear GBCA (Magnevist®) administrations
(range 1 to 8 times). No patients received macrocyclic GBCAs. The remaining 33
patients had no history of GBCA exposure. Scatterplots of T1 values versus the number
of previous GBCA administrations in the GP, DN, thalamus and pons are shown in Figure
1. The GP (P<.001), DN (P=.03), and thalamus (P<.002) showed
significant correlations with the number of previous gadolinium-based contrast
material administrations in T1 relaxation times. T2 relaxation time changes versus
number of previous linear GBCA administrations in the GP, DN, thalamus and pons
are shown in Figure 2. The GP, DN, thalamus, and pons demonstrated an inverse
relationship between T2 relaxation times and the number of previous gadolinium
administrations, with a significant correlation found in the DN (P=.01),
thalamus (P<.001), and pons (P<.01). The relationship between the
globally quantitative T1/T2 relaxation times and previous linear GBCA
administrations are shown in Figures 3 and 4. Whole brain evaluation in
patients with prior GBCA exposure showed an inverse relationship between T1
relaxation times and the number of previous gadolinium administrations,
especially for grey matter (P=.06), though this trend did not achieve
statistical significance. T1 relaxation times of grey matter were significantly
shorter in patients with prior GBCA exposure than those of patients with none
(with prior GBCA 939±72ms, without prior GBCA 1001±73ms, P=.043). T2 relaxation
times were also significantly shorter in patients with prior GBCA exposure than
those of patients without exposure (with prior GBCA 105.6±9.3ms, without prior
GBCA 112.7±7.9ms, P=.044), and also showed a significant correlation between T2
and the number of previous gadolinium administrations (P<.003).
Discussion
In this work, T1 and T2 relaxation times were assessed in
selected regions of brain parenchyma (GP, DN, thalamus and pons) and the whole
brain, and were demonstrated to be associated with the number of prior
gadolinium administrations. A stronger relationship was demonstrated in gray
matter. These results suggest that gadolinium accumulation may be seen in the
whole brain, as shown in several recent studies using brain specimen analysis, which
showed gadolinium deposition in several brain regions (1,2,4,5,7,8).
Prior works have focused on imaging
assessment using selected normalized signal intensity ratios from specific
regions of interest on T1 weighted images, such as the GP:thalamus and DN:pons
ratios (2,4,5,9,10). Herein, we show that prior
observations with qualitative MR images are further corroborated with fully
quantitative measures of T1 and T2 relaxation times.
Conclusions
Quantitative assessment using changes in T1 and T2
relaxation times demonstrated an association with the number of prior
gadolinium-based contrast agent administrations. Additional studies are needed
to investigate the clinical significance of these findings with large sample
size. Quantitative MRI may potentially be a useful method for noninvasive
assessment of gadolinium accumulation in the brain.
Acknowledgements
No acknowledgement found.References
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