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Among the reasons for the phenomenon are ultrasound's relative ease of use, immediate availability of results, noninvasiveness, low cost when compared to other imaging modalities, and-thus far-its perfect safety record. As it has gone from the laboratory to military uses to medical applications and from static white blips on a monitor to real-time gray-scale images with resolutions less than 1 mm, one wonders if ultrasound may have reached a dead end, in terms of new applications and techniques.

But reassurance comes in contemplating the vast amounts of money dedicated by ultrasound manufacturers to research and development. In fact, several modalities have been described in recent years that may presage a revolution almost as great as the advent of real-time, spectral Doppler and color imaging. These are three-dimensional ultrasound, ultrasound contrast media (UCM), and harmonic imaging. All three have already brought improvements in diagnostic capabilities.

At the moment, 3-D imaging is the best known of these, having burgeoned rapidly in the last five years in the U.S. (and much longer in Europe and Asia), as documented by the increasing number of presentations at scientific meetings and by articles in peer-reviewed journals and books.

Since all anatomic structures are three-dimensional, it makes sense to try to represent them as such. Experienced sonographers and sonologists do this by acquiring multiple 2-D slices in series and mentally building the "actual" image. This process is time-consuming and, of course, completely operator-dependent. This is similar to the experience most of us have had of patients who immediately "see" what is shown them on the ultrasound monitor, while others don't perceive what to us is an obvious fetal profile.

This aspect of 3-D is important because it enables the less skilled operator to acquire the data and create a meaningful representation. Powerful computers can perform the reconstruction quickly and objectively, after a set of data points has been acquired and stored. An evaluation can follow almost immediately (undoubtedly, soon in real-time) or it can happen later, by the physician or together with other experts. The latter may receive the images digitally, performing their analysis locally or on the other side of the planet.

One of the Holy Grails of diagnostic imaging is precise volume measurement. This is important in oncology where planning of therapy and follow-up depends largely on accurate volumetry. Similarly, in obstetrics, fetal weight estimation can have a big impact on planning and decision-making, at extremes of the scale-very small and very large fetuses. This is an area where 3-D imaging may develop outstanding capabilities.

In certain fields, 3-D has already proven its efficacy or promises clear advantages. Obstetrics and to a lesser extent gynecology are fields with the most extensive research and the most publications. In evaluating the fetus, 3-D may permit better definition of several malformations by allowing simultaneous viewing from multiple angles, and it will certainly render a more vivid picture for the family or referring care provider.2 A few publications have shown improved diagnosis of fetal anomalies that had been missed by 2-D scanning. The present consensus is that this may be the case in as many as 10% of patients (probably less in the case of experienced operators).

Visualization of the fetal face seems to be the most frequent use of 3-D because of the "pretty" images it can produce, perhaps improving early maternal bonding.

In gynecology, 3-D offers the advantage of assessing the uterine contour, demonstrating planes not otherwise available. It pictures both external surfaces and the endometrial cavity-a major help in diagnosing congenital Muellerian anomalies or adnexal pathology.3 In ophthalmology, given the anatomic limitations, 3-D allows for better correlation between bones and soft tissues, and more accurate determination of tumor of the anterior or posterior segment or hemorrhage volume.4

Prostate ultrasound is another region where 3-D has been shown to correctly identify the location, size, and, with the addition of 3-D color Doppler, the type of tumor.5 In fact, integration of spectral, color, and power Doppler with 3-D-and the addition of an ultrasound contrast agent-may be one of the most important contributions of the new technology to the diagnosis of early malignancy, such as in the breast.

It may lead to the discovery of vascular changes that precede the development of cancer.6 Vascularity of several abdominal organs (liver, pancreas, and spleen) has been examined by 3-D but obvious clinical benefits over existing modalities have not been clearly demonstrated.

The 3-D analysis of lymph nodes7 promises benefits. Vascular ultrasound has profited immensely from the introduction of 3-D scanning, particularly via the intravascular approach, since coronal views of the lumen can now be obtained, analyzed, and followed over time. This has improved the diagnosis of plaques, including volume measurements, the analysis of grafts, and the position of catheters. Despite major technical challenges, 3-D is also utilized in cardiac imaging, reportedly with better visualization of normal structures and increased diagnostic accuracy in complex anomalies. With the addition of the time dimension, this now becomes 4-D ultrasound.8

HARMONIC IMAGING

The second new technology improving visualization, harmonic imaging,9 was developed in tandem with contrast media, following the realization that ultrasound has some nonlinear properties. Returning echoes produced by the media are not only at the original fundamental generated by the transducer but at several different frequencies-multiples of the original one and secondary to vibrations of the contrast agent bubbles.

Insonated tissues will also vibrate under the influence of the changing pressures induced by the incident ultrasound wave, and they will reflect echoes at different frequencies. Whereas this was once considered noise or artifact and was suppressed or was assumed to be too weak to be measured, the information has now been captured and turned into meaningful data. A low-frequency transducer may be used (affording better penetration) but the image resolution is improved since the returning frequency is twice as high.

Harmonics are generated while the ultrasound wave travels through the tissues during the transmit phase of the pulse-echo cycle. The returning echoes, at higher frequency, travel only one way-back to the transducer, thereby reducing potential confusing information. Only echoes not at the "right" frequencies are canceled upon reception, thus reducing artifacts. Depending on the equipment vendor, this is called tissue harmonic imaging, native tissue harmonics, and so forth. The result is better signal-to-noise ratio with improved contrast and spatial resolutions. Since time (which equals depth, in ultrasound) is necessary for generation of the harmonics, they are helpful in larger, harder-to-image patients.

The procedure has been shown to improve imaging in patients pregnant above 22 weeks and weighing more than 200 pounds.10 Its advantages are less obvious in patients easier to scan, although some practitioners turn it on simply because of the better contrast. Improved imaging of the liver, gallbladder, pancreas, pelvis, kidneys, and retroperitoneal lymph nodes is on record.11-13 At the moment, only the second harmonic (twice the original frequency) is displayed, but research in multiple harmonics is under way, with the aim of obtaining even better contrast and improved information.

CONTRAST AGENTS

The third new wrinkle in ultrasound is the contrast agent.14 The idea of using contrast enhancement goes back more than 30 years, when Gramiak and Shah, working at the University of Rochester, noticed strong echoes in the aortic root when injecting saline through an intra-aortic catheter.

Ultrasound images depend on echoes being produced by the insonated structures (acoustic backscatter). It is therefore easy to conceptualize that increasing the amount of echo-producing substance in the insonated area will create additional echoes and thus, if properly processed, additional information. This may be important when dealing with tiny vessels beyond the resolution of gray-scale ultrasound, color imaging, or power Doppler.

The literature on UCM is already extensive, especially in adult echocardiography for imaging of cardiac cavities and valves, visualization of the coronary arteries, and analysis of myocardial perfusion and tissue viability.15 Other areas where UCM have been clinically used include the hepatic and renal vascular bed.16

In oncology UCM may offer tremendous advantages. Neoangiogenesis (creation of new blood vessels) is common to all malignant tumors, and these new vessels are usually abnormal-irregular in size, branching, and distribution, with flow in bizarre directions. Ultrasound alone cannot detect these small vessels but with the addition of UCM, they may be visualized. This has already been demonstrated in breast cancer17 and undoubtedly will move into other areas like ovarian cancer screening.

In obstetrics and gynecology, the use of UCM is limited,18 but placental perfusion19 and ovarian tumors are potential areas for this modality.

WHO'S PAYING?

In a world of managed care, economics is key. The inevitable questions arise: Who pays for routine scans with conventional ultrasound, and who pays for the advanced modalities? Will the new technology allow us to see more patients, see them faster, and at a lower cost? Will hospital stay be shorter? Will quality of life improve?

Unfortunately, the notion of better caregiving may not be the determining factor in answering these questions. Take 3-D ultrasound, for example. Since a 3-D machine costs more than a 2-D, the administrator will ask for a justification by increased productivity, and at the moment this case cannot be made. A counter-argument may be that if patients can see better what the caregiver is describing, their satisfaction level will be enhanced and this may increase the number of referrals. And if scanning time is shorter, more patients can be scheduled per session-although additional work is then needed to manipulate the stored data and extract meaningful diagnostic information.

In some places, a CPT code already exists for 3-D ultrasound-not for routine scanning, but performed as an expert, second opinion. A relevant point is that ultrasound continues to be the cheapest imaging modality after plain x-rays, and is much cheaper than CT or MR to buy, operate, and maintain.

Several other new and advanced techniques are being developed in the engineering laboratories or in clinical trials: sonoelasticity, intracavitary and intravascular ultrasound, very high frequency ultrasound, and "microsonography" (e.g., SonoCT from ATL Ultrasound, Bflow from GE Medical Systems, PhotoPic from Siemens, and ImageGate from Acuson), as well as extended field of view (Siescape from Siemens). Research is ongoing in expert systems to give more accurate and objective readings, in a context of developing telemedicine and teleconsulting.

New clinical applications for diagnostic ultrasound continue to be added to a long list. These include sonography of tendons, especially rotator cuff in shoulder disorders, evaluation of arthritic diseases, developmental dysplasia of the hip in infants, other periskeletal soft tissue lesions, and breast imaging.20 An extreme example is NASA's inclusion of an ultrasound scanner (HDI 5000, ATL Ultrasound) in several of its missions to study the effects of gravity loss.

Miniaturization also continues to allow more mobility and to bring ultrasound to the bedside, whether in the emergency room, the intensive care unit, or the battlefield. A major prerequisite to distribution and implementation of any innovation should be demonstration of its diagnostic value and resulting improvement in patient care. Its mere existence does not by itself justify its use.21

Taking account of all these new technologies and applications as well as the extensive research and development in the lab and in the clinic, it's apparent that ultrasound is alive and well and that its odyssey is in full flight in the new century.

DR. ABRAMOWICZ is chief of ob/gyn ultrasound at the University of Chicago.

References for this article are available at diagnosticimaging.com.

References

1. Nelson TR, Downey DB, Pretorius DH, Fenster A. Three-dimensional ultrasound. Philadelphia, New York, Baltimore: Lippincot, Williams & Wilkins, 1999.

2. Merz E, Bahlman F, Weber G, Macchiella D. Three-dimensional ultrasonography in prenatal diagnosis. J Perinat Med 1995;23:213-222.

3. Merz E. Three-dimensional transvaginal ultrasound in gynecological diagnosis. Ultrasound Obstet Gynecol 1999;14:81-86.

4. Downey DB, Nicolle DA, Levin MF, Fenster A. Three-dimensional ultrasound imaging of the eye. Eye 1996;10:75-78.

5.Sehgal CM, Broderick GA, Whittington R, et al. Three-dimensional US and volumetric assessment of the prostate. Radiology 1994;192:274-278.

6. Kurjak A, Kupesic S, Anic T , Kosuta D. Three-dimensional ultrasound and power Doppler improve the diagnosis of ovarian lesions. Gyn Oncol 2000;76:28-32.

7. Dietrich CF, Lee JH, Hermann G, et al. Enlargement of perihepatic lymph nodes in relation to liver histology and viremia in patients with chronic hepatitis C. Hepatology 1997;26:467-472.

8. Ofili OE, Nanda NC. Three-dimensional and four-dimensional echocardiography. Ultrasound Med Biol 1994;20:669-675.

9. Burns PN, Powers JE, Simpson DH, et al. Harmonic imaging principles and preliminary results. Angiology 1997;47:S63-S73.

10. Abramowicz JS: The non-linear revolution-Is the king (queen) dead? The non-linear revolution in medical ultrasound, Rochester: University of Rochester Center for Biomedical Ultrasound, 1998 (unpublished).

11. Shapiro RS, Wagreich J, Parsons RB, et al. Tissue harmonic imaging sonography: evaluation of image quality compared with conventional sonography. AJR 1998;171:1203-1206.

12. Hann LE, Bach AM, Cramer LD, et al. Hepatic sonography: comparison of tissue harmonic and standard sonography techniques. AJR 1999;173:201-206.

13. Tranquart F, Grenier N, Eder V, Pourcelot L. Clinical use of ultrasound tissue harmonic imaging. Ultrasound Med Biol 1999;6:889-894

14. Dawson P, Cosgrove DO, Grainger RG (Eds.). Textbook of contrast media. Oxford, UK: Isis Medical Media, 1999.

15. Meltzer RS, Vermulen HWJ, Valk NK, et al. New echocardiographic contrast agents: transmission through the lungs and myocardial perfusion imaging. Cardiovasc Ultrasonography 1982;1:277-282.

16. Goldberg BB, Liu JB, Forsberg F. Ultrasound contrast agents: a review. Ultrasound Med Biol 1994;20:319-333.

17. Kedar RP, Cosgrove DO, McCready VR, et al. Microbubble contrast agent for color Doppler US:effect on breast masses. Radiology 1996;198:679-686.

18. Abramowicz JS. Ultrasound contrast media and their use in obstetrics and gynecology. Ultrasound Med Biol 1997;23:1287-1298.

19. Abramowicz JS, Pillips DB, Jessee LN, et al. Sonographic investigation of flow patterns in the perfused human placenta and their modulation by vasoactive agents with enhanced visualization by the ultrasound contrast agent Albunex. J Clin Ultrasound 1999;27:513-522.

20.Weismann CF. Breast ultrasound: new frontiers in imaging? Ultrasound Obstet Gynecol 2000;15:279-281

21. Kossof G: Three-dimensional ultrasound-technology push or market pull? Ultrasound Obstet Gynecol 1995;5:217-218.