Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases

Abstract

A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases. The "minimum standard" recommended pulse sequences include: (i) parameter matched pre- and post-contrast inversion recovery (IR)-prepared, isotropic 3D T1-weighted gradient echo (IR-GRE); (ii) axial 2D T2-weighted turbo spin echo acquired after injection of gadolinium-based contrast agent and before post-contrast 3D T1-weighted images; (iii) axial 2D or 3D T2-weighted fluid attenuated inversion recovery; (iv) axial 2D, 3-directional diffusion-weighted images; and (v) post-contrast 2D T1-weighted spin echo images for increased lesion conspicuity. Recommended sequence parameters are provided for both 1.5T and 3T MR systems. An "ideal" protocol is also provided, which replaces IR-GRE with 3D TSE T1-weighted imaging pre- and post-gadolinium, and is best performed at 3T, for which dynamic susceptibility contrast perfusion is included. Recommended perfusion parameters are given.

Keywords: MRI; brain metastases; imaging; protocol.

Fig. 1

Comparison of 3D IR-GRE (A, C) and 3D TSE (B, D) T1-weighted imaging in a patient with metastatic lung carcinoma to the brain. Larger lesions (eg, right posterior frontal, white arrows, A and B) are well visualized with both techniques. Smaller lesions (eg, right posterior temporal, black arrows, C and D) may be better visualized with 3D TSE T1-weighted imaging due to more native vascular signal suppression and higher contrast:noise ratio relative to underlying brain.

Fig. 2

Metastatic brain tumor imaging protocol decision-making flow chart. If sites are using a 3T MRI scanner and have 3D TSE available, they should use Table 1 (ideal recommended 3T protocol). If sites are using a 3T MRI scanner and do not have 3D TSE, they should use Table 2 (minimum standard 3T protocol). If sites use a 1.5T scanner, they should use Table 3 (minimum standard 1.5T protocol). Note that DSC perfusion may be used with the minimum standard protocols at 3T and 1.5T as well as with the “ideal” 3T protocol.