Principles and Technologies for Electromagnetic Energy Based Therapies

Front Cover
PRINCIPLES AND TECHNOLOGIES FOR ELECTRO MAGNETIC ENERGY BASED
PRINCIPLES AND TECHNOLOGIES FOR ELECTRO MAGNETIC ENERGY BASED
Copyright
Contents
List of contributors
Preface
1 - Mathematical modeling of heat transfer in biological tissues (bioheat transfer)
	1.1 Introduction
	1.2 Mathematical models of bioheat transfer
	1.3 Thermal tissue properties
		1.3.1 Specific heat capacity
		1.3.2 Thermal conductivity
		1.3.3 Blood perfusion
		1.3.4 Thermal diffusivity
		1.3.5 Temperature dependence of thermal tissue properties
		1.3.6 Coupling between electromagnetic and heat-transfer equations
	1.4 Arrhenius model
		1.4.1 Modeling of blood perfusion change in response to hyperthermia
		1.4.2 Sensitivity of bioheat models to tissue property variations
	1.5 Experimental studies
	1.6 Example of a bioheat transfer model
		1.6.1 How to run the example model
		1.6.2 Model results and interpretation
	References
2 - Review of computational methods for therapeutic electromagnetic technologies
	2.1 Introduction
	2.2 Mathematical preliminaries
		2.2.1 Maxwell\'s equations
		2.2.2 Electrostatic and volume conductor formulations
		2.2.3 Current conservation formulations
		2.2.4 Bioheat formulation
		2.2.5 Boundary conditions
		2.2.6 Infinite domains
	2.3 Numerical techniques
		2.3.1 FDTD method
		2.3.2 FE method
		2.3.3 FE method example: the isopotential disc electrode
		2.3.4 BE method
	References
3 - Pulsed electric fields
	3.1 Background and history of electroporation
		3.1.1 Bioelectrics and external electric fields
		3.1.2 The discovery and development of electroporation
	3.2 Biological basis of electroporation
		3.2.1 Electroporation as a molecular phenomenon
		3.2.2 Cell behavior in an electric field
		3.2.3 Modeling the cell as an electrical circuit
		3.2.4 The interaction between electric pulse parameters and cellular biology
			3.2.4.1 Pulse parameters
			3.2.4.2 Physiological factors affecting EP
		3.2.5 Computational models of electroporation in bulk tissue
			3.2.5.1 Fundamental electromagnetic equations and electroporation thresholds
			3.2.5.2 Interaction between tissue conductivity and EP
			3.2.5.3 Thermal considerations during EP
			3.2.5.4 Stochastic models of pulse application and cell death
			3.2.5.5 EP-related neuromuscular stimulation and its mitigation
			3.2.5.6 Other biophysical effects
	3.3 Generator design
		3.3.1 Introduction
		3.3.2 Capacitance-based systems
		3.3.3 Other approaches
	3.4 Electrode design
		3.4.1 Types of electrodes used for EP
		3.4.2 Key considerations for electrode design
	3.5 Models and monitoring of EP
		3.5.1 In vitro
		3.5.2 Vegetable model
		3.5.3 Conductivity monitoring
		3.5.4 Ex vivo
		3.5.5 In vivo
	3.6 Medical applications of EP and related technologies
		3.6.1 Ablation
			3.6.1.1 Cancer
			3.6.1.2 Cardiac
			3.6.1.3 Veterinary
		3.6.2 Vaccination and gene therapy
	3.7 Summary
	References
4 - Radiofrequency ablation
	4.1 Fundamental principles
		4.1.1 Definitions
		4.1.2 Interaction between radiofrequency energy and biological tissue
		4.1.3 Historical perspective
	4.2 Instrumentation and system design
		4.2.1 Radiofrequency ablation electrodes
		4.2.2 Radiofrequency ablation generators
		4.2.3 How to protect surrounding tissues
	4.3 Preclinical evaluation
		4.3.1 Bench test
		4.3.2 Preclinical experimental studies
	4.4 Clinical applications
		4.4.1 Tumor ablation
		4.4.2 Ablation of cardiac arrhythmias
	4.5 Conclusions
	Financial support
	References
5 - Microwave ablation: physical principles and technology
	5.1 Components of a microwave ablation system
	5.2 Biophysics of MWA
		5.2.1 Computational models of microwave ablation
	5.3 MWA applicator design
		5.3.1 Cable selection: interconnecting cable and applicator shaft
		5.3.2 Antenna design metrics
		5.3.3 Example: analysis of a water-cooled monopole antenna
		5.3.4 Consideration of system operating frequency
		5.3.5 Emerging microwave ablation antenna designs
		5.3.6 Applicators with asymmetric ablation patterns
	5.4 Power delivery considerations
	5.5 Experimental assessment of ablation applicators
	5.6 Summary
	References
6 - Treating solid tumors using tumor treating fields: an overview of the theory and practices
	6.1 Introduction
	6.2 Section 1. Theory of TTFields
	6.3 Section 2. What TTFields does within the cell—experimental evidence
	6.4 Overview of cell cycle
	6.5 Stages of the cell cycle
	6.6 Effect of TTFields on cellular division
	6.7 Mechanism of action of TTFields
	6.8 TTFields effect is frequency, intensity, and time-dependent
	6.9 The effect of TTFields is directional
	6.10 Mechanism of action: what do TTFields actually do to cells?
	6.11 Other effects of TTFields on cells
	6.12 Modeling the effect of TTFields on cells
	6.13 Some basic considerations when analyzing the effect of TTFields on subcellular structures
	6.14 Power deposited by TTFields in a cell
	6.15 Dipole alignment and dielectrophoresis effects of TTFields
	6.16 Dipole alignment
	6.17 Dielectrophoresis
	6.18 Other theories on how TTFields may influence cell proliferation
	6.19 Section 3. Clinical applications of TTFields
		6.19.1 Designing a device for delivering TTFields in the clinical setting
	6.20 A brief overview of the use of TTFields in the clinic
	6.21 Section 4. TTFields distribution in the body
	6.22 Numerically simulating delivery of TTFields
		6.22.1 Governing equations
	6.23 Numerical simulations of TTFields distribution in the body
	6.24 The stages in creating the simulations
	6.25 Model creation
	6.26 Imaging data
	6.27 Modeling brain tumors
	6.28 Assigning electric properties to tissues and tumors
	6.29 Deriving electric properties from images
	6.30 Setting boundary conditions and solving the model
	6.31 The equation
	6.32 The solver
	6.33 Boundary conditions
	6.34 Section 5. TTFields dosimetry
	6.35 Section 6. Summary—TTFields dosimetry and treat planning
	References
7 - Neural stimulation technologies
	7.1 Introduction to neural stimulation
	7.2 A noninvasive approach
		7.2.1 Functional electrical stimulation
			7.2.1.1 Basic principles
			7.2.1.2 Technical requirements
			7.2.1.3 Example applications
			7.2.1.4 Future trends
	7.3 Invasive approaches
		7.3.1 Implantable neural interfaces
			7.3.1.1 Vagus nerve stimulation
		7.3.2 Deep brain stimulation
		7.3.3 Cochlear implants
	7.4 Neurostimulation in cerebral palsy as a case study
	References
8 - Electric field and wound healing
	8.1 Introduction: electrotherapy as a promising solution to the problem of nonhealing chronic ulcers
	8.2 Wound healing process requires cross-talk between multiple cell types: an overview
	8.3 Physiological EF generation in wounds
	8.4 Electric field and cell migration: an overriding guidance cues and the effects of EF on cell signaling mechanisms
	8.5 Different EF modalities for wound healing therapy
		8.5.1 Currently existing EF modalities for electrical wound stimulation
		8.5.2 Low-frequency pulsed electromagnetic fields
		8.5.3 Wireless EF stimulation of wound healing and the critical role of EF frequency in the regulation of cell responses
		8.5.4 Emerging therapies
	8.6 Future prospective for EF therapies for chronic ulcers
	References
9 - Radiofrequency and microwave hyperthermia in cancer treatment
	9.1 Introduction
	9.2 Hyperthermia physics
		9.2.1 Electromagnetic mechanisms of heating
		9.2.2 Maxwell\'s equations
		9.2.3 Heat transfer
	9.3 Electromagnetic-based heating systems
		9.3.1 Hyperthermia modalities
		9.3.2 Components of heating systems
			9.3.2.1 RF/MW signal pathway
			9.3.2.2 Thermometry
			9.3.2.3 Feedback loop coupling hyperthermia treatment planning with thermometry
			9.3.2.4 Case study—annular phased array system
	9.4 Thermal dosimetry
	9.5 Treatment planning
		9.5.1 SAR modeling
		9.5.2 Temperature modeling
		9.5.3 Optimization
	9.6 Treatment guidance
	9.7 Hyperthermia clinical studies
		9.7.1 Hyperthermia and radiation
		9.7.2 Hyperthermia and chemotherapy
		9.7.3 Summary of key HT clinical trials
	9.8 Future outlook
	Acknowledgments
	References
10 - History and development of microwave thermal therapy∗
	10.1 Introduction and background
		10.1.1 Hyperthermia
		10.1.2 Ablation
		10.1.3 Milestones of thermal therapy
	10.2 Hyperthermia to ablation [three phases: EARLY (hyperthermia), CURRENT (ablation), FUTURE (ablation)]
		10.2.1 Experimental performance characterization and verification
			10.2.1.1 EARLY
			10.2.1.2 CURRENT
			10.2.1.3 FUTURE
		10.2.2 Single antenna development
			10.2.2.1 EARLY
			10.2.2.2 CURRENT
			10.2.2.3 FUTURE
		10.2.3 Multiple antennas and arrays
			10.2.3.1 EARLY
			10.2.3.2 CURRENT
		10.2.4 Clinical use
			10.2.4.1 EARLY
			10.2.4.2 CURRENT
		10.2.5 Treatment planning
			10.2.5.1 EARLY
			10.2.5.2 CURRENT
			10.2.5.3 FUTURE
		10.2.6 Clinical thermal treatment
			10.2.6.1 EARLY
			10.2.6.2 CURRENT
			10.2.6.3 FUTURE
		10.2.7 Modeling with computer simulations
			10.2.7.1 EARLY
			10.2.7.2 CURRENT
		10.2.8 Navigation
			10.2.8.1 EARLY
			10.2.8.2 CURRENT
			10.2.8.3 FUTURE
		10.2.9 Thermal enhancement
	10.3 Summary
	References
11 - Nano-pulse stimulation, a nonthermal energy modality for targeting cells
	11.1 Nano-pulse stimulation of cells
		11.1.1 Nanoporation: a new method of electroporation
	11.2 Nanoporation targets both the plasma membrane and organelle membranes
	11.3 Practical applications of nano-pulse stimulation
	11.4 NPS effects on skin
		11.4.1 Seborrheic keratosis
		11.4.2 Sebaceous hyperplasia
		11.4.3 Cutaneous warts
	11.5 Development and translation
		11.5.1 Design controls
		11.5.2 Patent protection
		11.5.3 Teamwork
	References
12 - FDA regulation of energy-based therapy devices
	12.1 FDA premarket regulatory framework
	12.2 General controls
	12.3 510(k) premarket notification
		12.3.1 De novo submission
	12.4 PMA pathway
	12.5 Case studies
	12.6 510(k) example
		12.6.1 Summary of nonclinical/bench studies
		12.6.2 Summary of clinical testing
		12.6.3 Summary of usability testing
	12.7 De novo example
		12.7.1 Summary of nonclinical/bench studies
		12.7.2 Summary of clinical testing
		12.7.3 Summary of usability
	12.8 PMA example
		12.8.1 Summary of nonclinical/bench studies
		12.8.2 Summary of clinical testing
		12.8.3 Summary of usability
	12.9 Conclusion
13 - Clinical trials with electromagnetic ablation technologies
	13.1 Introduction
	13.2 Ethical considerations
		13.2.1 Helsinki and Institutional Review Board
		13.2.2 Prerequisites for clinical evaluation of an ablation device
	13.3 Human studies
		13.3.1 Trial design
		13.3.2 Feasibility and safety of the procedures
			13.3.2.1 Rationale
			13.3.2.2 Methods
			13.3.2.3 Challenges
		13.3.3 Tolerance and efficacy
			13.3.3.1 Rationale
			13.3.3.2 Methods
			13.3.3.3 Challenges
		13.3.4 Comparative evaluation with reference standard
			13.3.4.1 Rationale
			13.3.4.2 Methods
			13.3.4.3 Challenges
		13.3.5 Long-term evaluation
			13.3.5.1 Rationale
			13.3.5.2 Methods
			13.3.5.3 Challenges
	13.4 Conclusion
	References
Index
Back Cover