This document discusses non-thermal effects of diagnostic ultrasound, specifically radiation force and its potential biological effects. It outlines ultrasound basics and physics, defines key terms, and explores mechanical effects not related to heating, including cavitation, acoustic radiation force, and acoustic streaming which can cause fluid movement. Observations of effects on bone, lung, heart, perception, and development are provided, such as ultrasound accelerating bone healing and potentially altering neural migration through radiation force.

1. Non-Thermal Effects of Diagnostic Ultrasound
Radiation Force and its Possible Biological Effects
Outline:
1. Ultrasound basics, diagnostics, history, physics
-Sources:
• Diagnostic Ultrasound Imaging: Inside and Out – Thomas L. Szabo
• Musculoskeletal Sonography Technique, Anatomy, Semeiotics and
Pathological Findings in Rheumatic Diseases - Fabio Martino, Enzo
Silvestri, Walter Grassi, Giacomo Garlaschi
• Basics of Ultrasound Imaging -Vincent Chan and Anahi Perlas
2. Biological Effects of Ultrasound
-Sources:
• The Safe Use of Ultrasound in Medical Diagnostics - Edited by Gail ter Haar
(Chapter 5: Non-thermal effects of diagnostic ultrasound -J. Brian
Fowlkes. & Chapter 6: Radiation force and its possible biological effects
-Hazel C. Starritt)
• Effects of Ultrasound on Transforming Growth Factor-B Genes in Bone Cells
- J. Harle, F. Mayia , I. Olsen and V. Salih
• Biological Effects of Low Intensity Ultrasound The Mechanism Involved, and
its Implications on Therapy and on Biosafety of Ultrasound – Loreto B. Feril
Jr. and Takashi Kondo
• ISUOG statement on the non-medical use of ultrasound, 2009 - J.
Abramowicz, C. Brezinka, K. Salvesen and G. Ter Haar
• Fetal Thermal Effects of Diagnostic Ultrasound - Jacques S. Abramowicz,
MD, Stanley B. Barnett, MSc, PhD, Francis A. Duck, PhD, Peter D.
Edmonds, PhD, Kullervo H. Hynynen, MSc, PhD, Marvin C. Ziskin, MD
Terms and Definitions:
1. Basic Ultrasound Terminology
Ultrasound: Utilizes sound waves of very high frequency (2MHz or greater). It is
propagated (To cause (a wave, for example) to move in some direction or through a
medium; transmit.) via waves of compression and rarefaction, and requires a medium
(tissue) for travel. The higher the frequency, the less depth penetration. However, the
resolution is improved.
Resolution: Is the parameter of an ultrasound imaging system that characterizes its ability
to detect closely spaced interfaces and displays the echoes from those interfaces as
distinct and separate objects. The better the resolution, the greater the clarity of an
ultrasound image.

2. Transducers: Convert one form of energy to another. Ultrasound transducers convert
electric energy into ultrasound energy and vice versa. Transducers operate on
piezoelectricity meaning that some Materials (ceramics, quartz) produce a voltage when
deformed by an applied pressure, and reversely results in a production of pressure when
these materials are deformed by an applied voltage.
Pulsed Transducers: Consists of one transducer element which functions as both the
source and receiving transducers.
Mechanical Probes: Allows the sweeping of the ultrasound beam through the tissues
rapidly and repeatedly. This is accomplished by oscillating a transducer. The oscillating
component is immersed in a coupling liquid within the transducer assembly. In our case
the coupling fluid is deionized water. It is important that the fluid is bubble free, so that
your image is not compromised. Check the water level in the transducer assembly before
scanning and if you see air bubbles, make sure you fill it with the deionized water.
Attenuation: A decrease in amplitude and intensity, as sound travels through a medium.
Attenuation occurs with absorption (conversion of sound to heat), reflection (portion of
sound returned from the boundary of a medium, and scattering (diffusion or redirection of
sound in several directions when encountering a particle suspension or a rough surface).
These different forms of attenuation are responsible for artifacts that may be in your
image. Some of these artifacts are useful and some are not. Some artifacts are produced
by improper transducer location or machine settings.
Sound Waves: Audible sound waves lie within the range of 20 to 20,000 Hz. Clinical
ultrasound systems use transducers of between 2 and 17 MHz. Sound waves do not exist
in a vacuum, and propagation in gases is poor because the molecules are too widely
spaced which is why lung does not image well with ultrasound. A gel couplant is used
between the skin of the subject and the transducer face otherwise the sound would not be
transmitted across the air-filled gap. The strength of the returning echo is directly related
to the angle at which the beam strikes the acoustic interface. The more nearly
perpendicular the beam is the stronger the returning echo; smooth interfaces at right
angles are known as specular reflectors. This is best seen in the walls of a large blood
vessel such as the aorta or the carotid artery.
Transducers: The choice of which transducer should be used depends on the depth of the
structure being imaged. The higher the frequency of the transducer crystal, the less
penetration it has but the better the resolution. So if more penetration is required you need
to use a lower frequency transducer with the sacrifice of some resolution. The shape of
the beam is varied and is different for each transducer frequency. There is a fixed focused
region of the ultrasound beam which is indicated on the system with a small triangle to
the right of the image. This indicates the focal zone of that transducer and is where the
best resolution can be achieved with that particular transducer. Effort should be taken to
position the object of interest in the subject to within that focused area to obtain the best
detail. This can be achieved with the use of more or less ultrasound gel and moving the
transducer closer to or farther away from the subject.
A-Mode Amplitude modulation: A single dimension display consisting of a horizontal
baseline. This baseline represents time and or distance with upward (vertical) deflections
spikes depicting the acoustic interfaces)

3. Attenuation: The ultrasound beam undergoes a progressive weakening as it penetrates the
body due to absorption, scattering and beam spread. The amount of weakening is
dependent on frequency, tissue density, and the number and types of interfaces
B-Mode Brightness modulation: A two-dimensional display of ultrasound. The Amode
spikes are electronically converted into dots and displayed at the correct depth from the
transducer
Complex: A mass that has both fluid-filed and solid areas within it
Cystic: This term is used to describe any fluid-filled structure, for example, the urinary
bladder
Enhancement (acoustic): Sound is not weakened (attenuated) as it passes through a fluidfilled structure and therefore the structure behind appears to have more echoes than the
same tissue beside it
Frequency: The number of complete cycles per second (Hertz)
Gain: Refers to the amount of amplification of the returning echoes
Gel Couplant: A trans-sonic material which eliminates the air interface between the
transducer and the animal’s skin
Homogenous: Of uniform appearance and texture
Hypo-echoic: A relative term used to describe an area that has decreased brightness of its
echoes relative to an adjacent structure. Also a relative term used to describe a structure
which has increased brightness of its echoes relative to an adjacent structure
Interface: Strong echoes that delineate the boundary of organs, caused by the difference
between the acoustic impedance of the two adjacent structures; an interface that is usually
more pronounced when the transducer is perpendicular to it
M-Mode: is the motion mode displaying moving structures along a single line in the
ultrasound beam
Noise: An artifact that is usually due to the gain control being too high
Reverberation: An artifact that results from a strong echo returning from a large acoustic
interface to the transducer. This echo returns to the tissues again, causing additional
echoes parallel and equidistant to the first echo
Shadowing: Failure of the sound beam to pass through an object, e.g. a bone does not
allow any sound to pass through it and there is only shadowing seen behind it
Time-Gain Compensation: Compensation for attenuation is accomplished by amplifying
echoes in the near field slightly and progressively increasing amplification as echoes
return from greater depths
Velocity (of sound): Is the speed at which a sound wave is traveling. In soft tissue at 37
degrees C. sound travels at 1540 m/second
Time Gain Compensation (TGC): Equalizes differences in received reflection amplitudes
because of the reflector depth. Reflectors with equal reflector coefficients will not result
in equal amplitude reflections arriving at the transducer if their travel distances are
different. TGC allow you to adjust the amplitude to compensate for the path length
differences. The longer the path length the higher the amplitude. The TGC is located on
the right upper hand corner of the monitor, and is displayed graphically.
B-MODE (brightness mode): The mode that is used for the display of echoes that return
to the transducer. There is a change in spot brightness for each echo that is received by
the transducer. The returning echoes are displayed on a television monitor as shades of

4. gray. Typically the brighter gray shades represent echoes with greater intensity levels.
This mode allows you to scan.
M-MODE (motion mode): Is a graphic B-mode pattern that is a single line time display
that represents the motion of structures along the ultrasound beam, 1000fps. This mode
allows you to trace motion i.e. heart wall motion, vessel wall motion.
PW MODE (pulsed-wave mode): Frequency change of reflected sound waves as a result
of reflection motion relative to the transducer used to detect the velocity and direction of
blood flow. This reflection shift can be displayed graphically, as well as audibly. During
Doppler operation the reflected sound has the same frequency as the transmitted sound if
the blood is stationary ( we know that blood is not stationary it moves) therefore if the
blood is moving away from the transducer a lower frequency is detected (negative shift)
the spectrum appears below the baseline. If the blood is moving toward the transducer a
higher frequency (positive shift) is detected and the spectral displays above the baseline.
2. Effects of Diagnostic Ultrasound
Mechanical Effects: Effects related to cavitation or other interactions with ultrasound
with tissues without resulting in heating.
Thermal Effects: Effects of ultrasound related to temperature increases in tissue and the
absorption of ultrasound energy in tissue
Non-Thermal Effects: effects not related to temperature increases in tissue, has a variety
of source mechanisms
Cavitation: the variation of pressure in the ultrasound waves activates small pockets of
gas or vapor, either naturally occurring within the tissue or can be exogenous.
Inertial Cavitation: occurs when surrounding medium inertia controls the bubble motion,
the bubble collapse can be rapid with large increases in the temperature inside and around
the bubble causing mechanical stress to the area.
Cavitational Nuclei: initial gas bodies
Acoustic Radiation Force Impulse (ARFI): An ultrasound imaging mode that
uses acoustic radiation force to generate images of the mechanical properties of soft
tissue.
Ultrasound Contrast Agents: gas filled microbubbles administered intravenously.
Microbubbles have a high degree of echogenicity, which is the ability of an object to
reflect the ultrasound waves. This produces a contrast between the microbubbles and the
soft tissue surrounding it.
Safety Profiles: measurement of how safe the contrast material is
Radiation Force: A force generated in a material in an acoustic field. Radiation force
exerted on tissue is related to the amount of energy absorbed by the tissue. The formula is
Fv=2αI/c. α is the absorption coefficient of the tissue, I is the acoustic intensity, and c is
the speed of sound. Another formula is Fr=W/c, where W is the total power absorbed
from the ultrasound beam.
Absorption coefficient: a quantity that characterizes how easily a material or medium can
be penetrated by a beam of light, sound, particles, or other energy or matter.
Acoustic Impedance: (Z) is a measure of the resistance to sound passing through a
medium

5. Acoustic Intensity: Is a physical parameter that describes the amount of energy flowing
through a unit cross-sectional area of a beam each second or the rate at which the wave
transmits the energy over a small area
Acoustic Radiation Force: a physical phenomenon resulting from the interaction of an
acoustic wave with an obstacle placed along its path.
Acoustic Streaming: An effect related to radiation force where liquid can be forced to
flow. It has been used in diagnostics to differentiate fluid filled cysts from solid lesions. It
results from the generation of a force field in a liquid in the direction of wave
propagation. The movement is away from the transducer and is observable to the naked
eye. It occurs as a result of the absorption of the acoustic energy from the ultrasound.
Acoustic Streaming in vitro: speed of streaming is greater in amniotic fluid than in water
because of the difference in absorption coefficient.
Acoustic streaming In vivo: fluid movement reported in breast cysts, proposed diagnostic
tool to differentiate between solid and fluid filled cysts. Streaming can alter the thickness
of unstirred boundary layers.
Non-Linear Propagation: propagation of high amplitude pulses can lead to enhanced
absorption of ultrasound energy resulting in increased radiation force and streaming.
Attenuation coefficient: the difference between the energy that enters a body part and the
energy that is not detected. The difference is caused by the absorption and scattering of
energy within the body tissues.
Shear Viscosity: The shear viscosity of a fluid expresses its resistance to shearing flows,
where adjacent layers move parallel to each other with different speeds
Bulk Viscosity: When a compressible fluid is compressed or expanded evenly, without
shear, it may still exhibit a form of internal friction that resists its flow. The bulk
viscosity is important only when the fluid is being rapidly compressed or expanded, such
as in sound and shock waves. Bulk viscosity explains the loss of energy in those waves.
Mechanical Index: a real time output display to estimate the potential for inertial
cavitation in vivo. MI=Pr.3/√fc. Pr.3 is the rarefactional pressure of the acoustic field, fc
is the centre frequency. The index is based on the examination of the temperatures of the
bubbles when they collapse. This temperature can reach 5000 K, where free radicals can
be created. The mechanical index is roughly proportional to the mechanical work that can
be performed in a bubble in the rarfactional phase of the acoustic field.
Rarefaction: The instantaneous, local reduction in density of a gas resulting from passage
of a sound wave, or the region in which the density is reduced at some instant.
Rarefactional Pressure: the amplitude of a negative instantaneous sound pressure in
an ultrasound beam. Rarefaction is the reduction in pressure of the medium during
the acoustic cycle.
3. Observations of Effects
Bone: pulsed ultrasound, not diagnostic. Pulsed-ultrasound is used to heal fractures. It
accelerates the formation of fracture callus in humans.
Lung: diagnostic ultrasound exposure can cause localized lung hemorrhage in animals,
experiment.
Neurological Development: handedness. Neuronal migration changes in animals.

6. Heart: radiation force of ultrasound can reduce the strength of contraction of the heart in
a small animal
Human Perception: we are able to perceive radiation force, fetus will respond to
ultrasound during examination.
Contrast: microbubble contrast agents can result in biological effects depending on the
mechanical index.
Fluids: movement as a result of acoustic streaming
Cell Suspensions: thickness of unstirred layer changed with ultrasound
Soft tissue:
-physical effects: compression of blood vessels, accelerated healing of bone fractures in
vivo, alteration in gene expression, enhancement of soft tissue regeneration not due to
heat
-sensory effects: possible to feel radiation forces from an ultrasound beam on the skin,
decrease in aortic pressure of frogs, auditory nerve stimulated directly by ultrasound
-developmental effects: Partial inhibition of the neural migration in the embryonic
cerebral cortex of mice was found. This was most likely due to radiation force.

7. Heart: radiation force of ultrasound can reduce the strength of contraction of the heart in
a small animal
Human Perception: we are able to perceive radiation force, fetus will respond to
ultrasound during examination.
Contrast: microbubble contrast agents can result in biological effects depending on the
mechanical index.
Fluids: movement as a result of acoustic streaming
Cell Suspensions: thickness of unstirred layer changed with ultrasound
Soft tissue:
-physical effects: compression of blood vessels, accelerated healing of bone fractures in
vivo, alteration in gene expression, enhancement of soft tissue regeneration not due to
heat
-sensory effects: possible to feel radiation forces from an ultrasound beam on the skin,
decrease in aortic pressure of frogs, auditory nerve stimulated directly by ultrasound
-developmental effects: Partial inhibition of the neural migration in the embryonic
cerebral cortex of mice was found. This was most likely due to radiation force.