Doppler in Obstetrics by Nicolaides, Rizzo, Hecker & Ximenes
The 11-14 weeks scan by Nicolaides, Sebire, Snijiders & Ximenes
The 18-23 weeks scan by Pilu, Nicolaides, Ximenes & Jeanty
 
INTRODUCTION

Diagnostic ultrasound is generally perceived by users and patients as a safe technique with no adverse effects. Since ultrasound is so widely used in pregnancy, it is essential for all practitioners to ensure that its use remains safe. Ultrasound causes thermal and mechanical effects in tissue which are increased as the output power is increased.

In the last decade, there has been a general trend towards increased output with the introduction of color flow imaging, more use of pulsed ‘spectral Doppler’ and higher demands on B-mode imaging 1. In response to these increases, recommendations for the safe use of ultrasound have been issued by several bodies. In addition, recent regulations have changed the emphasis of responsibility so that more onus is now placed on the operator to ensure that ultrasound is used safely. This chapter summarizes the effects and the standards issued and outlines recommendations for safe use in obstetric practice.

EFFECTS

Ultrasound is a mechanical energy in which a pressure wave travels through tissue. Reflection and scattering back to the transducer are used to form the image. The physical effects of ultrasound are generally categorized as:

(1) Thermal effects – heating of tissue as ultrasound is absorbed by tissue. Heat is also produced at the transducer surface;

(2) Cavitation – the formation of gas bubbles at high negative pressure;

(3) Other mechanical effects – radiation forces leading to streaming in fluids and stress at tissue interfaces.

The implications of these effects have been determined by in vitro, animal and human epidemiological studies and are briefly summarized below.

Thermal effects
As the ultrasound waves are absorbed, their energy is converted into heat. The level of conversion is highest in tissue with a high absorption coefficient, particularly in bone, and is low where there is little absorption (e.g. amniotic fluid). The temperature rise is also dependent on the thermal characteristics of the tissue (conduction of heat and perfusion), the ultrasound intensity and the length of time for which the tissue volume is scanned. The intensity is, in turn, dependent on the power output and the position of the tissue in the beam profile. The intensity at a particular point is altered by many of the operator controls, for example power output, mode (B-mode, color flow, spectral Doppler), scan depth, focus, zoom and area of color flow imaging. With so many variables, it has proved difficult to model temperature rises in tissue. In vitro studies have been used with a ‘worst case’ model of tissue to predict temperature rises o, for instance in the formation of thermal indices (see below). The transducer face itself can become heated during an examination. Heat is localized to the tissue in contact with the transducer.
Cavitation

Cavitation is the formation of transient or stable bubbles, described as inertial or non-inertial cavitation. Inertial cavitation has the most potential to damage tissue and occurs when a gas-filled cavity grows, during pressure rarefaction of the ultrasound pulse, and contracts, during the compression phase. Collapse of the bubble can generate local high temperatures and pressures.

It has been hypothesized that ultrasonically induced cavita tion is the cause of hemorrhage in the lungs and intestines in animal studies 2–6 . In these studies, effects have been seen at tissue interfaces with gas. The absence of gas in fetuses means that the threshold for cavitation is high and does not occur at current levels of diagnostic ultrasound. The introduction of contrast agents leads to the formation of microbubbles that potentially provide gas nuclei for cavitation. The use of contrast agents lowers the threshold at which cavitation occurs, but this is not current practice in obstetrics.

 
Other mechanical effects
The passage of ultrasound through tissue causes a low-level radiation force on the tissue. This force produces a pressure in the direction of the beam and away from the transducer and should not be confused with the oscillatory pressure of the ultrasound itself. The pressure that results and the pressure gradient across the beam are very low, even for intensities at the higher end of the diagnostic range 7. The effect of the force is manifest in volumes of fluid where streaming can occur with motion within the fluid. The fluid velocities which result are low and are unlikely to cause damage.
 
Effects on fetuses

Effects are divided into mechanical and thermal. For mechanical effects, there is no evi-dence that cavitation occurs in fetal scanning. In a study of low-amplitude lithotripsy pulses in mouse fetuses, there has been concern that hemorrhage may be the result of tissue movement caused by radiation forces 8 . There is no evidence that this occurs in vivo in fetal scanning. The primary concern in fetal imaging is temperature rise. It is known that hyperthermia is teratogenic. The efforts of investigators have concentrated on defining the temperature increases and exposure times which may give rise to biological effects and on determining the ultrasound levels which might, in turn, lead to those temperature rises. With this information, criteria have been identified for the safe use of diagnostic ultrasound.

Temperature rises of 2.5°C have been demonstrated in excised unperfused guinea pig brain tissue after 2 minutes’ exposure to ultrasound at the high end of pulsed wave Doppler ultrasound intensity levels 9 . At the bone surface, temperature increases of up to 5°C were found. In a study on sheep using different intensity criteria 10 , the temperature rise in utero was found to be 40% lower than that in the equivalent non-perfused test. While the observed temperature increases occurred in high-intensity modes (typical of pulsed wave Doppler used at maximum power), these levels of intensity are achievable with some current scanner/transducer combinations.

The issue of sensitivity of fetal tissue to temperature rise is complex and is not completely understood. Acute and chronic temperature rises have been investigated in animals, but study designs and results are varied. Work carried out in this field is summarized elsewhere 11 .

The uncertainty over chronic changes is reflected in the WFUMB guidelines 12 . These state that ultrasound that produces temperature rises of less than 1.5°C may be used without reservation. They also state that ultrasound exposure causing temperature rises of greater than 4°C for over 5 min should be considered potentially hazardous. This leaves a wide range of temperature increases which are within the capability of diagnostic ultrasound equipment to produce and for which no time limits are recommended.

 
Epidemiology
Several studies have examined the development of fetuses receiving different levels of ultrasound investigation. In trials comparing ultrasound screened and non-screened groups, there has generally been no difference in birth weights between groups. There have been no unequivocal data to suggest that there is impaired development of hearing, vision, behavior or neurological function due to ultrasound screening. In a large, randomized trial of over 3200 pregnant women in which half were offered routine ultrasonography at 19 and 32 weeks, there was no evidence of impaired growth or neurological development up to follow-up at 8–9 years. There was a possible association of left-handedness amongst boys undergoing ultrasonography 13 . Scanning of this group was performed with B-mode only. There have been concerns that epidemiological studies to date do not reflect the higher output capabilities of modern scanners.
 

OUTPUT REGULATIONS, STANDARDS AND GUIDELINES – WHO DOES WHAT?

Regulations governing the output of diagnostic ultrasound have been largely set by the USA’s Food and Drug Administration (FDA), although the International Electrotechnical Commission (IEC) is currently in the process of setting internationally agreed standards.

The relevant national societies for ultrasound users (e.g. American Institutue of Ultrasound in Medicine (AIUM), British Medical Ultrasound Society (BMUS)) usually have safety committees who offer advice on the safe use of ultrasound. In 1992, the AIUM, in conjunction with the National Electrical Manufacturers Association (NEMA) developed the Output Display Standard (ODS), including the thermal index and mechanical index which have been incorporated in the FDA’s new regulations 14,15.

Within Europe, the Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) also addresses safety and has produced safety guidelines (through the European Committee for Ultrasound Radiation Safety). The World Federation (WFUMB) held safety symposia in 1991 (on thermal issues) and 1996 (thermal and non-thermal issues), at which recommendations were proffered. Following review, these were published in 1992 and 1998 as guidelines.

 
Past regulations

The initial FDA regulations on ultrasound output were produced in 1976. These imposed application-specific limits, based on existing output levels which had demonstrated no adverse effects. Limits were divided into:

(1) Ophthalmic applications;

(2) Fetal and other (including abdominal, pediatric, small parts);

(3) Cardiac;

(4) Peripheral vessels.

For spatial peak time-averaged intensity (I-SPTA) (the measure most associated with temperature rise), the maximum levels were:

Ophthalmic
17 mW/cm 2
Fetal and other
94 mW/cm 2
Cardiac
430 mW/cm 2
Peripheral vessel
720 mW/cm 2

Scanners typically had a key/button which limited output for obstetric applications. Although power and intensity limits could be exceeded in some scanners, especially when using pulsed wave Doppler or color Doppler, this required a deliberate effort on the behalf of the users.

 
Current regulations
In revising its regulations in 1993, the FDA 15 altered its approach to ultrasound safety. The new regulations combine an overall limit of I-SPTA of 720 mW/cm 2 for all equipment with a system of output displays to allow users to employ effective and judicious levels of ultrasound appropriate to the examination undertaken. The new regulations allow an eight-fold increase in ultrasound intensity to be used in fetal examinations. They place considerably more responsibility on the user to understand the output measurements and to use them in their scanning. The output display is based on two indices, the mechanical index (MI) and the thermal index (TI).
 
Mechanical index
The mechanical index is an estimate of the maximum amplitude of the pressure pulse in tissue. It gives an indication as to the relative risk of mechanical effects (streaming and cavitation). The FDA regulations allow a mechanical index of up to 1.9 to be used for all applications except ophthalmic (maximum 0.23).
 
Thermal index

The thermal index is the ratio of the power used to that required to cause a maximum temperature increase of 1°C. A thermal index of 1 indicates a power causing a temperature increase of 1°C. A thermal index of 2 would be twice that power but would not necessarily indicate a peak temperature rise of 2°C. Because temperature rise is dependent on tissue type and is particularly dependent on the presence of bone, the thermal index is subdivided into three indices:

(1) TIS: thermal index for soft tissue;

(2) TIB: thermal index with bone at/near the focus;

(3) TIC: thermal index with bone at the surface (e.g. cranial examination).

For fetal scanning, the highest temperature increase would be expected to occur at bone and TIB would give the ‘worst case’ conditions. The mechanical index and thermal index must be displayed if the ultrasound system is capable of exceeding an index of 1. The displayed indices are based on the manufacturer’s experimental and modelled data. These measurements are not infallible; an independent study has demonstrated significant discrepancies over declared I-SPTA output of up to 400% 16.

 
Future IEC standards
An IEC standard (Draft IEC 61681) is being drawn up to establish a safety classification for ultrasound equipment based on its ability to produce cavitation or a temperature rise. The standard proposes two classifications of equipment: class A, which has a lower output and for which no output display is required, and class B which has a higher output and for which an output display is required. The draft is currently undergoing review.
 
Guidelines
Ultrasound organizations have produced statements on the safe use of ultrasound. These are not regulatory statements but are intended to educate and advise. WFUMB guidelines have been issued in two special issues of Ultrasound in Medicine and Biology 12-17 . Statements and recommendations are given on B-mode scanning, Doppler imaging, transducer heating, thermal effects (see page 33). The AIUM have produced statements on the safety of ultrasound. They are available from the AIUM office and can be obtained from the AIUMwebsite – http://www.aium.org/stmts.htm. The European Committee for Ultrasound Radiation Safety has published statements 18,19 on the use of pulsed Doppler measurement in fetuses, stating that its use in routine examinations during the period of organogenesis is considered inadvisable at present.
 
A PRACTICAL APPROACH TO SAFE FETAL SCANNING
No injurious effects have been identified from ultrasound scanning of the fetus. However, changes in power output, increased use of Doppler ultrasound and a change in regulations governing outputs means that every measure should be taken by users to maintain safe practices.
Scanning practice
  • The ALARA ("As Low As Reasonably Achievable") principle should be maintained. Power outputs used should be adequate to conduct the examination. If in doubt, use a low power and increase it as necessary. Application keys for obstetrics should bring in each mode at its lowest output so that the operator is required to increase power if the examination demands it.
  • B-mode generally has the lowest power output and intensity. M-mode, color flow and spectral Doppler have higher outputs which can cause more heating at the site of examination. The examination should begin with B-mode and use color and spectral Doppler only when necessary.
  • The intensity (and temperature rise) is highly dependent on scanner settings.
    For example, the intensity changes in response to changes in:

    (a) Power Output,

    (b) Depth of examination,

    (c) Mode used (color flow, spectral Doppler),

    (d) Transmitted frequency used,

    (e) Color pulse repetition frequency (scale),

    (f) Region of color flow interest,

    (g) Focus.

  • If the display for the scanner/transducer combination shows thermal and mechanical indices, the indices should be readily visible. Of the thermal indices, TIB is most relevant to heating in the second and third trimesters. The operator should be aware of changes to the indices in response to changes in control settings.
  • Special care should be taken in febrile patients, since ultrasound heating will cause additional heating to the fetus.
  • The WFUMB recommends that ultrasound causing a temperature rise of no more than 1.5°C may be used without reservation on thermal grounds.
  • Thermal indices exceeding 1.5 should not be used routinely and, if required for specific diagnostic information, should be used for the minimum time necessary. The influence of higher intensity levels can be moderated by moving the transducer so that specific areas of tissue are not subjected to long periods of higher intensity investigation.
  • Do not scan for longer than is necessary to obtain the diagnostic information.
 
SELECTED WFUMB STATEMENTS ON THE SAFETY OF DIAGNOSTIC ULTRASOUND
 
B-mode imaging (issued 1992)
Known diagnostic ultrasound equipment as used today for simple B-mode imag- ing operates at acoustic outputs that are not capable of producing harmful temperature rises. Its use in medicine is therefore not contraindicated on thermal grounds. This includes endoscopic, transvaginal and transcutaneous applications.
 
Doppler (1992)

It has been demonstrated in experiments with unperfused tissue that some Doppler diagnostic equipment has the potential to produce biologically significant temperature rises, specifically at bone/soft tissue interfaces. The effects of elevated temperatures may be minimized by keeping the time during which the beam passes through any one point in tissue as short as possible. Where output power can be controlled, the lowest available power level consistent with obtaining the desired diagnostic information should be used.

Although the data on humans are sparse, it is clear from animal studies that exposures resulting in temperatures less than 38.5°C can be used without reservation on thermal grounds. This includes obstetric applications.

 
Transducer heating (1992)
A substantial source of heating may be the transducer itself. Tissue heating from this source is localized to the volume in contact with the transducer.
 
Recommendations on thermal effects (1997)

A diagnostic exposure that produces a maximum temperature rise of no more than 1.5°C above normal physiological levels (37°C) may be used without reservation on thermal grounds.

A diagnostic exposure that elevates embryonic and fetal in situ temperature to 4°C (4°C above normal temperature) for 5 min or more should be considered potentially hazardous.

 
REFERENCES

1. Henderson J, Willson K, Jago JR, et al. A survey of the acoustic outputs of diagnostic ultrasound equipment in current clinical use in the Northern Region. Ultrasound Med Biol 1995;21:699–705.

2. Baggs R, Penney DP, Cox C, Child SZ. Thresholds for ultrasonically induced lung hemorrhage in neonatal swine. Ultrasound Med Biol 1996;22:119–28.

3. Dalecki D, Child SZ, Raeman CH, Cox C, Carstensen EL. Ultrasonically-induced lung haemorrhage in young swine. Ultrasound Med Biol 1997;23:777–81.

4. Frizzell LA, Chen E, Chong L. Effects of pulsed ultrasound on the mouse neonate: hind limb paralysis and lung haemorrhage. Ultrasound Med Biol 1994;20:53–63.

5. Holland CK, Zheng X, Apfel RE, Alderman JL, Fernandez L, Taylor KJW. Direct evidence of cavitation in vivo from diagnostic ultrasound. Ultrasound Med Biol 1996;22:917–25.

6. Zacchary JG, O’Brien WD. Lung lesions induced by continuous and pulsed wave (diagnostic) ultrasound in mice, rabbits and pigs. Vet Pathol 1995;32:43–54.

7. Duck FA. Acoustic streaming and radiation pressure in diagnostic applications: what are the implications? In Barnett SB, Kossoff G, eds. Safety of Diagnostic Ultrasound. Carnforth, UK: Parthenon Publishing, 1998:87–98.

8. Dalecki D, Child SZ, Raeman CH, Penney DP, Mayer R, Cox C, Carstensen EL. Thresholds for fetal haemorrhages produced by a piezoelectric lithotripter. Ultrasound Med Biol 1997;23:287–97.

9. Bosward KL, Barnett SB, Wood AKW, Edwards MJ, Kossoff G. Heating of the guinea pig fetal brain during exposure to pulsed ultrasound. Ultrasound Med Biol 1993;19:415–24.

10. Duggan PM, Liggins GC, Barnett SB. Ultrasonic heating of the brain of the fetal sheep in utero. Ultrasound Med Biol 1995;21:553–60.

11. Tarantal AF. Effects of ultrasound exposure on fetal development in animal models. In Barnett SB, Kossoff G, eds. Safety of Diagnostic Ultrasound. Carnforth, UK: Parthenon Publishing, 1998:39–51.

12. Barnett SB, ed. Conclusions and recommendations on thermal and non-thermal mechanisms for biological effects of ultrasound. In WFUMBsymposium on Safety of Ultrasound in Medicine. Ultrasound Med Biol, 1998;24, special issue 13. Salveson K, Vatten L, Eik-Nes S, Hugdahl K, Bakketeig L. Routine ultrasonography in utero and subsequent handedness and neurological development. Br Med J 1993;307:159–64.

14. AIUM / NEMA. Standard for Real-Time Display of Thermal and Mechanical Acoustic Output Indices on Diagnostic Ultrasound Equipment. Rockville: American Institute of Ultrasound in Medicine, 1992 15. FDA. Revised 510(k) Diagnostic Ultrasound Guidance for 1993. Rockville, MD: Food and Drug Administration, Center for Devices and Radiological Health, 1993.

16. Jago JR, Henderson J, Whittingham TA, Willson K. How reliable are manufacturer’s reported acoustic output data? Ultrasound Med Biol 1995;12:135–6.

17. Barnett SB, Kossoff G. eds. Issues and recommendations regarding thermal mechanisms for biological effects of ultrasound. In WFUMB Symposium on Safety and Standardization in Medical Ultrasound. Ultrasound Med Biol 1992;18, special issue.

18. European Federation of Societies for Ultrasound in Medicine and Biology. Guidelines for the safe use of Doppler ultrasound for clinical applications. Report from the European Committee for Ultrasound Radiation Safety. Eur J Ultrasound 1995;2:167–8.

19. European Federation of Societies for Ultrasound in Medicine and Biology. Clinical safety statement for diagnostic ultrasound. Report from the European Committee for Ultrasound Radiation Safety. Eur J Ultrasound 1996;3:283.

Doppler in Obstetrics
Copyright © 2002 by Kypros Nicolaides, Giuseppe Rizzo, Kurt Hecker and Renato Ximenes
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