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Contrast Media |
1 From the Neuroradiology and MR Research Laboratory, University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98195 (K.R.M.); Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC (J.A.M.); Neuroradiology Research, University of Florida, Gainesville, Fla (I.M.S.); Department of Radiology, Southern Illinois University School of Medicine, Springfield, Ill (M.J.K.); Department of Radiology, University of Miami School of Medicine, Miami, Fla (B.C.B.); Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (F.J.W.); Department of Radiology, Scott and White Memorial Hospital, Temple, Tex (V.M.R.); Department of Radiology, Ohio State University-University Hospitals, Columbus, Ohio (M.V.K.); Department of Neuroradiology, Centre Hospitalier et Universitaire de Neuroradiologie, Nancy, France (S.K.); Department of Radiology, University Hospital, Newark, NJ (L.J.W.); Department of Neuroradiology, San Raffaele Hospital, Milan, Italy (N.A.); German Cancer Research Institute, Heidelberg, Germany (M.E.); and Department of Neuroradiology, Sahlgrenska University Hospital, Gothenburg, Sweden (L.G.). Received July 28, 2005; revision requested September 30; revision received November 10; accepted December 8; final version accepted February 6, 2006. K.R.M. and V.M.R. received partial support and consulted for Bracco Diagnostics. L.J.W. received support from Berlex and Bracco Diagnostics. Address correspondence to K.R.M. (e-mail: kmarav{at}u.washington.edu).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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Materials and Methods: This study was HIPAA-compliant at U.S. centers and was conducted at all centers according to the Good Clinical Practice standard. Institutional review board and regulatory approval were granted; written informed consent was obtained. Seventy-nine men and 78 women (mean age, 50.5 years ± 14.4 [standard deviation]) were randomized to group A (n = 78) or B (n = 79). Patients underwent two temporally separated 1.5-T MR imaging examinations. In randomized order, gadobenate followed by gadopentetate was administered in group A; order of administration was reversed in group B. Contrast agent administration (volume, speed of injection), imaging parameters before and after injection, and time between injections and postinjection acquisitions were identical for both examinations. Three blinded neuroradiologists evaluated images by using objective image interpretation criteria for diagnostic information end points (lesion border delineation, definition of disease extent, visualization of internal morphologic features of the lesion, enhancement of the lesion) and quantitative parameters (percentage of lesion enhancement, contrast-to-noise ratio [CNR]). Overall diagnostic preference in terms of lesion conspicuity, detectability, and diagnostic confidence was assessed. Between-group comparisons were performed with Wilcoxon signed rank test.
Results: Readers 1, 2, and 3 demonstrated overall preference for gadobenate in 75, 89, and 103 patients, compared with that for gadopentetate in seven, 10, and six patients, respectively (P < .0001). Significant (P < .0001) preference for gadobenate was demonstrated for diagnostic information end points, percentage of lesion enhancement, and CNR. Superiority of gadobenate was significant (P < .001) in patients with intraaxial and extraaxial lesions.
Conclusion: Gadobenate compared with gadopentetate at an equivalent dose provides significantly better enhancement and diagnostic information for CNS MR imaging.
© RSNA, 2006
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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A marked improvement in contrast enhancement is observed when higher doses (0.2–0.3 mmol/kg) of gadolinium-based agents are used (15–21). This has been shown not only to benefit the detection and delineation of small or poorly enhancing metastatic lesions but also to improve delineation of the extent of involvement of primary CNS tumors, and thereby to facilitate the more accurate guidance of surgical resections and the better demarcation of target volumes for radiosurgery (20–28). The increased exposure of patients to contrast material and the increased costs related to higher dose or delayed scanning techniques, however, have limited the use of these techniques in MR imaging of the CNS (29,30). An alternative means to improve the contrast enhancement of lesions of the CNS at MR imaging without having to increase the contrast agent dose and without using delayed imaging techniques that prolong the examination time would be highly clinically desirable.
Gadobenate dimeglumine (MultiHance; Bracco Diagnostics, Princeton, NJ), hereafter referred to as gadobenate, is a gadolinium-based MR contrast agent that was approved by the U.S. Food and Drug Administration for MR imaging of the CNS and related tissues on November 23, 2004 (http://www.fda.gov/cder/rdmt/ndaaps04cy.htm). Compared with gadopentetate dimeglumine (Magnevist; Berlex, Montvale, NJ), hereafter referred to as gadopentetate, and other approved gadolinium-based agents, gadobenate has markedly greater T1 and T2 relaxivities in blood (9.7 L · mmol–1 · sec–1 and 12.5 L · mmol–1 · sec–1, respectively) because of weak and transient interaction of the gadobenate contrast-effective moiety with serum proteins (31,32).
Researchers in a series of preliminary studies showed that the increased efficiency of gadobenate in shortening the T1 relaxation time may translate into improved conspicuity and detectability of CNS lesions, as well as in substantial improvement of lesion-to-brain contrast (33–35). Although the intraindividual crossover design of these earlier studies of Colosimo et al (33), Knopp et al (34), and Colosimo et al (35) is the most rigorous means of comparing the contrast enhancement effects of two or more contrast agents and requires comparatively few patients to reveal substantial differences compared with larger parallel group studies, these studies included a relatively small number of patients—22, 27, and 23 patients, respectively—and included only patients with intraaxial primary or secondary brain tumors.
Thus, the purpose of our study was to prospectively compare a dose of 0.1 mmol/kg of gadobenate with the same dose of gadopentetate for contrast material–enhanced MR imaging of various lesions of the CNS by using a multicenter double-blinded randomized intraindividual crossover design.
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MATERIALS AND METHODS |
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Patients
A total of 157 patients (79 men, 78 women; mean age, 50.5 years ± 14.4 [standard deviation]; range, 20–84 years), who were known to have or were suspected of having lesions of the brain (n = 149) or spine (n = 8) and who had been referred for MR imaging of the CNS, were enrolled in a consecutive manner at each of 11 participating centers between December 2003 and December 2004. Among the enrolling centers, two centers enrolled 36 and 33 patients each. The remaining centers enrolled the following numbers of patients: 25, 21, 13, nine, eight, seven, two, two, and one.
Patients were excluded (a) if they had received an investigational drug within 30 days prior to admission to the study or were scheduled to receive such a drug during the course of the study or within 24 hours of the administration of the second study agent or (b) if they had received any other contrast agent within 24 hours prior to administration of the first study agent or were expected to receive any other contrast agent within 24 hours of the administration of the second study agent. Patients were also excluded if they had class III or IV congestive heart failure according to the New York Heart Association classification (36) or other medical conditions or circumstances (eg, claustrophobia, hypersensitivity to gadolinium or other metals, pacemaker) that would substantially decrease the chances of obtaining reliable data. Finally, nursing or pregnant patients were ineligible, as were patients who had received or were going to receive any treatment (eg, whole-brain fractionated radiation therapy, steroid therapy, or stable chemotherapy) that could have changed the visualization of CNS lesions between the two examinations.
Eligible patients were randomized prospectively into two study groups, groups A and B, which were designated according to the sequence of administration of the contrast agents. Patients randomized to study group A (n = 78) received gadobenate for the first MR imaging examination and gadopentetate for the second examination, whereas patients randomized to study group B (n = 79) received gadopentetate for the first examination and gadobenate for the second examination.
MR Imaging
Patients underwent MR imaging with a 1.5-T system (Magnetom Vision [n = 34], Symphony [n = 8], or Sonata [n = 46], Siemens Medical Solutions, Malvern, Pa; Genesis Signa [n = 38], Signa LX [n = 21], or Signa Excite [n = 10], GE Medical Systems, Milwaukee, Wis) and a standard head coil for brain imaging or a phased-array spine coil for spinal imaging.
A standardized MR imaging protocol that comprised T1- and T2-weighted spin-echo (SE) acquisitions before the injection of contrast agent and a T1-weighted SE acquisition after the injection of contrast agent was used in all patients. The same imaging system, planes of view, and parameters were used for both examinations in each patient, and care was taken to ensure that image location and angulation were identical for the two examinations to image identical sections that could be directly compared by angling all transverse brain imaging examinations parallel to, and tangential with, the inferior callosal line. In each patient, pre- and postinjection T1-weighted SE sequences were performed with identical imaging parameters (repetition time msec/echo time msec, 
600/15; flip angle, 90°; number of signals acquired, one or two; section thickness, 3–5 mm; intersection gap, 30%). The interval between intravenous injection and the start of the postinjection T1-weighted image acquisition was carefully timed so that the delay was identical (3–10 minutes after contrast agent injection; average, 5 minutes) for the two examinations performed in each patient. The choice of field of view and matrix size were at the discretion of the investigator but were to be selected to obtain an image pixel size of 1.37 mm2 or smaller (eg, a 35-cm [field of view] ÷ 256 [matrix] = 1.37-mm pixel size) and also were identical for each of the two imaging examinations for a given patient. The preinjection T2-weighted SE sequence was performed with parameters of 3000–6000/80–120; flip angle, 90°; number of signals acquired, one or two; section thickness, 3–5 mm; and an intersection gap, 30% or less. Again, the only stipulation for field of view and matrix size was that the image pixel size should be 1.37 mm2 or smaller.
In both examinations, contrast agent administration was performed intravenously in an identical manner with either a power injector (n = 100) or a manual bolus injection (n = 57). Contrast agent administration by using a power injector was performed at a rate of 2 mL/sec with a 20-gauge needle unless patient-related factors (eg, small veins) necessitated use of a needle with a different size. When the contrast agent was administered manually, the calculated volume was delivered with a rapid hand injection (approximating an injection rate of 2 mL/sec) by injecting the medication during the appropriate number of seconds with a careful attempt to ensure that the same approximate rate of injection was used for both agents in each examination in each patient. Each contrast agent was administered in the order determined according to a randomization list at a dose of 0.1 mmol/kg, which corresponded to 0.2 mL/kg of a formulation of 0.5 mol/L. The same volume of contrast agent was injected in both examinations. The interval between the two MR imaging examinations was greater than 48 hours in all patients to prevent any effect of carryover but less than 7 days in all patients to minimize the chance of measurable disease progression or lesion evolution that could have changed the image appearance.
Image Evaluation
All images were evaluated by three independent neuroradiologists (M.E., N.A., L.G.) who had 12–17 years of experience and were not affiliated with the study centers. These neuroradiologists were fully blinded to the contrast agent used in each examination, to all patient clinical and radiologic information, and to all interpretations of on-site investigators. Each blinded reader evaluated the patient's images separately and independently.
All images obtained in each patient were evaluated in a global matched-pairs fashion. Images were presented for review at a multimonitor imaging workstation. For each randomized patient number, all images (first preinjection T1- and T2-weighted SE images and first postinjection T1-weighted SE images) from the first examination, labeled as examination 1, were displayed simultaneously with the corresponding images (second preinjection T1- and T2-weighted SE images and second postinjection T1-weighted SE images) from the second examination, labeled as examination 2. Each reader was able to perform all routine interactive image manipulation functions (eg, window, level, zoom, and pan) on both sets of images. An electronic case report form for each randomized patient was displayed on a separate monitor so that the readers could directly record their assessment findings. After the findings were recorded and the neuroradiologist had signed off, the assessment findings were automatically locked and could not be further modified.
All images from both examinations in each patient were evaluated preliminarily for technical adequacy. Images were considered technically adequate if the brain or the spine was clearly visualized, if evaluation and diagnosis were possible despite any artifacts that might partially compromise image quality, or if only partial evaluation was possible because of inadequate anatomic coverage of the brain or the spine. Images were only considered technically inadequate if artifacts completely compromised image interpretability. If the postinjection T1-weighted SE images from either examination were considered technically inadequate by any of the three readers, no further assessment was performed for that patient by that reader.
Assessment of Diagnostic Information
Technically adequate images were evaluated qualitatively for diagnostic information and were assigned scores in terms of (a) delineation of lesion border, (b) extent of disease (for extraaxial lesions, this quality pertained to the definition of the space in which the lesion was present, and for intraaxial lesions, it pertained to the invasion of white matter, gray matter, or both; the neuroanatomic distribution of the lesion; and its mass effect), (c) visualization of internal morphologic features of lesions (whether the internal architecture of the lesion was depicted and the intralesional features could be adequately identified), and (d) contrast enhancement of lesions (difference in signal intensity [SI] between the lesions and the surrounding normal brain or spinal tissue). All assessments were performed with three-point scales from –1 (for which examination 1 was rated as superior) through 0 (for which both examinations were rated as equal) to +1 (for which examination 2 was rated as superior). For the various end points, superiority was recorded on the electronic case report form for one of the examinations if it allowed better distinction of one or more lesions from surrounding tissues, structures, or edema; better detection of the extent of the lesion; clearer depiction of intralesional features; better difference in SI between lesions and surrounding normal brain or spinal tissue; or depiction of one or more lesions only after that examination.
On the electronic case report form, the readers also had to express their overall diagnostic preference. For cases in which a reader had an overall diagnostic preference for one examination rather than the other, this reader then had to select one or more of the following six reasons for this preference: contrast enhancement was superior, delineation of normal structure was better, delineation of at least one lesion was better, internal structure of lesions was better visualized, more lesions were identified, or diagnostic confidence was greater.
If diagnostic confidence was selected as a reason for global preference, one or more of the following specifications was required: detection of lesions, characterization of disease, assignment of a grade to disease (ie, high or low grade in the case of intraaxial gliomas), definition of extent of disease, or other reasons that had to be specified on the electronic case report form.
Quantitative Assessment
Quantitative evaluation of as many as three enhancing lesions per patient was performed by each of the three blinded readers independently by using a simultaneous matched-pairs approach. Measurements of SI were made at regions of interest (ROIs) positioned on areas of normal brain or spinal cord parenchyma, as well as on as many as three lesions identified on contrast-enhanced T1-weighted SE images from both examinations. Additional SI measurements were made in ROIs placed in selected areas external to the brain or the spine to determine the background noise. All measurements of SI at each ROI were made on a pixel-by-pixel basis by using quantitative analysis software (Analyze, version 4.0; Mayo Foundation, Rochester, Minn). The SI values determined were recorded directly on the electronic case report form.
To standardize the size and placement of ROIs within a patient, round, elliptical, or manually drawn ROIs were placed on the image frame from the MR imaging examination that provided the best visualization of the lesions. In the case of multiple lesions, ROIs were placed on as many as three visualized lesions in the largest most conspicuous areas. ROIs were as large as possible (ideally larger than 1 cm in diameter) but included only homogeneous areas. Strict care was taken to avoid the inclusion of vessels or other inhomogeneous structures or artifacts in the ROI. Each selected ROI on the postinjection T1-weighted SE image set was labeled and then appeared simultaneously on the corresponding preinjection T1-weighted SE image set and the pre- and postinjection T1-weighted SE image sets from the other MR imaging examinaton. This process ensured that ROIs of equal size were positioned at identical coordinates on all corresponding image sets. Each reader was able to manually adjust the position of the ROIs on each image to account for areas not in register.
ROIs positioned on normal brain (white matter) or spinal cord parenchyma were placed on the same image as the ROI for the lesion to include the largest possible area. Each reader positioned these ROIs with care to ensure that they were free of enhancing structures or artifacts and to exclude the possibility of contrast enhancement caused by lesion-related hemorrhage. The background noise was measured with the largest possible ROI placed in an area outside of the brain or the spine that was free of ghosting or motion artifacts.
The SI measurements were then used to calculate lesion SI enhancement, or percentage of enhancement, from before to after injection and lesion-to-brain or lesion-to-spine contrast-to-noise ratio (CNR), according to the following equations: %Enh = 100 · (SILpost – SILpre)/SILpre, where %Enh is percentage of enhancement, SILpost is postinjection SI of the lesion, and SILpre is preinjection SI of the lesion, and CNR = (SILpost – SINtpost)/SDnoise, where SINtpost is postinjection SI of normal tissue of the brain or spine, and SDnoise is the standard deviation of the noise.
Safety Assessments
The safety of the two study agents was evaluated for all patients (n = 157) who underwent at least one contrast-enhanced MR imaging examination. Monitoring for adverse events was performed from the moment the patient signed the informed consent form until 24 hours after the administration of the first study agent and then again from the moment the second study agent was administered until 24 hours after the administration of the second agent. Adverse events were classified by the 11 principal investigators (one per investigational center; including K.R.M., J.A.M., I.M.S., M.J.K., B.C.B., F.J.W., V.M.R., M.V.K., S.K., and L.J.W.) as either serious (ie, death, life-threatening, requiring or prolonging hospitalization) or not serious (rated as mild, moderate, or severe). The relationship of each adverse event to the study agent was classified as probable, possible, not related, or unknown.
Statistical Analysis
Power determination was based on a superiority test in which gadobenate was compared with gadopentetate for the three coprimary end points (delineation of the lesion border, visualization of internal morphologic features, and degree of contrast agent enhancement). The sample size calculation was based on the exact sign test of equality of paired proportion for a crossover study and was performed by using software (nQuery 5.0; Statistical Solutions, Saugus, Mass). When we assumed that the expected difference in proportion between the two groups was 15% and the proportion of discordant pairs was 32%, 135 patients who could be evaluated were needed to attain 85% power. When we assumed a rate of dropout of 15%, it was considered necessary to recruit 158 patients to ensure that 135 patients who could be evaluated would complete the study.
Comparison of the distribution of CNS diseases between study groups A and B was performed by using the Fisher exact test. Data analysis of blinded reader evaluations was performed by using a statistical software package (SAS, version 8.2; SAS Institute, Cary, NC). The primary objective of this study was to compare the qualitative assessments of visualization between the two study agents. All comparisons of diagnostic information obtained with the two agents were evaluated by using the Wilcoxon signed rank test (37). Separate comparisons were performed for all patients who could be evaluated together, as well as for the largest subsets of patients (ie, patients with gliomas [n = 47], patients with brain or spinal metastases [n = 37], and patients with meningiomas [n = 23]). Inferential analysis was not performed in smaller subsets of patients. Interreader agreement for diagnostic findings was assessed by using generalized weighted 
statistics (38) and was measured as the percentage of agreement.
Evaluation of quantitative data was performed by using paired t tests for pre- to postinjection changes in SI. Differences between gadobenate and gadopentetate in regard to study agent effect were analyzed by using a mixed-effect model. The change from preinjection was the response variable, and factors included in the model were patient, period, sequence, study agent, and preinjection score, where patient nested within sequence was the random effect. Statistical analyses of the coprimary qualitative end points (delineation of lesion border, visualization of internal morphologic features, and degree of contrast agent enhancement) were conducted at a Bonferroni-adjusted significant difference level of P < .017. All other statistical tests were conducted at a significant difference level of P < .05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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.001, all evaluations and all readers). In the case of gliomas and mestastases, a significant difference was noted for determinations of the extent of disease (Fig 3) (P < .008, readers 1 and 3; P .035, reader 2). For determinations of internal morphologic features of the lesion, a statistically significant preference for gadobenate was noted by all readers for gliomas (P .005), by readers 1 and 3 for metastases (P = .021 and P = .004, respectively), and by reader 3 for meningiomas (P < .008) (Fig 4). For lesions that occurred with lower frequency (schwannomas, pituitary adenomas, CNS tumors for which histologic proof was lacking), preference for gadobenate was again noted by all three blinded readers (Table 3), although confirmatory statistical testing was not performed because of the low numbers of lesions. Overall preference for gadobenate was also noted for other qualitative determinations of less frequent lesion types, although statistical testing was not performed.
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values that ranged from 0.43 for internal morphologic features of the lesion to 0.57 for definition of extent of disease for all three readers. For percentage of agreement, all three blinded readers agreed completely in their assessments in 62.9%, 72.8%, 60.3%, 62.9%, and 60.3% of all patients for evaluations of delineation of lesion border, definition of extent of disease, visualization of internal morphologic features of the lesion, degree of contrast enhancement of the lesion, and global diagnostic preference, respectively. Greater overall values of 99.3%, 100%, 98.7%, 97.4%, and 97.4% for evaluations of delineation of lesion border, definition of extent of disease, visualization of internal morphologic features of the lesion, degree of contrast enhancement of the lesion, and global diagnostic preference, respectively, were obtained for assessment of the percentage of agreement between two of three blinded readers.
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Quantitative Evaluation
For all three blinded readers, the lesion-to-brain or lesion-to-spine CNR (Table 5) was significantly greater (P < .0001, all readers) after administration of gadobenate than it was after administration of gadopentetate for similar overall numbers of evaluated lesions (122, 125, and 124 lesions for readers 1, 2, and 3, respectively). The mean difference ± standard deviation in percentage of enhancement after administration of gadobenate compared with that after administration of gadopentetate was 19.60 ± 31.46 (95% confidence interval: 13.97, 25.24), 26.26 ± 35.93 (95% confidence interval: 19.90, 32.62), and 27.34 ± 36.05 (95% confidence interval: 20.93, 33.75) for readers 1, 2, and 3, respectively. These values correspond to relative increases in percentage of enhancement after administration of gadobenate of 22.26%, 24.72%, and 25.61% for readers 1, 2, and 3, respectively (Fig 5). In each case, the difference between gadobenate and gadopentetate was significant (P < .0001, all readers).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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In our study, the significant (P < .0001) superior contrast enhancement performance for gadobenate that was noted by each of the three blinded readers in the absence of between-group variations caused by patient and disease distribution is a clear indication that this agent possesses preferential properties compared with gadopentetate for MR imaging of the CNS. As noted in previous studies about intraindividual comparisons with gadopentetate and other conventional gadolinium-based contrast agents both for MR imaging of the CNS (33–35) and for other indications (47–51), the preferential performance of gadobenate can be attributed to the markedly greater T1 relaxivity in blood of this agent (9.7 L · mmol–1 · sec–1 for gadobenate compared with 4.9 L · mmol–1 · sec–1 for gadopentetate). This greater T1 relaxivity in blood is ascribed to a slowing of the tumbling rate of the molecule in blood due to weak and transient interactions of the contrast-effective moiety of gadobenate with serum proteins such as albumin (31,32). That the superior performance of gadobenate compared with gadopentetate derives from the greater relaxivity of the former agent is indirectly supported by the results of a previous comparatively large-scale intraindividual crossover study between gadoteridol (ProHance; Bracco Diagnostics, Princeton, NJ) and gadopentetate (52). In a manner similar to the activity of gadopentetate, gadoteridol does not interact with serum proteins and has a similar T1 relaxivity of 4.6 L · mmol–1 · sec–1. Among 80 patients evaluated in this previous study, no differences were noted between the two agents by either of two blinded readers, either in terms of diagnostic information available on contrast-enhanced images or in terms of numbers of lesions detected (52).
For extraaxial lesions such as meningiomas, the greater lesion enhancement achievable with gadobenate might be expected to improve lesion conspicuity (53), but in terms of overall clinical effect, the advantages of this agent may only be limited. On the other hand, for intraaxial tumors such as primary gliomas and secondary CNS metastases, the benefits of the higher T1 relaxivity of gadobenate may be expected to be more marked. Specifically, the possibility to achieve improved delineation of lesion borders and a greater definition of the extent of disease in the case of gliomas may possibly have benefit for treatment planning such as surgical resection or radiation therapy because it is known that the margins of these lesions usually extend beyond the areas typically demarcated on T2-weighted MR images or contrast-enhanced T1-weighted MR images (54,55).
In an early study to evaluate the quantitative effects of contrast agent dose on lesion-to-brain enhancement, Yuh et al (41) noted that the mean contrast ratios (defined as the normalized lesion to normal tissue enhancement ratio compared with a standard 0.1 mmol/kg dose of gadopentetate) for gadoteridol doses of 0.05, 0.1, 0.2, and 0.3 mmol/kg were 0.84, 0.99, 1.31, and 1.63, respectively. In other words, a mean increase in quantitative lesion enhancement of approximately 30% was noted between a dose of 0.1 mmol/kg and a dose of 0.2 mmol/kg of gadoteridol. Similar findings have been noted previously in studies that involved a comparison of cumulative doses of gadobenate for the detection of cerebral metastases (56,57). In our study, similar mean increments of approximately 30% for gadobenate compared with gadopentetate were noted by all three blinded readers for both lesion-to-brain or lesion-to-spine CNR and percentage of lesion enhancement. Although the administered doses of gadobenate and gadopentetate were identical (0.1 mmol/kg), the greater quantitative enhancement achieved with gadobenate corresponds roughly to that which would be expected by doubling the dose of gadopentetate, as might be expected on the basis of the roughly twofold greater T1 relaxivity of gadobenate in blood.
A final consideration in regard to the lesion enhancement achievable with gadobenate concerns the possibility to increase the CNR (and signal-to-noise ratio) still further by modifying the sequence parameters to better reflect the benefits that derive from the weak protein interaction and the resulting increased T1 relaxivity of this agent. To this end, it is possible that a reduction of the echo time of the T1-weighted sequences compared with those typically employed with gadopentetate and other conventional gadolinium-based agents might further improve the signal enhancement obtained with gadobenate (58). Further investigations, however, are required to determine the optimal sequence parameters to use with gadobenate. Moreover, further work is also warranted to optimize the performance of gadobenate with higher-field-strength (3-T) systems.
A limitation of our study was that the potential effect of gadobenate on patient treatment and outcome was not evaluated. Whereas the greater diagnostic information available on gadobenate-enhanced images would be expected to benefit therapeutic procedures, particularly with regard to better definition of the target volumes at radiosurgery, a more comprehensive understanding of the precise extent to which the greater available diagnostic information contributes to improved patient management would require a dedicated assessment. A study aimed at a comparison of the use of gadobenate and gadopentetate in patients with CNS disease for improved patient treatment is currently under way.
In conclusion, findings in our study indicate that gadobenate at a dose of 0.1 mmol/kg provides significantly improved CNS lesion enhancement and greater quantitative lesion-to-brain enhancement than does gadopentetate at the same dose. Assessment by three fully blinded neuroradiologists revealed a clear unanimous preference for gadobenate-enhanced images (P < .0001). We believe, therefore, that gadobenate should be considered for contrast-enhanced MR imaging of the CNS.
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ADVANCES IN KNOWLEDGE |
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FOOTNOTES |
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Abbreviations: CNR = contrast-to-noise ratio • CNS = central nervous system • ROI = region of interest • SE = spin echo • SI = signal intensity
See Materials and Methods for pertinent disclosures.
Author contributions: Guarantors of integrity of entire study, K.R.M., F.J.W., L.G.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, K.R.M., M.J.K., V.M.R., L.G.; clinical studies, K.R.M., J.A.M., I.M.S., M.J.K., B.C.B., F.J.W., V.M.R., M.V.K., S.K., N.A., M.E., L.G.; statistical analysis, L.G.; and manuscript editing, K.R.M., J.A.M., F.J.W., L.J.W., M.E., L.G.
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G. Schneider, M. Uder, M. Koehler, M. A. Kirchin, A. Massmann, A. Buecker, and U. Geisthoff MR Angiography for Detection of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia Am. J. Roentgenol., April 1, 2008; 190(4): 892 - 901. [Abstract] [Full Text] [PDF]
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