Volumetric spectroscopic imaging of glioblastoma multiforme radiation treatment volumes

Abstract

Purpose: Magnetic resonance (MR) imaging and computed tomography (CT) are used almost exclusively in radiation therapy planning of glioblastoma multiforme (GBM), despite their well-recognized limitations. MR spectroscopic imaging (MRSI) can identify biochemical patterns associated with normal brain and tumor, predominantly by observation of choline (Cho) and N-acetylaspartate (NAA) distributions. In this study, volumetric 3-dimensional MRSI was used to map these compounds over a wide region of the brain and to evaluate metabolite-defined treatment targets (metabolic tumor volumes [MTV]).

Methods and materials: Volumetric MRSI with effective voxel size of ∼1.0 mL and standard clinical MR images were obtained from 19 GBM patients. Gross tumor volumes and edema were manually outlined, and clinical target volumes (CTVs) receiving 46 and 60 Gy were defined (CTV46 and CTV60, respectively). MTVCho and MTVNAA were constructed based on volumes with high Cho and low NAA relative to values estimated from normal-appearing tissue.

Results: The MRSI coverage of the brain was between 70% and 76%. The MTVNAA were almost entirely contained within the edema, and the correlation between the 2 volumes was significant (r=0.68, P=.001). In contrast, a considerable fraction of MTVCho was outside of the edema (median, 33%) and for some patients it was also outside of the CTV46 and CTV60. These untreated volumes were greater than 10% for 7 patients (37%) in the study, and on average more than one-third (34.3%) of the MTVCho for these patients were outside of CTV60.

Conclusions: This study demonstrates the potential usefulness of whole-brain MRSI for radiation therapy planning of GBM and revealed that areas of metabolically active tumor are not covered by standard RT volumes. The described integration of MTV into the RT system will pave the way to future clinical trials investigating outcomes in patients treated based on metabolic information.

Fig. 1

(A) Schema of workflow. Upper left-hand side (shaded in blue) denotes the steps carried out in MIDAS. Registration, radiation therapy (RT) volume contouring, and comparisons with metabolic tumor volumes (MTV) were performed with the MIM system. (B) Spectral quality mask (light blue), cerebrospinal fluid (CSF; dark blue), and brain segmentation (cerebellum and brainstem). (C) RT volumes and area of normal-appearing tissue (NAT). (D) RT volumes outside of the volume of magnetic resonance spectroscopic imaging within the “quality mask” (MRSI_Q) based on tumor location. A color version of this figure available at www.redjournal.org.

Fig. 2

(A) Magnetic resonance spectroscopic imaging (MRSI) data from the tumor region overlaid on the postcontrast T1. Shaded area indicates region of high choline. (B) Representative spectra from top: normal tissue, edema, lesion and enhancing edge, and edema. (C) Choline (Cho) and N-acetylaspartate (NAA) maps in the axial slice in (A). Blue and purple areas indicate MTV_Cho and MTV_NAA. GTV (red), edema (orange) and MTV_Cho overlaid on T1-weighted MRI. MTV Z metabolic tumor volumes. A color version of this figure available at www.redjournal.org.

Fig. 3

(A) Magnetic resonance spectroscopic imaging (MRSI) data from the tumor region, indicated by the red box on T2-MRI (inset). (B) Representative spectra from gross tumor volume (GTV), outside GTV/edema and normal-appearing tissue (NAT; green box). (C) Choline (Cho) and N-acetylaspartate (NAA) maps around region from A. Blue and purple areas indicate MTV_Cho and MTV_NAA. GTV (red) and edema (orange) overlaid on T2-MRI and metabolic volumes. MTV = metabolic tumor volumes. A color version of this figure available at www.redjournal.org.

Fig. 4

(A) Magnetic resonance spectroscopic imaging (MRSI) data from the tumor region, overlaid on the postcontrast T1. (B) Representative spectra from and around the enhancing lesion. (C) MTV_Cho (blue), GTV (red) and edema (orange) overlaid on postcontrast T1 in axial, sagittal, and coronal views. MTV = metabolic tumor volumes. A color version of this figure available at www.redjournal.org.

Fig. 5

(A) Coronal view of choline (Cho) and MTV_Cho (blue) maps. (B) N-acetylaspartate (NAA) and MTV_NAA (purple). (C) MTV_Cho and MTV_NAA overlaid on post-contrast T1 MRI. (D) Correlation of MTV_NAA and edema volumes. (E) Boxplot of the percentage of MTV_Cho and MTV_NAA outside of radiation therapy volumes. MTV Z metabolic tumor volumes.