This study investigates the use of contrast-enhanced magnetic resonance (MR) in MR-guided adaptive radiotherapy (MRgART) for upper abdominal tumors. Contrast-enhanced T1-weighted MR (cT1w MR) using half doses of gadoterate was used to guide daily adaptive radiotherapy for tumors poorly visualized without contrast. The use of gadoterate was found to be feasible and safe in 5-fraction MRgART and could improve the contrast-to-noise ratio of MR images. And the use of cT1w MR could reduce the interobserver variation of adaptive tumor delineation compared to plain T1w MR (4.41 vs. 6.58, p < 0.001) and T2w MR (4.41 vs. 7.42, p < 0.001).

Gd levels are higher in tissues of animals with compromised renal function, but studies to compare levels after exposure to different macrocyclic gadolinium-based contrast agents (GBCAs) are lacking. We compared Gd levels in tissues of subtotally nephrectomised (SN) rats after repeated exposure to macrocyclic GBCAs.
Sprague-Dawley SN male rats (19 per group) received 16 injections of gadoteridol, gadobutrol, or gadoterate meglumine at 0.6 mmol Gd/kg 4 times/weeks over 4 weeks. A control group of healthy male rats (n = 10) received gadoteridol at the same dosage. Plasma urea and creatinine levels were monitored. Blood, cerebrum, cerebellum, liver, femur, kidney(s), skin and peripheral nerves were harvested for Gd determination by inductively coupled plasma-mass spectrometry at 28 and 56 days after the end of treatment.
Plasma urea and creatinine levels were roughly twofold higher in SN rats than in healthy rats at all timepoints. At day 28, Gd levels in the peripheral nerves of gadobutrol- or gadoterate-treated SN animals were 5.4 or 7.2 times higher than in gadoteridol-treated animals (p < 0.001). Higher Gd levels after administration of gadobutrol or gadoterate versus gadoteridol were also determined in kidneys (p ≤ 0.002), cerebrum (p ≤ 0.001), cerebellum (p ≤ 0.003), skin (p ≥ 0.244), liver (p ≥ 0.053), and femur (p ≥ 0.271). At day 56, lower Gd levels were determined both in SN and healthy rats for all GBCAs and tissues, except the femur.
Gd tissue levels were lower following gadoteridol exposure than following gadobutrol or gadoterate exposure.

OBJECTIVE: Intravenous administration of gadolinium-based contrast agents (GBCA) in patients with impaired renal function has been of concern to primary care physicians due to the potential worsening of renal dysfunction and nephrogenic systemic fibrosis (NSF). Our objective was to compare the potential change in estimated glomerular filtration rate (eGFR) in patients with known severe renal dysfunction (eGFR <30 ml/min), following Gadoterate meglumine (GM) administration with patients who do not receive contrast.
METHODS: An IRB-approved retrospective analysis of all patients who underwent MRI examination at our institution, for any indication, between January 2016 and September 2020.
METHODS: pre-MRI eGFR <30 ml/min within 24 h of MRI, follow-up eGFR between 48 and 96 h post-MRI, and absence of peritoneal or hemodialysis. The individuals who received GM (492 scans) were identified as cases, and those who did not receive contrast (1101 scans) were identified as controls for our study. Delta-eGFR response was calculated and covariate-adjusted, and propensity score analysis was performed.
RESULTS: No significant eGFR decrease was observed in patients who received GM compared to those who did not receive GM in our study. Also, no relationship between comorbidity, severity and contrast selection was observed.
CONCLUSIONS: The use of Gadolinium contrast in MRI is often of critical importance for determining accurate anatomic relationships, differentiation of benign from malignant lesions, or determination of resolving vs. worsening disease. Though the risk of contrast administration can never be entirely ignored, especially in patients with low eGFR, our study indicates that safe administration of GM can be performed even in patients with severe kidney disease.

Gadobutrol (GB) and gadoterate meglumine (GM) are contrast agents used for contrast-enhanced magnetic resonance angiography (CEMRA). Supraaortic vasculature (SAV) CEMRAs are used to evaluate stroke risk and neurologic symptoms. There is a need to compare the SAV CEMRA image quality obtained with GB and GM.
To intra-individually compare MRA images obtained with equimolar GB and GM at 1.5 T in the SAV.
Prospective, crossover.
Twenty-eight subjects (54 ± 13 years; 17 female).
1.5 T; three-dimensional (3D) gradient recalled echo.
Quantitative image quality was measured by normalized signal intensity (SIn ) [SIn  = SI blood/SD blood] and contrast ratio (CR) [CR = SI blood/SI muscle], determined by an observer (JWC) with 1 year of vascular imaging experience. Three radiologists (AS, PA, and MU) with (5, 5, and 6 years of) vascular imaging experience evaluated image quality by Likert-scale ratings (of image impression, wall conspicuity, and artifact absence).
SIn and CR were compared with paired t-tests or Wilcoxon signed-rank tests and Bland-Altman plots. Qualitative ratings were compared with Wilcoxon signed-rank test.
No significant difference in SIn was found between GB and GM. CRs with GB were significantly higher than GM at the right common carotid (6.9 ± 2.5 vs. 4.8 ± 1), left internal carotid (7.3 ± 2 vs. 4.4 ± 1.2), right internal carotid (7.7 ± 2.2 vs. 5 ± 1.1), and left vertebral (6.6 ± 2.2 vs. 4.5 ± 1.1) arteries. Bland-Altman plots showed relatively greater differences between GB and GM at higher CRs and SIn s. GM showed significantly higher artifact than GB (3.56 ± 0.52 vs. 3.36 ± 0.46) and significantly lower overall image quality (10.73 ± 1.45 vs. 11.26 ± 1.58) at the left vertebral artery.
At 1.5 T and equimolar demonstration, GB (0.1 mL/kg, i.e., 0.1 mmol/kg) showed higher CRs in the SAV compared to GM (0.2 mL/kg, i.e., 0.1 mmol/kg) at most vessels. Subjective image quality was not significantly different between the two agents for most vessels.
2 TECHNICAL EFFICACY: Stage 2.

OBJECTIVE: To evaluate whether dynamic contrast enhanced (DCE) MRI with a split injection of 30% followed by 70% of a standard dose (30PSD and 70PSD) of gadoterate meglumine (DOTAREM) can improve diagnosis of prostate cancer (PCa).
METHODS: MRI for twenty patients was performed on a Philips Ingenia 3T scanner without an endorectal coil followed by subsequent radical prostatectomy. DCE 3D T1-FFE data were acquired with injection of 0.03 mmol/kg followed after 2 minutes by 0.07 mmol/kg of DOTAREM. Regions-of-interest on histologically verified PCa and normal tissue in different prostate zones and the iliac artery were drawn. Average signal intensity as function of time was calculated for each ROI and fitted by using the signal intensity form of the Tofts (SI-Tofts) model to extract physiological parameters (Ktrans and ve). In addition, the scaled arterial input function (AIF) obtained from 30PSD data was used to analyze 70PSD data.
RESULTS: The AIF obtained from 30PSD data showed both first and second passes clearly and had much higher peak magnitude than AIFs from 70PSD data. Ktrans was significantly (p < 0.05) larger in PCa than in normal tissue in peripheral zone (PZ) and central zone (CZ) for both 70PSD and 70PSD data analyzed with a scaled AIF. Ktrans in cancer overlapped with that of normal tissue in the transition zone (TZ). There was no statistical difference in ve between cancer and normal tissue. Receiver operating characteristic analysis showed that use of the AIF from 30PSD data to analyze 70PSD data increased the diagnostic efficacy of Ktrans in the PZ and CZ.
CONCLUSIONS: The split dose protocol for injection of Dotarem increased diagnostic accuracy of quantitative analysis with the SI-Tofts model.

OBJECTIVE: Several studies reported gadolinium deposition in the dentate nuclei (DN) and the globus pallidus (GP) that was associated to linear GBCA administrations rather than macrocyclic. It is therefore imperative to evaluate and assess the safety of cumulative administration of gadoterate meglumine (macrocyclic). Thus, T1-weighted images (T1WI) of multiple sclerosis (MS) patients longitudinally followed for 4 years were retrospectively analyzed.
METHODS: In this study 44 patients, 10 with clinically isolated syndrome (CIS), 24 relapsing-remitting MS (RRMS) and 10 primary-progressive MS (PPMS) were examined every 6 months (first four scans) and then with a 1-year interval (last two scans). Image processing consisted in reorienting unenhanced T1WI to standard space, followed by B1 inhomogeneity correction. A patient-specific template was then generated to normalize T1WI signal intensity (SI) and segment the DN and subcortical GM structures. All structures were then transformed to each patient space in order to measure the SI in each region. The cerebellar peduncles (CP) and semi-oval (SO) white matter were then manually delineated and used as reference to calculate SI ratios in the DN and subcortical GM structures. A linear mixed-effect model was finally applied to longitudinally analyze SI variations.
RESULTS: The SI measurements performed in all structures showed no significant increases with the cumulative GBCA administration.
CONCLUSIONS: This study showed no significant SI increases within the DN and subcortical GM structures of longitudinally followed MS patients even with the cumulative administration of the macrocyclic GBCA gadoterate meglumine.

OBJECTIVE: Feature tracking for assessing myocardial strain from cardiac magnetic resonance (CMR) cine images detects myocardial deformation abnormalities with prognostic implication, e.g., in myocardial infarction and cardiomyopathy. Standards for image acquisition and processing are not yet available. Study aim was analyzing the influence of spatial resolution and contrast agent on myocardial strain results.
METHODS: Seventy-five patients underwent CMR for analyzing peak systolic circumferential, longitudinal, and radial strain. Group A included n = 50 with normal left ventricular ejection fraction, no wall motion abnormality, and no fibrosis on late enhancement imaging. Group B included n = 25 with chronic myocardial infarct. For feature tracking, steady-state free precession cine images were acquired repeatedly. (1) Native standard cine (spatial resolution 1.4 × 1.4 × 8 mm3). (2) Native cine with lower spatial resolution (2.0 × 2.0 × 8 mm3). (3) Cine equal to variant 1 acquired after administration of gadoteracid.
RESULTS: Lower spatial resolution was associated with elevated longitudinal strain (- 21.7% vs. - 19.8%; p < 0.001) in viable myocardium in group A, and with elevated longitudinal (- 17.0% vs. - 14.3%; p = 0.001), circumferential (- 18.6% vs. - 14.6%; p = 0.002), and radial strain (36.8% vs. 31.0%; p = 0.013) in infarcted myocardium in group B. Gadolinium administration was associated with reduced circumferential (- 21.4% vs. - 22.3%; p = 0.001) and radial strain (44.4% vs. 46.9%; p = 0.016) in group A, whereas strain results of the infarcted tissue in group B did not change after contrast agent administration.
CONCLUSIONS: Variations in spatial resolution and the administration of contrast agent may influence myocardial strain results in viable and partly in infarcted myocardium. Standardized image acquisition seems important for CMR feature tracking.
CONCLUSIONS: • Feature tracking is used for calculating myocardial strain from cardiac magnetic resonance (CMR) cine images. • This prospective study demonstrated that CMR strain results may be influenced by spatial resolution and by the administration of gadolinium-based contrast agent. • The results underline the need for standardized image acquisition for CMR strain analysis, with constant imaging parameters and without contrast agent.

Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2 years of age.
To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2 years of age by evaluating adverse events following contrast administration.
Pediatric patients younger than 2 years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1 mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2 h after MRI, and by phone contact using a standard questionnaire 24 h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information.
One hundred fifty exams were completed in 150 patients (median age: 12.1 months, age range: 0.25-23 months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11 months, age range: 3-23 months). Within the initial 2 h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24 h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing.
No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2 h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

Nephrogenic systemic fibrosis (NSF) is a rare life-threatening condition strongly associated with the administration of gadolinium-based contrast agents in patients with severe or endstage renal impairment.
To prospectively determine the incidence of NSF in patients with renal impairment after administration of gadoterate meglumine.
Prospective.
In all, 540 patients with moderate, severe, or endstage renal impairment, scheduled to undergo a routine contrast-enhanced MRI with gadoterate meglumine. Mean age was 69.7 ± 12.7 years (range: 21-95) with 58.4% of males.
1.5T or 3.0T, sequence according to each site practice.
Medical history, indication(s) for current MRI and adverse events were recorded for each patient. Patients were followed up over 2 years after administration with three visits separated by at least 3 months to detect any signs/symptoms suggestive of NSF.
Descriptive.
Renal impairment was graded as moderate for 69.4% of patients, severe for 16.0% and endstage for 12.1%; 2.6% had undergone a kidney transplant. Estimated glomerular filtration rate ranged from 4 to 59 mL/min/1.73 m2 except one value of 74 mL/min/1.73 m2 in a patient with kidney transplant. Central nervous system exploration was the main MRI indication (34.7%) and mean dose injected was 0.22 ± 0.09 mL/kg. Overall, 446 patients (82.6%) attended at least one follow-up visit and completed the NSF questionnaire and 329 (60.9%) attended the 2-year visit. No suspicion of NSF was reported in all 446 patients, including 119 patients with severe or endstage renal impairment. No deaths and no adverse events were reported during the MRI examination and the usual period of follow-up after gadoterate meglumine administration.
No cases of NSF were observed in the 446 patients with moderate to endstage renal impairment followed up over a maximum of 2 years after injection of gadoterate meglumine.
2 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:607-614.

OBJECTIVE: To intraindividually compare the signal-enhancing effect of 0.5 M gadoterate meglumine and 1.0 M gadobutrol in dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging of the prostate.
METHODS: Fifty patients who underwent two 3-T MR examinations of the prostate were included in this IRB-approved retrospective uncontrolled, unrandomized study. All received two scans (mean time interval, 20.5 months) including T1-weighted DCE-MR imaging, one with 0.5 M gadoterate meglumine and one with 1.0 M gadobutrol. Equimolar doses of gadolinium (0.1 mmol/kg body weight) were administered with identical injection speed (2 mL/s), resulting in differing gadolinium delivery rate. An identical region of interest (ROItz) within a BPH-node was identified on both scans. The area under the time-enhancement curve of each ROItz from 0 to 180 s post contrast arrival and pharmacokinetic parameters were calculated. Relative enhancement and signal-to-noise (SNR) and contrast-to-noise (CNR) ratios in the delayed phase at about 180 s were compared between both agents.
RESULTS: There was a significantly larger area under the time-enhancement curve (5.53 vs 4.97 p = 0.0007) and higher relative enhancement of BPH nodules (2.23 vs 1.96 p < 0.0001) with gadobutrol compared with gadoterate meglumine. There were no significant differences in SNR (44.55 vs 37.63 p = 0.12), CNR (31.22 vs 26.39 p = 0.18), and pharmacokinetic parameters Ktrans (0.31 vs 0.32 p = 0.86), Ve (1.36 vs 0.98 p = 0.13), and Kep (0.34 vs 0.36 p = 0.12).
CONCLUSIONS: At equimolar doses, increased gadolinium delivery over time using gadobutrol provides higher relative enhancement parameters in BPH nodules compared with gadoterate meglumine, but does not translate into improved SNR or CNR.
CONCLUSIONS: • At equal injection rate and equimolar total dose, gadobutrol compared with gadoterate meglumine provides a significantly greater relative enhancement in DCE-MR imaging of BPH over the first 180 s. • There are no significant differences in SNRs, CNRs, and pharmacokinetic parameters between the two GBCAs.