OPTICAL EVALUATION OF ULTRASONIC SCATTERING IN ANIMAL TISSUE Pal Greguss Abt. Koharente Oprik, Gesellschaft f Strahbn- u. Umweltforschung m.b.H. and I. Physikalisches Znstitut der Technischen Hochschule Darmstadt Darrnstadt, Federal Republic of Germany

INTRODUCTION Medicine is such an inexact art that physicians are eagerly looking for any diagnostic help that biophysics can offer. When it became readily possible to generate ultrasonic waves in the megahertz frequency range, attempts have been made t o produce spatial images of the body. Since at that time the x ray was already quite a well-established clinical imaging technique, these attempts were largely confined t o produce x-ray-like pictures with the less harmful ultrasonic waves. It turned out in a little while, however, that using transmission techniques resulted in serious difficulties because of the fact that the interfaces that reflected o r refracted the ultrasonic waves are so numerous that the image produced o n the display is a result of quasi-randomly scattered wavefronts (in contrast to x-ray images, which are formed from the undeflected portion of the interrogating beam) originating from the structure we are looking for. Ultrasonic images produced by transmission techniques were intensity distributions resulting not only from changes in amplitude, but also from changes in phase; and although they contained a great deal of information, it was not possible t o make these images meaningful. If we consider that ultrasonic waves are coherent waves, we may wonder why n o attempts have been made t o use coherent data processing techniques t o decode the information from such a transmission recording. Even the degree of loss of coherence was not measured, although it may have given information perhaps of clinical value. One reason for this can be attributed t o the really spectacular results obtained by pulse-echo techniques. The images produced in this way are nowadays of excellent quality, but they give information only on the location and shape of the insonified organ, and little, if any, information on the biological function of the tissue. Acoustical histology is only possible if not only amplitude but also phase-bound information is processed, which is normally not the case in pulse-echo technique. Even the grayscale imaging method, which in a certain degree also takes care of low-amplitude scattered reflections, does not eliminate the guesswork in the diagnostic decisions. Recently it has been demonstrated that, acoustically, animal tissues behave as semiordered 3-D matrices in which t h e matrix spacing and arrangement is characteristic of the particular Therefore, it is nearly self-evident t o assume that light-scattering metrology methods could be adapted t o study ultrasonic scattering properties of animal tissues too. The scope of this presentation is to show that this question can be studied with rather simple instrumentation. Although the scattered ultrasonic field t o be studied has t o be visualized, the technique of visualization is not at all important, and there are no extreme requirements concerning the aperture of the image converter. Naturally, it is advantageous if t h e image converter works in real time.

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The visualized ultrasonic field can be used as direct input in a normal coherent optical data processing line. This is the case when the scattered ultrasonic field is visualized, e.g., via an electro-optical DKDP modulator, a gamma-Ruticon, o r an acoustical-to-optical conversion cell (AOCC) display. Although the first two are more sensitive than the latter one, we used in our experiments the AOCC display to avoid problems related t o electronics. EXPERIMENTAL ARRANGEMENT

A careful investigation of the question whether the optical evaluation of ultrasonic scattering would indeed be a processing technique of clinical value requires an experimental arrangement that is rather flexible. The basic unit of our experimental arrangement is shown in FIGURE 1. Principally it is a water-filled tank o n the short side of which an ultrasonic transducer is mounted. The opposite side is of an optically transparent material and has an incidence of 45' t o the axis of the ultrasonic beam, which therefore is reflected by it onto the side where visualization of the ultrasonic field takes place. We generally used an AOCC display, but sometimes sonosensitive plates too. The simplest experiment is t o put the sample to be investigated in front of the

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FIGURE 1. Schematics of the apparatus for the optical evaluation of ultrasonic scattering. The AOCC display can be replaced by any type of image converter, even by sonosensitive photographic plates.

AOCC ultrasonic transducer and manipulate the ultrasonic transmission pattern displayed o n the image converter. Recently we have shown4y5 that, since the ultrasonic beam is coherent, the circular symmetrical irradiance distribution of the optical replica of the ultrasonic beam cross section is independent of the initial stage of the beam, and by comparing its displayed diameter with t h e original diameter of the beam, data o n the mean square fluctuation of the index of refraction 6' can be obtained. The measurement is performed either by scanning the visualized ultrasonic field with a photomultiplier directly or by scanning its photographic image with a microphotodensitometer. In both cases, the obtained curve is proportional t o the ultrasound intensity distribution in the plane of the display and can be considered as an ultrasonic scattering envelope of the specimen under investigation. FIGURE 2 shows the intensity distribution of the ultrasonic beam after it has passed through different animal tissues, representing the patterns of the scattered ultrasonic fields. Since, however, we are not yet sure how characteristic these patterns are, we d o not specify the organ from which t h e sample was taken, and this holds also for the other similar pictures to be shown. We have found however that it is not really the beam spread but rather a parameter measuring the relative importance of scattering and free space diffrac-

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tion that may be a characteristic value of the specimen under investigation. Following the reasoning of Whitman and Beran,6 who defined a similar parameter for coherent light, we suggested the parameter

6 =0.58k3~*x~m2, where k = 2n/h, n = t h e index of refraction, which for soft tissue is assumed t o be about 1.06, x, = the smallest characteristic length associated with index of refraction variation, and can also be calculated from the beam spread. In the experimental arrangement shown in FIGURE 1 using an AOCC display, the illumination is generally from the same direction as the ultrasonic beam

FIGURE 2. Intensity distribution in an ultrasonic beam after it had passed through different animal tissues, i.e., the pictures represent the ultrasonic field scattered by the specimens under investigation.

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FIGURE 3. Photograph of the reconstructions of the visualized and holographically stored scattered ultrasonic field.

impinging o n the display. Since a laser can be used t o form the optical replica of the scattered ultrasonic field, there is n o problem in recording it as a hologram; only part of t h e illuminating laser beam then has t o be used as a reference beam by inserting a beam splitter and a front surface mirror into the illuminating beam before it reaches the apparatus. If we now assume that the hologram plate, after it is developed, has been placed exactly in its original position, then apart from a constant amplitude and phase factor, the reconstructed wave will be the exact replica of the visualized scattered ultrasonic field. To the viewer looking through the hologram there will be, therefore, n o difference between the visualized scattered ultrasonic field and this virtual image. F I G U R E 3 shows photographs of reconstructions recorded with this method. Any change in the scattering pattern will, however, show u p in the form of fringe patterns. Since the scattered pattern is a function of the wavelength, change in the frequency of the ultrasonic beam will cause a change in the scattering pattern. Knowing the amount of the frequency change we may draw conclusions concerning the scattering structure of the specimen. Since, however, i t is rather difficult t o achieve an effective coincidence of the virtual image with the visualized ultrasonic field, and since it is probably sufficient t o form a permanent record of the change in the scattered pattern occurring after a frequency alteration, t w o exposures of the hologram, once a t frequency N1 and once at frequency N , , superimposed prior t o processing, may solve the experimental difficulties of this real-time interferometry. The reconstruction of such a double-exposure hologram can be analyzed, e.g., by the method of Archbold and en no^.^ According t o this procedure t h e photograph of the reconstructed picture is illuminated by collimated light, is reimaged by means of a lens in whose focal plane a small circular aperture stop is placed.

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If this stop is offset from the axis by azimuth and field angles @ and a, the final image is formed only by light diffracted into that direction. Bright areas on the film observed through the aperture will correspond to pattern parts that have suffered displacement due to wavelength changes resolved in the azimuth direction # of magnitude D* given by

D* = nhmlsin a, where n is the order number of the diffraction spectrum, and m is the demagnification factor. Dark areas correspond to the half-order spectra, where n is replaced by (n + f )in the formula. If there is a variation in the magnitude and direction of the lateral displacement of the pattern, fringes will be seen to cover the image; by changing the value of the azimuth angle #, and by varying the angle &, the sensitivity can be changed. With a slight modification of the arrangement of FIGURE 1 the spatial coherent properties of the scattered ultrasonic field can be studied. A screen made from ultrasound-absorbing material with two holes is placed between the reflecting surface and the specimen under investigation, which then can be irradiated from above; i.e., the scattered field at right angle to the direction of the incident ultrasound is analyzed. The pattern to be seen on the acoustic image converter is the optical replica of the ultrasonic field, created by the two holes as secondary sources. The visibility of these interference fringes and speckles is practically independent of the distance between the holes and the distance between the screen and the scattering volume, provided that during the observation the specimen does not move. Therefore, this pattern can be recorded with visualization techniques requiring long exposure time, e.g., sonosensitive plates. FIGURE 4 shows such a speckle pattern. Up till now we assume that the visualized speckle pattern is arising from single scattering of the ultrasonic beam at a layer which can be considered to be only two-dimensional. Under these conditions, it can be modeled as being made up of a large number of individual gratings of more or less random orientation and different line spacing. In practice, however, the scattering layer has a definite thickness and may be highly convoluted, so that multiple scattering takes place before the scattering pattern is visualized. This means that the speckle pattern is

FIGURE 4. Ultrasonic speckle patterns recorded on sonosensitized photographic plates.

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FIGURE 5. Streak photographs of visualized ultrasonic speckle patterns of two different specimens.

likely t o change more rapidly o n changing the frequency or viewing direction than for a simple semi-two-dimensional scatterer. At present, we are looking into the possibility of using this phenomenon to study the characteristic scattering properties of different inorganic and organic specimens by projecting the visualized ultrasonic speckle pattern, in a similar way as described by Archbold and o n t o a slit having a width approximately the same as the speckle diameter. Instead of rotating the slit over the tilted specimen however, we change the frequency of the ultrasonic beam. The light transmitted through the slit exposes a photographic film which moves continuously behind the slit, t o give a streak pattern of the bright speckles. F I G U R E 5 shows such streak photographs of visualized ultrasonic speckle patterns of t w o different specimens. The length of an individual bright streak gives a measurement of the frequency change over which the speckle pattern remains correlated with itself. For specimen A there is less loss of correlation over the same frequency change than for specimen B. Now we are investigating whether the length of the individual bright streaks correlated to the frequency change will provide us information characteristic indeed t o the specimen under investigation. An alternative arrangement of analyzing the back scattering properties of specimens is shown in FIGURE 6. In this case, the interrogating ultrasonic beam is divided by a beam splitter, and the transmitted beam passes through an acoustic lens in the focal plane of which the specimen to be investigated is placed. The deflected part of the ultrasonic beam is redirected by an acoustic mirror, and may serve as a reference beam. If there is no scattering or diffraction

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AOCC

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FIGURE 6. Schematics of the apparatus for backscattering studies.

(e.g., only specular reflections occur), the usual pattern of the ultrasonic beam will be displayed o n the image converter. If, however, there is scattering o r diffraction, we get not only information o n these events, but also indications on the location of the structure responsible for the scattering. So, e.g., in the case of FIGURE 7 , we are dealing with a specimen having more or less random scattering properties with a detailed structure of preferred orientation.

FIGURE 7 . Scattering pattern of a specimen having more or less random scattering properties, with structure detail of preferred orientation, recorded with the experimental setup of F I G I ~ K6.I

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FIGURE 8. Schematics of the apparatus to record the ultrasonic Fourier transform of an ultrasonic field.

AOCC Recently we have demonstrated* that the visualized acoustic speckle pattern can be investigated by Fourier analysis in a way somewhat similar t o that described b y Asakura e t aZ.9 for the measurement of spatial coherence of the light field from a thermal source. Since, however, the scattered ultrasonic field generally maintains its coherent characteristics, with the use of appropriate acoustic lenses Fourier transformation can already be performed in the acoustic domain and only the result has t o be visualized. The remarkable property of the diffraction patterns is that although they sometimes may look complicated, they are composed of well-defined elementary diffraction patterns. So, e g . , circular contours show u p as concentric rings, and periodic line structures as bright spots. Since generally the elementary patterns are symmetrical, it is enough t o analyze only one half of the Fourier transform t o find useful marks that can help t o differentiate between specimens of different origin. This can be illustrated by using the experimental setup of FIGURE 1 and placing only an acoustic lens in front of the specimen in such a way that its focal plane coincides with the image converter, as shown in FIGURE 8. FIG U R E 9 shows that basically the same Fourier transform pattern can be obtained by using an acoustic lens t o create the Fourier transform of the scattered ultrasonic field as by visualizing first the scattered ultrasonic field and then

FIGURE 9. A visualized acoustic Fourier transform of a scattered ultrasonic field, and the optical Fourier transform of the visualized scattered ultrasonic field.

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forming its Fourier transform in a conventional coherent optical processor. The left side picture is an ultrasonic Fourier transform; the right side picture is an optical Fourier transform from the same object. Both patterns indicate that the specimen under investigation had a fibrous structure and there was a little dispersion of the alignments around the average alignment direction since the diffraction spots are somewhat elongated." Ten years ago Stroke" proved that Fourier holograms of extended incoherent sources of arbitrary spectral intensity distribution could be recorded with the aid of a two-beam interferometer with tilted mirrors. Recently we have demonstrated that this concept holds for acoustic sources too." Since correlation lengths in a scattered ultrasonic field are rather large, the spatial coherence of the field scattered by the medium could be studied by using a reversing front interferometer similar to that developed by Bertolotti et t o investigate atmospheric turbulences with a laser beam. FIGURE 10 shows the acoustic version of such a reversing front interferometer developed in our laboratory. It is basically a Michelson interferometer, only one of the diffracting mirrors is replaced by a roof reflector that reverses the wavefront transmitted through the semireflecting mirror. Therefore the fringes produced o n the observation plane are resulting from the interference of the reversed wavefront and the incident wavefront, and since their position depends o n the sine of the phase differences between the two interfering beams, the system will be very sensitive to fluctuations in the incoming angle of the beam. The visibility 6 of the fringes depends, however, o n both amplitude and phase fluctuations, and so the variance of the phase differences in a given point, 0 2 ( x , y )can be calculated by determining the envelope of the damped sinusoidal curve resulting from the densitometric analysis of the photographic recording of these fringes by using the following equation:

6 = exp [ - o 2 ( x , y ) / 2 1 . In FIGURE 11, t w o photographs of fringes obtained with this interferometer are shown. Specimen A causes less fluctuation in the incoming angle of the ultrasonic beam than specimen B, and so it shows less decrease of fringe visibility along the x directions than specimen B. Using a streak technique somewhat similar t o that used for FIGURE 5 one can record fringes as a function of frequency, and then process them optically. AOCC

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FIGURE 10. Schematics of the acoustic version of a reversing front interferometer.

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FIGURE 11. Fringes recorded with an acoustic reversing front interferometer.

CONCLUSIONS In making this brief survey of the new concept of coherent ultrasonic data processing methods I hope I have been able to give some idea of the expanding developments in a very exciting branch of ultrasonic metrology. I think it may be apparent from what I said that a new type of information can be acquired by ultrasound when using coherent data processing techniques. Ten years ago the application of holography to ultrasonic^'^ directed attention to the importance of phase-bound information. The resulting spatial images, however, were rather disappointing, and there is not too much hope that there will be a real breakthrough in this regard in the near future, especially not in the frequency range used in clinical medical diagnostics. The real merit of ultrasonic holography is that it directed attention to the coherent properties of ultrasound, and in my opinion, we should not fight against coherence as, e.g., in holographic imaging where nearly everybody tries to eliminate the resulting speckle; rather we should take advantage of the coherence and use it for processing the ultrasonically acquired data. I am aware that a lot of research has to be made before a real clinical tool is yielded; however, I am confident that, although this endeavor is an unlikely area for a “get-richquick program,” there is potentially a chance of early return.

ACKNOWLEDGMENTS The author wishes to thank Prof. W. Waidelich for stimulating discussions, and Dr. D. Haina for his critical remarks and for his assistance in performing the optical part of these experiments.

REFERENCES I . SENEPATI, N., P. P. LELE& A. WOODIN. 1972. A study of the scattering of sub-millimeter ultrasound from tissue and organs. Proc. IEEE Ultrasonic Symp.: S9. 2. HILL,C. R. & R. C. CHIVERS. 1970. Investigation of back scattering in relation to ultrasonic diagnosis. Conf. Proc. UBIOMED 70: 110. 3. CHIVERS, R. C . , C . R. HILL & D. NICHOLAS. 1973. Frequency dependence of ultrasonic backscattering cross sections: An indicator of tissue structure characteristics. In Ultrasonics in Medicine. Proc. 2nd World Congress on Ultrasonics in Medicine : 300.

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4. GREGUSS,P. 1975. Optical computing of ultrasonic scattering of soft tissues. Digest of Papers. International Optical Computing Conference: 115. 5 . GREGUS, P. 1975. Real-time optical computing of scattered ultrasonic fields. Ultrasonics. In press. 6. WHITMAN, A. M. & M. J. BERAN.1970. Beam spread of laser light propagating in random medium. J . Opt. SOC.Amer. 60: 1595. 7. ARCHHOLD, E. & A. E. ENNOS.1972. Displacement measurement from doubleexposure laser photographs. Optica Acta 19: 253-270. 8. GREGUSS,P. 1975. Methods and apparatus for analyzing scattered ultrasonic fields. Spring Meeting of the institute of Acoustics. March 26-27. Nottingham. 9. ASAKURA.T., H. FIJJII& K. MURATA. 1972. Measurement of spatialcoherence using speckle patterns. Optica Acta 19: 273-290. 10. LENDARIS, G. & G. STANLEY. 1970. Diffraction pattern sampling for automatic pattern recognition. Proc. IEEE 58: 198. 1 1 . STROKE,G. W. & A. T. FUNKHOUSER. 1965. Fourier-transform spectroscopy using holographic imaging without computing and with stationary interferometers. Phys. Lett. 16: 272. 12. GREGIISS,P. & W. WAIDELICH. 1975. Ultrasonic holographic Fourier spectroscopy via optical Fourier transforms. IEEE Transactions on Computer, Special Issue C-24: 412. 13. BEKTOLOI‘TI,M.. L. Muzir & D. SETTE.1970. Correlation measurements on partially Opt. SOC.Amer. 60: 1603. coherent beams by means of an interrogating technique. .I. 14. GRFGVSS,P. 1965. Ultraschall-Hologramme. Research Film 5: 330.

DISCUSSIONOF THE TWO PREVIOUS PAPERS DR. SKIRNICK:I’d like t o address both the authors. How would you compare the acoustical holography techniques with Bragg-imaging type techniques, in terms of resolution and ease of operation and other factors. DR. HOLBROOKE:Well, you’re talking t o a clinician and you get me into uneasy water when you start talking about Bragg-diffraction imaging. But m y understanding is that with the frequencies we’re using for clinical usage, one t o ten MHz, that there has been a great number of problems with Bragg diffraction. However, there has been some solution of those problems, and the possibility of using it in a clinically useful mode is growing. I really can’t get down and address t o any great degree the physics involved with Bragg diffraction versus acoustical holography. DR. GOLDMAN:Dr. Waidelich (representing Dr. Greguss) diplomatically agrees. DR. LEE: One of the obvious applications of acoustical holography would be for breast cancer screening. Has either of you tried it, and if so, what sort of results have you obtained? DR. HOLBROOKE:Simple question, good application, complicated answer. We’ve done a great deal of work, breast work, for this very purpose. One of the major problems that we’re having with acoustical holography in the breast, for example, is that you have a great deal of convolution in the tissues structure, and you’re dealing in this particular type of acoustical holography, with a focused image plane, and the images that you get are roughly analogous t o the collection of irregular sausages that have been sliced in an image plane. An advantage, an improvement that can be made in the interpretation, is the real-time aspect. You are able t o , in a stop-frame mode, slice through the tissues in a sequential fashion, and follow blood vessels in this type of situation. As far as visualization of the tissue pathology, itself, in the breast, we have been able t o visualize, interestingly enough, by the image absence rather than the appearance of tissues. Some of the other studies have said that breast cancer or breast tumors are acoustically

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opaque relative t o the rest of the breast tissue. We haven’t found this to be the case at all. The way we visualize a breast tumor, and we’ve been able t o d o it down t o less than a centimeter in an excised specimen-and I emphasize that, excised specimen-is t o see it by its absense. It appears approximately as a hole would in a mess of steel wool. However, we feel that in the long run there may be some potential application here. There are engineering problems t o be solved, and we have t o increase our clinical interpretative acuity of these images before we can really give you a definitive answer on that. Some encouragement is there though. DR. GOLDMAN:Is it true that the Holosonics will rent out this apparatus t o cancer detection centers for $12,000 a month? DR. HOLBROOKE:Not being a representative of Holosonics, I really can’t say. I do know that u p until recently, they were interested in having a clinical evaluation program under way, and the announced philosophy was that they would lease or rent the equipment for a variety of philosophic reasons, rather than a purchase option. However, I am sure that they would d o either. They’re interested in moving into the medical market. Their strong emphasis-and I underline this-is that any group that undertakes it should be willing to undertake it o n a long-term basis. This is not a problem that is going t o be solved overnight, either from an engineering point of view or from a medical one. And while the technique holds considerable promise for the future, it’s going to be a long, hardwon effort t o achieve that success. DR. JAKO: Working in the ear, nose, and throat area, I’m interested if this could be used t o study movement of the vocal cords. You have an average frequency of about 150-200 cycles per second; when you study the function, and the depth from the outside, you would have to go down probably 1 or 2 centimeters. And there is a little air gap between the vocal cords. DR. HOLBROOKE:The biggest impediment in the ear, nose and throat area is, of course, the air-tissue interface, in which the air body is acoustically opaque. You can’t really pass the sound through that. As I indicated in one of m y slides, you may be able very well t o use this as a tissue opacification medium and outline the tissue edge by the fact that the sound does reflect off of o r is by-passed by the air. As far as visualization of the vocal cords goes, this is probably going t o be fairly tough t o d o because of that air mass around the vocal cords. However, again as illustrated by the slide, we can pass the sounds very easily through cartilaginous tissues and can differentiate this cartilaginous tissue from surrounding area. I think, myself, that there is going t o be considerable application in the neck, not necessarily with the larynx, but with the visualization of the vessels of the neck, as well as tumors, etc., of the thyroid region. DR. SKIRNICK:I wanted t o address a question t o the last author. Do you expect that the speckle scale when you use ultrasonics is really speckle in the sense that we know of optical speckle. Just for some of the people in the audience that are not familiar: speckle is a phenomenon due t o coherent interaction of, let’s say, light o r something with a rough surface. And here, we’re talking about scales of roughness that may be o n the order of a millimeter. Is that the scale of roughness that one has in tissues? DR. WAIDELICH: I cannot answer this question. But I am sure Professor Greguss would say yes, and he hopes that this is possible t o do. He has started this work, and he has done the first experiment, and it’s the beginning. DR. SKIRNICK:It would also seem t o me that that, in imaging, one tries to remove the speckle and not deal with it. And it would seem that you would want t o get rid of that interference pattern by making-instead of using a coherent transducer, using some slight band width, maybe a megahertz o r two of bandwidth. When you degrade the speckle, you get much better edge definition, etc.

Optical evaluation of ultrasonic scattering in animal tissue.

OPTICAL EVALUATION OF ULTRASONIC SCATTERING IN ANIMAL TISSUE Pal Greguss Abt. Koharente Oprik, Gesellschaft f Strahbn- u. Umweltforschung m.b.H. and I...
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