Mathematical Cancer Therapy Planning in Deep Regional Hyperthermia 1

This paper surveys the mathematics required for a typically challenging problem from computational medicine: cancer therapy planning in deep regional hyperthermia. In the course of many years of close cooperation with clinics, the medical problem has given rise to many subtle mathematical problems, some of which were unsolved when the project started. Efficiency of numerical algorithms, i.e., computational speed and monitored reliability, plays a decisive role in the medical treatment. Off-the-shelf software had turned out to be insufficient to meet the requirements of medicine. Instead, new mathematical theory as well as new numerical algorithms had to be developed. In order to make our algorithms useful in the clinical environment, new visualization software, i.e., a ‘virtual lab’, including three-dimensional geometry processing of individual virtual patients, had to be designed and implemented. Moreover, before the problems could be attacked by numerical algorithms, careful mathematical modelling had to be done. Finally, parameter identification and constrained optimization for the PDEs had to be newly analysed and realized over the individual patient's geometry. Our new techniques had an impact on the specificity of the treatment of individual patients and on the construction of an improved hyperthermia applicator.

[1]  P. Deuflhard,et al.  Adaptive Multilevel Methods for Edge Element Discretizations of Maxwell's Equations , 1997 .

[2]  Paul S. Heckbert,et al.  Survey of Polygonal Surface Simplification Algorithms , 1997 .

[3]  Harry Yserentant,et al.  On the multi-level splitting of finite element spaces , 1986 .

[4]  Hans-Christian Hege,et al.  A 3D statistical shape model of the pelvic bone for segmentation , 2004, SPIE Medical Imaging.

[5]  Nicholas I. M. Gould,et al.  Trust Region Methods , 2000, MOS-SIAM Series on Optimization.

[6]  J. Rehberg,et al.  Hölder Continuity and Optimal Control for Nonsmooth Elliptic Problems , 2009 .

[7]  J. Pasciak,et al.  Uniform convergence of multigrid V-cycle iterations for indefinite and nonsymmetric problems , 1994 .

[8]  T Talaky,et al.  Interior Point Methods of Mathematical Programming , 1997 .

[9]  Ricardo H. Nochetto,et al.  Optimal multilevel methods for H(grad), H(curl), and H(div) systems on graded and unstructured grids , 2009 .

[10]  R. Hiptmair Multigrid Method for Maxwell's Equations , 1998 .

[11]  Peter Deuflhard,et al.  Differential equations in technology and medicine: Computational concepts, adaptive algorithms, and virtual labs , 2000 .

[12]  A. Quarteroni,et al.  On the coupling of 1D and 3D diffusion-reaction equations. Applications to tissue perfusion problems , 2008 .

[13]  Ralf Hiptmair,et al.  Multilevel solution of the time‐harmonic Maxwell's equations based on edge elements , 1999 .

[14]  M. Seebass,et al.  Impact of nonlinear heat transfer on temperature control in regional hyperthermia , 1999, IEEE Transactions on Biomedical Engineering.

[15]  Hans-Christian Hege,et al.  3D Reconstruction of Individual Anatomy from Medical Image Data: Segmentation and Geometry Processing , 2007 .

[16]  S. Gerber Perfusionsmodellierung in menschlichen Tumoren , 2007 .

[17]  J. Rhee,et al.  Implication of Blood Flow in Hyperthermic Treatment of Tumors , 1984, IEEE Transactions on Biomedical Engineering.

[18]  W. Beckman,et al.  The use of generalized cell-survival data in a physiologically based objective function for hyperthermia treatment planning: a sensitivity study with a simple tissue model implanted with an array of ferromagnetic thermoseeds. , 1994, International journal of radiation oncology, biology, physics.

[19]  Alain Damlamian,et al.  Two-Scale Convergence On Periodic Surfaces And Applications , 1995 .

[20]  Kim Butts Pauly,et al.  MR thermometry , 2008, Journal of magnetic resonance imaging : JMRI.

[21]  Sebastian Götschel,et al.  Solving Optimal Control Problems with the Kaskade 7 Finite Element Toolbox , 2012 .

[22]  R Vanderby,et al.  Temperature-dependent versus constant-rate blood perfusion modelling in ferromagnetic thermoseed hyperthermia: results with a model of the human prostate. , 1994, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[23]  Wolfgang Hackbusch,et al.  Multi-grid methods and applications , 1985, Springer series in computational mathematics.

[24]  M. Hintermüller,et al.  On the Length of the Primal-Dual Path in Moreau-Yosida-based Path-following for State Constrained Optimal Control: Analysis and Numerics , 2011 .

[25]  A. Bossavit Whitney forms: a class of finite elements for three-dimensional computations in electromagnetism , 1988 .

[26]  Jinchao Xu,et al.  Nodal Auxiliary Space Preconditioning in H(curl) and H(div) Spaces , 2007, SIAM J. Numer. Anal..

[27]  Martin Weiser,et al.  Konrad-zuse-zentrum F ¨ Ur Informationstechnik Berlin a Control Reduced Primal Interior Point Method for Pde Constrained Optimization a Control Reduced Primal Interior Point Method for Pde Constrained Optimization † , 2022 .

[28]  Michael Hinze,et al.  Discretization of interior point methods for state constrained elliptic optimal control problems: optimal error estimates and parameter adjustment , 2011, Comput. Optim. Appl..

[29]  Hans-Christian Hege,et al.  Numerical Algorithms and Visualization in Medical Treatment Planning , 1997, VisMath.

[30]  R. W. Lau,et al.  The dielectric properties of biological tissues: III. Parametric models for the dielectric spectrum of tissues. , 1996, Physics in medicine and biology.

[31]  Martin Weiser,et al.  Barrier Methods for a Control Problem from Hyperthermia Treatment Planning , 2010 .

[32]  Martin Weiser,et al.  On goal-oriented adaptivity for elliptic optimal control problems , 2013, Optim. Methods Softw..

[33]  Stefan Zachow,et al.  Adaptive Remeshing of Non-Manifold Surfaces , 2008, Eurographics.

[34]  Ralf Hiptmair,et al.  Numerical Methods for Computational Electromagnetism , 2002 .

[35]  W. Dewey,et al.  Arrhenius relationships from the molecule and cell to the clinic , 2009, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[36]  Peter Wust,et al.  Regularized antenna profile adaptation in online hyperthermia treatment. , 2010, Medical physics.

[37]  Alfred K. Louis,et al.  On the mathematical foundations of hyperthermia therapy , 1990 .

[38]  Timothy F. Cootes,et al.  Use of active shape models for locating structures in medical images , 1994, Image Vis. Comput..

[39]  Peter Schlag,et al.  Clinical use of the hyperthermia treatment planning system HyperPlan to predict effectiveness and toxicity. , 2003, International journal of radiation oncology, biology, physics.

[40]  Hans Lamecker,et al.  Variational and statistical shape modeling for 3D geometry reconstruction , 2008 .

[41]  P. Druet Higher integrability of the Lorentz force for weak solutions to Maxwell's equations in complex geometries , 2009 .

[42]  Luc Vincent,et al.  Watersheds in Digital Spaces: An Efficient Algorithm Based on Immersion Simulations , 1991, IEEE Trans. Pattern Anal. Mach. Intell..

[43]  Timothy A. Davis,et al.  Direct methods for sparse linear systems , 2006, Fundamentals of algorithms.

[44]  F. Potra,et al.  Asymptotic mesh independence of Newton-Galerkin methods via a refined Mysovskii theorem , 1992 .

[45]  Anton Schiela,et al.  An interior point method in function space for the efficient solution of state constrained optimal control problems , 2013, Math. Program..

[46]  Fredi Tröltzsch,et al.  Optimal Control of Three-Dimensional State-Constrained Induction Heating Problems with Nonlocal Radiation Effects , 2011, SIAM J. Control. Optim..

[47]  H. Whitney Geometric Integration Theory , 1957 .

[48]  P Wust,et al.  Electromagnetic phased arrays for regional hyperthermia: optimal frequency and antenna arrangement. , 2001, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[49]  N. Maratos,et al.  Optimal steady-state temperature distribution for a phased array hyperthermia system , 1993, IEEE Transactions on Biomedical Engineering.

[50]  Andreas Günther,et al.  An interior point algorithm with inexact step computation in function space for state constrained optimal control , 2011, Numerische Mathematik.

[51]  Martin Weiser,et al.  Optimization and Identification in Regional Hyperthermia , 2009 .

[52]  Peter Wust,et al.  HyperPlan - an integrated system for treatment planning in regional hyperthermia , 1996 .

[53]  Peter Wust,et al.  Adaptation of antenna profiles for control of MR guided hyperthermia (HT) in a hybrid MR-HT system. , 2007, Medical physics.

[54]  P. Deuflhard Newton Methods for Nonlinear Problems: Affine Invariance and Adaptive Algorithms , 2011 .

[55]  Stephen J. Wright Primal-Dual Interior-Point Methods , 1997, Other Titles in Applied Mathematics.

[56]  Richard P. Brent,et al.  An Algorithm with Guaranteed Convergence for Finding a Zero of a Function , 1971, Comput. J..

[57]  Andrew F. Peterson,et al.  Higher-order vector finite elements for tetrahedral cells , 1996 .

[58]  Thomas Lange,et al.  Shape Constrained Automatic Segmentation of the Liver based on a Heuristic Intensity Model , 2007 .

[59]  H C Charles,et al.  Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas. , 1996, Cancer research.

[60]  S T Clegg,et al.  Estimation of cell survival in tumours heated to nonuniform temperature distributions. , 1996, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[61]  Paresh Parikh,et al.  Generation of three-dimensional unstructured grids by the advancing-front method , 1988 .

[62]  Hans-Christian Hege,et al.  Fast LIC with Piecewise Polynomial Filter Kernels , 1997, VisMath.

[63]  Stefan Volkwein,et al.  Affine Invariant Convergence Analysis for Inexact Augmented Lagrangian-SQP Methods , 2002, SIAM J. Control. Optim..

[64]  K D Paulsen,et al.  Optimization of pelvic heating rate distributions with electromagnetic phased arrays. , 1999, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[65]  R Felix,et al.  Influence of patient models and numerical methods on predicted power deposition patterns. , 1999, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[66]  W. Rheinboldt,et al.  Error Estimates for Adaptive Finite Element Computations , 1978 .

[67]  Peter Monk,et al.  A finite element method for approximating the time-harmonic Maxwell equations , 1992 .

[68]  J. Lang,et al.  Optimization of Temperature Distributions for Regional Hyperthermia Based on a Nonlinear Heat Transfer Model a , 1998, Annals of the New York Academy of Sciences.

[69]  Ronald H. W. Hoppe,et al.  Finite element methods for Maxwell's equations , 2005, Math. Comput..

[70]  Peter Deuflhard,et al.  Adaptive Multilevel FEM as Decisive Tools in the Clinical Cancer Therapy Hyperthermia , 1998 .

[71]  Stefan Volkwein,et al.  SQP methods for parameter identification problems arising in hyperthermia , 2006, Optim. Methods Softw..

[72]  Roland W. Freund,et al.  Conjugate Gradient-Type Methods for Linear Systems with Complex Symmetric Coefficient Matrices , 1992, SIAM J. Sci. Comput..

[73]  Jinchao Xu,et al.  Iterative Methods by Space Decomposition and Subspace Correction , 1992, SIAM Rev..

[74]  Anton Schiela,et al.  Barrier Methods for Optimal Control Problems with State Constraints , 2009, SIAM J. Optim..

[75]  R B Roemer,et al.  Applications of bioheat transfer simulations in hyperthermia. , 1984, Cancer research.

[76]  Peter Deuflhard,et al.  Concepts of an adaptive hierarchical finite element code , 1989, IMPACT Comput. Sci. Eng..

[77]  A. Bensoussan,et al.  Asymptotic analysis for periodic structures , 1979 .

[78]  Hans-Christian Hege,et al.  amira: A Highly Interactive System for Visual Data Analysis , 2005, The Visualization Handbook.

[79]  P. Deuflhard,et al.  Numerical approaches to treatment planning in deep RF-hyperthermia. , 1989, Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al].

[80]  Alfio Quarteroni,et al.  Computational vascular fluid dynamics: problems, models and methods , 2000 .

[81]  Peter Deuflhard,et al.  Multiscale analysis of thermoregulation in the human microvascular system , 2004 .

[82]  Peter Deuflhard,et al.  Affine conjugate adaptive Newton methods for nonlinear elastomechanics , 2007, Optim. Methods Softw..

[83]  R. Hiptmair Finite elements in computational electromagnetism , 2002, Acta Numerica.

[84]  W. Wilmanns,et al.  Regional hyperthermia combined with systemic chemotherapy in advanced abdominal and pelvic tumors: first results of a pilot study employing an annular phased array applicator. , 1988, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[85]  Rolf Adams,et al.  Seeded Region Growing , 1994, IEEE Trans. Pattern Anal. Mach. Intell..

[86]  Peter Deuflhard,et al.  A New Nonlinear Elliptic Multilevel FEM Applied to Regional Hyperthermia , 1998 .

[87]  James M. Ortega,et al.  Iterative solution of nonlinear equations in several variables , 2014, Computer science and applied mathematics.

[88]  A. Bossavit Solving Maxwell equations in a closed cavity, and the question of 'spurious modes' , 1990 .

[89]  J. Nédélec Mixed finite elements in ℝ3 , 1980 .

[90]  Peter Wust,et al.  Perfusion measurement using DCE-MRI: Implications for hyperthermia , 2008, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[91]  P. Deuflhard,et al.  MULTISCALE ANALYSIS FOR THE BIO-HEAT TRANSFER EQUATION - THE NONISOLATED CASE , 2003 .

[92]  Jan Flusser,et al.  Image registration methods: a survey , 2003, Image Vis. Comput..

[93]  Detlev Stalling,et al.  Fast texture based algorithms for vector field visualization , 1999 .

[94]  A Szasz,et al.  Dose concept of oncological hyperthermia: heat-equation considering the cell destruction. , 2006, Journal of cancer research and therapeutics.

[95]  Peter Deuflhard,et al.  Newton Methods for Nonlinear Problems , 2004 .

[96]  Andrew G. Webb,et al.  Optimization of electromagnetic phased-arrays for hyperthermia via magnetic resonance temperature estimation , 2002, IEEE Transactions on Biomedical Engineering.

[97]  Michael Hinze,et al.  Convergence of a Finite Element Approximation to a State-Constrained Elliptic Control Problem , 2007, SIAM J. Numer. Anal..

[98]  P. Deuflhard,et al.  Numerische Mathematik 3 , 2011 .

[99]  Rolf Rannacher,et al.  Adaptive Finite Element Methods for Optimal Control of Partial Differential Equations: Basic Concept , 2000, SIAM J. Control. Optim..

[100]  Bodo Erdmann Ralf Kornhuber Adaptive Multilevel Methods in Three Space Dimensions Folkmar Bornemann , 2011 .

[101]  P Wust,et al.  A fast algorithm to find optimal controls of multiantenna applicators in regional hyperthermia. , 2001, Physics in medicine and biology.

[102]  E. Casas Control of an elliptic problem with pointwise state constraints , 1986 .

[103]  H. H. Penns Analysis of tissue and arterial blood temperatures in the resting human forearm , 1948 .

[104]  A. Massing 1D-Reduktion thermal signifikanter Aderstränge in der Hyperthermie-Modellierung , 2007 .

[105]  J. Pasciak,et al.  Parallel multilevel preconditioners , 1990 .

[106]  Karl Kunisch,et al.  Feasible and Noninterior Path-Following in Constrained Minimization with Low Multiplier Regularity , 2006, SIAM J. Control. Optim..

[107]  H. Yserentant Old and new convergence proofs for multigrid methods , 1993, Acta Numerica.