Contrast-enhanced MR imaging of brain lesions: a large-scale intraindividual crossover comparison of gadobenate dimeglumine versus gadodiamide

BACKGROUND AND PURPOSE: The higher relaxivity of gadobenate dimeglumine compared with gadodiamide is potentially advantageous for contrast-enhanced brain MR imaging. This study intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and quantitative lesion enhancement.MATERIALS AND METHODS: Adult patients with suggested or known brain lesions underwent 2 identical MR imaging examinations at 1.5T, one with gadobenate dimeglumine and the other with gadodiamide. The agents were administered in randomized order separated by 3–14 days. Imaging sequences and postinjection acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images qualitatively for diagnostic information (lesion extent, delineation, morphology, enhancement, and global preference) and quantitatively for contrast-to-noise ratio (CNR).RESULTS: One hundred thirteen of 138 enrolled patients successfully underwent both examinations. Final diagnoses were intra-axial tumor, metastasis, extra-axial tumor, or other (47, 27, 18, and 21 subjects, respectively). Readers 1, 2, and 3 demonstrated global preference for gadobenate dimeglumine in 63 (55.8%), 77 (68.1%), and 73 (64.6%) patients, respectively, compared with 3, 2, and 3 patients for gadodiamide (P < .0001, all readers). Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine was demonstrated for all qualitative end points and for CNR (increases of 23.3%–34.7% and 42.4%–48.9% [spin-echo and gradient-refocused echo sequences, respectively] for gadobenate dimeglumine compared with gadodiamide). Inter-reader agreement was good for all evaluations (κ = 0.47–0.69). Significant preference for gadobenate dimeglumine was demonstrated for all lesion subgroup analyses.CONCLUSION: Significantly greater diagnostic information and lesion enhancement are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared with gadodiamide at an equivalent dose.

Effective management of patients with tumors of the central nervous system (CNS) depends on accurate detection and characterization of enhancing lesions. Enhancement of tumors on gadolinium-enhanced MR imaging is a key imaging feature used in guiding surgical resection, delineating appropriate radiosurgical target volumes, and following patients for disease recurrence.^1,2Five gadolinium-based contrast agents are currently approved by the US Food and Drug Administration for MR imaging of the CNS. Although these agents have different molecular structures and physicochemical properties, they share the ability to transiently accumulate in areas with an abnormal blood-brain barrier, leading to faster T1 relaxation times and demonstrable contrast enhancement. Of these agents, gadobenate dimeglumine (Gd-BOPTA, MultiHance; Bracco, Milan, Italy) exhibits the highest R1 and R2 relaxivity in vivo.^3,4 The increased relaxivity derives from weak and transient interactions of the Gd-BOPTA contrast-effective molecule with serum albumin^5,6 and leads to increased signal-intensity (SI) enhancement relative to that obtained with other agents at an equivalent dose. Recent comparative studies in patients with brain or spinal tumors^7–12 have shown that this increased SI enhancement translates into significantly greater diagnostic performance compared with gadopentetate dimeglumine (Gd-DTPA, Magnevist; Bayer Healthcare, Leverskusen, Germany)^7–9 and an agent approved solely in Europe (gadoterate meglumine, Gd-DOTA; Dotarem; Guerbet, Aulnay-sous-Bois, France).¹⁰On the basis of R1 relaxivity values alone,^3,4 one might expect similar diagnostic superiority for gadobenate dimeglumine over gadodiamide (Gd-DTPA-BMA, Omniscan; GE Healthcare, Waukesha, Wis) when these agents are compared at equivalent doses, particularly given the similar diagnostic performance of gadodiamide and gadopentetate dimeglumine in patients with CNS disease.^13,14 However, whereas early interindividual parallel-group studies to compare gadobenate dimeglumine and gadodiamide revealed equivalence for a double (0.2 mmol/kg of body weight [BW]) dose (or a 1.5-fold dose) of gadobenate dimeglumine compared with a triple (0.3 mmol/kg BW) dose of gadodiamide, little if any differences were noted between single (0.1 mmol/kg BW) doses of these agents.^15,16 The aim of this study (MR EvaluatioN of MultiHance And OmniscaN for Contrast Enhancement [the MR-ENHANCE study]) was, therefore, to compare more accurately these 2 agents by using a controlled multicenter double-blind randomized intraindividual crossover study design in which each patient received 0.1-mmol/kg doses of both these agents in 2 identical MR imaging examinations.