Evaluating blood supply changes in the osteonecrosis of the femoral head using gadobutrol-based steady-state MR angiography.

OBJECTIVES: Assess the feasibility of using gadobutrol-based steady-state (SS) MR angiography (MRA) to evaluate the blood supply changes of osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: Participants were recruited in this prospective study from December 2021 to May 2022 in a single center. The number of superior retinacular arteries (SRAs), inferior retinacular arteries (IRAs), anterior retinacular arteries (ARAs), and overall retinacular arteries (ORAs), as well as the affected rates of SRA and IRA, were determined and compared between healthy and ONFH hips and between hips across the Association Research Circulation Osseous (ARCO) staging I-IV. RESULTS: Twenty healthy and 64 ONFH hips were evaluated in 54 participants. There were significant differences between ARCO I-IV for the number of ORAs (mean of 3.5, 2.3, 1.7, and 0.8 for ARCO I-IV, respectively; p < .001), SRAs (median of 2.5, 1, 0.5, and 0 for ARCO I-IV, respectively; p < .001), and the affected rate of SRAs (20.00%, 65.22%, 77.78%, 92.31% for ARCO I-IV, respectively, p = 0.002). There were significant differences between ONFH and healthy hips for the number of ORAs (median of 5 vs. 2; p < .001), SRAs (median of 3 vs. 1; p < .001), IRAs (median of 1 vs. 1; p < .001), ARAs (median of 0 vs. 0; p = 0.04), and also the affected rate of SRAs (5.00% vs. 67.20%, p < .001) and IRAs (30% vs. 84.4%, p < .001). CONCLUSION: Gadobutrol-enhanced SS MRA is a feasible method for evaluation of hemodynamics in ONFH. CLINICAL RELEVANCE STATEMENT: Gadobutrol-enhanced magnetic resonance angiography can evaluate blood supply changes of ONFH and therefore helps to aid in the diagnosis and guide treatment of ONFH. KEY POINTS: • Gadobutrol-enhanced magnetic resonance angiography showed changes in the retinacular artery related to the severity of femoral osteonecrosis. • Gadobutrol-enhanced magnetic resonance angiography revealed a reduced blood supply to the ischemic necrotic femoral head compared to the healthy counterparts.

Prospective T1 mapping to assess gadolinium retention in brain after intrathecal gadobutrol.

PURPOSE: A possible pathway behind gadolinium retention in brain is leakage of contrast agents from blood to cerebrospinal fluid and entry into brain along perivascular (glymphatic) pathways. The object of this study was to assess for signs of gadolinium retention in brain 4 weeks after intrathecal contrast enhanced MRI. METHODS: We prospectively applied standardized T1 mapping of the brain before and 4 weeks after intrathecal administration of 0.5 mmol gadobutrol in patients under work-up of cerebrospinal fluid circulation disorders. Due to methodological limitations, a safety margin for percentage change in T1 time was set to 3%. Region-wise differences were assessed by pairwise comparison using t-tests and forest plots, and statistical significance was accepted at .05 level (two-tailed). RESULTS: In a cohort of 76 participants (mean age 47.2 years ± 17.9 [standard deviation], 47 women), T1 relaxation times remained unchanged in cerebral cortex and basal ganglia 4 weeks after intrathecal gadobutrol. T1 was reduced from 1082 ± 46.7 ms to 1070.6 ± 36.5 ms (0.98 ±2.9%) (mean [standard deviation]) (p=0.001) in white matter, thus within the pre-defined 3% safety margin. The brain stem and cerebellum could not be assessed due to poor alignment of posterior fossa structures at scans from different time points. CONCLUSION: Gadolinium retention was not detected in the cerebral hemispheres 4 weeks after an intrathecal dose of 0.5 mmol gadobutrol, implying that presence of contrast agents in cerebrospinal fluid is of minor importance for gadolinium retention in brain.

MR and fluorescence imaging of gadobutrol-induced optical clearing of red fluorescent protein signal in an in vivo cancer model.

Multimodality registration of optical and MR images in the same tissue volume in vivo may be enabled by MR contrast agents with an optical clearing (OC) effect. The goals of this study were to (a) investigate the effects of clinical MR contrast agent gadobutrol (GB) and its combinations as a potential OC agent assisting in fluorescence intensity (FI) imaging in vivo and (b) evaluate MRI as a tool for imaging of topical or systemic application of GB for the purpose of OC. Subcutaneous tumor xenografts expressing red fluorescent marker protein were used as disease models. MRI was performed at 1 T 1 H MRI using T1 -weighted 3D gradient-echo (T1w-3D GRE) sequences to measure time-dependent MR signal intensity changes by region of interest analysis after image segmentation. Topical application of 1.0 M or 0.7 M GB-containing OC mixture with water and dimethyl sulfoxide showed similar 30-40% increases of tumor FI during the initial 15 min. Afterwards, the OC effect of GB on FI and tumor/background FI ratio showed a decrease over time in the case of 1.0 M GB, unlike the 0.7 M GB mixture, which resulted in a steady increase of FI and tumor/background ratio for 15-60 min. The use of T1w-3D GRE MR pulse sequences showed that concentrated 1.0 M GB resulted in MR signal loss of the skin due to high magnetic susceptibility and that signal loss coincided with the OC effect. Intravenous injection of 0.3 mmol GB/kg resulted in a rapid but transient 40% increase of FI of the tumors. Overall, 1 T MRI enabled tracking of GB-containing OC compositions on the skin surface and tumor tissue, supporting the observation of a time-dependent FI increase in vivo.

MRA of the Supraaortic Vasculature: Comparison of Gadobutrol and Gadoterate Meglumine at 1.5 T.

BACKGROUND: 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. PURPOSE: To intra-individually compare MRA images obtained with equimolar GB and GM at 1.5 T in the SAV. STUDY TYPE: Prospective, crossover. POPULATION: Twenty-eight subjects (54 ± 13 years; 17 female). FIELD STRENGTH/SEQUENCE: 1.5 T; three-dimensional (3D) gradient recalled echo. ASSESSMENT: 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). STATISTICAL TESTS: 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. RESULTS: 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. DATA CONCLUSION: 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. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Investigation of Effects of Gadolinium-Based Contrast Agents on Uterine Contractility Using Isolated Rat Myometrium.

BACKGROUND: Despite concerns about safety, gadolinium-based contrast agents (GBCAs) are still used for abdominal and pelvic imaging during pregnancy. Researchers have mainly focused on teratogenicity, while very little is known about their possible direct effects on uterine contractility, yet free gadolinium potentially impacts contractility through interaction with calcium channels. PURPOSE: To investigate possible effects of selected GBCAs (namely gadoteridol, gadoversetamide, gadobutrol, gadoterate meglumine, and gadoxetic acid) on the contractility of rat myometrium. STUDY TYPE: In vitro organ bath study. ANIMAL MODEL: Myometria were isolated from adult (10-12 weeks old) Sprague Dawley rats, both pregnant (N = 8) and nonpregnant (N = 36). FIELD STRENGTH/SEQUENCE: NA. ASSESSMENT: Myometrial strips were suspended in tissue bath containing physiological saline and isometric contractions were recorded. GBCAs were added to the tissue bath cumulatively, and their effects on contractility parameters (quantified by amplitude, frequency, and area under contractility curve [AUC]) were evaluated by 10-minute intervals. STATISTICAL TESTS: Normality data, checked by Shapiro-Wilk test, were transformed by arcsine when needed. One- or two-way analysis of variance was performed, where appropriate, followed by Student-Newman-Keuls test. A P value of <0.05 was considered statistically significant. RESULTS: All of the assayed GBCAs elicited some alterations in the myometrial contractility in a concentration-dependent manner. Gadoterate meglumine, gadoxetic acid, and gadoversetamide caused a concentration-dependent significant attenuation in AUC (oxytocin-induced, from 100% during control period to 45.1 ± 9.0% (nonpregnant) and 59.9 ± 8.5% (pregnant), for 90 µM gadoterate meglumine; respectively), and frequency of the spontaneous and oxytocin-induced contractions. Gadobutrol and gadoteridol at highest dose significantly attenuated mean AUC and frequency of oxytocin-induced contractions of nonpregnant myometrium. DATA CONCLUSION: Results from this in vitro study indicate that GBCAs elicit modulation of myometrial contractions at clinically relevant concentrations. These effects may account, at least partially, for the known potential side effects (rare cases of miscarriages and elective abortion) of these agents. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

Optimized 3D-FLAIR sequences to shorten the delay between intravenous administration of gadolinium and MRI acquisition in patients with Menière's disease.

OBJECTIVES: The aim of this study was to shorten the 4-h delay between the intravenous administration of gadolinium and MRI acquisition for hydrops evaluation using an optimized 3D-FLAIR sequence in patients with Menière's disease. METHODS: This was a single-center prospective study including 29 patients (58 ears), recruited between November 2020 and February 2021. All patients underwent a 3-T MRI with an optimized 3D-FLAIR sequence without contrast then at 1 h, 2 h, and 4 h after intravenous administration of gadobutrol. The signal intensity ratio was quantitatively assessed with the region of interest method. We also evaluated the volume of endolymphatic structures (saccule, utricle) then the presence of endolymphatic hydrops and blood-labyrinthine barrier impairment at each acquisition time. RESULTS: For all ears, the signal intensity ratio was significantly non-inferior at 2 h compared to 4 h, with a mean geometric signal intensity ratio at 0.83 (95% CI: 0.76 to 0.90, one-sided p < .001 for non-inferiority at -30% margin). Mean volume equivalence of saccule and utricle between 2 and 4 h was proven at a ± 0.20 standardized deviation equivalence margin. Intra-rater agreements (Cohen's kappa) were all greater than 0.90 for all endolymphatic hydrops location and blood-labyrinthine-barrier impairment between the 2- and 4-h assessments. CONCLUSIONS: We demonstrated that using an optimized 3D-FLAIR sequence we could shorten the acquisition from 4 to 2 h with a high reliability for the diagnosis of endolymphatic hydrops and blood-labyrinthine-barrier impairment. CLINICAL TRIAL REGISTRATION: Clinical trial no: 38RC15.173 KEY POINTS: • Magnetic resonance imaging with delayed 3D-FLAIR sequences allows the diagnosis of endolymphatic hydrops in patients with definite Menière's disease. • An optimized 3D-FLAIR sequence with a long TR of 16000 ms and a constant flip angle allows for reducing the delay between intravenous injection of gadobutrol and MRI acquisition from 4 to 2 h to diagnose endolymphatic hydrops. • Reducing this delay between intravenous injection and MRI acquisition could have implications for clinical practice for both patients and imaging departments.

Dynamic susceptibility MR perfusion imaging of the brain: not a question of contrast agent molarity.

PURPOSE: Dynamic susceptibility contrast (DSC) perfusion-weighted MR imaging (PWI) is increasingly used in clinical neuroimaging for a range of conditions. More highly concentrated GBCAs (e.g., gadobutrol) are often preferred for DSC imaging because it is thought that more Gd is present in the volume of interest during first pass for a given equivalent injection rate. However, faster injection of a less viscous GBCA (e.g., gadoteridol) might generate a more compact and narrower contrast bolus thus obviating any perceived benefit of higher Gd concentration. This preliminary study aimed to analyze and compare DSC examinations in the healthy brain hemisphere of patients with brain tumors using gadobutrol and gadoteridol administered at injection rates of 4 and 6 mL/s. METHODS: Thirty-nine brain tumor patients studied with DSC-PWI were evaluated. A simplified gamma-variate model function was applied to calculate the mean peak, area under the curve (AUC), and full-width at half-maximum (FHWM) of concentration-time curves derived from ΔR2* signals at four different regions-of-interest (ROIs). Qualitative assessment of the derived CBV maps was also performed independently by 2 neuroradiologists. RESULTS: No qualitative or quantitative differences between the two GBCAs were observed when administered at a flow rate of 4 mL/s. At a flow rate of 6 mL/s, gadoteridol showed lower FWHM values. CONCLUSION: Gadobutrol and gadoteridol are equivalent for clinical assessment of qualitative CBV maps and quantitative perfusion parameters (FHWM) at a flow rate of 4 mL/s. At 6 mL/s, gadoteridol produces a narrower bolus shape and potentially improves quantitative assessment of perfusion parameters.

Time optimization of gadobutrol-enhanced brain MRI for metastases and primary tumors using a dynamic contrast-enhanced imaging.

BACKGROUND: Recent advances in rapid imaging techniques necessitate the reconsideration of the optimal imaging delay time for contrast-enhanced T1-weighted imaging. The aim of our study was to determine the optimal contrast-enhanced T1-weighted imaging delay time from the obtained time-signal intensity curve (TIC) using gadobutrol in patients with brain metastases, primary brain tumors, and meningiomas. METHODS: This prospective study enrolled 78 patients with brain metastases (n = 39), primary brain tumors (n = 22), or meningiomas (n = 17) who underwent 7-min dynamic contrast-enhanced imaging with single-dose gadobutrol. Based on the time-to-peak (TTP) derived from the TIC, we selected four different time points for analysis. Lesion conspicuity, enhanced rate (ER) and contrast rate (CR) of 116 index lesions were evaluated. Statistical comparisons were made for the four different time points using the Friedman test. RESULTS: Maximum TTP (305.20 ± 63.47 s) was similar across all three groups (p = 0.342). Lesion conspicuity, CR and ER increased over time in all index lesions; however, no significant difference between the 5- and 7-min images was observed. The longest diameter in all groups differed significantly among time points (p < 0.001); the perpendicular diameter did not differ between the 5- and 7-min images. CONCLUSIONS: Maximum contrast enhancement and lesion conspicuity was achieved 5-7 min after a single gadobutrol injection for brain metastases detection and for primary brain tumor/meningioma evaluation. Acquiring images 5 min after gadobutrol injection is the optimal timing for brain tumor detection during MRI work-up.

Gadolinium Accumulation and Toxicity on In Vitro Grown Stevia rebaudiana: A Case-Study on Gadobutrol.

Gadolinium-based contrast agents are molecular complexes which are extensively used for diagnostic purposes. Apart from their tremendous contribution to disease diagnostics, there are several issues related to their use. They are extremely stable complexes and potential contaminants of surface and ground waters, an issue which is documented worldwide. The irrigation of fields with contaminated surface waters or their fertilization with sludge from wastewater treatment plants can lead to the introduction of Gd into the human food supply chain. Thus, this study focused on the potential toxicity of Gd on plants. For this purpose, we have studied the molecular effects of gadobutrol (a well-known MRI contrast agent) exposure on in vitro-grown Stevia rebaudiana. The effects of gadobutrol on plant morphology, on relevant plant metabolites such as chlorophylls, carotenoids, ascorbic acids (HPLC), minerals (ICP-OES), and on the generation of free radical species (MDA assay and EPR) were assessed. Exposures of 0.01, 0.05, 0.1, 1, and 3 mM gadobutrol were used. We found a correlation between the gadobutrol dose and the plant growth and concentration of metabolites. Above the 0.1. mM dose of gadobutrol, the toxic effects of Gd+3 ions became significant.

Gadolinium Clearance in the First 5 Weeks After Repeated Intravenous Administration of Gadoteridol, Gadoterate Meglumine, and Gadobutrol to rats.

BACKGROUND: Studies of gadolinium (Gd) clearance from animals in the first weeks after administration of gadolinium-based contrast agents (GBCAs) have previously looked at solitary timepoints only. However, this does not give information on differences between GBCAs and between organs in terms of Gd elimination kinetics. PURPOSE: To compare Gd levels in rat cerebellum, cerebrum, skin, and blood at 1, 2, 3, and 5 weeks after repeated administration of macrocyclic GBCAs. STUDY TYPE: Prospective. ANIMAL MODEL: One hundred eighty male Sprague-Dawley rats randomized to three groups (n = 60/group), received intravenous administrations of gadoteridol, gadoterate meglumine, or gadobutrol (0.6 mmol/kg for each) four times/week for 5 consecutive weeks. Rats were sacrificed after washout periods of 1, 2, 3, or 5 weeks. FIELD STRENGTH/SEQUENCE: Not applicable. ASSESSMENT: Cerebellum, cerebrum, skin, and blood were harvested for Gd determination by inductively coupled plasma-mass spectrometry (15 animals/group/all timepoints). STATISTICAL TESTS: Anova and Dunnett's test (data with homogeneous variances and normal distribution). Kruskal-Wallis and Wilcoxon's rank sum tests (data showing nonhomogeneous variances or a non-normal distribution, significance levels: P < 0.05, P < 0.01, and P < 0.001). RESULTS: Gd levels in cerebellum, cerebrum, and skin were significantly lower after gadoteridol than after gadoterate and gadobutrol at all timepoints. Mean cerebellum Gd concentrations after gadoteridol, gadoterate, and gadobutrol decreased from 0.693, 0.878, and 1.011 nmol Gd/g at 1 week to 0.144, 0.282, and 0.297 nmol Gd/g at 5 weeks after injection. Similar findings were noted for cerebrum and skin. Conversely, significantly higher Gd levels were noted in blood after gadoteridol compared to gadobutrol at 1, 2, and 3 weeks and compared to gadoterate at all timepoints. DATA CONCLUSION: Gadoteridol is eliminated more rapidly from rat cerebellum, cerebrum, and skin compared to gadoterate and gadobutrol in the first 5 weeks after administration, resulting in lower levels of retained Gd in these tissues. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 5.

Clinical Efficacy of Reduced-Dose Gadobutrol Versus Standard-Dose Gadoterate for Contrast-Enhanced MRI of the CNS: An International Multicenter Prospective Crossover Trial (LEADER-75).

BACKGROUND. Gadobutrol and gadoterate are widely used macrocyclic gadolinium-based contrast agents. Given gadobutrol's higher T1 relaxivity, a reduced gadobutrol dose should achieve essentially equivalent diagnostic efficacy as a standard dose of gadoterate. OBJECTIVE. The purpose of our study was to show efficacy of a 25% reduced dose of gadobutrol is noninferior to 100% standard dose of gadoterate for contrast-enhanced MRI of the CNS. METHODS. In this international prospective multicenter open-label crossover trial (LEADER-75 [Lower Administered Dose With Higher Relaxivity: Gadovist vs Dotarem]), adult patients with known or suspected CNS pathology underwent contrast-enhanced brain MRI with standard-dose gadoterate (0.1 mmol/kg); if an enhancing lesion was identified, a second MRI with reduced-dose gadobutrol (0.075 mmol/kg) was performed within 15 days of the first MRI. Three radiologists independently reviewed images to score three primary efficacy measures: subjective lesion enhancement, lesion border delineation, lesion internal morphology. A noninferiority analysis used readers' mean scores of the primary efficacy measures. Noninferiority of reduced-dose gadobutrol to standard-dose gadoterate for primary efficacy measures was defined as the difference in score between reduced-dose gadobutrol images and unenhanced images achieving at least 80% of the difference in score between standard-dose gadoterate images and unenhanced images. A post hoc analysis was performed to directly compare contrast-enhanced images for equivalence. Secondary efficacy variables included the number of lesions detected, reader confidence, diagnostic performance for malignancy, and reader preference in side-by-side comparison. RESULTS. The efficacy analysis included 141 patients (78 men, 63 women; mean age, 58.5 ± 13.5 [SD] years). Improvement of reduced-dose gadobutrol over unenhanced images was noninferior to improvement of standard-dose gadoterate over unenhanced images using a 20% noninferiority margin for all three primary efficacy measures using mean readings (p ≤ .025). In the post hoc analysis, the mean reading for the three primary efficacy measures differed by less than 1% between reduced-dose gadobutrol and standard-dose gadoterate, supporting equivalence of all measures using a narrow ± 5% margin (p ≤ .025). The total number of lesions detected by mean reading was 301 for reduced-dose gadobutrol versus 291 for standard-dose gadoterate. Mean reader confidence was 3.3 ± 0.6 for reduced-dose gadobutrol versus 3.3 ± 0.6 for standard-dose gadoterate. Sensitivity (58.7%), specificity (91.8%), and accuracy (70.2%) for malignancy from majority reading were identical for reduced-dose gadobutrol and standard-dose gadoterate. Reader preference was not different (95% CI, -0.10 to 0.11). CONCLUSION. A 25% reduced dose of gadobutrol is noninferior to standard-dose gadoterate for contrast-enhanced brain MRI. CLINICAL IMPACT. Use of reduced-dose gadobutrol should be considered for brain MRI, particularly in patients undergoing multiple contrast-enhanced examinations. TRIAL REGISTRATION. ClinicalTrials.gov NCT03602339; EU Clinical Trials Register EudraCT 2018-00690-78.

Off-label intrathecal use of gadobutrol: safety study and comparison of administration protocols.

PURPOSE: Magnetic resonance imaging (MRI) contrast agents have been used off-label for diagnosis of cerebrospinal fluid (CSF) leaks and lately also for assessment of the glymphatic system and meningeal lymphatic drainage. The purpose of this study was to further evaluate the short- and long-term safety profile of intrathecal MRI contrast agents. METHODS: In this prospective study, we compared the safety profile of different administration protocols of intrathecal gadobutrol (GadovistTM; 1.0 mmol/ml). Gadobutrol was administered intrathecal in a dose of 0.5 mmol, with or without iodixanol (VisipaqueTM 270 mg I/ml; 3 ml). In addition, a subgroup was given intrathecal gadobutrol in a dose of 0.25 mmol. Adverse events were assessed at 1 to 3 days, 4 weeks, and after 12 months. RESULTS: Among the 149 patients, no serious adverse events were seen in patients without history of prior adverse events. The combination of gadobutrol with iodixanol did not increase the occurrence of non-serious adverse events after days 1-3. Intrathecal gadobutrol in a dose of 0.25 mmol caused less severity of nausea, as compared with the dose of 0.5 mmol. The clinical diagnosis was the major determinant for occurrence of non-serious adverse events after intrathecal gadobutrol. CONCLUSION: This prospective study showed that intrathecal administration of gadobutrol in a dose of 0.5 mmol is safe. Non-serious adverse events were to a lesser degree affected by the administration protocols, though preliminary data are given that side effects of intrathecal gadobutrol are dose-dependent.

Diagnostic efficacy of contrast-enhanced breast MRI versus X-ray mammography in women with different degrees of breast density.

BACKGROUND: Detection of breast cancer in women with high breast densities is a clinical challenge. PURPOSE: To study the influence of different degrees of breast density on the sensitivity of contrast-enhanced breast magnetic resonance imaging (CE-BMRI) versus X-ray mammography (XRM). MATERIAL AND METHODS: We performed an additional analysis of two large Phase III clinical trials (G1; G2) which included women with histologically proven breast cancers, called "index cancers." Additional cancers were detected during image reading. We compared the sensitivity of CE-BMRI and XRM in women with different breast densities (ACR A→D; Version 5). For each study, six blinded readers evaluated the images. Results are given as the "Median Reader." RESULTS: A total of 774 patients were included, 169 had additional cancers. While sensitivity of CE-BMRI for detecting all index cancers was independent of breast density (ACR A→D) (G1: 83%→83%; G2: 91%→91%) the sensitivity of XRM declined (ACR A→D) (G1: 79%→62%; G2: 82%→64%). Thus, the sensitivity difference between both imaging modalities in ACR A breasts of 3% (G1) and 9% (G2) increased to 21% (G1) and 26% (G2) in ACR D breasts. Sensitivity of CE-BMRI for detecting at least one additional cancer increased with increasing breast density (ACR A→D) (G1: 50%→73%, G2: 57%→81%). XRM's sensitivity decreased (G1: 34%→20%) or remained stable (G2: 24%→25%). CONCLUSION: CE-BMRI showed significantly higher sensitivity compared to XRM.

[The pharmacological economic analysis of application of magnetic resonance contrast mediums containing gadolinium in case of multiple sclerosis].

The article considers issues of pharmacoeconomics of applying gadolinium-containing contrast medium in diagnostic of multiple sclerosis in patients. MATERIALS AND METHODS: The MS Excel calculator was applied to estimate costs and analyze impact on the budget under treatment of multiple sclerosis exacerbations, that were diagnosed using various gadolinium-containing contrast mediums. The direct medical costs for diagnostics with gadolinium-containing contrast medium and hospitalization due to exacerbation in accordance with mandatory medical insurance system were taken into account. THE RESULTS: At the expense of reducing number of multiple sclerosis exacerbations due to the use of single-molar gadolinium-containing contrast medium (gadobutrol) as compared with semi-polar gadolinium-containing contrast medium (gadodiamide, gadoteric acid and gadoteridol) in 1000 patients it is possible to reduce financial expenses from 1,968,642 to 7,175,520 RUB. CONCLUSION: The cost of magnetic resonance imaging diagnostics with contrast enhancement and treatment of multiple sclerosis exacerbations increases in the series: gadobutrol < gadodiamide (Jodas Expoim) < gadodiamide (GE Health Care) < gadoteridol < gadoteric acid.

Decreased native renal T1 up to one week after gadobutrol administration in healthy volunteers.

BACKGROUND: Gadolinium-based contrast agents (GBCAs) are widely used in MRI, despite safety concerns regarding deposition in brain and other organs. In animal studies gadolinium was detected for weeks after administration in the kidneys, but this has not yet been demonstrated in humans. PURPOSE: To find evidence for the prolonged presence of gadobutrol in the kidneys in healthy volunteers. STUDY TYPE: Combined retrospective and prospective analysis of a repeatability study. POPULATION: Twenty-three healthy volunteers with normal renal function (12 women, age range 40-76 years), of whom 21 were used for analysis. FIELD STRENGTH/SEQUENCE: Inversion recovery-based T1 map at 3T. ASSESSMENT: T1 maps were obtained twice with a median interval of 7 (range: 4-16) days. The T1 difference (ΔT1 ) between both scans was compared between the gadolinium group (n = 16, 0.05 mmol/kg gadobutrol administered after T1 mapping during both scan sessions) and the control group (n = 5, no gadobutrol). T1 maps were analyzed separately for cortex and medulla. STATISTICAL TESTS: Mann-Whitney U-tests to detect differences in ΔT1 between groups and linear regression to relate time between scans and estimated glomerular filtration rate (eGFR) to ΔT1 . RESULTS: ΔT1 differed significantly between the gadolinium and control group: median ΔT1 cortex -98 vs. 7 msec (P < 0.001) and medulla -68 msec vs. 19 msec (P = 0.001), respectively. The bias corresponds to renal gadobutrol concentrations of 8 nmol/g tissue (cortex) and 4 nmol/g tissue (medulla), ie, ~2.4 µmol for both kidneys (0.05% of original dose). ΔT1 correlated in the gadolinium group with duration between acquisitions for both cortex (regression coefficient (ß) 16.5 msec/day, R2 0.50, P < 0.001) and medulla (ß 11.5 msec/day, R2 0.32, P < 0.001). Medullary ΔT1 correlated with eGFR (ß 1.13 msec/(ml/min) R2 0.25, P = 0.008). DATA CONCLUSION: We found evidence of delayed renal gadobutrol excretion after a single contrast agent administration in subjects with normal renal function. Even within this healthy population, elimination delay increased with decreasing kidney function. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;52:622-631.

Intrathecal use of gadobutrol for gadolinium-enhanced MR cisternography in the evaluation of patients with otorhinorrhea.

PURPOSE: Intrathecal gadolinium-enhanced MR cisternography (IGE-MRC) has a high sensitivity to detect accurate localization of cerebrospinal fluid (CSF) leakage in otorhinorrhea patients. Our purpose in this study was to describe our experience in analyzing clinically suspected CSF leakage by IGE-MRC by using gadobutrol with emphasis on its safety and diagnostic performance. METHODS: We retrospectively reviewed our imaging and clinical database for the evaluation of patients admitted to our clinic with complaints of otorhinorrhea between 2017 and 2019. Two radiologists evaluated the imaging studies independently. Consensus data was used in the analysis. Medical record review and phone call were used for the follow-up. RESULTS: Of the 85 patients included in the retrospective analysis, 82 (96.5%) had rhinorrhea and 3 (3.5%) had otorrhea. Overall, 29 patients (34.1% of all patients) underwent operation for repair of the CSF leakage site. Beta-transferrin test was available and positive in 33 patients (38.8%). Five (5.9%) patients complained headaches after the procedure and complaints were resolved with increased water intake. Postprocedurally, 3 patients (3.5%) had vertigo and 1 patient (1.2%) complained nausea but spontaneous regression were observed in a few hours. None of the patients experienced a significant complication or adverse reaction during follow-up period. Sixty-seven patients (78.8%) had medical record and telephone follow-up. Mean follow-up duration with call was 14.2 months. CONCLUSION: IGE-MRC is a minimally invasive and highly sensitive imaging technique. The current results during our follow-up demonstrate the relative safety and feasibility of IGE-MRC by using gadobutrol to evaluate CSF leakage.

Dynamic contrast-enhanced MR imaging of the prostate: intraindividual comparison of gadoterate meglumine and gadobutrol.

OBJECTIVES: 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. KEY POINTS: • 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.

Elimination of Contrast Agent Gadobutrol with Sustained Low Efficiency Daily Dialysis Compared to Intermittent Hemodialysis.

BACKGROUND: In patients with renal failure, gadolinium-based contrast agents (GBCA) can be removed by intermittent hemodialysis (iHD) to prevent possible toxic effects. There is no data on the efficacy of GBCA removal via sustained low efficiency daily dialysis (SLEDD) which is mainly used in intensive care unit (ICU) patients. METHODS: We compared the elimination of the GBCA gadobutrol in 6 ICU patients treated with SLEDD (6-12 h, 90 L dialysate) with 7 normal ward inpatients treated with iHD (4 h, dialysate flow 500 mL/min). Both groups received 3 dialysis sessions on 3 consecutive days starting after the application of gadobutrol. Blood samples were drawn before and after each session and total dialysate, as well as urine was collected. Gadolinium (Gd) concentrations were measured using mass spectrometry and eliminated Gd was calculated from dialysate and urine. RESULTS: The initial mean plasma Gd concentration was 385 ± 183 µM for the iHD and 270 ± 97 µM for the SLEDD group, respectively (p > 0.05). The Gd-reduction rate after the first dialysis session was 83 ± 9 and 67 ± 9% for the iHD and the SLEDD groups, respectively (p = 0.0083). The Gd-reduction rate after the second and third dialysis was 94-98 and 89-96% for the iHD and the SLEDD groups (p > 0.05). The total eliminated Gd was 89 ± 14 and 91 ± 4% of the dose in the iHD and the SLEDD groups, respectively (p > 0.05). Gd dialyzer clearance was 95 ± 22 mL/min and 79 ± 19 mL/min for iHD and SLEDD, respectively (p > 0.05). CONCLUSIONS: Gd-elimination with SLEDD is equally effective as iHD and can be safely used to remove GBCA in ICU patients.

Flip angle optimization for balanced SSFP: Cardiac cine imaging following the application of standard extracellular contrast agent (gadobutrol).

PURPOSE: To investigate the effect of the flip angle (FA) on the blood-myocardium contrast and to define the FA leading to highest image quality in contrast-enhanced balanced steady-state free precession (bSSFP) images. bSSFP images provide excellent contrast between myocardium and blood with high signal-to-noise and contrast-to-noise ratios (SNR, CNR). In clinical practice, bSSFP images are typically acquired following the injection of extracellular contrast agents (ECAs), although ECAs decrease the blood-myocardium contrast. MATERIALS AND METHODS: First, a theoretical optimization was performed to determine the FA that maximizes CNR in bSSFP imaging 2-20 minutes after application of ECA. Second signal-ratios, contrast, SNR, and CNR were assessed in vivo in 25 patients in bSSFP images at 1.5T acquired before (FA = 50°) and 10-15 minutes after (FAs = 50°, 80°, 90°, 100°) application of a double-dose contrast agent. Image quality was assessed by two readers. RESULTS: Simulations yielded FAs in the range of 85-100° for optimal CNR in contrast-enhanced images. In vivo comparison of conventionally acquired cine images (FA 50°) showed an increase in CNR between blood and myocardium by 57% in diastole and 78% in systole in adapted contrast-enhanced bSSFP images (FA 100°). Contrast-enhanced images with an FA of 100° were rated highest in image quality assessment. CONCLUSION: By means of FA adaptation a similar blood-myocardium contrast can be achieved in contrast-enhanced bSSFP as in unenhanced bSSFP imaging with an increase in CNR. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:255-261.

Simultaneous acquisition of MR angiography and diagnostic images of abdomen at view-sharing multiarterial phases and comparing the effect of two different contrast agents.

BACKGROUND: Simultaneous acquisition of magnetic resonance angiography (MRA) and diagnostic images is challenging in contrast-enhanced upper abdominal MRI. PURPOSE: To evaluate the image quality of MRA of the abdomen acquired simultaneously with diagnostic MR images, and to compare the contrast effect, conspicuity of aortic branches, and pancreatic lesions in MRA between gadobutrol and gadoterate meglumine. STUDY TYPE: Prospective. POPULATION: Eighty-eight patients with known and suspected upper abdominal disease. FIELD STRENGTH/SEQUENCES: 3T/4D-eTHRIVE (T1 -weighted fat-suppressed 3D fast gradient echo) for multiarterial phase imaging. ASSESSMENT: The artery-to-muscle signal intensity ratio (SIR), conspicuity of aortic branches on the axial, maximum intensity projection (MIP), and volume-rendered (VR) images, and conspicuity of focal pancreatic lesions were compared between gadobutrol and gadoterate meglumine. The diameters of aortic branches were measured on axial MRA and computed tomography angiography (CTA) images and then compared. STATISTICAL TESTS: Quantitative and qualitative data were assessed with the Mann-Whitney U-test. The diameters of aortic branches between MRA and CTA were compared with a Spearman rank correlation test. RESULTS: View-sharing multiarterial phase imaging was successfully performed in all patients. The SIRs of common hepatic artery (P = 0.0051) and left renal artery (RA) (P = 0.045), vascular conspicuities of right and left hepatic arteries (P = 0.010 and 0.030) and right and left RAs on axial (P = 0.0065 and 0.036), and that of gastroduodenal artery on MIP (P = 0.039) with gadobutrol were significantly higher than those with gadoterate meglumine. The conspicuity of focal pancreatic lesions were comparable between the gadobutrol and gadoterate meglumine (P = 0.73). The vascular diameters on MRA and CTA were strongly correlated in all aortic branches (r = 0.842-0.942, P < 0.0001). DATA CONCLUSION: High-quality MRA of the abdomen was obtained simultaneously with the diagnostic MR images using view-sharing multiarterial phase imaging that also demonstrated comparable image quality between gadobutrol and gadoterate meglumine. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017.