Contrast-specific Imaging Techniques Research Articles

A Comparison of the Sensitivity of Contrast-Specific Imaging Modes on Clinical and Preclinical Ultrasound Scanners.

Ultrasonic contrast agents are used routinely to aid clinical diagnosis. All premium- and mid-range scanners utilise contrast-specific imaging techniques to preferentially isolate and display the nonlinear signals generated from the microbubbles when insonated with a series of ultrasound pulses. In this manuscript the abilities of four premium ultrasound scanners to detect and display the ultrasound signal from two commercially available contrast agents—SonoVue and DEFINITY®—are compared. A flow phantom was built using tubes with internal diameters of 1.6 mm and 3.2 mm, suspended at depths of 1, 5 and 8 cm and embedded in tissue-mimicking material. Dilute solutions of SonoVue and DEFINITY® were pumped through the phantom at 0.25 mL/s and 1.5 mL/s. Four transducers were used to scan the tubes—a GE Logiq E9 (C2-9) curvilinear probe, a Philips iU22 L9-3 linear array probe, an Esaote MyLab Twice linear array LA523 (4–13 MHz) and a Fujifilm VisualSonics Vevo3100 MX250 (15–30 MHz) linear array probe. We defined a new parameter to compare the ability of the ultrasound scanners to display the contrast enhancement. This was defined as the ratio of grey-scale intensity ratio in contrast-specific imaging mode relative to the B-mode intensity from the same region-of-interest within the corresponding B-mode image. The study demonstrated that the flow rates used in this study had no effect on the contrast-specific imaging mode to B-mode (CSIM-BM) ratio for the three clinical scanners studied, with SonoVue demonstrating broadly similar CSIM-BM ratios across all 3 clinical scanners. DEFINITY® also displayed similar results to SonoVue except when insonated with the Esaote MyLab Twice LA523 transducer, where it demonstrated significantly higher CSIM-BM ratios at superficial depths.

Application of contrast-enhanced ultrasound after liver transplantation: Current status and perspectives.

Liver transplantation is an effective treatment for patients with end-stage liver disease. Accurate imaging evaluation of the transplanted patient is critical for ensuring that the limited donor liver is functioning appropriately. Ultrasound contrast agents (UCAs), in combination with contrast-specific imaging techniques, are increasingly accepted in clinical use for the assessment of the hepatic vasculature, bile ducts and liver parenchyma in pre-, intra- and post-transplant patients. We describe UCAs, their technical requirements, the recommended clinical indications, image interpretation and the limitations for contrast-enhanced ultrasound applications in liver transplantation.

Clinical application and laboratory protocols for performing contrast echocardiography.

Technically difficult echocardiographic studies with suboptimal images remain a significant challenge in clinical practice despite advances in imaging technologies over the past decades. Use of microbubble ultrasound contrast for left ventricular opacification and enhancement of endocardial border detection during rest or stress echocardiography has become an essential component of the operation of the modern echocardiography laboratory. Contrast echocardiography has been demonstrated to improve diagnostic accuracy and confidence across a range of indications including quantitative assessment of left ventricular systolic function, wall motion analysis, and left ventricular structural abnormalities. Enhancement of Doppler signals and myocardial contrast echocardiography for perfusion remain off-label uses. Implementation of a contrast protocol is feasible for most laboratories and both physicians and sonographers will require training in contrast specific imaging techniques for optimal use. Previous concerns regarding the safety of contrast agents have since been addressed by more recent data supporting its excellent safety profile and overall cost-effectiveness.

Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2012

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2012: A WFUMB-EFSUMB Initiative in Cooperation with Representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Contrast-Enhanced Ultrasound Reveals Real-Time Temporospatial Changes in Uterine and Placental Vascular Perfusion During Early Pregnancy in Rhesus Macaques.

Classical morphological studies on preserved uterine tissue sections have provided an anatomical understanding of the uterine vascular changes that occur during early pregnancy, but little is known regarding the physiological changes (i.e. uterine blood flow) that occur in vivo during pregnancy initiation in primates. Doppler ultrasound (DUS), the prevailing technique used to detect the fetal heartbeat, lacks the sensitivity needed to measure the low velocity vascular perfusion associated with implantation and subsequent early placentation. Contrast-enhanced ultrasound (CEU) is a non-invasive method with high spatial resolution used to assess quantitative differences in vascular blood flow and volume. Thus, the goals of this study were to use CEU to characterize and quantify the temporal changes in the vascular adaptations associated with early pregnancy, and to compare the information provided by CEU and DUS. Adult female rhesus macaques (n = 5) in the time-mated breeding program at ONPRC were pair-caged with males of proven fertility for 96 hr during the window of ovulation, and mating was confirmed by video recording. DUS and CEU began 14 days after the first day of pairing (DAP) and continued every 3 days until a fetal heartbeat was detected by DUS. The uterus of sedated animals was first visualized on a Voluson Expert 730 system (GE HealthCare) with a 2D trans-abdominal probe with Doppler capability. CEU was performed with a contrast-specific imaging technique, via an Acuson Sequoia system (Siemens), during a continuous intravenous infusion of lipid microbubble contrast reagent (Definity). Vascular blood flow and blood volume were quantified for the myometrium, endometrium and placental lobes from replenishment kinetics on the intensity data obtained after a high power pulse sequence destroyed all microbubbles in the acoustical beam. A functional corpus luteum formed (P4 > 4 ng/mL) in all females and 80% (4/5) became pregnant, as confirmed by a fetal heartbeat observed on 28.0±1.2 DAP. CEU clearly delineated the primary and secondary lobes of the placenta ~2 days apart (paired t-test; P<0.05), on 19.8±1.0 and 22.0±1.2 DAP, respectively. DUS was not able to differentiate between the placental lobes and detected endometrial thickening on 22.8±1.0 DAP, 3 days after (P<0.05) CEU identified the primary placental lobe. Visualization of the primary lobe correlated with the vaginal bleeding associated with implantation. The CEU calculated vascular perfusion was greater (P<0.05) in the primary placental lobe, which exhibited a 29% increase in relative blood volume and a 40% increase in relative blood flow, compared with the secondary lobe on the day of heartbeat detection. CEU identified greater flow through the hypertrophied endometrial spiral arteries supplying the placental lobes compared with other regions of the endometrium, whereas changes in the myometrium were not seen. In sum, CEU has defined the temporospatial changes in vascular perfusion associated with the anatomical vascular remodeling during early pregnancy in primates. Thus, CEU has great potential as a tool for basic researchers examining the peri-implantation period in the primate endometrium. Furthermore, CEU has promise as a future application for obstetricians, to resolve vascular complications that arise during pregnancy, including ectopic implantation and preeclampsia. Supported by NIH grants HD055744, HD18185, HD07133 and RR000163. (platform)

TU‐D‐201C‐02: Subharmonic Imaging and Pressure Estimation

The use of gas filled microbubbles as contrast agents for ultrasound imaging (US) is well established by now. Such contrast agents are used world‐wide to improve the diagnostic capabilities of US especially when employed in combination with novel nonlinear contrast imaging modes such pulse inversion second harmonic and subharmonic imaging (SHI).Our group has investigated the use of SHI in breast imaging and has produced the first ever human SHI images as well as developed a new contrast imaging mode: dynamic cumulative maximum intensity (CMI) SHI. Fourteen patients with 16 breast lesions, who underwent breast biopsies with histopathological assessment, participated in a pilot study of mammography and contrast US. A Logiq 9 scanner (GE Healthcare, Milwaukee, WI) was modified to perform grayscale SHI (transmitting/receiving at 4.4/2.2 MHz). Of the 16 lesions, 4 were malignant. Mammography had a sensitivity of 100 % and a specificity of 20 %. Baseline grayscale US and PDI both achieved a sensitivity of 50 % and a specificity of 92 %, while contrast‐enhanced PDI produced 75 % and 75 %, respectively. SHI had a sensitivity of 75 % and specificity of 83 %. All the ultrasound modes produced higher specificities than mammography (p&lt;0.04). The area under the ROC curve (Az) for the diagnosis of breast cancer was 0.64 for grayscale and PDI, 0.67 with contrast enhanced PDI, 0.76 for mammography and 0.78 for SHI. For dynamic CMI‐SHI mode the Az increased to 0.90 and this was significantly better (p=0.03) than mammography. More recently, the utility of contrast microbubbles for quantitative measurements of hydrostatic pressure (in mmHg) have been explored. Changes in ambient pressure affect the reflectivity of ultrasound contrast microbubbles leading to an excellent correlation between subharmonic signals and hydrostatic pressure (r2&gt;0.90). We have proposed subharmonic aided pressure estimation (SHAPE; U.S. patent 6,302,845) and provided proof of concept of the feasibility of in vivo SHAPE. The heart and aorta of four dogs were scanned with a Sonix RP scanner (Ultrasonic Medical Corporation, Richmond, BC, Canada) modified to perform SHAPE. Simultaneously, the instantaneous pressures within the aorta were measured using a manometer‐tipped catheter. The instantaneous in vivo pressure measurements and those based on SHAPE were in good accordance over a pressure range of 0 to 70 mmHg (r2 from 0.65–0.85).In conclusion, a new contrast specific imaging technique, SHI, has been investigated for in vivo breast imaging and for quantitative measurements. SHI appear to improve the diagnosis of breast cancer relative to conventional ultrasound and mammography; albeit based on a very limited patient population. Some encouraging results in pressure estimation have been achieved.Learning Objectives:1. Understand the origin of subharmonic bubble signals2. Understand the pro's and con's of SHI3. Understand the principle of SHAPE

Diagnosis of liver cirrhosis with contrast-enhanced ultrasound

The assessment of the extent of liver fibrosis is very important for the prognosis and clinical management of chronic liver diseases. Although liver biopsy is the gold standard for the assessment of liver fibrosis, new non-invasive diagnostic methods are urgently needed in clinical work due to certain limitations and complications of biopsy. Noninvasive imaging studies play an important role in the diagnosis of focal liver disease and diffuse liver diseases. Among them, ultrasonography is the first choice for study of the liver in clinical work. With the development of ultrasound contrast agents and contrast specific imaging techniques, contrast-enhanced ultrasound (CEUS) shows good performance and great potential in the evaluation of liver fibrosis. Researchers have tried different kinds of contrast agent and imaging method, such as arrival time of contrast agent in the hepatic vein, and quantitative analysis of the enhancement level of liver parenchyma, to evaluate the degree of liver fibrosis during the past 10 years. This review mainly summarizes the clinical studies concerning the assessment of liver fibrosis using CEUS.

Cavitation and contrast: The use of bubbles in ultrasound imaging and therapy

Microbubbles and cavitation are playing an increasingly significant role in both diagnostic and therapeutic applications of ultrasound. Microbubble ultrasound contrast agents have been in clinical use now for more than two decades, stimulating the development of a range of new contrast-specific imaging techniques which offer substantial benefits in echocardiography, microcirculatory imaging, and more recently, quantitative and molecular imaging. In drug delivery and gene therapy, microbubbles are being investigated/developed as vehicles which can be loaded with the required therapeutic agent, traced to the target site using diagnostic ultrasound, and then destroyed with ultrasound of higher intensity energy burst to release the material locally, thus avoiding side effects associated with systemic administration, e.g. of toxic chemotherapy. It has moreover been shown that the motion of the microbubbles increases the permeability of both individual cell membranes and the endothelium, thus enhancing therapeutic uptake, and can locally increase the activity of drugs by enhancing their transport across biologically inaccessible interfaces such as blood clots or solid tumours. In high-intensity focused ultrasound (HIFU) surgery and lithotripsy, controlled cavitation is being investigated as a means of increasing the speed and efficacy of the treatment. The aim of this paper is both to describe the key features of the physical behaviour of acoustically driven bubbles which underlie their effectiveness in biomedical applications and to review the current state of the art.

Ultrasound Contrast Agents in Ischemic Stroke

The general indication for the use of ultrasound contrast agents in neurosonologic applications is an insufficient signal-to-noise ratio when investigating the cerebral macro- and microcirculation. Clinical problems that are often encountered in native sonography are ‘no flow, slow flow and low flow’ phenomena. In these cases, ultrasound contrast agents are used to differentiate between vessel occlusion and insufficient insonation conditions, as well as for the detection of very slow blood flow velocities and low flow volumes. Echo-contrast agents significantly increase the success rate of transcranial color duplex examinations of patients with acute cerebrovascular disease. Ultrasound contrast imaging also allows assessment of the cerebral microcirculation. There are a number of techniques available for performing perfusion studies. These generally utilize high mechanical index imaging, since until recently lower acoustic outputs were unable to detect microbubbles in the brain. New-generation microbubbles in combination with very sensitive contrast-specific ultrasound techniques now enable real-time visualization of stroke. Moreover, destruction sequences with assessment of microbubble replenishment using real-time, low mechanical index imaging are now available. This article reviews of state-of-the-art contrast-specific imaging techniques for ultrasound evaluation of acute stroke patients.

Microbubbles traversing the blood–brain barrier for imaging and therapy

In the last several years great progress has been made in the field of ultrasound perfusion imaging of the brain. Different approaches have been assessed and shown to be capable of early detection of cerebral perfusion deficits. Real-time low mechanical index imaging simplifies the acquisition of perfusion parameters and alleviates many of the previous imaging problems related to shadowing, uniplanar analysis, and temporal resolution. With the advent of this new, highly sensitive contrast-specific imaging technique new possibilities of real-time visualization of brain infarctions and cerebral hemorrhages have emerged. Microbubbles that traverse the blood-brain barrier (BBB) can also elicit bioeffects that may be used to open the BBB for targeted delivery of macromolecular agents to the brain. Possible ways in which substances cross the BBB after application of this novel approach include transcytosis, passage through endothelial cell cytoplasmic openings, opening of tight junctions, and free passage through injured endothelium. Although relatively little tissue damage occurs at low acoustic intensities capable of opening the BBB, no investigation has demonstrated a total lack of BBB injury when using ultrasound and microbubbles. Further studies are necessary to address the effects of ultrasound and microbubbles upon the various transport mechanisms of the BBB. Moreover, investigations aimed at elucidating how ultrasound and microbubbles interact at the molecular level of the BBB are necessary. Results of such studies will increase our understanding of the mechanisms of BBB opening and also allow a better appraisal of the safety of this technique for future clinical applications.

Sonografische Leberdiagnostik bei Tumorpatienten ohne und mit Kontrastmittel

In patients with known malignancy, correct detection and characterization of liver lesions has important therapeutic consequences. Conventional sonography is the most commonly used modality for liver imaging in tumor patients. However, it has a lower sensitivity for the detection of liver metastases compared to contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). The majority of liver metastases are hypoechoic and well defined in baseline ultrasound (US), while detection of isoechoic or small liver metastases <1 cm is difficult and the differentiation of liver metastases from benign liver lesions and other malignant liver tumors can be impossible with baseline US. The use of microbubble-based ultrasound contrast agents and contrast-specific imaging techniques advanced the accuracy of ultrasound in liver imaging. Levovist and SonoVue are the US contrast agents approved for liver imaging in Europe. Compared to Levovist, SonoVue allows continuous imaging of the liver in real-time over a period of up to 5 minutes. As a result, SonoVue became the preferred contrast agent for liver imaging in the recent years, while Levovist became less important. Important for the detection of liver metastases are the portal venous and late phases in which metastases show a wash-out and can be detected as hypoechoic lesions in homogeneous enhanced liver parenchyma. The detection of hepatic metastases is substantially improved by CEUS compared to conventional B-mode sonography. Several studies showed sensitivity in detecting liver metastases comparable to that of contrast-enhanced CT and MRI. Furthermore, the typical enhancement patterns of the different benign and malignant liver lesions allow reliable characterization and differentiation from liver metastases in the majority of cases. This paper provides information about the advantages and expedient application of contrast-enhanced ultrasound (CEUS) in tumor patients.

Contrast-enhanced ultrasonography (voiding urosonography) of vesicoureteral reflux: State of the art

Three methods are currently used to identify vesicoureteral reflux (VUR) in children, namely, radiographic voiding cystourethrography, radionuclide voiding cystography and, more recently, echo-enhanced voiding urosonography (VUS). Recent advances in tissue-harmonic and contrast-specific imaging techniques, together with the development of second-generation contrast agents, have improved the potential of ultrasonography both in the diagnosis and grading of VUR in children. Today, VUS is able to accurately assess the grade of reflux and the state of the urethra, previously considered fundamental limitations to the extensive use of this technique. The aim of our paper is to review the role of ultrasonography in the diagnosis of VUR, from the initial experiences up to the recent use of second-generation microbubbles combined with contrast-specific low-mechanical-index software. We discuss the advantages and limits of VUS with respect to radiographic and radionuclide imaging in the light of an analysis of the most recent literature, and we described the new VUS study technique using second-generation contrast media. Growing requests by paediatric nephrologists and surgeons require that even general radiologists become familiar with this technique.

Comparison of Contrast Enhanced Ultrasound and Contrast Enhanced CT or MRI in Monitoring Percutaneous Thermal Ablation Procedure in Patients with Hepatocellular Carcinoma: A Multi-Center Study in China

To evaluate the ability of contrast enhanced ultrasound (CEUS) in monitoring percutaneous thermal ablation procedure in patients with hepatocellular carcinoma (HCC) in comparison with contrast enhanced computed tomography (CECT) and/or magnetic resonance imaging (CEMRI). A total of 151 patients were enrolled in the study. Before the radio-frequency (RF) or microwave ablation treatment, tumor vascularity was assessed in 139 patients with three imaging modalities i.e., US (139 exams), CEUS (139 exams) and CECT (103 exams)/CEMR (36 exams). CEUS examination was performed using a sulphur hexafluoride-filled microbubble contrast agent (SonoVue ®, Bracco, Milan, Italy) and real-time contrast-specific imaging techniques. Within 30 ± 7 d after the ablation procedure, 118/139 patients were monitored to assess the tumor response to treatment. Before ablation, contrast enhancement within tumor was observed in 129/139 (92.8%) patients with CEUS and 133/139 (95.7%) patients with CECT/CEMRI. Compared with CECT/CEMRI, CEUS sensitivity and accuracy in detecting tumor vascularity were 97.0% and 94.2%, respectively. One month after treatment, no enhancement was seen in 110/118 (93.2%) both on CEUS and CECT/CEMRI. Concordance between CEUS and CECT/CEMR on the presence of residual vascularization was obtained in four patients (true positive). The specificity and accuracy of CEUS in detecting tumor vascularity were 98.2% and 96.6%, respectively. The periprocedural impact of SonoVue administration on the assessment of treatment extent was also evaluated in a subgroup of patients and CEUS showed its superiority compared with baseline US in defining treatment outcome. In conclusion, in the detection of HCC tumor vascularity and assessment of response to thermal ablation after 1 month, real time CEUS provided results comparable to those obtained with CECT/CEMRI. CEUS examination proved to be a safe and easy to access procedure, with potential for diagnostic impact in the clinical practice. (E-mail: lumd@21cn.com)

Transcutaneous contrast enhanced sonography of the chest for evaluation of pleural based pulmonary lesions: experience in 137 patients

Transcutaneous ultrasound enables visualization of pleural based lesions but with a poor correlation to specific pathology. Ultrasound contrast agents in conjunction with contrast specific imaging techniques are increasingly accepted in clinical use. Up to date there are no data about the use of contrast enhanced sonography (CES) in a large series of pleural based pulmonary lesions. From August 2004 to August 2005, 137 consecutive patients with pleural based pulmonary lesions on B-mode sonography were studied by CES using a transcapillary second-generation contrast agent (SonoVue(R)). The following CES parameters were retrospectively evaluated. Time to enhancement (TE) of contrast agent after i. v. application was determined and classified as short TE (< = 6 sec) vs. delayed TE (> 6 sec). Extent of enhancement (EE) was evaluated during the arterial phase (2 - 30 sec) and the parenchymal phase (1 - 5 minutes) by using the normal splenic tissue as an in vivo reference, and classified in reduced EE (anechoic/hypoechoic) vs. marked EE (isoechoic/hyperechoic) during both phases. Homogeneity of enhancement (HE) was classified as homogeneous vs. inhomogeneous. 60 patients had histologically confirmed malignant lesions due to central lung cancer (n = 31), and peripheral malignant lesions (n = 29). 77 patients had benign pleural based lesions including pneumonia (n = 32), pulmonary embolism (n = 20), compression atelectasis (17), and other benign pleural based lesions (n = 8). Malignant and benign lesions did not vary significantly regarding TE, EE, and HE. However, there were highly significant differences in the ratio of short vs. delayed TE and reduced vs. marked EE between the six disease groups. Characteristic patterns were short TE with marked EE in all compression atelectasis cases and in 62 % of patients with pneumonia. Delayed TE and reduced EE was seen in all patients with pulmonary embolism and in 62 % of patients with peripheral malignant lesions. Central lung cancer and benign nodules did not present with such specific patterns. No significant differences in HE were seen between subgroups. Pulmonary lesions are characterized by different CES-patterns of arterial supply as evidenced by TE and EE which depends on underlying causes, but CES does not allow to distinguish benign from malignant pleural based lesions in general.

Transcutaneous Contrast-Enhanced Sonography of Peripheral Lung Lesions

Transpulmonary sonography contrast agents, in conjunction with contrast-specific imaging techniques, are increasingly accepted in clinical use for diagnostic imaging of several organs. Anatomically, the lung is characterized by dual blood sources, supplied from both the pulmonary and bronchial arteries. Contrast-enhanced sonography enables us to determine whether the pulmonary or the bronchial arteries are the source of blood to lung lesions, depending on the time to enhancement and the extent of enhancement after contrast agent application. This article reports our first experience with transcutaneous contrast-enhanced sonography for the diagnosis and differential diagnosis of peripheral lung lesions.

Contrast specific imaging in the detection and localization of prostate cancer.

Prostate cancer (PCa) is the most common cancer in elderly men and is one of the most important causes of death from cancer in men. The diagnosis of PCa is based on a combination of digital rectal examination, PSA and transrectal ultrasound (TRUS). However, this combination does not reach the accuracy of detection and localization necessary for proper decisions on treatment methods. Therefore, biopsies are performed in all cases for which the suspicion of PCa is raised. Even with biopsies, staging and grading of PCa is far from optimal. More accurate imaging is necessary to improve the biopsy sampling, the goals being to replace systematic biopsies by a targeted approach and to improve staging and grading of PCa. Ultrasound imaging of the prostate remains the first choice of imaging to visualize the prostate, however, gray-scale ultrasound imaging has an accuracy of about 50-60% for the detection of PCa and TRUS used for local staging has an even lower accuracy. The development of PCa is associated with changes in the metabolism of tumor cells, and therefore with changes in the blood perfusion of the involved tissue. This paper focuses on contrast specific imaging techniques to visualize these changes in blood perfusion. Techniques such as color and power Doppler imaging, and contrast enhanced imaging techniques using color and power Doppler, harmonic imaging and intermittent imaging are discussed.

Detection and characterisation of liver metastases

Modern liver imaging of cancer patients requires an imaging modality that is not only highly sensitive in detecting lesions but also provides reliable characterisation of lesions and thus allows differentiation of metastases from frequently found benign lesions. Conventional ultrasound (US) has a relatively poor sensitivity and specificity for imaging liver metastases and US used to be inferior to CT and MRI mainly due to a lack of contrast agents. This has changed with the advent of microbubble contrast agents for US. The use of recent contrast agents such as SonoVue (Bracco, Italy) combined with low mechanical index contrast-specific imaging techniques such as Contrast Pulse Sequencing provides dynamic real time imaging of focal liver lesions in the arterial, portal venous and delayed phase. This improves lesion detection and characterisation. To investigate the benefit of SonoVue for detecting liver metastases we studied 40 cancer patients with liver lesions on reference imaging (CT or MRI), 37 of them had metastases. The mean number of reference confirmed metastases per patient increased from 1.85+/-1.79 on conventional ultrasound to 2.73+/-2.50 post SonoVue (p < 0.05). CEUS showed more individual metastases than baseline in 12 (34%) patients. Using CT or MRI as the reference, the mean sensitivity to individual metastases increased from 69% on baseline US to 90% post contrast (p < 0.0005). The role of SonoVue in characterisation of focal liver lesions was evaluated in 63 patients. One lesion was studied per patient. Based on standardised dynamic enhancement criteria for each lesion type, the number of correctly diagnosed lesions improved from 41 (65%) on baseline US to 58 (92%) post contrast (p < 0.001). On CEUS all 27 metastases were correctly diagnosed, while baseline US misinterpreted 2 of these. The number of correctly diagnosed benign lesions (n = 28) increased from 12 (43%) on baseline to 25 (89%) post SonoVue. In conclusion, detection and characterisation of focal liver lesions by US are markedly improved by the use of SonoVue. Contrast agents add a new dimension to sonography allowing it to rival CT and MRI, especially for lesion characterisation.

Ultrasound contrast agents

Ultrasound contrast agents consist of tiny gas bubbles encapsulated by a stabilising membrane or shell. When combined with recent contrast-specific ultrasound techniques, they provide substantial enhancement of vessels and solid organs. The clinical use and the diagnostic value of ultrasound contrast agents are in principle comparable to those of contrast agents for CT and MRI. They add an additional dimension of information to sonography, which results in considerable improvement of diagnostic accuracy in many cases. This paper reviews the physicochemical properties of various microbubble contrast agents, discusses non-linear bubble behaviour and contrast-specific imaging techniques. An overview of the most important radiological clinical applications in the liver, kidney and spleen is given.

Ultrasound Imaging of Focal Liver Lesions with a Second-Generation Contrast Agent

For several years, the major diagnostic objective in using US contrast agents has been to detect flow in the circulation at a lower level than that otherwise possible in Doppler techniques. However, it turned out that enhanced color and power Doppler could provide fine details on small and deep vessels, but were not sensitive enough to detect contrast agents in the microcirculation. As a result, the usefulness of contrast agents in the field of liver imaging was limited to the evaluation of the vascular architecture of focal lesions. Recently, the development of new US techniques that produce images based on nonlinear acoustic effects of US interaction with microbubble contrast agents has opened new prospects for US imaging of the liver. These contrast-specific imaging techniques, in fact, can display microbubble enhancement in gray-scale, thus maximizing contrast and spatial resolution and enabling the analysis of the microcirculation. These techniques offer high sensitivity either to microbubble movement or to microbubble collapse independent of the level of the applied acoustic peak pressure. At low acoustic peak pressure levels grossly reflected by a low mechanical index (MI) the microbubble destruction can be reasonably neglected and the microbubble movement effect due to blood circulation is predominant. In contrast, when increasing the acoustic peak pressure levels (high MI), the destruction phenomena become the most important: the signal, in fact, is produced by microbubble collapse, and is related to microbubble concentration and not to blood flow velocity (1–3). We performed a pilot clinical study aimed at investigating the usefulness of both destructive (high MI) and non-destructive (low MI) gray-scale US techniques, in combination with a second-generation contrast agent, for the detection and characterization of focal liver lesions.