A Novel Methodology for Applying Multivoxel MR Spectroscopy to Evaluate Convection-Enhanced Drug Delivery in Diffuse Intrinsic Pontine Gliomas

Abstract

Background and purpose: Diffuse intrinsic pontine gliomas are inoperable high-grade gliomas with a median survival of less than 1 year. Convection-enhanced delivery is a promising local drug-delivery technique that can bypass the BBB in diffuse intrinsic pontine glioma treatment. Evaluating tumor response is critical in the assessment of convection-enhanced delivery of treatment. We proposed to determine the potential of 3D multivoxel (1)H-MR spectroscopy to evaluate convection-enhanced delivery treatment effect in these tumors.

Materials and methods: We prospectively analyzed 3D multivoxel (1)H-MR spectroscopy data for 6 patients with nonprogressive diffuse intrinsic pontine gliomas who received convection-enhanced delivery treatment of a therapeutic antibody (Phase I clinical trial NCT01502917). To compare changes in the metabolite ratios with time, we tracked the metabolite ratios Cho/Cr and Cho/NAA at several ROIs: normal white matter, tumor within the convection-enhanced delivery infusion site, tumor outside of the infused area, and the tumor average.

Results: There was a comparative decrease in both Cho/Cr and Cho/NAA metabolite ratios at the tumor convection-enhanced delivery site versus tumor outside the infused area. We used MR spectroscopy voxels with dominant white matter as a reference. The difference between changes in metabolite ratios became more prominent with increasing time after convection-enhanced delivery treatment.

Conclusions: The comparative change in metabolite ratios between the convection-enhanced delivery site and the tumor site outside the infused area suggests that multivoxel (1)H-MR spectroscopy, in combination with other imaging modalities, may provide a clinical tool to accurately evaluate local tumor response after convection-enhanced delivery treatment.

© 2016 by American Journal of Neuroradiology.

Figures

Fig 1.

ROI selection. A, Axial T1-weighted FLAIR image shows regional hypointensity at the CED infusion site. B, The CED infusion site (white arrow) is also visible on the axial T2 FLAIR image with surrounding T2-hyperintense signal (outlined in white) indicative of the CED infusion volume of distribution. C, The corresponding axial T2-FLAIR with multivoxel MR spectroscopy is shown with the selected CED infusion site voxel (yellow box). D, Enlarged view of the MR spectra for the selected CED infusion site voxel. E and F, The axial T1-weighted FLAIR and axial T2-FLAIR images of the noninfusion site section. G, The selected tumor non-CED infusion site voxel (yellow box) is outside the CED infusion volume of distribution. H, The enlarged view of the MR spectra for the selected tumor non-CED infusion site voxel.

Fig 2.

Color metabolite maps. Relative intensities of metabolites NAA (A), Cho (B), Cho/Cr (C), and Cho/NAA (D) are shown in this postCED1 infusion section. The CED infusion site is visible and is located in the area of the pons with a higher intensity signal of Cho, Cho/Cr, and Cho/NAA and lower NAA intensity.

Fig 3.

Metabolite ratios for normal white matter. Cho/Cr (A) and Cho/NAA (B) ratios for normal cerebellar or cerebral white matter for each patient are shown throughout the course of treatment, and the mean value at each time point is shown in red. Both metabolite ratios for each patient remained stable and in the expected normal range.

Fig 4.

Metabolite ratios for CED infusion site, tumor non-CED infusion site, and average tumor for individual patients. A–D, Patients 1–4 show a similar trend with a comparative decrease in Cho/Cr and Cho/NAA with time for the CED infusion site compared with the tumor non-CED infusion site and average tumor voxels. E and F, Patients 5 and 6 show a slight increase in Cho/Cr and Cho/NAA for the CED infusion site and a comparatively larger increase in both ratios for the tumor non-CED infusion site and the average tumor.

Fig 5.

CED infusion site versus tumor non-CED infusion site Cho/Cr and Cho/NAA comparison. The change in metabolite ratios Cho/Cr (A) and Cho/NAA (B) from the baseline preCED scan to postCED1, postCED2, and postCED3 scans is calculated for the group of patients at both the CED infusion site and tumor non-CED infusion site. The change in Cho/Cr and Cho/NAA at the CED infusion site compared with the tumor non-CED infusion site is calculated by using the Wilcoxon signed rank test. While no statistical claims can be made, the decreasing P values for both metabolite ratios suggest that a comparative reduction in the ratios becomes more pronounced with time.