Potential Biological Effects of Ultrasound and It Safety

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Potential Biological Effects of Ultrasound and It
Safety

• Evans Agyei Sakyi (Diagnostic Sonographer)
• International Maritime Hospital
• Imaging Department

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Objectives

• Systematically review the biologic effects of
  ultrasound on human studies
• Types of safety indices.
• To appropriately weigh the risks and benefits of
  its uses especially when targeting certain organ
  tissues in the body
• To make informed judgements about ultrasound
  safety, and in order to protect patients from
  excessive exposure.
• Evidence of long-term adverse effects
• Safety guidelines issued by recognized bodies
• The current thoughts on the bioeffects of
  ultrasound

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Introduction

• Diagnostic ultrasound is an imaging modality that
  is useful in a wide range of clinical
  applications, and in particular, prenatal
  diagnosis.
• From its official introduction into the medical
  world in 1942 by karl Dussick, its metamorphosis
  into todays high-tech equipment has led to a
  general trend towards increased power output and
  the potential for associated risks
• The acoustic output of modern equipment is
  generally much greater than that of the early
  equipment and in view of the continuing progress
  in equipment design and applications, outputs may
  be expected to continue to be subject to change.
• There is no evidence that diagnostic ultrasound
  has produced any harm to patients since it has
  been in use.
• Investigations into the possibility of subtle or
  transient effects are still at an early stage.
  Consequently diagnostic ultrasound can only be
  considered safe if used prudently.

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Venous/Arterial Doppler
Obstetrics
Echocardiography

• Ultrasound is a type of mechanical energy that
  penetrates tissues as an oscillating wave of
  alternating pressure

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Ultrasound Interaction with Tissues
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The Revolution of ultrasound

• Pierre Curies discovery of the piezoelectric
  effect in 1880 launched the ultrasound technology
  revolution
• First applied in ships for depth detection and
  metallurgy for fracture identification
• Soon thereafter medical applications appreciated
  it used

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Primary advantage of ultrasound

• Real-time assessment of organ/organ tissues
• Absence of radiation
• Decreased cost
• Portability

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Historical Background

• The potential for ultrasound to produce biologic
  effects was first reported in 1917. (Langevin
  demonstrated that fish in a small tank died when
  exposed to ultrasound)
• The thermal effects of ultrasound were used in
  1940s to cauterize tissues during surgery and to
  destroy cancerous cells in situ
• Fry et al. examined the detrimental effects of
  focused ultrasound on neural tissue, including
  reversible and irreversible impairments in nerve
  conduction abnormalities
• Transient (43.5s) ultrasound exposure (35W/cm2)
  caused transient conduction blockade in the
  ventral abdominal ganglia of crayfish.
• Brief exposure to an ultrasound beam of similar
  intensity produced complete paralysis with
  destruction of neurons in the lumbar region of
  intact frogs

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• Intact Frog

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Cont.

• These facts emphasized that ultrasound produces
  important thermal effects that are capable of
  interfering with body tissues similar to the
  actions of heat.
• The potential hazard of ultrasound depends mainly
  on four diverse yet mutually dependent factors.
• Ultrasound exposure (total acoustic output power)
  
• Target tissue composition (This determines the
  acoustic absorption coefficients more
  proteinaceous tissue is susceptible to thermal
  injury, higher fluid and gas content tissue
  susceptible to cavitational activity)
• Tissue susceptibility (Rapid proliferating tissue
  are more susceptible to ultrasound effects, than
  static cell population)
• Clinical settings (type of transducer used, the
  depth of penetration and overlying layers of
  tissue)

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AIUM and NEMA consensus

• AIUM (America Institute of Ultrasound in
  Medicine) and NEMA(National Electrical
  Manufactures Association) stated in their report
  that manufacturers of ultrasound equipment should
  provide detailed information about parameters
  including power, transmission duration, and mode-
  continuous versus pulsed.
• This were identified as important determinants of
  adverse biologic effects in animal experiments,
  i.e.
• Intensities (responsible for temperatures
  increase)
• Wavelength-related pressures (responsible for
  mechanical effect)

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Standard for ultrasound Equipment

• The Standard for Real Time Display of Thermal and
  Mechanical Indices on Diagnostic Ultrasound
  Equipment, commonly referred to as the Output
  Display Standard, was developed in 1992. (TI and
  MI)
• The output display standard currently is the only
  information required by the food and drug
  administration to alert the clinical user of the
  potential of an ultrasound device to produce
  tissue injury.
• TI and MI are to be displaced at the top right
  corner. The location may varying depending on the
  manufacturer.
• Acoustic power is the primary determinant of
  thermal and mechanical indices but the ultrasound
  mode color Doppler blood flow imaging, area of
  interest, transmission frequency, pulse
  repetition frequency and focal zone also affect
  thermal and mechanical indices.

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Thermal Effects

• Ultrasound increases temperature in the focal
  area of the beam
• The magnitude and duration of this temperature
  elevation is quantified as the thermal dose
  delivered to the tissue.

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Measurement of Thermal Effects

• The thermal index is defined as the ratio of the
  total system power to the power required to cause
  a 10C increase in temperature
• Types of Thermal Indices
• Three different thermal indices-depending on the
  structures encountered in the path of the
  ultrasound beam
• Soft tissue (TIs)
• Bone (TIb)
• Cranium (TIc)

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Biologic Consequences of Thermal Effects

• During ultrasound propagation, a portion of the
  energy is absorbed and converted into heat, which
  could lead to a temperature increase.
• (70 of the total temperature increase associated
  with ultrasound occurs within the first minute of
  exposure but temperature does continues to rise
  as exposure time is prolonged).
• The relative protein content of each tissues is
  also an important determinant of absorption, and
  hence, temperature rise. Absorption coefficients
  of tissues are directly related to protein
  content, thereby providing a surrogate marker for
  potential increase in tissue temperature.
• Absorption coefficients vary between 1(skin,
  tendon, spinal cord) and 10 (bone) dB/cm MHz
• (Heat produces a wide variety of tissue injury
  including necrosis and apoptosis, abnormal cell
  migration, altered gene expression, and membrane
  dysfunction).

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cont.

• The greatest temperature increase from ultrasound
  exposure occurs in bone because of its high
  absorption coefficient.
• Temperature also increases in tissues adjacent to
  bone
• Ultrasound intensity and exposure duration cause
  direct increase in tissue temperature, a wider
  beam width reduces the rate and extent of
  temperature rise by permitting the energy to be
  distributed over a larger perfusion territory.
• The use of a narrow write-zoom box increases this
  potential (Thermal hazard)

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• Focused beam and Wide beam

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Mechanical Effects of ultrasound
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• Ultrasound energy creates mechanical forces
  independent of thermal effects, thereby causing
  biologic effects that are not related to
  temperature rise alone (nonthermal)
• The mechanical effects results in shear forces,
  pressure changes and release of various reactive
  molecules.

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Biologic consequences of Mechanical Effects

• Gas-containing structures (eg. Lungs, intestines)
  are most susceptible to the effects of acoustic
  cavitation.
• Petechial hemorrhages developed on the mucosal
  surface of the intestines after ultrasound
  exposure at or above typical diagnostic
  frequencies
• Increased small intestinal cell apoptosis through
  a cavitation mechanism
• Mechanical effects also occur in tissues near
  bone.
• A combination of thermal and nonthermal effects
  are purported to be responsible for hemorrhage
  adjacent to bone.
• These potential effect increases with acoustic
  intensity, pulse repetition frequency, and
  transducer frequency
• Single beam modes (A-mode, M-mode and spectral
  pulsed Doppler) have a greater potential for
  non-thermal hazard than scanned modes (B-mode,
  Color Doppler)

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Cavitation
Ultrasonic cleaning

• Cavitation is the formation and then immediate
  implosion of cavities in a liquid that are the
  consequence of forces acting upon the liquid

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• Fat Reduction using the principle of cavitation
• Ultrasonic lipolysis
• Can achieve volume reduction of tissue
• Causes the formation of micro-bubbles collapse,
  they affect fat cell wall and allow triglycerides
  to pass out of the cell

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• Cell apoptosis through cavitation mechanism

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Determinants of Mechanical Effects

• The interaction of ultrasound with gas bubbles or
  contrast agents causes rapid and potentially
  large changes in bubble size (cavitation). This
  may increase temperature and pressure within the
  bubble and thereby cause mechanical stress on
  surrounding tissues, precipitate fluid micro-jet
  formation, and generate free radicals.
• Ultrasound wavelength has an important role in
  bubble formation and growth short wavelength
  ultrasound (observed at higher frequencies) does
  not provide sufficient time for significant
  bubble growth, therefore cavitation is less
  likely under these circumstances compared with
  long wavelengths
• Acoustic cavitation (Inertial/Transient
  Noninertial/Stable)
• Measurement of Mechanical Effects
• Defined as the ratio of the peak rarefactional
  negative pressure adjusted for tissue attenuation
  and square root of the frequency (mechanical
  index Pr.3/vf)

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Safety Standard (bmus)

• Medical ultrasound imaging should only be used
  for medical diagnosis
• Ultrasound equipment should only be used by
  people who are fully trained in its safe and
  proper operation. This requires
• An appreciation of the potential thermal and
  mechanical bio-effects of ultrasound
• A full awareness of equipment settings
• Examination times should be kept as short as is
  necessary to produce a useful diagnostic result
• The operator should aim to stay within the
  recommended scan times (especially for obstetrics
  examinations)
• Output levels should be kept as low as is
  reasonably achievable whilst producing a useful
  diagnostic result
• Scans in pregnancy should not be carried out for
  the sole purpose of producing souvenir videos or
  photographs
• Freeze frame or cine loop should be used to
  reviewed and discussed images without continuing
  the exposure.
• Endo-cavity probes (e.g. vaginal, rectal or
  oesophageal probes) should not be used if there
  is noticeable self heating of the probe when
  operating in air.

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Known biologic Effects

• Cellular Effects of Ultrasound
• Facilitate an influx of calcium ions in
  fibroblasts probably due to mechanical effect on
  ion channels
• Causes efflux of intracellular potassium ions
  (Acoustic microstreaming)
• Thrombus formation after ultrasound-induced
  endothelial damage
• Repetitive ultrasound exposure reduced leukocyte
  production in monkeys in utero
• A decrease in somite numbers was noted when
  embryo cultures were exposed to ultrasound for
  15min at 400C (Non-thermal mechanism form of
  injury)

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Cont.

• Genetic Effects of Ultrasound
• It remains unclear whether ultrasound contributes
  directly to genetic aberrations. Chromosomal
  aberrations, enhanced sister chromatid exchange,
  and other mutations has been investigated
  extensively as possible consequences of
  ultrasound exposure, but whether these actions
  lead to meaningful physiologic consequences is
  controversial.

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Cont.

• Fetal Effects of Ultrasound
• In a large randomized controlled trial from
  Helsinki, 9000 women were randomly divided into
  groups. The women in one group were scanned at
  16-20weeks whereas the women in the other group
  were not. Comparing the results from these groups
  revealed 20 miscarriages in the scanned group and
  none in the controls.
• Multiple ultrasound exposure in utero  was
  associated with a small increase in the incidence
  of low birth weight compared with a single
  exposure, but this difference was not
  statistically significant, and was eliminated as
  the children developed. The authors subsequently
  followed the growth, development, and behavior of
  the children for another 8 yrs. They reported a
  delay in language and speech development at 1yr
  in ultrasound-exposed children, but no other
  significant differences were observed between
  groups. This finding was most likely related to
  parenting and not to ultrasound exposure per se 
  because the difference was not observed during
  later development. The results of these
  epidemiologic studies clearly requires
  qualification because ultrasound devices
  available then had lesser acoustic output. The
  studies were also performed before output display
  standard was established.
• Research from other bodies have concluded that
  there are insufficient evidence of a direct
  causal link between ultrasound exposures in utero
  and subsequent biologic consequences in neonates
  and children.

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Cont.

• Neural Effects of Ultrasound
• Fry et al. demonstrated that focused ultrasound
  is capable of causing reversible suppression of
  neural transmission
• Ultrasound exposure to the lumbar plexus causes
  hind limb paralysis in experimental animals (Hind
  limb paralysis was observed at room temperature
  after a 4.3s ultrasound exposure (35W/cm2) to the
  lumbar area, but more prolonged exposure duration
  7.3s was required to produce similar neurologic
  damage to cooler temperature (1-20C))
  Histologic analysis revealed neuronal and myelin
  destruction in the spinal cord and axonal
  degeneration, chromatolysis, pyknosis with intact
  mesenchymal structures and clumping of myelin in
  the peripheral nerves and cauda equina

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Cont.

• Ocular Effects of Ultrasound
• Focused, higher intensity ultrasound was used for
  destruction of intraocular lesions (intraocular
  tumors)
• Prolonged exposure also produces cataracts
• Transient chemosis, conjunctival injection,
  corneal clouding, lens opacities, reduction in
  intraocular tension, or permanent destruction of
  the ciliary body were also reported after focused
  ultrasound exposure

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Cont.

• Pulmonary Effects of Ultrasound
• Ultrasound-induced lung haemorrhage has been
  widely reported in experimental animals (example
  of acoustic cavitation), but perphaps rather
  surprisingly, humans do not appear to be
  susceptible to this form of nonthermal injury.

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recommended exposure times at different index
values for different applications (Bmus)

• Obstetric examination
• TIs should be monitored for scans during the
  first 10 weeks after LMP.
• TIB should be monitored for scans following 10
  weeks after LMP
• TI up to 0.7 no time restriction, but observe
  ALARA
• TI up to 1.0 maximum exposure time of an embryo
  or fetus should be restricted to no more than 60
  minutes
• TI up to 1.5 maximum exposure time of an embryo
  or fetus should be restricted to no more than 30
  minutes
• TI up to 2.0 maximum exposure time of an embryo
  or fetus should be restricted to no more than 15
  minutes
• TI up to 2.5 maximum exposure time of an embryo
  or fetus should be restricted to no more than 4
  minutes
• TI up to 3.0 maximum exposure time of an embryo
  or fetus should be restricted to no more than 1
  minute
• TI gt 3.0 scanning of embryo or fetus is not
  recommended, however briefly

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Cont.

• Neonatal scanning
• MI gt 0.3 possibility of minor damage to neonatal
  lung or intestine. Restrict exposure time as much
  as possible
• TI use Tis for all transcranial and spinal
  scanning using the time limits given for
  obstetrics
• ABDOMINAL, PERIPHERAL VASCULAR AND OTHER SCANNING
• Use TIB with less restrictive time limits than
  those for obstetric scanning for example
  unrestricted time limit with ALARA for TIB lt 1.0
  TIB gt 6.0 is not recommended.
• FETAL HEART MONITORING
• This modality is not contraindicated on safety
  grounds even when used for extended periods due
  to low acoustic power levels

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• Eye scanning
• TI gt 1.0 eye scanning is not recommended other
  than as part of a fetal scan.
• TRANSCRANIAL ULTRASOUND EXAMINATIONS
• TIC should be monitored.
• TIC gt 3.0 is not recommended.
• USE OF CONTRAST AGENTS
• MI gt 0.7 risk of cavitation exists if a contrast
  agent containing microspheres is used and there
  is a theoretical risk of cavitation without the
  use of contrast agent. The risks increase with MI
  above this threshold

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Conclusion

• Dr. John Steed, head of obstetrics and
  gynaecology at the Virginia Commonwealth
  University School of Medicine said that
  although there is no proof that ultrasound is
  damaging, we used to think that about X-rays
  (Indeed, X-rays were vigorously promoted for
  viewing the baby in the womb, and other
  radiological procedures but it was many years
  later that research showed that X-ray exposure
  caused cancer in the children who were exposed as
  babies).
• The use of higher intensity ultrasound combined
  with longer duration of exposure, may unmask
  detrimental effects and awareness of the possible
  biologic consequences of ultrasound and the
  factors associated with their occurrence may
  permit the clinician to balance optimal
  visualization and the risk of ultrasound-related
  complications. However, it should be borne in
  mind that the greatest danger in diagnostic
  ultrasound is misdiagnosis.

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References

• Is ultrasound safe? The Obstetrician
  Gynaecologist Authors Jolly J, Cooke I, Love M.
  20068222-227
• Potential Adverse Ultrasound-related Biological
  Effects A Critical Review. Hariharan Shankar,
  M.B.B.S. Paul S. Pagel, M.D., Ph.D. November
  2011
• Guidelines for the safe use of diagnostic
  ultrasound equipment, BMUS
• Who says ultrasound is safe? AIMS Journal 2004/5.
  Vol 16, No 4
• Bioeffects_Paper_July_2015
• 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
• Clinical Ultrasound (Third Edition), Hazel C.
  Strarritt, Francis A. Duck, 2011

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Thank You