First-pass whole-body magnetic resonance angiography (MRA) using the blood-pool contrast medium gadofosveset trisodium: comparison to gadopentetate dimeglumine

OBJECTIVES: To evaluate gadofosveset trisodium for first-pass magnetic resonance angiography (MRA) in the setting of whole-body MRA (WB-MRA). MATERIALS AND METHODS: Forty patients were examined using either 10 mL gadofosveset trisodium (n = 20) or 30 mL gadopentetate dimeglumine (n = 20), followed by arterial-phase imaging of 4 consecutive anatomic regions. Signal intensity was measured in 2 vessels per region. Relative contrast values (RC) were calculated. Arterial contrast, venous overlay, and image quality were rated by 2 radiologists. The Mann-Whitney U test was used to test for significance. RESULTS: Compared with gadopentetate dimeglumine, gadofosveset trisodium enhanced imaging revealed higher RC values in 2 vessel regions, with the differences being significant in 3 of 4 vessel segments. Gadofosveset trisodium revealed lower RC values in 2 regions with significant differences in 2 segments. Qualitative evaluation revealed higher ratings for gadofosveset trisodium regarding all 3 criteria with significant differences in 2 regions. CONCLUSIONS: Gadofosveset trisodium serves well for first-pass imaging in WB-MRA.     

Gadobenate dimeglumine (MultiHance) for magnetic resonance angiography: review of the literature

Although limited in number, reports describing the use of Gd-BOPTA for 3D CE-MRA reveal that this agent is safe, well tolerated and effective for CE-MRA at doses up to 0.3 mmol/kg bodyweight. The use of Gd-BOPTA leads to additional diagnostically relevant information comparable to that attainable with conventional DSA and superior to that on non-enhanced MRA in most arterial territories. In studies in which Gd-BOPTA is compared at equal dose with other gadolinium-based MR contrast agents, Gd-BOPTA has consistently shown significantly better quantitative and qualitative performance. Thus, Gd-BOPTA can be considered to have a very favorable risk/benefit ratio for MRA. In summary, it is likely the documented superiority of Gd-BOPTA for MR angiography will lead to its broad usage for this indication wherever the agent becomes available.     

Intraindividual comparison of gadopentetate dimeglumine,gadobenate dimeglumine,and gadobutrol for pelvic 3D magnetic resonance angiography

RATIONALE AND OBJECTIVES: To compare the effect on image quality of a 1.0 mol/L gadolinium chelate with that of two 0.5 mol/L gadolinium compounds. MATERIALS AND METHODS: Five healthy volunteers underwent a mono-station 3D MRA exam (Siemens SONATA, Erlangen, Germany) four times using four separate gadolinium preparations. All subjects first received a fixed volume of undiluted gadobutrol (1 mol/L), which corresponded to a dose between 0.1 and 0.15 mmol/kg body weight. This gadobutrol dosage was then diluted with saline into twice the volume and administered as a bolus at twice the injection rate. For Gd-DTPA and Gd BOPTA, because these contrast agents are 0.5 mol/L preparations, the volume and flow rate were doubled to match diluted gadobutrol volume and concentration. Quantitative and qualitative analysis of the angiographic data sets was performed on nine arterial segments. RESULTS: Image quality was rated diagnostic for all image data sets without statistically significant differences between any of the compounds (P > 0.3). Quantitative measurements of Gd BOPTA (SNR: 81.15; CNR: 68.91) and both standard and diluted forms of gadobutrol (SNR: 84.33; CNR: 71.62; SNR(diluted): 79,23; CNR(diluted): 66.26) yielded significantly higher results (P < 0.02) in comparison with Gd-DTPA (SNR: 49.55; CNR: 38.24). The difference between either form of gadobutrol and Gd BOPTA was not shown to be statistically significant (P > 0.3), whereas both the SNR and CNR of standard gadobutrol were significantly higher than diluted gadobutrol. CONCLUSION: Gadobutrol- and Gd BOPTA-MRA exams lead to improved delineation of the pelvic arterial morphology compared with MRA exams performed with Gd-DTPA.     

Low-dose gadobenate dimeglumine versus standard dose gadopentetate dimeglumine for contrast-enhanced magnetic resonance imaging of the liver: an intra-individual crossover comparison

RATIONALE AND OBJECTIVES: Gadobenate dimeglumine (Gd-BOPTA) has a two-fold higher T1 relaxivity compared with gadopentetate dimeglumine (Gd-DTPA) and can be used for both dynamic and delayed liver MRI. This intraindividual, crossover study was conducted to compare 0.05 mmol/kg Gd-BOPTA with 0.1 mmol/kg Gd-DTPA for liver MRI. MATERIALS AND METHODS: Forty-one patients underwent two identical MR examinations separated by >or= 72 hours. Precontrast T1-FLASH-2D and T2-TSE sequences and postcontrast T1-FLASH-2D sequences were acquired during the dynamic and delayed (1-2 hours) phases after each contrast injection. Images were evaluated on-site by two independent, blinded off-site readers in terms of confidence for lesion detection, lesion number, character and diagnosis, enhancement pattern, lesion-to-liver contrast, and benefit of dynamic and delayed scans. Additional on-site evaluation was performed of the overall diagnostic value of each agent. RESULTS: Superior diagnostic confidence was noted by on-site investigators and off-site assessors 1 and 2 for 6, 4 and 2 patients with Gd-BOPTA, and for 3, 1 and 2 patients with Gd-DTPA, respectively. No consistent differences were noted for other parameters on dynamic phase images whereas greater lesion-to-liver contrast was noted for more patients on delayed images after Gd-BOPTA. More correct diagnoses of histologically confirmed lesions (n = 26) were made with the complete Gd-BOPTA image set than with the complete Gd-DTPA set (reader 1: 68% vs. 59%; reader 2: 78% vs. 68%). The overall diagnostic value was considered superior after Gd-BOPTA in seven patients and after Gd-DTPA in one patient. CONCLUSION: The additional diagnostic information on delayed imaging, combined with the possibility to use a lower overall dose to obtain similar diagnostic information on dynamic imaging, offers a distinct clinical advantage for Gd-BOPTA for liver MRI.     

Intraindividual comparison of 1.0 M gadobutrol and 0.5 M gadopentetate dimeglumine for time-resolved contrast-enhanced three-dimensional magnetic resonance angiography of the upper torso

PURPOSE: To compare the signal characteristics and bolus dynamics of 1.0 M gadobutrol and 0.5 M Gd-DTPA for time-resolved, three-dimensional, contrast-enhanced (CE) MRA of the upper torso. MATERIALS AND METHODS: Ten healthy volunteers were examined with time-resolved three-dimensional CE-MRA (scan time per three-dimensional data set: 0.86 second; voxel size: 3.6 x 2 x 6.3 mm(3)). Each volunteer underwent eight individual examinations after intravenous injection of 0.05 and 0.1 mmol/kg body weight (b.w.) of 1.0 M gadobutrol and 0.5 M Gd-DTPA using two injection rates (2.5 and 5 mL/second). The data analysis included quantitative measurements of the peak signal-to-noise ratio (SNR) and bolus dispersion (full width at half maximum (FWHM)) in the pulmonary artery, left atrium, and thoracic and abdominal aortas. RESULTS: No significant differences in the peak SNR and bolus dispersion were observed between gadobutrol and Gd-DTPA for all dose levels and injection rates in any of the vascular segments. For both contrast agents a dose of 0.1 mmol/kg b.w. injected with 5 mL/second achieved the highest SNR in all vascular segments. CONCLUSION: For the imaging parameters used in this study, higher-concentrated gadolinium chelates offer no relevant advantages for time-resolved three-dimensional CE-MRA of the upper torso.     

Gadobenate dimeglumine 0.5 M solution for injection (MultiHance) as contrast agent for magnetic resonance imaging of the liver: mechanistic studies in animals

Mechanistic studies regarding the action of gadobenate dimeglumine (Gd-BOPTA/Dimeg; MultiHance) in animals are presented, and the relevance of the results to protocols for MR imaging of the liver are discussed. Gd-BOPTA/Dimeg maintains all the characteristics of an extracellular contrast agent, but owing to a weak affinity for serum albumin, provides in these applications stronger signal intensities than contrast agents without such affinity at the same dose. This property can be taken advantage of for dynamic liver imaging. A unique property of Gd-BOPTA/Dimeg is that the contrast effective ion, Gd-BOPTA2-, enters hepatocytes selectively and reversibly through the sinusoidal plasma membrane using transport mechanisms other than the organic anion transport polypeptide. In a rate-limiting step, the ion is excreted by the multispecific organic anion transporter into the bile. The increase in liver distribution space of Gd-BOPTA2-, as compared to that of purely extracellular contrast agents, is identified as the principal mechanism of normal parenchymal signal enhancement. Microviscosity effects inside hepatocytes add to the relaxation effectiveness of Gd-BOPTA2-, while its presence in the bile and an affinity for intracellular macromolecules play subordinate roles only. Gd-BOPTA2- persists in hepatocytes beyond the times characteristic of dynamic imaging, providing delayed-phase contrast between normal hepatocytes and tumor cells. As a result, the conspicuity of small focal lesions and thus their detection is improved. Additionally, Gd-BOPTA/Dimeg allows sites of abscesses and systemically damaged tissue to be distinguished from healthy liver. Taken together these mechanistically-supported properties qualify the product as a versatile general MR contrast agent with added merits in liver imaging.     

Three-dimensional time-of-flight (3D TOF) magnetic resonance angiography (MRA) and contrast-enhanced MRA of intracranial aneurysms treated with platinum coils

Background: Contrast-enhanced magnetic resonance angiography (CE-MRA) is less prone to flow-related signal intensity loss than three-dimensional time-of-flight (3D TOF) MRA and may therefore be more sensitive for detection of residual patency in platinum coil-treated intracranial aneurysms.

Purpose: To compare MRA and CE-MRA in the follow-up of intracranial aneurysms treated with platinum coils.

Material and Methods: CE-MRA and 3D TOF MRA (pre- and postcontrast injection) of the intracranial vasculature was performed at 1.5T in 38 patients (47 aneurysms) referred for DSA in the follow-up of coiled intracranial aneurysms.

Results: DSA showed aneurysm patency in 22/47 investigations. Patent aneurysm components were observed with CE-MRA in 18/22 cases, and with 3D TOF MRA in 21/22 cases. There was no significant difference in patent aneurysm component size between CE-MRA and 3D TOF MRA. In addition, CE-MRA showed six, 3D TOF MRA before contrast injection showed seven, and 3D TOF MRA after contrast injection showed eight cases with patent aneurysm components not observed on DSA.

Conclusion: 3D TOF MRA was highly sensitive for detection of patent aneurysm components, and at least as sensitive as CE-MRA. Residual aneurysm patency seems to be better visualized with MRA than with DSA in some cases.     

Evaluation of a novel time-efficient protocol for gadobenate dimeglumine (Gd-BOPTA)-enhanced liver magnetic resonance imaging

OBJECTIVE: We sought to evaluate gadobenate dimeglumine for the detection and characterization of focal liver lesions in the unenhanced and already pre-enhanced liver. MATERIALS AND METHODS: Sixty patients were evaluated prospectively. Unenhanced T1-weighted gradient echo (T1wGRE) and T2-weighted turbo spin echo (T2wTSE) images were acquired followed by contrast-enhanced T1wGRE images during the dynamic, equilibrium, and delayed phases after the bolus injection of 0.05 mmol/kg gadobenate dimeglumine. An identical series of dynamic images was then acquired after the delayed scan following a second 0.05 mmol/kg bolus of gadobenate dimeglumine. Images were evaluated randomly in 2 sessions by 3 independent blinded readers. Evaluated images in the first session comprised the unenhanced images, the first or second set of dynamic images, and the delayed images. The second session included the unenhanced images, the dynamic images not yet evaluated in the first session, and the delayed images. The 2 reading sessions were compared for lesion characterization and diagnosis, and kappa (kappa) values for interobserver agreement were determined. Quantitative evaluation of lesion contrast enhancement was also performed. RESULTS: The enhancement behavior in the second dynamic series was similar to that in the first series, although pre-enhancement of the normal liver resulted in reduced lesion-liver contrast-to-noise ratios and the visualization of some lesions only on arterial phase images. Typical imaging features for the lesions included in the study were visualized clearly in both series. Strong agreement (kappa=0.56-0.89; all evaluations) between the 2 images sets was noted by all readers for differentiation of benign from malignant lesions and for definition of specific diagnosis, and between readers for diagnoses established based on images acquired in the unenhanced and pre-enhanced liver. CONCLUSION: Dynamic imaging in the hepatobiliary phase gives similar information as dynamic imaging of the unenhanced liver. This might prove advantageous for screening protocols involving same session imaging of primary extrahepatic tumors and liver.     

Intrathecal gadolinium (gadopentetate dimeglumine) enhanced magnetic resonance myelography and cisternography: results of a multicenter study

RATIONALE AND OBJECTIVES: This cooperative multicenter human study was designed to evaluate the safety, magnetic resonance (MR) imaging characteristics, and clinical response to a single gadolinium contrast agent: gadopentetate dimeglumine. MATERIAL AND METHODS: Ninety-five patients (age range: 1 month to 78 years; sex: 50 males, 45 females) were included in this prospective study. The patients presented clinically with a variety of cranial or spinal signs and symptoms for which an intrathecal contrast myelogram or cisternogram was requested by clinical staff. Via lumbar puncture (20-25 g needle), 3 to 5 mL/ml of cerebrospinal fluid were withdrawn and mixed with a single volume of 0.5 (n = 63), 0.7 (n = 13), 0.8 (n = 12), or 1.0 (n = 7) cc/mL of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany). This was then injected into the subarachnoid space, and the needle was removed. Immediate and delayed (up to 96 hours) T1- and T2-weighted MR imaging was performed on super conductive, high-field (1.0-1.5 tesla) imaging units in two or three planes. All patients were hospitalized for an observation period of 24 hours following the procedure, and follow-up neurologic examinations were performed serially for 6 to 12 months afterward. RESULTS: No patient manifested gross behavioral changes, neurologic alterations, or seizure activity at any time following the procedure. Nineteen patients (20%) experienced postural postlumbar puncture headache, six patients had nausea (6%), and two patients had episodes of vomiting (2%), all which resolved within the first 24 hours of the lumbar puncture with conservative bed rest. CONCLUSION: This cooperative study demonstrates the general safety and feasibility of low dose (0.5-1.0 mL/ml) intrathecal gadopentetate dimeglumine administration. The potential useful clinical applications include the evaluation of obstructions and communications of the various subarachnoid spaces, spontaneous or traumatic/postsurgical craniospinal cerebrospinal fluid leaks, and subarachnoid space CSF flow and parenchymal CNS interstitial diffusion dynamics. This worldwide cooperative study seeks to progressively perform human studies for further definitive evaluation of the practical clinical applications, of the relationship of this technique to other imaging studies and modalities, and the long-term safety of the procedure in a larger number of subjects.     

Comparison of gadopentetate dimeglumine and albumin-(Gd-DTPA)30 for microvessel characterization in an intracranial glioma model

To compare the performance of macromolecular albumin gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)₃₀ and low molecular weight gadopentetate dimeglumine for microvessel characterization, we examined an intracranial 9L glioma model in which increased angiogenesis, hypervascularity, and hyperpermeability mimic characteristics of clinical malignant brain tumors. Dynamic MRI data were analyzed using a bidirectional, two-compartment kinetic model to extract quantitative estimates for fractional blood volume (fBV) and permeability surface area product (PS). Three criteria were used for comparison of contrast agent performance: (a) tumor conspicuity, defined as the contrast-to-noise ratio (CNR); (b) dynamic range of differential permeability estimates between tumor and normal brain; (c) reasonableness of blood volume estimates. Gadopentetate was superior to macromolecular albumin-(Gd-DTPA)₃₀ for detection of 9L brain gliomas and for measurements of hyperpermeability.     

Comparison of the iron oxide-based blood-pool contrast medium VSOP-C184 with gadopentetate dimeglumine for first-pass magnetic resonance angiography of the aorta and renal arteries in pigs

RATIONALE AND OBJECTIVES: VSOP-C184 at a dose of 0.045 mmol Fe/kg has been shown to be an efficient blood pool contrast medium for equilibrium magnetic resonance angiography (MRA) that can be administered as a bolus. The present study was performed to determine whether VSOP-C184 is also suitable for first-pass MRA. MATERIALS AND METHODS: Fifteen MRA examinations at 1.5 T were performed in minipigs using a fast 3D fast low-angle shot (FLASH) sequence (repetition time = 4.5 ms, echo time = 1.7 ms, excitation angle = 25 degrees, matrix 256, body phased-array coil). The citrate-stabilized iron oxide preparation VSOP-C184 was investigated (total particle diameter: 7.0 +/- 0.15 nm; core size: 4 nm) and compared with gadopentetate dimeglumine (Gd-DTPA). The following doses were tested: VSOP-C184: 0.015, 0.025, and 0.035 mmol Fe/kg; Gd-DTPA: 0.1 and 0.2 mmol Gd/kg; n = 3 examinations/dose. Data were analyzed quantitatively (signal enhancement (ENH) and vessel edge definition (VED)) and qualitatively. RESULTS: First-pass MRA using the 3 doses of VSOP-C184 yielded the following ENH: aorta: 9.4 +/- 2.6; 12.31 +/- 1.2; 16.53 +/- 1.7; renal arteries: 7.6 +/- 2.2; 9.9 +/- 1.0; 13.2 +/- 0.5. The values for the 2 doses of Gd-DTPA were aorta: 12.9 +/- 1.0; 16.8 +/- 2.2; renal arteries: 11.2 +/- 1.23; 11.3 +/- 1.7. VED for the 3 doses of VSOP-C184 was aorta: 106.3 +/- 31.0; 135.3 +/- 58.8; 141.3 +/- 71.0; renal arteries: 102.2 +/- 24.3; 146.8 +/- 63.0; 126.9 +/- 37.6 and for the 2 doses of Gd-DTPA, aorta: 157.2 +/- 47.8; 164.2 +/- 36.8; renal arteries: 165.9 +/- 30.4; 170.3 +/- 38.2 respectively. The differences between VSOP-C184 and Gd-DTPA are clinically not relevant and statistically not significant (p > or = .05). Qualitative evaluation of image quality, contrast, and delineation of vessels showed the results obtained with VSOP-C184 at doses of 0.025 and 0.035 mmol Fe/kg to be similar to those of Gd-DTPA at 0.1 and 0.2 mmol Gd/kg. CONCLUSION: VSOP-C184 is suitable for first-pass MRA at doses of 0.025 and 0.035 mmol Fe/kg and thus, in addition to its blood pool characteristics, allows for selective visualization of the arteries without interfering venous signal.     

Low-dose 3D time-resolved magnetic resonance angiography (MRA) of the supraaortic arteries: correlation with high spatial resolution 3D contrast-enhanced MRA

Purpose

To evaluate the feasibility of low‐dose, 3D time‐resolved contrast‐enhanced magnetic resonance angiography (TR‐CEMRA) in the assessment of the supraaortic vessel, and to compare the results with high‐resolution contrast‐enhanced MRA (HR‐CEMRA).

Materials and Methods

This was an Institutional Review Board‐approved retrospective study. Forty‐five consecutive patients underwent contrast‐enhanced 3D TR‐CEMRA and 3D HR‐CEMRA for evaluation of neurovascular disease at 3.0 T. Gadobutrol was administered at a constant dose of 1 mL for TR‐CEMRA (independent of patient weight), and 0.1 mmol/kg for HR‐CEMRA. Two readers evaluated image quality using a four‐point scale (from 0 = excellent to 3 = nondiagnostic), and subsequently graded each stenosis into clinically relevant categories: normal (0%), mild stenosis (<50%), moderate to severe (>50%), and occlusion.

Results

The overall image quality for low‐dose TR‐CEMRA was in the diagnostic range (median 0, range 0–3). On the grading of stenosis, TR‐CEMRA using the TWIST sequence correlated with HR‐CEMRA (r = 0.668, P < 0.001). In terms of the comparison of TR‐CEMRA with HR‐CEMRA, of the 675 supraaortic arterial segments evaluated for stenosis or occlusion, agreement occurred in 611 of 675 (90.5%), overestimation in 41 of 675 (6.1%), and underestimation 23 of 675 (3.4%).

Conclusion

TR‐CEMRA achieved by administration of a small contrast dose (1 cc) yields rapid and important functional and anatomical information in the evaluation of supraaortic arteries. Due to limited spatial resolution, TR‐CEMRA at the current parameters has a tendency to overestimate the stenosis of smaller intracranial arteries compared to HR‐CEMRA. J. Magn. Reson. Imaging 2011;33:71–76. © 2010 Wiley‐Liss, Inc.     

Gadobenate dimeglumine as a contrast agent for dynamic breast magnetic resonance imaging: effect of higher initial enhancement thresholds on diagnostic performance

RATIONALE AND OBJECTIVE: Gadobenate dimeglumine (Gd-BOPTA), a high-relaxivity contrast agent, has been recently proposed for dynamic MR imaging of the breast. The objective of this study was to optimize the diagnostic performance of Gd-BOPTA-enhanced dynamic breast MR imaging by using adjusted initial enhancement thresholds. METHODS: Thirty-four patients with 36 breast lesions (malignant/benign = 28/8) underwent dynamic breast MRI with 0.1 mmol/kg Gd-BOPTA and 120-second time resolution. A score system based on shape (round/oval/lobular = 0; linear/dendritic/stellate = 1), margins (defined = 0; undefined = 1), pattern (homogeneous = 0; inhomogeneous = 1; rim = 2), kinetics (continuous = 0; plateau = 1; washout = 2), and initial enhancement was used. Initial enhancement was determined with standard (<50% = 0; 50%-100% = 1; >100% = 2) and adjusted (<100% = 0; 100%-240% = 1; >240% = 2) thresholds. Scores of 0 to 3 indicated benign lesions and scores of 4 to 8 malignant lesions. Diagnostic performance was assessed in terms of sensitivity, specificity, positive and negative predictive values, and overall accuracy. RESULTS: The initial enhancement was >100% for 26 malignant and 7 benign lesions and >240% for 16 and 1 lesions, respectively. The overall score was 5.89 +/- 1.34 with standard thresholds and 5.50 +/- 1.53 with adjusted thresholds (P = 0.003) for cancers, 4.00 +/- 1.93 and 3.25 +/- 1.75 (P = 0.028) for benign lesions, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy was 96%, 13%, 79%, 50%, and 78%, respectively, with standard thresholds and 96%, 75%, 93%, 86%, and 92%, respectively, with adjusted thresholds. A ductal carcinoma in situ was false negative whereas a fat necrosis and a papilloma were false positive with both thresholds. Three fibroadenomas, 1 adenosis, and 1 fibrosis were false positive with standard thresholds but true negatives with adjusted thresholds. CONCLUSIONS: Lesion characterization with Gd-BOPTA requires higher thresholds for initial enhancement than those used with conventional Gd-chelates, leading to improved specificity, predictive values, and accuracy.     

Dose comparison of single- vs. double-dose in contrast-enhanced magnetic resonance angiography of the carotid arteries: Intraindividual cross-over blinded trial using Gd-DTPA

PURPOSE: To compare and contrast the pattern and characteristics of the cerebral blood volume (CBV) response to ethanol (EtOH) in rats under awake and anesthetized conditions. MATERIALS AND METHODS: Acute EtOH (0.75 g/kg) challenge-induced CBV changes were measured using a contrast-enhanced functional MRI CBV method in 15 male Sprague Dawley rats under three experimental conditions: 1.0% to 1.2% isoflurane (N = 5); 0.8% halothane (N = 5); and awake with no anesthetic (N = 5). Physiological parameters were collected from bench settings in nine rats from the above different conditions. Four parameters: 1) area under the curve (AUC%); 2) the maximum signal change (Max%); 3) EtOH absorption rate (alpha(2)); and 4) EtOH elimination rate (alpha(1)) were employed to compare EtOH-induced MRI signals between the awake and anesthetized groups. RESULTS: Both awake and anesthetized animals responded with an increase in CBV to EtOH challenge. However, the presence of anesthesia promoted a significant preferential flow to subcortical areas not seen in the awake condition. CONCLUSION: Unclear mechanisms of anesthesia add a layer of uncertainty to the already complex interpretation of EtOH's influence on neuronal activity, cellular metabolism, and hemodynamic coupling.