Characterisation of Focal Liver Lesions with Contrast-enhanced Ultrasound: MR and CT CorrelationD P O’Regan, P S Rangi, A K Lim, C J Harvey, D O Cosgrove, M J BlomleyImaging Sciences Department, Hammersmith Hospital, Imperial College, London, UK

Introduction

Ultrasound contrast agents, used in conjunction with specifi c imaging techniques, are increasingly being used for a variety of clinical applications. The contrast agents currently used are characterised by a microbubble struc-

ture consisting of sulphur hexafl uoride gas stabilised by a phospholipid shell. They have a diameter of between 1—7μm and, unlike CT and MR contrast agents, remain within the vascular compartment. There is a complex interaction of the microbubble and the ultrasound beam. The microbubbles expand and contract emitting harmonic signals at multiples of the insonating frequency. At low acoustic power the frequency of the scattered signal is linearly related to the power of the incident beam. As the acoustic power increases, more complex non-linear interactions occur and at a high mechanical index (MI) microbubble disruption may be ob-served. The availability of more stable microbubble structures, such as SonoVue (Bracco, Italy) has allowed the devel-opment of contrast specifi c low-MI imaging modes to be developed. This is of considerable advantage for the de-tection and characterisation of focal lesions1,2. An added opportunity offered by the latest contrast specifi c modes, is the use of a destructive (high MI) pulse to destroy the bubbles and to observe reperfusion of the lesion. In the liver these techniques allow the arterial phase, portal phase and sinusoidal phase to be imaged succes-sively in real-time. Liver lesions have characteristic enhancement patterns according to their microvascular struc-ture. For instance, malignant lesions do not sequester microbubbles as they do not contain normal liver tissue and thus they appear as focal defects against the normal enhanced liver parenchyma2. A characteristic pattern of en-hancement may be observed in other liver lesions that is similar to that described in other enhanced imaging tech-niques. For instance, peripheral nodular enhancement with centripetal fi lling may be observed in haemangiomas, while typical spoke-wheel arterial enhancement is seen in focal nodular hyperplasia. A particular advantage of contrast enhanced ultrasound (CE-US) is that lesions that are so often indeterminate on unenhanced US, such as regernerative nodules and focal fatty change, characteristically are isoenhancing to the surrounding liver parenchyma. This poster will review four typical liver lesions that have been imaged using both CE-US and cross-sectional imaging as part of our research work in characterising focal hepatic lesions.

Cavernous Haemangioma

Arterial Portal Sinusoidal

Metastases Complete/rim enhancement hypoenhancing hypoenhancing

Hepatocellular carcinoma Hyperenhancing +/- non-enhancing necrosis Iso-/hypoenhancing hypoenhancing

Haemangioma Peripheral nodular enhancement Centripetal fi lling Complete enhancement

Focal nodular hyperplasia Hyperenhancing, spoke wheel arteries Hyperenhancing with non-enhancing central scar

Iso/hyperenhancing with hypoen-hancing scar

Focal Fatty Sparing isoenhancing isoenhancing isoenhancing

Regenerative nodule Typically isoenhancing isoenhancing isoenhancing

Enhancement patterns of focal liver lesions4

Dynamic imaging following the administration of SonoVue demonstrates the characteristic enhancement pattern of an hae-mangioma (top row). Images were acquired in low mechanical index Pulse Inversion mode (Philips, Holland) so that no background signal from unenhanced liver parenchyma is displayed. The lesion shows peripheral nodular enhancement (fi gs i - ii) with subsequent centripetal fi lling (fi g iii). This pattern of enhancement and the lesion’s disappearance in the delayed phase (fi g iv) strongly suggests a benign lesion. An equivalent pattern of enhancement is seen on the dynamic Gadolinium enhanced gradient T1 weighted MR, imaged at 20s, 60s and 120 seconds (fi gs v - vii).

Liver metastases

The top row of images were acquired using Vascular Recognition Imaging (VRI—Toshiba, Japan) that depicts the micro-bubbles as an overlay that is colour-coded for fl ow direction, as in colour Doppler, but additionally shows non-moving mi-crobubbles as a green tint. Images are acquired in real-time immediately following contrast injection (fi g i) and demon-strate the metastases as hypervascular lesions in the arterial phase (fi g ii), while in the later sinusoidal phase SonoVue has cleared from the vessels and the metastasis appears as a void against the liver parenchyma (fi g iii -iv). The enhanced CT (fi g v) demonstrates both target lesion metastases as well as more diffuse involvement in the left lobe.

Hepatocellular carcinoma

This hepatocellular carcinoma shows intralesion enhancement with foci of hypoenhancing necrosis on VRI mode in the ar-terial phase (fi g i). In the later phases (fi gs ii - iii) there is washout of contrast and the lesion appears as a defect against background sinusoidal liver enhancement. This pattern of enhancement has a high sensitivity for malignancy. The CT (fi g iv) shows a lesion of mixed attenuation during portal phase imaging. Radiological surveillance of cirrhotic livers for HCC has limited sensitivity and specifi city. However, the use of microbubble contrast agents has shown promise and may detect oc-cult carcinomas before they are apparent on MRI5.

Focal nodular hyperplasia

On the B-mode unenhanced image (fi g i) the focal nodular hyperplasia shows subtly different echotexture. Following SonoVue injection the subsequent images were acquired with the Pulse Inversion technique. In the arterial phase (fi g ii) there is “spoke wheel” enhancement of the lesion. In the delayed phases (fi gs iii - iv) the liver has increased in echogenicity to match the lesion and a hypoenhancing central scar is visible. A gradient T1-weighted Gd-enhanced MR demonstrates a similar appearance (fi g v) in the arterial phase.

Conclusion

These examples show how CE-US may be useful in clinical practice in non-invasively characterising focal liver lesions. As a general indicator benign lesions are hyperenhancing during the sinusoidal phase, while malignant lesions ap-pear as voids against background parenchymal enhancement. Ultrasound Microbubble contrast agents have dramatically extended the clinical and research applications of ul-trasound. Microbubbles are no longer regarded as only a ‘Doppler rescue’ agent but also for detecting, characterising and quantifying fl ow in normal or pathological tissues. The stability of the new generation of microbubbles such as SonoVue together with the advancement of ultrasound technology, has allowed real time imaging with these agents. This has led to improved liver lesion characterisation and with tissue specifi c agents, improved detection of focal liver lesions to rival that of CT and MR . Their use is in clinical practice is both straightforward and well-tolerated with a good safety profi le. Current research is being directed towards development of the next generation of microbubbles, which are ca-pable of encapsulating therapeutic agents and releasing them when exposed to high MI US signals. These could in-clude genes6, thrombolytics and oncological drugs and has the clinical potential of increasing the therapeutic effi cacy while decreasing systemic side-effects

An electronmicrograph showing the ultrastructure of the envelope of the gas-fi lled microbubbles.

References

1. Bryant TH, Blomley MJ, Albrecht T, Sidhu PS, Leen EL, Basilico R, Pilcher JM, Bushby LH, Hoffmann CW, Harvey CJ, Lynch M, MacQuarrie J, Paul D, Cosgrove DO. Improved characterization of liver lesions with liver-phase uptake of liver-specifi c microbubbles: prospective multicenter study. Radiology. 2004 Sep;232(3):799-809.2. Leen E, Angerson WJ, Yarmenitis S, Bongartz G, Blomley M, Del Maschio A, Summaria V, Maresca G, Pezzoli C, Llull JB. Multi-centre clinical study evaluating the effi cacy of SonoVue (BR1), a new ultrasound contrast agent in Doppler investigation of focal hepatic lesions. Eur J Radiol. 2002 Mar;41(3):200-3. Cosgrove D, Blomley M. Liver tumors: evaluation with contrast-enhanced ultrasound. Abdom Imaging. 2004 Jul-Aug;29(4):446-544. EFSUMB Study Group, Guidelines for the use of Contrast agents in Ultrasound, Ultraschall in Med 2004; 25: 249-2565. Harvey CJ, Lim AK, Blomley MJ, Taylor-Robinson SD, Gedroyc WM, Cosgrove DO. Detection of an occult hepatocellular carcinoma using ultrasound with liver-specifi c microbubbles. Eur Radiol. 2002 Dec;12 Suppl 3:S70-3.6. Lu QL, Liang HD, Partridge T, Blomley MJ. Microbubble ultrasound improves the effi ciency of gene transduction in skeletal muscle in vivo with reduced tissue damage. Gene Ther. 2003 Mar;10(5):396-405.

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