Dose Of Gadolinium-based Contrast Agent Research Articles

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<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<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.

Age-related changes in the distribution of intravenously administered gadolinium-based contrast agents leaked into the cerebrospinal fluid in patients with suspected endolymphatic hydrops.

The purpose of this retrospective study was to investigate the relationship between age and leakage of intravenously administered gadolinium-based contrast agents (GBCAs) into the cerebrospinal fluid (CSF) by volumetric segmentation of the whole-cranium CSF. In 30 patients clinically diagnosed with suspected endolymphatic hydrops, the three-dimensional real inversion recovery (3D-real IR) images were obtained at pre- and 4h post-intravenous administration of a single dose of GBCA. The volume of interest was set on the whole-cranium CSF in the 3D-real IR image. The signal intensity (SI)-increase of the ventricular CSF and the extra-ventricular CSF at 4h post-administration of GBCA compared to pre-administration was measured. The relationship between the age of the patient and the SI-increase was evaluated. A correlation between age and the SI-increase was observed in the whole-cranium CSF. The correlation coefficient between age and the SI-increase in the ventricular CSF was higher than that in the extra-ventricular CSF. An age-related leakage of the intravenously administered GBCAs was found in the whole-brain CSF. The age-related change in the distribution of the GBCA leakage was more prominent in the ventricular CSF than in the extra-ventricular CSF.

Assessment of Gadobutrol Safety in Combination with Ionizing Radiation Using a Preclinical MRI-Guided Radiotherapy Model.

MR-linac technology enhances the precision of therapeutic radiation by clarifying the tumor-normal tissue interface and provides the potential for adaptive treatment planning. Accurate delineation of tumors on diagnostic magnetic resonance imaging (MRI) frequently requires gadolinium-based contrast agents (GBCAs). Despite generally being considered safe, previous literature suggests that GBCAs are capable of contrast-induced acute kidney injury (AKI). It is unclear if the risk for AKI is enhanced when GBCAs are administered concurrently with ionizing radiotherapy. During irradiation, gadolinium may be liberated from its chelator which may induce AKI. The goal of this work was to determine if radiation combined with GBCAs increased the incidence of AKI. Using a preclinical MRI-guided irradiation system, where MRI acquisitions and radiation delivery are performed in rapid succession, tumor-bearing mice with normal kidney function were injected with GBCA and treated with 2, 8 or 18 Gy irradiation. Renal function was assessed on days three and seven postirradiation to assess for AKI. No clinically relevant changes in blood urea nitrogen and creatinine were observed in any combination of GBCA and radiation dose. From these data, we conclude that GBCA in combination with radiation does not increase the risk for AKI in mice. Additional investigation of multiple doses of GBCA administered concurrently with irradiation is warranted to evaluate the risk of chronic kidney injury.

MR Imaging of Endolymphatic Hydrops: Utility of iHYDROPS-Mi2 Combined with Deep Learning Reconstruction Denoising.

Purpose:MRI of endolymphatic hydrops (EH) 4 h after intravenous administration of a single dose of gadolinium-based contrast agent is used for clinical examination in some institutions; however, further improvement in image quality would be valuable for wider clinical utility. Denoising using deep learning reconstruction (Advanced Intelligent Clear-IQ Engine [AiCE]) has been reported for CT and MR. The purpose of this study was to compare the contrast-to-noise ratio of endolymph to perilymph (CNREP) between the improved hybrid of reversed image of the positive endolymph signal and the native image of the perilymph signal multiplied with the heavily T2-weighted MR cisternography (iHYDROPS-Mi2) images, which used AiCE for the three source images (i.e. positive endolymph image [PEI], positive perilymph image [PPI], MR cisternography [MRC]) to those that did not use AiCE. We also examined if there was a difference between iHYDROPS-Mi2 images with and without AiCE for degree of visual grading of EH and in endolymphatic area [EL] ratios.Methods:Nine patients with suspicion of EH were imaged on a 3T MR scanner. iHYDROPS images were generated by subtraction of PEI images from PPI images. iHYDROPS-Mi2 images were then generated by multiplying MRC with iHYDROPS images. The CNREP and EL ratio were measured on the iHYDROPS-Mi2 images. Degree of radiologist visual grading for EH was evaluated.Results:Mean CNREP ± standard deviation was 1681.8 ± 845.2 without AiCE and 7738.6 ± 5149.2 with AiCE (P = 0.00002). There was no significant difference in EL ratio for images with and without AiCE. Radiologist grading for EH agreed completely between the 2 image types in both the cochlea and vestibule.Conclusion:The CNREP of iHYDROPS-Mi2 images with AiCE had more than a fourfold increase compared with that without AiCE. Use of AiCE did not adversely affect radiologist grading of EH.

Iron Sucrose as MRI Contrast Agent in Ischemic Stroke Model

Despite the growing concern about the safety of gadolinium-based contrast agents (GBCAs), they are still the most commonly used. Ferumoxytol, as an off-label alternative MRI contrast agent, cannot be administered by a rapid bolus for dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI). To assess the feasibility of iron sucrose (IS) as a contrast agent for MR angiography (MRA) and DSC-PWI. Prospective animal model. Thirty-six normal rats (16 for MRA, 20 for biocompability tests) and 36 occlusion of the middle cerebral artery (MCAO) model rats. 3.0T; head and neck angiography, using a fast spoiled gradient-recalled-echo (FSPGR) sequence and DSC-MRI using echo planar imaging(EPI) sequence. MRA was performed on normal rats to examine the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of different doses of IS. DSC-PWI was performed on MCAO rats at 0, 24, 48, and 72 hours postreperfusion to investigate the lesion detectability of IS. Arterial spin labeling (ASL) and DSC-PWI enhanced by GBCAs were conducted on MCAO rats as controls. Kruskal-Wallis test was used to compare qualitative assessment. One-way analysis of variance (ANOVA) was used to compare the parametric data. Pearson's r values were evaluated between relative cerebral blood flow(rCBF)-ASL, rCBF-DSCIS , and rCBF obtained from DSC-PWI enhanced by GBCA. The mean SNR and CNR of the common carotid artery at doses of 10 mg Fe/kg of IS were comparable with the standard dose of GBCAs (SNR: 68.04 ± 12.55 vs. 67.72 ± 14.66; CNR: 23.78 ± 7.21vs. 21.63 ± 6.83). In MCAO rat models, rCBF and relative cerebral blood volume (rCBV) of ipsilateral striatum declined (0.72 ± 0.14, 0.86 ± 0.11) with prolonged relative mean transit time (rMTT) and relative time-to-peak (rTTP) (1.27 ± 0.24, 1.07 ± 0.03) following occlusion. Hyperperfusion was observed in all rats at 48 and 72 hours postreperfusion, in 4/6 rats at 24 hours postreperfusion for IS-mediated DSC-PWI. IS may be an effective contrast agent for both MRA and DSC-PWI in ischemic stroke models. 1 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;52:836-849.

Safety of Gadolinium-Based Contrast Agents in Patients with Stage 4 and 5 Chronic Kidney Disease: a Radiologist's Perspective.

Gadolinium-based contrast agents (GBCAs) have been used for contrast-enhanced magnetic resonance imaging (MRI) since 1988 with >450 million intravenous GBCA doses administered worldwide and overall have had an excellent safety record (1,2). Numerous studies have demonstrated the benefit of GBCAs for a variety of diagnostic indications including improving sensitivity and specificity for malignancy, demyelination, central nervous system malignancy, and infection (3⇓⇓⇓–7). Initially, it was thought that GBCAs would be safer than iodinated contrast media for patients with kidney disease because they are less nephrotoxic at clinically administered doses (8). Although some case reports have linked AKI to GBCA administration, most cases involve patients with advanced renal disease or diabetes and with doses that exceed US Food and Drug Administration (FDA) recommendations (8). The safety of GBCAs in patients with kidney disease came into question in 2006 when a strong association was found between the use of GBCAs in patients with severe kidney disease and the development of nephrogenic systemic fibrosis (NSF) (9⇓–11). NSF results in fibrosis of the skin and internal organs and can be fatal. A conclusive mechanism of causation for NSF has not been determined. Several mouse models of NSF have been developed to investigate the underlying pathophysiology; however, they tend to use doses which are higher than those approved by the FDA and older linear agents (12⇓–14). A confounding issue is that many people with severe kidney disease received multiple exposures to GBCAs and did not develop NSF. Conversely, patients with only one administration of a GBCA have developed NSF (15,16). It is unclear if this could at least partially relate to interspecies differences. Multiple factors may contribute, most notably patient-specific risk factors and the stability of the GBCA, which is …

Brain tissue gadolinium retention in pediatric patients after contrast-enhanced magnetic resonance exams: pathological confirmation.

Retained gadolinium from gadolinium-based contrast agents (GBCAs) used in MR exams has been inferred based on signal changes on serial brain MRI and subsequently demonstrated pathologically in adults. Retention has been similarly inferred in children but pathological demonstration in pediatric patients is limited. The long-term effects of retained gadolinium are unknown but are potentially of greater concern in children given their increased vulnerability from continuing development and their expected longer period of exposure. Several factors can influence gadolinium retention. In adults as well as in children, greater accumulation has been demonstrated based on MR signal changes with linear compared with macrocyclic gadolinium chelates, attributed to lower chelate affinity with linear agents. Effects of age at exposure on retention are unknown, while differences in GBCA washout rates are still under investigation and might affect gadolinium retention relative to time of GBCA administration. The purpose of this study was to confirm whether gadolinium brain deposits are present in pediatric patients who received GBCAs and to quantify the amounts present. Brain autopsy specimens from 10 pediatric patients between 1year and 13years of age who underwent at least one contrast-enhanced MR exam were analyzed for elemental gadolinium using inductively coupled plasma mass spectrometry. Brain samples included white matter, basal ganglia (putamen, globus pallidus), thalamus, dentate nucleus and tumor tissue as available. Type and dose of contrast agent, number and timing of contrast-enhanced MR exams and renal function (estimated glomerular filtration rate [eGFR]) were documented for each child. Patient exposures ranged from 1 dose to 20 doses of GBCAs including both macrocyclic and linear ionic agents. Gadolinium was found to be present in brain tissue in all children and was generally highest in the globus pallidus. Those who received only macrocyclic agents showed lower levels of gadolinium retention. This study demonstrates pathological confirmation of gadolinium retention in brain tissue of a series of pediatric patients exposed to GBCAs including not only linear ionic agents but also macrocyclic agents with both nonionic and ionic compounds. The distribution and deposition levels in this small pediatric population are comparable with the findings in adults. While the clinical significance of these deposits remains unknown, at this point it would be prudent to exert caution and avoid unnecessary use of GBCAs in pediatric patients.

Long-Term Evaluation of Gadolinium Retention in Rat Brain After Single Injection of a Clinically Relevant Dose of Gadolinium-Based Contrast Agents.

PurposeThe aim of this study was to investigate the presence and chemical forms of residual gadolinium (Gd) in rat brain after a single dose of Gd-based contrast agent.MethodsFour groups of healthy rats (2 sacrifice time-points, n = 10/group, 80 rats in total) were randomized to receive a single intravenous injection of 1 of the 3 Gd-based contrast agents (GBCAs) (gadoterate meglumine, gadobenate dimeglumine, or gadodiamide) or the same volume of 0.9% saline solution. The injected concentration was 0.6 mmol/kg, corresponding to a concentration of 0.1 mmol/kg in humans after body surface normalization between rats and humans (according to the US Food and Drug Administration recommendations). Animals were sacrificed at 2 washout times: 1 (M1) and 5 (M5) months after the injection. Total Gd concentrations were determined in cerebellum by inductively coupled plasma mass spectrometry. Gadolinium speciation was analyzed by size-exclusion chromatography coupled to inductively coupled plasma mass spectrometry after extraction from cerebellum.ResultsA single injection of a clinically relevant dose of GBCA resulted in the detectable presence of Gd in the cerebellum 1 and 5 months after injection. The cerebellar total Gd concentrations after administration of the least stable GBCA (gadodiamide) were significantly higher at both time-points (M1: 0.280 ± 0.060 nmol/g; M5: 0.193 ± 0.023 nmol/g) than those observed for macrocyclic gadoterate (M1: 0.019 ± 0.004 nmol/g, M5: 0.004 ± 0.002 nmol/g; P < 0.0001). Gadolinium concentrations after injection of gadobenate were significantly lower at both time-points (M1: 0.093 ± 0.020 nmol/g; M5: 0.067 ± 0.013 nmol/g; P < 0.05) than the Gd concentration measured after injection of gadodiamide. At the 5-month time-point, the Gd concentration in the gadoterate group was also significantly lower than the Gd concentration in the gadobenate group (P < 0.05). Gadolinium speciation analysis of the water-soluble fraction showed that, after injection of the macrocyclic gadoterate, Gd was still detected only in its intact, chelated form 5 months after injection. In contrast, after a single dose of linear GBCAs (gadobenate and gadodiamide), 2 different forms were detected: intact GBCA and Gd bound to soluble macromolecules (above 80 kDa). Elimination of the intact GBCA form was also observed between the first and fifth month, whereas the amount of Gd present in the macromolecular fraction remained constant 5 months after injection.ConclusionsA single injection of a clinically relevant dose of GBCA is sufficient to investigate long-term Gd retention in the cerebellar parenchyma. Administration of linear GBCAs (gadodiamide and gadobenate) resulted in higher residual Gd concentrations than administration of the macrocyclic gadoterate. Speciation analysis of the water-soluble fraction of cerebellum confirmed washout of intact GBCA over time. The quantity of Gd bound to macromolecules, observed only with linear GBCAs, remained constant 5 months after injection and is likely to represent a permanent deposition.

Evaluation of 3.0-T MRI Brain Signal after Exposure to Gadoterate Meglumine in Women with High Breast Cancer Risk and Screening Breast MRI.

Background Otherwise healthy women at high risk for breast cancer undergo annual contrast agent-enhanced breast MRI screening examinations, resulting in high cumulative doses of gadolinium-based contrast agents (GBCAs). Whereas the majority of studies showed no T1 signal ratio increase in deep brain nuclei after more than six doses of macrocyclic GBCA, this has not been explored in a healthy study population. Purpose To assess whether women who are administered large cumulative doses of macrocyclic GBCA with breast MRI at high-risk breast cancer screening exhibit T1 alterations in deep brain nuclei. Materials and Methods In this prospective study from November 2017 to March 2018, healthy women who were either exposed (because of high-risk breast cancer screening) or unexposed to only gadoterate meglumine underwent 3.0-T brain MRI with a dedicated head coil, including T1 mapping and magnetization-prepared rapid gradient-echo sequences. T1 times and T1 signal intensities were measured in the dentate nucleus (DN), globus pallidus (GP), crus anterior of capsula interna (CA), and pons. Ratios of DN to pons and GP to CA were calculated, and univariable Pearson correlation coefficients were calculated. Multivariable analysis included partial regression analysis. Results This study evaluated 25 women (mean age, 51 years ± 11 [standard deviation]) who were exposed to a mean GBCA dose of 129 mL (median 112 mL; range, 70-302 mL) and 16 women (mean age, 37 years ± 10) who were never exposed to any GBCA. Infratentorially, no correlation between cumulative GBCA dose and T1 times or signal intensity ratios was detected (P = .66 and .55, respectively). In partial correlation analysis by considering age as a confounder, there was a moderate negative correlation between GP-to-CA ratio and GBCA dose (r = -0.40; P = .01) but not for GP T1 times (r = 0.19; P = .24). Conclusion After administration of relatively large cumulative doses of gadoterate dimeglumine, healthy women at high risk for breast cancer who underwent annual contrast-enhanced breast MRI screening did not exhibit T1 signal increase in deep brain nuclei at 3.0-T MRI. © RSNA, 2019.

Switching from linear to macrocyclic gadolinium-based contrast agents halts the relative T1 -Weighted signal increase in deep gray matter of children with brain tumors: A retrospective study.

Studies have shown signal intensity (SI) changes in the brains of children exposed to repeated doses of a gadolinium-based contrast agent (GBCA). The trajectory of changes in relative dentate nucleus (DN) and globus pallidus (GP) SI in children receiving multiple doses of GBCA will alter when switched from linear to macrocyclic agents. Retrospective longitudinal. Thirty-five children, age range 0.5-17.0 years, undergoing brain tumor follow-up between 2006 and 2017. Unenhanced T1 WI, serial scans at both 1.5T and 3T. Regions of interest were drawn on DN, GP, and SIs normalized to middle cerebellar peduncle (DN/MCP) and cerebral white matter (GP/CWM), respectively. A change in SI ratios as a function of dose (slope gradient) calculated according to the type of contrast agent received: linear only, macrocyclic only, or switchover from linear to macrocyclic. For the latter, gradients were compared before and after switchover. The effect of anticancer treatment on slope gradient was tested. One-sample t-test or Mann-Whitney U-test for slope gradients differing from zero. Independent samples t-tests to compare slope gradient groups. Paired sample t-tests to compare slope gradients before and after switchover. A significant (P < 0.05) increase in SI ratio was observed following multiple doses of linear but not macrocyclic agents: mean percentage increase per dose in SI was 0.063% vs. -0.034% for DN/MCP, and 0.078% vs. 0.004% for GP/CWM ratios. A significant (P < 0.05) change of SI trajectory in the DN/MCP ratio was demonstrated when switching from a linear to macrocyclic agent. There was no difference in SI trajectory between patients who had anticancer therapies and those who did not, DN/MCP P = 0.740; GP/BWM P = 0.694. Switching from linear to macrocyclic gadolinium-based contrast agents seems to halt the relative T1 signal increase in deep gray matter in children. Anticancer treatments appeared to have no impact on the trajectory of T1 SI. 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:288-295.

Impact of nasopharyngeal irradiation and gadolinium administration on changes in T1 signal intensity of the dentate nucleus in nasopharyngeal malignancy patients without intracranial abnormalities.

Irradiation has been found to increase T1 signal intensity (SI) of the dentate nucleus (DN) by accelerating the gadolinium deposition in patients after multiple gadolinium-based contrast agent (GBCA) administrations. Several reports have focused on this phenomenon in patients with brain tumors; however, data in patients receiving irradiation with no intracranial abnormalities (NIAs) are lacking. To explore how nasopharyngeal irradiation affected SI changes on unenhanced T1 -weighted imaging (T1 WI) in the DN in nasopharyngeal malignancy (NPM) patients who presented with NIAs and who had multiple injection doses (IDs) of linear GBCAs. Single-center, retrospective, case-control study. In all, 132 subjects: 66 NPM patients, 66 matched controls. 1.5T and 3T/T1 WI, T2 WI, and fluid-attenuated inversion recovery (FLAIR). Radiation doses (RDs) were calculated by a radiotherapy technician. SIs were measured by a radiologist. The DN-to-cerebellar white matter (CWM) SI ratios and their relative percentage change (Rchange ) were compared. Shapiro-Wilk test, paired t-test, independent t-test, Mann-Whitney U-test, Pearson and Spearman correlation. DN/CWM b ratios or R change from the NPM group were significantly higher than those from the control group (P < 0.001). No significant difference of DN/CWM a ratios was found between the two groups (P > 0.05). Positive correlations between R change , DN/CWM b ratio, and the number of IDs were found in both the NPM and control groups (P < 0.01). The overall changes of DN/CWM b ratio or R change between NPM and control groups were higher for the higher-IDs subgroup (≥10) than for the lower-IDs subgroup (<10). Nasopharyngeal irradiation appeared to increase SI in T1 WI in NPM patients with NIAs and repeated GBCA administrations relative to control patients who also underwent GBCA administrations, especially when IDs ≥10. However, no significant association between R change and RDs to the DNs was found. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:250-259.

Quantification of Endolymphatic Space Volume after Intravenous Administration of a Single Dose of Gadolinium-based Contrast Agent: 3D-real Inversion Recovery versus HYDROPS-Mi2.

Purpose:Recently, the use of 3D real inversion recovery (3D-real IR) imaging has been proposed for the evaluation of endolymphatic hydrops (EH). This method shows similar contrast between the endolymphatic and perilymphatic spaces and surrounding bone compared with the hybrid of reversed image of positive endolymph signal and native image of perilymph signal multiplied with heavily T2-weighted MR cisternography (HYDROPS-Mi2) image. We measured the volume of the endolymphatic space using 3D-real IR and HYDROPS-Mi2 images, and compared the measurements obtained with both techniques.Methods:HYDROPS-Mi2 and 3D-real IR images were obtained for 30 ears from 15 patients with clinical suspicion of EH; imaging was performed 4 h after intravenous administration of a single dose of gadolinium-based contrast agent. We measured the volume of the endolymphatic space in the cochlea and vestibule by manually drawing the regions of interest. The correlation between endolymphatic volume determined from HYDROPS-Mi2 images and 3D-real IR images was calculated.Results:There was a strong positive linear correlation between the cochlear and vestibular endolymphatic volume determined from HYDROPS-Mi2 and 3D-real IR images. The Spearman’s rank correlation coefficient (ρ) between the measurements obtained with both images was 0.805 (P < 0.001) for the cochlea and 0.826 (P < 0.001) for the vestibule.Conclusion:The endolymphatic volume measured using 3D-real IR images strongly correlated with that measured using HYDROPS-Mi2 images. Thus, 3D-real IR imaging might be a suitable method for the measurement of endolymphatic volume.

Gadolinium-based contrast agents: why nephrologists need to be concerned.

The hegemony of gadolinium-based contrast agent-induced adverse events stretches beyond those who have renal impairment. 'Nephrogenic' systemic fibrosis is a misnomer: gadolinium-based contrast agents are the known trigger for the disease; kidney impairment is a risk factor. Impaired (true) glomerular filtration may be one catalyst for gadolinium-based contrast agent-induced adverse events, but it is increasingly evident that the same cluster of symptoms occurs in patients with normal renal function. It has been known for nearly 30 years that gadolinium-based contrast agents distribute and are cleared according to a three compartment model. Single doses of gadolinium-based contrast agents can trigger 'nephrogenic' systemic fibrosis in nondialysis dependent patients. Manifestations have occurred years after exposure. Renal insufficiency alone is not an adequate explanation for 'nephrogenic' systemic fibrosis, and the continuum of its symptoms with the adverse events reported by patients with normal renal function clearly indicate that the physiologic reactions are largely undefined. Gadolinium-based contrast agents should be used with extreme caution.

Efficacy of diffusion-weighted imaging in symptomatic and asymptomatic multiple sclerotic plaques.

Introduction:Magnetic resonance imaging (MRI) currently accompanies clinical findings in disease diagnosis, patients’ follow-up, assessment of drugs complications, and evaluation of treatment response. Although contrast-enhanced MRI (CE-MRI) is considered as the imaging modality of choice for multiple sclerosis (MS), due to disease chronicity, applying multiple doses of gadolinium-based contrast agents (GBCAs) increases the risk of nephrogenic syndrome in patients with acute (ARF) and chronic renal syndromes (CRF). Moreover, the effect of gadolinium on the fetus is not well-known in pregnant patients. Therefore, this study evaluates the possibility of replacing postcontrast images with physiologically based MRI sequences such as diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC).Method:We prospectively evaluated 26 patients with known multiple sclerosis. The patients with MS attacks and the asymptomatic patients who were referred for follow-up were enrolled. Conventional MRI including postcontrast T1W, DWI, and ADC were performed for all patients. The signal intensity (SI) of all enhancing and nonenhancing plaques of more than 10 × 10 mm size were investigated in all sequences and analyzed.Results:A total of 83 plaques were detected in T2-FLAIR sequences of which 51 plaques were enhanced (68%) after gadolinium administration. While 42 MS plaques had hypersignal intensity in DWI (56%), 32 plaques had iso- or hyposignal intensities in DWI (44%). No statistically significant values were obtained.Conclusion:Although DWI could not replace CE-MRI, using these two modalities together could increase detection of active MS plaques and alter patients’ therapy and prognosis.

Reducing the dose of gadolinium-based contrast agents for DCE-MRI guided SBRT: The effects on inter and intra observer variability for preoperative target volume delineation in early stage breast cancer patients

Background and purposeThis study aimed to determine the effects of reducing the dose of contrast agent (CA) in a DCE-MRI scan on inter- and intra-observer variability in the context of MRI-guided target volume delineation for stereotactic body radiation therapy of early stage breast cancer patients. This is in hopes of reducing risks to patients due to findings of residual CA in brain and bone. Materials and methodsTwenty-three patients receiving neoadjuvant radiation therapy were enrolled. Five observers delineated the gross target volume (GTV) using DCE-MRI for guidance. 14/23 patients received the full clinical dose of CA and 9/23 received half. Clinical target volumes (CTV) were created through a 0.5 cm uniform expansion. Several metrics were used to quantify the inter and intra-observer reliability including differences in delineation volume and the reliability coefficient. ResultsThere were no significant differences in the volume, though half contrast patients had a lower median for both the GTV and CTV (difference of 0.26 cm3 and 1.27 cm3, respectively). All indicated a high degree of agreement between and within observers for both dose groups. However, the full dose group had a greater inter-observer variability, most likely due to the full CA causing more pronounced enhancement in the periphery. ConclusionsReducing the dose of contrast agent did not significantly alter inter- or intra-observer variability. These results have prompted our centre to reduce the dose of gadolinium in all patients enrolled in the SIGNAL trial.

MRI gadolinium dosing on basis of blood volume.

Gadolinium-based contrast agents (GBCAs) for MRI are generally administrated in direct relationship to body weight. Instead, we propose a model for GBCA dosing on the basis of blood volume. The new method was tested by exploring the associations between MRI T1 mapping indices and weight in the MESA (Multi-Ethnic Study of Atherosclerosis. Empirically derived methods based on sex and body habitus were used to calculate blood volumes. GBCA dose (in mL) in blood (in L) was calculated as the injected volume divided by the blood volume (i.e., DBV). Of the 1219 participants with cardiac MRI T1 mapping, 845 studies had standard dose of 0.15 mmol/kg (cohort 1) and 166 studies had 30 mL of GBCA regardless of weight (cohort 2). We also created a specific cohort with similar DBV (N = 357; cohort 3). Postcontrast blood relaxation rate R1blood and DBV were significantly correlated (R = 0.641; P < 0.001). R1blood was significantly associated with weight in cohort 1 and 2, but the correlation coefficient was positive for cohort 1 and negative for cohort 2, indicating GBCA overdosing in cohort 1 and underdosing in cohort 2 in heavy relative to lean subjects. R1blood was not associated with weight in cohort 3. Simulated results demonstrated that less contrast should be administrated for heavy subjects compared to the conventional weight-based dose. GBCA dosing on the basis of blood volume could improve the efficacy and safety of contrast-enhanced MRI studies. This method could be implemented to standardize dose and augment precision in study comparisons.

Editors' note: Journal Club: MRI reveals acute inflammation in cortical lesions during early MS

In “Journal Club: MRI reveals acute inflammation in cortical lesions during early MS,” Bateman et al. discussed an article that showed evidence of early leukocortical lesions in multiple sclerosis (MS), suggesting that gray matter pathology may be related to blood–brain barrier breakdown. Commenting on the journal club article, Drs. Cyprian Olchowy and Anna Olchowy point to the fact that patients in the study discussed received triple the recommended dose of gadolinium-based contrast agent (GBCA). They explain that the study started before the link between gadolinium administrations and increased signal intensity in the dentate nucleus and globus pallidus was discovered in the human brain. They add that currently, a study with monthly injections of triple-dose GBCA would not be possible due to justified safety concerns. In “Journal Club: MRI reveals acute inflammation in cortical lesions during early MS,” Bateman et al. discussed an article that showed evidence of early leukocortical lesions in multiple sclerosis (MS), suggesting that gray matter pathology may be related to blood–brain barrier breakdown. Commenting on the journal club article, Drs. Cyprian Olchowy and Anna Olchowy point to the fact that patients in the study discussed received triple the recommended dose of gadolinium-based contrast agent (GBCA).

Progressive T1 Shortening of the Dentate Nucleus in Patients With Multiple Sclerosis: Result of Multiple Administrations of Linear Gadolinium Contrast Agents Versus Intrinsic Disease.

The purpose of this article is to study the effect of the administration of multiple IV doses of gadolinium-based contrast agent on the intrinsic T1 hyperintensity in the dentate nucleus and globus pallidus in patients with multiple sclerosis (MS). A retrospective review of imaging in patients with relapsing-remitting MS was performed. Images of 20 patients who received four or more doses of gadolinium-based contrast agent were reviewed. Patients received the linear agent gadopentetate dimeglumine before 2011 and the macrocyclic agent gadobutrol from 2011 onward. Dentate nucleus-to-pons and globus pallidus-to-thalamus signal intensity (SI) ratios were evaluated. SI ratios were compared over time with multiple injections of gadolinium. Similar SI ratios were evaluated for six patients who received gadopentetate dimeglumine and then underwent multiple subsequent MRI studies without contrast agent administration. The increase in the dentate nucleus-to-pons SI ratio after multiple administrations of the linear agent gadopentetate dimeglumine (mean = 1.44; SD = 2.50) was significantly higher than that with the macrocyclic agent gadobutrol (mean = -0.11; SD = 2.33) (p < 0.001). The globus pallidus-to-thalamus and dentate nucleus-to-CSF ratios also increased with multiple contrast injections over time, but the changes were not found to be statistically significant. The increase in SI in the dentate nucleus was not observed in patients who stopped receiving contrast injections, after showing a previous increase over time with gadolinium. In patients with MS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images and was significantly greater with the administration of a linear agent than with a macrocyclic agent. This increase in SI over time is likely a reflection of gadolinium deposition and not due to intrinsic disease, as previously postulated.

Brain Irradiation and Gadobutrol Administration in Pediatric Patients with Brain Tumors: Effect on MRI Brain Signal Intensity.

Purpose To determine whether treatment affects MRI signal intensity in pediatric patients with primary brain tumors independent of the administration of macrocyclic gadolinium-based contrast agents (GBCAs). Materials and Methods This retrospective, single-center study included 78 patients (mean age, 7.7 years ± 5.4) with primary brain tumors who underwent macrocyclic GBCA-enhanced MRI from 2015 to 2018. Three groups were compared: (a) patients who had undergone radiation therapy (37 patients, 26 of whom had undergone concurrent chemotherapy), (b) patients who had undergone chemotherapy only (17 patients), and (c) patients who had received no treatment ("no-treatment group," 24 patients). The signal intensity in the globus pallidus (GP), thalamus, dentate nucleus (DN), and pons was measured on unenhanced T1-weighted images. GP-to-thalamus and DN-to-pons signal intensity ratios were compared among groups with analysis of variance by using the Kruskal-Wallis test, followed by post hoc pairwise tests with Tukey adjustment, and were analyzed relative to group, total cumulative doses of GBCA, age, and sex with multivariable linear models. Results The mean number of GBCA-enhanced MRI examinations in the radiation therapy, chemotherapy-only, and no-treatment groups was 7.11, 7.29, and 4.96, respectively (P < .01 for the radiation therapy and chemotherapy groups compared with the no-treatment group). The DN-to-pons ratio in the radiation therapy group was higher than that in both the no-treatment group and the chemotherapy-only group (P < .01 for both). There was no significant difference in the DN-to-pons ratios between the chemotherapy-only group and the no-treatment group (P = .99). The GP-to-thalamus ratios did not differ among all three groups (P = .09). There was no dose-dependent effect of GBCA on the DN-to-pons and GP-to-thalamus ratios when adjusting for the effects of treatment (P = .21 and P = .38, respectively). Conclusion Brain irradiation contributes to a higher dentate nucleus signal intensity in pediatric patients with brain tumor independent of the administration of macrocyclic gadolinium-based contrast agents. © RSNA, 2018.

Gd accumulation in tissues of healthy mice upon repeated administrations of Gadodiamide and Gadoteridol

The aim of this work was to investigate, by five different administration protocols, the impact of the dosage, the time passed after the last injection and the frequency of injections, on accumulation and distribution of Gd-containing species in the body tissues of healthy mice upon repeated injections of Gadolinium Based Contrast Agents (GBCAs).Gadodiamide and Gadoteridol have been compared. The amount of Gd retained in several tissues/organs (cerebrum, cerebellum, spleen, liver, kidneys, eyes, skin, bone and muscle) has been assessed by ICP-MS upon administration of the GBCAs i) at three weeks or three months after the last administration, ii) when one, three or twelve doses of GBCA were administered and iii) when administrations were made every two weeks.Gd was found in all tissues after the administration of Gadodiamide. Conversely, in the case of Gadoteridol, Gd was detected only in spleen, kidneys, liver and bone. The amounts of Gd found in spleen, liver and kidneys markedly decrease upon increasing the time that has passed after the last administration, whereas, in the case of Gadodiamide, the decrease of Gd found in bone, cerebrum and cerebellum appears to occur at a much slower rate. Overall, areas of long term deposition appear to be bone and spleen for both GBCAs.In conclusion, our findings demonstrate that intravenous multiple administrations of GBCAs is associated with extensive multiorgan retention which is reduced but not eliminated by the use of the macrocyclic Gadoteridol as well as by adopting reduced and/or less frequent dosing.