Safety of Lumason® (SonoVue®) in special populations and critically ill patients.

Evidence for the safe use of Lumason® (SonoVue®), an ultrasound enhancing agent (UEA), in special patient populations is critical to enable healthcare professionals to make informed decisions concerning its use in such patients. Herein, we provide insight on the safety and tolerability of Lumason® in special patient populations. Findings are presented from clinical pharmacology studies conducted in patients with compromised cardiopulmonary conditions, from a retrospective study performed in critically ill patients, and from post-marketing surveillance data from over 20 years of market use of Lumason® (SonoVue®). No detrimental effects of Lumason® on cardiac electrophysiology were observed in patients with coronary artery disease (CAD), and no significant effects on pulmonary hemodynamics were noted in patients with pulmonary hypertension or congestive heart failure. Similarly, no effects on several assessments of pulmonary function (e.g., FVC) were observed in patients with chronic obstructive pulmonary disease (COPD), and no clinically meaningful changes in O2 saturation or other safety parameters were observed after administration of Lumason® to patients with diffuse interstitial pulmonary fibrosis (DIPF). The retrospective study of critically ill patients revealed no significant difference for in-hospital mortality between patients administered Lumason® for echocardiography versus those who had undergone echocardiography without contrast agent. Post-marketing surveillance revealed very low reporting rates (RR) for non-serious and serious adverse events and that serious hypersensitivity reactions were rare. These findings confirm that Lumason® is a safe and well tolerated UEA for use in special populations and critically ill patients.

The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study).

BACKGROUND AND PURPOSE: Gadobenate dimeglumine (MultiHance) has higher r1 relaxivity than gadoterate meglumine (Dotarem) which may permit the use of lower doses for MR imaging applications. Our aim was to compare 0.1- and 0.05-mmol/kg body weight gadobenate with 0.1-mmol/kg body weight gadoterate for MR imaging assessment of brain tumors. MATERIALS AND METHODS: We performed crossover, intraindividual comparison of 0.1-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 1) and 0.05-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 2). Adult patients with suspected or known brain tumors were randomized to Arm 1 (70 patients) or Arm 2 (107 patients) and underwent 2 identical examinations at 1.5 T. The agents were injected in randomized-sequence order, and the 2 examinations were separated by 2-14 days. MR imaging scanners, imaging sequences (T1-weighted spin-echo and T1-weighted high-resolution gradient-echo), and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images for diagnostic information (degree of definition of lesion extent, lesion border delineation, visualization of lesion internal morphology, contrast enhancement) and quantitatively for percentage lesion enhancement and lesion-to-background ratio. Safety assessments were performed. RESULTS: In Arm 1, a highly significant superiority (P < .002) of 0.1-mmol/kg gadobenate was demonstrated by all readers for all end points. In Arm 2, no significant differences (P > .1) were observed for any reader and any end point, with the exception of percentage enhancement for reader 2 (P < .05) in favor of 0.05-mmol/kg gadobenate. Study agent-related adverse events were reported by 2/169 (1.2%) patients after gadobenate and by 5/175 (2.9%) patients after gadoterate. CONCLUSIONS: Significantly superior morphologic information and contrast enhancement are demonstrated on brain MR imaging with 0.1-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate. No meaningful differences were recorded between 0.05-mmol/kg gadobenate and 0.1-mmol/kg gadoterate.

Evaluation of image quality, radiation dose and diagnostic performance of dual-energy CT datasets in patients with hepatocellular carcinoma.

AIM: To evaluate image quality and diagnostic accuracy of different dual-energy computed tomography (DECT) datasets for identification of hepatocellular carcinoma (HCC), assess the reliability of virtual unenhanced (VU) images in replacing standard unenhanced (SU) images, and quantify effective dose (ED) at different tube voltages. MATERIAL AND METHODS: Thirty cirrhotic patients underwent liver contrast-enhanced DECT. Two blinded observers retrospectively evaluated conventional unenhanced and VU images, 140 kVp/80 kVp/mixed tube potential arterial datasets and conventional portal-venous/late phases in consensus. Final diagnosis was based on pathological proof or imaging criteria. Image quality, ED, sensitivity, and specificity of arterial datasets were calculated. RESULTS: Thirty-eight HCC and 18 benign lesions were detected at 80 kVp, 33 HCC and 22 benign lesions were detected at 140 kVp, and 36 HCC and 20 benign lesions were detected at mixed tube potentials. Final diagnosis confirmed 37 HCC and 20 benign lesions. There was no significant difference in diagnostic confidence between 80 kVp, 140 kVp, and mixed tube potential arterial datasets (p>0.05). Image quality was adequate for all datasets, with increased quality at higher tube potential (80 versus 140 kVp, p=0.001; mixed versus 140 kVp, p=0.001; 80 kVp versus mixed, p=0.0024). Significant ED reduction was observed between 140 and 80 kVp datasets (p<0.001). CONCLUSIONS: The 140 kVp dataset provided higher image quality. The 80 kVp images were more sensitive in detecting HCC. VU images are adequate in replacing SU images. The ED of the 80 kVp dataset was significantly lower.

Compensatory biliary and urinary excretion of gadobenate ion after administration of gadobenate dimeglumine (MultiHance(®)) in cases of impaired hepatic or renal function: a mechanism that may aid in the prevention of nephrogenic systemic fibrosis?

OBJECTIVE: To determine whether increased elimination of gadobenate ion via the hepatobiliary pathway might compensate for reduced/absent elimination via the urinary pathway in the event of compromised renal function, as a possible protective mechanism against nephrogenic systemic fibrosis (NSF). METHODS: 15 male Crl:CD(®) R(SD)Br rats (Charles River Italia, Como, Italy) randomized to three treatment groups: (1) animals with occluded bile ducts, (2) animals with occluded renal vessels and (3) control animals, each received 0.25 mmol kg(-1) of bodyweight of gadobenate dimeglumine (MultiHance(®); Bracco Imaging SpA, Milan, Italy). Urine and bile were collected from 0-30, 30-60, 60-120, 120-240 and 240-480 min after gadobenate dimeglumine administration prior to exsanguination. Determinations of gadobenate ion in blood, bile and urine were performed by high-performance liquid chromatography. Gadolinium (Gd(3+)) levels in excised liver and kidneys were determined by X-ray fluorescence. RESULTS: The recovery of gadobenate ion in the urine of rats with bile duct occlusion was significantly higher than that in the urine of normal rats (89.1 ± 4.2% vs 60.6 ± 2.8%; p < 0.0001). Conversely, mean recovery in the bile of rats with renal vessel occlusion was significantly higher than that in the bile of normal rats (96.16 ± 0.55% vs 33.5 ± 4.7%; p < 0.0001). Gadobenate ion was not quantifiable in any group 8 h post-injection. CONCLUSION: Compensatory elimination may be an effective means to overcome compromised renal or hepatobiliary elimination. ADVANCES IN KNOWLEDGE: The absence of NSF in at-risk patients administered with gadobenate dimeglumine may in part reflect greater Gd(3+) elimination via the hepatobiliary route.

Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study).

BACKGROUND AND PURPOSE: Gadobutrol (Gadavist) and gadoteridol (ProHance) have similar macrocyclic molecular structures, but gadobutrol is formulated at a 2-fold higher (1 mol/L versus 0.5 mol/L) concentration. We sought to determine whether this difference impacts morphologic contrast-enhanced MR imaging. MATERIALS AND METHODS: Two hundred twenty-nine adult patients with suspected or known brain tumors underwent two 1.5T MR imaging examinations with gadoteridol or gadobutrol administered in randomized order at a dose of 0.1 mmol/kg of body weight. Imaging sequences and T1 postinjection timing were identical for both examinations. Three blinded readers evaluated images qualitatively and quantitatively for lesion detection and for accuracy in characterization of histologically confirmed brain tumors. Data were analyzed by using the Wilcoxon signed rank test, the McNemar test, and a mixed model. RESULTS: Two hundred nine patients successfully completed both examinations. No reader noted a significant qualitative or quantitative difference in lesion enhancement, extent, delineation, or internal morphology (P values = .69-1.00). One hundred thirty-nine patients had at least 1 histologically confirmed brain lesion. Two readers found no difference in the detection of patients with lesions (133/139 versus 135/139, P = .317; 137/139 versus 136/139, P = .564), while 1 reader found minimal differences in favor of gadoteridol (136/139 versus 132/139, P = .046). Similar findings were noted for the number of lesions detected and characterization of tumors (malignant/benign). Three-reader agreement for characterization was similar for gadobutrol (66.4% [κ = 0.43]) versus gadoteridol (70.3% [κ = 0.45]). There were no significant differences in the incidence of adverse events (P = .199). CONCLUSIONS: Gadoteridol and gadobutrol at 0.1 mmol/kg of body weight provide similar information for visualization and diagnosis of brain lesions. The 2-fold higher gadolinium concentration of gadobutrol provides no benefit for routine morphologic imaging.

Malignant tumours of the small intestine: a review of histopathology, multidetector CT and MRI aspects.

Small bowel neoplasms, including adenocarcinoma, carcinoid tumour, lymphoma and gastrointestinal stromal tumours, represent a small percentage of gastrointestinal cancers, yet are among those with the poorest prognosis compared with other gastrointestinal malignancies. Unclear clinical scenarios and difficult radiological diagnosis often delay treatment with negative effects on patient survival. Recently, multidetector CT (MDCT) and MRI have been introduced as feasible and accurate diagnostic techniques for the identification and staging of small bowel neoplasms. These techniques are gradually replacing conventional barium radiography as the tool of choice. However, the inherent technical and physiological challenges of small bowel imaging require a familiarity with patient preparation and scan protocols. Adequate knowledge of the histopathology and natural evolution of small bowel neoplasms is also important for differential diagnosis. The aim of this article is to review MDCT and MRI protocols for the evaluation of small bowel tumours and to provide a concise yet comprehensive guide to the most relevant imaging features relative to histopathology.

Contrast-enhanced breast MR imaging of claustrophobic or oversized patients using an open low-field magnet.

PURPOSE: A number of women who should undergo magnetic resonance (MR) imaging of the breast cannot use this diagnostic tool due to claustrophobia or excessive body size for the restricted confines of standard closed MR systems. Our aim was to evaluate the performance of open low-field magnet breast MR imaging in such patients using a high-relaxivity contrast agent. MATERIALS AND METHODS: Of 397 consecutive patients undergoing breast MR imaging, 379 (95.5%) were studied at 1.5 T. Due to claustrophobia (n=15) or large body size (n=3), 18 patients (4.5%) were studied on a 0.2-T open magnet using a body coil. A 3D dynamic T1-weighted gradient-echo 94-s sequence was acquired with intravenous injection of gadobenate dimeglumine (0.1 mmol/kg). The standard of reference was pathological examination for 16 lesions classified with a maximal Breast Imaging Reporting and Data System (BI-RADS) score from 3 to 5, fine-needle aspiration cytology and >or=2-year follow-up for two lesions classified as BI-RADS 3, and >or=2-years follow-up for five lesions classified as BI-RADS 2. RESULTS: Diagnostic MR image quality was achieved for 20/23 lesions in 15/18 patients. Three lesions (two invasive cancers and a cyst) were not assessed due to patient movement and considered as two false negatives and one false positive. Thus, an 86% sensitivity [13/15; 95% confidence interval (CI): 70%-100%], an 87% specificity (7/8; 95% CI: 65%-100%) and an 87% accuracy (20/23; 95% CI: 73%-100%) were obtained. The intraclass correlation coefficient between MR and pathologic lesion size was 0.845. CONCLUSION: In claustrophobic or oversized patients, open low-field breast MR with gadobenate dimeglumine yields good diagnostic performance.

Follow-up of coiled cerebral aneurysms at 3T: comparison of 3D time-of-flight MR angiography and contrast-enhanced MR angiography.

BACKGROUND AND PURPOSE: Our aim was to compare contrast-enhanced MR angiography (CE-MRA) and 3D time-of-flight (TOF) MRA at 3T for follow-up of coiled cerebral aneurysms. MATERIALS AND METHODS: Fifty-two patients treated with Guglielmi detachable coils for 54 cerebral aneurysms were evaluated at 3T MRA. 3D TOF MRA (TR/TE = 23/3.5; SENSE factor = 2.5) and CE-MRA by using a 3D ultrafast gradient-echo sequence (TR/TE = 5.9/1.8; SENSE factor = 3) enhanced with 0.1-mmol/kg gadobenate dimeglumine were performed in the same session. Source images, 3D maximum intensity projection, 3D shaded surface display, and/or 3D volume-rendered reconstructions were evaluated in terms of aneurysm occlusion/patency and artifact presence. RESULTS: In terms of clinical classification, the 2 MRA sequences were equivalent for 53 of the 54 treated aneurysms: 21 were considered fully occluded, whereas 16 were considered to have a residual neck and 16 were considered residually patent at follow-up MRA. The remaining aneurysm appeared fully occluded at TOF MRA but had a residual patent neck at CE-MRA. Visualization of residual aneurysm patency was significantly (P = .001) better with CE-MRA compared with TOF MRA for 10 (31.3%) of the 32 treated aneurysms considered residually patent with both sequences. Coil artifacts were present in 5 cases at TOF MRA but in none at CE-MRA. No relationship was apparent between the visualization of patency and either the size of the aneurysm or the interval between embolization and follow-up. CONCLUSION: At follow-up MRA at 3T, unenhanced TOF and CE-MRA sequences are similarly effective at classifying coiled aneurysms as occluded or residually patent. However, CE-MRA is superior to TOF MRA for visualization of residual patency and is associated with fewer artifacts.

A comparison of Gd-BOPTA and Gd-DOTA for contrast-enhanced MRI of intracranial tumours.

A two-centre intra-individual crossover study was performed in 23 patients with suspected high-grade glioma or metastases to assess and compare the safety and enhancement characteristics of two different MRI contrast media (gadobenate dimeglumine, Gd-BOPTA and gadoterate meglumine, Gd-DOTA) at equivalent doses of 0.1 mmol/kg body weight. T1-weighted spin-echo (SE) and T2-weighted fast SE images were obtained before and T1-weighted images 0, 2, 4, 6, 8 and 15 min after injection. T1-weighted images with magnetisation transfer contrast were acquired 12 min after injection. Qualitative assessment by blinded, off-site readers (reader 1:19 patients; reader 2:21) and on-site investigators (23) revealed significant (P< or =0.005) overall preference for Gd-BOPTA over Gd-DOTA for contrast enhancement (Gd-BOPTA preferred in 18, 15 and 18 cases; Gd-DOTA in 0, 1 and 1 and no preference in 1, 5 and 4; off-site readers 1 and 2, and on-site investigators, respectively). A similar significant preference for Gd-BOPTA was expressed by off-site readers and on-site investigators for lesion-to-brain contrast, lesion delineation, internal lesion structure, and overall image preference. Quantitative assessment by off-site readers revealed significantly (p<0.05) greater lesion enhancement with Gd-BOPTA than with Gd-DOTA at all times from 2 min after injection.

Magnetic resonance imaging of metastatic disease to the brain with gadobenate dimeglumine.

Seventy-four patients with one to eight proven intraaxial brain metastases received a total cumulative dose of 0.2 mmol/kg bodyweight gadobenate dimeglumine, administered as sequential injections of 0.05, 0.05 and 0.1 m mol/kg over a 20-min period. MR imaging was performed before the first administration (T2- and T1-weighted sequences) and after each injection of contrast agent (T1-weighted sequences only). Quantitative assessment of images revealed significant (P <0.01) dose-related increases in lesion-to-brain (L/B) ratio and percent enhancement of lesion signal intensity. Qualitative assessment by two independent, blinded assessors revealed additional lesions in 22%, 25% and 38% (assessor 1) and 29%, 32% and 34% (assessor 2) of patients after each cumulative dose when compared with combined T1- and T2-weighted pre-contrast images. Significantly more lesions (P < 0.01) were noted by both assessors after the first injection and by one assessor after each subsequent injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted in 12%, 16% and 28% of patients by assessor 1 following each dose and in 24%, 27% and 30% of patients by assessor 2. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced MRI. For patients with one lesion observed after an initial dose of 0.05 mmol/kg, additional lesions were noted by assessors 1 and 2 in 9.1% and 11.8% of patients, respectively, after a cumulative dose of 0.1 mmol/kg and in a further 9.1% and 5.9% of patients, respectively, after a cumulative dose of 0.2 mmol/kg. No safety concerns were apparent.

Gadobenate dimeglumine-enhanced magnetic resonance imaging of intracranial metastases: effect of dose on lesion detection and delineation.

Seventy-four patients with one to eight proven intraaxial metastatic lesions to the brain received a total gadobenate dimeglumine dose of 0.3 mmol/kg of body weight, administered as three sequential bolus injections of 0.1 mmol/kg, at 10-minute intervals over a 20-minute period. Quantitative and qualitative assessments of efficacy were performed after each injection and a full evaluation of safety was conducted. Cumulative dosing produced significant (P < 0.01) dose-related increases in lesion-to-brain (L/B) ratio and lesion signal intensity (SI) enhancement. Two independent, blinded assessors noted additional lesions, compared to unenhanced images in 31% and 33%, 49% and 42%, and 50% and 48% of patients after each cumulative dose, respectively. Significantly more lesions were noted after the first injection, compared to unenhanced images (P = 0.002 and P < 0.001; assessors 1 and 2, respectively), and after a second injection, compared to the first (P < 0.001 and P = 0.039; assessors 1 and 2, respectively). Neither assessor noted significantly more lesions after the third injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted by assessors 1 and 2 for 27% and 26%, 48% and 35%, and 42% and 41% of patients, respectively, following each injection. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced magnetic resonance imaging (MRI). For patients with one lesion observed after 0.1 mmol/kg of gadobenate dimeglumine, additional lesions were noted for 24% and 17% of patients (assessors 1 and 2, respectively) following a second 0.1 mmol/kg injection. Only assessor 2 noted additional lesions following the third 0.1 mmol/kg injection. The findings of on-site investigators concurred with those of the two off-site assessors. No safety concerns were apparent.

Focal nodular hyperplasia: morphologic and functional information from MR imaging with gadobenate dimeglumine.

PURPOSE: To determine whether gadobenate dimeglumine (Gd-BOPTA) is able to provide morphologic and functional information for characterization of focal nodular hyperplasia (FNH). MATERIALS AND METHODS: Sixty-three consecutive patients with proved FNH were retrospectively examined. Magnetic resonance (MR) imaging with T2-weighted turbo spin-echo and T1-weighted gradient-echo sequences was performed. Images were acquired prior to and during the dynamic phase of contrast-material enhancement and 1-3 hours after administration of 0.1 mmol/kg Gd-BOPTA. Qualitative analysis of signal intensity and homogeneity on images in the various phases of the MR study and examination for the presence of central scar or atypical features were performed. On the basis of features observed in the precontrast and dynamic phases, lesions were defined as typical or atypical. Intensity and enhancement patterns of the lesions and scars were also evaluated in the delayed phase. RESULTS: One hundred FNHs were depicted on MR images. Seventy-nine of 100 lesions demonstrated typical morphologic and enhancement characteristics. On delayed phase images, 72% of 100 FNHs appeared hyperintense; 21%, isointense; and 7%, slightly hypointense. The delayed pattern of enhancement was homogeneous, heterogeneous, and peripheral in 58%, 22%, and 20% of 100 FNHs, respectively. Atypical morphologic features and lesion and/or scar enhancement were observed in 21 of 100 FNHs. On delayed phase images, 76% of 100 atypical FNHs appeared hyperintense, 14% isointense, and 10% slightly hypointense. Hyperintensity and isointensity allowed the correct characterization in 90% of atypical FNHs. CONCLUSION: Gd-BOPTA during both dynamic and delayed phases provides morphologic and functional information for the characterization of FNH.

Safety assessment of gadobenate dimeglumine (MultiHance): extended clinical experience from phase I studies to post-marketing surveillance.

Clinical trials completed by September 2000 on gadobenate dimeglumine (Gd-BOPTA; MultiHance) included 2540 adult and pediatric subjects that were administered this agent. For adult patient volunteers, the overall incidence of adverse events (AEs) was 19.8%, although marked study- and indication-related differences were apparent. Events potentially related to Gd-BOPTA administration were reported for 15.1% of adult patients. The vast majority of AEs were non-serious, mild, transient, and self-resolving. Headache, injection site reaction, nausea, taste perversion, and vasodilation were the most common AEs, reported with a frequency of between 1.0% and 2.6%. Serious AEs potentially related to Gd-BOPTA were reported for five (0.2%) patients overall. Controlled studies revealed no differences between Gd-BOPTA and other gadolinium chelates or placebo in the incidence and type of AEs. Similarly, no differences with respect to adult patients and/or comparator were noted in studies on pediatric subjects and subjects with renal or liver insufficiency. Post-marketing surveillance of approximately 100000 doses revealed an overall AE incidence of < 0.03% with serious AEs reported for < 0.005% of patients.

Detection of intracranial metastases: a multicenter, intrapatient comparison of gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal dosage.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (MultiHance) with other commercially available MRI contrast agents for the detection of intracranial metastases. METHODS: A retrospective assessment was performed on MR images from 22 patients enrolled in a prior phase II clinical trial of gadobenate dimeglumine. Each patient underwent two examinations: a first examination with one of three "comparator" agents (gadopentetate dimeglumine, gadodiamide, and gadoterate meglumine) at a dosage of either 0.1 or 0.2 mmol/kg, and then a similar examination with gadobenate dimeglumine at equal dosage. All images were evaluated randomly for lesion number and location in unpaired and then paired fashion by two independent, masked neuroradiologists. A third assessor performed quantitative assessments on the available complete sets of digitally recorded images (10 cases). RESULTS: The findings for the comparator agents were pooled. Sensitivity for lesion detection with gadobenate dimeglumine (93%-100%) was markedly superior to that of comparator-enhanced examinations (65%-73%). The increase of lesion-to-brain contrast of the main lesion was consistently greater with gadobenate dimeglumine than with comparator agents relative to unenhanced contrast (+43% vs. +27%). CONCLUSIONS: Gadobenate dimeglumine proved to be a more efficacious agent than comparator contrast agents for the detection of intracranial metastatic lesions: superior efficacy was noted by both reviewers for total lesion count as well as for sensitivity and positive predictive value for lesion detection. The higher relaxivity of gadobenate dimeglumine might explain the superior sensitivity of gadobenate dimeglumine-enhanced MRI for the detection of central nervous system metastases.

Iomeprol: current and future profile of a radiocontrast agent.

RATIONALE AND OBJECTIVES: To review the safety and efficacy profiles of iomeprol by examining the most indicative comparative clinical studies of iomeprol with widely used low-osmolar ionic or nonionic contrast agents, and to illustrate the recent development in iomeprol liposomal formulations for liver imaging and intravascular enhancement. METHODS: Randomized, double-blind, comparative studies were performed of iomeprol versus iopamidol, iopromide, ioxaglate, iopentol, iodixanol, ioversol, and iohexol. In all studies, safety controls included pre- and postadministration physical examinations, monitoring of vital signs, electrocardiography, clinical laboratory investigations, and 24- or 72-hour postadministration monitoring of patients for adverse events. Technically adequate images were rated for diagnostic efficacy by masked assessors. RESULTS: Iomeprol showed similar safety and diagnostic efficacy compared with the nonionic monomers iopamidol, iohexol, and ioversol, and no statistically significant differences were observed. No differences in diagnostic efficacy between iomeprol and iopromide were observed, but in one study on 1,200 patients, the incidence of adverse events and adverse reactions was significantly higher with iopromide than with iomeprol. Iomeprol caused significantly less heat/pain than iopentol in one study; it showed similar safety and tolerability to the nonionic dimer iodixanol, the two agents causing no or modest, superimposable pain and heat sensation at injection and showing similar renal tolerability after intra-arterial injection. A comparison of iomeprol versus ionic dimer ioxaglate in 2,000 patients undergoing percutaneous coronary interventions showed that the incidence of thrombus-related events was similar with the two agents, but ioxaglate caused a significantly higher incidence of allergy-like reactions. First results with iomeprol-containing liposomal formulations show that these agents may facilitate the CT assessment of intrahepatic malignancies and CT angiography procedures. CONCLUSIONS: The overall results of numerous randomized, double-blind, comparative clinical studies in a variety of indications show that the diagnostic efficacy of iomeprol solutions does not differ significantly from that of the low-osmolar contrast media available on the marketplace when similar iodine strengths are used, although iomeprol may have better tolerability and safety than the ionic dimer and some of the nonionic monomers in selective applications. First results obtained with iomeprol-containing liposomal formulations are promising and may foster additional clinical testing.

Phase III, randomized, double-blind, cross-over comparison of gadoteridol and gadopentetate dimeglumine in magnetic resonance imaging of patients with intracranial lesions.

This study compares the efficacy and safety of gadoteridol with that of gadopentetate dimeglumine for enhanced MRI in subjects with intracranial lesions. A total of 92 subjects at three European centres underwent one MRI study enhanced with 0.1 mmol/kg gadoteridol and another with 0.1 mmol/kg gadopentetate dimeglumine. Contrast agents were assigned in random order, separated by 3-7 days. Eighty subjects were evaluated for efficacy. The presence of pathology, degree of enhancement, location and number of lesions, as well as additional information gained, were compared for each subject's unenhanced and enhanced scans for both the gadoteridol and gadopentetate dimeglumine examination. Safety was evaluated in all treated subjects by means of pre- and post-dose vital signs, laboratory tests and by monitoring for adverse events. There was no significant difference in the number of lesions visualized pre- and post-contrast for the two contrast agents. A high degree of correlation was noted between the two blinded readers. When post-contrast image sets were compared between contrast agents, there was no significant difference in superiority of one agent over the other for any of the evaluators (P > 0.05). No significant differences for any safety parameter were noted between the two agents. Gadoteridol and gadopentetate dimeglumine are effective and well tolerated for use in contrast-enhanced MRI of the CNS at a dose of 0.1 mmol/kg.

Detection of malignant primary hepatic neoplasms with gadobenate dimeglumine (Gd-BOPTA) enhanced T1-weighted hepatocyte phase MR imaging: results of off-site blinded review in a phase-II multicenter trial.

OBJECTIVE: To investigate the efficacy of gadobenate dimeglumine (Gd-BOPTA) enhanced MR imaging for the detection of liver lesions in patients with primary malignant hepatic neoplasms. MATERIALS AND METHODS: Thirty-one patients with histologically proven primary malignancy of the liver were evaluated before and after administration of Gd-BOPTA at dose 0.05 or 0.10 mmol/kg. T1-weighted spin echo (T1W-SE) and gradient echo (T1W-GRE) images were evaluated for lesion number, location, size and confidence by three off-site independent reviewers and the findings were compared to reference standard imaging (intraoperative ultrasound, computed tomography during arterial portography or lipiodol computed tomography). Results were analyzed for significance using a two-sided McNemar's test. RESULTS: More lesions were identified on Gd-BOPTA enhanced images than on unenhanced images and there was no significant difference in lesion detection between either concentration. The largest benefit was in detection of lesions under 1 cm in size (7 to 21, 9 to 15, 16 to 18 for reviewers A, B, C respectively). In 68% of the patients with more than one lesion, Gd-BOPTA increased the number of lesions detected. CONCLUSION: Liver MR imaging after Gd-BOPTA increases the detection of liver lesions in patients with primary malignant hepatic neoplasm.

Evaluation of the accuracy of gadobenate dimeglumine-enhanced MR imaging in the detection and characterization of focal liver lesions.

OBJECTIVE: We evaluated the extent to which hepatic lesion characterization and detection is improved by using gadobenate dimeglumine for enhancement of MR images. MATERIALS AND METHODS: Eighty-six patients were imaged before gadobenate dimeglumine administration, immediately after the 2 mL/sec bolus administration of a 0.05 mmol/kg dose (dynamic imaging), and at 60-120 min after the IV infusion at 10 mL/min of a further 0.05 nmol/kg dose (delayed imaging). The accuracy for lesion characterization was assessed for a total of 107 lesions. Sensitivity for lesion detection was assessed for a total of 149 lesions detected on either intra-operative sonography, iodized oil CT, CT during arterial portography, or follow-up contrast-enhanced CT as the gold standard. RESULTS: The accuracy in differentiating benign from malignant liver lesions increased from 75% and 82% (the findings of two observers) on unenhanced images alone, to 89% and 80% on dynamic images alone (p<0.001, p = 0.8), and to 90.7% when combining the unenhanced and dynamic image sets (p<0.001, p = 0.023). Delayed images did not further improve accuracy (90% and 91%; p = 0.002, p< 0.05). A similar trend was apparent in terms of accuracy for specific diagnosis: values ranged from 49% and 62% on unenhanced images alone, to 76% and 70% on combined unenhanced and dynamic images (p<0.001, p = 0.06), and to 75% and 70% on inclusion of delayed images (p<0.001, p = 0.12). The sensitivity for lesion detection increased from 77% and 81% on unenhanced images alone, to 87% and 85% on combined unenhanced and dynamic images (p = 0.001, p = 0.267), and to 92% and 89% when all images were considered (p<0.001, p = 0.01). CONCLUSION: Contrast-enhanced dynamic MR imaging with gadobenate dimeglumine significantly increases sensitivity and accuracy over unenhanced imaging for the characterization of focal hepatic lesions, and delayed MR imaging contributes to the improved detection of lesions.

Focal liver lesions: evaluation of the efficacy of gadobenate dimeglumine in MR imaging--a multicenter phase III clinical study.

PURPOSE: To evaluate gadobenate dimeglumine (Gd-BOPTA) for dynamic and delayed magnetic resonance (MR) imaging of focal liver lesions. MATERIALS AND METHODS: In 126 of 214 patients, MR imaging was performed before Gd-BOPTA administration, immediately after bolus administration of a 0.05- mmol/kg dose of Gd-BOPTA, and 60-120 minutes after an additional intravenously infused 0.05-mmol/kg dose. In 88 patients, imaging was performed before and 60-120 minutes after a single, intravenously infused 0.1-mmol/kg dose. T1- and T2-weighted spin-echo and T1-weighted gradient-echo images were acquired. On-site and blinded off-site reviewers prospectively evaluated all images. Intraoperative ultrasonography, computed tomography (CT) during arterial portography, and/or CT with iodized oil served as the reference methods in 110 patients. RESULTS: Significantly more lesions were detected on combined pre- and postcontrast images compared with on precontrast images alone (P <. 01). All reviewers reported a decreased mean size of the smallest detected lesion and improved lesion conspicuity on postcontrast images. All on-site reviewers and two off-site reviewers reported increased overall diagnostic confidence (P <.01). Additional lesion characterization information was provided on up to 109 (59%) of 184 delayed images and for up to 50 (42%) of 118 patients in whom dynamic images were assessed. Gd-BOPTA would have helped change the diagnosis in 99 (47%) of 209 cases and affected patient treatment in 408 (23%) of 209 cases. CONCLUSION: Gd-BOPTA increases liver lesion conspicuity and detectability and aids in the characterization of lesions.