The integration of quantitative multi-modality imaging data into mathematical models of tumors

Quantitative imaging data obtained from multiple modalities may be integrated into mathematical models of tumor growth and treatment response to achieve additional insights of practical predictive value. We show how this approach can describe the development of tumors that appear realistic in terms of producing proliferating tumor rims and necrotic cores. Two established models (the logistic model with and without the effects of treatment) and one novel model built a priori from available imaging data have been studied. We modify the logistic model to predict the spatial expansion of a tumor driven by tumor cell migration after a voxel's carrying capacity has been reached. Depending on the efficacy of a simulated cytotoxic treatment, we show that the tumor may either continue to expand, or contract. The novel model includes hypoxia as a driver of tumor cell movement. The starting conditions for these models are based on imaging data related to the tumor cell number (as estimated from diffusion-weighted MRI), apoptosis (from 99mTc-Annexin-V SPECT), cell proliferation and hypoxia (from PET). We conclude that integrating multi-modality imaging data into mathematical models of tumor growth is a promising combination that can capture the salient features of tumor growth and treatment response and this indicates the direction for additional research.

[1]  Hertz On the Contact of Elastic Solids , 1882 .

[2]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[3]  M Hoehn-Berlage,et al.  High resolution quantitative relaxation and diffusion mri of three different experimental brain tumors in rat , 1995, Magnetic resonance in medicine.

[4]  Mark Muzi,et al.  Kinetic modeling of 3'-deoxy-3'-fluorothymidine in somatic tumors: mathematical studies. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  Y. Dzenis,et al.  Adhesive contact in filaments , 2007 .

[6]  H. Othmer,et al.  Mathematical modeling of tumor-induced angiogenesis , 2004, Journal of mathematical biology.

[7]  Glyn Johnson,et al.  Dynamic contrast-enhanced perfusion MR imaging measurements of endothelial permeability: differentiation between atypical and typical meningiomas. , 2003, AJNR. American journal of neuroradiology.

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

[9]  K. Kendall,et al.  Surface energy and the contact of elastic solids , 1971, Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences.

[10]  Susumu Mori,et al.  Unique patterns of diffusion directionality in rat brain tumors revealed by high‐resolution diffusion tensor MRI , 2007, Magnetic resonance in medicine.

[11]  Peter R C Gascoyne,et al.  Dielectrophoretic segregation of different human cell types on microscope slides. , 2005, Analytical chemistry.

[12]  N. deSouza,et al.  Diffusion-weighted magnetic resonance imaging and its application to cancer , 2006, Cancer imaging : the official publication of the International Cancer Imaging Society.

[13]  R. Davis,et al.  Imaging of apoptosis (programmed cell death) with 99mTc annexin V. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[14]  Hubert Vesselle,et al.  FLT: measuring tumor cell proliferation in vivo with positron emission tomography and 3'-deoxy-3'-[18F]fluorothymidine. , 2007, Seminars in nuclear medicine.

[15]  J. Israelachvili Intermolecular and surface forces , 1985 .

[16]  Roland Bares,et al.  Hypoxia-imaging with 18F-Misonidazole and PET: Changes of kinetics during radiotherapy of head-and-neck cancer , 2007 .

[17]  Gargi Chakraborty,et al.  Quantitative metrics of net proliferation and invasion link biological aggressiveness assessed by MRI with hypoxia assessed by FMISO-PET in newly diagnosed glioblastomas. , 2009, Cancer research.

[18]  Bharat Bhushan Springer Handbook of Nanotechnology , 2007 .

[19]  G Powathil,et al.  Mathematical modeling of brain tumors: effects of radiotherapy and chemotherapy , 2007, Physics in medicine and biology.

[20]  John V Frangioni,et al.  New technologies for human cancer imaging. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Olivier Clatz,et al.  Biocomputing: numerical simulation of glioblastoma growth using diffusion tensor imaging , 2008, Physics in medicine and biology.

[22]  Thomas E Yankeelov,et al.  Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results. , 2007, Magnetic resonance imaging.

[23]  I. Whittle,et al.  The development of necrosis and apoptosis in glioma: experimental findings using spheroid culture systems* , 2001, Neuropathology and applied neurobiology.

[24]  K. L. Kiran,et al.  Mathematical modelling of avascular tumour growth based on diffusion of nutrients and its validation , 2009 .

[25]  V. Busini,et al.  Mechanistic modelling of avascular tumor growth and pharmacokinetics influence—Part I , 2007 .

[26]  William M. Wells,et al.  Medical Image Computing and Computer-Assisted Intervention — MICCAI’98 , 1998, Lecture Notes in Computer Science.

[27]  Dai Fukumura,et al.  Imaging angiogenesis and the microenvironment   , 2008, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[28]  R. Celotta,et al.  Manipulation of Adsorbed Atoms and Creation of New Structures on Room-Temperature Surfaces with a Scanning Tunneling Microscope , 1991, Science.

[29]  Christos Davatzikos,et al.  Modeling Glioma Growth and Mass Effect in 3D MR Images of the Brain , 2007, MICCAI.

[30]  Chung-Yuen Hui,et al.  Adhesive contact of cylindrical lens and a flat sheet , 1996 .

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

[32]  Valerie A Longo,et al.  Dynamic Small-Animal PET Imaging of Tumor Proliferation with 3′-Deoxy-3′-18F-Fluorothymidine in a Genetically Engineered Mouse Model of High-Grade Gliomas , 2008, Journal of Nuclear Medicine.

[33]  Otto Muzik,et al.  Imaging proliferation in vivo with [F-18]FLT and positron emission tomography , 1998, Nature Medicine.

[34]  P. Dario,et al.  From "macro" to "micro" manipulation: models and experiments , 2004, IEEE/ASME Transactions on Mechatronics.

[35]  Luigi Preziosi,et al.  Cancer Modelling and Simulation , 2003 .

[36]  J. Thiran,et al.  Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. , 2006, Radiographics : a review publication of the Radiological Society of North America, Inc.

[37]  J C Gore,et al.  Effects of cell volume fraction changes on apparent diffusion in human cells. , 2000, Magnetic resonance imaging.

[38]  Rolf F. Barth,et al.  Rat brain tumor models in experimental neuro-oncology: the C6, 9L, T9, RG2, F98, BT4C, RT-2 and CNS-1 gliomas , 2009, Journal of Neuro-Oncology.

[39]  Elisa Riedo,et al.  Young modulus dependence of nanoscopic friction coefficient in hard coatings , 2003 .

[40]  Lining Sun,et al.  A Flexible Experimental System for Complex Microassembly under Microscale Force and Vision-Based Control , 2007 .

[41]  Bin Wu,et al.  Mechanical properties of ultrahigh-strength gold nanowires , 2005, Nature materials.

[42]  F. Blankenberg,et al.  Time course of apoptotic tumor response after a single dose of chemotherapy: comparison with 99mTc-annexin V uptake and histologic findings in an experimental model. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[43]  Vittorio Cristini,et al.  Two-Dimensional Chemotherapy Simulations Demonstrate Fundamental Transport and Tumor Response Limitations Involving Nanoparticles , 2004 .

[44]  Piotr A Wielopolski,et al.  MR angiography of tumor-related vasculature: from the clinic to the micro-environment. , 2005, Radiographics : a review publication of the Radiological Society of North America, Inc.