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Therapeutic ultrasound:Personalised dose management
Jean-François Aubry
Institut Langevin (CNRS UMR 7587), INSERM U979, ESPCI ParisTech, Paris 7 University, France
Invited Associate Prof, Univ of Virginia, Department of Radiation Oncology
President of the International Society for Therapeutic Ultrasound (www.ISTU.org)
Applications of Ultrasound in Medicine
• Diagnostic Ultrasound
• Therapeutic ultrasound:- Thrombolysis- Lithotripsy- Histotripsy- Bone repair- Drug delivery- Fat removal- Cancer treatments
-12MPaduring 1µs
skin
transducer Mechanical effectKidney stones destruction(Lithotripsy)
Biological effects of ultrasound
~60°Cduring 3s4MPa
skin
Normal Cells
Dead Cells
Frontier of the lesion
transducer
liver
Thermal effect:Tissue ablation
1mm
Biological effects of ultrasound
Example of MR-guided Therapeutic Ultrasound
Courtesy of Y. Medan and A. Hananel, Insightec
(Uterine Fibroid)
What does MR guidance provide?
• - 3D anatomic information for tumor
targeting
• - Beam path representation for safe
treatment
Example of MR-guided Therapeutic Ultrasound
Courtesy of Y. Medan and A. Hananel, Insightec
• - Post treatment T1 images
• (+ Gd injection)
• - Thermal Dose evaluation
•
Example of MR-guided Therapeutic Ultrasound
What does MR guidance provide?
43 ( ),43
0
tT t
eqt R dt-= ò {0.25 430.5 43
if T CR if T C< °= > °
Equivalent exposure time at 43°C(necrosis if >240eq min in muscle)
Courtesy of Y. Medan and A. Hananel, Insightec
Similar to radiation dose (D. Schlesinger et al, "Equivalence of cell survival data for radiation dose and thermal dose in ablative treatments“, Int. J. of Hyperthermia (2017)
MR-guided Feed back loop control
Temporal analysis of the temperature control with the minimum, mean, and maximum temperature of 195 voxels regulated at 14°C during 100 s.
Mougenot et al, Three-dimensional spatial and temporal temperature control with MR thermometry-guided focused ultrasound, MRM, 2009
MR-guided Feed back loop control
Profound Medical, real-time Magnetic Resonance Imaging with transurethral, robotically-driven therapeutic ultrasound and closed-loop thermal feedback control
MR-guided Feed back loop control
Profound Medical, real-time Magnetic Resonance Imaging with transurethral, robotically-driven therapeutic ultrasound and closed-loop thermal feedback control
5
Operator Console
Treatment Bed
Example of Ultrasound-guided FUS (USgFUS; or USgHIFU)
Haifu Model JC Focused Ultrasound Tumour Therapeutic System
Courtesy of J. Kennedy, F. Wu
Integrated Treatment Transducer (diagnostic US probe and HIFU transducer) in degassed water reservoir
Therapeutic frequency: 0.8MHz—2.4MHz
Courtesy of J. Kennedy, F. Wu
Example of Ultrasound-guided FUS (USgFUS; or USgHIFU)
Example of change seen on ultrasound image during treatment(Left = Before, Right = After)
Courtesy of J. Kennedy, F. Wu
Example of Ultrasound-guided FUS (USgFUS; or USgHIFU)
Ultrasonic Backscattering-Based Monitoring
Principle: detecting bubbles(cavitation or boiling)
CourtesyV. Khokhlova
))()(1)(())(,( 0 zTzzczTzc db+=
zztczT ¶
¶-=D )()(2)(
0 dba
R. Seip et al, IEEE UFFC,1997C. Simon et al., IEEE UFFC 45(4),1998 Tissue dependent parameter
Ultrasonic speckle motion detection :
• Sound Speed variations– Apparent displacement of scatterers
• Thermal Expansion– Physical displacement of scatterers
a : thermal expansion coefficient
• Temperature versus scatterers displacement
(Bamber et al. 1979)
0>b0<b
In muscleIn fat
Principle of Ultrasonic Thermometry
Temperature Monitoring during HIFU
n HIFU Beam- 10 s- 1500 W.cm-2
n 1 image/s
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21°C
32 °C
DT
M. Pernot, M. Tanter, J. Bercoff, K.R. Waters and M. Fink IEEE-UFFC, 2004, 51, pp 606-615
Limitations of US thermometry
n A priori Knowledge of :
n Motion Artifacts: scaterrer displacement can be hidden by tissue motionè High frame rate imaging can help to reduce motion artifacts
)(20ba-
c
Courtesy E. Ebbini
Conventional Imaging Ultrafast Imaging
RAM
Parallel Processing
Principles of Ultrafast Ultrasonic Imaging
In vivo experiments on sheep brain
Bmode image
Skull base
Trepanated sheep
Gateau et al, Phys. Med. Biol. 2011
In vivo experiments on sheep brain
Coherent subtractionNo nucleation Nucleation
Ultrafast images 550 µs after the high amplitude excitation
Gateau et al, Phys. Med. Biol. 2011
In vivo experiments on sheep brain
Coherent subtractionNo nucleation Nucleation
Ultrafast images 550 µs after the high amplitude excitation
Gateau et al, Phys. Med. Biol. 2011
In vivo experiments on sheep brain
Ultrafast imaging of bubble cloud formation
Currently impossible to image such events with MRI !
Ultrasound-based feedback loop control ?
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3 mm
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T (°C)
US- thermal map
Not accurrate enough for in vivo feedback control
Ultrasound-based feedback loop control ?
But cavitation can be used as a feedback control
A.Poizat,Phd,UniversitédeLyon,2016
Cavitation dose
Frequency
No cavitationCavitation (stable)
Ultrasound-based feedback loop control ?
But cavitation can be used as a feedback control
A.Poizat,Phd,UniversitédeLyon,2016
Ultrasound-based feedback loop control ?
But cavitation can be used as a feedback control
Gerold etal,Acoustic cavitationsub-millisecond signalprocessing forultrasound surgery ,JASA,2016
Currently being implementedon the EchoPuse®
(Theraclion, Malakof, France)
MR monitoring
Take home message
Real time thermal mapping
Possibility of feedback loop control
US monitoring
Real time cavitation mapping
Possibility of feedback loop control
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