Therapeutic Ultrasound 1st Edition by Jean Michel Escoffre 3319225364 9783319225364

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ISBN-10 :  3319225364 

ISBN-13 :  9783319225364

Author:  Jean-Michel Escoffre 

This book highlights advances and prospects of a highly versatile and dynamic research field: Therapeutic ultrasound. Leading experts in the field describe a wide range of topics related to the development of therapeutic ultrasound (i.e., high intensity focused ultrasound, microbubble-assisted ultrasound drug delivery, low intensity pulsed ultrasound, ultrasound-sensitive nanocarriers), ranging from the biophysical concepts (i.e., tissue ablation, drug and gene delivery, neuromodulation) to therapeutic applications (i.e., chemotherapy, sonodynamic therapy, sonothrombolysis, immunotherapy, lithotripsy, vaccination). This book is an indispensable source of information for students, researchers and clinicians dealing with non-invasive image-guided ultrasound-based therapeutic interventions in the fields of oncology, neurology, cardiology and nephrology.

Therapeutic Ultrasound 1st Table of contents:

Part I: High Intensity Focused Ultrasound Ablation of Pathological Tissue
1: HIFU Tissue Ablation: Concept and Devices
1.1 Introduction
1.2 Principles of HIFU
1.3 History of HIFU
1.4 Exposure Dosimetry
1.5 HIFU Treatment Delivery
1.5.1 Transducer Materials
1.6 Clinical Devices
1.6.1 Extracorporeal Devices
1.6.2 Trans-rectal Devices
1.6.3 Interstitial Devices
1.7 Summary
References
2: Prostate Focused Ultrasound Therapy
2.1 Introduction
2.2 History and Principle of PCa Treatment by HIFU
2.3 HIFU Devices Dedicated to PCa Treatment
2.3.1 Ablatherm® with Ultrasound Integrated Imaging
2.3.2 Sonoblate 500
2.3.3 Focal One
2.3.4 MRgFUS Devices
2.4 Long-Term Outcomes of HIFU in PCa Treatment
2.4.1 HIFU as Primary Care Treatment
2.4.2 Salvage After HIFU Failure
2.4.2.1 HIFU Retreatment
2.4.2.2 External Radiation Therapy (ERBT)
2.4.2.3 Salvage Surgery
2.4.3 Salvage HIFU After ERBT or Brachytherapy
2.4.3.1 ERBT Failure
2.4.3.2 Brachytherapy Failure
2.5 Focal Therapy with HIFU
2.5.1 The Current Role of Imaging in PCa Focal Therapy
2.5.1.1 Patient Selection and Treatment Planning: The Need for Better PCa Mapping
2.5.1.2 Postoperative Evaluation of the Ablated Area
2.5.1.3 Detection of Post-HIFU Local Recurrences
2.5.2 Outcomes of HIFU Focal Therapy
2.5.2.1 Sub-total HIFU Strategy
2.5.2.2 Hemi-Ablation Strategy (UK Experience)
2.5.2.3 Zonal Treatment (Belgium Experience)
2.5.2.4 Hemi-ablation Strategy (French Experience)
2.5.2.5 Focal Therapy (Uni- and Multi-­focal Strategy: UK Experience)
2.5.2.6 Focal Therapy (Edouard Herriot Experience)
2.5.2.7 Hemi-Salvage HIFU for Radio-­Recurrent PCa
2.5.2.7.1 UK Pilot Study (Ahmed et al. 2012a, b)
2.5.2.7.2 Multicenter Study (Baco et al. 2014)
Conclusion
References
3: MRI-Guided HIFU Methods for the Ablation of Liver and Renal Cancers
3.1 Introduction
3.2 Obstruction of the Ultrasonic Beam Path by the Thoracic Cage
3.2.1 Apodization Methods Based on an Anatomical Model of the Thoracic Cage Using Binarized Apo
3.2.1.1 Phase Conjugation
3.2.1.2 Constrained Optimization Using the Boundary Element Method (BEM)
3.2.1.3 Apodization Methods Based on Direct Detection of Scattering or Attenuating Structures
3.2.2 Decomposition of the Time-­Reversal Operator
3.2.2.1 Pulse-Echo Detection
3.2.2.2 Cavitation-Enhanced Back-Projection
3.3 Challenges Associated with Physiological Motion of the Liver and Kidney
3.3.1 Motion Compensation Strategies for HIFU Ablation on Abdominal Organs
3.3.2 MR Guided Thermometry and Dosimetry in Abdominal Organs
3.3.2.1 Compensation of Motion Related Errors in Thermal Maps
3.3.2.2 Challenges Associated with Real-Time Volumetric MR-Temperature Imaging
Conclusion
References
4: Magnetic Resonance-Guided High Intensity Focused Ultrasound Ablation of Breast Cancer
4.1 Introduction
4.2 Role of MR Imaging in HIFU Ablation of Breast Lesions
4.2.1 Imaging of Breast Cancer
4.2.2 MRI for Guidance of HIFU Treatment
4.3 High Intensity Focused Ultrasound of the Breast
4.3.1 Technique
4.3.2 HIFU Breast Systems
4.4 Clinical Studies
4.4.1 Benign Lesions
4.4.2 Invasive Breast Cancer with Resection
4.4.3 Invasive Breast Cancer Without Resection
4.5 Clinical and Technical Challenges
4.5.1 Challenges for Improvement
4.5.1.1 Patient Selection
4.5.1.2 Treatment Margins
4.5.2 Thermometry
4.5.3 Pathology
4.5.4 Sentinel Lymph Node Procedure
4.6 Experience with the Dedicated Breast System
4.7 Future Directions
Conclusion
References
5: HIFU for Palliative Treatment of Pancreatic Cancer
5.1 Clinical Management of Pancreatic Cancer
5.2 Devices and Methods
5.3 Preclinical Studies
5.4 Ultrasound-guided HIFU System Clinical Trials
5.5 MR-guided HIFU System Clinical Trials
5.6 Clinical Experience with HIFU Treatment of Neuroendocrine Tumors
5.7 Concurrent Gemcitabine and HIFU Therapy
Conclusions
References
6: MR-Guided Transcranial Focused Ultrasound
6.1 Influence of the Skull Bone
6.2 Skull Aberration Correction Techniques
6.2.1 Minimally Invasive Correction
6.2.2 Non Invasive Correction
6.3 Thermal Therapy
6.3.1 Thalamotomy
6.3.2 Expansion of Treatment Envelope
6.3.2.1 Improvements in Aberration Correction
6.3.2.2 Choice of the Frequency
6.3.2.3 Cavitation-Enhanced Heating
6.4 Non Thermal Therapy
6.4.1 Mechanical Ablation
6.4.2 BBB Opening
6.4.3 Neuromodulation
6.5 Conclusions and Future Prospects
References
7: Focused Ultrasound and Lithotripsy
7.1 Introduction
7.2 Localized High Pressure on Kidney Stones
7.2.1 Cavitation Control Waveform (C-C waveform)
7.2.2 Observation of Cavitation on Stones
7.2.2.1 High Frequency
7.2.2.2 Low Frequency
7.2.3 Stone Fragmentation
7.3 Ultrasound Lithotripsy with Cavitation Monitoring
7.3.1 Experimental Setup and Ultrasound Sequence for Subharmonic Detection
7.3.2 Subharmonic Signal Level and Stone Erosion Volume
7.3.2.1 Subharmonic Signal Level
7.4 Motion Compensation System for Ultrasound Lithotripsy
7.4.1 Image-guided Motion Compensation System
7.4.2 Body Motion Compensation System for Focused Ultrasound Treatment
Conclusion
References
8: Heat-Based Tumor Ablation: Role of the Immune Response
8.1 Introduction
8.2 Methods of Thermal Ablation Technique
8.2.1 High-Intensity Focused Ultrasound Ablation
8.2.2 Radiofrequency Ablation
8.2.3 Laser Ablation
8.2.4 Microwave Ablation
8.2.5 Cryoablation
8.3 Mechanisms of Thermal Ablation and Immune Response
8.3.1 Direct Thermal and Non-­thermal Effects on Tumor
8.3.2 Direct Thermal Effects on Tumor Blood Vessels
8.3.3 Indirect Effects After Thermal Ablation
8.4 Antitumor Immune Response After Thermal Ablation
8.4.1 HIFU Ablation
8.4.2 Radiofrequency Ablation
8.4.3 Laser Ablation
8.4.4 Cryoablation
8.4.5 Microwave Ablation
Conclusion
References
Part II: Drug and Gene Delivery Using Bubble-Assisted Ultrasound
9: Droplets, Bubbles and Ultrasound Interactions
9.1 Introduction
9.2 Nonlinear Propagation
9.2.1 Basic Equations for the Nonlinear Ultrasound Beam
9.2.2 Numerical Solution for the Nonlinear Ultrasound Beam
9.2.3 Nonlinear Pressure Field at the Focus of the Beam
9.3 Bubble Dynamics
9.3.1 Dynamics of a Gas Bubble
9.3.2 Linearization
9.3.3 Pressure Emitted by the Bubble
9.3.4 Secondary Bjerknes Force
9.4 Droplet Dynamics
9.4.1 Oscillatory Translations
9.4.2 Focusing inside a Spherical Droplet
9.4.2.1 Case 1: Droplets much Larger in Size than the Wavelength
9.4.2.2 Case 2: Droplets Similar or Smaller in Size than the Wavelength
9.4.3 Radial Vapor Bubble Expansion
9.4.4 Activation Below Boiling Point
References
10: Sonoporation: Concept and Mechanisms
10.1 Introduction
10.2 Mechanisms of Barrier Permeabilization and Molecular Delivery
10.2.1 Acoustical Phenomena
10.2.2 Hypothesized Impacts of Acoustic Phenomena on Cell Membrane and Molecular Uptake
10.2.2.1 Pore Formation
10.2.2.2 Endocytosis
10.2.2.3 Membrane Wounds
Conclusions
References
11: Design of Microbubbles for Gene/Drug Delivery
11.1 Introduction
11.2 Formulation
11.2.1 General Consideration
11.2.1.1 Shell Components
11.2.1.2 UCA Stability and Lifetime
11.2.2 Conditions Allowing Drug Delivery
11.2.3 Drug Delivery with UCA and Ultrasound
11.2.3.1 Plain UCA with Free Drug
11.2.3.2 Drug-Loaded UCA
11.2.3.2.1 Drug in/on the Shell
11.2.3.2.2 Nanoparticles on UCA
11.2.3.2.3 UCA in Drug-Loaded Liposomes
11.2.3.2.4 Hard Shell
11.2.3.2.5 Nanoemulsion
11.2.3.2.6 Monosize
11.2.4 Optimization of Drug Delivery
11.2.5 Characterization of UCA
11.3 Clinical Translation and Regulatory Issues
Conclusion
References
12: Co-administration of Microbubbles and Drugs in Ultrasound-Assisted Drug Delivery: Comparison
12.1 Introduction
12.2 Co-administration Approach: Microbubbles that Do Not Carry the Drug
12.2.1 Cell Membrane as a Barrier to Cross
12.2.2 Vessel Wall: The First In-Vivo Barrier for Drug Delivery from the Bloodstream
12.2.3 Tissue Geometry, Mechanics and Distance as Barriers to Drug Delivery
12.3 Drug-Carrying Sonosensitive Particles
12.3.1 Drug-Loaded Nano/Microbubbles
12.3.2 Formulations and Properties
12.3.2.1 Drug-Particle Formulations Via Hydrophobic Interaction (Non-�covalent Binding)
12.3.2.2 Electrostatic Complexes
12.3.2.3 Covalent Coupling of Drug Substances onto Microbubbles
12.3.2.4 Particle-Decorated Microbubbles
12.3.2.5 Liposomal Bubbles
12.3.3 Problems to be Addressed: Formulation and Stability of Drug-Carrier Particles
12.4 Selection of the Best Technique: Optimal Approaches for Particular Tasks
Conclusion
References
13: Drug-Loaded Perfluorocarbon Nanodroplets for Ultrasound-­Mediated Drug Delivery
13.1 Introduction
13.2 Ultrasound Effects in Drug Delivery: Anticipated Mechanisms
13.2.1 Thermal Effects
13.2.2 Mechanical Action of Ultrasound: Cavitation
13.2.3 Mechanical Action of Ultrasound in the Absence of Cavitation
13.3 Phase-shift Perfluorocarbon Nanoemulsions as Drug Carriers for Ultrasound-­mediated Drug De
13.3.1 Generation of Perfluorocarbon Nanoemulsions
13.3.1.1 General Approach
13.3.1.2 Polymeric Micelles as a Starting Point for Generation of Drug-­loaded PFC Nanodroplets
13.3.2 Droplet-to-bubble Phase Transition in PFP Nanoemulsions
13.3.2.1 Vaporization of the PFP Droplets: Mechanism and Therapeutic Applications
13.3.2.2 Droplet-to-bubble Phase Transitions in Perfluoro-15-crown-­5-ether Nanoemulsions
13.4 Therapeutic Outcomes and Anticipated Mechanisms of Ultrasound-Mediated Drug Delivery using P
13.5 Conclusions and Future Prospects
References
14: Bubble-Assisted Ultrasound: Application in Immunotherapy and Vaccination
14.1 Introduction
14.2 Ab-Based Immunotherapy
14.2.1 Applications in Neurology
14.2.2 Applications in Oncology
14.3 Dendritic Cell-Based Vaccination
14.4 Cytokine Gene Therapy
14.5 Conclusions and Future Prospects
References
15: Sonoporation: Applications for Cancer Therapy
15.1 Introduction
15.2 Tumor Microenvironment and Pathways of Sonoporation-Mediated Drug Delivery
15.2.1 Tumor Treatment Through a Transvascular-Interstitial-­Intracellular Pathway
15.2.1.1 Transvascular Transport by Modulating Vascular Integrity
15.2.1.2 Interstitial Transport
15.2.1.3 Transmembrane Transport of Tumor Parenchymal Cells
15.2.2 Destruction of Tumor Vascular
15.2.2.1 Enhanced Cellular Uptake of Drugs in Vascular Endothelial Cells
15.2.2.2 Mechanical Destruction of the Tumor Vasculature
15.3 Treatment Protocols in Preclinical Experiments
15.3.1 Mixing Drugs with Microbubbles Versus Loading a Drug onto Microbubbles
15.3.1.1 Mixture of Drug and Microbubbles
15.3.1.2 Drug-Loaded Microbubbles
15.3.2 Routes of Microbubbles and Antitumor Agent Administration
15.3.2.1 Intravenous Injection
15.3.2.2 Intratumoral Injection
15.3.2.3 Intraperitoneal Injection
15.3.3 Ultrasound Parameters
15.3.4 Treatment Schedule
15.4 Application in Cancer Therapies
15.4.1 Cancer Therapy
15.4.1.1 Enhanced Tumoricidal Effects
15.4.1.2 Reduction of Toxicity of Chemotherapeutics
15.4.1.3 Reversal of Drug Resistance
15.4.2 Adjuvant Treatment to Other Cancer Therapies
15.4.3 Cancer Vaccination
15.5 First Clinical Case Study
15.6 Prospects and Conclusions
15.6.1 Mechanisms of Microbubble-­Tissue Interaction In-vivo
15.6.2 Advance in Multifunctional Microbubbles
15.6.3 Optimization of Drug Delivery Protocol
15.6.4 Development of a Dedicated Ultrasound System for Drug Delivery
15.6.5 Safety Studies
Conclusions
References
16: Microbubble-Assisted Ultrasound for Drug Delivery in the Brain and Central Nervous System
16.1 Barriers Protecting the Central Nervous System (CNS)
16.2 Formation of the BBB
16.3 Bypassing the BBB for Effective Drug Delivery
16.4 Focused Ultrasound (FUS)-Mediated Barrier Opening
16.5 Advantages of FUS for Drug Delivery Through the BBB
16.6 Mechanisms of FUS
16.7 FUS and Microbubbles for Drug Delivery
16.7.1 Drug Delivery to the Brain in Rodent Models
16.7.2 Drug Delivery to the Primate Brain
16.7.3 Effects of FUS Alone on the Brain
16.8 Future Considerations
References
17: Microbubbles and Ultrasound: Therapeutic Applications in Diabetic Nephropathy
17.1 Introduction
17.2 Diabetic Nephropathy
17.2.1 Pathophysiology of Diabetic Nephropathy
17.2.2 Causes of DN
17.2.3 Endothelial Dysfunction
17.3 Animal Models of Diabetic Nephropathy
17.4 Current Therapeutic Strategies and Challenges
17.4.1 Glycemic Control
17.4.2 Renin Angiotensin System (RAS) Blockade
17.4.3 Kidney Transplantation
17.5 Gene Therapy: Techniques and Vectors – Applications in Diabetic Nephropathy
17.5.1 Viral Gene Delivery
17.5.2 Non-viral Gene Delivery
17.5.2.1 Chemical Methods
17.5.2.2 Physical Methods
17.6 Ultrasound-Mediated Gene Delivery
17.6.1 Microbubbles
17.6.2 UMGD: Methodology and Mechanisms
17.6.3 UMGD: In-Vivo Applications
17.7 Ultrasound-Mediated Gene Delivery: Applications in Diabetic Nephropathy
17.8 Future Perspectives on UMGD for Diabetic Nephropathy
References
18: Drug and Gene Delivery using Sonoporation for Cardiovascular Disease
18.1 Treatment Paradigms: Times Are Changing
18.2 Mode of Delivery: Enteral vs Parenteral
18.3 Parenteral Therapy and Clinical Applications: Lipid Therapy (mAb, Proteins, Gene Therapy)
18.4 Newer Therapeutic Delivery Systems: Acoustic Microspheres
18.5 Therapeutic Cardiovascular Applications of Sonoporation
18.5.1 Sonothrombolysis
18.5.2 Suppression of Arterial Neointimal Formation
18.5.3 Generation of de novo HDL Cholesterol
18.6 Summary of CEUS for Cardiovascular Diagnostic and Therapeutic Applications
References
19: Sonothrombolysis
19.1 Clinical Challenges of Thrombo-Occlusive Disease
19.1.1 Thrombus Formation During Cardiovascular Disease
19.1.1.1 Stroke
19.1.1.2 Deep Vein Thrombosis and Pulmonary Embolism
19.1.1.3 Myocardial Infarction
19.1.2 Frontline Therapy: Thrombolytic Drugs
19.2 Mechanisms of Thrombolytic Enhancement
19.2.1 Thermal Effects of Ultrasound
19.2.2 Primary Mechanical Effects
19.2.3 Secondary Mechanical Effects (Acoustic Cavitation)
19.2.3.1 Classification of Cavitation
19.2.3.2 Know Thy Sound Field
Ultrasound Catheter
Transcranial Doppler
Sub-megahertz Ultrasound
Focused Ultrasound
19.2.3.3 Know Thy Liquid (i.e., Know Thy Cavitation Nuclei)
Endogenous Nuclei
Exogenous Nuclei
19.2.3.4 Know When Something Happens
19.3 Experimental Evidence for Ultrasound-Enhanced Efficacy
19.3.1 Assessment of Sonothrombolysis in the Laboratory
19.3.1.1 In-Vitro, Ex-Vivo, and In-Vivo Studies
19.3.1.2 Ultrasound Exposure Conditions
Ultrasound Therapy Without a Thrombolytic
Ultrasound Therapy with Microbubbles, but Without a Thrombolytic
Ultrasound Therapy with a Thrombolytic
Ultrasound Therapy with Microbubbles and a Thrombolytic
19.3.1.3 Conclusions of Bench Top Studies
19.3.2 Clinical Trials
19.3.2.1 Catheter-Directed Thrombolysis
19.3.2.2 Transcranial Insonation
19.3.2.3 Conclusions of Clinical Studies
19.4 Conclusions and Future Directions
References
Part III: Other Ultrasound Therapy
20: Ultrasound-Mediated Polymeric Micelle Drug Delivery
20.1 Introduction
20.2 Ultrasound
20.2.1 The Thermal Effect of Ultrasound
20.2.2 The Cavitation Effect of Ultrasound
20.2.3 Ultrasound Sonochemistry
20.2.3.1 Ultrasound Degradation
20.2.3.2 Ultrasound-Initiated Polymerization
20.2.3.3 Ultrasonic In-situ Polymerization
20.2.3.4 Site-Specific Ultrasound Degradation
20.2.4 High Intensity Focused Ultrasound (HIFU)
20.3 Micelles
20.4 Ultrasound-Mediated Polymeric Micelle Drug Delivery
20.4.1 Ultrasound-Triggered Physical Breakdown of Micelle and Reversible Release of Payload
20.4.2 Ultrasound-Triggered Chemical Disruption of Polymeric Micelles and Irreversible Payload Re
20.5 Perspectives
References
21: Stimulation of Bone Repair with Ultrasound
21.1 Introduction
21.2 LIPUS Physics
21.2.1 LIPUS Exposure Conditions
21.2.2 Rationale for LIPUS
21.2.3 The Influence of Geometrical Configurations on In-vitro Stimulation
21.2.4 The LIPUS ‘Dose’ and the Need for Standardization
21.3 Potential Bio-effects of LIPUS
21.3.1 Thermal Effects
21.3.2 Non-thermal effects
21.3.3 Effects at the Tissue and Cellular Scales
21.3.4 Intracellular Effects
21.3.5 Molecular Effects
21.3.6 Other Effects
21.4 LIPUS and Mechanotransduction
21.5 LIPUS-Induced Bone Healing: Biological Evidence
21.5.1 LIPUS-Stimulated Gene Expression and Signaling Molecule Release
21.5.1.1 Inflammation
21.5.1.2 Angiogenesis
21.5.1.3 NO and PGE2
21.5.1.4 Early Osteogenesis
21.5.1.5 Proliferation of Osteoprogenitors and Osteoblasts
21.5.1.6 Ossification
21.5.1.7 BMPs
21.5.1.8 Chondrogenesis
21.5.1.9 Bone Remodeling
21.5.1.10 Immune Response
21.5.2 Regeneration of Tissues Other than Bone in Response to LIPUS
21.5.3 Mechanotransduction Signaling Pathways Associated with LIPUS
21.5.3.1 Transmembrane Mechanoreceptors
21.5.3.2 Pathways Associated with PGE2 and NO Signaling Messengers
21.5.3.3 Osteogenesis-�Associated Pathways
21.5.3.4 Chondrogenesis-�Associated Pathways
21.5.4 Ultrasound-Mediated Modulation of the Extra-­Cellular Environment
21.6 Other Forms of Ultrasound Treatments Improving Bone Regeneration
21.6.1 Synergistic Effect of LIPUS Combined with Essential Participants in Bone and Cartilage R
21.6.2 Acoustic Shock Waves
21.6.3 Ultrasound and Tissue Engineering
21.6.4 Ultrasound-Triggered Delivery of Growth Factors
21.7 Clinical Data
21.7.1 Regulatory Agreement
21.7.2 Clinical Evidence
21.7.3 Health Economics of LIPUS
21.8 Discussion
Conclusion
References
22: Sonodynamic Therapy: Concept, Mechanism and Application to Cancer Treatment
22.1 Background
22.1.1 Conventional Approaches to Cancer Treatment
22.1.2 Alternatives to Convention: Stimulus-responsive Therapeutic Approaches
22.1.3 Photodynamic Therapy
22.2 Sonodynamic Therapy (SDT)
22.2.1 The Concept
22.2.2 Sonosensitizers
22.2.3 Mechanism(s) of Activation
22.2.3.1 Direct Ultrasound-­Mediated Generation of ROS
22.2.3.2 The Role of Sonoluminescence
22.2.3.3 Sensitizer-Dependent Destabilization of Cell Membranes
22.3 Application of SDT in the Treatment of Cancer
22.3.1 In-Vitro Studies Examining SDT Efficacy
22.3.2 In-Vivo Studies Examining SDT Efficacy
22.3.3 Towards Clinical Trials with SDT

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