Bioeffects Notes #5

Mechanisms 1: Thermal Mechanisms

- - - - evidence of thermal mechanism:

In some instances the biological change observed when tissues are exposed to ultrasound is shown to be the same as that which would have occurred if the same temperature elevation had been imposed without sound.

- - - - evidence of mechanical mechanisms:

In other circumstances significant temperature elevation is prevented by cooling the system, pulsing the ultrasound or by other means and there are still observable effects.

Heat is produced by ultrasound as it interacts with tissue:

1. Absorption -Viscous Shearing action - friction

2. Relaxation - lag in conversion of kinetic energy to mechanical energy at transfer point

The amount of heat generated in tissue is most dependent on the absorption coefficient of the tissue. The stiffer and denser the material the greater the absorption coefficient. Bone and teeth have high absorption coefficients. Collagen deposition in tissue increases the absorption coefficient.

Absorption coefficient of the medium (nepers/cm2 or dB/cm2/MHz)

(adult lung > adult bone > fetal bone > fat > muscle > liver > water)

The absorption coefficient of bone is 30 times greater than that of soft tissue and the rate of heat deposition in bone can be as high as 50 faster than in soft tissue.

Gas bubbles become point sources of heat within tissue by capturing sound energy through multiple reflections within the bubble --- with the effect that all sound energy is converted to heat within the bubble. Gas also responds to acoustic energy with the greatest change in temperature. Tissues containing gas absorb more sound energy, i.e. adult lung.

Thermal Variations in Mammals:

Hypothermia less than	36C	96.8F
Mammals Normal Temperature	37C	98.6F
Febrile	38C	100.4F
Mild Fever	38.5C	101.3F
Average Fever	39.5C	103.1F
High Fever	40.5C	104.9F
Severe Fever more than	42C	107.6F

Warm-blooded animals endowed with mechanisms to maintain core temperature within a certain narrow range. Diurnal variation of 0.3 to 1.0 degree C. Sleep cycles, exercise cycles related to diurnal pattern. Most adults have experienced a 4 degree Celsius increase on one or more occasions with no obvious harm. Variance of 9 degrees Celsius compatible with life. Hypothermia is more benign and even useful in medical surgeries.

Skin temperature can vary over a wide range and vary with different locations (example sunbathing). Vasodilation and increased blood flow with erythema help maintain internal termperature.

The extent of vascularization determines the cooling efficiency so that highly vascular organs are less susceptible to heating than bone which has poor vascularization. Some studies show heating of tissue increases with age (decreased circulation).

Mammalian Thermal Effects:

Actively dividing tissues are most susceptible to heat.

Metabolic rates are effected by internal increases as small as 0.5 degrees.

Heat interference with enzyme synthesis and interactions can affect cell growth and development and may lead to abnormalities in DNA synthesis and repair processes.

Some tissues more susceptible to heat - testes, eye (2 degrees celsius may damage).

Fetal Thermal Effects

Fetus more susceptible to heat than adult mammals. Frequently reported effects on fetus include retardation of growth of systems such as the heart, brain, and skeleton. Non-specific effects including generalized fetal weight reduction are associated with intrauterine heating.

Fetal body temperature normally 0.5 degrees Celsius above mother's body temperature.

Brain growth retarded in guinea pigs when an increase of 2.5 degrees Celsius maintained for less than an hour.

Especially during period of organogenesis - embryo is susceptible to fetal anomalies or death with elevations of 2.5 - 5 degrees Celsius for an hour or more.

No confirmed reports of adverse effects to living mammals from increases of 1 degree Celsius or less.

Temperature rises of 1.5 degrees Celsius not likely to be significant in the fetus. Temperature increases above 3 degrees Celsius considered potentially hazardous.

Maternal febrile illness that causes the human body temperature to rise above 38.9C in early stages of pregnancy has been associated with fetal anomalies. Women who have babies with CNS defects report febrile illness early in pregnancy more often than mothers with normal infants.

Duration of exposure important:

Safety range of exposures determined in studies on rats looking for brain anomalies as the end point.

Additional studies have confirmed development of major brain abnormality, exencephaly, in mice following exposure of 42.3C for 5 minutes.

Production of heat by ultrasound:

Heat produced by ultrasound is immediate, resulting in tissue temperature elevations within seconds of exposure as opposed to minutes required to elevate featl temperature under whole-body heating conditions. The impact of this difference is not clearly understood thought it is likely that potential protective mechanisms that come into play with gradual heating may not be as effective with ultrasound.

Production depends on acoustic energy and volume of tissue exposed

Unit: Joules per cubic cm. per sec.

Parameters of Importance:

TA intensity

Absorption coefficient of the medium (nepers/cm2)

(adult lung > bone > fat > muscle > liver > water)

Cross-sectional area of the beam

Duration of the exposure

Heat-transport process (thermal conductivity and blood flow)

Frequency (absorption coefficient increases with frequency)

Attenuation model

Scanned mode (B-mode imaging and color Doppler) or unscanned mode (spectral Doppler and M-mode)

Additional Pulsed parameters of importance:

Isata

Isppa

dwell time

pulse repetition frequency

Heat predictable when excluding heat transport, beam diameter, and attenuation -

Continuous wave example:

q=time averaged rate per unit volume of heat with continuous wave ultrasound

q=2aI where a=absorption coefficient and I= intensity

where I=1 W/cm2 and a=0.1 Np/cm(liver tissue)

dT/dt=0.048 degrees C/sec or 2.9 degrees C/min

Pulsed wave example:

In situ Ispta of 500mw/cm2 at 5 MHz yields maximum rate of change of 0.035 degrees C/sec. Under worse conditions (no heat removal) a dwell time of 29 seconds would result in 1 degree temperature increase.

Estimated maximum temperature increase from a single pulse of in situ Isppa of 500W/cm2 would be 0.000035 degrees celsius (20-40 micro degrees celsius).

Actual measurements:

10 minute physical therapy treatment of continuous wave ultrasound produces heat increase of 3-4 degrees celsius at muscle/bone interface.

Doppler machines can produce 3 degree temperature increases at bone/soft tissue interfaces.

Temperature increases of 4 degrees Celsius have been measured at or near bone/soft tissue interfaces in animal fetuses in utero during exposure to conditions similar to those used in spectral pulsed Doppler equipment.

Studies:

Mouse skull - insonations of 90 sec. with I(SPTA) of 1.5 W/cm2 - temperature elevation over 5 degrees C

Sheep in utero exposed to 0.3W/cm2 I(SATA) for 120sec - mean temperature increase 1.7 degrees C internal parietal

Guinea Pigs 2.5W/cm2 I(SPTA) for 120 sec. - 4.9 degrees C

In vitro embalmed bone, HP Sono 1000 system in triplex mode - increase 11 degrees C external, 8 degrees C internal with transducer head close (0.2 cm) to the bone, heat reduced by 33% when distance increased to 1 cm.

Diagnostic ultrasound equipment very diverse in its heating ability. In general -

Higher pulse repetition produces greater heating, i.e. M-mode greater heat potential than real-time imaging.

Pulsed Doppler machines with long pulses (poor noise to signal ratio) and frequent pulsing (8000 - 12000) most potential for heat production among pulsed machines.

Moderately focused beams produce greater temperature rises.

Higher temperature increases related to increase in intensity or in duration of exposure.

Tissue varies in its heating properties. In general -

Non-homogeneity of tissue increases heat absorption as interfaces capture energy

Gas bubbles in tissue capture heat and greatly increase heat absorption

In tissue temperature varies in time and space in a complex way.

Radiation force - acoustic microstreaming - can relate to temperature differences in the tissue.

Soft tissue near bone (example fetal aorta) of most concern

Models do not take into account heat loss by conduction or heat generation metabolically

Thermal and Mechanical Indexes: (MI and TI)

Developed 1987 - 1989

Standard adopted and Published in 1992

Based on Safety, not historical limits

Designed for voluntary human use to determine risk/benefit and for user education. Regulators may also use the indices to provide uniform presentation to consumers and to comply with 510k guidelines.

Mechanical Index and Thermal Index - no units

less than 1 - no adverse effects likely

greater than 1 - risk/benefits need to be assessed

Thermal Index:

Ratio of the in situ acoustic power (W') to the acoustic power required to raise tissue temperature by 1 degrees celsius.

TI = W' / W deg

Attenuation models:

TIS - soft tissue

applicable to abdominal, first trimester

assumes homogeneous soft tissue beam path

Layered Tissue Model

Interfaces near surface and at a distance

applicable to obstetrical scanning with a full bladder

TIB - bone

bone at focal zone

bone near the skin surface as in neonatal sonography or in a BPD with the head anterior in the uterus

Predict what is potentially occurring, not what is actually occurring.

TI less than one does not need to be displayed. TI over one needs to be displayed.

Measured in scanned mode, unscanned mode

Scanned refers to steering of successive ultrasound pulses through the field of view (linear, sector). Unscanned refers to single pulse of sound in one line of emission until manually moved

Ultrasound distributed over smaller volume in unscanned mode.

Temperature Profiles of Above:

ALARA:

Use lowest output power

Decrease duration of exposure

Decrease focus on bone

Review risk/benefit level

Be aware of mitigating factors:

Obesity decreases risk

Amount perfusion (cardiac and renal)

Vulnerable tissues (fetal, eye, testes)

Presence of bone, gas, or inhomogeneities

Limit exposure time when TI exceeds 1

Maximum safe exposure duration is 4 to the power of 6-TI minutes

If patient febrile - exposure time limit reduced by increasing TI by increments of 1 for each degree of fever above 37 degrees celsius