Comparative Evaluation of Lower Gadolinium Doses for MR Imaging of Meningiomas: How Low Can We Go?

DISCUSSION

Decreasing the gadolinium dose in the follow-up MRIs of meningiomas to a low dose (62% of standard) or a micro dose (25% of the standard) resulted in a statistically significant decrease in signal difference between the tumor and the adjacent brain tissue as well as between the tumor and the venous sinuses on quantitative analysis. However, these quantitative differences were only clinically relevant for the micro dose, as the low dose was noninferior to the standard dose in terms of proportion of cases with suboptimal differentiation. A further reduction in contrast dose to a micro dose (25% of standard) significantly increased the proportion of suboptimal cases.

Our results agree with previous studies that found a directly proportional relationship between lesion enhancement and increasing the dose of contrast agent¹⁰; for example, Haustein et al¹¹ assessed the efficacy of gadopentetate dimeglumine, at concentrations of 0.025 mmol/kg, 0.05 mmol/kg, and 0.1 mmol/kg for imaging varying intracranial tumors. Our study differs from this one, however, in several points, namely that we examined a different contrast agent, gadobutrol, and focused solely on assessment of meningiomas rather than multiple various intracranial tumors.

There have been prior studies, like ours, that have looked at the effect of reducing the dose of gadolinium administered. However, these studies specifically studied whether more highly concentrated gadolinium agents, namely gadobenate dimeglumine, could be suited for reduced-dose protocols.¹² In their study, Delano et al¹² compared 0.05 mmol/kg and 0.1 mmol/kg gadobenate in patients undergoing MRI of various intracranial tumors and found that while a dose of 0.05 mmol/kg was found noninferior to a full 0.1 mmol/kg dose, a significantly higher lesion-to-brain ratio and contrast-to-noise ratio was observed with higher doses.

Previous studies have suggested that noncontrast sequences alone are sufficient for follow-up imaging of intracranial meningiomas.^7–8,13 A recent study by Boto et al¹⁴ demonstrated robust agreement between T1 3D-gadolinium and T2WI sequences of meningioma diameter and volume, suggesting that noncontrast T2W1 sequences are sufficient for follow-up of untreated meningiomas. However, they did not include small volume and residual operated tumors. Similarly, a recent study by Raban et al¹⁵ demonstrated that volumetric T2WI detects changes in meningioma volume with comparable accuracy to criterion standard T1 3D-gadolinium imaging; however, their results were only reliable for tumors with higher tumor volumes and posterior fossa locations. The key distinction between our study and prior investigations is that we also included patients with small residual and recurrent meningiomas, which constitute a substantial proportion of those undergoing repeat brain MRIs.

Previous studies advocating for the use of noncontrast imaging have found that visualization of venous sinus invasion by meningiomas is often hindered on T1 gadolinium-weighted sequences without a black-blood technique,¹⁴ as enhancement of the meningioma is sometimes difficult to distinguish from opacification of the venous sinus itself, and that vascular invasion is often better depicted on T2WI sequences as an absence of flow void and by direct visualization of the edges of the meningioma itself. Similarly, our study also revealed that the differentiation of meningiomas from the adjacent dural venous sinuses is challenging. At the standard dose, 12% of studies showed suboptimal differentiation between the tumor and the sinus, and this percentage increased to 18% and 46% at the low and micro doses, respectively, hindering accurate assessment of tumor sinus invasion. Although T1-weighted 3D gradient-echo sequences are commonly used for meningioma follow-up, the assessment of venous sinus invasion is limited with this technique, and a blackblood sequence would be preferred.

Meningiomas, although typically slow-growing tumors, can show significant growth in a considerable proportion of patients.¹⁶ Consequently, long-term imaging follow-up with repeat exposure to GBCAs is often required, which may lead to potential adverse health effects such as gadolinium deposition in tissues and nephrogenic systemic fibrosis in those with kidney issues.^4,17,18 Contrast administration also increases imaging costs and is becoming an environmental concern as gadolinium is increasingly detected in waste waters, becoming a new water microcontaminant.^5,6 Future research in this area could focus on cost-effectiveness analyses that will provide valuable information for informed decision-making. This approach empowers stakeholders to make more informed choices that prioritize patient well-being but also optimize resource allocation, ensuring that health care resources are utilized judiciously.

We believe that one of the strengths of our study is that we did not exclude skull base, small, or operated meningiomas, making our results more generalizable and allowing greater external validity than if we had only focused on convexity meningiomas as in other studies.⁷ There are a few limitations: First, in part of our cohort, the meningioma diagnosis had been confirmed with histopathology, but not in all cases. Therefore, we cannot exclude the possibility that other dural-based lesions such as solitary fibrous tumors were also included. Second, our analysis included a “range of doses” when defining standard, low, and micro doses instead of specific dosage, which increases the complexity of application of results in clinical practice. Additionally, the dose of contrast that patients within the same group received was variable. For example, some subjects in the micro group may have received only 10% of a standard dose, while others may have received up to 40%. Grouping the patients into such broad dose ranges does not allow for concrete recommendations on the optimal dose, but smaller dose ranges would have prevented meaningful comparisons due to small sample size. Third, the time between contrast administration and imaging is known to impact contrast enhancement. Given the retrospective nature of the study, time from contrast administration to imaging was not under our control and may have varied between studies. Fourth, different doses were given at different time points, and although we expect enhancing characteristics of these tumors to be largely stable over time, we cannot confirm this type of stability. Overall, the goal of imaging follow-up of meningiomas is to determine whether interval growth or, more rarely, tumor regression has occurred. This was not the primary outcome of our study because the different doses were scanned at different time points, and therefore we would not have been able to truly compare the different doses to the outcome of progression.