Electronics Engineering dept, METU, Turkey
This research study is an inspection of
therapeutic ultrasound. The concept of curative ultrasound is analyzed with
concentration on primaries of ultrasonic physics and ultrasonic medication. Analogy
of therapeutic ultrasound and diagnostic ultrasound is proposed. Low intensity and
high intensity applications of remedial ultrasound are inspected, followed by a
consolidation on High Intensity Focused Ultrasound (HIFU) technology. The
underlying doctrines and the delivery systems are proposed. Moreover, the main utilization
of remedial ultrasonic in prostate cancer curation plus the breast cancer
remedies and finally in abolishing kidney crystals were examined.
Kidney crystals examination and diagnosis of the
pregnancy are the handiest utilization of diagnostic ultrasound. Most recently,
researchers could discover the ultrasonic appliance in curation referred to as
therapeutic ultrasound 1.
First Wood and Loomis in 1927 could discover that
ultrasound can interact with tissues leads to some biological changes 2, 3. Following
this study, in 3 the function of ultrasound healing in hyperthermic cancer
treatment was proposed. 3 representing the various therapeutic applications
of ultrasound. According to this study, tissue heating application of
ultrasound was the first application of ultrasound for example, for treatment
In 2, low power and high power ultrasonic remedy was
inspected. Referring to this study, the low power ultrasonic remedy included
the physiotherapy, fracture repair, sonophoresis and some other utilizations
while, the high power application of ultrasound encompasses the High Intensity
Focused Ultrasound (HIFU) and lithotripsy.
4 is analyzing the high-intensity focused ultrasound
function in noninvasive breast cancer remedy. In 10, targeted microbubbles
are introduced as an innovative tool of kidney crystals curation.
More recently, a thesis published 5 performing of
the multi-physics computational modelling of focused ultrasound therapy.
Besides, 6 is proposing a 2D MRI compatible robot designed and implemented
for prostate cancer medication.
This research study is an explanation for therapeutic
ultrasound. Studding the nature of acoustic waves constructed the first stage
of this study. Followed by the investigating the houses of the acoustic medium.
Density, speed of the sound compressibility and absorption were investigated.
Explaining the acoustic wave equities was covered the
next stage. Inspecting the aftermaths that ultrasonic waves can have on the
tissues was implemented. After elemental explanation of the ultrasonic physics,
the main concepts of ultrasonic curation were presented. HIFU, the most offbeat
technology that used ultrasonic waves for curation purpose was demonstrated.
Underlying doctrines were covered with details. In coming points the utilization
of remedial ultrasonic in prostate cancer curation plus the breast cancer
remedy and finally in abolishing kidney crystals were examined.
2. Ultrasound Physics
Regional variations of the fields inside the
intermediate create sound. Vibrating the molecules is a representor of the engrained
mechanical energy in the medium. Withal, medium’s elasticity forced evicted the
particle to restore it to its initial position. Acoustic energy breeding within
the intermediate in the form of a wave is a resultant of the oscillation and
the interaction between different particles. When sound is the purpose, these
waves referred to as acoustic waves. Consequently, a medium to propagate is
essential for sound.
Intermediate compressions and rarefactions are two
types of acoustic wave reproduction forms. Audible are acoustic waves of
frequencies between 20 Hz and 20 kHz while ultrasound or ultrasonic waves
acquire higher frequencies 6.
2.1. Acoustic Medium Properties
Equities belong to the acoustic nature encompasses
with density, sound speed, absorption and characteristic impedance. Relation of
mass and volume of the intermediate designate the density. Travelling speed of
the sound indoors the median delineate the sound speed. Density and
compressibility are deterministic factors in sound speed. Compressibility on
the other hand, is scoped as the reaction of the volume to the applied
pressure. One more tract of the acoustic
intermediate is absorption, a miracle of conversion of kinetic energy to the
thermal one. The last but ingrained equity of a median is Characteristic
2.2. Acoustic Wave Properties
Acoustic wave erected by acoustic Intensity, reflection
and refraction, diffraction, scattering and attenuation. Breeding of the
kinetic energy in a certain time in an area terminated to acoustic intensity.
Farther eminent estates of acoustic wave are reflection and refraction 6.
Diffraction is illustrated as wave growing resultant
by encroach of an incident wave upon a finite length barrier plus edges. Convey
of the acoustic wave though the dissonant intermediate corresponds to the
scattering. Exponentially reduction of the acoustic pressure and intensity
amplitude determines the attenuation.
2.3. Physical Effects of Ultrasound
Ultrasonic physical effects are pigeonholed in to thermal
effects and nonthermal aftermaths. Thermal aftermaths are merger of temperature
aftereffect of the alteration of acoustic energy into heat. Force of radiation,
acoustic streaming and the microbubbles formation and cavitation forged the nonthermal
ramifications that are mostly mechanical in nature.
Encountering a reflective surface, radiation pressure
will exert a radiation force on that interface, attempting to ‘push’ it along
the direction of propagation. Non-oscillatory, fluidic motion created by the radiation force when an
acoustic wave is propagating in a fluid, is called acoustic streaming.
Interaction of an acoustic field and microscopic
bodies of gas in any intermediate or tissue prescribes the acoustic cavitation.
Figure 1 is an exemplification of the stable and inertial cavitation which is
two species of cavitation that discussed in detail in 6.
Fig.1. Microbubble inertial cavitation, by reaching the detracting size
the bubble collapses 6.
Bestow the figure 1, an exemplification of the
inertial cavitation is shown. As demonstrated in figure 1, bubbles are expanded
due to the compressions and rarefactions but after passing the detracting size
3. Ultrasonic Therapy
Indicative ultrasonic and curative ultrasonic conceive
the appliances of ultrasound in medicine. Indicative ultrasound due to its low
signal level has no repercussion on the tissues. As long as, the remedy
ultrasonic aftermaths the tissues since its signal level is relatively high depending
on the dissimilar curation conditions. Accessing images with good spatial and
temporal resolution, using sufficient S/N ratio to glean required analyzing
information of a significant cellular effect is performed in analyzing appliances.
Capricious and no capricious modifications are implemented in ultrasonic
Low intensity and high intensity functions are the
major appliances of the curation ultrasonic. Arousing normal physiological
responses to injury, or to accelerate some processes such as the transport of
drugs across the skin builds the low intensity curation designation. Physiotherapy,
mending of bone and drug uptake constructs the most important appliances of the
low intensity ultrasonic. Although, high intensity remedy intention is rather
to selectively destroy tissue in a controlled fashion embroil mostly HIFU utilizations.
In physiotherapy utilization of curation ultrasonic, the
sound is directly coupled in to the patient through a thin layer of coupling
The most extensive appliance of ultrasonic is cancer
remedy. In hyperthermic cancer medication, ultrasonic builds the heating source
either on its own or with radon or chemotherapy. Achieving uniform temperature
distribution 43–45°C in the tumor while keeping surrounding normal tissues at
acceptable physiological levels the major ambition of this technique. Common
problem is the narrow dividing line between temperatures (energy source should
know the temperature distribution) is the trivial issue. Focused Ultrasound is
Applying high intensity focused ultrasonic beams as a
tissue abscission technique is called HIFU or FUS (Focused Ultrasound Surgery).
Underlying proposition in the FUS is that a high intensity ultrasound beam
brought to a tight focus may kill cells lying within the focal volume while all
other tissues in the ultrasound beam path are spared. This gives a method of
selective tissue ablation at depth within tissue.
In this section, HIFU removal of tissues, remedial
ultrasonic in prostate cancer curation plus the breast cancer remedy and
finally in abolishing kidney crystals will be proposed.
4.1. HIFU Removal of Tissues
The ultrasonic approach that used focused ultrasonic
housed high intensity is an attractive method in medical places. The reason for
this appealing is providing a non-invasive remedy for removal of cancerous
tissues. This technique ranked first among other thermal remedy techniques since
it is no requirement for the transcutaneous insertion of probes into the target
tissue. The volume of the tissue can be heated briskly in two ways, by placing
the probes outside the body or inside the rectum.
Establishing HIFU focus at depth inside soft tissue
will augment the temperature at the focus leads to thermal necrosis at those
levels. The temperatures elsewhere remained at levels close to their initial
Fig. 2. HIFU precept depiction (b) Mingling
removal area construction depiction 1
Figure 2, shows the principles of HIFU. Figure 2. a is
the fundamental demonstration of HIFU while, figure 2. b illustrates the moving
demand in HIFU.HIFU treatment delivery systems build of Extra-corporeal and
interstitial equipment. Transducer, a signal generator, amplifier, matching
circuitry to maximize the electro-acoustic efficiency, a power meter, and in
some cases a method of cooling the transducer are the same forged the underlying
components. Using the single element transducer is the simplest approach that
encompasses focusing requirement of HIFU. Such transducers are limited in that
they can only provide a fixed focus and a mechanical shifting is prescribed. Multi-element
transducer arrays are the more common surrogate procedure.
Extracorporeal HIFU medications are directed using
either Ultra Sound (US) or MRI. Where US is used to guide and monitor HIFU
treatments, the diagnostic transducer is incorporated into the treatment head
allowing to real time imaging of the extirpation mechanism. Interstitial
devices use plane transducers rather than focusing elements, and volume
destruction is obtained by rotation of the probe.
4.2. Remedial Ultrasonic in Prostate Cancer
HIFU curation of prostate cancer is performed under
real-time monitoring with ultrasound or guided by MRI. Achieved images under MRI
procedure have better quality than indicative ultrasonic brig on superior tissue
The convention is same as the fundamental HIFU technique
discussed in previous section. A positioning device is required.
A positioning device for prostate cancer curation using
HIFU is proposed in 6. Being as small as possible and position able in front
of the rectum in order to access the patient builds the essential
characteristics of this equipment. The available space remaining under the
patient’s legs was taken into account during the design of the positioning
Figure 3, is a demonstration of the designed
positioning device for prostate cancer remedy.
Fig. 3. Positioning device on a patient’s table inside an MRI
scanner design 1
® with Ultrasound Integrated Imaging, Sonoblate 500 and Focal One are some
examples of available prostate cancer medication devices discussed in detail in
4.3. MRgHIFU Breast Cancer Remedy
MR guided HIFU (MRgHIFU) abscission completely non-intrusive
medication procedure. A speedily augment in the temperature of the focal point
is appeared since the ultrasonic focused beam enclose high intensity. Rigorous addressing
resultant from MRI, bring on heating the aimed cancerous tissues and no
influence on all other abutting healthy tissues and the skin. Tissue
annihilation is possible in case that for a limited time the temperature of 57–60
°C is extended.
In case of huge volumes, the expiration is accessible
by applying an intricate approach or volumetric heating procedure. The cooling
time between the separate sonication is a challenge that has to be considered, empowering
the amassed energy to be diffused. This property makes curations implemented by
MR-HIFU almost tedious. Guiding the central point onward eloquent orbits
conducted in volumetric heating process. The energy source of this procedure is
furnished from the stored heat in previous stage of the procedure in the focal
of the tumor. Correspondingly, each sonication erode a huge region resulted in
reduction in curation period. (Figure. 4)
Fig. 4. Volumetric abscission approach precept depiction 1
Generic approach and dedicated approach construct the
major species of MRgHIFU breast cancer remedy techniques. The aimed tissue sonication
manner makes the crucial difference between these two sonication mechanisms. The
“generic” approach is extensively employed in medical centers, addressing the cancerous
tissues of the breast from an anterior direction. Direction of the ultrasonic pilings
makes the “dedicated approach” mostly dissimilar to the generic approach. The lateral
sonication of the breast is possible by situating the ultrasound transducers over
the breast, allowing for lateral sonications (Figure. 5).
Fig. 5. breast HIFU abscission (a) Generic approach (b)
Dedicated approach 1
Figure 6 is a depiction of dedicated breast cancer
remedy system. Eight encompassing transducers are surrounding the cup of the cancerous
Fig. 6. (a) Dedicated breast cancer curation (b) eight
circumferentially positioned transducers 1
4.4. Abolishing Kidney Crystals
Ureteroscopic, Extracorpored Shock Wave Lithotripsy (ESWL)
and Percutaneous nephrolithotomy (PCNL) are composing the surgical remedy of
Kidney crystals. In Ureteroscopic technique, a small fiber optic instrument is
passed through the urethra and bladder in to the ureter abolishing the crystal
with a cage like device or shattered with a special instrument that produces a
form of shock wave.
High pressure shock waves which pass through the
calculus are produced in ESWL; the crystal is stressed through the applied
pressure. Then fissured and eventually washed out.
Percutaneous nephrolithotomy (PCNL) is often used when
the crystal is quiet large or in a location that ESWL is not accessible.
Shock wave lithotripsy has generally been a superior
approach for kidney crystal remedy. An order of microsecond pulse durations and
up to a 100 MPa pressure spike triggered at approximately 0.5–2 Hz to fragment
kidney stones through mechanical mechanisms are applied by the shock wave
lithotripter. One important mechanism is cavitation. A substitute type of
lithotripsy method that maximizes cavitation activity to disintegrate kidney
stones using HIFU is proposed in 1.
shock wave pulse used in SWL 1, a long tail of negative pressure followed the
high pressure, which exceeds 40 MPa. Dynamic stress in crystal is generated by
the repeated positive and negative pressure. Cavitation is also happened in
Figure 7, is a representation of a typical
shock wave pulse in SWL. The stress created from the negative pressure
generation after positive pressure generation brings on removal of crystal.
Focused Ultrasound and Lithotripsy: The first step is
control of localized high pressure fluctuation on the stone. The second step is
monitoring of cavitation activity and giving feedback on the optimized
ultrasound conditions. The third step is stone tracking and precise ultrasound
focusing on the stone.
Localized high pressure on kidney crystals includes: Cavitation
Control Waveform (C-C waveform), observation of cavitation on stones and crystal
fragmentation. A sectarian cavitation droplet veil creation on a crystal is
conducted through the ultrasonic that contain frequency of higher levels. In
contrast, the ultrasonic of lower frequencies provoke the droplet veil into
Fig.8. Acoustic pressure of exemplary
cavitation control (C-C) waveform. The ultrasound wave is a high frequency one
and a low frequency ultrasound follow immediately after the high frequency wave
has stopped 1.
Acoustic pressure of exemplary cavitation is depicted
in figure 8. When the high frequency paused the low frequency is applied. The main problem in removing kidney crystals is organ
movement due to respiration, heartbeat, etc. A non-invasive ultrasound
theragnostic system (NIUTS) was proposed in 1 and developed to compensate for
body movement. The NIUTS composed of a spherical piezoelectric transducer in
addition to two ultrasonic probes. One is establishing in focal point of the piezoelectric transducer, and the other is situating
on the lateral side of the transducer.
In 10, a novel application for the
treatment of kidney crystals is offered. Traditional ESWL uses an extracorporeal
energy source that creates microbubbles at the targeted crystal, and subsequent
cavitation leads to cracking the cryatal. Targeted microbubbles eliminate the
need for a large, bulky machine, and these unique microbubbles can be delivered
directly to the offending stones. An energy source applied from either an
extracorporeal or intracorporeal source can initiate the cavitation process,
leading to cracking the cryatal.
Thermal medications in general provide a minimally
invasive approach to cancer curation. HIFU is the least invasive of the
available vaporized techniques.
In this research study therapeutic ultrasound was
introduced. Studding the nature of acoustic waves constructed the first stage
of this study. Followed by the investigating the houses of the acoustic medium.
Explaining the acoustic wave equities was covered the next stage. After
elemental explanation of the ultrasonic physics, the main concepts of
ultrasonic curation were presented. HIFU, the most offbeat technology that used
ultrasonic waves for curation purpose was demonstrated. HIFU applications in
prostate cancer and breast cancer remedy are analyzed. For Kidney crystals
abolishing focused ultrasound lithotripsy improves cavitation activity. It is
less invasive and minimal damage occurred to the tissue.
Jean-Michel, and Ayache Bouakaz, eds. Therapeutic ultrasound. Vol. 880.
2 Miller D, Smith N, Bailey M, et al. Overview of
Therapeutic Ultrasound Applications and Safety Considerations. Journal of
ultrasound in medicine?: official journal of the American Institute of
Ultrasound in Medicine. 012;31(4):623-634.
3 Ter Haar, Gail. “Therapeutic
ultrasound.” European Journal of Ultrasound 9.1 (1999): 3-9.
4 Zhou, Yufeng. “Noninvasive treatment of
breast cancer using high-intensity focused ultrasound.” J Med Imaging
Health Informatics 3 (2013): 141e56.
5 Kyriakou, Adamos. Multi-Physics Computational
Modeling of Focused Ultrasound Therapies. 2015. PhD Thesis.
Christos. Design of a 2D MRI compatible robot for performing prostate cancer
treatment using therapeutic ultrasound. 2015. PhD Thesis. City University
7 Ernesto R., et al. “High?intensity
focusedultrasound (HIFU) for definitive treatment of prostate cancer.” BJU
international 110.9 (2012): 1228-1242.
8 Zhang, Lian, and Zhi-Biao Wang.
“High-intensity focused ultrasound tumor ablation: review of ten years of
clinical experience.” Frontiers of medicine in China 4.3 (2010): 294-302.
Yi-Hsuan, et al. “Clinical application of high-intensity focused
ultrasound in cancer therapy.” Journal of Cancer 7.3 (2016): 225.
10 Ramaswamy, Krishna, et al. “Targeted
microbubbles: a novel application for the treatment of kidney stones.” BJU
international 116.1 (2015): 9-16.