Characterizing tumor invasiveness of glioblastoma using multiparametric magnetic resonance imaging

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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.


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.


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).


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.

ABBREVIATIONS 5-ALA = 5-aminolevulinic acid; CE = contrast enhancing; Cho = choline; CI = confidence interval; Cr = creatine; CSI = chemical shift imaging; DSC = dynamic susceptibility contrast-enhancement; DTI = diffusion tensor imaging; DTI-p = DTI-isotropic; DTI-q = DTI-anisotropic; EOR = extent of resection; FSL = Functional MRI of the Brain Software Library; Glx = glutamate + glutamine; HR = hazard ratio; IDH-1 = isocitrate dehydrogenase 1; Lac = lactate; MGMT = O-6-methylguanine-DNA methyltransferase; mIns = myoinositol; MRS = magnetic resonance spectroscopy; NAA = N-acetylaspartate; NAWM = normal-appearing white matter; OS = overall survival; PFS = progression-free survival; rCBV = relative cerebral blood volume; RIC = relative invasiveness coefficient; ROI = region of interest.

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Article Information

Correspondence Chao Li: University of Cambridge, United Kingdom.

INCLUDE WHEN CITING Published online April 26, 2019; DOI: 10.3171/2018.12.JNS182926.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



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    A demonstration of ROIs in a DTI-q image (A) and postcontrast T1-weighted image (B). The q-ROI (purple) shows the abnormality revealed on a DTI-q map. The CE-ROI (blue) is a CE tumor region excluding the DTI-q abnormality. Figure is available in color online only.

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    A demonstration of calculation of the RIC. Tumor regions are segmented from postcontrast T1 (left) and DTI-q images (right), respectively. The smallest ellipsoids are fitted to the tumor volume. The characteristic radii of ROIs (rCE, rq) are calculated as the semimajor axis of ellipsoids. An RIC is calculated as the ratio of rCE/rq. Figure is available in color online only.

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    Bar graphs of the metabolic signatures of ROIs. Both tumor ROIs display abnormal metabolic signatures. The q-ROI shows significantly higher levels of Cho/Cr, Lac/Cr, and Glx/Cr than CE-ROI. **p < 0.01, ***p < 0.001. Figure is available in color online only.

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    Kaplan-Meier survival plots of patient clusters. The log-rank test showed patients with an RIC > 0.89 displayed worse OS (A, p = 0.002) and PFS (B, p = 0.001).

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    Two case examples of tumor invasiveness revealed by CE tumor regions and DTI-q abnormalities. A and B: Case 1 is a 64-year-old man, with a CE tumor of 62.6 cm3 and RIC of 0.81. C and D: Case 2 is a 69-year-old man, with a CE tumor of 31.2 cm3 and RIC of 1.31. A and C indicate the CE-ROI (blue) and q-ROI (purple) in each case. B and D indicate the rCBV maps on a voxel-wise basis across the CE-ROI and q-ROI. Both patients received tumor resection with the guidance of neuronavigation and 5-ALA fluorescence for maximal resection. Complete resection was achieved in both patients according to the 72-hour postoperative MR images. Pathological assessment confirmed both were MGMT promoter unmethylated and IDH-1 wild-type glioblastomas. Both patients received concomitant and adjuvant temozolomide chemoradiotherapy following the Stupp protocol. The PFS and OS of case 1 were 563 and 697 days, respectively. The PFS and OS of case 2 were 159 and 317 days, respectively. Figure is available in color online only.




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