Unenhanced T1-weighted Magnetic Resonance Images 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.

Pulvinar Sign, Stroke and Their Relationship with Fabry Disease: A Systematic Review and Metanalysis.

Background: Fabry disease (FD) is the second most common lysosomal storage disorder. This disorder affects multiple systems that include the cardiac, renal, and nervous system. The pulvinar sign (PS) is a relatively common sign seen in patients with FD. The PS is a bilateral, symmetrical pulvinar high signal relative to the signal intensity seen on unenhanced T1-weighted brain MR imaging. Methods: We conducted a systematic review with metanalysis to analyze the pool prevalence of the disorder. We used the Moose Guidelines and PRISMA Protocol for this systematic review and Robins 1 to access the BIAS of the study. To analyze the pool prevalence, we used “Open Meta-Analysis” software for analyzing the study. We used “Review Manager 5.4” to analyze the odds ratio between patients with and without the PS and patients with and without stroke among patients with FD. Results: We gather 12 studies from 2003 to 2021 for the analysis of this study. The pool prevalence of the study was 0.146 (0.076–0.217) (62/385 cases) with a 95% CI (0.0945–0.415) (p < 0.01). The prevalence was much higher in men (59 cases) than in women (3 cases). There was no relationship between the pulvinar sign and patients with stroke among patients with Fabry disease. Odds ratio 1.97 95% CI (0.35–11.21), p = 0.44; Tau2 = 0.77. There seems to be a correlation with renal failure (RF), but there were very few studies to conduct a metanalysis with RF. Conclusions: The prevalence of the PS among all studies was 23.9%; the prevalence of this sign is higher among males. We found that FD patients who had strokes did not have higher odds of presenting with the Pulvinar Sign than the FD patients who did not suffer a stroke. Patients with renal failure and FD seem to have a higher tendency to have the PS, but there were not enough studies to analyze that theory. Overall, we think the pulvinar sign has a poor prognostic value in patients with Fabry’s disease.

Absence of T1 Hyperintensity in the Brain of Thalassemia Patients after Multiple Administrations of Gadobutrol

Gadolinium based contrast agents (GBCA) are used in magnetic resonance imaging (MRI) in order to improve the detection and the characterization of pathophysiologic processes. Many studies have reported an association between increased signal intensities (SI) on unenhanced T1-weighted MRI images in different brain regions and the history of repeated intravenous administrations of GBCAs in patients with normal renal function. We conducted a prospective study aimed to evaluate signal changes in the dentate nucleus (DN), globus pallidus (GP), pons, and thalamus (normalized to the deep cerebellum white matter) in T1-MRI images after serial injections of Gadobutrol for the study of the heart in patients with thalassemia.Among the thalassemic patients who underwent a brain MRI within a pilot study for iron overload assessment, we selected two groups of patients: 15 patients transfused and chelated with≥4 Gadobutrol administrations at a high dose (0.2 mmol/Kg per scan) and 8 thalassemia patients who never received Gadobutrol. Moreover, we included 13 healthy subjects who never received Gadobutrol as control group. Iron overload was assessed by the T2* technique.Signal intensity (SI) ratios in all regions were comparable among the three groups (see Table) and were not correlated with the number of Gadobutol administrations. No correlation was detected between SI ratios and T2* values.It is important to underline that thalassemia patients represent an high-risk population for the GBCA accumulation, due to the fact that, in presence of siderosis, ferric ions can compete with Gadolinium ions for the ligand, destabilizing the gadolinium complex. Nevertheless, our study describes the lack of increased SI after repeated administration of Gadobutrol, a nonionic macrocyclic agent. All our patients were chelated when they received the GBCA. Different studies showed the ability of all three iron chelators to chelate other metals. So, a potential role of chelation therapy may be supposed. [Display omitted] DisclosuresPepe:Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.

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.

Diffusion-Weighted MR Imaging of Primary and Secondary Lung Cancer: Predictive Value for Response to Transpulmonary Chemoembolization and Transarterial Chemoperfusion.

To examine predictive value of apparent diffusion coefficient (ADC) in diffusion-weighted imaging (DWI) for response of patients with primary and secondary lung neoplasms undergoing transpulmonary chemoembolization (TPCE) and transarterial chemoperfusion (TACP) treatment. Thirty-one patients (mean age ± SD 64 ± 12.4 y) with 42 lung target lesions (13 primary and 29 secondary) underwent DWI and subsequent ADC analysis on a 1.5T MR imaging scanner before and 30.3 days ± 6.4 after first session of TPCE or TACP. After 3.1 treatment sessions ± 1.4 performed in 2- to 4-week intervals, morphologic response was analyzed by comparing tumor diameter and volume before and after treatment on unenhanced T1-weighted MR images. On a per-lesion basis, response was classified according to Response Evaluation Criteria In Solid Tumors. Threshold ADC increase of 20.7% indicated volume response with 88% sensitivity and 78% specificity (area under the curve [AUC]= 0.84). Differences between ADC changes in volume response groups were significant (P= .002). AUC for volume response predicted by ADC before treatment was 0.77. Median ADC before treatment and mean ADC change were 1.09× 10-3 mm2/second and 0.36× 10-3 mm2/second ± 0.23, 1.45× 10-3 mm2/second and 0.14× 10-3 mm2/second ± 0.16, and 1.30× 10-3 mm2/second and 0.06× 10-3 mm2/second ± 0.19 in partial response, stable disease, and progressive disease groups. In primary lung cancer lesions, strong negative correlation of ADC change with change in diameter (ρ=-.87, P < .001) and volume (ρ=-.66, P= .016) was found. In metastases, respective correlation coefficients were ρ=-.18 (P= .356) and ρ=-.35 (P= .061). ADC quantification shows considerable diagnostic value for predicting response and monitoring TPCE and TACP treatment of patients with primary and secondary lung neoplasms.

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.

Age-Dependent Signal Intensity Changes in the Structurally Normal Pediatric Brain on Unenhanced T1-Weighted MR Imaging.

Various pathologic and nonpathologic states result in brain parenchymal signal intensity changes on unenhanced T1-weighted MR imaging. However, the absence of quantitative data to characterize typical age-related signal intensity values limits evaluation. We sought to establish a range of age-dependent brain parenchymal signal intensity values on unenhanced T1WI in a sample of individuals (18 years of age or younger) with structurally normal brains. A single-center retrospective study was performed. Gadolinium-naïve pediatric patients with structurally normal MR brain imaging examination findings were analyzed (n = 114; 50% female; age range, 68 days to 18 years). ROI signal intensity measurements were obtained from the globus pallidus, thalamus, dentate nucleus, pons, and frontal lobe cortex and subcortical white matter. Multivariable linear regression was used to analyze the relationship between signal intensity values and age. Results demonstrated a statistically significant association between signal intensity values and linear age in all neuroanatomic areas tested, except the frontal gray matter, (P < .01). There were no statistically significant differences attributable to patient sex. Age-dependent signal intensity values were determined on unenhanced T1WI in structurally normal pediatric brains. Increased age correlated with increased signal intensity in all brain locations, except the frontal gray matter, irrespective of sex. The biologic mechanisms underlying our results remain unclear and may be related to chronologic changes in myelin density, synaptic density, and water content. Establishing age-dependent signal intensity parameters in the structurally normal pediatric brain will help clarify developmental aberrations and enhance gadolinium-deposition research by providing an improved understanding of the confounding effect of age.

Visible T1-hyperintensity of the dentate nucleus after multiple administrations of macrocyclic gadolinium-based contrast agents: yes or no?

ObjectivesTo investigate the appearance of visible dentate nucleus (DN) T1-hyperintensity and quantify changes in DN/pons (DN/P) signal intensity (SI) ratio in MS patients after the exclusive administration of macrocyclic GBCAs.Materials and methodsOne hundred forty-nine patients with confirmed MS were evaluated. Patients received at least two administrations of gadobutrol (n = 63), gadoterate (n = 57), or both (n = 29). Two experienced neuroradiologists in consensus evaluated unenhanced T1-weighted MR images from all examinations in each patient for evidence of visible DN hyperintensity. Thereafter, SI measurements were made in the left and right DN and pons on unenhanced T1-weighted images from the first and last scans. A two-sample t test compared the DN/P SI ratios for patients with and without visible T1-hyperintensity.ResultsVisible T1-hyperintensity was observed in 42/149 (28.2%) patients (19 after gadobutrol only, 15 after gadoterate only, 8 after both), typically at the 4th or 5th follow-up exam at 3–4 years after the initial examination. Significant increases in DN/P SI ratio from first to last examination were determined for patients with visible T1-hyperintensity (0.998 ± 0.002 to 1.153 ± 0.016, p < 0.0001 for gadobutrol; 1.003 ± 0.004 to 1.110 ± 0.014, p < 0.0001 for gadoterate; 1.004 ± 0.011 to 1.163 ± 0.032, p = 0.0004 for both) but not for patients without visible T1-hyperintensity (p > 0.05; all groups).ConclusionMultiple injections of gadobutrol and/or gadoterate can lead to visible and quantifiable increases in DN/P SI ratio in some patients with MS.

Signal Hyperintensity on Unenhanced T1-Weighted Brain and Cervical Spinal Cord MR Images after Multiple Doses of Linear Gadolinium-Based Contrast Agent.

The clinical implications of gadolinium deposition in the CNS are not fully understood, and it is still not known whether gadolinium tends to be retained more in the brain compared with the spinal cord. In this study, we assessed the effects of linear gadolinium-based contrast agents on the T1 signal intensity of 3 cerebral areas (dentate nucleus, globus pallidus, and the less studied substantia nigra) and the cervical spinal cord in a population of patients with MS. A single-center population of 100 patients with MS was analyzed. Patients underwent 2-16 contrast-enhanced MRIs. Fifty patients received ≤5 linear gadolinium injections, and 50 patients had ≥6 injections: Fifty-two patients had both Gd-DTPA and gadobenate dimeglumine injections, and 48 patients received only gadobenate dimeglumine. A quantitative analysis of signal intensity changes was independently performed by 2 readers on the first and last MR imaging scan. The globus pallidus-to-thalamus, substantia nigra-to-midbrain, dentate nucleus-to-middle cerebellar peduncle, and the cervical spinal cord-to-pons signal intensity ratios were calculated. An increase of globus pallidus-to-thalamus (mean, +0.0251 ± 0.0432; P < .001), dentate nucleus-to-middle cerebellar peduncle (mean, +0.0266 ± 0.0841; P = .002), and substantia nigra-to-midbrain (mean, +0.0262 ± 0.0673; P < .001) signal intensity ratios after multiple administrations of linear gadolinium-based contrast agents was observed. These changes were significantly higher in patients who received ≥6 injections (P < .001) and positively correlated with the number of injections and the accumulated dose of contrast. No significant changes were detected in the spinal cord (mean, +0.0008 ± 0.0089; P = .400). Patients with MS receiving ≥6 linear gadolinium-based contrast agent injections showed a significant increase in the signal intensity of the globus pallidus, dentate nucleus, and substantia nigra; no detectable changes were observed in the cervical spinal cord.

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.

Gadolinium Deposition in Deep Brain Structures: Relationship with Dose and Ionization of Linear Gadolinium-Based Contrast Agents.

Dose-dependent association between hyperintensity in deep brain structures on unenhanced T1WIs and gadolinium-based contrast agent administrations has been demonstrated with subsequent histopathological confirmation of gadolinium deposition. Our aim was to determine whether greater exposure to linear gadolinium-based contrast agent administration is associated with higher signal intensity in deep brain structures on unenhanced T1-weighted MR imaging. Secondary objective was to compare signal intensity differences between ionic and nonionic linear gadolinium-based contrast agents. Subjects with secondary-progressive MS originally enrolled in a multicenter clinical trial were studied retrospectively. Eighty subjects (high-exposure cohort) received 9 linear gadolinium-based contrast agent administrations (30 nonionic/50 ionic) between week -4 and year 1 and a tenth administration by year 2. One hundred fifteen subjects (low-exposure cohort) received 2 administrations (40 nonionic/75 ionic) between week -4 and year 1 and a third administration by year 2. Signal intensities were measured on unenhanced T1WIs by placing sample-points on the dentate nucleus, globus pallidus, caudate, thalamus, pons, and white matter, and they were normalized using the following ratios: dentate/pons, globus pallidus/white matter, caudate/white matter, and thalamus/white matter. Between week -4 and year 1, subjects in the high-exposure cohort showed increased signal intensity ratios in all regions (P < .01), while the low-exposure cohort showed only an increase in the dentate nucleus (P = .003). Between years 1 and 2, when both cohorts received only 1 additional gadolinium-based contrast agent, no significant changes were observed. In the high-exposure cohort, significantly higher changes in signal intensity ratios were observed in subjects receiving linear nonionic than in those receiving linear ionic gadolinium-based contrast agents. Hyperintensity in deep brain structures from gadolinium deposition is related to the number of doses and the type of linear gadolinium-based contrast agent (nonionic greater than ionic) administration.

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.

Central nervous system gadolinium accumulation in patients undergoing periodical contrast MRI screening for hereditary tumor syndromes

BackgroundPatients with hereditary tumor syndromes undergo periodical magnetic resonance imaging (MRI) screening with Gadolinium contrast. Gadolinium accumulation has recently been described in the central nervous system after repeated administrations. The prevalence and rate of accumulation in different subgroups of patients are unknown. Neither are the mechanism nor clinical impact. This may cause uncertainty about the screening. To explore the prevalence and rate of Gadolinium accumulation in different subgroups, we retrospectively analyzed MRIs of patients with von Hippel-Lindau disease (VHL) and Tuberous Sclerosis Complex (TSC).MethodsWe determined the prevalence and rate of accumulation in the dentate nucleus and globus pallidus on unenhanced T1-weighted MRI from VHL and TSC patients. We compared the signal intensities of these regions to the signal intensity of the pons. We evaluated the impact of number of MRIs, kidney function and liver function on Gadolinium accumulation.ResultsTwenty eight VHL patients and 24 TSC patients were included. The prevalence of accumulation in the dentate nucleus and globus pallidus increased linearly according to number of Gadolinium enhanced MRIs and was higher in the VHL group (100%). A significant linear correlation between number of MRIs and increased signal intensity was observed in the VHL group.ConclusionsGadolinium accumulation occurs in almost all patients undergoing contrast MRI screening after >5 MRIs. We advocate a screening protocol for patients with hereditary tumor syndromes that minimizes the Gadolinium dose. This can be accomplished by using a single administration to simultaneously screen for brain, spine and/or abdominal lesions, using an MRI protocol focused on either VHL- or TSC-specific lesions. Higher prevalence and rate of accumulation in VHL patients may be explained by the typical vascular leakage accompanying central nervous system hemangioblastomas.

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.

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.

Gadolinium Brain Deposition after Macrocyclic Gadolinium Administration: A Pediatric Case-Control Study.

Purpose To determine whether signal intensity (SI) in T1 sequences as a potential indicator of gadolinium deposition increases after repeated administration of the macrocyclic gadolinium-based contrast agents (GBCAs) gadoteridol and gadoterate meglumine in a pediatric cohort. Materials and Methods This retrospective case-control study of children with brain tumors who underwent nine or more contrast material-enhanced brain magnetic resonance (MR) imaging studies from 2008 to 2015 was approved by the local ethics board. Informed consent was obtained for MR imaging. Twenty-four case patients aged 5-18 years and appropriate control patients with nonpathologic MR neuroimaging findings (and no GBCA administration), matched for age and sex, were inculded. SI was measured on unenhanced T1-weighted MR images for the following five regions of interest (ROIs): the dentate nucleus (DN), pons, substantia nigra (SN), pulvinar thalami, and globus pallidus (GP). Paired t tests were used to compare SI and SI ratios (DN to pons, GP to thalamus) between case patients and control patients. Pearson correlations between relative signal changes and the number of GBCA administrations and total GBCA dose were calculated. Results The mean number of GBCA administrations was 14.2. No significant differences in mean SI for any ROI and no group differences were found when DN-to-pons and GP-to-pulvinar ratios were compared (DN-to-pons ratio in case patients: mean, 1.0083 ± 0.0373 [standard deviation]; DN-to-pons ratio in control patients: mean, 1.0183 ± 0.01917; P = .37; GP-to-pulvinar ratio in case patients: mean, 1.1335 ± 0.04528; and GP-to-pulvinar ratio in control patients: mean, 1.1141 ± 0.07058; P = .29). No correlation was found between the number of GBCA administrations or the total amount of GBCA administered and signal change for any ROI. (Number of GBCA applications: DN: r = -0.254, P = .31; pons: r = -0.097, P = .65; SN: r = -0.194, P = .38; GP: r = -0.175, P = .41; pulvinar: r = -0.067, P = .75; total amount of administered GBCA: DN: r = 0.091, P = .72; pons: r = 0.106, P = .62; SN: r = -0.165, P = .45; GP: r = 0.111, P = .61; pulvinar: r = 0.173, P = .42.) Conclusion Multiple intravenous administrations of these macrocyclic GBCAs in children were not associated with a measurable increase in SI in T1 sequences as an indicator of brain gadolinium deposition detectable by using MR imaging. Additional imaging and pathologic studies are needed to confirm these findings. © RSNA, 2017 Online supplemental material is available for this article.