Thomas Balzer

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.

Magnetic resonance imaging of focal liver lesions. Comparison of the superparamagnetic iron oxide resovist versus gadolinium-DTPA in the same patient

RATIONALE AND OBJECTIVES The authors assess the efficacy of static and dynamic magnetic resonance (MR) imaging using the superparamagnetic iron oxide SHU-555A (Resovist) versus standard dose of gadolinium (Gd)-DTPA in patients with focal liver lesions. METHODS Magnetic resonance imaging was performed in 30 patients suffering from histopathologically verified malignant (n = 22) and benign (n = 8) liver lesions. T2-weighted conventional and fat-suppressed as well as T1-weighted sequences were used before, during, and after fast intravenous administration of Resovist (1 mL/minute) at three doses of 4, 8, and 16 mumol/kg body weight. One week before the Resovist-enhanced MR imaging study 20 patients underwent Gd-DTPA-enhanced MR imaging. RESULTS Detection rate was improved for metastatic lesions revealing 36 lesions unenhanced versus 53 focal lesions using Resovist-enhanced MR imaging. Gadolinium-DTPA-enhanced scans showed no additional lesion versus unenhanced and Resovist-enhanced MR imaging. Static and dynamic imaging demonstrated no measurable percentage signal intensity loss (PSIL) using Resovist-enhanced MR imaging versus a percentage enhancement of 79.7% in Gd-DTPA enhanced scans. In the dynamic T2-weighted sequences, hepatocellular carcinoma nodules (n = 4) showed a rapid decrease in signal intensity starting at 44 seconds. Postinfusion of Resovist followed by a low, constant increase in signal intensity. Gadolinium-DTPA enhanced scans showed a percentage enhancement of 73.4 focal nodular hyperplasia (FNH) and hemangioma revealed a strong and early dose-dependent PSIL 44 to 60 seconds postinfusion with a prolonged signal loss for the FNH in the late study. Statistical evaluation revealed a statistically significant superiority of Resovist-enhanced MR imaging concerning the detection and delineation of focal liver lesions compared with unenhanced and Gd-DTPA enhanced scans (P < 0.05). CONCLUSIONS The fast infusion of the new superparamagnetic contrast agent Resovist shows advantages for dynamic and static MR imaging of focal liver lesions.

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 manufacturers 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.

Saccharide based contrast agents

“Microbubbles”, gaseous bubbles with microscopic diameters, are extremely effective scatterers of ultrasound. Because of their unique acoustic properties, microbubbles play a key role in the basic mode of action of ultrasound contrast media. This role is comparable to that of iodine in X-ray contrast media and of gadolinium in magnetic resonance contrast media [1, 2, 31]. However, single microbubbles, without any additional protection against gas diffusion (between gas bubble and carrier fluid, i.e. blood serum) have a very short lifetime of only a few seconds [4]. This is one of the reasons for the frequently described problems of reproducibility and efficacy with selfmade “contrast agents”. The underlying physico-chemical interactions of in vivo bubble stabilization are difficult and complex.

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.

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

ObjectiveThe aim of this study was to provide a systematic safety analysis of gadobutrol after more than 29 million applications in clinical routine. Materials and MethodsForty-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. ResultsIn 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. ConclusionsGadobutrol is well tolerated and has a favorable safety profile for patients of all age groups.

Diagnostic value of contrast enhancement in vascular Doppler ultrasound

Vascular Doppler ultrasound is a rapidly developing area which was substantially advanced by the introduction of color Doppler. Two-dimensional flow imaging with color Doppler simplifies the diagnostic image analysis, because it provides an overview of the vascular flow within the image plane, and it helps to position quickly the Doppler sample volume appropriate for PW recordings and spectral analysis. In some indications, color Doppler competes with angiography, although the basic diagnostic information differs. Whereas angiography demonstrates the vessel anatomy in a projected image, color Doppler is a “velocity-map” of vascular hemodynamics in variable tomographic image planes. Thus in many cases both techniques should provide additional information for one another. However, whether or not an angiogram, as compared to color Doppler, might provide the substantial supplementary information needed for further decisions regarding individual patient management, depends on the individual case. Further, amongst many other factors, it depends on the degree of diagnostic confidence in the findings of the Doppler examination. One important variable related to the diagnostic confidence in the Doppler findings is the technical quality of the image with respect to the pulse curve recordings, which are related to the signal-to-noise (S/N) ratio, as demonstrated in Figure 1.

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 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.

Does Intravenous Administration of Gadoxetate Disodium Have Any Effect on Breath-hold Times

We appreciate Dr Li and colleague’s interest in our recent article (1). Most dose reduction efforts from the users and the CT manufacturers have focused on modifying tube current (milliampere) because of its known linearity with the quantum noise and a relative ease of its application in the clinical practice. A lower tube potential (kilovolt), on the other hand, results in a substantially higher dose reduction owing to its quadratic relationship with radiation dose but also introduces excessive image noise (2,3). Therefore, to maximize the dose benefits from the iterative reconstruction technique, we applied a low kilovolt peak (80 and 100 kVp vs 120 kVp) in combination with the ATCM technique using a higher NI of 30 but also fixed the upper limit of the tube current to 150 mA (range, 75– 150 mA). We agree that 82% dose reduction (1.8 mGy vs 9.9 mGy) cannot be achieved by just increasing the NI from 25 to 30, but Dr Li and colleagues have overlooked the contributions of lower kilovolt peak and lower maximum milliamperage in lowering dose. Our study provides evidence that the radiation exposure from CT can be lowered substantially while achieving appropriate image quality for urolithiasis diagnosis by using reduced kilovolt peak and milliamperage in conjunction with iterative reconstruction (1).