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 1H-MR spectroscopy to evaluate convection-enhanced delivery treatment effect in these tumors. MATERIALS AND METHODS We prospectively analyzed 3D multivoxel 1H-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 TherewasacomparativedecreaseinbothCho/CrandCho/NAAmetaboliteratiosatthetumorconvection-enhanceddelivery 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 1H-MR spectroscopy, in combination with other imaging modalities, may provide a clinical tool to accurately evaluate local tumor response after convection-enhanced delivery treatment.

Convection-Enhanced Delivery in Malignant Gliomas: A Review of Toxicity and Efficacy

“…Methods that do not utilize additional gadolinium appear more attractive, but they may compromise the drug efficacy. Multivoxel 1 H-MR Spectroscopy through analysis of metabolites ratio of Cho/Cr and Cho/NAA is able to describe the tumor site with and without CED infusion [102], but the resolution of this technique needs to be increased for adequate analysis in the future. DW-MRI is another noninvasive approach that can monitor the response of CED delivery of Taxol [103].…”

Magnetic resonance spectroscopic imaging in gliomas: clinical diagnosis and radiotherapy planning

“… 29 Thus, SVS does not provide information on spatial heterogeneity and does not help in the definition of the spatial extent of the lesion, causing it to be less useful for treatment planning (for RT or surgery) and follow-up assessment. 30 …”

“…These software ( i.e. FuncTool Performance 30 by General Electric and Syngovia by Siemens) can be used to process MRSI data and calculate area under the major peaks NAA, Cho, and Cr to generate color maps. Overlay images can be generated by applying the MRSI grid onto the corresponding CE- T 1 W or T 2 W/FLAIR anatomical images.…”

Convection Enhanced Delivery of Topotecan for Gliomas: A Single-Center Experience

“…The most important reason for this is to validate the drug distribution parameters and their correlation with radiological findings such as gadolinium enhancement while proving safety. Newer techniques such as MR spectroscopy or PET imaging may also be important to validate for different classes of therapeutic molecules [ 45 , 46 , 47 ]. Neurobehavioral testing including performance outcomes are critical for determining dose limiting toxicities associated with CED.…”