In vitro characterisation of ultrasound-induced heating effects in the mother and fetus: A clinical perspective

Abstract

Introduction

The quantification of heating effects during exposure to ultrasound is usually based on laboratory experiments in water and is assessed using extrapolated parameters such as the thermal index. In our study, we have measured the temperature increase directly in a simulator of the maternal–fetal environment, the ‘ISUOG Phantom’, using clinically relevant ultrasound scanners, transducers and exposure conditions.

Methods

The study was carried out using an instrumented phantom designed to represent the pregnant maternal abdomen and which enabled temperature recordings at positions in tissue mimics which represented the skin surface, sub-surface, amniotic fluid and fetal bone interface. We tested four different transducers on a commercial diagnostic scanner. The effects of scan duration, presence of a circulating fluid, pre-set and power were recorded.

Results

The highest temperature increase was always at the transducer–skin interface, where temperature increases between 1.4°C and 9.5°C were observed; lower temperature rises, between 0.1°C and 1.0°C, were observed deeper in tissue and at the bone interface. Doppler modes generated the highest temperature increases. Most of the heating occurred in the first 3 minutes of exposure, with the presence of a circulating fluid having a limited effect. The power setting affected the maximum temperature increase proportionally, with peak temperature increasing from 4.3°C to 6.7°C when power was increased from 63% to 100%.

Conclusions

Although this phantom provides a crude mimic of the in vivo conditions, the overall results showed good repeatability and agreement with previously published experiments. All studies showed that the temperature rises observed fell within the recommendations of international regulatory bodies. However, it is important that the operator should be aware of factors affecting the temperature increase.

Introduction

Progress in technology has significantly improved the quality of ultrasound images, and thus, the number of pathologies which can be detected is constantly increasing. With better resolution, diagnosis can be made earlier in pregnancy, bringing with it relevant improvements in the potential for intervention, and thus in the final outcome. While there is the aim of providing clinicians with the best possible tools, it is important to ensure that available new devices and protocols are safe for the mother and the fetus.¹,² Although widely recognised as safe,^3–5 two main bioeffect mechanisms of ultrasound are possible. These are classified as those that are thermal and those that are mechanical in origin.⁶ The potential for harm from thermal or mechanical bioeffects is shown on the scanner display by two safety indices referred to as the thermal index (TI) and the mechanical index, respectively. The former refers to the theoretical equilibrium temperature reached in tissue after a sufficiently long exposure, and the latter refers to the risk of mechanical damage though bubble oscillation. The calculation of these parameters requires the measurement of the acoustic pressure and the acoustic power under ‘free-field’ conditions in water tanks. However, in practice, the process involves a number of approximations which do not necessarily reflect the clinical environment.⁷

Several different organisations have released guidelines for the safe conduct of obstetric scans. A recent review by Harris et al.⁸ found that the indications for prenatal/neonatal examinations are in general agreement. In particular, the British Medical Ultrasound Society⁹ states that a temperature increase of ≥4°C for 4 minutes or of ≥5°C for 1 minute is hazardous for the fetus and recommends that the temperature rise is kept well below these levels. Recent statements from the International Society of Ultrasound in Obstetrics and Gynaecology (ISUOG) Bioeffects and Safety Committee underline the importance of applying the ALARA (As Low As Reasonably Achievable) principles, namely to limit the exposure time for Doppler modes and to discourage the use of ultrasound for non-medical purposes.¹⁰,¹¹

This study addresses an existing challenge in ultrasound safety from a novel perspective. It aims to characterise the temperature changes that occur in the mother and fetus when exposed to ultrasound in a clinical setting by using clinically relevant ultrasound machines, transducers and exposure parameters. The study was carried out using a custom-built simulator of the maternal–fetal environment, the ‘ISUOG phantom’, which enables temperature recordings from sensors embedded in tissue mimics representing the skin surface, sub-surface, amniotic fluid and fetal bone interface. Despite the limitations of using a phantom model, it has the clear advantage of overcoming the technological (and, arguably, ethical) barriers to performing a similar in vivo study on pregnant women in the clinic.

Methods

The ISUOG phantom

The ISUOG phantom is a temperature-controlled, fixed geometry hollow Nylon cylinder, with an external diameter of 150 mm, an internal diameter of 120 mm and a height of 130 mm. It is designed to simulate the anatomy encountered during abdominal obstetric examinations using a simplified multi-layer geometry and tissue mimicking materials which simulate the acoustic properties of skin, soft tissue, amniotic fluid and bone. A schematic of the phantom is shown in Figure 1.

Figure 1.

Schematic diagram of maternal–fetal ISUOG phantom; the position of the thermocouples is indicated by the white dots.

The top window comprises an acoustically transparent membrane (12-µm Mylar, Goodfellow Cambridge Ltd., UK) which protects the internal layers.

The first (top) layer is 1.5-mm thick silicone rubber (SILEX Ltd, UK) commonly used to simulate the skin.¹² To mimic soft tissues, an agar-based gel was selected and produced in-house. This is based on the recipe described by Brewin et al.¹³ and is the standard formulation suggested by regulatory bodies (IEC60601-2-37 Annex DD)¹² for performing temperature tests on diagnostic transducers. A gel block 25 mm thick was in contact with the silicone rubber layer. Behind a 25-mm fluid gap, two further gel blocks of thicknesses 5 mm and 25 mm sandwiched a 5-mm thick high-density polyethylene disk designed to mimic a soft tissue–bone interface. The phantom was filled with a solution of deionised water and 11.9% w/w of glycerol to preserve the agar-based gel and simulate the acoustic properties of the amniotic fluid.¹⁴

The attenuation coefficient α and speed of sound of the tissue mimicking materials at the relevant frequencies are shown in Table 1 and were measured at the National Physical Laboratory using a substitution technique described by Rajagopal et al.¹⁵ These values are comparable to those of real tissues listed in the 2018 version of the IT’IS foundation database for tissue properties.¹⁶

Table 1.

Speed of sound (SoS) and attenuation (α) of the materials for the ISUOG phantom.

	4 MHz		6 MHz		7 MHz		9 MHz
	α (dB/cm)	SoS (m/s)	α (dB/cm)	SoS (m/s)	α (dB/cm)	SoS (m/s)	α (dB/cm)	SoS (m/s)
Skin mimic	9.7	1009	24.8	1010	33.2	1011	49.1	1013
Soft tissue mimic	2.46	1541	3.55	1542	4.12	1542	5.30	1542
Bone mimic	18.2	2476	31.1	2490	38.2	2496	50.9	2502
Amniotic fluid mimic	0.04	1535	0.08	1535	0.11	1535	0.2	1535

Uncertainties in SoS and attenuation are 1% and 10%, respectively. Measurements were carried out at 20°C using a substitution method.¹⁵

An 8 W resistive heater (Silicon Heater Mat, RS Components, UK) was placed at the bottom of the phantom. The internal temperature was kept stable using a custom-made controller which drove the heater and a peristaltic pump. With the circulation pump on, the phantom mimicked the conditions of the embryonic period after establishment of the utero-placental circulation.

Four 75-µm fine wire K-type insulated thermocouples (5SRTC-TT-KI-40-1 M, Omega Engineering, UK) were embedded in the phantom at the proximal skin surface, distal skin surface, at the back of the first block of soft tissue mimicking material and at the soft tissue–bone interface. The thermocouples are smaller than half the wavelength at the highest frequency under examination.

A fifth thermocouple was placed outside the acoustic field to control the temperature of the circulating solution. The temperature data from all thermocouples were recorded using a TC08 datalogger (PicoTech, UK) connected to a computer. The sampling period was 1 second as in the previous study by Miloro et al.¹⁷

Experimental setup

A standard commercially available ultrasound scanner, routinely used in clinical practice, was tested. It was equipped with four different transducers: two convex transducers with centre frequencies of 4 and 6 MHz, a linear transducer with centre frequency 9 MHz and a 4-D transvaginal transducer with centre frequency of 7 MHz. 4-D function was not tested during the experiments.

Before each test, the internal temperature of the phantom was allowed to stabilise to a physiologically relevant temperature (between 35°C and 37°C). Ultrasound coupling gel was applied to the top surface of the phantom to ensure good acoustic coupling. The temperature at the surface was in the range 27°C to 29°C in all experiments.

The transducers were clamped to a rigid base and aligned with the axis of the phantom using the thermocouples as reference points. A schematic and a photograph of the setup are shown in Figure 2.

Figure 2.

Schematic (left) and photograph (right) of maternal–fetal ISUOG phantom setup.

Experimental protocols

Five different sets of experiments were carried out to assess the influence of the transducer, the pre-set, the exposure duration, the power setting and the circulatory flow. The TI for each setting was recorded. Repeated measurements were performed on consecutive days.

1. Exposure duration studies: the 9 MHz transducer was used in a first trimester pre-set mode. Simulated skin and fetal bone interface temperature changes were recorded for 30 minutes in B-mode and pulsed wave (PW) Doppler modes and were repeated three times.

2. Fluid circulation studies: the 9 MHz transducer in first trimester pre-set mode was used. Simulated skin and fetal bone interface temperature changes were recorded for 30 minutes in B-mode and PW Doppler mode with amniotic fluid mimic flow either on or off. Measurements were repeated three times.

3. Transducer studies: surface temperature changes were recorded during 3-minute exposures in B-mode, colour Doppler and PW Doppler modes using the four transducers described above. The ultrasound equipment was operated in first trimester pre-set mode.

4. Pre-set studies: the 9 MHz transducer was used with first trimester, second trimester and fetal cardiac pre-sets. Surface temperature changes were recorded during 3-minute exposures for B-mode, colour Doppler and PW Doppler modes and were repeated three times.

5. Power studies: the 4 MHz and the 9 MHz transducers were used. The surface temperature changes were recorded for 30 minutes at the power level of the first trimester pre-set in B-mode (63% and 79% for the 4 MHz and the 9 MHz transducer, respectively) and for 100% power.

A summary of the protocols is shown in Table 2. The focal zone was always positioned over the thermocouple at the tissue–bone interface. Additional information on the pre-set parameters is provided in Table 3.

Table 2.

Summary of the scanner settings and transducers used.

Test ID	Transducer	Mode	Pre-set	Duration
Duration	9 MHz	B-mode and PW Doppler	1st trimester	1 to 30 minutes
Circulation	9 MHz	B-mode and PW Doppler	1st trimester	30 minutes
Transducer	All	B-mode, colour flow and PW Doppler	1st trimester	3 minutes
Pre-set	9 MHz	B-mode, colour flow and PW Doppler	1st trimester, 2nd trimester and fetal echocardiogram	3 minutes
Power	4 MHz and 9 MHz	B-mode	1st trimester	30 minutes

PW: pulsed wave.

Table 3.

Additional information on pre-set parameters.

Settings	B-mode		Colour Doppler		PW Doppler
	Transmitted frequency (MHz)	Spatial compound	Transmitted frequency (MHz)	Pulse repetition frequency (Hz)	Transmitted frequency (MHz)	Pulse repetition frequency (Hz)
4 MHz 1st trimester	4	ON	2.5	1953	2	1953
6 MHz 1st trimester	6	ON	3.25	1953	2.5	3906
7 MHz 1st trimester	5.5	ON	3.25	1953	2.5	3906
9 MHz 1st trimester	8	ON	4	1953	4	3906
9 MHz 2nd trimester	8	OFF	4	1953	4	3906
9 MHz Fetal cardiac	8	ON	4	5580	4	7102

PW: pulsed wave.

Results

All results are presented as mean and standard deviation where appropriate. Two-tailed paired Student’s t-tests were used to determine statistical significance between groups.

Thermal indices

Two different values of the TI, indicating the potential thermal hazard in soft tissue (TIS) and at the tissue–bone interface (TIB), were recorded. International standards do not require the TI to be displayed when it is less than 0.4, so in some cases, these values were not available.¹⁸ Thermal indices displayed for the configurations used in the work are reported in Table 4.

Table 4.

Thermal indices displayed for the configurations used in the study.

Transducer mode	TIS			TIB
	B-mode	Colour Doppler	PW Doppler	B-mode	Colour Doppler	PW Doppler
4 MHz 1st trimester	–	0.7	0.6	–	0.7	3
6 MHz 1st trimester	–	1.2	1.1	–	1.2	3.4
7 MHz 1st trimester	–	0.6	0.7	–	0.6	2.4
9 MHz 1st trimester	–	1.1	1.4	–	1.1	2.9
9 MHz 2nd trimester	–	1.1	1.4	–	1.1	2.9
9 MHz Fetal cardiac	–	1.1	1.4	-	1.1	3

PW: pulsed wave; TIS: thermal index in soft tissue; TIB: thermal index in bone.

Exposure duration studies

A representative example of the temperature changes measured by the four thermocouples is shown in Figure 3.

Figure 3.

Temperature changes during a 30-minute exposure for the four thermocouples using the 9 MHz transducer in PW Doppler mode.

The maximum temperature increase is at the transducer–skin interface. A lower temperature increase is observed for the thermocouple positioned under the skin. No changes were observed for the sensor positioned in the deeper soft tissue mimicking material, while measurable variations were seen at the tissue–bone interface, probably due to the higher attenuation coefficient of the bone mimic (see also Table 1).

The example in Figure 3 is representative of the different experiments performed during this work. The complete dataset is provided as additional material to this paper. However, for clarity, the following discussion will focus on the results of the transducer–skin mimic interface and on the tissue–bone interface when relevant.

An analysis of the maximum temperature rises at the transducer–skin mimicking interface (surface) and at the bone–tissue interface is shown in Figure 4 and reported in Table 5. Results refer to B-mode and PW Doppler using the 9 MHz linear transducer. Results shown are an average of three independent tests.

Figure 4.

Results of the study of effect of exposure duration on maximum temperature achieved at the skin surface and at the bone–soft tissue interface for the different modes using the 9 MHz linear transducer.

PW: pulsed wave.

Table 5.

Temperature rise at different times for the 9 MHz transducer.

Time (minutes)	Surface temperature rise (°C), mean (SD)		Bone temperature rise (°C), mean (SD)
	B-mode	PW Doppler	B-mode	PW Doppler
1	2.5 (1.0)	3.3 (0.3)	0.0 (0.1)	0.2 (0.1)
3	4.0 (1.0)	4.7 (0.4)	0.0 (0.1)	0.3 (0.1)
10	5.9 (1.0)	6.2 (0.5)	0.0 (0.1)	0.4 (0.2)
30	7.1 (0.8)	7.3 (0.8)	0.1 (0.3)	0.7 (0.5)

PW: pulsed wave.

At the skin interface, 35% to 44% of the mean 30-minute surface temperature rise was observed after 1 minute and 56% to 64% after 3 minutes. At the bone–tissue interface, 34% of the mean 30-minute temperature rise was observed after 1 minute and 42% after 3 minutes.

Fluid circulation studies

The results of the study of the effects of circulatory flow, designed to mimic the embryonic and fetal stages of the pregnancy, are shown in Figure 5 for B-mode and PW Doppler. Statistical analysis showed no significant variation between the two conditions (p > 0.13 in all cases). The maximum temperature increase at the soft tissue–bone interface was 0.1°C for B-mode, and, for clarity, these have been omitted in the figure.

Figure 5.

The effect of flow on the temperature rise at the ISUOG phantom surface (n = 3) following exposure to B Mode (left) and PW Doppler (right) for different exposure times. The values for the tissue–bone interface have been omitted for B-mode.

PW: pulsed wave.

Transducer studies

The results for 3-minute exposures using the four different transducers are shown in Figure 6 and summarised in Table 6. Only the measurements for the thermocouple at the surface are reported as the values for the tissue–bone interface were negligible for all the experiments.

Figure 6.

Temperature changes at the phantom surface (n = 3) for three different TA transducers and one TV transducer.

TA: transabdominal; TV: transvaginal; PW: pulsed wave.

Table 6.

Temperature rise at the skin interface for the four different transducers.

Scanning mode	Surface temperature rise (°C), mean (SD)
	1–9 MHz	2–6 MHz	3–4 MHz	4–7 MHz
B-mode	3.9 (0.4)	2.3 (0.5)	2.0 (0.3)	1.4 (0.2)
Colour Doppler	5.2 (0.5)	3.8 (0.9)	3.8 (0.6)	2.9 (0.5)
PW Doppler	5.7 (0.8)	4.4 (1.0)	4.0 (0.5)	3.7 (0.6)

PW: pulsed wave.

The lowest temperature increase for the three modes was always for the transvaginal transducer. The 9 MHz transducer gave the highest temperature increase.

Pre-set study

Three different pre-sets were tested for the 9 MHz transducer: first trimester, second trimester and fetal cardiac, as these are commonly used in clinical practice.¹⁹ For this set of experiments, only the measurements for the thermocouple at the surface are reported. Results are shown in Figure 7. In the B-mode setting, the greatest difference in temperature was seen between the second trimester and fetal cardiac pre-sets, the difference being 0.6°C (p = 0.03). The differences were not significantly different between the first trimester and fetal cardiac pre-sets in colour Doppler (difference 0.4°C, p = 0.40) and between the second trimester and fetal cardiac pre-sets in spectral Doppler (difference 0.1°C, p = 0.93). Table 7 summarises the results for the three pre-sets.

Figure 7.

The effect of different pre-sets on the US-induced temperature rise at the transducer–skin interface (n = 3).

PW: pulsed wave.

Table 7.

Temperature rise at the skin interface for the three different pre-sets using the 9 MHz transducer.

Scanning mode	Surface temperature rise (°C), mean (SD)
	1st trimester	2nd trimester	Fetal echo
B-mode	3.9 (0.4)	3.8 (0.2)	4.3 (0.3)
Colour Doppler	5.2 (0.5)	5.5 (0.5)	5.6 (0.4)
Spectral Doppler	5.7 (0.8)	5.8 (0.7)	5.7 (0.3)

Power studies

Finally, the effect of power settings was analysed for the first trimester pre-set. The results for the transducer–skin mimic interface are shown in Figure 8. For the 4 MHz transducer, a change in power output setting from 63% to 100% showed a significant increase in heating effect. The mean temperature increase rose from 4.3°C to 6.7°C (p < 0.005). This change in maximum temperature would be expected if there was a direct proportionality applied to the value of the temperature increase at 63% power.

Figure 8.

The effect of power on the US-induced temperature rise at the ISUOG phantom transducer–skin mimic interface (n = 3) for the 4 MHz (left) and 9 MHz transducers (right).

TA: transabdominal.

Similar results are obtained for the 9 MHz transducer, with a change from 79% to 100% leading to an increase in temperature from 7.1°C to 9.6°C (p < 0.05).

With the temperature resolution available with the sensors used in this phantom, no statistically significant changes in temperature was detected at the bone interface for any of these exposure configurations.

Discussion

As previously reported,¹⁷ the maximum temperature increase is seen at the ultrasound transducer–skin interface and is likely to be due to transducer self-heating.²⁰ It is important to note that this effect is not considered in calculation of the TI. The temperature at the tissue–bone interface increases more slowly than at other sites, suggesting a more important contribution from acoustic absorption than from direct heating. In agreement with previous studies, Doppler modes showed the highest temperature increase.

In none of the experiments described here did the temperature measured at the tissue–bone interface and within the soft tissue mimic approach the safety limits reported in the most recent guidelines,⁹ as all the measured values were below 1°C, which is the lowest level for which time limits are suggested. Nevertheless, due to the large variety of possible equipment and setting combinations, constant vigilance of the relevant parameters is recommended.

Significant temperature increases are recorded at the skin interface. However, it is important to note that the starting temperature for the sensors at the interface was significantly lower than for that within the phantom (on average 28°C as opposed to 36°C); it should be noted that we were of course measuring temperature rise rather than absolute temperature.

Under these conditions, all the transducers and all the tests undertaken were compliant with the relevant standards.¹² Unsurprisingly, endocavitary transducers have the most stringent requirements for their maximum surface temperature. This is reflected in the lower temperature increase shown by the transvaginal transducer. One of the transducers displayed a TIB higher than that recommended by the guidelines, namely with PW Doppler mode in first trimester settings. Such a setting should never be used in clinical practice.

The results for long exposures show that most of the heating happens within 3 minutes, which is a typical scanning time, even for an experienced clinician.²¹

The results from experiments with and without use of the water circulation pump suggest that the establishment of utero-placental circulation has only a small influence on the temperature rise induced by ultrasound. There was a marginally greater heating effect in the simulated embryonic period than in the fetal period, but this was not statistically significant. The implication, assuming the model holds, is that ultrasound has an equivalent thermal effect in the embryonic and fetal periods; however, it must be remembered that up to eight weeks after conception, organogenesis is taking place in the embryo, and in this period, cell damage might lead to fetal anomalies or subtle developmental changes.⁹

Large temperature differences were seen between different transducers in all modes of operation. In particular, the differences between the 7 MHz transvaginal transducer and the 9 MHz linear transducer (lowest and highest temperature increase respectively) were 2.6°C, 2.4°C and 2.0°C for B-mode, colour Doppler and PW Doppler, respectively. While these differences where expected, it is worth noticing that the thermal indices in Table 2 did not correlate with the final temperature increases seen when different transducers are used.

With regards to the choice of pre-set, it is of little consequence whether first or second trimester is chosen. The fetal echocardiogram pre-set resulted in a small but statistically significantly greater heating effect. Also, in this case, there is a limited correlation between the displayed TI and the actual temperature increase. Nonetheless, it is worth remarking that for a specific combination of scanner and transducer, higher TIs generally correspond to greater temperature increases.

The power setting is important for reducing the temperature increase without compromising the image quality.²² For the two transducers examined (4 MHz and 9 MHz), the temperature increase was proportional to the power setting. Settings such as gain, focal zone and tissue harmonic also affect the quality of the image. Alteration of these settings, always controlling the displayed TI, should be preferred to increasing the acoustic power in order to improve the quality of image.

The results presented in this manuscript are relevant for the phantom used for the study. Several factors could affect the translation of the results reported in this manuscript to clinical situations. Measurement artefacts have been minimised by accurate identification of the thermocouple. Positioning of the transducer and alignment of the thermocouples were verified by B-mode image. The measurement conditions are considered conservative compared to patient measurements, as the transducer was held in a stationary fixed position, which is not the case for the majority of diagnostic scans. The geometry of the phantom is fixed, while each patient and examination presents a unique combination of insonated tissues (with their patient-specific acoustic properties) and anatomical features. Furthermore, perfusion, which can facilitate heat dispersion, is not present in the phantom.

In conclusion, although the ISUOG phantom provides a crude mimic of the in vivo conditions, the overall results showed good repeatability and agreement with previously published experiments.¹⁷,²⁰

Although all measurements fell within the recommendations of the international regulatory bodies, it is important that any operator should be aware of factors affecting the temperature increase.

ORCID iDs

Stephanie F Smith https://orcid.org/0000-0001-9290-3773

Piero Miloro https://orcid.org/0000-0001-6809-2296