Global diffusion tensor imaging derived metrics differentiate glioblastoma multiforme vs. normal brains by using discriminant analysis: introduction of a novel whole-brain approach

Abstract Background. Histological behavior of glioblastoma multiforme suggests it would benefit more from a global rather than regional evaluation. A global (whole-brain) calculation of diffusion tensor imaging (DTI) derived tensor metrics offers a valid method to detect the integrity of white matter structures without missing infiltrated brain areas not seen in conventional sequences. In this study we calculated a predictive model of brain infiltration in patients with glioblastoma using global tensor metrics. Methods. Retrospective, case and control study; 11 global DTI-derived tensor metrics were calculated in 27 patients with glioblastoma multiforme and 34 controls: mean diffusivity, fractional anisotropy, pure isotropic diffusion, pure anisotropic diffusion, the total magnitude of the diffusion tensor, linear tensor, planar tensor, spherical tensor, relative anisotropy, axial diffusivity and radial diffusivity. The multivariate discriminant analysis of these variables (including age) with a diagnostic test evaluation was performed. Results. The simultaneous analysis of 732 measures from 12 continuous variables in 61 subjects revealed one discriminant model that significantly differentiated normal brains and brains with glioblastoma: Wilks’ λ = 0.324, χ2 (3) = 38.907, p < .001. The overall predictive accuracy was 92.7%. Conclusions. We present a phase II study introducing a novel global approach using DTI-derived biomarkers of brain impairment. The final predictive model selected only three metrics: axial diffusivity, spherical tensor and linear tensor. These metrics might be clinically applied for diagnosis, follow-up, and the study of other neurological diseases.

[1]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[2]  Yingjuan Chang,et al.  Monitoring of acute axonal injury in the swine spinal cord with EAE by diffusion tensor imaging , 2009, Journal of magnetic resonance imaging : JMRI.

[3]  Marcos Dipinto,et al.  Discriminant analysis , 2020, Predictive Analytics.

[4]  J. Smirniotopoulos,et al.  Glioblastoma multiforme: radiologic-pathologic correlation. , 1996, Radiographics : a review publication of the Radiological Society of North America, Inc.

[5]  P. Lachenbruch Statistical Power Analysis for the Behavioral Sciences (2nd ed.) , 1989 .

[6]  R. Zimmerman Imaging of adult central nervous system primary malignant gliomas. Staging and follow‐up , 1991, Cancer.

[7]  Carl-Fredrik Westin,et al.  Processing and visualization for diffusion tensor MRI , 2002, Medical Image Anal..

[8]  B. Tabachnick,et al.  Using Multivariate Statistics , 1983 .

[9]  Gareth J. Barker,et al.  Diffusion tensor imaging of post mortem multiple sclerosis brain , 2007, NeuroImage.

[10]  Julie F. Pallant,et al.  SPSS Survival Manual , 2020 .

[11]  P. Vachata,et al.  Distant white-matter diffusion changes caused by tumor growth. , 2013, Journal of neuroradiology. Journal de neuroradiologie.

[12]  J. Tsuruda,et al.  Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. , 1990, Radiology.

[13]  D. Le Bihan,et al.  Diffusion tensor imaging: Concepts and applications , 2001, Journal of magnetic resonance imaging : JMRI.

[14]  P. Desmond,et al.  Diffusion Tensor Imaging in Glioblastoma Multiforme and Brain Metastases: The Role of p, q, L, and Fractional Anisotropy , 2008, American Journal of Neuroradiology.

[15]  Andy P. Field,et al.  Discovering Statistics Using SPSS , 2000 .

[16]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[17]  Sheng-Kwei Song,et al.  Axial Diffusivity Is the Primary Correlate of Axonal Injury in the Experimental Autoimmune Encephalomyelitis Spinal Cord: A Quantitative Pixelwise Analysis , 2009, The Journal of Neuroscience.

[18]  David Moher,et al.  The STARD Statement for Reporting Studies of Diagnostic Accuracy: Explanation and Elaboration , 2003, Annals of Internal Medicine [serial online].

[19]  R. Komotar,et al.  Predictors of Long-Term Survival in Patients With Glioblastoma Multiforme: Advancements From the Last Quarter Century , 2013, Cancer investigation.

[20]  T. Carpenter,et al.  Enhanced visualization and quantification of magnetic resonance diffusion tensor imaging using the p:q tensor decomposition. , 2006, The British journal of radiology.

[21]  Y H Chan,et al.  Biostatistics 104: correlational analysis. , 2003, Singapore medical journal.

[22]  N A Obuchowski,et al.  Sample size determination for diagnostic accuracy studies involving binormal ROC curve indices. , 1997, Statistics in medicine.

[23]  T. Cloughesy,et al.  Nonlinear distortion correction of diffusion MR images improves quantitative DTI measurements in glioblastoma , 2014, Journal of Neuro-Oncology.

[24]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[25]  Jun Yoshino,et al.  Demyelination increases radial diffusivity in corpus callosum of mouse brain , 2005, NeuroImage.

[26]  S. Ng,et al.  Differentiation of Brain Abscesses from Necrotic Glioblastomas and Cystic Metastatic Brain Tumors with Diffusion Tensor Imaging , 2011, American Journal of Neuroradiology.

[27]  T. Mikkelsen,et al.  The Corpus Callosum Wallerian Degeneration in the Unilateral Brain Tumors: Evaluation with Diffusion Tensor Imaging (DTI). , 2013, Journal of clinical and diagnostic research : JCDR.

[28]  C. Raftopoulos,et al.  Immediate post-operative MRI suggestive of the site and timing of glioblastoma recurrence after gross total resection: a retrospective longitudinal preliminary study , 2013, European Radiology.

[29]  Ernesto Roldan-Valadez,et al.  Diagnostic performance of regional DTI-derived tensor metrics in glioblastoma multiforme: simultaneous evaluation of p, q, L, Cl, Cp, Cs, RA, RD, AD, mean diffusivity and fractional anisotropy , 2013, European Radiology.

[30]  Ernesto Roldan-Valadez,et al.  Secondary MRI-findings, volumetric and spectroscopic measurements in mesial temporal sclerosis: a multivariate discriminant analysis. , 2012, Swiss medical weekly.

[31]  M. Buyse,et al.  Designing phase II trials in cancer: a systematic review and guidance , 2011, British Journal of Cancer.

[32]  B. Drayer,et al.  Human cerebral gliomas: correlation of postmortem MR imaging and neuropathologic findings. , 1989, Radiology.

[33]  Ignace Lemahieu,et al.  Experimental Performance Assessment of SPM for SPECT Neuroactivation Studies Using a Subresolution Sandwich Phantom Design , 2002, NeuroImage.

[34]  L. D.,et al.  Brain tumors , 2005, Psychiatric Quarterly.

[35]  R. Haase,et al.  Multivariate analysis of variance. , 1987 .

[36]  G. Maira,et al.  The influence of surgery on recurrence pattern of glioblastoma , 2013, Clinical Neurology and Neurosurgery.

[37]  T. Mikkelsen,et al.  Predicting survival in glioblastomas using diffusion tensor imaging metrics , 2010, Journal of magnetic resonance imaging : JMRI.

[38]  R. Tanaka,et al.  Magnetic resonance imaging and histopathology of cerebral gliomas , 2004, Neuroradiology.

[39]  Geoffrey S Young,et al.  Advanced MRI of adult brain tumors. , 2007, Neurologic clinics.