Splanchnic vessels

Ultrasound in Med. & Biol., Vol. 26, Supplement 1, pp. S73–S75, 2000 Copyright © 2000 World Federation for Ultrasound in Medicine & Biology Printed in the USA. All rights reserved 0301-5629/00/$–see front matter

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● Part II: Clinical Applications SPLANCHNIC VESSELS MICHEL LAFORTUNE,* PETER N. BURNS,† HEIDI PATRIQUIN‡ and MICHEL DAUZAT§ *Department of Radiology, University of Montreal, Hoˆpital Saint-Luc, Montreal, Quebec, Canada; †Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; ‡Department of Radiology, University of Montreal, Hoˆpital Sainte-Justine, Montreal, Quebec, Canada; and §Unite´ d’Exploration Vasculaire, CHU, Nıˆmes, France

INTRODUCTION

presentation software. One of the major limitations of current Doppler methods is that they present only the flow velocities toward or away from the transducer, that is, in one dimension. This has little practical impact in peripheral vascular applications, where the vessels are, for the most part, parallel to the skin surface; but, in the complex geometry of the liver, for example, the ability to show true velocity, regardless of vessel direction, would be a major advantage. Curiously, although such promise of fully resolved, or “vector” Doppler measurement has been with us for some time, it is by no means clear how we would present 2-D velocity data in a colour-coded image that would be as readily interpretable as the current red-blue colour maps, with which we have become so familiar. Studies of liver and abdominal masses and their relationship with the feeding and surrounding vessels, for example, would be enhanced greatly by 2-D velocity resolution and 3-D presentation.

Sonography of the hepatobiliary and gastrointestinal systems has been transformed in the past decade by the additional haemodynamic information provided by Doppler sonography. What can we expect in the next millennium? As a starting point, we can review applications in this area and identify the direction of developments in the technology. We may then combine these with the evolving clinical uses of splanchnic vessel imaging to arrive at some expectations for the next decade. IMAGING OF SPLANCHNIC VESSELS The development of abdominal sonography and, especially, the evolution of its Doppler modality from continuous wave to pulsed-duplex and to colour Doppler imaging, has revolutionised imaging of the splanchnic vessels and improved our understanding of splanchnic haemodynamics in healthy and pathological states. Computed tomography (CT) and magnetic resonance imaging (MRI) entered the field during this period and greatly improved the precision of imaging of the abdominal vessels. Sonography, however, has maintained its advantages of ease of performance without preparation or sedation, its noninvasive nature and its relatively low cost. Real-time imaging in any anatomic plane, exquisite delineation of vascular structures and determination of flow velocity, waveform and direction continue to be its major attractions. Three-dimensional (3-D) ultrasound (US) imaging, today still inferior to that accomplished by CT and MRI, will no doubt improve with the arrival of 2-D arrays, improvement of image acquisition, Doppler analysis and

DOPPLER SONOGRAPHY OF SPLANCHNIC VESSELS Doppler sonography improved our understanding of liver and splanchnic blood flow in health and disease. Previously, vascular studies required catheterisation with injection of contrast material that is invasive and, in itself, can change the dynamics of the system. Quantitative investigations into splanchnic blood flow were necessarily confined to animals. US has permitted, for the first time, examination of the healthy person in the resting state and after normal physiological activities, such as eating or exercise, with effects on splanchnic hemodynamics that are clearly demonstrable. Patients with tumours, cirrhosis, or other diseases of the liver can be examined similarly and their splanchnic circulation can be studied in the resting state and after the injection of various drugs used in the treatment of their disease (e.g., vasoactive drugs or sclerotherapy). Portal

Address correspondence to: Dr. Michel Lafortune, Department of Radiology, Centre hospitalier de l’Universite´ de Montrea´l, Hopˇital Saint-Luc, 1058 Saint-Denis Street, Montreal, Quebec H2X 3J4 Canada. S73

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hypertension can also be recognised through its effect on the splanchnic circulation and the recognition of portosystemic collaterals. The effects of tumour-induced angiogenesis within the liver can be recognised not only by visualising abnormal morphology of vessels, but also by the increased velocity and calibre of the hepatic artery leading to the involved lobe or segment (Taourel et al. 1998). Such quantitative volumetric flow measurements using Doppler sonography, however, require a rigorous technique and are still fraught with errors. In the future, it will be necessary to be able to obtain flow measurements from the hepatic and portal circulations with the same precision that can be currently be achieved only with large vessels such as the ascending aorta. With such a tool, it will be interesting and useful to relate the volume of blood flow in the left gastric vein to the risk of bleeding from oesophageal varices. Because thrombosis of the main portal vein precludes liver transplantation in most patients, determination of critical threshold blood volume in prethrombotic states could predict impending portal venous thrombosis in potential liver graft recipients. The understanding of drug-induced haemodynamic changes and the method of action of drugs in patients with portal hypertension will be greatly increased after accurate splanchnic volume flow measurements are possible. Comparative measurements of portal and hepatic arterial blood flow may be useful in the prediction and follow-up of liver metastasis in cancer patients. Transplantation of livers from living donors requires an even finer analysis of the vascular anatomy of the liver, both before and during the procedure. We will need sonographic machines with better resolution, which will allow us to outline the numerous anatomical variations of the vascularisation of the liver, especially of the hepatic artery. Physiological adaptation to stenosis of the hepatic, splenic or mesenteric arteries can be easily studied with Doppler sonography. Acceleration of velocity at the site of stenosis is followed by a dampening of the waveform in the distal arterial bed (pulsus tardus parvus) and the direction of blood flow in segmental or mesenteric arteries changes as patent arteries come to the rescue of regions poorly vascularised because of a stenosis or occlusion. The vascularisation of individual bowel loops can also be reliably seen using Doppler sonography. There is evidence that angiogenesis associated with Crohn’s disease and, perhaps, other inflammatory bowel conditions results in blood flow changes both in the mesenteric arteries, as well as in the vasculature within the bowel wall itself (Spalinger et al. 2000). These studies will also be improved with greater accuracy in volumetric measurements. In spite of such advances, current Doppler only scratches the surface of the liver vasculature, most of which lies at the sinusoidal or presinusoidal levels,

Volume 26, Supplement 1, 2000

whose function is vital to understanding the organ and its diseases. One exciting intimation of the significance of the microvasculature has come from flow volume estimates in the hepatic artery in patients who have primary cancer elsewhere. It has become apparent that flow assessment can predict the risk of metastasis in a liver found by all other means to be free of disease (Leen et al. 1996). The potential prognostic value of subclinical angiogenesis in liver cancer is only now being explored, and US is the ideal way to do it. Clearly, completely new tools are needed if we are to be able to detect and quantify flow at the capillary and arteriolar levels. In spite of the depth of the hepatic circulation, it is often the target of interventions that require catheter or needle placement in deep tissue. The prospect, therefore, arises of the use of needle or catheter-borne Doppler devices, perhaps even combined with high-frequency imaging. If the Doppler operates in the 20 –50-MHz range, flow velocities on the order of 1 mm/s, capillary or sinusoidal, can be detected. US imaging at these frequencies could provide a guiding image with a resolution of 50 –100 ␮m. This could form the basis of surgical or laparoscopic guidance in, for example, lesion ablation. A little further off, transducers in the 100 –200 MHz range may be inserted percutaneously, and offer the examiner histological resolution of tissue imaged in vivo, in situ, revealing the liver parenchyma and its various infiltrative processes, including microscopic angiogenesis. The sonographer will approach the pathologist with this microsonographic technique. Today, however, the beginnings of an entirely new method to detect the microvasculature from the skin surface have already become apparent. Microbubble US contrast material, in combination with new imaging techniques discussed elsewhere in this Supplement, are sure to offer an important advance in splanchnic vascular investigation in the new millennium. Originally designed to enhance the blood echo and, hence, the signal-to–noise ratio of a Doppler examination, microbubble contrast in abdominal sonography has led to a plethora of exciting new possibilities. Harmonic grey-scale imaging with microbubble contrast can show the large liver vessels without the problem of motion artefact, which still haunts conventional Doppler, especially high and near the diaphragm where transmitted cardiac and respiratory motion becomes significant. The ability of the US beam to disrupt microbubbles, at first thought to be a drawback of the contrast materials, now promises to provide entirely new diagnostic information in the liver. By allowing bubbles to accumulate in the organ, and then disrupting them with high-incident pressure US, harmonic images can be made of the distribution of blood in the liver, regardless of the calibre of vessel or speed of flow. In this way, the first US images of the total vascular volume of liver tissue have been made. Focal liver lesions

Splanchnic vessels ● M. LAFORTUNE et al.

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Fig. 1. US contrast image of liver metastasis in the postvascular phase, with pathological correlation. Pulse inversion harmonic image shows distribution of the agent Levovist威 after its vascular phase. The agent persists in healthy liver tissue, but not in the metastatic lesions.

are already revealing distinct patterns using this method (Wilson et al. 2000). Furthermore, by documenting the pattern of reperfusion of tissue after the disruption of the bubbles (a process that can take up to 10 s), the relative flow rate at the tissue level can be determined. The newer technique of pulse inversion imaging increases the resolution of these images and offers the additional benefit of bubble detection at low incident intensity, which does not disrupt them. This mode can visualise long, contiguous lengths of liver and tumour vessels that cannot be seen with Doppler US, with or without contrast (Burns et al. 2000). By combining such “interval-delay” contrast imaging of the microvascular volume with real-time vessel imaging, pulse inversion contrast sonography offers the prospect of vascular information previously obtainable only with triple-phase CT. As contrast imaging methods improve, so will the ability of US to provide specific and local information about liver and lesional blood flow. The microbubble agents themselves are the subject of rapid development that is likely to intensify in the near future. In spite of their fragility and somewhat daunting current cost, they offer the only true intravascular agent available in radiological imaging. This is particularly important for the liver, where transit times across lesions such as haemangiomata can amount to tens of minutes, a time comparable to the extravasation time of most CT and MR agents by diffusion. For the liver, furthermore, the potential for specific targeting of agents is immense. Already, agents are available that are taken into the reticuloendothelial system intact, and that can be disrupted and, hence, detected at leisure after the vascular phase of the injection has passed. Other agents persist selectively in the sinusoids themselves and can be used to delineate their extent in a diseased liver by simple use of pulse inversion imaging (Fig. 1).

After liver tissue has been targeted, microbubbles might be used to deliver therapeutic agents that, in the liver, will include cytotoxic drugs or genetic material itself. Very early work attempting to transfer cells with reporter genes that express identifiable proteins or enzymes in the cell has provided promising results (Unger 1997). CONCLUSION US is assured of its continued place in the frontline of diagnosis in the haemodynamic consequences of the many diseases of the liver. The near future is likely to see this role expanded to that of the guidance, monitoring and, possibly, even the administration of minimally invasive therapy. We can be sure that, however medicine of the new millennium will encounter the challenges posed by this most important and fascinating of organs, a US machine will not be far away. REFERENCES Burns PN, Wilson SR, Hope Simpson D. Pulse inversion imaging of liver blood flow: an improved method for characterization of focal masses with microbubble contrast. Invest Radiol 2000 (in press). Leen E, Angerson WG, Cooke TG, McArdle CS. Prognostic power of Doppler perfusion index in colorectal cancer. Correlation with survival. Ann Surg 1996;223:199 –203. Spalinger J, Patriquin H, Miron M, et al. Vessel density in intestinal loops in Crohn’s disease in children: a reflection of disease activity. Radiology 2000 (in press). Taourel P, Blanc P, Dauzat M, et al. Doppler study of mesenteric, hepatic, and portal circulation. Hepatology 1998;28:932–936. Unger EC. Drug delivery applications of ultrasound contrast agents. In: Second European Symposium on Ultrasound Contrast Imaging. Books of Abstracts, Erasmus University Rotterdam:, 1997:54 –56. Wilson SR, Burns PN, Muradali D, et al. Microbubble contrast agents and harmonic imaging of the liver: imaging features in 30 patients with known hemangioma, hepatocellular and liver metastases. Radiology 2000 (in press).