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 pa tients treated based on metabolic information.

Association of Radiomics and Metabolic Tumor Volumes in Radiation Treatment of Glioblastoma Multiforme

“…From a larger study of 56 treatment-naïve patients with histopathology-confirmed glioma, 20 were grade IV (8, 21). The institutional ethics committee and the research committee Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India approved the study protocol, and informed consent was obtained from the patients or their care providers.…”

“…The institutional ethics committee and the research committee Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India approved the study protocol, and informed consent was obtained from the patients or their care providers. In a prior study, 1 patient was removed because of lack of T2w/FLAIR sequence (8); 2 more patients were removed for this work because they did not have CE-T1w imaging. Thus in this report the remaining 17 patients were analyzed.…”

“…The MTVs for these maps were then determined using a comparison with the signal amplitudes in normal-appearing tissue contralateral to the tumor (Fig. 1C) (8). The intersections of CTVs and MTVs were constructed.…”

“…N -Acetyl aspartate is related to mature neuronal density and viability and is therefore decreased in tumor tissue where the neuronal cell density is reduced (8–10). In a previous study, volumetric 3-dimensional MRSI was used to construct metabolic tumor volume (MTV) maps of aberrant expression of Cho and NAA (8). When compared with the standard RT clinical target volumes (CTVs), a considerable fraction of MTV Cho was outside of these volumes.…”

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

“…The same group showed that this additional metabolic information would not only change the size but also would result in a substantial shift of the volumes if considered for radiation target delineation. 76 By this means, Parra et al 77 compared metabolic tumour volumes with standard RT volumes using an advanced volumetric three-dimensional (3D) MRSI approach and found in an observational study of n 5 19 patients with GBM that on average, one-third Cho-defined volume was not covered by the CTV receiving 60 Gy. Park et al 78 studied the CNI2 volume at therapy initiation in another observational study of n 5 23 patients with GBM and showed that one-third of recurrent-enhancing GBM volume within this metabolically active tumour region was not initially covered by the 60-Gy RT target.…”