Mathematical Modeling of Human Glioma Growth Based on Brain Topological Structures: Study of Two Clinical Cases

Gliomas are the most common primary brain tumors and yet almost incurable due mainly to their great invasion capability. This represents a challenge to present clinical oncology. Here, we introduce a mathematical model aiming to improve tumor spreading capability definition. The model consists in a time dependent reaction-diffusion equation in a three-dimensional spatial domain that distinguishes between different brain topological structures. The model uses a series of digitized images from brain slices covering the whole human brain. The Talairach atlas included in the model describes brain structures at different levels. Also, the inclusion of the Brodmann areas allows prediction of the brain functions affected during tumor evolution and the estimation of correlated symptoms. The model is solved numerically using patient-specific parametrization and finite differences. Simulations consider an initial state with cellular proliferation alone (benign tumor), and an advanced state when infiltration starts (malign tumor). Survival time is estimated on the basis of tumor size and location. The model is used to predict tumor evolution in two clinical cases. In the first case, predictions show that real infiltrative areas are underestimated by current diagnostic imaging. In the second case, tumor spreading predictions were shown to be more accurate than those derived from previous models in the literature. Our results suggest that the inclusion of differential migration in glioma growth models constitutes another step towards a better prediction of tumor infiltration at the moment of surgical or radiosurgical target definition. Also, the addition of physiological/psychological considerations to classical anatomical models will provide a better and integral understanding of the patient disease at the moment of deciding therapeutic options, taking into account not only survival but also life quality.

[1]  J. Murray,et al.  A quantitative model for differential motility of gliomas in grey and white matter , 2000, Cell proliferation.

[2]  Alan R Palmer,et al.  The sound-level-dependent growth in the extent of fMRI activation in Heschl’s gyrus is different for low- and high-frequency tones , 2003, Hearing Research.

[3]  M. Assanah,et al.  Glial Progenitors in Adult White Matter Are Driven to Form Malignant Gliomas by Platelet-Derived Growth Factor-Expressing Retroviruses , 2006, The Journal of Neuroscience.

[4]  K. Houkin,et al.  The impact of extent of resection and histological subtype on the outcome of adult patients with high-grade gliomas. , 2012, Japanese journal of clinical oncology.

[5]  M. Roth,et al.  An fMRI study of music sight-reading , 2002, Neuroreport.

[6]  K. Welvaart The Extent of the Resection , 1980 .

[7]  M. Berger,et al.  Extent of resection influences outcomes for patients with gliomas. , 2011, Revue neurologique.

[8]  Hugues Duffau,et al.  Awake surgery for WHO Grade II gliomas within "noneloquent" areas in the left dominant hemisphere: toward a "supratotal" resection. Clinical article. , 2011, Journal of neurosurgery.

[9]  Hugues Duffau,et al.  Awake surgery for incidental WHO grade II gliomas involving eloquent areas , 2012, Acta Neurochirurgica.

[10]  D. Louis Collins,et al.  Design and construction of a realistic digital brain phantom , 1998, IEEE Transactions on Medical Imaging.

[11]  H. Steiger,et al.  Glioblastoma multiforme of the elderly: the prognostic effect of resection on survival , 2011, Journal of Neuro-Oncology.

[12]  K. Aldape,et al.  A multigene predictor of outcome in glioblastoma. , 2010, Neuro-oncology.

[13]  V. Quaranta,et al.  Integrative mathematical oncology , 2008, Nature Reviews Cancer.

[14]  J. Murray,et al.  The interaction of growth rates and diffusion coefficients in a three-dimensional mathematical model of gliomas. , 1997, Journal of neuropathology and experimental neurology.

[15]  Bharat B. Biswal,et al.  Intensity-dependent Activation of the Primary Auditory Cortex in Functional Magnetic Resonance Imaging , 2003, Journal of computer assisted tomography.

[16]  D. Silbergeld,et al.  Isolation and characterization of human malignant glioma cells from histologically normal brain. , 1997, Journal of neurosurgery.

[17]  G. Winocur,et al.  Dissociation of pathways for object and spatial vision: a PET study in humans , 1995, Neuroreport.

[18]  R. McLendon,et al.  Direct In Vivo Evidence for Tumor Propagation by Glioblastoma Cancer Stem Cells , 2011, PloS one.

[19]  Mitchel S Berger,et al.  An extent of resection threshold for newly diagnosed glioblastomas. , 2011, Journal of neurosurgery.

[20]  J Rönnberg,et al.  Signed and spoken language perception studied by positron emission tomography , 1997, Neurology.

[21]  D. Steindler,et al.  The origins of glioma: E Pluribus Unum? , 2011, Glia.

[22]  Kristin R. Swanson,et al.  The Evolution of Mathematical Modeling of Glioma Proliferation and Invasion , 2007, Journal of neuropathology and experimental neurology.

[23]  Paul E Kinahan,et al.  Applying a patient-specific bio-mathematical model of glioma growth to develop virtual [18F]-FMISO-PET images. , 2011, Mathematical medicine and biology : a journal of the IMA.

[24]  Carlos Falcón,et al.  Activation patterns of the primary auditory cortex in normal-hearing subjects: a functional magnetic resonance imaging study , 2007, Acta oto-laryngologica.

[25]  Michal Lavidor,et al.  Lexical ambiguity resolution in Wernicke's area and its right homologue , 2009, Cortex.

[26]  L. Taylor Diagnosis, treatment, and prognosis of glioma , 2010, Neurology.

[27]  Henry Brem,et al.  Supratentorial Glioblastoma Multiforme: The Role of Surgical Resection Versus Biopsy Among Older Patients , 2010, Annals of Surgical Oncology.

[28]  R. Fisher THE WAVE OF ADVANCE OF ADVANTAGEOUS GENES , 1937 .

[29]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.

[30]  S E Petersen,et al.  Direct comparison of episodic encoding and retrieval of words: an event-related fMRI study. , 1999, Memory.

[31]  John A. Detre,et al.  Activation of human auditory cortex during speech perception: Effects of monaural, binaural, and dichotic presentation , 2008, Neuropsychologia.

[32]  E. Rolls,et al.  Taste‐olfactory convergence, and the representation of the pleasantness of flavour, in the human brain , 2003, The European journal of neuroscience.

[33]  A. Katz,et al.  Complete Radiologic Response in an Anaplastic Oligodendroglioma Treated with Temozolomide and Bevacizumab , 2009, Case Reports in Oncology.

[34]  R. Gilbertson,et al.  Tumorigenesis in the brain: location, location, location. , 2007, Cancer research.

[35]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[36]  James E. Goldman,et al.  Cell migration in the normal and pathological postnatal mammalian brain , 2009, Progress in Neurobiology.

[37]  F. Dhermain IRM de perfusion, de perméabilité et morphologique : application en radiothérapie neuro-oncologique , 2010 .

[38]  Alexander R A Anderson,et al.  Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: in Silico Modeling Integrates Imaging and Histology Nih Public Access Author Manuscript Introduction , 2011 .

[39]  Manfred Westphal,et al.  The neurobiology of gliomas: from cell biology to the development of therapeutic approaches , 2011, Nature Reviews Neuroscience.

[40]  A. Evans,et al.  MRI simulation-based evaluation of image-processing and classification methods , 1999, IEEE Transactions on Medical Imaging.

[41]  Susan M. Chang,et al.  Role of extent of resection in the long-term outcome of low-grade hemispheric gliomas. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  J C Mazziotta,et al.  Automated labeling of the human brain: A preliminary report on the development and evaluation of a forward‐transform method , 1997, Human brain mapping.

[43]  M. Abdollahi,et al.  Evaluating the prognostic factors effective on the outcome of patients with glioblastoma multiformis: does maximal resection of the tumor lengthen the median survival? , 2010, World neurosurgery.

[44]  W. Gaillard,et al.  Auditory comprehension of language in young children , 2003, Neurology.

[45]  R. Guillevin,et al.  Simulation of anisotropic growth of low‐grade gliomas using diffusion tensor imaging , 2005, Magnetic resonance in medicine.

[46]  W.J.R. Dunseath,et al.  fMRI of the Responses to Vibratory Stimulation of Digit Tips , 2000, NeuroImage.

[47]  R Shane Tubbs,et al.  Korbinian Brodmann (1868-1918) and his contributions to mapping the cerebral cortex. , 2011, Neurosurgery.

[48]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[49]  Edward J. Dropcho,et al.  Low-grade gliomas in adults , 2004, Current treatment options in neurology.

[50]  J. Costello,et al.  Epigenetic mechanisms in glioblastoma multiforme. , 2009, Seminars in cancer biology.

[51]  Alan C. Evans,et al.  MRI Simulation Based Evaluation and Classifications Methods , 1999, IEEE Trans. Medical Imaging.

[52]  J M Wardlaw,et al.  Velocity of radial expansion of contrast-enhancing gliomas and the effectiveness of radiotherapy in individual patients: a proof of principle. , 2008, Clinical oncology (Royal College of Radiologists (Great Britain)).

[53]  Z L Gokaslan,et al.  A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. , 2001, Journal of neurosurgery.

[54]  Patrick J. Kelly,et al.  Gliomas: Survival, origin and early detection , 2010, Surgical neurology international.

[55]  Satoshi O. Suzuki,et al.  MAP‐2e, a Novel MAP‐2 Isoform, Is Expressed in Gliomas and Delineates Tumor Architecture and Patterns of Infiltration , 2002, Journal of neuropathology and experimental neurology.

[56]  Y. Lamarre,et al.  Unmyelinated tactile afferents signal touch and project to insular cortex , 2002, Nature Neuroscience.

[57]  F. Dhermain [Role of perfusion, vascular permeability and anatomic MR imaging in radiation therapy for gliomas]. , 2010, Bulletin du cancer.

[58]  K Hendrickson,et al.  Predicting the efficacy of radiotherapy in individual glioblastoma patients in vivo: a mathematical modeling approach , 2010, Physics in medicine and biology.