Unenhanced T1-weighted Magnetic Resonance Research Articles

T1 signal intensity in the dentate nucleus after the administration of the macrocyclic gadolinium-based contrast agent gadoterate meglumine: An observational study

Introduction and aimsContradictory results have been reported about hyperintensity of the globus pallidus and/or dentate nucleus on unenhanced T1-weighted magnetic resonance (MR) images after exposure to various gadolinium-based contrast agents. This change in signal intensity varies with different gadolinium-based contrast agents. We aimed to determine whether signal intensity in the dentate nucleus is increased in unenhanced T1-weighted images in patients who have undergone multiple studies with the macrocyclic gadolinium-based contrast agent gadoterate meglumine. We thoroughly reviewed the literature to corroborate our results. Materials and methodsWe included patients who had undergone more than 10 MR studies with gadoterate meglumine. We quantitatively analyzed the signal intensity in unenhanced T1-weighted MR images measured in regions of interest placed in the dentate nucleus and the pons, and we calculated the dentate nucleus-to-pons signal intensity ratios and the differences between the ratio in the first MR study and the last MR study. We used t-tests to evaluate whether the differences between the signal intensity ratios were different from 0. We also analyzed the subgroups of patients who had been administered <15 and ≥15 doses of gadoterate meglumine. We used Pearson correlation to determine the relationships between the differences in the signal intensity ratios and the number of doses of gadoterate meglumine administered. ResultsThe 54 patients (26 men) had received a mean of 13.8±3.47 doses (range, 10−23 doses). The difference in the dentate nucleus-pons signal intensity ratio between the first and last MR study was -0.0275±0.1917 (not significantly different from 0; p=0.2968) in the entire group, -0.0357±0.2204 (not significantly different from 0; p = 0.351 in the patients who had received <15 doses (n=34), and -0.0135±0.1332 (not significantly different from 0; p = 0.655) in those who had received ≥15 doses (n=20). Differences in signal intensity ratios did not correlate significantly with the accumulated dose of gadoterate meglumine (P = 0.9064; ρ = -0.0164 [95%]). ConclusionsReceiving more than 10 doses of gadoterate meglumine was not associated with increased signal intensity in the dentate nucleus.

Signal Intensity Changes in the Dentate Nucleus and Globus Pallidus of Multiple Sclerosis Patients Undergoing Multiple Brain Magnetic Resonance Imaging with Gadolinium-Based Contrast Agents

Objective: To investigate the correlation between cumulative doses of gadolinium-based contrast agents and increased signal intensity (SI) in the dentate nucleus (DN) and globus pallidus (GP). Methods: Our retrospective trial involved 21 multiple sclerosis patients (11 women, 10 men; mean age: 39.21±10.24, range: 20 to 57 years) who underwent a serial number of multiple cranial magnetic resonance imaging (MRI) examinations in the radiology department of our tertiary care center. Average signal intensities on the DN, pons, GP and thalamus on unenhanced T1-weighted magnetic resonance images were taken into account. The signal intensity in the DN was proportioned to the signal intensity in the pons, whereas the signal intensity in GP to the signal intensity in the thalamus. Any relationship between the DN-to-pons or GP-to-thalamus signal intensity ratios and previous gadolinium-based contrast administrations was sought by means of repeated measures ANOVA. Results: Increases in both DN-to-pons and GP-to-thalamus signal intensity ratios displayed a significant correlation with previous administrations of gadolinium-based contrast agents (p&lt;0.001 for both). A remarkable increase was detected in DN-to-pons and GP-to-thalamus signal intensity ratios between the first and last MRI examinations (p&lt;0.001 for both). Conclusion: Our results support the association between increase in the SI of the DN and GP to the number of gadolinium-enhanced MRI scans in MS patients. The increase in T1 SI seems to be linked with the number of enhanced MRI scans.

Intensidad de la señal en T1 en el núcleo dentado tras la administración del agente de contraste con gadolinio macrocíclico gadoterato de meglumina: un estudio observacional

Introduction and aimsContradictory results have been reported about hyperintensity of the globus pallidus and/or dentate nucleus on unenhanced T1-weighted magnetic resonance (MR) images after exposure to various gadolinium-based contrast agents. This change in signal intensity varies with different gadolinium-based contrast agents. We aimed to determine whether signal intensity in the dentate nucleus is increased in unenhanced T1-weighted images in patients who have undergone multiple studies with the macrocyclic gadolinium-based contrast agent gadoterate meglumine. We thoroughly reviewed the literature to corroborate our results. Materials and methodsWe included patients who had undergone more than 10 MR studies with gadoterate meglumine. We quantitatively analyzed the signal intensity in unenhanced T1-weighted MR images measured in regions of interest placed in the dentate nucleus and the pons, and we calculated the dentate nucleus-to-pons signal intensity ratios and the differences between the ratio in the first MR study and the last MR study. We used t-tests to evaluate whether the differences between the signal intensity ratios were different from 0. We also analyzed the subgroups of patients who had been administered<15 and ≥15 doses of gadoterate meglumine. We used Pearson correlation to determine the relationships between the differences in the signal intensity ratios and the number of doses of gadoterate meglumine administered. ResultsThe 54 patients (26 men) had received a mean of 13.8±3.47 doses (range, 10-23 doses). The difference in the dentate nucleus-pons signal intensity ratio between the first and last MR study was -0.0275±0.1917 (not significantly different from 0; p=0.2968) in the entire group, -0.0357±0.2204 (not significantly different from 0; p=0.351 in the patients who had received <15 doses (n=34), and -0.0135±0.1332 (not significantly different from 0; p=0.655) in those who had received ≥15 doses (n=20). Differences in signal intensity ratios did not correlate significantly with the accumulated dose of gadoterate meglumine (P=0.9064; ρ=-0.0164 [95%]). ConclusionsReceiving more than 10 doses of gadoterate meglumine was not associated with increased signal intensity in the dentate nucleus.

Effect of Long-Term Retention of Gadolinium on Metabolism of Deep Cerebellar Nuclei After Repeated Injections of Gadodiamide in Rats.

The aim of this study was to determine potential metabolism and histological modifications due to gadolinium retention within deep cerebellar nuclei (DCN) after linear gadolinium-based contrast agent injection (gadodiamide) in rats at 1 year after the last injection. Twenty female rats received 20 doses of gadodiamide (0.6 mmol of gadolinium per kilogram each) over 5 weeks. They were followed at 1 week (M0), 6 weeks (M1), and 54 to 55 weeks (M13) postinjections to evaluate hypersignal on unenhanced T1-weighted magnetic resonance imaging and metabolic alterations by H magnetic resonance spectroscopy (H-MRS). At 1 year postinjections, brains were sampled to determine the localization of gadolinium within cerebellum by laser ablation inductively coupled mass spectroscopy and to evaluate morphological changes by semiquantitative immunofluorescence analysis. There is a significant increase of the ratio DCN/brainstem for the gadodiamide group at M0 (+7.2% vs control group = 0.989 ± 0.01), M1 (+7.6% vs control group = 1.002 ± 0.018), and it lasted up to M13 (+4.7% vs control group = 0.9862 ± 0.008). No variation among metabolic markers (cellular homeostasis [creatine, choline, taurine], excitatory neurotransmitter [glutamate], and metabolites specific to a cellular compartment [N-acetyl aspartate for neurons and myo-inositol for glial cells]) were detected by H-MRS between gadodiamide and saline groups at M0, M1, and M13. At M13, laser ablation inductively coupled mass spectroscopy demonstrated that long-term gadolinium retention occurred preferentially in DCN. No histological abnormalities (including analysis of astrocytes, neurons, and microglial cells) were found in the rostral part of DCN. Repeated administration of gadodiamide lead to a retention of gadolinium preferentially within DCN at 1 year postinjections. This retention did not lead to any detectable changes of the measured metabolic biomarkers nor histological alterations.

Re: “Increased signal intensity in the unenhanced T1-weighted magnetic resonance in the brain after repeated administrations of a macrocyclic-ionic gadolinium-based contrast agent”

Re: “Increased signal intensity in the unenhanced T1-weighted magnetic resonance in the brain after repeated administrations of a macrocyclic-ionic gadolinium-based contrast agent”

Increased signal intensity in the unenhanced T1-weighted magnetic resonance in the brain after repeated administrations of a macrocyclic-ionic gadolinium-based contrast agent

Amaç: Manyetik rezonans görüntülemede (MRG) kullanılan makrosiklik-iyonik gadolinium- bazlı kontrast (GBKA) ajandır. Bu çalışmanın amacı gadoterat meglumin ile tekrarlıyan beyin MRG yapılmış akciğer kanserli hastalardaki dentat nucleus (DN), pons (P), globus pallidus (GP), talamusdaki (T) sinyal intensite (Sİ) artımı ile ilişkisini belirlemektir.

Gadolinium Presence in the Brain After Administration of the Liver-Specific Gadolinium-Based Contrast Agent Gadoxetate: A Systematic Comparison to Multipurpose Agents in Rats.

Clinical studies have reported different results regarding the signal intensity (SI) increase in the dentate nucleus on unenhanced T1-weighted magnetic resonance imaging (MRI) after repeated administrations of gadolinium-based contrast agents (GBCAs). The aim of this study was to evaluate MRI SI changes and gadolinium (Gd) brain concentrations in an animal model after repeated administration of liver-specific linear gadoxetate in comparison to multipurpose linear and macrocyclic GBCAs. Recently, it was demonstrated that small amounts of GBCAs are able to cross the blood-cerebrospinal fluid (CSF) barrier. Therefore, a secondary aim was to test if the administration of these GBCAs directly into the CSF results in a similar MRI pattern and brain Gd concentration than after systemic intravenous injection. Forty-eight Han-Wistar rats were equally divided into the following 4 groups: gadoxetate (liver-specific linear), gadodiamide (multipurpose linear), gadobutrol (multipurpose macrocyclic), and control (saline, artificial CSF). For systemic application, 6 animals per group received 8 intravenous injections on 4 consecutive days per week over 2 weeks using a dose of 0.15 mmol/kg for gadoxetate and 0.6 mmol/kg for multipurpose GBCAs per injection, which corresponds to the recommended clinical dose in humans. For CSF application, 6 animals per group received one intracisternal administration of 0.31 μmol Gd (gadoxetate) and 1.25 μmol Gd (multipurpose GBCAs) or an equal volume of artificial CSF. Brain MRI was performed after a period of 5 weeks to evaluate the SI in deep cerebellar nuclei (DCN) and brain stem. Subsequently, animals were euthanized and their brains were dissected for Gd quantification by inductively coupled plasma-mass spectrometry. Visually evident increased SIs in the DCN were observed in blinded image review only after administration of gadodiamide. The respective SI ratios between DCN and brain stem were significantly higher compared with the control groups (P = 0.009 and P = 0.002 for intravenous and intracisternal application, respectively), whereas no difference was found for gadoxetate and gadobutrol (P ≥ 0.9). Inductively coupled plasma-mass spectrometry revealed the lowest Gd content in the brain tissue after administration for gadoxetate. The mean Gd concentrations in the cerebellum were 0.08 nmol/g (gadoxetate), 2.66 nmol/g (gadodiamide), and 0.26 nmol/g (gadobutrol) after intravenous administration, and 0.28 nmol/g (gadoxetate), 3.23 nmol/g (gadodiamide), and 0.69 nmol/g (gadobutrol) after intracisternal application. This rat study demonstrates distinct differences in the presence of gadolinium in the brain between the liver-specific linear gadoxetate and the multipurpose linear GBCA gadodiamide. No MRI signal alterations were observed after 8 dose-adapted intravenous or a single intracisternal administrations of gadoxetate and multipurpose macrocyclic gadobutrol. The Gd concentrations in the brain 5 weeks after intravenous administration of gadoxetate were an order of magnitude lower compared with gadodiamide and slightly lower than for gadobutrol. Likely reasons for these differences are the 4-fold lower dose, the dual excretion pathway, and the higher complex stability of gadoxetate compared with multipurpose linear GBCAs. The similar findings for both routes of GBCA administration underlines the assumption that the very small amount of GBCAs that cross the blood-CSF barrier is further transported into the brain tissue.

Signal intensity increases in dentate nucleus/globus pallidus/pulvinar on unenhanced T1WI MR images after multiple examinations with gadodiamide.

Elevated signal intensity (SI) in the dentate nucleus (DN), globus pallidus (GP) and pulvinar (PUL) was reportedly observed on unenhanced T1-weighted (T1WI) magnetic resonance (MR) images in patients receiving multiple enhanced MR examinations. We aimed to clarify whether this phenomenon influences the long-term neurological status of patients. We studied 196 radiosurgically treated patients undergoing ≥10 MR examinations using a single dose of gadodiamide and the same 1.5 Tesla MR unit. SI ratios were calculated by referencing the brainstem (BS) for the DN and the thalamus (TH) for the GP and PUL. We compared the SI ratios at the first, fifth, and 10th, and at the most recent examinations. The neurological symptoms of all 196 patients were assessed at each MR examination by one of the authors (MY). The DN/BS and GP/TH SI ratios were significantly increased at the fifth examination ( p < .0001, p = 0.0094) and, thereafter, gradually increased. Although the PUL/TH SI ratio was not significantly increased at the fifth examination ( p = 0.2515), a significant increase was noted at the 10th examination ( p < .0001). There were no significant predictive factors for DN/BS SI increases. Younger age, no brain metastasis, and normal estimated glomerular filtration rate were related to GP/TH SI ratio increases ( p = 0.0308, p = 0.0001, p = 0.0306). Higher age and total bilirubin level were related to an increased PUL/TH SI ratio ( p = 0.0276, p = 0.0097). No patients experienced gadodiamide-related health problems. Although the SI ratios rose as numbers of gadodiamide administrations increased, no adverse health effects have developed to date.

Increased signal intensity in the dentate nucleus on unenhanced T1-weighted MR images after multiple gadolinium-based contrast material administrations: a preliminary study

Objective To compare changes in signal intensity (SI) of the dentate nucleus (DN), pons and cerebrospinal fluid (CSF) on unenhanced T1-weighted magnetic resonance imaging (MRI) scans after multiple administrations of the linear gadolinium-based contrast agent. Methods Clinical and imaging data of forty-nine patients who underwent at least 4 consecutive enhanced MRI examinations were analyzed retrospectively (unenhanced T1-weighted MRI scans were performed before and after consecutive enhanced MRI examinations). The mean SI of DN, pons and CSF were measured on unenhanced T1-weighted images. The SI ratio of DN to pons was calculated by dividing the SI in the DN by that in the pons, and so was The DN to CSF SI ratio. The difference of SI ratio of DN-to-pons and DN-to-CSF in the same patient before and after repeated contrast-enhanced T1WI were analyzed by paired-samples t tests. Linear regression analysis was used to analyze whether the SI ratios of DN-to-pons, DN-to-CSF were correlated with any clinical factor. Results The SI ratios of DN-to-pons and DN-to-CSF after multiple contrast administrations were higher than those before enhancement, and the differences were statistically significant. The SI ratios of DN-to-pons and DN-to-CSF before and after repeated contrast enhancement were 0.98±0.62, 1.05±0.54; 3.89±0.94, 4.97±1.61 (t=-8.494, -4.526, P 0.05). Conclusions This study indicates that serial injections of linear gadolinium-based contrast agent may lead to an increase in SI in the DN. Key words: Gadolinium; Dentate nucleus; Magnetic resonance imaging

Signal Changes in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Magnetic Resonance Images After Intrathecal Administration of Macrocyclic Gadolinium Contrast Agent.

The aim of this study was to evaluate signal changes in the dentate nucleus and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance (MR) images (T1 WI) in a cohort of patients who have received intrathecal macrocyclic ionic gadolinium-based contrast agent (GBCA) gadoterate meglumine. A group of 20 patients (male/female ratio, 8:12; mean age, 39.5 ± 15.5 years) who had not received intravenous GBCA but had received an intrathecal macrocyclic ionic GBCA (plus baseline and an additional final magnetic resonance imaging [MRI] for reference) from 2012 to 2017 were retrospectively included in this institutional review board-approved study. Two radiologists inspected T1-weighted 2-dimensional spin echo (n = 7) and 3-dimensional isotropic turbo field echo (n = 13) images on a 3 T MRI system to conduct visual evaluation and quantitative analysis. Baseline and final examination signal intensity (SI) ratios were assessed across time by using the same pulse sequences. For visual analysis, SI changes on the GP, thalamus (Th), cerebellar peduncle (CP), and dentate nucleus (DN) were graded as a 3-point scale. For quantitative analysis, SI ratio differences between the baseline and final MR examinations were estimated for the DN-to-CP and GP-to-Th ratios. One-sample t tests were used to investigate whether they differed from 0. In addition, to investigate significant differences between the SI ratios for various pulse sequences, t tests were performed. The regression analysis was additionally used to find any correlation between SI ratio differences and various confounding variables including age, sex, or the mean interval between the baseline and final MR examinations. The SI ratio differences did not deviate significantly from 0, neither for the DN/CP ratio (0.013 ± 0.0584, P = 0.287) nor the GP/Th ratio (-0.0113 ± 0.0546, P = 0.366). The DN-to-CP and GP-to-Th SI ratio differences did not significantly deviate from 0 in the patient groups in either of the imaging sequences (P > 0.05) as well. Age, sex, and the mean interval between examinations did not influence SI ratio differences between examinations (P > 0.05). Intrathecal macrocyclic GBCA administration was not associated with measurable T1 SI changes in the GP and DN as an indicator of brain gadolinium deposition detectable by MRI.

Pediatric Brain: Gadolinium Deposition in Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images Is Dependent on the Type of Contrast Agent.

The aim of this study was to identify the signal intensity (SI) changes in the dentate nucleus (DN) and the globus pallidus (GP) on unenhanced T1-weighted magnetic resonance (MR) images after multiple administration of gadolinium-based contrast agents (GBCAs) in children and compare those changes between linear and macrocyclic GBCAs. This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. We identified 92 children who underwent at least 4 consecutive MR examinations exclusively using either linear GBCA (gadodiamide or gadopentetate dimeglumine, n = 41) or macrocyclic GBCA (gadoterate meglumine, n = 51). Signal intensity ratio changes in the DN to pons and GP to thalamus between the first and last MR examinations were calculated. The SI ratios in the linear group increased significantly between the first and last MR examinations (mean difference: DN to pons, 0.0461 ± 0.0480, P < 0.001; GP to thalamus, 0.0332 ± 0.0385, P < 0.001), but not in the macrocyclic group (mean difference: DN to pons, -0.0010 ± 0.0371, P = 0.855; GP to thalamus, 0.0007 ± 0.0294, P = 0.867). In the linear regression analysis, the numbers of administrations of gadodiamide and gadopentetate dimeglumine were highly associated with the differences in SI ratios (DN to pons, P < 0.001 and P = 0.003; GP to thalamus, P < 0.001 and P = 0.002, respectively). The SIs of the DN and GP on unenhanced T1-weighted images increased after serial administrations of linear GBCA, but not macrocyclic GBCA, in children. The number of linear GBCA administration had a linear association with the SI changes in the DN and GP.

Changes in signal intensity in the dentate nucleus at unenhanced T1-weighted magnetic resonance imaging depending on class of previously used gadolinium-based contrast agent.

Signal increase on T1-weighted magnetic resonance imaging (MRI) in the dentate nucleus has been reported in adults after multiple injections of gadolinium-based contrast agents. Linear contrast agents are more prone to cause this increase. Studies in children are still rare and focus mostly on the analysis of one single agent. To compare signal intensity chances in children after more than four injections of either only linear or only macrocyclic contrast agents. Seventy children (examined from October 2001 to February 2016) were included in this retrospective study. Signal intensities in the dentate nucleus and pons were measured on non-enhanced T1-weighted images from the first and last MRI scans. A two-sample t-test compared the dentate nucleus-to-pons signal intensity ratio differences for linear versus macrocyclic gadolinium-based contrast agent applications and also the number of applications (4-8, 9-12 or >12). Patients' charts were analysed to evaluate potentially associated neurological symptoms. Patients had contrast-enhanced MRI using either only linear (n=16) or only macrocyclic (n=54) gadolinium-based contrast agents. In patients with >12 injections, dentate nucleus-to-pons signal intensity ratio was statistically different concerning the contrast agent class (0.16±0.125 for macrocyclic vs. 0.0005±0.13 for linear agents). For linear agents, a statistically significant increase was found between 4-8 injections (-0.051±0.087) and >12 injections (0.16±0.125). No neurological symptoms were recorded in patients with signal changes. Multiple injections of linear gadolinium-based contrast agents lead to a signal increase of the dentate nucleus in children. Signal intensity increases depend on the number of injections of linear contrast agents.

Evaluation of Gadolinium Retention After Serial Administrations of a Macrocyclic Gadolinium-Based Contrast Agent (Gadobutrol): A Single-Institution Experience With 189 Patients.

There has been controversy as to whether gadobutrol, one of the widely used macrocyclic gadolinium-based contrast agents, can lead to gadolinium retention after serial injections. Our aim was to validate whether serial administrations of gadobutrol can cause signal increase in the dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance (MR) images due to gadolinium retention. A total of 189 patients who had undergone at least 2 contrast-enhanced MR scans using only gadobutrol between August 2009 and August 2016 were retrospectively included. The DN-to-pons and GP-to-thalamus signal intensity (SI) ratio differences on unenhanced T1-weighted MR images were calculated by subtracting the SI ratios at the first MR images from those at the last MR images. One-sample t tests were used to evaluate whether the SI ratio differences differed from 0. Linear regression and Pearson correlations were performed to assess correlations between SI ratio differences and various confounding variables, including the number of MR scans, mean time interval between MR scans, age, sex, history of radiation therapy or chemotherapy, and renal and liver functions. Patients underwent a mean of 5.9 ± 6.3 contrast-enhanced MR scans with a mean interval of 42.8 ± 49.5 weeks between the scans. Sixty-three patients underwent 6 or more MR scans, whereas 126 patients underwent fewer than 6 MR scans. Neither the DN-to-pons SI nor the GP-to-thalamus SI ratio differences differed significantly from 0, with mean values of -0.012 ± 0.115 (P = 0.148) and 0.012 ± 0.111 (P = 0.126), respectively. Serial administrations of gadobutrol did not result in signal increases in the DN or GP on unenhanced T1-weighted MR images due to gadolinium retention.

Magnetic Resonance Imaging for the Assessment of Long Bone Tumors.

Background:Wide resection margins of osseous tumors are associated with a low incidence of local recurrence, making accurate measurement of the intraosseous extent of primary malignant long bone tumors is crucial. We compared the intraosseous tumor extent assessed by magnetic resonance imaging (MRI) with the gross specimen to evaluate the accuracy of MRI.Methods:A total of 255 patients with primary malignant tumors in the long bones were included. Using MRI, we defined the length of tumor as the distance from the articular surface to the boundary between abnormal and normal marrow signal. The extent of the abnormal intraosseous signal was measured on unenhanced T1-weighted (T1WI) magnetic resonance images after chemotherapy. All gross surgical specimens were sectioned, and tumor extent was measured. Wilcoxon signed-rank test was used to test the differences between MRI and gross specimen findings. Spearman's correlation analysis was used to test the correlation between groups.Results:Median tumor length by gross specimen (112 mm; range, 45–300 mm) was longer than that by MRI (108 mm; range, 45–304 mm; Z = −6.916, P < 0.001). Of 255 images, tumor length was accurately represented on 27 T1WI magnetic resonance images, overestimated on 79 images, and underestimated on 149 images. The median difference between imaging and gross specimen measurements was 2.0 mm (range: 1.0–15.0 mm) for the 79 cases where tumor length was overestimated, and 5.0 mm (range: 1.0–18.0 mm) for the 149 cases where tumor length was underestimated. The Spearman correlation demonstrated a high correlation of tumor length on gross specimen with the tumor length on MRI (R = 0.99, P < 0.01).Conclusions:We conclude that preoperative MRI could be a useful method in determining intramedullary malignant bone tumor boundaries and may serve as an accepted assessment method of long bone tumors before limb-sparing surgery.

Signal Enhancement of the Dentate Nucleus at Unenhanced MR Imaging after Very High Cumulative Doses of the Macrocyclic Gadolinium-based Contrast Agent Gadobutrol: An Observational Study.

Purpose To test for measurable visual enhancement of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance (MR) images in a cohort of patients with a primary brain tumor who had not received linear gadolinium-based contrast agents (GBCAs) but had received many injections of macrocyclic GBCAs. Materials and Methods Seventeen patients with high-grade gliomas who had received 10-44 administrations of the macrocyclic GBCA gadobutrol (0.1 mmol/kg of body weight) were retrospectively included in this regional ethics committee-approved study. Two neuroradiologists inspected T1-weighted MR images with optimized window settings to visualize small differences in contrast at the baseline and at the last examination for the presence of visual DN signal enhancement. Signal intensity (SI) in the DN was normalized to the SI of the pons, and a one-sample t test was used to test for differences between baseline normalized SI (nSI) in the DN (nSIDN) and the average change in nSIDN of all postbaseline MR imaging sessions (ΔnSIDNavg) or the change in nSIDN from baseline to the last MR imaging session (ΔnSIDN). Linear and quadratic correlation analyses were used to examine the association between the number of macrocyclic GBCA administrations and ΔnSIDN or ΔnSIDNavg. Results The mean ± standard deviation number of macrocyclic GBCA administrations was 22.2 ± 10.6 administered throughout 706 days ± 454. Visually appreciable signal enhancement was observed in two patients who had received 37 and 44 macrocyclic GBCA injections. Mean ΔnSIDN was greater than zero (0.03 ± 0.05; P = .016), and there was a significant linear association between the number of macrocyclic GBCA injections and ΔnSIDN (r = 0.69, P = .002) and ΔnSIDNavg (r = 0.77, P < .001). Conclusion A small but statistically significant dose-dependent T1-weighted signal enhancement was observed in the DN after multiple macrocyclic GBCA injections. Visually appreciable enhancement in the DN was observed on contrast-optimized images in two patients who had received 37 and 44 standard doses of macrocyclic GBCAs. © RSNA, 2017 Online supplemental material is available for this article.

Erratum to: Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children.

Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naive patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children.

Sodium MRI of T1 High Signal Intensity in the Dentate Nucleus due to Gadolinium Deposition in Multiple Sclerosis.

Recently, several studies reported increased signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance imaging (MRI) as a possible consequence of multiple applications of gadolinium-based contrast agents. The aim of this study was to investigate with sodium (23 Na) MRI possible tissue abnormalities of the DN in multiple sclerosis (MS) patients. Sodium and conventional MRI were performed on a clinical 3T scanner. Total sodium concentrations (TSCs) of the DN, as well as DN-to-pons and DN-to-cerebellum SI ratios on unenhanced T1-weighted MRI were calculated. A total of 18 subjects (6/18 normal controls, 12/18 MS patients [6/12 with T1 hyperintense DN]) were investigated. There was no significant difference of TSC values of the DN in MS patients with a T1-hyperintense DN (33.70 ± 2.14 mM) compared to MS patients without those signal abnormalities (33.29 ± 1.67 mM; P = .67) or to healthy controls (33.14 ± 1.12; P = .32). Normal sodium signal in the T1-hyperintense DN in MS patients may point to relative tissue integrity despite gadolinium deposition in this area.

Correlation between high signal intensity in cerebrum nucleus on unenhanced T1-weighted MR images and number of previous gadolinium-based contrast agent administration

To explore the correlation between the number of previous gadolinium-based contrast agent administrations and high signal intensity (SI) in the cerebrum nucleus on unenhanced T1-weighted magnetic resonance images. Thirty-nine patients who previously underwent at least three contrast-enhanced brain MRI examinations were enrolled in the study. The right globus pallidus, right thalamus, right dentate nucleus, pons and white matter of right frontal lobe were selected as region of interests (ROI). The mean SIs of the ROI were measured on unenhanced T1-weighted images. The SI ratios of globus pallidus, right thalamus, right dentate nucleus and pons to white matter were calculated, respectively. The correlation of SI ratio variation with the number of previous contrast agent administration and clinical features was analyzed with Spearman analysis. The dentate nucleus-to-white matter SI ratios of the last and first MRI scan were 1.113±0.136 and 1.014±0.096(P<0.01), respectively; while the SI ratio differences between the last and first MRI scan of globus pallidus-to-white matter, the thalamus-to-white matter and the pons-to-white matter were not significant (all P>0.05). The dentate nucleus-to-white matter SI ratio was correlated with the number of previous gadolinium-based contrast agent administrations (r=0.329, P<0.05), but not with age, sex, underlying disease, treatment and history of diabetes (all P>0.05). High SI in the dentate nucleus on unenhanced T1-weighted images may be a consequence of the number of previous gadolinium-based contrast agent administrations.

Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children.

Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. This retrospective study included 50 patients, mean age: 8years (standard deviation: 4.8years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naïve patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children.

Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study

To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. We retrospectevely included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. • Gadolinium may deposit in the human brain after multiple GBCA administrations. • Gadolinium deposition is associated with increased T1W signal intensity • Increase in signal intensity is most apparent within the DN and GP • Multiple administrations of gadoxetate disodium do not increase T1W signal.