Extracellular Gadolinium-based Contrast Agent Research Articles

Pharmacokinetics, safety, and tolerability of the novel tetrameric gadolinium-based MRI contrast agent gadoquatrane in healthy Chinese and Japanese men: Two randomized dose-escalation studies including concentration–QTc modeling

PurposeTo investigate the pharmacokinetics, safety, and tolerability of the novel tetrameric high-relaxivity gadolinium-based contrast agent gadoquatrane in Japanese (Study 1) and Chinese men (Study 2). Participants and methodsIn two similarly designed single-center, randomized, single-blind, placebo-controlled, consecutive-cohort dose-escalation studies, healthy volunteers were randomly assigned to intravenous administration of gadoquatrane (0.01–0.1 mmol gadolinium/kg body weight) or placebo. Study procedures included blood sampling and collection of urine for pharmacokinetic analyses and safety assessments. ResultsTwenty-five healthy Japanese men (mean age ± standard deviation: 26±5.9 years) and 23 healthy Chinese men (31±7.6 years old) were evaluated. In both studies, the pharmacokinetic profile of gadoquatrane was characterized by rapid distribution of the drug into the extracellular space and fast renal elimination. Postdose gadolinium concentrations rapidly declined with a geometric mean effective half-life of 1.3–1.4 h. The exposure increased approximately dose-proportionally with dose. The body weight-normalized volume of distribution was constant across dose levels (0.21–0.24 L/kg). Total recovery of gadolinium in urine amounted to 82–95 % (Study 1) and 96–99 % (Study 2) of the dose administered.Only a few mild, transient adverse events were reported, none of which gave rise to any safety concerns. Exploratory drug concentration–QTc modeling indicated no risk of a clinically relevant QT/QTc prolongation at the anticipated diagnostic dose. ConclusionGadoquatrane was safe and well tolerated at all doses tested. The pharmacokinetic profile was essentially the same as that of other extracellular macrocyclic gadolinium-based contrast agents and was consequentially also similar for Japanese and Chinese participants.

Late/delayed gadolinium enhancement in MRI after intravenous administration of extracellular gadolinium-based contrast agents: is it worth waiting?

The acquisition of images minutes or even hours after intravenous extracellular gadolinium-based contrast agents (GBCA) administration ("Late/Delayed Gadolinium Enhancement" imaging; in this review, further termed LGE) has gained significant prominence in recent years in magnetic resonance imaging. The major limitation of LGE is the long examination time; thus, it becomes necessary to understand when it is worth waiting time after the intravenous injection of GBCA and which additional information comes from LGE. LGE can potentially be applied to various anatomical sites, such as heart, arterial vessels, lung, brain, abdomen, breast, and the musculoskeletal system, with different pathophysiological mechanisms. One of the most popular clinical applications of LGE regards the assessment of myocardial tissue thanks to its ability to highlight areas of acute myocardial damage and fibrotic tissues. Other frequently applied clinical contexts involve the study of the urinary tract with magnetic resonance urography and identifying pathological abdominal processes characterized by high fibrous stroma, such as biliary tract tumors, autoimmune pancreatitis, or intestinal fibrosis in Crohn's disease. One of the current areas of heightened research interest revolves around the possibility of non-invasively studying the dynamics of neurofluids in the brain (the glymphatic system), the disruption of which could underlie many neurological disorders.

The combination of non-contrast abbreviated MRI and alpha foetoprotein has high performance for hepatocellular carcinoma screening

ObjectivesThis study aimed to compare two abbreviated MRI (AMRI) protocols to complete MRI for HCC detection: non-contrast (NC)-AMRI without/with alpha foetoprotein (AFP) and dynamic contrast-enhanced (Dyn)-AMRI.MethodsThis retrospective single-center study included 351 patients (M/F: 264/87, mean age: 57y) with chronic liver disease, who underwent MRI for HCC surveillance between 2014 and 2020. Two reconstructed AMRI sets were obtained based on complete MRI: NC-AMRI (T2-weighted imaging (WI) + diffusion-WI) and Dyn-AMRI (T2-WI + dynamic T1-WI) and were assessed by 2 radiologists who reported all suspicious lesions, using LI-RADS/adapted LI-RADS classification. The reference standard was based on all available patient data. Inter-reader agreement was assessed and MRI diagnostic performance was compared to the reference standard.ResultsThe reference standard demonstrated 83/351 HCC-positive patients (prevalence: 23.6%, median size: 22 mm, and positive MRIs: 83/631). Inter-reader agreement was substantial for all sets. Sensitivities of Dyn-AMRI and complete MRI (both 92.8%) were similar, higher than NC-AMRI (72.3%, p < 0.001). Specificities were not different between sets. NC-AMRI + AFP (92.8%) had similar sensitivity to Dyn-AMRI and complete MRI. In patients with small size HCCs (≤ 2 cm), sensitivities of Dyn-AMRI (85.3%) and complete MRI (88.2%) remained similar (p = 0.564), also outperforming NC-AMRI (52.9%, p < 0.05). NC-AMRI + AFP had similar sensitivity (88.2%) to Dyn-AMRI and complete MRI (p = 0.706 and p = 1, respectively).ConclusionsDyn-AMRI has similar diagnostic performance to complete MRI for HCC detection, while both outperform NC-AMRI, especially for small size HCCs. NC-AMRI + AFP demonstrates similar sensitivity to Dyn-AMRI and complete MRI.Clinical relevance statementDue to the low sensitivity of ultrasound for hepatocellular screening, new screening methods are needed. Abbreviated MRI (AMRI) is a candidate, especially non-contrast AMRI with serum alpha foetoprotein as the acquisition time is low, without the need for contrast medium injection.Key Points• Dynamic contrast-enhanced abbreviated MRI using extracellular gadolinium-based contrast agent and complete MRI have similar diagnostic performance for hepatocellular carcinoma detection in an at-risk population.• Non-contrast abbreviated MRI with alpha foetoprotein has similar diagnostic performance to dynamic contrast-enhanced abbreviated MRI and complete MRI, including when considering small size hepatocellular carcinoma ≤ 2 cm.• Non-contrast abbreviated MRI and dynamic contrast-enhanced abbreviated MRI can be performed in 7 and 10 min, excluding patient setup time.

Preclinical Profile of Gadoquatrane: A Novel Tetrameric, Macrocyclic High Relaxivity Gadolinium-Based Contrast Agent.

ObjectivesThe aim of this report was to characterize the key physicochemical, pharmacokinetic (PK), and magnetic resonance imaging (MRI) properties of gadoquatrane (BAY 1747846), a newly designed tetrameric, macrocyclic, extracellular gadolinium-based contrast agent (GBCA) with high relaxivity and stability.Materials and MethodsThe r1-relaxivities of the tetrameric gadoquatrane at 1.41 and 3.0 T were determined in human plasma and the nuclear magnetic relaxation dispersion profiles in water and plasma. The complex stability was analyzed in human serum over 21 days at pH 7.4 at 37°C and was compared with the linear GBCA gadodiamide and the macrocyclic GBCA (mGBCA) gadobutrol. In addition, zinc transmetallation assay was performed to investigate the kinetic inertness. Protein binding and the blood-to-plasma ratio were determined in vitro using rat and human plasma. The PK profile was evaluated in rats (up to 7 days postinjection). Magnetic resonance imaging properties were investigated using a glioblastoma (GS9L) rat model.ResultsThe new chemical entity gadoquatrane is a macrocyclic tetrameric Gd complex with one inner sphere water molecule per Gd (q = 1). Gadoquatrane showed high solubility in buffer (1.43 mol Gd/L, 10 mM Tris-HCl, pH 7.4), high hydrophilicity (logP −4.32 in 1-butanol/water), and negligible protein binding. The r1-relaxivity of gadoquatrane in human plasma per Gd of 11.8 mM−1·s−1 (corresponding to 47.2 mM−1·s−1 per molecule at 1.41 T at 37°C, pH 7.4) was more than 2-fold (8-fold per molecule) higher compared with established mGBCAs. Nuclear magnetic relaxation dispersion profiles confirmed the more than 2-fold higher r1-relaxivity in human plasma for the clinically relevant magnetic field strengths from 0.47 to 3.0 T. The complex stability of gadoquatrane at physiological conditions was very high. The observed Gd release after 21 days at 37°C in human serum was below the lower limit of quantification. Gadoquatrane showed no Gd3+ release in the presence of zinc in the transmetallation assay. The PK profile (plasma elimination, biodistribution, recovery) was comparable to that of gadobutrol. In MRI, the quantitative evaluation of the tumor-to-brain contrast in the rat glioblastoma model showed significantly improved contrast enhancement using gadoquatrane compared with gadobutrol at the same Gd dose administered (0.1 mmol Gd/kg body weight). In comparison to gadoterate meglumine, similar contrast enhancement was reached with gadoquatrane with 75% less Gd dose. In terms of the molecule dose, this was reduced by 90% when compared with gadoterate meglumine. Because of its tetrameric structure and hence lower number of molecules per volume, all prepared formulations of gadoquatrane were iso-osmolar to blood.ConclusionsThe tetrameric gadoquatrane is a novel, highly effective mGBCA for use in MRI. Gadoquatrane provides favorable physicochemical properties (high relaxivity and stability, negligible protein binding) while showing essentially the same PK profile (fast extracellular distribution, fast elimination via the kidneys in an unchanged form) to established mGBCAs on the market. Overall, gadoquatrane is an excellent candidate for further clinical development.

Pharmacoeconomic Study on the Application of Magnetic Resonance Imaging with Gadoxetic Acid in Addition to Contrast-Enhanced Computed Tomography in Diagnosis of Hepatocellular Carcinoma

Objective: to evaluate pharmacoeconomic advantages of the application of magnetic resonance imaging (MRI) with hepatobiliary-specific contrast agent – gadoxetic acid in addition to contrast-enhanced computed tomography (CT) in the diagnosis of hepatocellular carcinoma (HCC).Material and methods. We performed the modeling and obtained the results of the pharmacoeconomic study: effectiveness analysis, cost analysis, and cost-effectiveness analysis. The cost analysis included only direct medical costs (the cost of contrast-enhanced CT, gadolinium-based contrast agent (GBCA) for MRI, and therapy per a patient with verified HCC diagnosis after diagnostic procedures). The financing was performed from the Compulsary Health Insurance Fund. The calculations were made per 1 patient.Results. The effectiveness analysis showed that the diagnostic scheme CT + MRI with gadoxetic acid was the most effective complex for the diagnosis of HCC because its application provided 50% of patients with 5-year overall survival (4.8 years), which was significantly higher than in patients who were diagnosed HCC with CT + MRI with extracellular GBCA (2.3 years) or CT (3.7 years). The cost-effectiveness analysis showed that the diagnostic scheme with gadoxetic acid was dominant because each disability-adjusted life year required fewer costs (14 862 rubles) in comparison with CT + MRI with extracellular GBCA (25 293 rubles) or CT (46 540 rubles). According to the results of the incremental cost-effectiveness ratio analysis, the application of the diagnostic complex with gadoxetic acid was characterized by the lowest rate of additional costs per 1 disability-adjusted life year.Conclusion. The pharmacoeconomic study showed that the application of MRI with a hepatospecific contrasting agent – gadoxetic acid in addition to contrast-enhanced CT was an effective and economically beneficial method of early HCC diagnosis.

Contrast-enhanced body magnetic resonance angiography: how we do it.

This review introduces the basic principles of contrast-enhanced magnetic resonance (MR) angiography and details four contrast-enhanced MR angiography sequences for body imaging with extracellular gadolinium-based contrast agents in pediatric patients. Specifically, this review covers (1) respiratory-navigated, cardiac-gated MR angiography; (2) time-resolved MR angiography; (3) conventional MR angiography; and (4) modified spoiled gradient echo variants. We present and discuss indications, technical considerations, sequence optimization, advantages and disadvantages, along with practical tips and illustrative case examples for each sequence.

Steady State Magnetic Resonance Angiography of the Thoracic Aorta Using Inversion-recovery Steady-State Free Precession and a High Relaxivity Contrast Agent.

To evaluate image quality and aortic dimension measurement accuracy of high resolution, motion compensated steady-state magnetic resonance angiography (SS-MRA) with a high relaxivity, extracellular fluid gadolinium-based contrast agent compared with standard first-pass contrast enhanced MRA (FP-CEMRA) in patients with thoracic aortic aneurysms. Sixty-nine patients (mean age, 51.7 y, 25% female) diagnosed with thoracic aortic aneurysms who underwent MRA on a 1.5 T scanner using FP-CEMRA and SS-MRA techniques were retrospectively identified. Quantitative analysis was performed by measuring the aortic diameters at 6 locations within the thoracic aorta for each technique. Two radiologists independently performed the qualitative analysis by assessing the image quality (1 to 5), presence of artifact (1 to 4), signal-to-noise (1 to 4), contrast-to-noise (1 to 4), and wall conspicuity (1 to 4) in the aorta at 4 different locations: the aortic root, the ascending aorta, the aortic arch, and the descending aorta. The aortic dimensions obtained by SS-MRA had a good correlation with FP-CEMRA. Means for the aortic diameters between the FP-CEMRA and the SS-MRA at all 6 locations demonstrated minimal mean differences (0.013 to 0.044 mm).Qualitative assessment of aorta at 4 locations by 2 reviewers demonstrated that SS-MRA had on average superior image quality at the aortic root and ascending aorta for both reviewers (P<0.05) and at the descending aorta for one reader (P<0.05). Otherwise, both techniques were comparable at the ascending aorta. SS-MRA demonstrated less artifact at the aortic root and the ascending aorta (P<0.05). Aortic dimension measurements provided by SS-MRA with a high relaxivity, extracellular fluid gadolinium-based contrast agent are comparable to the conventional FP-CEMRA. Furthermore, SS-MRA qualitatively demonstrated comparable to better overall image quality than FP-CEMRA at different aortic locations. Therefore, SS-MRA may provide a comparable alternative, or complementary examination to conventional FP-CEMRA in patients who have difficulty breath holding, or in situations where contrast bolus timing was poor.

Intravenous gadolinium-based hepatocyte-specific contrast agents (HSCAs) for contrast-enhanced liver magnetic resonance imaging in pediatric patients: what the radiologist should know.

Hepatocyte-specific contrast agents (HSCAs) are a group of intravenous gadolinium-based MRI contrast agents that can be used to characterize hepatobiliary pathology. The mechanism by which these agents are taken up by hepatocytes and partially excreted into the biliary tree improves characterization of hepatic lesions and biliary abnormalities relative to conventional extracellular gadolinium-based contrast agents (GBCAs). This manuscript presents an overview of HSCA use in pediatric patients with the intent to provide radiologists a guide for clinical use. We review available HSCAs and discuss dosing and age specifications for use in children. We also review various hepatic and biliary indications for HSCA use in children, with emphasis on the imaging characteristics distinct to HSCAs, as well as discussion of pitfalls one can encounter when imaging with HSCAs. Given the growing concern regarding gadolinium deposition in soft tissues and brain, we also discuss safety of HSCA use in children.

Gadoxetate disodium-related event during image acquisition: a prospective multi-institutional study for better MR practice.

To acknowledge the facts of gadoxetate disodium-related events in Japan and to achieve better MR practice by analyzing large cohort data with various MR parameters. This prospective multi-institutional study included 1993 patients (1201 men, mean age 66.4 ± 12.8years), who received dynamic MRI with gadoxetate disodium (gadoxetate group, n = 1646) or extracellular gadolinium-based contrast agents (other-GBCAs group, n = 347) between January and November 2016. Recorded data covered adverse reactions including dyspnea, breath-hold failure during acquisition, respiratory artifacts rated with a four-point scale, and MR parameters. We compared data between the two groups in whole cohort and age-, gender-, and institution-matched subcohort using χ2 test (n = 640). Logistic regression model was used to reveal independent associates of substantial artifacts in arterial phase imaging. Transient dyspnea rarely occurred in gadoxetate or other-GBCAs group (both < 1%). Gadoxetate group (vs other-GBCAs group) showed higher rates of breath-hold failure (whole cohort, 18.2% vs 7.7%, p < 0.001; subcohort, 17.6% vs 6.3%, p < 0.001) and substantial artifacts in arterial phase (7.2% vs 2.2%, p = 0.001; 7.4% vs 1.7%, p = 0.001). With single arterial phase protocol, substantial artifacts under gadoxetate were independently associated with age (odds ratio [OR] = 1.04, p < 0.001), hearing difficulty (OR = 2.92, p = 0.008), breath-hold practice required (OR = 1.61, p = 0.039), and short acquisition time (OR = 0.43, p = 0.005). Multiple arterial phase acquisition did not reduce the incident rate of substantial artifacts. Gadoxetate disodium was associated with breath-hold failure and substantial artifacts in arterial phase imaging, but not with dyspnea in Japan. Shorter acquisition time should be used to sustain image quality in gadoxetate disodium-enhanced arterial phase imaging. • Gadoxetate disodium administration leads to breath-hold failure and substantial imaging artifacts in arterial phase MRI in Japan. • Contrast agent-induced dyspnea in arterial phase and adverse reactions are rare in Japan, without showing differences between gadoxetate disodium or other extracellular gadolinium-based contrast agents. • Shorter acquisition time significantly reduces gadoxetate-induced imaging artifacts in the arterial phase.

Physicochemical and Pharmacokinetic Profiles of Gadopiclenol: A New Macrocyclic Gadolinium Chelate With High T1 Relaxivity.

ObjectivesWe aimed to evaluate gadopiclenol, a newly developed extracellular nonspecific macrocyclic gadolinium-based contrast agent (GBCA) having high relaxivity properties, which was designed to increase lesion detection and characterization by magnetic resonance imaging.MethodsWe described the molecular structure of gadopiclenol and measured the r1 and r2 relaxivity properties at fields of 0.47 and 1.41 T in water and human serum. Nuclear magnetic relaxation dispersion profile measurements were performed from 0.24 mT to 7 T. Protonation and complexation constants were determined using pH-metric measurements, and we investigated the acid-assisted dissociation of gadopiclenol, gadodiamide, gadobutrol, and gadoterate at 37°C and pH 1.2. Applying the relaxometry technique (37°C, 0.47 T), we investigated the risk of dechelation of gadopiclenol, gadoterate, and gadodiamide in the presence of ZnCl2 (2.5 mM) and a phosphate buffer (335 mM). Pharmacokinetics studies of radiolabeled 153Gd-gadopiclenol were performed in Beagle dogs, and protein binding was measured in rats, dogs, and humans plasma and red blood cells.ResultsGadopiclenol [gadolinium chelate of 2,2′,2″-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,6,9-triyl)tris(5-((2,3-dihydroxypropyl)amino)-5-oxopentanoic acid); registry number 933983-75-6] is based on a pyclen macrocyclic structure. Gadopiclenol exhibited a very high relaxivity in water (r1 = 12.2 mM−1·s−1 at 1.41 T), and the r1 value in human serum at 37°C did not markedly change with increasing field (r1 = 12.8 mM−1·s−1 at 1.41 T and 11.6 mM−1·s−1 at 3 T). The relaxivity data in human serum did not indicate protein binding. The nuclear magnetic relaxation dispersion profile of gadopiclenol exhibited a high and stable relaxivity in a strong magnetic field. Gadopiclenol showed high kinetic inertness under acidic conditions, with a dissociation half-life of 20 ± 3 days compared with 4 ± 0.5 days for gadoterate, 18 hours for gadobutrol, and less than 5 seconds for gadodiamide and gadopentetate. The pharmacokinetic profile in dogs was typical of extracellular nonspecific GBCAs, showing distribution in the extracellular compartment and no metabolism. No protein binding was found in rats, dogs, and humans.ConclusionsGadopiclenol is a new extracellular and macrocyclic Gd chelate that exhibited high relaxivity, no protein binding, and high kinetic inertness. Its pharmacokinetic profile in dogs was similar to that of other extracellular nonspecific GBCAs.

The dynamics of extracellular gadolinium-based contrast agent excretion into pleural and pericardial effusions quantified by T1 mapping cardiovascular magnetic resonance

IntroductionExcretion of cardiovascular magnetic resonance (CMR) extracellular gadolinium-based contrast agents (GBCA) into pleural and pericardial effusions, sometimes referred to as vicarious excretion, has been described as a rare occurrence using T1-weighted imaging. However, the T1 mapping characteristics as well as presence, magnitude and dynamics of contrast excretion into these effusions is not known.AimsTo investigate and compare the differences in T1 mapping characteristics and extracellular GBCA excretion dynamics in pleural and pericardial effusions.MethodsClinically referred patients with a pericardial and/or pleural effusion underwent CMR T1 mapping at 1.5 T before, and at 3 (early) and at 27 (late) minutes after administration of an extracellular GBCA (0.2 mmol/kg, gadoteric acid). Analyzed effusion characteristics were native T1, ΔR1 early and late after contrast injection, and the effusion-volume-independent early-to-late contrast concentration ratio ΔR1early/ΔR1late, where ΔR1 = 1/T1post-contrast - 1/T1native.ResultsNative T1 was lower in pericardial effusions (n = 69) than in pleural effusions (n = 54) (median [interquartile range], 2912 [2567–3152] vs 3148 [2692–3494] ms, p = 0.005). Pericardial and pleural effusions did not differ with regards to ΔR1early (0.05 [0.03–0.10] vs 0.07 [0.03–0.12] s− 1, p = 0.38). Compared to pleural effusions, pericardial effusions had a higher ΔR1late (0.8 [0.6–1.2] vs 0.4 [0.2–0.6] s− 1, p < 0.001) and ΔR1early/ΔR1late (0.19 [0.08–0.30] vs 0.12 [0.04–0.19], p < 0.001).ConclusionsT1 mapping shows that extracellular GBCA is excreted into pericardial and pleural effusions. Consequently, the previously used term vicarious excretion is misleading. Compared to pleural effusions, pericardial effusions had both a lower native T1, consistent with lesser relative fluid content in relation to other components such as proteins, and more prominent early excretion dynamics, which could be related to inflammation. The clinical diagnostic utility of T1 mapping to determine quantitative contrast dynamics in pericardial and pleural effusions merits further investigation.

Dual phase infusion with bolus tracking: technical innovation for cardiac and respiratory navigated magnetic resonance angiography using extracellular contrast.

This technical innovation paper describes a technique for performing cardiac-gated, respiratory-navigated cardiovascular magnetic resonance angiography using an extracellular gadolinium-based contrast agent at 1.5 Tesla (T) with a dual phase bolus injection and slow infusion technique.

Gadobutrol: A Review in Contrast-Enhanced MRI and MRA.

Intravenous gadobutrol [Gadovist™ (EU); Gadavist® (USA)] is a second-generation, extracellular non-ionic macrocyclic gadolinium-based contrast agent (GBCA) that is approved for use in paediatric (including term neonates) and adult patients undergoing diagnostic contrast-enhanced (CE) MRI for visualization of pathological lesions in all body regions or for CE MRA to evaluate perfusion and flow-related abnormalities. Its unique physicochemical profile, including its high thermostability and proton relaxation times, means that gadobutrol is formulated at twice the gadolinium ion concentration of other GBCAs, resulting in a narrower bolus and consequently, improved dynamic image enhancement. Based on > 20 years of experience in the clinical trial and real-world settings (> 50 million doses) and its low risk for developing nephrogenic systemic fibrosis (NSF), gadobutrol represents an effective and safe diagnostic GBCA for use in CE MRI and MRA to visualize pathological lesions and vascular perfusion and flow-related abnormalities in all body regions in a broad spectrum of patients, including term neonates and other paediatric patients, young and elderly adult patients, and those with moderate or severe renal or hepatic impairment or cardiovascular (CV) disease.

Gadolinium-based relative contrast enhancement in primary sclerosing cholangitis: additional benefit for clinicians?

To evaluate the benefit of extracellular gadolinium-based contrast agent (GBCA) enhanced magnetic resonance imaging (MRI) in addition to conventional non-enhanced T2-weighted imaging (WI) for quantification of inflammatory or fibrotic alterations in the liver parenchyma of patients with primary sclerosing cholangitis (PSC). MRI (3 T) examinations were reviewed retrospectively by two radiologists in 27 PSC patients (age 42.9±15.6 years), and 19 controls. Regions of interest (ROIs) were drawn onto T2 hyperintense and T2 isointense areas and copied to section position matched non-enhanced and delayed-phase contrast-enhanced T1WI. Signal intensities (SI) obtained from ROIs of the multiphase T1WI were used to calculate relative liver enhancement (RLE). The interobserver agreement of RLE and quantified T2 signal was calculated using Bland-Altman analysis. RLE assessed for both T2 hyperintense (RLEhyper) and T2 isointense (RLEiso) areas were compared in patients and controls (RLEhealthy). The interobserver agreement of RLE in affected hyperintense areas (bias -0.77, limits of agreement -51.7 to 50.1) was superior to the quantification of T2 signal only in these areas (bias -3.35, limits of agreement -162.4 to 155.7). The RLEhyper (86.2±9.7%) was higher than the RLEiso (59.8±6.2%, p=0.03) and the RLEhealthy (53.2±2.7%, p=0.002). The mean RLEiso was not significantly different from the RLEhealthy (p=0.3). The extracellular gadolinium-based RLE of T2 hyperintense areas could be a useful add-on for routine follow up MRI in the detection of early inflammatory changes, possibly preceding formation of fibrotic scarring in PSC patients, if validated in larger cohorts.

Is there an added value of a hepatobiliary phase with gadoxetate disodium following conventional MRI with an extracellular gadolinium agent in a single imaging session for detection of primary hepatic malignancies?

To determine added value of hepatobiliary phase (HBP) using gadoxetate disodium compared to MRI with extracellular gadolinium-based contrast agent (GBCA) for detection of primary hepatic malignancies in a single imaging session. IRB approved this HIPAA compliant retrospective study. Within 90days of resection or liver transplant, thirty patients underwent MRI with extracellular GBCA followed by separate injection of gadoxetate for HBP. Two sets of images were reviewed: Set #1-unenhanced and enhanced images with an extracellular GBCA and set #2-with addition of HBP. Data were analyzed in two groups, cases with hepatocellular carcinoma (HCC) only and cases with either HCC and/or cholangiocarcinoma. Observer diagnostic accuracy (Az), sensitivity, and specificity were calculated. 14/30 subjects had HCC (46%, CI 28-66%), 2/30 (2%, CI 1-22%) cholangiocarcinoma, and 14/30 (46%, CI 28-66%) no malignancy. There was no significant change in A z value with addition of gadoxetate in the detection of HCC (range 0.84-0.97 set #1 and 0.85-0.97 set #2, p>0.05). Sensitivity and specificity showed no significant differences (p>0.05) between the image sets for all readers. When stratified by lesion size, there was no significant difference in accuracy, sensitivity, or specificity for any reader (p>0.05). When compared to extracellular GBCA, gadoxetate HBP imaging does not result in a significant difference in accuracy or sensitivity in diagnosis of HCC or cholangiocarcinoma and may result in a decrease in specificity.

Contrast Enhanced MRI in the Diagnosis of HCC.

Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide. Imaging plays a critical role in HCC screening and diagnosis. Initial screening of patients at risk for HCC is performed with ultrasound. Confirmation of HCC can then be obtained by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), due to the relatively high specificity of both techniques. This article will focus on reviewing MRI techniques for imaging HCC, felt by many to be the exam of choice for HCC diagnosis. MRI relies heavily upon the use of gadolinium-based contrast agents and while primarily extracellular gadolinium-based contrast agents are used, there is an emerging role of hepatobiliary contrast agents in HCC imaging. The use of other non-contrast enhanced MRI techniques for assessing HCC will also be discussed and these MRI strategies will be reviewed in the context of the pathophysiology of HCC to help understand the MR imaging appearance of HCC.

Application of Extracellular Gadolinium-based MRI Contrast Agents and the Risk of Nephrogenic Systemic Fibrosis

Application of Extracellular Gadolinium-based MRI Contrast Agents and the Risk of Nephrogenic Systemic Fibrosis

Application of Extracellular Gadolinium-based MRI Contrast Agents and the Risk of Nephrogenic Systemic Fibrosis

Nephrogenic systemic fibrosis (NSF) is a serious, sometimes fatal disease. Findings in recent years have shown that a causal association between gadolinium containing contrast media and NSF is most likely. Therefore, the regulatory authorities have issued guidelines on the use of gadolinium-containing contrast media which have reduced the number of new cases of NSF to almost zero. However, it is for precisely this reason that the greatest care must still be taken to ensure that these guidelines are complied with. The most important factors are renal function, the quantity of gadolinium administered and coexisting diseases such as inflammation. All of these factors crucially influence the quantity of gadolinium released from the chelat in the body. This free gadolinium is thought to be the trigger for NSF. Other important factors are the stability of the gadolinium complex and furthermore the route of its elimination from the body. Partial elimination via the liver might be an additional protective mechanism. In conclusion, despite the NSF risk, contrast-enhanced MRI is a safe diagnostic procedure which can be used reliably and safely even in patients with severe renal failure, and does not necessarily have to be replaced by other methods.

Ischemic Late Gadolinium Enhancement

Chou, Shinn-Huey S. MD; Walker, Christopher M. MD; Chung, Jonathan H. MD Author Information

Gadobutrol: A Review of Its Use for Contrast-Enhanced Magnetic Resonance Imaging in Adults and Children

Since the introduction of the first gadolinium-based contrast agent (GBCA) approximately 25years ago, magnetic resonance imaging (MRI) using GBCAs has revolutionized diagnostic and follow-up imaging of pathological lesions, with clinical applications expanded to encompass almost all fields of medicine. Intravenous gadobutrol (Gadovist™ [EU]; Gadavist(®) [USA]) is a second-generation extracellular non-ionic macrocyclic GBCA that is used in patients undergoing diagnostic contrast-enhanced MRI for visualization of pathological lesions in the CNS and all other body regions or for contrast-enhanced magnetic resonance angiography (MRA) to evaluate perfusion and flow-related abnormalities. Its unique physicochemical profile, along with the high thermostability of macrocyclic GBCAs, means gadobutrol is formulated at twice the gadolinium ion concentration of other currently licensed GBCAs. This reduces the injection volume and provides a narrower bolus, thereby improving image enhancement. Based on extensive clinical experience in a broad range of patients, including paediatric and adult patients (younger and elderly adults), and those with moderate to severe hepatic or renal impairment or cardiovascular disorders, gadobutrol is an effective and generally well tolerated extracellular GBCA for patients undergoing diagnostic contrast-enhanced MRI and contrast-enhanced MRA. As with all macrocyclic GBCAs, the potential for gadobutrol to cause nephrogenic systemic fibrosis appears to be lower than with linear GBCAs.