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Ultrasonics: A window into biomedical science
ultrasonics: P.N.T.
a window
into biomedical
science
Wells
Department
of Medical
and Department BSI 6SY. UK
Physics and Bioengineering,
of Clinical
Radiology,
University
United
Bristol Healthcare
of Bristol, Bristol General
NHS
Hospital,
Trust Bristol
Ultrasonics has always been concerned with biomedical research. When the journal started, most applications were in therapy and surgery, but diagnosis soon became dominant. Many key developments received early publication: these included Doppler ultrasound, real-time imaging, tumour neovascularization and, arguably most significant of all, phased array scanning. Now in its thirtieth year of publication, Ultrasonics has contributed greatly to the development of biomedical science and it promises to have an important continuing role. Keywords:
biomedicine;
bioeffects;
tissue properties;
The masthead of Ultrasonics states that it is ‘the world’s leading journal devoted solely to the whole science and technology of ultrasound’. As the journal enters its thirtieth year of publication, it has established this position by developing a reputation for careful peer review, rapidity and quality of production, timeliness, internationality and breadth of coverage. Thus, although there are several other specialist journals to which biomedical ultrasonic researchers can consider sending their papers, Ultrasonics often seems to them to be clearly the right place to report their work. Examination of the 29 volumes of the journal consequently provides a unique window through which a reader can observe the evolution of the whole of this important aspect of ultrasonic science over the last 30 years.
The
early
years
The first article in the very first issue of Ultrasonics was on a medical subject. In 1963, the development of ultrasonic diagnosis was in its infancy and it was in therapeutic and surgical applications that ultrasound was important. One of these fashionable surgical applications was the treatment of Miniere’s disease’, in which ultrasound in the low megahertz frequency range was applied directly to one of the semicircular canals, usually after a surgical approach through the mastoid process of the temporal bone. Equipment was required to measure the ultrasonic power; the calorimeters and radiation force balances that were used were described in the second issue of the journal’. This second issue also contained a review of the use of ultrasound in agriculture3, in which ultrasonic methods for increasing the germination of seeds and growth rates and yields of crops were described, along with the use of ultrasound to accelerate metabolic processes and to destroy bacteria, viruses and fungi. There was also a mention of the ultrasonic control of insect pests and the measurement of hackfat thickness in meat
0041-624X/92/010003-05 @ 1992 Butterworth-Heinemann
Ltd
instrumentation
animals. Eight years later, the same author reviewed the beneficial effects of ultrasound on plants4. Although ultrasonic diagnosis was still in its infancy in 1963, researchers chose to publish their results in Ultrasonics soon after the journal began to appear. The third issue had two such articles: these were concerned with two-dimensional echoencephalography and ophthalmic diagnosi@. Although the ophthalmic applications have continued to evolve to the present day, the advent of X-ray computed tomography (CT) was virtually (but perhaps only temporarily) to halt progress in ultrasonic studies of the brain in the intact skull. In 1963, however, the invention of CT was still a decade ahead. From the beginning, the journal has included conference reports. The very first issue had two reports of medical meetings, one of which was, in retrospect, a key event in the development of medical ultrasound’. This was Ultrasound as a Diagnostic and Surgical Tool, organized by Douglas Gordon in London, 5-6 December 1962. Although the dates chosen coincided with one of the worst of London’s fogs so that many would-be participants were unable to attend. there were contributors from Australia, Germany, Italy, Sweden, the USA and the USSR, as well as the UK. It was agreed that similar meetings should in future be organized by the British Institute of Radiology in association with the Hospital Physicists’ Association. This was an important milestone in the gestation of what is now the British Medical Ultrasound Society. Volume 2 of the journal established the important role that it was to have as a vehicle in the development of biomedical ultrasound. There were papers on echo sounding for fish8,9 (a subject still very much alive in the journal 20 years laterlo), the detection of animal ultrasound”, a mobility aid for the blind”, the measurement of ultrasonic power in the milliwatt rangel and ultrasonic propagation in ocular tissues14. In addition, two articles of great significance in the development of diagnostic ultrasound were published in
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Ultrasonics:
a window
into biomedical
science:
P. N. 1. Wells
the journal in 1964. In the first of these, George Kossoff and his colleagues” demonstrated that it is the spot size of the display that should be used as the design criterion in ultrasonic visualization systems. The spot size sets limits on the performance required from the transducer, the scanner, the deflexion system and the receiver. The second key paper was the first accessible publication in English of the development of intravenous probes that had been carried out in Japan64. Although there have been a few sporadic efforts to emulate this, it is really only within the last five years or so that the approach has really been taken seriously and its clinical value has begun to be widely appreciated. Thus, by the beginning of 1965, Ultrasonics was well recognized by the then small and close-knit biomedical community interested in this emerging science. During the next few years, numerous important developments were reported in the journal. What was probably the first sector scanner using an array of transducers was described but hardly noticed in a paper on ophthalmology’7. There was a review of ultrasonic physiotherapy”. There was an early discussion of artefacts in ultrasonic scans r9. Improvements in ultrasonic foetal cephalometry were described”. In 1966, the journal contained four papers in a special medical ultrasonics section. Even more significantly, two of these papers21v22 were devoted to the study of blood flow and were amongst the first publications to bring the Japanese discovery of the ultrasonic Doppler effect to the attention of the English-sneaking scientific community. Despite the record number of authors (nine) and unusual brevity (one and a half pages) of the paper concerned with Doppler signals from solid tissues22, this application has hardly progressed; but the study of blood flow21 was a precursor to what is now of the utmost clinical importance. Likewise, one of the other two papers was on the esoteric use of ultrasound to measure changes in mesenteric blood volume in a dog23, whilst the other was on resolution enhancement using a large aperture24 and is a largely forgotten foundation of modern high performance imaging systems. This latter paper contained the prophetic statement that ‘the chief limitation on (medical) image resolution will be changes of velocity within complex tissues’. The special section on medical ultrasonics that was published in 1966 was a prelude to the special medical issue that appeared in April 1967. This consisted of 13 articles which to a large extent reflected the contemporary preoccupations with obstetrics, cardiology, ophthalmology and (now apparently misguidedly) echoencephalography and neurosurgery. With the benefit of hindsight, there were two really important papers in this issue of the journal. The first was concerned with ultrasonic ‘cinematography’ of the living heart: a mechanical scanner2’ was described that could produce pictures at a frame rate of seven per second, and which was arguably the first ‘real-time’ imaging system. The other, by Tom Brown26 described the visualization of soft tissues in three dimensions; although the system was slow and the significance of the results were shamelessly uncomprehended by many people at the time, subsequent developments have shown that Brown was a victim of being much in advance of his time and, in fact, a visionary whose inventiveness only received recognition through election to honorary membership of the British Medical Ultrasound Society nearly 20 years later.
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Ultrasonics
International
Under the sponsorship of the journal, a meeting on Ultrasonics for Industry was held in 1967: this was the first stage in the evolution of the present Ultrasonics International conference series. Some papers from the 1967 meeting were published in 1968; onez7 dealt with the design of medical ultrasonic equipment and is really the best description in the open literature of the diasonograph, the instrument with which Ian Donald did such wonderful work and which first popularized diagnostic ultrasound in the early 1960s. Ultrasonics International continues to the present day but that is another story.
Clinical
radiology
Although Ultrasonics is primarily a basic science and engineering journal, occasionally it has served as the depository for purely clinical papers. The first of these was published in 1967 and was devoted to the role of ultrasonic imaging in the diagnosis of thyroid diseases28. Although similar articles have since appeared from time to time, it has to be admitted that they sometimes seem ill at ease alongside their more traditional partners and, perhaps sadly, the good ones usually have had to be drawn to the attention of busy clinicians who tend only to read their own specialist journals. The journal has a reputation for rapid publication and therefore it has always been attractive to those wishing to establish precedence in new research. For example, the discovery of the characteristic ultrasonic Doppler blood flow signals from malignant tumours was first reported in Ultrasonics in 197729, less than six months after the original experiments.
Bioeffects From the earliest days of medical diagnostic ultrasound, the question of bioeffects and safety has been important. The journal has published numerous papers in this area, beginning with a study of the effect of ultrasound on the brain3’: the results were negative. A useful paper on the measurement of peak acoustic intensity appeared in 196931. There was an analysis of the oscillation of a vibrating capillary in the context of its bioeffects32. One of the early publications on ultrasonic haemolysis appeared in 1970 33. In 1976, the journal had an article on the ultrasonic stimulation of the healing of varicose ulcers34 Four years later, cavitational bioeffects were reviewed3’. Then, in 1985, a plane layered model was analysed in terms of in situ ultrasound exposures3”. In the 1987 special issue on sonochemistry there was an article on the evidence for free radicals produced in aqueous solutions by diagnostic ultrasound37; the conclusions were rather alarmist. Happily, a negative result was obtained in a search for an ultrasonic effect on mitotic index38 and the ultrasonic enhancement of diffusion through skin 39 is not a cause for concern. In 1990, a special issue (edited by Roy Williams4’) was devoted to ultrasonic bioeffects. It contained eleven papers which, as the editor wrote ‘help to correct some previous errors of interpretation as well as providing some new experimental evidence which takes us a few small steps closer to our ultimate goal of being able properly to assess the potential hazards associated with
Ultrasonics:
the uses of ultrasound in medicine’. It is with this sentiment in mind that three subsequent papers41V42,43 need to be read. Properties
of tissues
Data on the acoustic properties of tissues have been published in the journal. The first such paper appeared in 197144: it presented values of propagation speed in body fluids and brain tumours as measured by a sing-around system. Subsequently, the results of measurements of speed and attenuation in various tissues were published in 197745 and some data for bone were presented in 198146. In 1986, a pulse freq uency spectral shift method for in oiuo measurement of attenuation was described47 and data on post rigor bovine skeletal muscle4* and homogenated muscle49 were presented. In the same year, the potential for characterizing biological media by means of their non-linearities was reviewed5’ and the zero-crossing counting method for estimating attenuation in tissue was analysed”. The dependence of speed on water content and tissue structure was studied in 198752. A key paper on ultrasonic wave fluctuations through tissue appeared a year later53, thus taking up again the prediction made in the journal 20 years before24 that this phenomenon would limit the performance of imaging systems. Diagnostic
instrumentation
Of all the biomedical ultrasonic papers published over the years in the journal, arguably the most significant is that of Jan Somers4 in which he first described electronic sector scanning by means of a phased array transducer designed for medical diagnosis. This array, which operated at 1.5 MHz, consisted of 21 elements. On transmission, the beam was steerable within a 90“ sector and it was proposed that the necessary time delays on reception could be provided by electrically variable delay lines. Twenty years later, two articles in the journal discussed the influence of errors in amplitude55 and phase56 on the performance of beam-steered arrays. Another 1968 paper57 described the first water-immersion scanner for two-dimensional breast imaging in which the patient was prone; this arrangement was subsequently adopted in several commercially developed systems. Indeed, in 1973 the journal carried an article on velocity compensation with this technique58. Maintaining the tradition of publishing comprehensive technical descriptions of medical diagnostic systems, 1969 saw a paper on a time-to-voltage analogue converter for ultrasonic cardiology59. In 1972, the first catheter-tip array for intracardiac scanning was described6’: the device consisted of 32 elements in a cylinder with an outer diameter of only 3 mm. Also in 1972, for the first time in the open literature George Kossoff identified the grey scale display as a method of improving the clinical value of twodimensional scanning6i; nowadays, it is accepted as a sine qua non. Other developments reported in the journal included automatic sensitivity control in two-dimensional scanning62, B-scanning and holography in ophthalmic diagnosis63, a directional detector for ultrasonic Doppler blood flow signal analysis64, the ultrasonic fluctuation velocimeter(j5, the use of transducer groups to improve beam shape in linear array scanning@j and an early mechanically oscillated scanning system for two-
a window
into biomedical
science:
P. N. T. Wells
dimensional imaging67. The journal published the pioneering work on the use of spectral analysis to determine basic tissue properties in differential diagnosis’j8. The adaptive correlation ratemeter, now widely used in ultrasonic foetal heart-rate monitors, was described in 1978’j9. Technical details of a tremendously successful servo-controlled mechanical real-time sector scanner were also published in 19787o. Three years later, speckle in ultrasonic imaging was discussed and its reduction by incoherent image summation was described7i; and in 1986, speckle reduction by adaptive filtering was introduced72, to be followed by real-time implementation of the technique in 199173. In 1985, a paper was published dealing with the acoustic matching of medical ultrasound transducers74. This year also saw the beginning of a series of four articles on transducers in medical ultrasound, dealing with materials75, vibration modes, matching layers and grating 10bes~~,applications in echocardiology and safety 78. The first of a series of papers on ultrasonic waveguides was published in 198879, followed by others in 198980 and 199181. Most recently, the status of ultrasonic contrast agents has been reviewed82: these materials are likely to become very significant. The vector problem in ultrasonic Doppler studies of blood flow remains important; two-dimensional time domain processing 83, however, is an alternative approach which, although computationally demanding, offers a feasible solution. Also in 1989, the medical application of research extending over more than 15 years into time delay spectrometry was described84. Another recent and significant Doppler paper has analysed the effect of frequency dependent processes on the geometry of the sample volume’ 5. The future The tenth anniversary issue of the journal (January 1973) carried a little piece entitled ‘What future for biomedical ultrasonics?‘86. It recognized that ultrasonic diagnosis had been placed on firm scientific ground and correctly forecast an important role for digital techniques. It predicted that there would be 400 major scanning systems in the UK by 1982. Probably there were; there are about 2000 now. Then in 1983, R.W.B. Stephens reviewed 20 years of Ultrasonicss7 in a characteristically modest way. Of particular interest to ‘human needs’, he identified the importance of ‘the medical and biological applications of ultrasonic diagnosis and therapeutics’, predicting that ‘with improved instrumentation and techniques it may be possible to give, for example, earlier warning of disease’. This has certainly turned out to be the case already but there is no end in sight to the ways in which advances can continue to be made. These advances will depend, in the future as much as they have in the past, on the spread of knowledge. In this, Ultrasonics will surely have a leading role. References 1
2
3
Bullen, M.A., Wells, P.N.T., Freundlich, H.F. and James, J.A. A physical survey of the ultrasonic treatment of Mtnitre’s disease Ultrasonics (1963) 1 2-S Wells, P.N.T., Bullen, M.A., Follett, D.H., Freundlich, H.F. and James, J.A. The dosimetry of small ultrasonic beams Ultrasonics (1963) 1 106-110 Gordon, A.G. The use of ultrasound in agriculture Ultrasonics (1963) 1 70-77
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Gordon, A.G. Beneficial effects of ultrasound on plants - a review Ukrusanics (1971) 9 88-94 de Vlieger, M., de Sterke, A., Molin, C.E. and van der Ven, C. Ultrasound for two-dimensional echo-encephalography Ultrasonics (1963) 1 148-151 Freeman, M.H. Ultrasonic pulse-echo techniques in ophthalmic examination and diagnosis Ultrasonics (1963) 1 152-160 Gordon, D. Ultrasound as a diagnostic and surgical tool Ultmsonics (1963) 1 56-57 Haslett, R.W.G. Physics applied to echo sounding for fish Ulrrasonics ( 1964) 2 1- 11 Hopkin, P.R. and Haslett, R.W.G. A new ultrasonic lish-detection equipment for trawlers Ultrasonics (1964) 2 65-70 Do, M.A. and Surti, A.M. Accumulative uncertainties in the quantitative evaluation of signals from fish UItrusonics (1982) 20 217-223 Pye, J.D. and Flinn, M. Equipment for detection of animal ultrasound Uhsonics (1964) 2 23-28 Kay, L. An ultrasonic sensing probe as a mobility aid for the blind Ultrasonics (1964) 2 53-59 Wells, P.N.T., Bullen, M.A. and Freundlich, H.F. Milliwatt ultrasonic radiometry Ultrasonics (1964) 2 124- 128 Greguss, P. Ultrasonic propagation in the heterodispersive media of the eye Ultrasonics (1964) 2 134-136 Kossoff, G., Robinson, D.E., Liu, C.N. and Garrett, W.J. Design criteria for ultrasonic visualization systems Ultrusonic,s (1964) 2 29-38 Kimoto, S., Omoto, R., Tsunemoto, M., Muroi, T., Atsumi, K. and Uchida, R. Ultrasonic tomography of the liver and detection of heart atria1 septal defect with the aid of ultrasonic intravenous probe Ultrasonics (1964) 2 82-88 Buschmann, W. New equipment and transducers for ophthalmic diagnosis Ultrasonics (1965) 3 18-21 Patrick, M.K. Ultrasound in physiotherapy UItrusonics (1966) 4 10-14 Robinson, D.E., Kossoff, G. and Garrett, W.J. Artefacts in ultrasonic echoscopic visualization Ultrasonics ( 1966) 4 186- 194 Hall, A.J., Fleming, J.E. and Abdulla, U. Ultrasonic fetal cephalometry - some improvements and future developments Ulrrasonics ( 1970) 8 34-35 Kaneko, Z., Shiraishi, J., Omizo, H., Kato, K.. Motomiya, M., Izumi, T. and Okumura, T. Analysing blood flow with a sonograph Ultrusonics (1966) 4 22-25 Yoshitoshi, Y., Machii, K., Sekiguchi, H., Mishina, Y., Ohta, S., Hanaoka, Y., Kohashi, Y., Shimuzi, S. and Kuno, H. Doppler measurement of mitral valve and ventricle wall velocities UItrusonics (1966) 4 27-28 Mullins, G.L. and Guntherotb, W.G. Continuous recording of changes in mesenteric blood volume Ultrasonics (1966) 4 24-25 Tburstone, F.L. and McKinney, W.M. Resolution enhancement in scanning of tissue Ultrasonics (1966) 4 25-27 Asberg, A. Ultrasonic cinkmatography of the living heart C’ltrusonics (1967) 5 113-l 17 Brown, T.G. Visualization of soft tissue in two and three dimensions limitations and development Ultrusonics ( 1967) 5 118-124 Brown, T.G. Design of medical ultrasonic equipment Ultrasonics (1968) 6 107-111 Fujimoto, Y., Oka, A., Omoto, R. and Hirose, M. Ultrasonic scanning of the thyroid gland as a new diagnostic approach Ultrasonics ( 1967) 5 177- 180 Wells, P.N.T., Halliwell, M., Skidmore, R., Webb, A.J. and Woodcock, J.P. Tumour detection by ultrasonic Doppler bloodflow signals Ultrasonics (1977) 15 231-232 Garg, A.G. and Taylor, A.R. An investigation into the effect of pulsed ultrasound on the brain Ultrusonics (1967) 5 208~212 Kossoff, G. The measurement of peak acoustic intensity generated bv nulsed ultrasonic equipment Ultrasonics (1969) 7 249%251 Williams, A.R. and Nyborg, W.L. Microsonation using a transverselv oscillating capillarv Ultrusonics (1970) 8 36 -38 Howkins, S:D. and Weinstock, 6. The effect of focussed ultrasound on human blood Uilrrasonics (1970) 8 174-176 Dvson, M.. Franks, C. and Suckling, J. Stimulation of healing of varicose ulcers by ultrasound Ulrrusonics (1976) 14 232-236 Graham. E.. Hedges. M., Leeman, S. and Vaughan, P. Cavitational bioetTec& at 1.5 GHz Ultrusonics (1980) 18 225-228 Smith, S.W., Stewart, H.F. and Jenkins, D.P. A plane layered model to estimate in situ ultrasound exposures Ultrasonics ( 1985) 23 31-40 Christman, C.L., Carmichael, A.J., Mossoka, M.M. and Riesz, P. Evidence for free radicals produced in aqueous solutions by
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diagnostic ultrasound Ultrasonics (1987) 25 31-34 Miller, M.W., Church, C.C. and Cox. C. Lack of effect of continuous wave ultrasound exposure on in viva Chinese hamster cheek pouch epithelial mitotic index Ultrasonics (1988) 26 277-279 Mortimer, A.J., Trollopc, B.J., Villeneuve, E.J. and Roy, O.Z. Ultrasound-enhanced diffusion through isolated frog skin Ultrasonics (1988) 26 348-351 Williams, A.R. Editorial Ultrasonics (1990) 28 131 Suneetha, N. and Kumar, R.P.S. Enzymatic studies in foetal brain and liver of mouse following in utero exposure to ultrasound Ultrusonics (1991) 29 257-260 Cardinale, A., Lagalla, R., Giambanco, V. and Aragona, F. Bioeffects of ultrasound: an experimental study on human embryos Ultrasonics (1991) 29 261-263 Watmough, D.J., Davies, H.M., Quan, K.M., Wytch, R. and Williams, A.R. Imaging microbubbles and tissues using a linear focussed scanner operating at 20 MHz: possible implications for the detection of cavitation thresholds Ultrasonics (1991) 29 312-317 van Venrooij, G.E.P.M. Measurement of ultrasound velocity in human tissue Ultrasonics (1971) 9 240-242 Bhagat, P., Kadaba, M., Ware, R. and Cockerill, W. Frequency dependence of acoustic parameters of freshly excised tissues of Sprague-Dawley rats Ultrasonics (1977) 15 179-182 Behari, J. and Singh, S. Ultrasound propagation in ‘in Coo bone Ultrusonics (1981) 19 87-90 Ferrari, L., Jones, J.P. and Gonzalez, V.M. In do measurement of attenuation Ultrasonics (1981) 24 66-72 Shore, D., Woods, M.O. and Miles, C.A. Attenuation of ultrasound in post rigor bovine skeletal muscle Ultrasonics (1986) 24 81-87 Wood, M.O. and Miles, C.A. Ultrasound speed and attenuation in homogenates of bovine skeletal muscle UIrrusonics ( 1986) 23 260-266 Bjerne, L. Characterization of biological media by means of their non-linearity Ultrasonics (1986) 24 254-259 Deurinckx, A.J., Ferrari, L.A., Hoefs, J.C., Sankar, P.V., Fleming, D. and Cole-Beuglet, C. Estimation of acoustic attenuation in liver using one megabyte of data and the zero-crossings technique Ultrasonics (1986) 24 325-332 Sarvazyan, A.P., Lyrchikov, A.G. and Gorelov, S.E. Dependence of ultrasonic velocity in rabbit liver on water content and structure of the tissue Ultrasonics (1987) 25 244-247 Aindow, J.D. and Chivers, R.C. Ultrasonic wave fluctuations through tissue: an experimental pilot study Ultrasonics (1988) 26 9op 101 Somer, J.C. Electronic sector scanning for ultrasonic diagnosis Ultrasonics ( 1968) 6 153- 159 Lancbe, C.T., Vissers, J.M., Mientki, S., Ligtvoet, C.M. and Born, N. Influence of amplitude errors on beam-steered phased arrays Ultrasonics (1987) 25 147-153 LancCe, C.T., Vissers, J.M., Mientki, S., Ligtvoet, C.M. and Born, N. Influence of phase errors on beam-steered phased arrays Ultrasonics (1987) 25 154-159 Wells, P.N.T. and Evans, K.T. An immersion scanner for two-dimensional ultrasonic examination of the human breast Ultrasonics (1968) 6 220-228 Jellins, J. and Kossoff, G. Velocity compensation in water-coupled breast echography Ultrasonics (1973) 11 223-226 Wells, P.N.T. and Ross, F.G.M. A time-to-voltage analogue converter for ultrasonic cardiology Ultrasonics ( 1969) 7 17 1 - 176 Born, N., Lancie, C.T. and van Egmond, F.C. An ultrasonic intracardiac scanner Ultrasonics (1972) 10 72-76 Kossoff, G. Improved techniques in ultrasonic cross sectional echography Ultrasonics (1972) 10 221-227 McDicken, W.N., Evans, D.H. and Robertson, D.A.R. Automatic sensitivity control in diagnostic ultrasonics Ultrasonics (1974) 12 173-176 Chivers, R.C. B-scanning and holography in ophthalmic diagnosis Ultrasonics (1974) 12 209-213 de Jong, D.A., Megens, P.H.A., de Vlieger, M., ThGn, H. and Holland, W.P.J. A directional quantifying Doppler system for measurement of transport velocity of blood Ultrasonics (1975) 13 138-141 Atkinson, P. An ultrasonic fluctuation velocimeter Ultrasonics (1975) 13 275-278 Whittingham, T.A. A hand-held electronically switched array for rapid ultrasonic scanning Ultrasonics (1976) 14 29-33 Shaw, A., Paton, J.S., Gregory, N.L. and Wheatley, D.J. A real time two-dimensional ultrasonic scanner for clinical use Ultrasonics (1976) 14 35-40
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Lizzi, F., Katz, L., Louis, L. St. and Coleman, D.J. Applications of spectral analysis in medical ultrasonography Ultrasonics (1976) 14 77-80 Takeuchi, Y. and Hogaki, M. An adaptive correlation ratemeter: a new method for Doppler fetal heart rate measurement Ultrasonics (1978) 16 127-137 Matzuk, T. and Skolnick, M.L. Novel ultrasonic real-time scanner featuring servo controlled transducers displaying a sector image Ultrasonics (1978) 16 171-178 Wells, P.N.T. and Halliwell, M. Speckle in ultrasonic imaging Ultrasonics (1981) 19 225-229 Bamber, J.C. and Daft, C. Adaptive filtering for reduction of speckle in ultrasonic pulse-echo images Ultrasonics (1986) 24 41-44 Bamber, J.C. and Pbelps, J.V. Real-time implementation of coherent speckle suppression in B-scan images Ultrasonics (1991) 29 218-224 Persson, H.W. and Hertz, C.H. Acoustic impedance matching of medical ultrasound transducers Ultrasonics (1985) 23 83-89 Lancbe, C.T., Souquet, J., Ohigasbi, H. and Born, N. Transducers in medical ultrasound: part one. Ferro-electric ceramics versus polymer piezoelectric materials Ultrasonics (1985) 23 138-142 de Jong, N., Souquet, J., Faber, G. and Born, N. Transducers in medical ultrasound: part two. Vibration modes, matching layers and grating lobes Ultrasonics (1985) 23 176-182 Lancbe, C.T., Daigle, R., Sahn, D.J. and Tbijssen, J.M. Transducers in medical ultrasound: part three. Transducer applications in
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echocardiology Ultrasonics (1985) 23 199-205 Wells, P.N.T., de Jong, N., Born, N. and Somer, J. Transducers in medical ultrasound: part four. Transducer safety Ultrasonics (1986) 24 230-232 Nicholson, N.C. and McDicken, W.N. Waveguides in medical ultrasonics Ultrasonics (1988) 26 27-30 Nicholson, NC, McDicken, W.N. and Anderson, T. Waveguides in medical ultrasonics: an experimental study of mode propagation Ultrasonics (1989) 27 101-106 Nicholson, N.C. and McDicken, W.N. Mode attenuation in waveguides used in medical ultrasonics Ultrasonics (1991) 29 133-137 de Jong, N., Ten Cate, F.J., Lancbe, C.T., Roelandt, J.R.T.C. and Born, N. Principles and recent developments in ultrasound contrast agents Ultrasonics (1991) 29 324-330 Trahey, G.E., Hubbard, S.M. and von Ramm, O.T. Angle independent ultrasonic blood flow detection by frame-to-frame correlation of B-mode images Ultrasonics (1988) 26 271-276 Heyser, RX., Hestenes, J.D., Rooney, J.A., Gammell, P.M. and le Croissette, D.H. Medical ultrasound imager based on time delay spectrometry Ultrasonics (1989) 27 31-38 Fish, P.J. and Cope, J.A. Effect of frequency dependent processes on pulsed Doppler sample volume Ultrasonics ( 1991) 29 275-282 Wells, P.N.T. Biomedical ultrasonics Ultrasonics (1973) 11 16 Stevens, R.W.B. Twenty years of Ultrasonics Ultrasonics (1983) 21 9-10
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a window
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science
Wells
Department
of Medical
and Department BSI 6SY. UK
Physics and Bioengineering,
of Clinical
Radiology,
University
United
Bristol Healthcare
of Bristol, Bristol General
NHS
Hospital,
Trust Bristol
Ultrasonics has always been concerned with biomedical research. When the journal started, most applications were in therapy and surgery, but diagnosis soon became dominant. Many key developments received early publication: these included Doppler ultrasound, real-time imaging, tumour neovascularization and, arguably most significant of all, phased array scanning. Now in its thirtieth year of publication, Ultrasonics has contributed greatly to the development of biomedical science and it promises to have an important continuing role. Keywords:
biomedicine;
bioeffects;
tissue properties;
The masthead of Ultrasonics states that it is ‘the world’s leading journal devoted solely to the whole science and technology of ultrasound’. As the journal enters its thirtieth year of publication, it has established this position by developing a reputation for careful peer review, rapidity and quality of production, timeliness, internationality and breadth of coverage. Thus, although there are several other specialist journals to which biomedical ultrasonic researchers can consider sending their papers, Ultrasonics often seems to them to be clearly the right place to report their work. Examination of the 29 volumes of the journal consequently provides a unique window through which a reader can observe the evolution of the whole of this important aspect of ultrasonic science over the last 30 years.
The
early
years
The first article in the very first issue of Ultrasonics was on a medical subject. In 1963, the development of ultrasonic diagnosis was in its infancy and it was in therapeutic and surgical applications that ultrasound was important. One of these fashionable surgical applications was the treatment of Miniere’s disease’, in which ultrasound in the low megahertz frequency range was applied directly to one of the semicircular canals, usually after a surgical approach through the mastoid process of the temporal bone. Equipment was required to measure the ultrasonic power; the calorimeters and radiation force balances that were used were described in the second issue of the journal’. This second issue also contained a review of the use of ultrasound in agriculture3, in which ultrasonic methods for increasing the germination of seeds and growth rates and yields of crops were described, along with the use of ultrasound to accelerate metabolic processes and to destroy bacteria, viruses and fungi. There was also a mention of the ultrasonic control of insect pests and the measurement of hackfat thickness in meat
0041-624X/92/010003-05 @ 1992 Butterworth-Heinemann
Ltd
instrumentation
animals. Eight years later, the same author reviewed the beneficial effects of ultrasound on plants4. Although ultrasonic diagnosis was still in its infancy in 1963, researchers chose to publish their results in Ultrasonics soon after the journal began to appear. The third issue had two such articles: these were concerned with two-dimensional echoencephalography and ophthalmic diagnosi@. Although the ophthalmic applications have continued to evolve to the present day, the advent of X-ray computed tomography (CT) was virtually (but perhaps only temporarily) to halt progress in ultrasonic studies of the brain in the intact skull. In 1963, however, the invention of CT was still a decade ahead. From the beginning, the journal has included conference reports. The very first issue had two reports of medical meetings, one of which was, in retrospect, a key event in the development of medical ultrasound’. This was Ultrasound as a Diagnostic and Surgical Tool, organized by Douglas Gordon in London, 5-6 December 1962. Although the dates chosen coincided with one of the worst of London’s fogs so that many would-be participants were unable to attend. there were contributors from Australia, Germany, Italy, Sweden, the USA and the USSR, as well as the UK. It was agreed that similar meetings should in future be organized by the British Institute of Radiology in association with the Hospital Physicists’ Association. This was an important milestone in the gestation of what is now the British Medical Ultrasound Society. Volume 2 of the journal established the important role that it was to have as a vehicle in the development of biomedical ultrasound. There were papers on echo sounding for fish8,9 (a subject still very much alive in the journal 20 years laterlo), the detection of animal ultrasound”, a mobility aid for the blind”, the measurement of ultrasonic power in the milliwatt rangel and ultrasonic propagation in ocular tissues14. In addition, two articles of great significance in the development of diagnostic ultrasound were published in
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the journal in 1964. In the first of these, George Kossoff and his colleagues” demonstrated that it is the spot size of the display that should be used as the design criterion in ultrasonic visualization systems. The spot size sets limits on the performance required from the transducer, the scanner, the deflexion system and the receiver. The second key paper was the first accessible publication in English of the development of intravenous probes that had been carried out in Japan64. Although there have been a few sporadic efforts to emulate this, it is really only within the last five years or so that the approach has really been taken seriously and its clinical value has begun to be widely appreciated. Thus, by the beginning of 1965, Ultrasonics was well recognized by the then small and close-knit biomedical community interested in this emerging science. During the next few years, numerous important developments were reported in the journal. What was probably the first sector scanner using an array of transducers was described but hardly noticed in a paper on ophthalmology’7. There was a review of ultrasonic physiotherapy”. There was an early discussion of artefacts in ultrasonic scans r9. Improvements in ultrasonic foetal cephalometry were described”. In 1966, the journal contained four papers in a special medical ultrasonics section. Even more significantly, two of these papers21v22 were devoted to the study of blood flow and were amongst the first publications to bring the Japanese discovery of the ultrasonic Doppler effect to the attention of the English-sneaking scientific community. Despite the record number of authors (nine) and unusual brevity (one and a half pages) of the paper concerned with Doppler signals from solid tissues22, this application has hardly progressed; but the study of blood flow21 was a precursor to what is now of the utmost clinical importance. Likewise, one of the other two papers was on the esoteric use of ultrasound to measure changes in mesenteric blood volume in a dog23, whilst the other was on resolution enhancement using a large aperture24 and is a largely forgotten foundation of modern high performance imaging systems. This latter paper contained the prophetic statement that ‘the chief limitation on (medical) image resolution will be changes of velocity within complex tissues’. The special section on medical ultrasonics that was published in 1966 was a prelude to the special medical issue that appeared in April 1967. This consisted of 13 articles which to a large extent reflected the contemporary preoccupations with obstetrics, cardiology, ophthalmology and (now apparently misguidedly) echoencephalography and neurosurgery. With the benefit of hindsight, there were two really important papers in this issue of the journal. The first was concerned with ultrasonic ‘cinematography’ of the living heart: a mechanical scanner2’ was described that could produce pictures at a frame rate of seven per second, and which was arguably the first ‘real-time’ imaging system. The other, by Tom Brown26 described the visualization of soft tissues in three dimensions; although the system was slow and the significance of the results were shamelessly uncomprehended by many people at the time, subsequent developments have shown that Brown was a victim of being much in advance of his time and, in fact, a visionary whose inventiveness only received recognition through election to honorary membership of the British Medical Ultrasound Society nearly 20 years later.
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Under the sponsorship of the journal, a meeting on Ultrasonics for Industry was held in 1967: this was the first stage in the evolution of the present Ultrasonics International conference series. Some papers from the 1967 meeting were published in 1968; onez7 dealt with the design of medical ultrasonic equipment and is really the best description in the open literature of the diasonograph, the instrument with which Ian Donald did such wonderful work and which first popularized diagnostic ultrasound in the early 1960s. Ultrasonics International continues to the present day but that is another story.
Clinical
radiology
Although Ultrasonics is primarily a basic science and engineering journal, occasionally it has served as the depository for purely clinical papers. The first of these was published in 1967 and was devoted to the role of ultrasonic imaging in the diagnosis of thyroid diseases28. Although similar articles have since appeared from time to time, it has to be admitted that they sometimes seem ill at ease alongside their more traditional partners and, perhaps sadly, the good ones usually have had to be drawn to the attention of busy clinicians who tend only to read their own specialist journals. The journal has a reputation for rapid publication and therefore it has always been attractive to those wishing to establish precedence in new research. For example, the discovery of the characteristic ultrasonic Doppler blood flow signals from malignant tumours was first reported in Ultrasonics in 197729, less than six months after the original experiments.
Bioeffects From the earliest days of medical diagnostic ultrasound, the question of bioeffects and safety has been important. The journal has published numerous papers in this area, beginning with a study of the effect of ultrasound on the brain3’: the results were negative. A useful paper on the measurement of peak acoustic intensity appeared in 196931. There was an analysis of the oscillation of a vibrating capillary in the context of its bioeffects32. One of the early publications on ultrasonic haemolysis appeared in 1970 33. In 1976, the journal had an article on the ultrasonic stimulation of the healing of varicose ulcers34 Four years later, cavitational bioeffects were reviewed3’. Then, in 1985, a plane layered model was analysed in terms of in situ ultrasound exposures3”. In the 1987 special issue on sonochemistry there was an article on the evidence for free radicals produced in aqueous solutions by diagnostic ultrasound37; the conclusions were rather alarmist. Happily, a negative result was obtained in a search for an ultrasonic effect on mitotic index38 and the ultrasonic enhancement of diffusion through skin 39 is not a cause for concern. In 1990, a special issue (edited by Roy Williams4’) was devoted to ultrasonic bioeffects. It contained eleven papers which, as the editor wrote ‘help to correct some previous errors of interpretation as well as providing some new experimental evidence which takes us a few small steps closer to our ultimate goal of being able properly to assess the potential hazards associated with
Ultrasonics:
the uses of ultrasound in medicine’. It is with this sentiment in mind that three subsequent papers41V42,43 need to be read. Properties
of tissues
Data on the acoustic properties of tissues have been published in the journal. The first such paper appeared in 197144: it presented values of propagation speed in body fluids and brain tumours as measured by a sing-around system. Subsequently, the results of measurements of speed and attenuation in various tissues were published in 197745 and some data for bone were presented in 198146. In 1986, a pulse freq uency spectral shift method for in oiuo measurement of attenuation was described47 and data on post rigor bovine skeletal muscle4* and homogenated muscle49 were presented. In the same year, the potential for characterizing biological media by means of their non-linearities was reviewed5’ and the zero-crossing counting method for estimating attenuation in tissue was analysed”. The dependence of speed on water content and tissue structure was studied in 198752. A key paper on ultrasonic wave fluctuations through tissue appeared a year later53, thus taking up again the prediction made in the journal 20 years before24 that this phenomenon would limit the performance of imaging systems. Diagnostic
instrumentation
Of all the biomedical ultrasonic papers published over the years in the journal, arguably the most significant is that of Jan Somers4 in which he first described electronic sector scanning by means of a phased array transducer designed for medical diagnosis. This array, which operated at 1.5 MHz, consisted of 21 elements. On transmission, the beam was steerable within a 90“ sector and it was proposed that the necessary time delays on reception could be provided by electrically variable delay lines. Twenty years later, two articles in the journal discussed the influence of errors in amplitude55 and phase56 on the performance of beam-steered arrays. Another 1968 paper57 described the first water-immersion scanner for two-dimensional breast imaging in which the patient was prone; this arrangement was subsequently adopted in several commercially developed systems. Indeed, in 1973 the journal carried an article on velocity compensation with this technique58. Maintaining the tradition of publishing comprehensive technical descriptions of medical diagnostic systems, 1969 saw a paper on a time-to-voltage analogue converter for ultrasonic cardiology59. In 1972, the first catheter-tip array for intracardiac scanning was described6’: the device consisted of 32 elements in a cylinder with an outer diameter of only 3 mm. Also in 1972, for the first time in the open literature George Kossoff identified the grey scale display as a method of improving the clinical value of twodimensional scanning6i; nowadays, it is accepted as a sine qua non. Other developments reported in the journal included automatic sensitivity control in two-dimensional scanning62, B-scanning and holography in ophthalmic diagnosis63, a directional detector for ultrasonic Doppler blood flow signal analysis64, the ultrasonic fluctuation velocimeter(j5, the use of transducer groups to improve beam shape in linear array scanning@j and an early mechanically oscillated scanning system for two-
a window
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dimensional imaging67. The journal published the pioneering work on the use of spectral analysis to determine basic tissue properties in differential diagnosis’j8. The adaptive correlation ratemeter, now widely used in ultrasonic foetal heart-rate monitors, was described in 1978’j9. Technical details of a tremendously successful servo-controlled mechanical real-time sector scanner were also published in 19787o. Three years later, speckle in ultrasonic imaging was discussed and its reduction by incoherent image summation was described7i; and in 1986, speckle reduction by adaptive filtering was introduced72, to be followed by real-time implementation of the technique in 199173. In 1985, a paper was published dealing with the acoustic matching of medical ultrasound transducers74. This year also saw the beginning of a series of four articles on transducers in medical ultrasound, dealing with materials75, vibration modes, matching layers and grating 10bes~~,applications in echocardiology and safety 78. The first of a series of papers on ultrasonic waveguides was published in 198879, followed by others in 198980 and 199181. Most recently, the status of ultrasonic contrast agents has been reviewed82: these materials are likely to become very significant. The vector problem in ultrasonic Doppler studies of blood flow remains important; two-dimensional time domain processing 83, however, is an alternative approach which, although computationally demanding, offers a feasible solution. Also in 1989, the medical application of research extending over more than 15 years into time delay spectrometry was described84. Another recent and significant Doppler paper has analysed the effect of frequency dependent processes on the geometry of the sample volume’ 5. The future The tenth anniversary issue of the journal (January 1973) carried a little piece entitled ‘What future for biomedical ultrasonics?‘86. It recognized that ultrasonic diagnosis had been placed on firm scientific ground and correctly forecast an important role for digital techniques. It predicted that there would be 400 major scanning systems in the UK by 1982. Probably there were; there are about 2000 now. Then in 1983, R.W.B. Stephens reviewed 20 years of Ultrasonicss7 in a characteristically modest way. Of particular interest to ‘human needs’, he identified the importance of ‘the medical and biological applications of ultrasonic diagnosis and therapeutics’, predicting that ‘with improved instrumentation and techniques it may be possible to give, for example, earlier warning of disease’. This has certainly turned out to be the case already but there is no end in sight to the ways in which advances can continue to be made. These advances will depend, in the future as much as they have in the past, on the spread of knowledge. In this, Ultrasonics will surely have a leading role. References 1
2
3
Bullen, M.A., Wells, P.N.T., Freundlich, H.F. and James, J.A. A physical survey of the ultrasonic treatment of Mtnitre’s disease Ultrasonics (1963) 1 2-S Wells, P.N.T., Bullen, M.A., Follett, D.H., Freundlich, H.F. and James, J.A. The dosimetry of small ultrasonic beams Ultrasonics (1963) 1 106-110 Gordon, A.G. The use of ultrasound in agriculture Ultrasonics (1963) 1 70-77
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Gordon, A.G. Beneficial effects of ultrasound on plants - a review Ukrusanics (1971) 9 88-94 de Vlieger, M., de Sterke, A., Molin, C.E. and van der Ven, C. Ultrasound for two-dimensional echo-encephalography Ultrasonics (1963) 1 148-151 Freeman, M.H. Ultrasonic pulse-echo techniques in ophthalmic examination and diagnosis Ultrasonics (1963) 1 152-160 Gordon, D. Ultrasound as a diagnostic and surgical tool Ultmsonics (1963) 1 56-57 Haslett, R.W.G. Physics applied to echo sounding for fish Ulrrasonics ( 1964) 2 1- 11 Hopkin, P.R. and Haslett, R.W.G. A new ultrasonic lish-detection equipment for trawlers Ultrasonics (1964) 2 65-70 Do, M.A. and Surti, A.M. Accumulative uncertainties in the quantitative evaluation of signals from fish UItrusonics (1982) 20 217-223 Pye, J.D. and Flinn, M. Equipment for detection of animal ultrasound Uhsonics (1964) 2 23-28 Kay, L. An ultrasonic sensing probe as a mobility aid for the blind Ultrasonics (1964) 2 53-59 Wells, P.N.T., Bullen, M.A. and Freundlich, H.F. Milliwatt ultrasonic radiometry Ultrasonics (1964) 2 124- 128 Greguss, P. Ultrasonic propagation in the heterodispersive media of the eye Ultrasonics (1964) 2 134-136 Kossoff, G., Robinson, D.E., Liu, C.N. and Garrett, W.J. Design criteria for ultrasonic visualization systems Ultrusonic,s (1964) 2 29-38 Kimoto, S., Omoto, R., Tsunemoto, M., Muroi, T., Atsumi, K. and Uchida, R. Ultrasonic tomography of the liver and detection of heart atria1 septal defect with the aid of ultrasonic intravenous probe Ultrasonics (1964) 2 82-88 Buschmann, W. New equipment and transducers for ophthalmic diagnosis Ultrasonics (1965) 3 18-21 Patrick, M.K. Ultrasound in physiotherapy UItrusonics (1966) 4 10-14 Robinson, D.E., Kossoff, G. and Garrett, W.J. Artefacts in ultrasonic echoscopic visualization Ultrasonics ( 1966) 4 186- 194 Hall, A.J., Fleming, J.E. and Abdulla, U. Ultrasonic fetal cephalometry - some improvements and future developments Ulrrasonics ( 1970) 8 34-35 Kaneko, Z., Shiraishi, J., Omizo, H., Kato, K.. Motomiya, M., Izumi, T. and Okumura, T. Analysing blood flow with a sonograph Ultrusonics (1966) 4 22-25 Yoshitoshi, Y., Machii, K., Sekiguchi, H., Mishina, Y., Ohta, S., Hanaoka, Y., Kohashi, Y., Shimuzi, S. and Kuno, H. Doppler measurement of mitral valve and ventricle wall velocities UItrusonics (1966) 4 27-28 Mullins, G.L. and Guntherotb, W.G. Continuous recording of changes in mesenteric blood volume Ultrasonics (1966) 4 24-25 Tburstone, F.L. and McKinney, W.M. Resolution enhancement in scanning of tissue Ultrasonics (1966) 4 25-27 Asberg, A. Ultrasonic cinkmatography of the living heart C’ltrusonics (1967) 5 113-l 17 Brown, T.G. Visualization of soft tissue in two and three dimensions limitations and development Ultrusonics ( 1967) 5 118-124 Brown, T.G. Design of medical ultrasonic equipment Ultrasonics (1968) 6 107-111 Fujimoto, Y., Oka, A., Omoto, R. and Hirose, M. Ultrasonic scanning of the thyroid gland as a new diagnostic approach Ultrasonics ( 1967) 5 177- 180 Wells, P.N.T., Halliwell, M., Skidmore, R., Webb, A.J. and Woodcock, J.P. Tumour detection by ultrasonic Doppler bloodflow signals Ultrasonics (1977) 15 231-232 Garg, A.G. and Taylor, A.R. An investigation into the effect of pulsed ultrasound on the brain Ultrusonics (1967) 5 208~212 Kossoff, G. The measurement of peak acoustic intensity generated bv nulsed ultrasonic equipment Ultrasonics (1969) 7 249%251 Williams, A.R. and Nyborg, W.L. Microsonation using a transverselv oscillating capillarv Ultrusonics (1970) 8 36 -38 Howkins, S:D. and Weinstock, 6. The effect of focussed ultrasound on human blood Uilrrasonics (1970) 8 174-176 Dvson, M.. Franks, C. and Suckling, J. Stimulation of healing of varicose ulcers by ultrasound Ulrrusonics (1976) 14 232-236 Graham. E.. Hedges. M., Leeman, S. and Vaughan, P. Cavitational bioetTec& at 1.5 GHz Ultrusonics (1980) 18 225-228 Smith, S.W., Stewart, H.F. and Jenkins, D.P. A plane layered model to estimate in situ ultrasound exposures Ultrasonics ( 1985) 23 31-40 Christman, C.L., Carmichael, A.J., Mossoka, M.M. and Riesz, P. Evidence for free radicals produced in aqueous solutions by
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diagnostic ultrasound Ultrasonics (1987) 25 31-34 Miller, M.W., Church, C.C. and Cox. C. Lack of effect of continuous wave ultrasound exposure on in viva Chinese hamster cheek pouch epithelial mitotic index Ultrasonics (1988) 26 277-279 Mortimer, A.J., Trollopc, B.J., Villeneuve, E.J. and Roy, O.Z. Ultrasound-enhanced diffusion through isolated frog skin Ultrasonics (1988) 26 348-351 Williams, A.R. Editorial Ultrasonics (1990) 28 131 Suneetha, N. and Kumar, R.P.S. Enzymatic studies in foetal brain and liver of mouse following in utero exposure to ultrasound Ultrusonics (1991) 29 257-260 Cardinale, A., Lagalla, R., Giambanco, V. and Aragona, F. Bioeffects of ultrasound: an experimental study on human embryos Ultrasonics (1991) 29 261-263 Watmough, D.J., Davies, H.M., Quan, K.M., Wytch, R. and Williams, A.R. Imaging microbubbles and tissues using a linear focussed scanner operating at 20 MHz: possible implications for the detection of cavitation thresholds Ultrasonics (1991) 29 312-317 van Venrooij, G.E.P.M. Measurement of ultrasound velocity in human tissue Ultrasonics (1971) 9 240-242 Bhagat, P., Kadaba, M., Ware, R. and Cockerill, W. Frequency dependence of acoustic parameters of freshly excised tissues of Sprague-Dawley rats Ultrasonics (1977) 15 179-182 Behari, J. and Singh, S. Ultrasound propagation in ‘in Coo bone Ultrusonics (1981) 19 87-90 Ferrari, L., Jones, J.P. and Gonzalez, V.M. In do measurement of attenuation Ultrasonics (1981) 24 66-72 Shore, D., Woods, M.O. and Miles, C.A. Attenuation of ultrasound in post rigor bovine skeletal muscle Ultrasonics (1986) 24 81-87 Wood, M.O. and Miles, C.A. Ultrasound speed and attenuation in homogenates of bovine skeletal muscle UIrrusonics ( 1986) 23 260-266 Bjerne, L. Characterization of biological media by means of their non-linearity Ultrasonics (1986) 24 254-259 Deurinckx, A.J., Ferrari, L.A., Hoefs, J.C., Sankar, P.V., Fleming, D. and Cole-Beuglet, C. Estimation of acoustic attenuation in liver using one megabyte of data and the zero-crossings technique Ultrasonics (1986) 24 325-332 Sarvazyan, A.P., Lyrchikov, A.G. and Gorelov, S.E. Dependence of ultrasonic velocity in rabbit liver on water content and structure of the tissue Ultrasonics (1987) 25 244-247 Aindow, J.D. and Chivers, R.C. Ultrasonic wave fluctuations through tissue: an experimental pilot study Ultrasonics (1988) 26 9op 101 Somer, J.C. Electronic sector scanning for ultrasonic diagnosis Ultrasonics ( 1968) 6 153- 159 Lancbe, C.T., Vissers, J.M., Mientki, S., Ligtvoet, C.M. and Born, N. Influence of amplitude errors on beam-steered phased arrays Ultrasonics (1987) 25 147-153 LancCe, C.T., Vissers, J.M., Mientki, S., Ligtvoet, C.M. and Born, N. Influence of phase errors on beam-steered phased arrays Ultrasonics (1987) 25 154-159 Wells, P.N.T. and Evans, K.T. An immersion scanner for two-dimensional ultrasonic examination of the human breast Ultrasonics (1968) 6 220-228 Jellins, J. and Kossoff, G. Velocity compensation in water-coupled breast echography Ultrasonics (1973) 11 223-226 Wells, P.N.T. and Ross, F.G.M. A time-to-voltage analogue converter for ultrasonic cardiology Ultrasonics ( 1969) 7 17 1 - 176 Born, N., Lancie, C.T. and van Egmond, F.C. An ultrasonic intracardiac scanner Ultrasonics (1972) 10 72-76 Kossoff, G. Improved techniques in ultrasonic cross sectional echography Ultrasonics (1972) 10 221-227 McDicken, W.N., Evans, D.H. and Robertson, D.A.R. Automatic sensitivity control in diagnostic ultrasonics Ultrasonics (1974) 12 173-176 Chivers, R.C. B-scanning and holography in ophthalmic diagnosis Ultrasonics (1974) 12 209-213 de Jong, D.A., Megens, P.H.A., de Vlieger, M., ThGn, H. and Holland, W.P.J. A directional quantifying Doppler system for measurement of transport velocity of blood Ultrasonics (1975) 13 138-141 Atkinson, P. An ultrasonic fluctuation velocimeter Ultrasonics (1975) 13 275-278 Whittingham, T.A. A hand-held electronically switched array for rapid ultrasonic scanning Ultrasonics (1976) 14 29-33 Shaw, A., Paton, J.S., Gregory, N.L. and Wheatley, D.J. A real time two-dimensional ultrasonic scanner for clinical use Ultrasonics (1976) 14 35-40
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Lizzi, F., Katz, L., Louis, L. St. and Coleman, D.J. Applications of spectral analysis in medical ultrasonography Ultrasonics (1976) 14 77-80 Takeuchi, Y. and Hogaki, M. An adaptive correlation ratemeter: a new method for Doppler fetal heart rate measurement Ultrasonics (1978) 16 127-137 Matzuk, T. and Skolnick, M.L. Novel ultrasonic real-time scanner featuring servo controlled transducers displaying a sector image Ultrasonics (1978) 16 171-178 Wells, P.N.T. and Halliwell, M. Speckle in ultrasonic imaging Ultrasonics (1981) 19 225-229 Bamber, J.C. and Daft, C. Adaptive filtering for reduction of speckle in ultrasonic pulse-echo images Ultrasonics (1986) 24 41-44 Bamber, J.C. and Pbelps, J.V. Real-time implementation of coherent speckle suppression in B-scan images Ultrasonics (1991) 29 218-224 Persson, H.W. and Hertz, C.H. Acoustic impedance matching of medical ultrasound transducers Ultrasonics (1985) 23 83-89 Lancbe, C.T., Souquet, J., Ohigasbi, H. and Born, N. Transducers in medical ultrasound: part one. Ferro-electric ceramics versus polymer piezoelectric materials Ultrasonics (1985) 23 138-142 de Jong, N., Souquet, J., Faber, G. and Born, N. Transducers in medical ultrasound: part two. Vibration modes, matching layers and grating lobes Ultrasonics (1985) 23 176-182 Lancbe, C.T., Daigle, R., Sahn, D.J. and Tbijssen, J.M. Transducers in medical ultrasound: part three. Transducer applications in
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echocardiology Ultrasonics (1985) 23 199-205 Wells, P.N.T., de Jong, N., Born, N. and Somer, J. Transducers in medical ultrasound: part four. Transducer safety Ultrasonics (1986) 24 230-232 Nicholson, N.C. and McDicken, W.N. Waveguides in medical ultrasonics Ultrasonics (1988) 26 27-30 Nicholson, NC, McDicken, W.N. and Anderson, T. Waveguides in medical ultrasonics: an experimental study of mode propagation Ultrasonics (1989) 27 101-106 Nicholson, N.C. and McDicken, W.N. Mode attenuation in waveguides used in medical ultrasonics Ultrasonics (1991) 29 133-137 de Jong, N., Ten Cate, F.J., Lancbe, C.T., Roelandt, J.R.T.C. and Born, N. Principles and recent developments in ultrasound contrast agents Ultrasonics (1991) 29 324-330 Trahey, G.E., Hubbard, S.M. and von Ramm, O.T. Angle independent ultrasonic blood flow detection by frame-to-frame correlation of B-mode images Ultrasonics (1988) 26 271-276 Heyser, RX., Hestenes, J.D., Rooney, J.A., Gammell, P.M. and le Croissette, D.H. Medical ultrasound imager based on time delay spectrometry Ultrasonics (1989) 27 31-38 Fish, P.J. and Cope, J.A. Effect of frequency dependent processes on pulsed Doppler sample volume Ultrasonics ( 1991) 29 275-282 Wells, P.N.T. Biomedical ultrasonics Ultrasonics (1973) 11 16 Stevens, R.W.B. Twenty years of Ultrasonics Ultrasonics (1983) 21 9-10
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