Characterizing tumor invasiveness of glioblastoma using multiparametric magnetic resonance imaging

Chao Li MD, PhD1,2, Shuo Wang PhD3, Jiun-Lin Yan MD, PhD1,4,5, Turid Torheim PhD6,7, Natalie R. Boonzaier PhD1,8, Rohitashwa Sinha MRCS1, Tomasz Matys PhD, FRCR3,9, Florian Markowetz PhD6,7, and Stephen J. Price PhD, FRCS1,10
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  • 1 Cambridge Brain Tumor Imaging Laboratory, Division of Neurosurgery, Department of Clinical Neurosciences,
  • | 3 Department of Radiology,
  • | 6 Cancer Research UK Cambridge Institute, and
  • | 10 Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, United Kingdom;
  • | 2 Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;
  • | 4 Department of Neurosurgery, Chang Gung Memorial Hospital, Keelung, Taiwan;
  • | 5 Chang Gung University College of Medicine, Taoyuan, Taiwan;
  • | 7 CRUK & EPSRC Cancer Imaging Centre in Cambridge and Manchester, Cambridge;
  • | 8 Developmental Imaging and Biophysics Section, Great Ormond Street Institute of Child Health, University College London; and
  • | 9 Cancer Trials Unit, Department of Oncology, Addenbrooke’s Hospital, Cambridge, United Kingdom
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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.


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.

Supplementary Materials

    • Supplementary Table 1 (PDF 425 KB)

Illustration from Ivan et al. (pp 1517–1528). Copyright Kenneth Probst. Published with permission.

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