Enhancement in treatment planning for magnetic nanoparticle hyperthermia: Optimization of the heat absorption pattern

In clinical applications of magnetic nanoparticle hyperthermia for cancer treatment it is very important to ensure a maximum damage to the tumor while protecting the normal tissue. The resultant heating pattern by the nanoparticle distribution in tumor is closely related to the injection parameters. In this study we develop an optimization algorithm to inversely determine the optimum heating patterns induced by multiple nanoparticle injections in tumor models with irregular geometries. The injection site locations, thermal properties of tumor and tissue, and local blood perfusion rates are used as inputs to the algorithm to determine the optimum parameters of the heat sources for all nanoparticle injection sites. The design objective is to elevate the temperature of at least 90% of the tumor above 43°C, and to ensure only less than 10% of the normal tissue is heated to temperatures of 43°C or higher. The efficiency, flexibility and capability of this approach have been demonstrated in a case study of two tumors with simple or complicated geometry. An extensive experimental database should be developed in the future to relate the optimized heating pattern parameters found in this study to their appropriate nanoparticle concentration, injection amount, and injection rate. We believe that the optimization algorithm developed in this study can be used as a guideline for physicians to design an optimal treatment plan in magnetic nanoparticle hyperthermia.

[1]  L. Rosenhead Conduction of Heat in Solids , 1947, Nature.

[2]  H. H. Pennes Analysis of tissue and arterial blood temperatures in the resting human forearm. , 1948, Journal of applied physiology.

[3]  R. Gilchrist,et al.  Selective Inductive Heating of Lymph Nodes , 1957, Annals of surgery.

[4]  M. Maeda,et al.  [Heat conduction]. , 1972, Kango kyoshitsu. [Nursing classroom].

[5]  C. Song Effect of local hyperthermia on blood flow and microenvironment: a review. , 1984, Cancer research.

[6]  M. Dewhirst,et al.  The utility of thermal dose as a predictor of tumor and normal tissue responses to combined radiation and hyperthermia. , 1984, Cancer research.

[7]  J. Sylvester,et al.  Clinical application of thermal isoeffect dose. , 1987, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[8]  M. N. Özişik Boundary value problems of heat conduction , 1989 .

[9]  M. Dewhirst,et al.  Relationships among tumor temperature, treatment time, and histopathological outcome using preoperative hyperthermia with radiation in soft tissue sarcomas. , 1992, International journal of radiation oncology, biology, physics.

[10]  Koichi Murakami,et al.  Temperature-sensitive amorphous magnetic flakes for intratissue hyperthermia , 1994 .

[11]  T. Secomb,et al.  Theoretical models for drug delivery to solid tumors. , 1997, Critical reviews in biomedical engineering.

[12]  W. Kaiser,et al.  Physical limits of hyperthermia using magnetite fine particles , 1998 .

[13]  Jeffrey C. Lagarias,et al.  Convergence Properties of the Nelder-Mead Simplex Method in Low Dimensions , 1998, SIAM J. Optim..

[14]  H. H. Pennes Analysis of tissue and arterial blood temperatures in the resting human forearm. 1948. , 1948, Journal of applied physiology.

[15]  J. Valvano,et al.  BIOHEAT TRANSFER , 1999 .

[16]  Chieko Azuma,et al.  Using units of CEM 43°C T90, local hyperthermia thermal dose can be delivered as prescribed , 2000 .

[17]  W Andrä,et al.  Electromagnetic heating of breast tumors in interventional radiology: in vitro and in vivo studies in human cadavers and mice. , 2001, Radiology.

[18]  P. Moroz,et al.  Magnetically mediated hyperthermia: current status and future directions , 2002, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[19]  R. E. Rosensweig,et al.  Heating magnetic fluid with alternating magnetic field , 2002 .

[20]  J. Kumaradas,et al.  Optimization of a beam shaping bolus for superficial microwave hyperthermia waveguide applicators using a finite element method. , 2003, Physics in medicine and biology.

[21]  Liang Zhu,et al.  Effect of Blood Flow on Thermal Equilibration and Venous Rewarming , 2003, Annals of Biomedical Engineering.

[22]  Klaus Jung,et al.  Evaluation of magnetic fluid hyperthermia in a standard rat model of prostate cancer. , 2004, Journal of endourology.

[23]  Werner A. Kaiser,et al.  Enhancement of AC-losses of magnetic nanoparticles for heating applications , 2004 .

[24]  N Siauve,et al.  Optimization of the sources in local hyperthermia using a combined finite element-genetic algorithm method , 2004, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[25]  Chieko Azuma,et al.  Thermal Dose Is Related to Duration of Local Control in Canine Sarcomas Treated with Thermoradiotherapy , 2005, Clinical Cancer Research.

[26]  H. Bagaria,et al.  Transient solution to the bioheat equation and optimization for magnetic fluid hyperthermia treatment , 2005, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[27]  Roland Felix,et al.  The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma , 2006, Journal of Neuro-Oncology.

[28]  Zeljko Vujaskovic,et al.  Re-setting the biologic rationale for thermal therapy , 2005, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[29]  Klaus Jung,et al.  Magnetic fluid hyperthermia (MFH)reduces prostate cancer growth in the orthotopic Dunning R3327 rat model , 2005, The Prostate.

[30]  Werner A. Kaiser,et al.  Towards breast cancer treatment by magnetic heating , 2005 .

[31]  M. Heinkenschloss,et al.  Real-Time PDE-Constrained Optimization , 2007 .

[32]  Peter Wust,et al.  Thermotherapy of prostate cancer using magnetic nanoparticles: feasibility, imaging, and three-dimensional temperature distribution. , 2007, European urology.

[33]  Jean-Paul Fortin,et al.  Intracellular heating of living cells through Néel relaxation of magnetic nanoparticles , 2008, European Biophysics Journal.

[34]  Maher Salloum,et al.  An in-vivo experimental study of temperature elevations in animal tissue during magnetic nanoparticle hyperthermia , 2008, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[35]  Liang Zhu,et al.  Controlling nanoparticle delivery in magnetic nanoparticle hyperthermia for cancer treatment: Experimental study in agarose gel , 2008, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[36]  Andreas Antoniou,et al.  Practical Optimization: Algorithms and Engineering Applications , 2007, Texts in Computer Science.