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Recent progress in diagnostic ultrasound techniques

While revolutionary advances in CT and MR have attracted much attention in recent years, a quieter but still major evolution has been taking place in the world of ultrasonography

Norbert Gritzmann
Professor of Radiology
Radiologie KH Barmherzige Brüder
Salzburg, Austria

David H Evans PhD DSc
Professor of Medical Physics
Department of Cardiovascular
Sciences
School of Medicine
University of Leicester
Department of Medical Physics
Leicester Royal Infirmary
Leicester, UK

The introduction of multi-row technology has revolutionised CT in the past few years. Fast sequences, high SENSE factors and strong gradients have improved MR substantially. This has led to new indications for both techniques, as for example in cardiac imaging. Has similar progress occurred in ultrasound
imaging? The answer to this question must surely be yes. The improvements may not appear as revolutionary as in CT or MR, but there is little doubt that giant strides have been made
in ultrasound technology and that the resultant images are constantly improving and contributing more diagnostic information. In what follows, some new applications of sonography are evaluated.

Ultrasonic contrast agents (UCAs) and contrast-enhanced ultrasound (CEUS)
CEUS and the liver
The liver is at present the main target organ for CEUS,[1] but an adequate image quality before contrast enhancement is a prerequisite. Modern ultrasound machines with sophisticated signalprocessing techniques can use very low mechanical index pulses that do not disrupt the shells of the UCAs and thus allow excellent visualisation of the vascular system. The evaluation of blood flow kinetics using ultrasound is at least equal to
that of CT and MR since continuous visualisation of the contrast agent is possible, and because ultrasonic contrast agents remain within the intravascular space.

Furthermore, it is possible by the use of relatively high-intensity pulses (still within the diagnostic range) to destroy the agent in a particular region and watch the reperfusion of that region. UCAs are used in many centres for the routine differentiation of focal liver lesions.[2,3]

In the case of malignant lesions of the liver, more lesions are visualised with than without the use of UCAs, and in the late phase an accurate differentiation of benign and malignant focal liver lesions is possible, comparable to that obtained with multidetector CT.[4] Also, the therapeutic effect of radiofrequency ablation of tumours can, and should, be monitored with UCAs.

CEUS and the heart
One of the most important uses of UCAs is echocardiography.
It has many roles such as improving endocardial border definition, evaluation of shunts and regurgitation, imaging of myocardial perfusion, and assessing coronary arteries and
coronary blood flow reserve.

CEUS and other organs
Although mainly used in the liver, UCAs have a developing role in the pancreas, kidney and spleen. A potential new application is in the differentiation of tumours of the pancreas.[5] In particular, hypervascularised endocrine tumours can be recognised as being strongly supplied with arterial blood. Even proof of avascular necrosis in pancreatitis might be possible using UCAs. Traumatic parenchymal lesions in the liver, spleen and kidneys can be visualised substantially more accurately than in native scans. Liver, spleen and kidney infarcts can be diagnosed far better than with standard imaging,[6] and focal
nephritis can also be visualised with UCAs. Another potential application might be the evaluation of complex cystic lesions in the kidneys. UCAs are also useful in the assessment of urinary reflux in children. In the arterial system the differentiation between complete occlusion and subtotal stenoses, which can be crucial in deciding upon therapy, particularly in the carotid
arteries, will become a new indication for the use of UCAs.

In small parts applications inflammation can be visualised with high sensitivity using UCAs. Rheumatoid arthritis may be diagnosed during the early soft tissue phase of the disease.
Particularly exciting is the prospect of molecular imaging with UCAs.[7]

Work is continuing on the development of agents that target, amongst other things, tumours, thrombus, the reticuloendothelial system, inflammation and the lymphatic system. Perhaps even more exciting is the potential for therapy using UCAs by the local selective release of drugs from UCAs using ultrasound pulses. Bubble destruction can be achieved using only diagnostic intensities, and indeed it is important
in many applications to keep the ultrasound intensity relatively low so as not to inadvertently destroy the contrast agent.

Limitations of CEUS

In general, the skill level required to use CEUS exceeds that required for native ultrasound examinations as the investigator requires extra knowledge of contast agents, the kinetics of contrast agents and the vascularisation of tumours. The method is also more time-consuming, and of course to some degree negates one of the greatest advantages of ultrasound, its complete noninvasiveness. Another issue with UCAs has
been the unwillingness of the different healthcare systems, financed through the public purse or through insurance companies, to finance the additional costs of these agents. In the liver, pancreas, liver, spleen and kidneys, contrast agents
are obligatory in CT and MR studies, so it is difficult to understand why ultrasound is singled out in this way when it can provide therapeutically relevant information in many situations.

Broadband transducers and harmonic Imaging
Important progress has been made in transducer design such that broadband transducers are commonplace. They allow the ultrasonic interrogation frequency to be optimised for the scanning depth; high frequencies close to the transducer
to give the best possible resolution, and lower frequencies from deep structures to optimise the signal-to-noise ratio. Tissue harmonic imaging and its variants such as pulse inversion harmonic imaging, which require broadband transducers to
receive both the fundamental and harmonic frequencies,
have become standard in many applications. These techniques increase the contrast of lesions, and some artefacts are reduced, but have the disadvantage of being limited to shallower depths. Many high-end ultrasound machines now use pulse encoding to provide better penetration at a given frequency, or an increase in frequency for the same penetration depth.

Volume acquisition techniques
Due to the great computing power of modern ultrasound machines it is possible to quickly acquire 3D and even 4D datasets. In obstetric ultrasound, where the presence of amniotic fluid makes segmentation very easy, 3D is very popular, and it is becoming more widespread in cardiology
applications; in radiology, however, the real indications are far more rare.

The demonstration of lumps in the breast and the reconstruction of frontal planes can provide additional information. The optimisation of ultrasound-guided biopsy in real time using 4D ultrasound can be advantageous as the location of the needle tip can sometime be better appreciated
than in 2D ultrasound. Also, volumetric scanning of the thyroid gland provides better volume estimation, and similar techniques might be of advantage in comparing tumour volumes.

Compound scanning techniques
While tissue boundaries do not act as perfect specular reflectors, the energy returning from a boundary tends to fall off away from the normal, and therefore it can be advantageous to interrogate lesions from different directions and combine the information thus obtained. This can result in a better delineation and detection of lesions,[8] but may also reduce diagnostically useable artefacts such as posterior shadowing. Also, the frame rate of the real-time image is reduced.

Elastography
Another emerging field is that of elastography, where ultrasound is used to produce maps of the compressibility or elasticity of regions of tissue. This is being clinically evaluated as a means of detecting and differentiating lesions in the
breast, prostate, thyroid gland and liver amongst other organs.[9–11]

Portable devices
A major trend in diagnostic ultrasound has been towards miniaturisation, and there are now many machines available that are comparable in size to laptop computers. Some of these machines produce excellent images, although they do not include all the facilities available on a standard cart-based machine, and are particularly useful when it is better to take the ultrasound machine to the patient rather than visa versa.

Thus these machines are particularly useful in critical care and emergency departments, but are also finding their way into many other hospital departments where they are used for simple tasks such as image guidance for the placement of central venous catheters, for venous access lines and for nerve blocks, and for simple imaging tasks such as diagnosis of cholecystolithiasis, urinary obstruction and cysts.

One concern regarding the new small portable (and inexpensive) machines is that they are finding their way into clinical environments where the users are not imaging experts. It is clearly vital that proper training is given to practitioners
wishing to use such instruments even for relatively straightforward tasks.

Panoramic techniques
These serve as a clear way of demonstrating and documenting pathologies but do not aid the diagnostic process greatly.[12]

New clinical application areas
A number of new clinical applications of sonography have been introduced in the past few years. A particularly interesting innovation is the diagnosis of peripheral nerve entrapment syndromes (for example, carpal tunnel syndrome). Superficial
nerves can be visualised with superb resolution ultrasonically, and the modality can be useful for assessing traumatic nerve lesions.

The ultrasonic guidance of peripheral nerve blocks is becoming routine in many centres, and the guidance of radiofrequency ablation of tumours is frequently performed. Small parts
and superficial imaging can produce stunning images through the use of higher and higher frequencies.

The dynamic investigation of joints and tendons has suggested new indications in sports medicine and rheumatology. In superficial tissues, ultrasound can be regarded as the gold standard for differential diagnosis of lymphadenopathies.
Detection and imaging of flow in both peripheral and central vessels has become substantially more sensitive and artefact free. Finally, the use of high-intensity focused ultrasound (HIFU) for the destruction of tumours is undergoing clinical
trials in several centres.

Other considerations
One of the drawbacks of ultrasound is that it remains highly examiner-dependent. The practitioner scanning the patient usually has to make a diagnosis directly during the examination. A retrospective evaluation and/or a second opinion is much more difficult than with other imaging
procedures. Real-time scans are not usually recorded, although longer digital video loops could help to solve this problem, and the capture of complete 3D datasets could allow examiners
retrospectively to carry out virtual scans.

Because of the unusual examiner dependence of ultrasound, it is particularly vital that ultrasonic practitioners remain abreast of both clinical and technological developments, and it is hoped that industry will continue to support education and training initiatives to ensure ultrasound practitioners perform at the highest levels, thus supporting the continued growth of
the technique.

Although the need for the practitioner to spend time with the patient at the bedside is often considered a disadvantage, it also has advantages in that it leads to good intensive physician–patient communication that is highly appreciated by most patients and can often be of considerable benefit.

References
1. Claudon M, Cosgrove D, Albrecht T, Bolondi L, Bosio M, Calliada F, et al. Guidelines and good clinical practice
recommendations for contrast enhanced ultrasound (CEUS) – update 2008. Ultraschall Med 2008 Feb;29(1):28-44.
2. Dietrich CF, Schreiber-Dietrich D, Schuessler G, Ignee A. [Contrast enhanced ultrasound of the liver – state
of the art.] Dtsch Med Wochenschr 2007 Jun 1;132(22):1225-31. (In German.)
3. Li R, Guo Y, Hua X, He Y, Ding J, Guo A, Luo M. Characterization of focal liver lesions: Comparison of pulseinversion harmonic contrast-enhanced sonography with contrast-enhanced CT. J Clin Ultrasound 2007 Mar;35(3):
109-17.
4. Catala V, Nicolau C, Vilana R, Pages M, Bianchi L, Sanchez M, Bru C. Characterization of focal liver lesions: comparative study of contrast-enhanced ultrasound versus spiral computed
tomography. Eur Radiol 2007 Apr;17(4):1066-73.
5. D’Onofrio M, Zamboni G, Faccioli N, Capelli P, Pozzi Mucelli R. Ultrasonography of the pancreas. 4. Contrast-enhanced imaging. Abdom Imaging 2006 Jul 13; Epub.
6. Von Herbay A, Schick D, Horger M, Gregor M. [Low-MI sonography with the contrast agent SonoVue in the diagnosis
of infarction of the spleen, kidney, liver and pancreas.] Ultraschall Med 2006 Oct;27(5):445-50. (In German.)
7. Liang H-D, Blomley MJK. The role of ultrasound in molecular imaging. Br J Radiol 2003:76:S140-S150.
8. Techavipoo U, Varghese T. Improvements in elastographic contrastto-noise ratio using spatial-angular compounding. Ultrasound Med Biol 2005 Apr;31(4):529-36.
9. Bae U, Dighe M, Dubinsky T, Minoshima S, Shamdasani V, Kim Y. Ultrasound thyroid elastography using carotid artery pulsation: preliminary study. J Ultrasound Med 2007 Jun;26(6):797-805.
10. Friedrich-Rust M, Ong MF, Herrmann E, Dries V, Samaras P, Zeuzem S, et al. Real-time elastography for noninvasive
assessment of liver fibrosis in chronic viral hepatitis. AJR Am J Roentgenol 2007 Mar;188(3):758-64.
11. Itoh A, Ueno E, Tohno E, Kamma H, Takahashi H, Shiina T, et al. Breast disease: clinical application of US elastography for diagnosis. Radiology 2006 May;239(2):341-50.
12. Krombach GA, Truong S, Staatz G, Mahnken A, Prescher A, Tacke J, et al. [Panoramic ultrasonography of the abdominal wall for delineation of the anatomy and diagnosis of pathological findings.] Rofo 2001 Aug;173(8):714-9. (In German.)

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