Consensus recommendations for a dynamic susceptibility contrast MRI protocol for use in high-grade gliomas

Abstract

Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction. In summary, full-dose preload, full-dose bolus dosing using intermediate (60°) FA and field strength-dependent TE (40-50 ms at 1.5 T, 20-35 ms at 3 T) provides overall best accuracy and precision for cerebral blood volume estimates. When single-dose contrast agent usage is desired, no-preload, full-dose bolus dosing using low FA (30°) and field strength-dependent TE provides excellent performance, with reduced contrast agent usage and elimination of potential systematic errors introduced by variations in preload dose and incubation time.

Keywords: DSC-MRI; cerebral blood volume; clinical trial; consensus protocol; high-grade glioma.

Fig. 1

DSC-MRI methodology in the literature varies greatly, as seen in the subgroup meta-analysis by Patel et al of studies using mean lesion rCBV for recurrent high-grade tumor vs treatment effect. These studies used a wide range of DSC-MRI parameters including TE, FA, preload dose, and post-processing leakage correction (PPLC).

Fig. 2

Possible BTIP-compliant DSC-MRI preload + bolus dose paradigms. Either a single total dose must be split between preload and DSC-MRI before post-GBCA imaging or a full dose preload must be given with DSC-MRI after post-contrast imaging.

Fig. 3

Computational approach for determining optimal BTIP-compliant DSC-MRI parameters using simulated DSC-MRI signal with GBCA leakage: heat maps of CBV error versus theoretical CBV without leakage for different combinations of acquisition parameters. Schemes with particularly high fidelity at 3T include 60° FA with full-dose preload and bolus (asterisk with dashed box) and low FA without preload (asterisk with solid box).

Fig. 4

Computational approach for determining optimal BTIP-compliant DSC-MRI parameters using a digital reference object matched to glioblastoma training data: performance comparison for intermediate and low flip angle schemes. For double-dose contrast with full-dose preload, both schemes have excellent accuracy and precision at 1.5T and 3T. For single-dose contrast without preload, intermediate FA performs poorly but low FA maintains excellent performance, even at 1.5T. For each dosing scheme, low FA had equal or better performance than intermediate FA. CCC = Concordance correlation coefficient (accuracy); CV = coefficient of variation (precision).

Fig. 5

(A) DRO-based simulations demonstrate that even without preload, low FA (30°) acquisitions give very accurate CBV (along the line of unity) with much less bias compared with intermediate FA (60°) acquisitions, even at 1.5T. (B) Excellent CBV agreement has been observed in vivo at 3T for “0 + 1” and “1 + 1” dosing schemes, according to Lin’s concordance correlation (CCC).