Langevin's Ultrasonic Metrology.

This article proposes that Paul Langevin should be considered the originator of ultrasonic metrology. He established the theoretical foundation for the use of radiation pressure for the measurement of acoustic power, by considering the energy density at a target in a beam. This approach was used for calibrating the ultrasonic transducers he helped to develop for submarine detection and underwater communications during the First World War (WWI). Within a decade, he developed two calibrated devices to measure acoustic power and average intensity, a torsion balance, and the first electronic power meter. He patented a piezoelectric non-resonant quartz hydrophone and a quartz probe to explore transducer surface vibration. Design criteria for the instruments included a rugged design that could allow measurements to be carried out not only in the laboratory but also at sea. Langevin was also influential in establishing an ultrasonics transducer laboratory in Toulon in 1923 where these instruments were used. New quartz pulse-echo transducer designs were developed and evaluated there, and performance certification was provided for manufactured transducers for both naval and civil systems. Early workers in ultrasonics recognized Langevin's original and pioneering contributions, which were the enabling technology for modern ultrasonic metrology.

The origins of medical physics.

The historical origins of medical physics are traced from the first use of weighing as a means of monitoring health by Sanctorius in the early seventeenth century to the emergence of radiology, phototherapy and electrotherapy at the end of the nineteenth century. The origins of biomechanics, due to Borelli, and of medical electricity following Musschenbroek's report of the Leyden Jar, are included. Medical physics emerged as a separate academic discipline in France at the time of the Revolution, with Jean Hallé as its first professor. Physiological physics flowered in Germany during the mid-nineteenth century, led by the work of Adolf Fick. The introduction of the term medical physics into English by Neil Arnott failed to accelerate its acceptance in Britain or the USA. Contributions from Newton, Euler, Bernoulli, Nollet, Matteucci, Pelletan, Gavarret, d'Arsonval, Finsen, Röntgen and others are noted. There are many origins of medical physics, stemming from the many intersections between physics and medicine. Overall, the early nineteenth-century definition of medical physics still holds today: 'Physics applied to the knowledge of the human body, to its preservation and to the cure of its illnesses'.

Thermally-mediated ultrasound-induced contraction of equine muscular arteries in vitro and an investigation of the associated cellular mechanisms.

We have previously shown that MHz frequency ultrasound causes contraction of the carotid artery in vitro. We now extend this investigation to equine mesenteric arteries and investigate the cellular mechanisms. In vitro exposure of the large lateral cecal mesenteric artery to 4-min periods of 3.2 MHz continuous wave ultrasound at acoustic powers up to 145 mW induced reversible repeatable contraction. The magnitude of the response was linearly dependent on acoustic power and, at 145 mW, the mean increase in wall stress was 0.020 ± 0.017 mN/mm(2) (n = 34). These results are consistent with our previous study and the effect was hypothesised to be thermally mediated. A 2°C temperature rise produced an increase in intracellular calcium, measured by Fluo-4 fluorescence. Inhibition of the inward-rectifier potassium ion channel with BaCl(2) (4 µM) increased the response to ultrasound by 55% ± 49%, indicating a similar electrophysiologic basis to the response to mild hyperthermia. In small mesenteric arteries (0.5-1.0 mm diameter) mounted in a perfusion myograph, neither ultrasound exposure nor heating produced measureable vasoconstriction or a rise in intracellular calcium and we conclude that temperature-sensitive channels are absent or inactive in these small vessels. It, therefore, appears that response of blood vessels to ultrasound depends not only on the thermal properties of the vessels and surrounding tissues but also on the electrophysiology of the smooth muscle cells.

Three-dimensional ultrasound imaging of mammary ducts in lactating women: a feasibility study.

OBJECTIVE: The main function of the breast is to produce milk for offspring. As such, the ductal system, which carries milk from the milk-secreting glands (alveoli) to the nipple, is central to the natural function of the breast. The ductal system is also the region in which many malignancies originate and spread. In this study, we aimed to assess the feasibility of manual mapping of ductal systems from 3-dimensional (3D) ultrasound data and to evaluate the structures found with respect to conventional understanding of breast anatomy and physiology. METHODS: Three-dimensional ultrasound data of the breast were acquired using a mechanical system, which captures data in a conical shape covering most of the breast without excessive compression. Manual mapping of the ductal system was performed using custom software for data from 4 lactating volunteers. RESULTS: Observational results are presented for ultrasound data from the 4 lactating volunteers. For all volunteers, only a small number of ductal structures were engorged with milk, suggesting that the lactiferous activity of the breast may be localized. These enlarged ducts were predominantly found in the inferior lateral quadrant of each breast. The observation was also made that the enlarged, milk-storing parts of the duct were spread throughout the ductal system and not directly below the nipple as conventional anatomy suggests. CONCLUSIONS: Ultrasound visualization of the 3D structure of milk-laden ducts in an uncompressed breast has been shown. Using manual tracing, it was possible to track milk-laden ducts of diameters less than 1 mm.

Ultrasound-induced contraction of the carotid artery in vitro.

Ultrasound is known to produce a range of nonlethal responses in cells and tissues. Frequencies in the kilohertz ultrasound range have been shown to produce relaxation in large arteries. The present work explores the effects of insonation at MHz frequencies, representative of those used diagnostically and therapeutically, in an in vitro preparation of the carotid artery. Fresh 12.7 mm wide rings of equine common carotid artery obtained from the abattoir were mounted in a purpose-made myograph. They were immersed in a bath of Krebs-Ringer buffer at 37 degrees C and were positioned at the focus of an ultrasound beam from a weakly focused 3.2 MHz source. Continuous wave insonation produced contraction. The tension increased rapidly over the first 2 min, followed by a slower increase for the duration of the exposure up to 15 min. At a power of 145 mW a maximum contractile stress of 0.04 +/- 0.03 mN/mm(2) (mean +/- SD, n = 77) was measured, which was approximately 4% of the maximum wall stress generated by noradrenaline (0.1 mM). The magnitude of the response was weakly dependent on power in the range 72-145 mW and was not significantly different for pulsed and continuous wave stimulation where time averaged power was constant. The response was unaffected by mechanical removal of the endothelium. The ultrasound beam generated insufficient radiation force to produce a measurable effect and streaming at the vessel surface was very small compared with flow rates known to produce physiologic effects. The temperature rise at the beam focus was approximately 0.3 degrees C and we hypothesise that this contributes to the observed response, probably through changes in ion channel activity in smooth muscle cell membranes. (E-mail: e.martin@exeter.ac.uk).

Hazards, risks and safety of diagnostic ultrasound.

The safety of exposure to diagnostic ultrasound is evaluated using a structured approach to risk assessment, based on the acoustic output of present ultrasound scanners. Thermal hazard is described, the magnitude and probability of temperature rise is reviewed, and the severity of harm from any outcome is reviewed. Similar assessments are made separately for acoustic cavitation and gas-body effects, which have previously been considered together. Finally, radiation pressure is considered in a similar manner. In each case, means to minimize the risk are suggested where appropriate. The highest risks are associated with the use of gas-bubble contrast agents. It is concluded that there is a medium risk associated with trans-cranial Doppler use, and that this use of ultrasound deserves more detailed safety review. The risks associated with the current practice of obstetric ultrasound are low. Whilst the severity of radiation pressure as a hazard is low, it is always present. Little is known about any associated cell responses and so the associated risk cannot be evaluated.

Fetal thermal effects of diagnostic ultrasound.

Processes that can produce a biological effect with some degree of heating (ie, about 1 degrees C above the physiologic temperature) act via a thermal mechanism. Investigations with laboratory animals have documented that pulsed ultrasound can produce elevations of temperature and damage in biological tissues in vivo, particularly in the presence of bone (intracranial temperature elevation). Acoustic outputs used to induce these adverse bioeffects are within the diagnostic range, although exposure times are usually considerably longer than in clinical practice. Conditions present in early pregnancy, such as lack of perfusion, may favor bioeffects. Thermally induced teratogenesis has been shown in many animal studies, as well as several controlled human studies; however, human studies have not shown a causal relationship between diagnostic ultrasound exposure during pregnancy and adverse biological effects to the fetus. All human epidemiologic studies, however, were conducted with commercially available devices predating 1992, that is, with acoustic outputs not exceeding a spatial-peak temporal-average intensity of 94 mW/cm2. Current limits in the United States allow a spatial-peak temporal-average intensity of 720 mW/cm2 for fetal applications. The synergistic effect of a raised body temperature (febrile status) and ultrasound insonation has not been examined in depth. Available evidence, experimental or epidemiologic, is insufficient to conclude that there is a causal relationship between obstetric diagnostic ultrasound exposure and obvious adverse thermal effects to the fetus. However, very subtle effects cannot be ruled out and indicate a need for further research, although research in humans may be extremely difficult to realize.

Transient elastography using impulsive ultrasound radiation force: a preliminary comparison with surface palpation elastography.

The use of impulsive acoustic radiation force for transient strain imaging was investigated and compared with conventional elastography. A series of experiments were performed to evaluate the performances of the technique on gelatine phantoms containing inclusions and to determine a range of applications where radiation force elastography may be useful compared with static elastography. Slip boundaries and cylindrical inclusions of varying elastic modulus were placed in background materials. A focused ultrasound transducer was used to apply localised radiation force to a small volume of tissue mimic (100 mm3) for durations of 8 ms. A conventional real-time ultrasound imaging probe was used to obtain radio- frequency echo signals. The resulting strains were mapped using ultrasound correlation-based methods. The instantaneous strain immediately following cessation of the radiation force was observed at depth within homogeneous gels and within stiff inclusions. The highly localised and transient strain that is produced at depth permits the sensing of variations in tissue elastic properties that are difficult to detect with conventional elastography, due to greater independence from boundary conditions. In particular, radiation force elastograms were more homogeneous in the background and within the inclusions and displayed a superior contrast-transfer-efficiency, particularly for regions that had negative modulus contrast or that were disconnected from the background or the anterior medium by a low friction boundary.

Medical and non-medical protection standards for ultrasound and infrasound.

Protection from inappropriate or hazardous exposure to ultrasound is controlled through international standards and national regulations. IEC standard 60601 part 1 establishes requirements for the mechanical, electrical, chemical and thermal safety for all electro-medical equipment. The associated part 2 standard for diagnostic medical ultrasonic equipment sets no upper limits on ultrasonic exposure. Instead, safety indices are defined that are intended to advise users on the degree of thermal and mechanical hazard. At present the display of these safety indices satisfies regulatory requirements in both the USA and Europe. Nevertheless there are reservations about the effectiveness of this approach to protection management. In the USA, there are national regulatory limits on diagnostic exposure, based on acoustic output from clinical equipment in use over 20 years ago. The IEC 60601 part 2 standard for therapeutic equipment sets 3 W cm(-2) as the limit on acoustic intensity. Transducer surface temperature is controlled for both diagnostic and therapy devices. For airborne ultrasound, interim guidelines on limits of human exposure published by the IRPA are now 2 decades old. A limit on sound pressure level of 100 dB for the general population is recommended. The absence of protection standards for infrasound relates to difficulties in measurement at these low frequencies.

Elastography for breast cancer diagnosis using radiation force: system development and performance evaluation.

The use of impulsive acoustic radiation force for strain imaging was investigated. A focused ultrasound transducer was used to apply localized radiation force to a small volume of tissue mimic (100 mm3) for durations of 8 ms. A conventional real-time ultrasound imaging probe was used to obtain echo signals. The resulting strains were mapped using ultrasound correlation-based methods. The instantaneous strain immediately following cessation of the radiation force was observed at depth within homogeneous gels and within stiff inclusions, and was seen to vary approximately linearly with Young's modulus of the material. The highly localized and transient strain that is produced may permit the sensing of variations in tissue elastic properties that are difficult to detect with conventional elastography because of greater independence from boundary conditions. For example, the characteristic, bi-directional, high strain artefacts attributable to stress concentration, often seen with static elastography at tissue-inclusion interfaces, do not appear using the transient radiation force strain imaging technique.

Broadband attenuation and nonlinear propagation in biological fluids: an experimental facility and measurements.

The design and construction of a versatile experimental facility for making measurements of the frequency-dependence of attenuation coefficient (over the range 1 MHz to 25 MHz) and nonlinear propagation in samples of biological fluids is described. The main feature of the facility is the ability to perform all of the measurements on the same sample of fluid within a short period of time and under temperature control. In particular, the facility allows the axial development of nonlinear waveform distortion to be measured with a wideband bilaminar polyvinylidene difluoride membrane hydrophone to study nonlinear propagation in biological fluids. The system uses a variable length bellows to contain the fluid, with transparent Mylar end-windows to couple the acoustic field into the fluid. Example results for the frequency-dependence of attenuation of Dow Corning 200/350 silicone fluid, used as a standard fluid, are presented and shown to be in good agreement with alternative measurements. Measurements of finite amplitude propagation in amniotic fluid, urine and 4.5% human albumin solutions at physiological temperature (37 degrees C) are presented and compared with theoretical predictions using existing models. The measurements were made using a 2.25-MHz single-element transducer coupled to a polymethyl methacrylate lens with a focal amplitude gain of 12 in water. The transducer was driven with an eight-cycle tone burst at source pressures up to 0.137 MPa. In general, given an accurate knowledge of the medium parameters and source conditions, the agreement with theoretical prediction is good for the first five harmonics.

Broadband measurements of the frequency dependence of attenuation coefficient and velocity in amniotic fluid, urine and human serum albumin solutions.

The frequency dependence of attenuation coefficient in amniotic fluid, urine and 4.5% and 20% human serum albumin solutions over the frequency range 5 MHz to 25 MHz was measured at both room temperature and physiological temperature using a variable path length technique. A 15 MHz (13 mm diameter) transducer was used to produce a broadband single-cycle pulse and a 4 mm diameter bilaminar polyvinylidene difluoride membrane hydrophone was used to detect the attenuated pulse. Standard time-of-flight measurement techniques were used to measure the acoustic velocity in the same fluid samples. At physiological temperature, the attenuation coefficients in amniotic fluid, urine and 4.5% and 20% human albumin solution were found to be 0.0053 f(1.65), 0.0047 f(1.67), 0.019 f(1.57) and 0.167 f(1.27) dB cm(-1), respectively, where f is in MHz. The velocities in amniotic fluid, urine and 4.5% human albumin solution at physiological temperature were found to be 1541.1 m s(-1) +/- 1.3 m s(-1), 1551.3 m s(-1) +/- 1.3 ms(-1) and 1547.3 m s(-1) +/- 1.0 m s(-1), respectively. The results provide unique data over the diagnostic and therapeutic ultrasonic frequency range that can be used as input data for theoretical models that attempt to simulate nonlinear pressure fields and temperature rises from medical ultrasonic transducers.

The cooling effect of liquid flow on the focussed ultrasound-induced heating in a simulated foetal brain.

There is a need to investigate the thermal effects of diagnostic ultrasound (US) to assist the development of appropriate safety guidelines for obstetric use. The cooling effect of a single liquid flow channel was measured in a model of human foetal brain and skull bone heated by a focussed beam of simulated pulsed spectral Doppler US. Insonation conditions were 5.7 micros pulses, repeated at 8 kHz from a focussed transducer operating with a centre frequency of 3.5 MHz, producing a beam of -6 dB diameter of 3.1 mm at the focus and power outputs of up to 255 +/- 5 mW. Brain perfusion was simulated by allowing distilled water to flow at various rates in a 2 mm diameter wall-less channel in the brain soft tissue phantom material. This study established that the cooling effect of the flowing water; 1. was independent of the acoustic source power, 2. was more effective close to the flow channel, for example, there was a marked cooling at a distance of 1 mm and negligible cooling at a distance of 3 mm from the channel; and 3. initially increased at low flow rates, but further increase above normal perfusion had very little effect.

Ultrasound-induced heating in a foetal skull bone phantom and its dependence on beam width and perfusion.

The cooling effect of single and multiple perfusing channels has been measured in a model of human foetal skull bone heated by wide and narrow beams of simulated pulsed spectral Doppler ultrasound (US). A focussed transducer operating with a centre frequency of 3.5 MHz, that emitted pulses of 5.7 micros duration with a repetition frequency of 8 kHz, was used. This produced a beam of power 100 +/- 2 mW with -6 dB diameters of 3.1 mm and 7.8 mm at 9 cm and 6 cm, respectively, from the transducer face. Arterial perfusion was simulated by allowing distilled water to flow in a large single channel or a grid of fine channels near the heated bone target. This study has established that: 1. perfusion-induced cooling is significantly enhanced when the bone phantom is heated by a wide rather than a narrow beam; 2. irrespective of the US beam width, a grid of small channels is more effective in cooling a heated bone target than a single larger diameter channel with the same volume flow rate; 3. the measured temperature rise and rate of temperature rise support the prediction of inverse proportionality to the US beam width; and 4. the perfusion time constants determined in our phantom model are 2 to 30 times larger than that assumed for the thermal index (TIB) algorithm.

Nonlinear acoustics in diagnostic ultrasound.

The propagation of ultrasonic waves is nonlinear. Phenomena associated with the propagation of diagnostic ultrasound pulses cannot be predicted using linear assumptions alone. These include a progressive distortion in waveform, the generation of frequency harmonics and acoustic shocks, excess deposition of energy and acoustic saturation. These effects occur most strongly when ultrasound propagates within liquids with comparatively low acoustic attenuation, such as water, amniotic fluid or urine. Within soft tissues, similar effects occur, although they are limited by absorption and scattering. Nonlinear effects are of considerable importance during acoustic measurements, especially when these are used to predict in situ exposure. Harmonic generation may be used to create images. These offer improvements over conventional B-mode images in spatial resolution and, more significantly, in the suppression of acoustic clutter and side-lobe artifacts. B/A has promise as a parameter for tissue characterisation, but methods for imaging B/A have shown limited success.