Characterizing tumor invasiveness of glioblastoma using multiparametric magnetic resonance imaging

J Neurosurg 132:1465–1472, 2020

The objective of this study was to characterize the abnormalities revealed by diffusion tensor imaging (DTI) using MR spectroscopy (MRS) and perfusion imaging, and to evaluate the prognostic value of a proposed quantitative measure of tumor invasiveness by combining contrast-enhancing (CE) and DTI abnormalities in patients with glioblastoma.

METHODS Eighty-four patients with glioblastoma were recruited preoperatively. DTI was decomposed into isotropic (p) and anisotropic (q) components. The relative cerebral blood volume (rCBV) was calculated from the dynamic susceptibility contrast imaging. Values of N-acetylaspartate, myoinositol, choline (Cho), lactate (Lac), and glutamate + glutamine (Glx) were measured from multivoxel MRS and normalized as ratios to creatine (Cr). Tumor regions of interest (ROIs) were manually segmented from the CE T1-weighted (CE-ROI) and DTI-q (q-ROI) maps. Perfusion and metabolic characteristics of these ROIs were measured and compared. The relative invasiveness coefficient (RIC) was calculated as a ratio of the characteristic radii of CE-ROI and q-ROI. The prognostic significance of RIC was tested using Kaplan-Meier and multivariate Cox regression analyses.

RESULTS The Cho/Cr, Lac/Cr, and Glx/Cr in q-ROI were significantly higher than CE-ROI (p = 0.004, p = 0.005, and p = 0.007, respectively). CE-ROI had significantly higher rCBV values than q-ROI (p < 0.001). A higher RIC was associated with worse survival in a multivariate overall survival (OS) model (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.06–1.85, p = 0.016) and progression-free survival (PFS) model (HR 1.55, 95% CI 1.16–2.07, p = 0.003). An RIC cutoff value of 0.89 significantly predicted shorter OS (median 384 vs 605 days, p = 0.002) and PFS (median 244 vs 406 days, p = 0.001).

CONCLUSIONS DTI-q abnormalities displayed higher tumor load and hypoxic signatures compared with CE abnormalities, whereas CE regions potentially represented the tumor proliferation edge. Integrating the extents of invasion visualized by DTI-q and CE images into clinical practice may lead to improved treatment efficacy.

Three-dimensional MRS–guided glioma resection

Metabolic approach

J Neurosurg 124:1585–1593, 2016

The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy (1H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D 1H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection.

Methods: Choline (Cho)–N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D 1H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection.

Results: Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional 1HMRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up.

Conclusions: This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D 1H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.

Potential of MR spectroscopy for assessment of glioma grading

Glioma grading by MR spectroscopy

Clinical Neurology and Neurosurgery 115 (2013) 146– 153

Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids.

Methods: In this review, we describe potential of MRS for grading of gliomas.

Results: Low-grade gliomas are generally characterized by a relatively high concentration of Nacetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies.

Conclusions: Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade.

Diagnostic value of proton magnetic resonance spectroscopy in the noninvasive grading of solid gliomas: comparison of maximum and mean choline values

Neurosurgery 65:908–913, 2009 DOI: 10.1227/01.NEU.0000356982.82378.BA

Magnetic resonance spectroscopy is widely used in addition to magnetic resonance imaging in the characterization of brain tumors. Compounds containing choline (Cho) have an important role in the evaluation of tumor malignancy. For this purpose, various ratios of Cho and other metabolites, such as creatine (Cr), have been assessed. The aim of this study was to compare normalized mean and maximum levels of Cho as single parameters in the noninvasive grading of gliomas.

METHODS: Proton spectroscopic imaging data of 63 patients with suspected World Health Organization (WHO) grade II or III gliomas were acquired at 3 T. Cho concentrations of the tumor were analyzed by a frequency domain fit and normalized to the corresponding contralateral healthy brain tissue. Metabolite images were used to determine the maximum and mean Cho as well as Cr concentrations of the tumor. Furthermore, contrast enhancement of the tumor was analyzed on standard magnetic resonance imaging. All patients subsequently underwent tumor resection or stereotactic biopsy to confirm diagnosis of glioma. Statistical analysis using the Kruskal-Wallis test, Mann-Whitney U test, and receiver operating characteristic curve analysis was performed with BiAS software (Epsilon Verlag GmbH, Frankfurt, Germany).

RESULTS: Histopathological examinations revealed WHO grades II (n=27), III (n=26), and IV (n=10). There was a statistically significant difference in both normalized maximum and mean Cho between WHO grade II and non-necrotic WHO grade III/IV gliomas (mean, 1.45 ±0.28 versus 2.16±0.36, P<0.05; maximum, 1.64±0.32 versus 3.32±0.55, P<0.0001). Receiver operating characteristic analyses rendered a 2.02 cutoff value for maximum Cho with a sensitivity and specificity of 86.1% and 77.8%, respectively. For mean Cho, we found a cutoff value of 1.52 (sensitivity, 77.8%; specificity, 63.0%). The diagnostic accuracy of maximum Cho was superior to that of mean Cho and also the ratio of Cho/Cr (82.5% versus 71.4% and 72.1%, respectively), but all 3 parameters were superior to contrast enhancement of the tumor (61.9%).

CONCLUSION: Both maximum and mean Cho differ between low- and high-grade gliomas. Compared with contrast enhancement, mean Cho, and Cho/Cr, maximum Cho of the tumor provides the highest accuracy in discriminating between low- and high-grade tumors, indicating usefulness of this single parameter in the process of therapeutic decision making.