Characterization Of Liver Lesions Research Articles

Functional MR imaging of the liver

The diagnostics of diffuse liver disease traditionally rely on liver biopsies and histopathological analysis of tissue specimens. However, a liver biopsy is invasive and carries some non-negligible risks, especially for patients with decreased liver function and those requiring repeated follow-up examinations. Over the last decades, magnetic resonance imaging (MRI) has developed into a valuable tool for the non-invasive characterization of focal liver lesions and diseases of the bile ducts. Recently, several MRI methods have been developed and clinically evaluated that also allow the diagnostics and staging of diffuse liver diseases, e.g. non-alcoholic fatty liver disease, hepatitis, hepatic fibrosis, liver cirrhosis, hemochromatosis and hemosiderosis. The sequelae of diffuse liver diseases, such as a decreased liver functional reserve or portal hypertension, can also be detected and quantified by modern MRI methods. This article provides the reader with the basic principles of functional MRI of the liver and discusses the importance in a clinical context.

Percutaneous real-time sonoelastography as a non-invasive tool for the characterization of solid focal liver lesions: A prospective study

BackgroundReal-time sonoelastography is currently used for the characterization of superficial solid lesions such as thyroid and breast masses. This study evaluates the usefulness of percutaneous sonoelastography for the characterization of solid focal liver lesions. Methods30 out of 43 patients with 38 known liver lesions were included in a prospective, diagnostic study. Qualitative analysis (pattern of deformation, elasticity type of liver tumour) and semi-quantitative measurements (strain ratio, hardness percentage, histogram) were evaluated. Sensitivity, specificity, positive and negative predictive values were calculated and the area under the receiver operating characteristics curve was constructed. ResultsPatterns A and C-D are specific of benign lesions and metastases respectively. The patterns for haemangiomas, focal nodular hyperplasia and metastases were significantly different to each other in terms of strain ratio, hardness percentage and histogram (p<0.05). A statistically significant difference (p<0.001) was observed between the median values of the 3 measured parameters for benign (1.02; 12%; 47) and malignant lesions (1.66; 65%; 20.5) respectively. The area under the receiver operating characteristics curve values for strain ratio, hardness percentage and histogram were 0.88, 0.89, and 0.86 respectively for cut-off values of 1.2, 45, and 30. ConclusionsBy percutaneous sonoelastography it is possible to differentiate benign versus malignant focal liver lesions, metastases in particular, with good diagnostic performance.

Contrast enhancement ultrasound application in focal liver lesions characterization: a retrospective study about guidelines application (SOCEUS-CEUS survey).

The SOCEUS survey aims to evaluate how contrast-enhanced ultrasound (CEUS) is effectively used in the focal liver lesions characterization. In the survey were involved Verona, Brescia and Trieste Radiological Centers and Arezzo and Bologna Non-radiological Centers. Inclusion criteria were liver focal lesion detection at conventional ultrasound and studied by means of CEUS, with or without CT or MRI examinations, done previous or subsequent to CEUS. 1069 forms were collected. Patients with benign lesions, who did not undergo any other studies, were 255/561 (45.5%). Among patients with diagnosis of hemangioma at CEUS, those who had no other investigations were 129/267 (48.3%). Patients with malignant lesions who had studies pre-CEUS (CT and/or MRI) were 328/508 (65%), whereas those who had examinations post-CEUS (CT and/or MRI) were 218/508 (42.9%). Concordance rate between CEUS and CT investigations pre- and post-CEUS was, respectively, 66 and 89%. Concordance rate between CEUS and MRI studies pre- and post-CEUS was, respectively, 87.5 and 81.5%. This study proves contrast-enhanced ultrasound correct application in the involved centers.

Possibilities of sonographic image fusion: Current developments

For diagnostic and interventional procedures ultrasound (US) image fusion can be used as a complementary imaging technique. Image fusion has the advantage of real time imaging and can be combined with other cross-sectional imaging techniques. With the introduction of US contrast agents sonography and image fusion have gained more importance in the detection and characterization of liver lesions. Fusion of US images with computed tomography (CT) or magnetic resonance imaging (MRI) facilitates the diagnostics and postinterventional therapy control. In addition to the primary application of image fusion in the diagnosis and treatment of liver lesions, there are more useful indications for contrast-enhanced US (CEUS) in routine clinical diagnostic procedures, such as intraoperative US (IOUS), vascular imaging and diagnostics of other organs, such as the kidneys and prostate gland.

Evaluation of the diagnostic accuracy of CEUS in children with benign and malignant liver lesions and portal vein anomalies

Comparison of the diagnostic findings of MRI, CT and CEUS in children with benign and malignant and portal venous anomalies of the liver. Retrospective analysis of the diagnostic findings of CEUS, MRI and CT scans in 56 children (age 0-17 years) with a total of 60 benign and malignant liver lesions and anomalies of the portal vein/perfusion. All patients underwent CEUS using sulphur hexafluoride microbubbles and a multi-frequency probe (1-5 MHz, 6-9 MHz). Cine-loops were stored up to 3 minutes. MRI was performed in 38 lesions. CT was performed in 8 lesions. Out of the 56 patients 49 liver lesions (48 benign, 1 malignant), 9 anomalies of the portal vein/perfusion and 2 of the biliary system were detected. 16/49 lesions were analyzed histopathologically. Using CEUS, the characterization of the lesions was possible in 45 out of 49 cases. In 32 cases, CEUS provided the exact diagnosis. Only two benign lesions were falsely categorized as malignant.Findings of MRI and CEUS were concordant in 84% of cases (n = 32/38). CEUS considered 1 benign lesion to be malignant. 2 lesions were not detectable and in 3 lesions no definite diagnosis was established using MRI.Findings of CT and CEUS were concordant in 5 of 8 cases. In 21 lesions CEUS as the only imaging modality was found to be sufficient for diagnostics. Despite the restricted indications for using CEUS in children, it offers a high diagnostic detection rate (93%) for characterization of liver lesions and portal vein anomalies.

Liver Contrast-Enhanced Ultrasound Improves Detection of Liver Metastases in Patients with Pancreatic or Periampullary Cancer

The aim of this study is to provide a diagnostic performance evaluation of contrast-enhanced ultrasonography (CEUS) in detecting liver metastases in patients with suspected of pancreatic or periampullary cancer. Computed tomography (CT) is often insufficient for detection of liver metastases, but their presence plays a crucial role in the choice of therapy. Eighty-nine patients with suspected pancreatic or periampullary cancer were included in this prospective study with retrospective analysis. Patients underwent an abdominal CT and CEUS. Fifteen patients had liver metastases. The CT sensitivity was 73.3% (11/15), the specificity 93.2% (69/74), the positive predictive value (PPV) 68.8% (11/16) and the negative predictive value (NPV) 94.6% (69/73). Based on CEUS, the sensitivity was 80% (12/15), specificity 98.6% (73/74), PPV 92.3% (12/13) and NPV 96.1% (73/76). CEUS improved characterization of liver lesions in patients with suspected pancreatic or periampullary cancer compared with CT. CEUS can better detect benign liver lesions and distinguish false-positive or indeterminate CT results.

Contrast-enhanced ultrasound for characterisation of focal liver lesions, practical advice

This review article reports on evidence-based and clinical aspects of contrast-enhanced ultrasound of liver masses. The advanced possibilities of contrast-enhanced ultrasound to detect and characterise liver tumors are described as well as limitations and pitfalls of the method. The choice of the ultrasound device and contrast agents as well as the qualifications of the examiners according to guidelines are discussed.

Contrast-Enhanced Ultrasound of Focal Liver Lesions.

The purpose of this article is to discuss the use of contrast-enhanced ultra-sound (CEUS) in focal liver lesions. Focal liver lesions are usually detected incidentally during abdominal ultrasound. The injection of microbubble ultrasound contrast agents improves the characterization of focal liver lesions that are indeterminate on conventional ultrasound. The use of CEUS is recommended in official guidelines and suggested as a second diagnostic step after ultrasound detection of indeterminate focal liver lesions to immediately establish the diagnosis, especially for benign liver lesions, such as hemangiomas, avoiding further and more expensive examinations.

Is Strain Elastography (IO-SE) Sufficient for Characterization of Liver Lesions before Surgical Resection--Or Is Contrast Enhanced Ultrasound (CEUS) Necessary?

AimTo evaluate the diagnostic accuracy of IO-SE in comparison to IO-CEUS for the differentiation between malignant and benign liver lesions.Material and MethodsIn a retrospective diagnostic study IO-CEUS and SE examinations of 49 liver lesions were evaluated and compared to histopathological examinations. Ultrasound was performed using a multifrequency linear probe (6–9 MHz). The loops of CEUS were evaluated up to 5 min. The qualitative characterization of IO-SE was based on a color coding system (blue = hard, red = soft). Stiffness of all lesions was quantified by a specific scaling of 0–6 (0 = low, 6 = high) using 7 ROIs (2 central, 5 peripheral).ResultsAll malignant lesions displayed a characteristic portal venous washout and could be diagnosed correctly by IO-CEUS. 3/5 benign lesions could not be characterized properly either by IO-CEUS or IO-SE prior to resection. Thus for IO-CEUS sensitivity, specificity, positive and negative predictive value and accuracy were 100%, 40%, 94%, 100% and 94%. Lesion sizes were between 8 and 59 mm in diameter. Regarding the IO-SE, malignant lesions showed a marked variability. In qualitative analysis, 31 of the malignant lesions were blue colored denoting overall induration. Thirteen malignant lesions showed an inhomogenous color pattern with partial indurations. Two of the benign lesions also displayed overall induration. The other benign lesions showed an inhomogenous color mapping. Calculated sensitivity of the SE was 70.5%, specificity 60%, PPV 94%, NPV 18.75%, and accuracy 69%.ConclusionIO-CEUS is useful for localization and characterization of liver lesions prior to surgical resection whereas IO-SE provided correct characterization only for a limited number of lesions.

Focal masses in a non-cirrhotic liver: The additional benefit of CEUS over baseline imaging

Incidentally detected focal liver lesions are commonly encountered in clinical practice presenting a challenge in the daily department work flow. Guidelines for the management of incidental focal liver lesions have been published but comments, illustrations and recommendations regarding practical issues are crucial. The unique features of contrast-enhanced ultrasound in non-invasive assessment of focal liver lesion enhancement throughout the vascular phases in real-time has allowed an impressive improvement in the diagnostic accuracy of ultrasound.We highlight the additional benefit of contrast-enhanced ultrasound over conventional B-mode ultrasound imaging in detection, characterization, differential and final diagnosis of focal liver lesions, as well as for liver metastases screening. The current roles of cross-sectional imaging are explained in detail, with indications and limitations for each procedure. The advantages of CEUS, such as non-ionizing radiation exposure, cost benefits, non-iodinate contrast agents, and repeatability are also described ultimately improving patient management.

Activity-based cost analysis of contrast-enhanced ultrasonography (CEUS) related to the diagnostic impact in focal liver lesion characterisation.

PurposeThis study was done to assess the clinical-diagnostic impact and cost of contrast-enhanced ultrasound (CEUS) versus computed tomography (CT) and magnetic resonance (MR) imaging in the characterisation of focal liver lesions.Materials and methodsCEUS with sulphur hexafluoride-filled microbubbles (SonoVue bolus 2.4 ml) was performed in 157 patients with 160 focal liver lesions identified by other diagnostic techniques. CEUS images were obtained during the arterial (15 to 35 s from contrast injection), portal venous (40 to 70 s) and late phase (up to 300 s from microbubble injection). Contrast-enhanced CT was performed with a 64-row multidetector CT. MRI was performed before and after administration of the liver-specific contrast agent gadobenate dimeglumine (Gd-BOPTA). A patient-by-patient activity-based cost analysis was performed.ResultsCEUS led to a change in the diagnostic workup in 131/157 patients (83.4 %) and in the therapeutic workup in 93/157 patients (59.2 %). CEUS allowed for the final diagnosis to be established in 133/157 patients (84.7 %). The full cost of CEUS was lower than that of contrast-enhanced CT and MR imaging.ConclusionsCEUS determined a change in the diagnostic and therapeutic workup in the characterisation of focal liver lesions and reduced the full costs of the diagnostic process.Main messages: • CEUS allows a correct diagnosis in more than 80 % of focal liver lesions. • CEUS has a significant impact on the diagnosis of focal liver lesions. • CEUS examination of focal liver lesions reduces total costs. • Dynamic MR with hepato-specific contrast medium remains the reference standard for lesion characterisation. • CEUS is low-cost, versatile and accurate in the characterisation of focal liver lesions.

Ultrasound elastography: liver.

Ultrasound elastography, also termed sonoelastography, is being used increasingly in clinical practice to aid the diagnosis and management of diffuse liver disease. Elastography has been shown to be capable of differentiating advanced and early-stage liver fibrosis, and consequently a major application in clinical liver care includes progression to cirrhosis risk stratification through (1) assessment of liver fibrosis stage in HCV and HBV patients, (2) distinguishing non-alcoholic steatohepatitis from simple steatosis in non-alcoholic fatty liver disease patients, and (3) prognostic evaluation of liver disease is autoimmune liver disease. In addition, elastographic characterization of focal liver lesions and evaluation of clinically significant portal hypertension have the potential to be clinically useful and are areas of active clinical research.

2092035 How Useful Is Contrast Enhanced Ultrasound in the evaluation of Focal Liver Lesions. A Monocentric Experience

2092035 How Useful Is Contrast Enhanced Ultrasound in the evaluation of Focal Liver Lesions. A Monocentric Experience

Contrast-Enhanced Ultrasound in the Characterization of Complex Cystic Focal Liver Lesions

Complex cystic focal liver lesions (FLLs) found at non-contrast ultrasound (US) may turn out to be malignant. In this prospective, monocentric study we investigated the value of contrast-enhanced US (CEUS) in the differential diagnosis of complex cystic FLLs. In the past 3 years, all patients with complex cystic FLLs unclassifiable at US underwent CEUS with low-transmit insonation power. We evaluated 36 consecutive patients with 61 FLLs (1–6/patient, mean = 2). The diameter of the lesions ranged from 1.1 to 7.9 cm (mean = 3.9 cm). Sixteen patients had an extrahepatic malignancy. There were 42 malignant lesions and 19 benign lesions. No lesion had a certain diagnosis at conventional US, whereas 16 FLLs were classified as probable (benign or malignant) and 45 as uncertain. CEUS correctly categorized 95% of the malignant cases. CEUS was not able to differentiate the biliary cystadenoma from its malignant counterpart and misdiagnosed two abscesses. Complete non-enhancement throughout three phases or sustained enhancement in the portal/late phase was exhibited in most benign complex cystic FLLs, except for 1 (of the 3) cystadenomas and in 2 (of the 4) abscesses. On the other hand, all malignant lesions presented a contrast washout with a hypo-enhancing appearance. CEUS may provide added diagnostic value in all complex cystic FLLs found uncertain at conventional US, potentially avoiding the use of more invasive and expensive imaging modalities.

Magnetic resonance imaging of the chest in the evaluation of cancer patients: state of the art.

Recent studies have demonstrated that the use of paramagnetic hepatobiliary contrast agents in the acquisition of magnetic resonance images remarkably improves the detection and differentiation of focal liver lesions, as compared with extracellular contrast agents. Paramagnetic hepatobiliary contrast agents initially show the perfusion of the lesions, as do extracellular agents, but delayed contrast-enhanced images can demonstrate contrast uptake by functional hepatocytes, providing further information for a better characterization of the lesions. Additionally, this intrinsic characteristic increases the accuracy in the detection of hepatocellular carcinomas and metastases, particularly the small-sized ones. Recently, a hepatobiliary contrast agent called gadolinium ethoxybenzyl dimeglumine, that is simply known as gadoxetic acid, was approved by the National Health Surveillance Agency for use in humans. The authors present a literature review and a practical approach of magnetic resonance imaging utilizing gadoxetic acid as contrast agent, based on patients' images acquired during their initial experiment.

Ultrasound with microbubbles

Conventional ultrasound has well known short comings in the detection and characterisation of focal liver lesions. A false negative rate of up to 30% has been quoted in the detection of liver metastases and its accuracy in the characterisation of focal liver lesions is poor compared to computed tomography (CT) and magnetic resonance (MR). Ultrasound microbubble contrast agents have redressed these limitations. Ultrasound microbubbles have been available for over 20 years and are licensed for clinical use in most parts of the world. The characterization of focal liver lesions is the most important application of contrast-enhanced US (CEUS), with an accuracy rivalling that of CT and MR [1-8]. Microbubbles consist of a low solubility complex gas such as a perfluoro gas surrounded by a phospholipid shell. They are similar in size to red blood cells, in comparison to the molecular sizes of CT and MR contrast agents. They are pure intravascular agents. Following an intravenous injection they last in the circulation for about 5 minutes. By good fortune, microbubbles resonate in an ultrasound field at the frequencies used in everyday diagnostic sonography. During resonance they emit ‘fingerprint like’ harmonic signals (overtones) which can be selectively detected by the microbubble-specific software available on commercial ultrasound systems. Microbubbles are imaged using low acoustic power modes to reduce their destruction and thus allow real-time imaging. They are better tolerated than MR and CT agents with fewer and less severe adverse effects and are not nephrotoxic. The most widely used agent in Europe is Sonovue (Bracco). The liver demonstrates three phases of enhancement after an i.v. bolus injection: the arterial, portal and late phases. The late phase occurs as the vascular phases subside, when the microbubbles are sequestered in the sinusoids of the liver. Enhancement is visualized in real time alongside a B-mode greyscale image. The enhancement characteristics of liver lesions at CEUS are similar to those seen on CT and MR imaging. Since CEUS operates in real time, fast changes during the arterial phase are better captured than on CT or MR. This presentation discusses the enhancement characteristics of malignant and benign liver lesions. As a general rule, however, lesions which do not washout in the late phase (i.e. remain hyperenhancing or isoenhancing to liver parenchyma) tend to be benign (with the exception of simple cysts, haematomas, ablation cavities and abscesses, which do not enhancement in any phase), whereas lesions which do not retain contrast in the late phase (i.e. demonstrate washout) are usually malignant. Hepatic metastases have variable appearances on B-mode ultrasound. On CEUS, hypervascular metastases typically demonstrate avid enhancement throughout the lesion in the arterial phase whilst hypovascular metastases show rim enhancement in the arterial phase with both types showing washout in the late phases appearing as defects. CEUS significantly increases the conspicuity of metastases compared to B mode, allowing the detection of isoechoic and lesions down to 3mm. CEUS and intervention: The use of CEUS may allow better visualisation of a lesion than on B-mode ultrasound and allow a targeted ultrasound-guided biopsy. CEUS may also be used during interstitial ablation of a focal malignant liver lesion. The operator is able to perform repeated injections of microbubbles in order to establish whether viable tumour remains, and whether immediate further on-table ablative therapy is required. Benign liver lesions have characteristic enhancement patterns on CEUS. Haemangiomas demonstrate gradual peripheral nodular enhancement with progressive centripetal filling whereas focal nodular hyperplasia typically demonstrate avid arterial centrifugal enhancement in a Correspondence: chris.harvey@imperial.nhs.uk Imperial College Healthcare NHS Trust, Hammersmith Hospital, London W12 0HS, UK Harvey Cancer Imaging 2015, 15(Suppl 1):O19 http://www.cancerimagingjournal.com/content/15/S1/O19

Comparative pathological study of liver fluke infection in ruminants

A comparative study was conducted from October 2013 to June 2014 on 135 cattle, 175 sheep and 190 goats with a total of 500 ruminants to assess pathological changes on liver infected with fluke at ELFORA export abattoir in Bishoftu, Ethiopia. The animals were included in the study using systematic random sampling. The gross lesions included firm and enlarged livers with tense capsule, haemorrhagic spots, multi focal nodules and enlarged hepatic lymph nodes. The bile ducts were thickened and distended with adult fluke especially in chronic cases. Frequently observed histologic lesions were, hepatic portal fibrosis with large amount of fibrin in the portal area, hepatocytes degeneration, fatty changes and periportal necrosis. Fibrous connective tissue of various amount with fibroblasts and infiltration of mononuclear cells, in particular lymphocytes were common lesions in tracts migrated by parasites. Biliary cirrhosis with epithelial hyperplasia were also observed in cattle and sheep. Eosinophilic hepatitis, talengechtasis and hepatocytes degeneration and necrosis were evident in the parenchyma. Chronic lesions were less prominent in goats’ and even no cirrhotic case examined in goat. Cytological examination showed large number of lymphocytes and few plasma cells and eosinophils. The findings of the present study indicated that gross, histopathological and cytological examination supports one another in characterization of liver lesions hence could be used together in diagnosis of ruminant fasciolosis. However, additional diagnostic tests would be added for better confirmation.

CT Appearance of Hepatocellular Carcinoma after Locoregional Treatments: A Comprehensive Review.

Hepatocellular carcinoma (HCC) is a major health problem worldwide, affecting more than 600,000 new patients per year. Curative treatments are available in a small percentage of patients, while most of them present in stages requiring locoregional treatments such as thermoablation, transarterial chemoembolization, and/or radioembolization. These therapies result in specific imaging features that the general radiologist has to be aware of in order to assess the response to treatment and to correctly manage the follow-up of treated patients. Multiphasic helical computed tomography has become a popular imaging modality for detecting hypervascular tumors and characterizing liver lesions. On this basis, many staging and diagnostic systems have been proposed for evaluating response to all different existing strategies. Radiofrequencies and microwaves generate thermoablation of tumors, and transarterial chemoembolization exploits the double effect of the locoregional administration of drugs and embolizing particles. Eventually radioembolization uses a beta-emitting isotope to induce necrosis. Therefore, the aim of this comprehensive review is to analyze and compare CT imaging appearance of HCC after various locoregional treatments, with regard to specific indications for all possible procedures.

Effects of Gray-Scale Ultrasonography Immediate Post-Contrast on Characterization of Focal Liver Lesions.

This study compared the imaging features of conventional gray scale ultrasound (US) before and after contrast-enhanced ultrasound (CEUS) for focal liver lesions and 22 evaluated the role of US post-CEUS in characterizing liver lesions. 126 patients with 158 focal liver lesions underwent CEUS and US post-CEUS examination and entered this study. There were 74 hepatocellular carcinomas (HCC), 43 hepatic metastases, and 41 hemangiomas. Imaging features of US pre-CEUS and US post-CEUS were analyzed offsite by two blinded experienced radiologists to evaluate size, boundary, echogenicity, internal texture, posterior acoustic enhancement, spatial resolution, and contrast resolution. In the end with pathological and clinical evidence, the diagnostic accuracy rate of US pre-CEUS was 53.8% (85/158 lesions), lower than that of CEUS (88.0%, 139/158 lesions); with the complementation of US post-CEUS the rate rose to 93.0% (147/158 lesions). US post-CEUS could improve the visibility of typical structures of focal liver lesions and might provide important complementary information for CEUS diagnosis. It also increases the visibility of small liver lesions compared with US pre-CEUS and helps to guide local interventional procedure.

Microbubbles: from cancer detection to theranostics

Microbubbles have proven to be useful as diagnostic agents for ultrasound[1,2]. However, they have the potential for a far wider range of uses, both in unmodified form (thus minimising regulatory barriers) and in new forms[3]. These future uses may be divided into diagnostic and therapeutic categories. Routine diagnostic uses of microbubbles relevant to oncology are mainly in the liver, where they have been endorsed by NICE for the characterisation of focal liver lesions[4]. The key attribute here is the fact that malignancies do not have the functioning sinusoidal system that accounts for the late retention of microbubbles in the normal liver and in solid focal lesions - in this application, microbubbles are as effective as CT with contrast but less costly. Many similar oncological uses exploit microbubbles' exquisite ability to define both the macro- and microvasculature of tissue. Examples include characterising BI-RADS 3 and 4a breast masses, distinguishing pancreatic adenocarcinoma (hypoperfused) from focal pancreatitis (well perfused) and distinguishing complex-appearing real cysts from cystic carcinomas. A potentially important extension is to develop targeted microbubbles that attach preferentially to cell surface molecules of interest[5]. Since conventional microbubbles of micron diameter cannot escape from the blood pool, the initial target is the blood vasculature. Ligands to VEGF1 can be attached to microbubbles; numerous preclinical studies have shown these to be effective ways to image malignant neovascularisation and the first human trial in prostate cancer has been completed[6]. A difficulty has been the relatively poor binding power of the targeted microbubbles, especially in the non-immunogenic form suitable for human use. The same strategies that are used for molecular imaging in nuclear medicine and MR can be deployed: improve the specific binding or wait for clearance of the unbound agent from the blood stream. Another approach makes use of the fast time resolution of ultrasound and tries to recognise which microbubbles are fixed and which are moving, thus enabling the bound population to be selectively imaged. Efforts have also been made to detect differences in the echoes from free versus bound microbubbles. An important advance in allowing access to tissue beyond the endothelium is the development of nanodroplets, made by cooling and pressurising microbubbles - at around 200nm in diameter, they are able to cross the endothelium, especially where its is leaky[7]. Sonication with acceptable ultrasound intensity can then be used to reform the original microbubbles, with their ligands intact. This opens the way to imaging tissues beyond the endothelium. The simplest approach to therapy employing microbubbles is to make use of their mechanical vibrations[8] and this has been used to accelerate thrombus breakdown to promote revascularisation of the middle cerebral artery[9]. An interesting approach uses low ultrasound frequencies and intensities along with microbubbles to ‘massage’ the endothelium or other surfaces (remote palpation), relying on the effect of acoustic radiation force impulses (ARFI) to move microbubbles along the ultrasound beam[10]. This allows temporary opening of tight endothelial junctions, for example to open the blood-brain barrier and improve the penetration of co-administered i.v. drugs. Co-administration obviates some of the regulatory barriers to modified microbubbles and has been used to augment chemotherapy of pancreatic cancer with gemcitabine[11]. Further such trials are anticipated. Microbubbles might also be used to augment high intensity focussed ultrasound (HIFU) which would speed up the method, thus removing one of the main barriers to its wider use. The most direct approach to treatment with microbubbles is to tag them with active drugs such as chemotherapeutic agents; breaking these microbubbles with high MI pulses releases the agent so that high concentrations can be achieved locally. This has been shown in small animals to minimise the cardiotoxicity of adriamycin in breast cancer[12]. This therapeutic avenue could be combined with the nanodroplets method and with remote palpation to access tumours. Thus, the diagnostic and therapeutic possibilities for microbubbles are extensive; clinically useful approaches in oncology can be anticipated in the not too distant future.