DIAGNOSTIC ULTRASOUND INSTRUMENTS AND ULTRASOUND INTENSITY
Ultrasonic imaging devices and Doppler blood flow studies utilize pulsed wave (PW) ultrasound while continuous wave (CW) ultrasound is applied in fetal functional tests (Table 1.1). The ultrasound intensity differs between PW and CW machines (Fig. 1.1), i.e. temporal peak intensity is large in PW and weak in CW ultrasound, while temporal average intensity is almost identical in simple PW B-mode imaging device and CW machines (Table 1.1).4
However, pulsed Doppler flow velocity measurement needs high peak and average intensity due to its long pulse and high repetition frequency (Figs 1.1A and B). The temporal average intensity of color and power Doppler flow mapping is lower than pulsed Doppler but higher than simple B-mode machine.
ULTRASOUND INTENSITY OF DOPPLER ULTRASOUND
The maximum intensity of adult Doppler ultrasound was 1–3 W/cm2 which was as high as the ultrasonic physiotherapy for the tissue heating, where the transducer was always moved on the bone and young patient's bone and pregnant woman were contraindicated from the concern on ultrasound safety. The difference between therapeutic ultrasound and pulsed Doppler device is the exposure duration, which is short in Doppler flow measurement. Thermal effect is therefore a big concern in Doppler ultrasound. Temperature rises not only at the sample volume but also in all tissues passed by the ultrasound beam. Ultrasound intensity is lower in color/power Doppler flow mapping than pulsed Doppler because of the scanning motion of Doppler ultrasound beam in the region of interest (ROI). Temporal average intensity of color Doppler is lower than adult Doppler devices and within the limit of non-hazardous FDA regulation which is 720 mW/cm2. Thermal effect is discussed in the first place in pulsed Doppler, where the safety is determined by ultrasound intensity and exposure duration.
Figures 1.1A and B: Two types of diagnostic ultrasound waves. (A) Pulse wave (PW): 1/t is repetition frequency; (B) Continuous wave (CW)
THE EFFECT OF HEATING ON MAMMAL FETUSES
Teratogenic effects were reported by biologists in the exposure of mammal animal embryos and fetuses to experimental high temperature of 39–50°C in various mammals. The results are summarized in the National Council for Radiation Protection and Measurement (NCRP) report 2 in 1992, where a discrimination line clearly separates hazardous and non-hazardous areas.
There is no hazard in the area under the line determined by connecting high temperature/short exposure and low temperature/long exposure points. Non-hazardous exposure is as short as one minute in 43°C and infinite in physiological body temperature. Absolute temperature is studied when the temperature rise derived from TI is added 37°C in ultrasound exposure because TI is calculated in the worst case of temperature elevation by the exposure to standard tissue model.
NON-HAZARDOUS EXPOSURE TIME OF THE FETUS TO THE HEAT
The revised safety statement on diagnostic ultrasound of American Institute of Ultrasound in Medicine (AIUM)5 published in 1998, is based on the NCRP report2 in 1992, where inverse relation is found between hazardous temperature level and exposure time. They stated that the fetus tolerated 50 hours at 2°C rise (absolute temperature was 39°C) and 1 min at 6°C rise (43°C). They showed the relation of the temperature rise (T) above 37°C and the non-hazardous exposure time (t min) by the equation 1. The author modified the equation 1 and obtained non-hazardous time (t min) from the temperature rise with the equation 2;5
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Figure 1.2: Tolerable exposure time of animal fetuses to the temperature rise and TI.
From the equation 2 in the text t = 10(3.6–0.6T)
T: temperature rise = thermal index (TI)
t: non-hazardous time (min)
Relations of non-hazardous exposure time, temperature rise and body temperature are known by the equation 2 (Table 1.2 and Fig. 1.2). The thermal safety of ultrasound is known by the TI which is theoretically equal to the temperature rise.
STRATEGY FOR THE SAFETY OF DIAGNOSTIC ULTRASOUND EQUIPMENTS
The safety to electrical and mechanical impacts is proved in ultrasound devices by the manufacturer under international and domestic guidelines. In a Doppler scanner, the TI, MI, transducer temperature and other related indices are displayed on the monitor screen when they are excessively high values3, making the users to keep the safety of ultrasound diagnosis. Obstetric setting should be confirmed before Doppler flow velocity measurements during pregnancy, in order to keep the safety of Doppler ultrasound. Ultrasonic examinations should be done only by medical indications. Although ISUOG safety statement7 reported that there is no reason to withhold the use of scanners that have received current FDA clearance in the absence of gas bodies, AIUM5 stated that for the current FDA regulatory limit at 720 mW/cm2, the best available estimate of the maximum temperature increase can exceed 2°C. Pulsed ultrasound intensity threshold to suppress cultured cell-growth curve was 240 mW/cm2 in our studies.10 The FDA regulation may be still controversial from the opinions and reports.
Prevention of Thermal Damage due to Ultrasound Exposure
The TI is a useful index of the temperature rise by ultrasound exposure. Standard tissue models are used in the TI determination in the worst case, i.e. TI is determined by the highest temperature rise. One TI stands for one degree celsius temperature elevation, e.g. temperature rises for 3°C and absolute temperature is 40°C if TI is 3. Since local temperature rise is estimated only by TI at present, TI is the index to estimate tissue temperature in ultrasound examination, to study ultrasonic thermal effect and to avoid possible thermal damage of intense ultrasound. Soft tissue TI (TIS) is used in case of embryo of no bone before 10 weeks of pregnancy and bone TI (TIB) is applied in the fetus with bone.
No hazardous thermal effect is expected when the temperature rise of exposed tissue is less than 1.5°C. An ultrasound examination is totally safe with the TI less than one in daily practice, particularly in the screening of pregnancy and research works. The output power is reduced if the displayed TI is higher than one, until the TI is lower than one. Revised safety statement AIUM5 stated that equal or less than 2°C temperature rise above 37°C was tolerated up to 50 hours and that the upper limit of safe exposure duration was 16 min at 4°C rise and 1 min at 6°C rise above normal, respectively. The AIUM opinion on the effect of high temperature is similar to the report of NCRP.2
Although the statement5 is useful in a retrospective criticism after the ultrasound exposure, fetal exposure with the temperature rise for 4–6°C may be medically 6controversial because absolute temperature is 41–43°C. Non-hazardous exposure time at such temperature higher than 40°C is critically short,2,5 where remained safe margin is very narrow, excess heating may not be completely avoided in the highest temperature. The author proposes practically applicable safe exposure time in the prospective situation before a Doppler ultrasound diagnosis.
Two Modes in Ultrasonic Exposure Duration
Two modes can be used in the Doppler ultrasound. The mode of TI lower than one (AIUM) or the temperature rise below 1.5°C (WFUMB) after temperature equilibrium can be adopted for the infinite exposure in the research work or pregnancy screening where the exposure time is hardly expected before the study.
Diagnostic pulsed Doppler study is another situation where users require improved Doppler flow wave by the higher TI than one. Some ultrasound lecture showed us higher TI than one in Doppler studies where the safety is proved by short exposure time. The technique was the same as the NCRP report, where short exposure to high temperature was nonhazardous. Doppler examinations with higher TI than one can be permitted by short exposure.
Non-hazardous exposure time to high temperature, temperature rise and high TI is obtained by the application of the equation 2 (Table 1.2 and Fig. 1.2). Exposure time is 250 min when TI is 2 and temperature is 39°C, it is 1hr if TI is 3 and temperature 40°C and 15 min when TI is 4 and the temperature is 41°C. The fetus is tolerable for 4min if the TI is 5 and absolute temperature is 42°C, and finally, one min’ exposure time is allowed, if TI is 6 and temperature is 43°C, in the revised safety statement of AIUM.5 The statement is useful in the confirmation of Doppler ultrasound safety in the past examination. On the other hand, however, the setting of exposure time is required in prospective situation before examination.
Prospective Setting of Exposure Time before Examination
Exposure time is preset before the Doppler examination in the case of higher TI than one with the intention to improve Doppler flow wave. The author recommends to determine actual exposure time by dividing the non-hazardous time of NRCP with the “safety factor” at 50 before every examination with high TI (Tables 1.2 and 1.3, Fig. 1.2). The method was similar to the past regulation of simple B-mode devices in Japan, where threshold intensity was divided by 100 and the output power was regulated to be lower than 10 mW/cm2 and the safety was generally accepted before the Doppler flow studies. As ultrasound intensity may increase for about three times if standing wave is present, three is the lowest safety factor. In addition, the intensity may increase by the distortion of ultrasonic wave measured by A/B ratio and possible estimation error of TI.9 These situations are added up to the safety factor and therefore, the author proposes the safety factor up to 50.
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For example, non-hazardous exposure time limit is 252 min at 39°C in AIUM statements (Table 1.2), where the temperature rises for 2°C and corresponding TI is 2. In author's recommendation, 252 min are divided by 50 and actual exposure time is 5 min. By the same manner, 1 min exposure time is preset when TI is 3 (Table 1.3).
Higher TI than 3 is not recommended because absolute temperature is higher than 40°C that will be medically controversial. The author's setting is close to the BMUS safety statement 11 where the exposure time is 4 min when TI is 2 and 1 min if TI is 2.5.
Other Thermal Issues
Caution should be paid for the temperature of the tissue exposed to Doppler ultrasound in febrile patients, where the basic temperature is higher than 37°C.1 For example, if TI is 2 in 38°C febrile patient, the temperature rise above physiologic condition is 3°C, the situation is the same as TI 3 in nonfebrile normal temperature case, and 7therefore, 1 minute's exposure time is appropriate. Surface temperature of transvaginal transducer should not be 41°C or more.1 The user should concern the direct heating of attached tissues and pelvic organs.
Animal fetal skull was heated and the temperature elevation was more than 4°C by the exposure to intense ultrasound.6 Thermal damage of the brain surface can not be denied. Therefore, maximal intensity of Doppler ultrasound is inadvisable in intracranial flow studies even in late pregnancy. Exposure duration and TI should be documented in patient records in the study where TI is higher than one. The safety indices including TI and MI are documented in the “Methods” of Doppler ultrasound study reports.
The Safety of 3D Ultrasound
Simple B-mode imaging is not concerned for the thermal effect, because of its very low output intensity, e.g. the output of B-mode machine is regulated in Japan10 to be lower than SPTA 10 mW/cm2. The gray level data is acquired in 3D imaging by repeated scan of real-time B mode array transducer, the scans are completed within a few seconds, the image data are stored in the computer memory and the unique 3D images are processed in the computer after the ultrasound exposure. A point of fetal body would be exposed to ultrasound infrequently in whole scans. Therefore, 3D ultrasound exposure at a point of the fetus or embryo and possible heating caused by ultrasound would be the same as a simple B-mode.
Accordingly, possible temperature rise and thermal effect in 3D ultrasound are almost the same as simple B-mode, therefore 3D technique will be as safe as the simple B-mode ultrasound in its thermal effect. Doppler flow study accompanied by 3D ultrasound is regulated by its own thermal effects. The mechanical effect of pulsed ultrasound in 3D is equal to the simple B-mode and it is determined by its temporal peak (TP) intensity, sound pressure or mechanical index (MI). The 3D ultrasound is safe in mechanical effects if the MI is lower than one, as commonly recommended.
The Safety of 4D Ultrasound
Although the 4D ultrasound image is obtained by computer processing of 10–24 frames of fetal 3D pictures in a second, most fetal parts are expected not to be exposed to ultrasound repeatedly, because the fetus is moving and therefore a fetal part continuously changes its position. Thermal effect of ultrasound will not be concerned in 4D, despite large number of ultrasound scan is repeated, because simple B-mode is the base of 3D and 4D imaging and thermal effect is not concerned in the B-mode. The 4D ultrasound is considered to be long scan of simple B-mode scan. Therefore, there will be no problem caused by ultrasonic thermal effect in 4D surface imaging. Although, theoretically, there is no limit of B-mode ultrasound examination if the thermal index (TI) is less than one, the duration of 4D fetal studies would be limited in diagnostic or scientific purposes. Doppler study accompanied by 4D ultrasound is regulated by its own thermal effects. As for the safety of mechanical effect of pulsed ultrasound, 4D ultrasound is safe to the fetus or embryo when the MI is less than one and the duration is prudent.
MECHANICAL EFFECTS OF DIAGNOSTIC ULTRASOUND
Mechanical index (MI) is used for the estimation of mechanical bioeffect where MI is rarefactional sound pressure (Pr) expressed in Mega-Pascal (MPa), divided by square root of ultrasound frequency in MHz, e.g. MI is 2 when Pr is 2 MPa and the US frequency is 1 MHz. MI indicates non-thermal effect of ultrasound particularly for the cavitation in the presence of gas bubbles in liquids. Although gas containing contrast medium is still infrequent in OB/GY, its common use in adult circulation should be carefully studied. It is also taken into account that common B-mode is weak in thermal effect, while its pulse peak intensity is not much different from Doppler machines. However, the free radical formed by the inertial cavitation hardly reaches floating cells in the fluid due to short life span and no cavitation may occur within the cell due to high viscosity of cell plasma. Effects of acoustic streaming, capillary blood cell stasis by standing waves or the positive ultrasound pressure require further basic studies. Since hemorrhages are found in neonatal animal lung by the exposure to intense ultrasound, lower MI than one should be used in neonatal lung examination. Although recently the failure of neuronal cell migration in fetal mouse brain was reported after exposure of pregnant mouse to real time B-mode transducer with high pulse average intensity, the report needed 30 minutes or more exposure time to develop the effect.12 AIUM stated that fetal mice exposed to ultrasound were found to have small but detectable effects only after extended duration of ultrasound exposure, conditions beyond those commonly used in diagnostic ultrasound imaging. The whole brain exposure in the rapidly developing mouse brain used in this study differs significantly from the short duration of diagnostic ultrasound imaging to selected sites in the human fetus. 8Similar opinions were stated by the Japan Society of Ultrasound in Medicine and Japan Society of Biomedical Engineering in Obstetrics and Gynecology.
NON-MEDICAL USE OF DIAGNOSTIC ULTRASOUND
Although the use of diagnostic ultrasound should be limited for medical purposes and users are responsible to the safety of ultrasound, i.e. users must keep the knowledge on possible ultrasound bioeffect and use the ultrasound under the ALARA (as low as reasonably achievable) principle, nonmedical ultrasound in entertainment or keepsake ultrasound, fetal portrait studios or prenatal boutiques which record intrauterine fetal 3D/4D ultrasound on DVD are recent problems concerning ultrasound safety. There are also ethical concerning and false reassuring problem in the topics.13–16
The WFUMB13 disapproves of the use of ultrasound for the sole purpose of providing souvenir images of the fetus. Because the safety of an ultrasound examination cannot be assured, the use of ultrasound without medical benefit should be avoided. Furthermore, ultrasound should be employed only by health professionals who are well trained and updated in ultrasound clinical usage and bioeffects. The use of ultrasound to provide keepsake images or video of the fetus may be acceptable if it is undertaken as part of normal clinical diagnostic ultrasound examination, provided that it does not increase exposure to the fetus. Ultrasound imaging for nonmedical reasons is not recommended unless carried out for education, training or demonstration purposes. Live scanning of pregnant models for equipment exhibition at ultrasound congresses is considered a nonmedical practice that should be prohibited since it provides no medical benefit and afford potential risk to the fetus. When using ultrasound for nonmedical reasons, the ultrasound equipments display should be used to ensure that TI<0.5 and MI<0.3.13
The safe obstetric ultrasound intensity level was reported to be one thermal index (1TI) and one mechanical index (1MI) in general opinions of medical ultrasound authorities (Fig. 1.2). There can be possible biological hazardous effects in the ultrasound intensity above the levels. In particular case where the user's knowledge is abundant on the ultrasound safety, the TI may be allowed to be 2 but the exposure time should be limited less than 5 mins (Table 1.3).
In our detailed ultrasound radiation experiments insulating the heating of the transducer in the thermostat water, the cultured fetal amniotic origin cell line floated in the culture medium held in ultrasound translucent container was exposed quantitative ultrasound 20–30 mins and the cell growth curve was compared to the sham of no radiation in the same thermostat water. The cell growth curve showed no difference to the sham below the SPTA 240 mW/cm2 (SPTP 20 W/cm2) of pulsed ultrasound, while the growth curve was suppressed after the exposure to the output intensity ultrasound above the threshold output intensity.11 Since Japan Society of Ultrasonics in Medicine authorized the results, Japan Industrial Standard (JIS)10 regulated medical ultrasound output intensity at the level lower than SPTA 10 mW2, afterwards the medical ultrasound safety was generally recognized.
Although the regulated intensity is low level, the standing wave in case of ultrasound reflection may increase the intensity and the deformed pulsed ultrasound waves may further increase the intensity. The prudent JIS setting will contribute the safety of medical ultrasound even in its accidental increase, while possible increase of output intensity to get further clear fetal image in nonmedical entertainment will easily exceed the safe threshold intensity level. The risk should be prevented by the skilful medical staff with rich safety knowledge and prudent use of diagnostic ultrasound equipment.
In summary of the opinion of ultrasound safety specialists, the non-medical use of diagnostic ultrasound for solely entertainment is not recommended or not permitted from the standpoint of diagnostic ultrasound.13–16
CONCLUSION
The strategies to keep the safety of each diagnostic ultrasound equipments depends on their system, because the thermal effect estimated by TI has been the main criteria in the safety. Simple B-mode, 3D and 4D ultrasound, fetal heart detector and fetal monitor, are not contraindicated due to thermal effect because of their low temporal average intensity. Pulsed Doppler machines are the main target in the safety due to its high temporal average intensity. Non-hazardous exposure time of NCRP/AIUM criteria and the temperature rise estimated by TI are useful in retrospective criticism on the past examination. The principle of safe diagnostic ultrasound in daily practice is to keep the TI below one, where obstetrical setting is useful. Research works and pregnancy screening strictly follow the 9principle. Moderately higher TI is allowed when more improved Doppler flow wave is required, where the author recommends the exposure time less than 5 min if TI is 2 and 1 min if TI is 3. Higher TI than 3 is not used. Attention should be paid to the decreased safety in febrile patient. Transvaginal transducer temperature should be lower than 41°C. Although 3D and 4D ultrasound are safe, the study duration should be prudent in 4D. The MI is recommended to be less than one, particularly in the studies on air containing neonatal lung. Fetal mice brain effects detected after extended duration of ultrasound exposure were conditions beyond the short exposure in common clinical imaging.
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