Studies on experimental animals help determine conditions for thermal and non-thermal bioeffects.
Non-thermal or mechanical mechanisms of interaction of sound with tissues include:
Radiation Force
Streaming
Cavitation
Stable
Non-Stable (Unstable)
Tissue exposed to ultrasound experiences both force and heat due to ultrasound absorption.
Radiation force is the force exerted by a sound beam on an absorber or reflector.
Extreme forces can move and damage tissue, deforming or disrupting structures.
During ultrasound passage, material experiences local stress due to energy density gradients.
This stress originates from the non-linearity of acoustic propagation.
In a medium with absorption coefficient \alpha, the force per unit volume from radiation pressure is 2 \alpha I/c.
When an object is placed in the beam, it experiences a force from the integration of radiation pressure over its surface.
Radiation force can cause flow in an absorbing fluid (streaming).
Acoustic streaming occurs when acoustic field propagation in a fluid causes a rise in fluid flow.
Acoustical streaming causes movements of interstitial fluid along cell membranes.
Micro-streaming causes circular currents inside interstitial fluid.
Acoustic and micro-streaming can alter cellular activity by transporting materials within the field.
Ultrasound produces an oscillating pressure wave that propagates through tissues.
This pressure wave can cause micro-bubbles to form and grow within tissues.
At high intensities and pressure, the oscillation of these bubbles causes them to collapse.
There are two forms of cavitation:
Stable (non-inertial)
Unstable (transient or inertial)
Small micro-bubbles oscillate in a medium due to ultrasound presence.
Cavitation bubbles expand and contract with the varying ultrasound pressure wave.
Generally considered safe, but streaming of surrounding liquid can occur, resulting in shear stresses on cells or intracellular organelles.
Detection of cavitation in tissues under continuous wave, high-intensity conditions has been reported.
This type of cavitation has the greatest potential to damage tissue.
High ultrasound field intensity causes micro-bubbles to oscillate so greatly that they collapse, generating high pressures and temperatures in the localized area.
This increases the potential for biological damage.
Bubble collapse produces pressure discontinuities (shock waves), extremely high temperatures, and light emission in clear liquids.
Transient cavitation has the potential for significant destructive effects.
Demonstrated in small mammalian animal experiments, causing lung capillary bleeding at pressure thresholds of 1 MPa, which is within the diagnostic range.
Although reported in mammalian experiments, it has not been observed in humans.
Knowledge of the potential risk and hazard for biological damage due to this form of destructive cavitation is especially pertinent in early pregnancy.
A mechanical index (MI) has been formulated to assist users in evaluating the likelihood of cavitation-related adverse biological effects for diagnostically relevant exposures.
The mechanical index (MI) is related to the likelihood of cavitation being produced and is defined as the peak rarefactional pressure (P_r) (negative pressure) divided by the square root of the ultrasound frequency:
MI = \frac{P_r}{\sqrt{frequency}}
Different bubble sizes are susceptible to cavitation at different frequencies. For example, 4 MHz and 9 MHz cavitate bubbles of different sizes.
This is important in contrast-enhanced ultrasound, where cavitation of the bubbles is desired.
The threshold value of the current MI for lung hemorrhage in the mouse is approximately 0.4. The corresponding threshold for the intestine is MI = 1.4.
Thresholds for adverse nonthermal effects depend on tissue characteristics, exposure duration (ED), and ultrasound parameters like frequency (f_c), pulse duration (PD), and pulse repetition frequency (PRF).
The value of Pr(negative pressure) is significant here and from equation we can see that the value of MI is directly proportional to Pr. This means if Prdoubles then MI doubles and, conversely, if Pris halved then MI is halved.
Frequency is inversely related to MI, meaning as frequency increases, the value of MI decreases.
FDA regulations allow a mechanical index of up to 1.9 for all applications except ophthalmic (maximum 0.23). The used range varies from 0.05 to 1.9.
The values of the TI and MI must be displayed if the ultrasound system is capable of exceeding an index of 1.
Radiation Force:
Cells in tissues are attached to one another through complex linkages.
When acoustic forces are insufficient to disrupt these attachments, cells return to their resting position if displaced.
This mechanism forms the basis of radiation force elastography, otherwise known as Shear Wave Elastography.
The transient displacement causes a transient shear stress on the boundary of the beam and generates a shear wave that travels radially outwards from the direction of the primary beam.
Streaming:
Acoustic streaming has been used to identify cysts non-invasively.
Micro-streaming can cause a change in cell membrane structure, function, and permeability, which is suggested to aid in tissue repair.
The streaming effect of ultrasound mechanical energy has therapeutic application.
Cavitation:
Above diagnostic output levels, cavitation plays an important role in the destruction of kidney stones in shock wave lithotripsy.
Stable cavitation is considered beneficial to injured tissue and speeds up the process of healing.
Effects of cavitation and microstreaming that have been demonstrated in vitro include stimulation of fibroblast repair and collagen synthesis, tissue regeneration, and bone healing.
BIOLOGICAL EFFECT | MI > | ACTION BY OPERATOR |
---|---|---|
Possibility of minor damage to neonatal lung or intestines | 0.3 | Reduce exposure times as much as possible |
Theoretical risk of cavitation | 0.7 | Reduce exposure times as much as possible |
Risk of cavitation during contrast agent studies | Overall exposure time of an embryo or fetus should be restricted | |
Increased risk of heating | TI > 0.7 | |
Increased risk of heating | TI > 1 | |
Significant risk of heating | TI > 3 | Eye scanning not recommended |
Overall exposure time of an embryo or fetus should be restricted | ||
Scanning of an embryo or fetus not recommended |
Tissue exposed to ultrasound experiences force and heat from ultrasound absorption.
Non-thermal effects of ultrasound are called mechanical bioeffects.
Mechanical bioeffects include radiation force, acoustic streaming, and cavitation.
Stable cavitation causes oscillation of gas bubbles within organs (lungs and bowel), causing them to vibrate and have associated streaming.
In non-stable cavitation, continuous expansion and contraction of gas bubbles cause implosion, release of free radicals, and raised temperature.
Prenatal:
MI should be kept <0.4 if gas bodies are present.
If no gas bubbles, MI can be higher but should still be kept as low as possible.
Post-natal:
MI <0.4 if gas bodies present (lungs).
Can be as high as 1.9 as needed when no gas bodies are present.
Mechanical bioeffects of ultrasound can be beneficial in diagnoses and treatment of some conditions.
Sonographers should exercise the ALARA principles when performing diagnostic ultrasound and take note of the values of the MI and TI at all times. Always keep MI and TI as low as reasonably achievable.