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Therapeutic Ultrasound
Spring 2008
Diagnostic Radiology
• X-Ray Images
– High resolution: < 0.1 mm
– Most used in the world
Diagnostic Radiology
• Fluoroscope Images
– Continuously capturing images
– Monitoring of surgery
Diagnostic Radiology
• CT Images
– 2D/3D
– High resolution 1mm
MRI
• MRI (Magnetic Resonance Imaging)
–
–
–
–
–
–
.
Proton Magnetization
3D image
Excellent in Soft Tissue Contrast
Safer than CT
Resolution 1 mm range
fMRI: functional, physiological imaging
Medical Ultrasound
• Medical Ultrasound Imaging
– OBGYN
– Cardiac Vascular Imaging
• Well known Therapeutic Ultrasound
– Liposuction
– Lithotripsy
.
Ultrasound Imaging
• Safest of all
– OBGYN
• Low resolution: 5 mm~1mm
•
fast imaging: for heart imaging
– Cardiovascular imaging
• Doppler imaging: blood perfusion
.
Medical Ultrasound
• Unknown therapeutic ultrasound
– Ultrasound surgery: HIFU
– Targeted drug delivery
– Trasndermal drug delivery
– Gene delivery
– Hypo-plastic Left Heart Syndrome
– ….
Lithotripsy
• A lithotriptor is a medical device used in the
non-invasive treatment of kidney stones
(urinary calculosis) and biliary calculi (stones in
the gallbladder or in the liver).
• The scientific name of this procedure is
Extracorporeal Shock Wave Lithotripsy (ESWL).
• Lithotripsy was developed in the early 1980s in
Germany by Dornier Medizintechnik.
Shock Waves
in Atmosphere: Supersonic Aircraft
in Nature: Thunder and Lightning
in Medicine: Treatment of Kidney Stones
Shock Waves
Sound
p

Shock Wave
p
100.000.000 Pa (1.000 Bar)
2,2 msec
10 Pa
(0.0001
Bar)
t
t
< 2 sec
E.g. big church organ playing
concert pitch in 5 m distance
E.g. Lithotripter shock wave focus
Lithotripsy
Characteristics of shock waves (in medical applications)
Pressure
up to 100 MPa (= 1.000 bar)
High peak pressure
Steep rise time
Short pulse time
≈10ns
Low tensile wave components
≈300 ns
Velocity in water = 1500 m/sec
Time
≈ 10 MPa
Lithotriptor
Electromagnetic Shock Wave
+
High Energy Density
in Treatment Zone
Low Energy Density
at Skin Level
(Anaesthesia-free treatment)
Focus Size
Shock Wave Applications
Urinary Stones
Biliary Stones
Shock Wave Lithotripsy
Tendinopathy
Pseudarthrosis
Shock Wave Therapy
Shock Wave Applications
Kidney stone
+
Shock wave source parameter
-6dB
Focus
size
approx.
100 mm
150 mm
approx.
5 mm
144 mm
Pressure:
3 – 75 MPa
Energy Flux Density:
0.005 – 0.65 mJ/mm2
Established Orthopaedic Therapies with Shock Waves
- Chronic Pain associated with Tendon Disorders
- Pseudarthrosis (non-union) of bones
+
Orthopaedic Therapy with Shock Waves
(calicifying tendinitis of the shoulder)
right shoulder
left shoulder
Pre-shock wave application
Enhanced blood flow and
perfusion related to shock
wave application
post-shock wave application
Indication for possible
application in
Cardiology
Shock Wave Applications
Cardiac Shock Wave Therapy
Shock Wave Treatment of Angina Pectoris
Angina Pectoris
* European Heart Journal (1997) 18 394-413
Angina Pectoris
Definition
• Angina Pectoris occurs when there is an imbalance between myocardial
perfusion and the demand of the myocardium
• The pathological substrate of this is almost invariably narrowing of the
coronary arteries (coronary atherosclerosis)
• It is usually considered that the coronary artery must be narrowed by at least
50 – 70% in luminal diameter before coronary artery blood flow is inadequate
to meet the metabolic demands of the heart with exercise of stress
Epidemiology
• It is estimated that in countries with relatively high coronary heart disease
rates, the total prevalent number of patients with angina pectoris may be as
high as 30.000 to 40.000 per 1 million total population*
* European Heart Journal (1997) 18 394-413
Angina Pectoris
Classification of Angina Pectoris (CCS*)
• Class I
Ordinary physical exercise does not cause angina pectoris
• Class II
Slight limitation of ordinary activities
• Class III
Marked limitation of ordinary activities
• Class IV
Inability to carry on any physical activity without discomfort
Aims of Treatment
• To improve prognosis by preventing myocardial infarction and death
• To minimise or abolish symptoms
* Canadian Cardiovascular Society
Angina Pectoris
Present Treatment Options
• Pharmacological treatment of patients with stable angina pectoris
• Percutaneous transluminal coronary angioplasty (PTCA) and implantation of
stents
• Coronary artery bypass grafting (CABG)
• Other revascularisation techniques
Data on Recurrent Angina
• 24% of patients had recurrence of angina pectoris in the first year after
coronary artery bypass surgery, 40 % had recurrence after 6 years¹
• After 2 years 31% of patients in the angioplasty group had angina pectoris,
compared with 22% in the surgical group²
• Restenosis occurs in 35 – 40% of cases with angiographic control
¹ Coronary Artery Surgery Study (CASS)
² Coronary angioplasty versus coronary artery bypass surgery RITA trail, Lancet 1993; 341: 573-90
Angina Pectoris
Angina Pectoris
Present Coronary Artery Disease Treatment Options
Narrowed coronary arteries
▼
Ischemia
▼
Angina Pectoris
Atherosclerosis
Pharmacological Treatment
Angioplasty/Stenting
Coronary Artery Bypass Surgery
▼
Multiple interventions
Blocked coronary arteries
▼
Necrosis
▼
Myocardial Infarction
Lyses
Emergency Angioplasty/Stenting &
Coronary Artery Bypass Surgery
▼
Multiple interventions
Refractory Angina Pectoris:
unresponsive to both maximal drug treatment and revascularisation techniques
and/or diffuse and distal coronary artery disease
New alternative treatments
Angina Pectoris
New alternative treatment options with various degrees of invasiveness
Cardiac Shock Wave Therapy
• Pharmacological
Treatment
• Neurostimulation (TENS & SCS)
• Enhanced External Counter
Pulsation (EECP)
• Laser Revascularisation (PTMR &
TMLR)
• Therapeutic Angiogenesis
Coronary Arteriogram
Pre SW (4wks)
Post SW (8wks)
Control
Number of visible Coronary arteries
15
SW
Control
10
SW
5
0
Pre treatment
Post treatment
Shimokawa et al. (Circulation Vol. 110, No. 19, Nov. 9. 2004)
Cardiac Shock Wave Therapy (Inclusion Criteria)
Refractory stable angina pectoris
• Guideline medication
• Canadian Cardiovascular Society (CCS) classification III & IV CCS
classification I & II for patients refusing or not tolerating other
therapies
• ≥ 18 years, both gender
Liposuction
• Modern liposuction first burst on the scene in a presentation by
the French surgeon, Dr Yves-Gerard Illouz, in 1982.
• Dr. Michele Zocchi invented a technique whereby a sound wave
generator is attached to a sterile hand piece with a titanium rod
which vibrates at a very high but slightly audible pitch. (UAL)
• External ultrasound-assisted liposuction (XUAL or EUAL)
– XUAL is a type of UAL where the ultrasonic energy is applied from
outside the body, through the skin, making the specialized cannula of
the UAL procedure unnecessary.
• Ultrashape
– No suction, just external ultrasound treatment
– 500cc / treatment
Types of Liposuction
○ Dry liposuction
 No injections of local anesthesia
 This technique was abandoned because of the excessive
blood loss
 Blood composed approximately thirty percent (30%) of the
tissue that was removed.
○ Wet Liposuction :
 Wet Technique also required general anesthesia.
 the injection of approximately 100 milliliters of local
anesthesia containing epinephrine.
 Blood composed approximately 15% to 20% of the tissue
removed by liposuction using the wet technique.
Types of Liposuction
○ Tumescent Liposuction
 The word "tumescent" means swollen and firm
 injecting a large volume of very dilute lidocaine (local
anesthetic) and epinephrine (capillary constrictor) into
subcutaneous fat
 the targeted tissue becomes swollen and firm, or
tumescent
 liposuction totally by local anesthesia.
○ UAL liposuction :
 the use of a large volume of tumescent fluid
 Internal UAL is the term used to describe the technique
where a long metal probe is inserted into fat through a
large incision.
 External UAL requires the use of tumescent fluid and uses
a metal paddle applied to the skin and directs ultrasonic
energy into subcutaneous fat.
Types of Liposuction
○ Powered Liposuction :
 PAL devices use power supplied by an electric motor or compressed air
 a rapid in-and-out movement or a spinning rotation of an attached
liposuction cannula
○ LASER Liposuction
 Using Laser instead of Ultrasound
* Ultrashape (no suction)
○ UltraShape technology uses focused ultrasound waves which
are directed at a specific target point on the body where they
selectively break down unwanted fat cells without affecting
surrounding structures.
UAL
Ultrashape
Ultrasound Surgery
Ultrasound Surgery
Ultrasound Surgery
• Characteristics of ultrasound surgery
Radiotherapy
•
Particle wave
• Deliver high energy in the
intervening tissue
• Adverse effect in the
intervening tissue
• In order to avoid collateral
damage focus size becomes
order of 10x10x100 cm3 range
ultrasound surgery
•
Mechanical Wave
• Absorption less than 5%
Most energy propagates thru
• Non-toxicity in the
intervening tissue
• Focus size is 1x1x10 mm3
(Selectivity is much better)
Ultrasound Surgery
• Frequency: around 1MHz
– Wavelength: around 1.54 mm
• Focus size: 1 x 1 x 10 mm3
Ultrasound Surgery
• Target organs
– Liver, prostate, kidney, brain, pancreas, uterus…
• Problems in ultrasound surgery
– Noninvasive Evaluation tool
• Ultrasound Imaging
• MRI Imaging
– Long Surgery Period
– Aberration Correction
• Rib cage, Skull
Physical mechanism of US
• What does cause the tissue damage?
– Thermal damage
• Even though very small amount of energy is
absorbed the target area, if the focus is tight enough
and the delivered energy is large enough, there will
be heat accumulation.
• The accumulated heat can kill cells
– Caviational damage
• Mechanical rapid collapse of bubble(micro size) inside
liquid(body) have highly localized (um range) high
concentrated energy effect. Mechanically rupture
and high temperature can be induced
Thermal Dose
• Dose
– Concept from radiation dose
– Radiation dose
• Total absorbed energy from radiation
• Factor of attuenaution
• Thermal dose
– Acoustic energy absorbed thermally
– Hyperthermia
• Sensitization of tissue to enhance other treatment effect
• Less than 43°C
– Ultrasound surgery/ tissue ablation
• Treatment method
• Usually more than 43°C
Thermal Dose
• Thermal dose
tT
D ( x, y , z )   R
T ( x , y , z ;t ) Tref
dt
0
where R  e

H
CT0 ( T0 1)
– Tref : reference temperature 43°C
– R : 4 when T(t) ≥ 43°C
2 when T(t) ≤ 43°C
– Example
•
•
•
•
At
At
At
At
43°C
44°C
45°C
55°C
50-250 miniutes (usually assumed 240)
120 minute
60 minute
3.5 sec
Thermal Dose
• Use of thermal dose
– Temperature rise estimation
• Tissue damage
• Surgery planning
– Temperature monitoring
• Tissue damage estimation
• Immediate feedback information
• Ultrasound guided Ultrasound surgery
– Thermal expansion
• MR guided Ultrasound surgery
– Proton chemical shift
Thermal Dose
• Temperature estimation procedure
–
–
–
–
Acoustic field calculation
Acoustic intensity calculation
Deposited power calculation
Bioheat transfer function calculation
• 3D + temporal -> 4D partial differential equation
– Thermal dose calculation
– Usually the optimization requires repetition of above procedure
Ultrasound Surgery Equipment
• Extracorporeal type
Ultrasound Surgery Equipment
• Transrectal type
Ultrasound Surgery
Ultrasound Surgery
Positioning System
Imaging Transducer
Therapy Transducer
Canine
Water Bolus
Kidney
Ultrasound Surgery
Ultrasound Surgery
Ultrasound Imaging Guidance
Ultrasound Surgery
Ultrasound Lesion Detection
• Step 5 Applying to 2nd set of data in 2D
Imaging Modalities for US
• MR guided Ultrasound surgery
Ultrasound guided Ultrasound surgery
• Characteristics
– easy to build
• Shielding
• System cross talk
– Fast imaging
• almost real time
– cheap
– low resolution
• 10 times worse than MRI
• speckles
– difficult in temperature measurement
Ultrasound guided Ultrasound surgery
• Improvement
– Tissue characterization
: Evaluation tool for various soft tissues
characteristics
•
•
•
•
•
Elasticity
Temperature
Attenuation coefficient
Reflectivity
Blood perfusion rate
MR guided Ultrasound surgery
• Characteristics
– High Resolution
– High sensitivity to temperature
• Large calculation time
– Difficulty to build
• System cross talk
• Static Magnetic field
– Slow imaging
• Reconstruction period
– Body motion problem
MR guided Ultrasound surgery
• Improvement
– Temperature measurement
• Calculation period
– Body motion control
– Fast reconstruction
– Cost
Ultrasound Induced Embolization:
droplet vaporization
• Droplet: micro-size bubble seed
– Becoming macro-size bubble by high
frequency ultrasound
Canine Brain: Occipital lobe
Hypo-plastic Left Heart Syndrome
• Shunt: Perforation on Septum
• Erosion induced by Focused Ultrasound
– Histotripsy
– Cavitation, micro-streaming
Porcine Atrial Wall
Targeted Drug Delivery
Targeted drug delivery
• Radiation Force
Targeted drug delivery
• Microstreaming
Targeted Drug Delivery
• Asymmetric Cavitation
Transdermal Drug Delivery
• Stratum Corneum
– Major resistance of transdermal transport
• Some drugs has high permeability
– Developed into a patches
• Ultrasound transdermal protein delivery
– FDA approval in 1995
Bone Growth
• Low Intensity Pulse Ultrasound
– Bone tissue: Piezo characteristic
• Equivalent with electromagnetic pulse
– Mechanical Shear stress effect on osteoblast
• Ultrasound field induced Micro-streaming
Urinary Reflux
• Creation of Bubbles in Bladder
– Focused Ultrasound
Rabbit bladder