Gadolinium Presence in Rat Skin: Assessment of Histopathologic Changes Associated with Small Fiber Neuropathy.

Background The presence of gadolinium traces in the skin after administration of gadolinium-based contrast agents (GBCAs) raised safety concerns regarding a potential association with small fiber neuropathy (SFN). Purpose To investigate signs of SFN in rat foot pads by quantification of the intraepidermal nerve fiber density (IENFD) after multiple GBCA administrations and to evaluate gadolinium concentration, chemical species, and clearance. Materials and Methods Fifty rats received eight intravenous injections of either gadodiamide, gadobutrol, gadoterate, gadoteridol (8 × 0.6 mmol per kilogram of body weight), or saline (1.2 mL per kilogram of body weight), within 2 weeks and were sacrificed 5 days or 5 weeks after the last injection. IENFD was determined with protein gene product (PGP) 9.5 immunofluorescent staining and blinded and automated image analysis. The gadolinium and GBCA concentrations were measured with inductively coupled plasma mass spectrometry (ICP-MS), laser ablation ICP-MS, and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). P values were calculated using linear contrasts of model analysis. Results The IENFD (measured as geometric mean [SD] and in number of nerve fibers per millimeter of epidermis) was not significantly altered after 5 days (saline, 8.4 [1.1]; gadobutrol, 9.7 [1.2]; gadoterate, 9.2 [1.2]; gadoteridol, 9.9 [1.3]; gadodiamide, 10.5 [1.2]) or 5 weeks (saline, 19.7 [1.4]; gadobutrol, 16.4 [1.6]; gadoterate, 14.3 [1.6]; gadoteridol, 22.2 [1.8]; gadodiamide, 17.9 [1.4]). Gadolinium skin concentrations were highest for gadodiamide after 5 days (16.0 nmol/g [1.1]) and 5 weeks (10.6 nmol/g [1.2], -33%). Macrocyclic agents were lower at 5 days (gadoteridol, 2.6 nmol/g [1.2]; gadobutrol, 2.7 nmol/g [1.1]; and gadoterate, 2.3 nmol/g [1.2]) and efficiently cleared after 5 weeks (gadoteridol, -95%; gadobutrol and gadoterate, -96%). The distribution of gadolinium and IENF did not visually overlap. For macrocyclic agents, gadolinium was found in sweat glands and confirmed to be intact chelate. Conclusion There were no signs of SFN in rat foot pads using multiple dosing regimens at two time points after administration of GBCAs. Macrocyclic GBCAs exhibited lower levels of gadolinium in the skin and were effectively eliminated within 5 weeks compared with linear gadodiamide, and intact macrocyclic GBCA was detected in sweat glands. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Clement in this issue.

10 Years of Nephrogenic Systemic Fibrosis: A Comprehensive Analysis of Nephrogenic Systemic Fibrosis Reports Received by a Pharmaceutical Company from 2006 to 2016.

OBJECTIVES: The aim of this study was to critically assess the evaluation and categorization process for nephrogenic systemic fibrosis (NSF) based on reports received by Bayer from 2006 to 2016. MATERIALS AND METHODS: A total of 779 NSF reports received by Bayer globally from 2006 to 2016 were included in the analysis. Arlington Medical Resources provided gadolinium-based contrast agent (GBCA) market share. Reports were conservatively categorized based on the Cowper/Girardi criteria. A statistical model simulated the impact of market share and market introduction on the number of unconfounded reports. RESULTS: For all reports, reported onset of disease ranged from 1996 and 2012. Of 779 reports, 325 involved a Bayer product only, 208 involved only products from other companies (or unknown GBCA), and 246 involved both Bayer and non-Bayer products. Most of all reports (86%) originated from the United States.Through 2006, Magnevist and Omniscan dominated the US market (>80% combined market share). All other GBCAs with fewer NSF reports comprised the remaining combined market share of less than 20% or were introduced after May 2007, after safety recommendations came into effect.A total of 563 reports (220 single-agent and 343 multiagent reports) involved Magnevist. In at least 150 of the 343 reports, a different GBCA (Omniscan, 118; OptiMARK, 15; MultiHance, 6; and macrocyclic agent, 11) showed the closest temporal relationship to onset of NSF-like symptoms.The simulation model demonstrated that patients receiving a GBCA with lower market share and late market introduction are less likely to be observed in an unconfounded setting. CONCLUSIONS: Year of market introduction, as well as US market share in 2000 to 2007, greatly influenced the absolute number of NSF reports for each GBCA, their a priori probability to cause NSF, as well as their a priori probability to be associated with unconfounded cases of NSF. Variability in case interpretation and pharmacovigilance approaches also influence the absolute number of unconfounded cases and should therefore not be used for comparative risk assessments. This should be primarily based on objective product parameters such as structure, stability, pharmacokinetics, and dose.

Gadobutrol in Renally Impaired Patients: Results of the GRIP Study.

OBJECTIVE: The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. RESULTS: A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. The mean time since renal disease diagnosis was 1.83 and 5.49 years in the moderate and severe renal impairment cohort, respectively. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF. CONCLUSIONS: No safety concerns with gadobutrol in patients with moderate to severe renal impairment were identified. There were no NSF cases.

Safety of Gadobutrol: Results From 42 Clinical Phase II to IV Studies and Postmarketing Surveillance After 29 Million Applications.

OBJECTIVE: The aim of this study was to provide a systematic safety analysis of gadobutrol after more than 29 million applications in clinical routine. MATERIALS AND METHODS: Forty-two clinical development phase II to IV studies on gadobutrol or comparator and the postmarketing safety surveillance database for gadobutrol (1998-2015) were analyzed. Adverse events (AEs) and drug-related AEs were evaluated in the clinical development database and spontaneous adverse drug reactions (ADRs) in the postmarketing database. Subgroup analyses were run on patients with special medical history and on patients of different age groups. RESULTS: In the clinical development studies, 6809 and 2184 patients received gadobutrol or comparators, respectively. The incidence of drug-related AEs was 3.5% for both groups. With the exception of nausea (0.7% related cases in both groups), all other drug-related AEs were 0.3% or less in both groups. Hypersensitivity reactions were sporadic (<0.1%). Patients with history of allergies to contrast agents experienced slightly more drug-related AEs. No differences were seen between age groups.The overall reporting rate of ADRs from postmarketing surveillance was 0.05%. The most frequent ADRs were anaphylactoid/hypersensitivity reactions, nausea, vomiting, and dyspnea.For 3 single-agent reports of nephrogenic systemic fibrosis, using a conservative approach, association with gadobutrol could not be excluded. CONCLUSIONS: Gadobutrol is well tolerated and has a favorable safety profile for patients of all age groups.

What Evidence Is There That Gadobutrol Causes Increasing Signal Intensity within the Dentate Nucleus and Globus Pallidus on Unenhanced T1W MRI in Patients with RRMS?

KEY POINTS : The study by Stojanov et al does not convincingly support the conclusion that gadobutrol causes higher T1 enhancement in brain on unenhanced MRI. The study by Stojanov et al does not rule out confounding factors . The study by Stojanov et al has limitations in study design.

Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study.

PURPOSE: Contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood-brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0.5 M at a dose of 0.1 mmol/kg bodyweight. MATERIALS AND METHODS: Prospective, multicenter, double-blind, crossover trial in patients who underwent unenhanced MRI followed by enhanced imaging with gadobutrol or gadoteridol. Three blinded readers assessed the magnetic resonance images. The primary efficacy variables included number of lesions detected, degree of lesion contrast-enhancement, lesion border delineation, and lesion internal morphology. RESULTS: Of the 402 treated patients, 390 patients received study drugs. Lesion contrast-enhancement, lesion border delineation, and lesion internal morphology were superior for combined unenhanced/gadobutrol-enhanced imaging vs unenhanced imaging (P < 0.0001 for all). Compared with gadoteridol, gadobutrol was non-inferior for all primary variables and superior for lesion contrast-enhancement, as well as sensitivity and accuracy for detection of malignant disease. The percentage of patients with at least one drug-related adverse event was similar for gadobutrol (10.0%) and gadoteridol (9.7%). CONCLUSION: Gadobutrol is an effective and well-tolerated macrocyclic contrast agent for MRI of the CNS. Gadobutrol demonstrates greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity.

Safety of gadoxetate disodium: Results from the clinical phase II-III development program and postmarketing surveillance.

PURPOSE: To summarize the safety data of gadoxetate disodium, reported in 12 Phase II and III clinical development studies and in the postmarketing surveillance database. MATERIALS AND METHODS: Patients with liver lesions received gadoxetate disodium-enhanced liver magnetic resonance imaging (MRI). Adverse events (AEs) were recorded and evaluated with regard to a potential drug relationship. Subgroup analyses were run on patients with special medical history. Worldwide spontaneous AEs and adverse drug reactions (ADRs) from postmarketing safety surveillance were analyzed. RESULTS: A total of 1989 patients were included in the clinical development program. A total of 1581/1989 (79.5%) patients received the finally approved dose of 0.025 mmol/kg body weight. 10.1% of patients reported AEs, 4.1% were classified as related AEs. Nausea and headache were the most frequently reported related AEs, with 1.1% each. Age, history of contrast media allergy, liver cirrhosis, or impaired liver or renal function did not significantly impact the frequency and type of AEs. The postmarketing safety surveillance database encompassed more than 2.2 million patients. Nausea was the most frequent ADR, with a reporting rate of 0.00652%; all other symptoms were below 0.004%. CONCLUSION: Gadoxetate disodium for liver MRI has an excellent safety profile.

Cost impact of diagnostic imaging for lower extremity peripheral vascular occlusive disease.

OBJECTIVE: The evaluation of peripheral vascular disease in the primary care setting is routinely performed by contrast-enhanced magnetic resonance angiography (CE-MRA) and digital subtraction angiography (DSA). However, limited data are available on the relative costs and clinical outcomes following these diagnostic procedures. The objective of this study is to assess and compare costs associated with diagnostic imaging in peripheral vascular occlusive disease (PAOD). METHODS: US veterans (n = 19,209) with CE-MRA or DSA for the assessment of PAOD from fiscal year (FY) 1999 to FY 2004. Main outcome measure(s) using the Department of Veterans Affairs' (VA) costing algorithms, cost, and log-cost of interventions (e.g., revascularization, stent, angioplasty), amputations or mortality rates within 30/90 days and 1 year of DSA or CE-MRA were compared, and adjusted for patient characteristics and disease severity using multivariate regression. Imaging modality selection bias was evaluated with propensity score, instrumental variables, and Heckman methods using untransformed costs and log-costs with smearing retransformation. RESULTS: Initial CE-MRA imaging was significantly more likely among patients with prior renal disease or bypass surgery [odds ratio (OR) > 2; P < 0.001], and less likely among patients with prior amputation, peripheral vascular disease (PVD), claudication, or other cardiovascular disease (OR < 0.7; P < 0.001). After adjusting for endogenous choice of initial imaging modality, 30-day treatment costs were US$3500-$4300 lower (P < 0.001) for patients with initial CE-MRA. Eighty-two percent of DSA imaging patients had no additional procedures or events within 30 days, and 65% at 90 days. Less than 3.2% (3.6%) of patients had any repeat imaging within 30 (90) days of initial imaging. CONCLUSIONS: Relative to DSA, CE-MRA imaging was associated with substantial treatment episode savings, beyond the US$950 direct savings in imaging cost per procedure. Substituting CE-MRA for DSA among those not planning or requiring any follow-up procedures within 30 days, could have reduced outpatient imaging costs by up to 55%, and reduced VA system costs by US$13.2 million over the six-year period.

Diagnostic efficacy of gadoxetic acid (Primovist)-enhanced MRI and spiral CT for a therapeutic strategy: comparison with intraoperative and histopathologic findings in focal liver lesions.

A multicenter study has been employed to evaluate the diagnostic efficacy of magnetic resonance imaging (MRI) using the new liver-specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist), as opposed to contrast-enhanced biphasic spiral computed tomography (CT), in the diagnosis of focal liver lesions, compared with a standard of reference (SOR). One hundred and sixty-nine patients with hepatic lesions eligible for surgery underwent Gd-EOB-DTPA-enhanced MRI as well as CT within 6 weeks. Pathologic evaluation of the liver specimen combined with intraoperative ultrasound established the SOR. Data sets were evaluated on-site (14 investigators) and off-site (three independent blinded readers). Gd-EOB-DTPA was well tolerated. Three hundred and two lesions were detected in 131 patients valid for analysis by SOR. The frequency of correctly detected lesions was significantly higher on Gd-EOB-DTPA-enhanced MRI compared with CT in the clinical evaluation [10.44%; 95% confidence interval (CI): 4.88, 16.0]. In the blinded reading there was a trend towards Gd-EOB-DTPA-enhanced MRI, not reaching statistical significance (2.14%; 95% CI: -4.32, 8.6). However, the highest rate of correctly detected lesions with a diameter below 1 cm was achieved by Gd-EOB-DTPA-enhanced MRI. Differential diagnosis was superior for Gd-EOB-DTPA-enhanced MRI (82.1%) versus CT (71.0%). A change in surgical therapy was documented in 19 of 131 patients (14.5%) post Gd-EOB-DTPA-enhanced MRI. Gd-EOB-DTPA-enhanced MRI was superior in the diagnosis and therapeutic management of focal liver lesions compared with CT.

Liver tumor characterization: comparison between liver-specific gadoxetic acid disodium-enhanced MRI and biphasic CT--a multicenter trial.

OBJECTIVE: In our multi center trial we compared the potentials of biphasic contrast-enhanced computed tomography (CT) and a novel tissue-specific magnetic resonance imaging (MRI) contrast agent gadoxetic acid disodium in liver lesion characterization. METHODS: A total of 176 patients with 252 liver lesions were analyzed. There were 104 malignant and 148 benign lesions. High-field strength (1.0 T or 1.5 T) MR systems with T1-and T2-weighted sequences were used with and without fat suppression. After gadoxetic acid disodium injection, dynamic imaging and hepatocyte phase MR imaging were performed. Biphasic with 150 mg I/kg of body weight (100-200 mL) spiral CT was also performed. Image reading consisted of on-site (by study investigators) and fully blinded off-site (by E.S.P; C.R; and A.S) evaluations. The classification (benign or malignant) and characterization (lesion type) outcomes of both techniques were assessed. All imaging results were verified against a standard of reference. RESULTS: Both on-site and off-site evaluations demonstrated increases in the lesion classification accuracy with gadoxetic acid disodium-enhanced MRI when compared with spiral CT. This improvement was also shown for characterization. Gadoxetic acid disodium was well tolerated. CONCLUSIONS: Gadoxetic acid disodium offers a safe and diagnostically powerful tool for the evaluation of patients with focal liver lesions with a reliable assessment of lesion classification and characterization.

Assessment of utilization and pharmacovigilance based on spontaneous adverse event reporting of gadopentetate dimeglumine as a magnetic resonance contrast agent after 45 million administrations and 15 years of clinical use.

PURPOSE: Although contrast agents have become indispensable tools in magnetic resonance and their safe and effective use the foundation of many essential diagnostic procedures, only limited summary information on their utilization and pharmacovigilance is available to the community. After voluntary access to the manufacturer spontaneous adverse event database, we assessed the available data for gadopentetate dimeglumine. MATERIAL AND METHODS: Gadopentetate dimeglumine (Gd-DTPA, Magnevist; Berlex/Schering AG, Berlin, Germany) became commercially available in 1988 and is currently marketed in 101 countries. Using the manufacturer's continuous and cumulative database on product distribution and spontaneous adverse event (AE) reporting, we categorized AEs and assessed their cumulative occurrence after 10, 20, and 45 million applications that occurred in 1993, 1997, and 2002, respectively. Furthermore, we reviewed publications in Medline to assess prevalence of the 4 most common MR contrast agents in the indexed literature. RESULTS: Gd-DTPA has been used in more than 45 million magnetic resonance imaging procedures since 1988 and is currently used globally in more than 5 million applications annually. The broadest category of spontaneously reported AEs, subjective symptoms, occurs in less than 0.01% of procedures. Within the total AEs reported, the distribution of serious and nonserious reports was 9.3% and 90.7%, respectively. The rates of AE reporting have changed over time, with increased rates in the second reporting period (1993 to 1997), followed by substantially lower rates in subsequent years. AE reporting rates are the most comprehensive data available; however, there will always be some underestimation of the true event rates. Although no substantial differences were noted among major age groups, substantial differences in reporting frequency were found among regions, with the United States reporting nearly twice as many AEs as Europe in the postmarketing phase. CONCLUSION: The postmarketing utilization and pharmacovigilance analysis of Gd-DTPA has revealed temporal changes and regional differences, overall with an excellent safety profile. Its extensive utilization and safety information have firmly established it as highly used and safe magnetic resonance imaging agent.

Efficacy and safety of MR imaging with liver-specific contrast agent: U.S. multicenter phase III study.

PURPOSE: To assess prospectively the efficacy and safety of postcontrast magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) compared with that of precontrast MR imaging in patients who are known to have or are suspected of having liver lesions and who are scheduled for hepatic surgery. MATERIALS AND METHODS: Investigational review board approval and written informed consent were obtained. HIPAA went into effect after data collection. A total of 172 patients were enrolled. After precontrast MR imaging, 169 patients (94 men, 75 women; mean age, 61 years; age range, 19-84 years) received an intravenous bolus of 25 micromol/kg Gd-EOB-DTPA and underwent dynamic gradient-recalled-echo and delayed MR imaging 20 minutes after injection. Arterial and portal phase computed tomography (CT) were performed within 6 weeks of MR imaging. The standard of reference was surgery with intraoperative ultrasonography (US) and biopsy and/or pathologic evaluation of resected liver segments and/or 3-month follow-up of nonresected segments if intraoperative US was not available. Three blinded reviewers and unblinded site investigators identified liver lesions on segment maps. The Wilcoxon signed rank test was used to compare differences in per-patient sensitivity of precontrast and postcontrast MR images. Adverse events were recorded, and patient monitoring and laboratory assay were performed at time of injection and up to 24 hours after contrast material administration. RESULTS: At MR imaging, 316 lesions were identified in 131 patients. In 77% (P = .012), 72% (P = .15), and 71% (P = .027) of patients for readers 1, 2, and 3, respectively, more lesions were seen at precontrast and postcontrast MR imaging combined than at precontrast MR imaging alone. Sensitivity values for blinded readings were significantly greater at postcontrast MR imaging than at precontrast MR imaging for two of three blinded readers. For all blinded readers, combined precontrast and postcontrast MR images showed no difference in sensitivity compared with helical CT scans. The use of MR imaging, however, yielded fewer patients with at least one false-positive lesion (37%, 31%, and 34% of patients for readers 1, 2, and 3, respectively) than did helical CT (45%, 36%, and 43% of patients for readers 1, 2, and 3, respectively). CONCLUSION: Compared with precontrast MR imaging, postcontrast MR imaging with Gd-EOB-DTPA demonstrated improved sensitivity for lesion detection in the majority of blinded readers, with no substantial adverse events.

Interference of gadolinium-containing contrast-enhancing agents with colorimetric calcium laboratory testing.

OBJECTIVES: The purpose of this study was to evaluate the extent to which various commercially available gadolinium-containing contrast-enhancing (CE) agents can interfere with the measurement of calcium levels by currently used laboratory methods, suggesting (spurious) hypocalcemia or hypercalcemia with a potential risk for the patient. MATERIALS AND METHODS: Serum and plasma from healthy volunteers were spiked with various concentrations of 4 marketed CE agents. The calcium concentration was measured by widely used laboratory methods: the colorimetric systems Cobas Mira and Vitros 950 analyzer. RESULTS: The measurement of calcium in serum and in plasma was not affected by the presence of gadopentetate dimeglumine (Magnevist, Schering AG, Berlin, Germany) or gadobenate dimeglumine (MultiHance, Bracco-Byk Gulden, Constance, Switzerland) in clinically relevant concentrations (up to 5 mM CE agent). Gadodiamide (Omniscan, Amersham Health, Cork, Ireland) and gadoversetamide (OptiMARK, Mallinckrodt, St. Louis, MO) did produce noticeable-and therefore potentially misleading-effects at these concentrations. CONCLUSIONS: The study demonstrates that gadopentetate dimeglumine and gadobenate dimeglumine generate no interference with colorimetric methods for calcium determination, whereas strong interference was shown for gadodiamide and gadoversetamide under clinically relevant conditions.

Improved detection of focal liver lesions at MR imaging: multicenter comparison of gadoxetic acid-enhanced MR images with intraoperative findings.

PURPOSE: To evaluate the safety and efficacy of gadoxetic acid disodium-enhanced magnetic resonance (MR) imaging for the detection of focal liver lesions, with results of histopathologic examination and/or intraoperative ultrasonography used as a standard of reference. MATERIALS AND METHODS: One hundred sixty-nine patients who were known to have or suspected of having focal liver lesions and were scheduled for liver surgery were included in this study. Results in 131 patients could be included in the efficacy analysis. MR imaging was performed before and immediately and 20 minutes after bolus injection of 0.025 mmol/kg of the liver-specific hepatobiliary contrast agent gadoxetic acid. T1-weighted gradient-echo (with and without fat saturation and including dynamic data sets) and T2-weighted fast spin-echo/turbo spin-echo sequences were performed. All images were evaluated on site and by three independent and blinded off-site reviewers. Lesion matching based on the standard-of-reference results was performed. Differences in lesion detection with precontrast and with postcontrast MR images were assessed with the two-sided Wilcoxon signed rank test. RESULTS: Gadoxetic acid was well tolerated. In the on-site review, the number of patients in whom all lesions were correctly matched increased from 89 of 129 patients at precontrast MR imaging to 103 of 129 patients at postcontrast MR imaging. In the off-site evaluation, the number of patients in whom all lesions were correctly matched and the corresponding sensitivity values increased from 72 (55.8%), 68 (52.7%), and 66 (51.2%) with the precontrast images to 88 (68.2%), 69 (53.5%), and 76 (58.9%) with the postcontrast images for readers 1, 2, and 3, respectively. Two of the three blinded readers showed a statistically significant difference in lesion detection between precontrast and postcontrast MR imaging (P <.001 and P =.008). A large number of additionally correctly detected and localized lesions were smaller than 1 cm. CONCLUSION: MR imaging with gadoxetic acid is safe and improves lesion detection and localization.

Ferucarbotran (Resovist): a new clinically approved RES-specific contrast agent for contrast-enhanced MRI of the liver: properties, clinical development, and applications.

Ferucarbotran (Resovist) is the second clinically approved superparamagnetic iron oxide developed for contrast-enhanced MRI of the liver. The purpose of this review is to provide an overview on the properties, clinical development, and application of ferucarbotran. Safety data obtained during clinical phases I-III revealed a total of 162 adverse events within 1053 patients, of which 75 were classified as possibly, probably, or definitely drug related. The majority of events occurred within the first 3 h (73 of 75) and was of mild intensity. The agent significantly improves the detection of hypovascular focal liver lesions with a comparable sensitivity in lesion detection to CTAP but without a relevant loss in specificity. Furthermore, ferucarbotran leads to a significant improvement of the sensitivity for lesion classification and characterization of the most frequent liver lesions. Contrast-enhanced MRA is not feasible and the angiographic effect is not sufficient to allow for postprocessing of data into maximum intensity projections. Intraindividual studies at low-field (0.2 T) and high-field (1.5 T) showed similar rates for lesion detection. The time window for contrast-enhanced MRI of the liver is at least 1 day up to 4 days. The compound can be regarded as safe and well tolerated. Even bolus injections caused no cardiovascular side effects, lumbar back pain, or clinically relevant laboratory changes. The examination time can be kept short with T1- and T2-weighted pre-contrast sequences, dynamic MRI over 10 min, and finally accumulation phase T2-weighted MRI. Patients who may benefit in particular are surgical candidates for resection, transplantation, or interventional therapies, and patients with liver cirrhosis and/or suspected hepatocellular carcinoma to either exclude malignancy or to define the extent of disease, the location of lesions, and the type of newly detected lesions.

Preoperative evaluation of malignant liver tumors: comparison of unenhanced and SPIO (Resovist)-enhanced MR imaging with biphasic CTAP and intraoperative US.

The purpose of this study was to evaluate the diagnostic efficacy of iron-oxide-enhanced MRI vs CT during arterial portography (CTAP) and intraoperative ultrasound (IOUS) in detection of liver neoplasms. Seventeen patients with malignant focal liver lesions (liver metastases, n=7), hepatocellular carcinomas (HCC, n=9), and cholangiocellular carcinoma (CCC, n=1) underwent presurgical Resovist-enhanced MRI and CTAP. Two independent observers (A and B) assessed the blinded images of unenhanced and iron-oxide-enhanced MRI vs CTAP for the presence, number, and location of the liver lesions. These results were compared lesion by lesion and segment by segment with the results of intraoperative ultrasound ( n=17) serving as the reference standard. Eighty lesions were detected by intraoperative ultrasound in 17 patients. In comparison with IOUS (lesion-by-lesion analysis) the sensitivity was 86.8% for CTAP, 65% for combined unenhanced MR imaging, and 86.8% for combined Resovist-enhanced MRI as well as 86.8% for the combination of unenhanced and Resovist-enhanced MRI. Compared with the sensitivity of combined unenhanced MRI the sensitivity of CTAP as well as the sensitivity of combined Resovist-enhanced MRI was significantly higher (p<0.05). False-positive results were much higher in CTAP as compared with combined unenhanced and SPIO-enhanced MRI. Using the segment-by-segment analysis the specificity of combined unenhanced MRI with 100% (96.7-100%) as well as combined Resovist-enhanced MRI with 100% (96.7-100%) was significantly higher (p<0.05) in comparison with the specificity of CTAP with 91.1% (83.2-96.1%). The accuracy of combined unenhanced MRI was 100% (93.2-100%), combined Resovist-enhanced MRI 100% (93.6-100%) and of CTAP 85.2% (72.9-93.4%). In the detection of focal liver lesions iron-oxide-enhanced MR imaging is superior to unenhanced MRI and similar to CTAP.