Retrospective Analysis of the Safety and Cost Implications of Pediatric Contrast-Enhanced Ultrasound at a Single Center.

OBJECTIVE: Because of concern over medical ionizing radiation exposure of children, contrast-enhanced ultrasound (CEUS) has generated interest as an inexpensive, ionizing radiation-free alternative to CT and MRI. CEUS has received approval for pediatric hepatic use but remains off-label for a range of other applications. The purposes of this study were to retrospectively analyze adverse incidents encountered in pediatric CEUS and to assess the financial benefits of reducing the number of CT and MRI examinations performed. MATERIALS AND METHODS: All pediatric (patients 18 years and younger) CEUS examinations performed between January 2008 and December 2015 were reviewed. All immediate reactions deemed due to contrast examinations were documented in radiology reports. Electronic patient records were examined for adverse reactions within 24 hours not due to an underlying pathologic condition. With tariffs from the U.K. National Institute of Clinical Excellence analysis, CEUS utilization cost ($94) was compared with the CT ($168) and MRI ($274) costs of the conventional imaging pathway. RESULTS: The records of 305 pediatric patients (187 boys, 118 girls; age range, 1 month-18 years) undergoing CEUS were reviewed. Most of the studies were for characterizing liver lesions (147/305 [48.2%]) and trauma (113/305 [37.1%]); the others were for renal, vascular, and intracavitary assessment (45/305 [14.8%]). No immediate adverse reactions occurred. Delayed adverse reactions occurred in two patients (2/305 [0.7%]). These reactions were transient hypertension and transient tachycardia. Neither was symptomatic, and both were deemed not due to the underlying disorder. The potential cost savings of CEUS were $74 per examination over CT and $180 over MRI. CONCLUSION: Pediatric CEUS is a safe and potentially cost-effective imaging modality. Using it allows reduction in the ionizing radiation associated with CT and in the gadolinium contrast administration, sedation, and anesthesia sometimes required for MRI.

Intravenous and Intracavitary Use of Contrast-Enhanced Ultrasound in the Evaluation and Management of Complicated Pediatric Pneumonia.

Pediatric pneumonia can be complicated by necrotizing pneumonia or a parapneumonic effusion either in the form of an empyema or a clear effusion. Ultrasonography (US) and computed tomography represent well-established modalities for evaluation of complicated pediatric pneumonia. Contrast-enhanced ultrasound (CEUS) was recently introduced and is gaining increasing acceptance in pediatric imaging. In this case series, we present our initial experience with both intravenous and intracavitary use of CEUS in children with complicated pneumonia. Intravenous CEUS accurately and confidently showed necrotizing pneumonia and delineated pleural effusions, whereas intracavitary CEUS accurately identified the chest catheter location and patency and showed the presence of loculations, suggesting the use of fibrinolytics.

Quantitative Maximum Shear-Wave Stiffness of Breast Masses as a Predictor of Histopathologic Severity.

OBJECTIVE: The objective of our study was to compare quantitative maximum breast mass stiffness on shear-wave elastography (SWE) with histopathologic outcome. SUBJECTS AND METHODS: From September 2008 through September 2010, at 16 centers in the United States and Europe, 1647 women with a sonographically visible breast mass consented to undergo quantitative SWE in this prospective protocol; 1562 masses in 1562 women had an acceptable reference standard. The quantitative maximum stiffness (termed "Emax") on three acquisitions was recorded for each mass with the range set from 0 (very soft) to 180 kPa (very stiff). The median Emax and interquartile ranges (IQRs) were determined as a function of histopathologic diagnosis and were compared using the Mann-Whitney U test. We considered the impact of mass size on maximum stiffness by performing the same comparisons for masses 9 mm or smaller and those larger than 9 mm in diameter. RESULTS: The median patient age was 50 years (mean, 51.8 years; SD, 14.5 years; range, 21-94 years), and the median lesion diameter was 12 mm (mean, 14 mm; SD, 7.9 mm; range, 1-53 mm). The median Emax of the 1562 masses (32.1% malignant) was 71 kPa (mean, 90 kPa; SD, 65 kPa; IQR, 31-170 kPa). Of 502 malignancies, 23 (4.6%) ductal carcinoma in situ (DCIS) masses had a median Emax of 126 kPa (IQR, 71-180 kPa) and were less stiff than 468 invasive carcinomas (median Emax, 180 kPa [IQR, 138-180 kPa]; p = 0.002). Benign lesions were much softer than malignancies (median Emax, 43 kPa [IQR, 24-83 kPa] vs 180 kPa [IQR, 129-180 kPa]; p < 0.0001). Usual benign lesions were soft, including 62 cases of fibrocystic change (median Emax, 32 kPa; IQR, 24-94 kPa), 51 cases of fibrosis (median Emax, 36 kPa; IQR, 22-102 kPa), and 301 fibroadenomas (median Emax, 45 kPa; IQR, 30-79 kPa). Eight lipomas (median Emax, 14 kPa; IQR, 8-15 kPa), 154 cysts (median Emax, 29 kPa; IQR, 10-58 kPa), and seven lymph nodes (median Emax, 17 kPa; IQR, 9-40 kPa) were softer than usual benign lesions (p < 0.0001 for lipomas and cysts; p = 0.007 for lymph nodes). Risk lesions were slightly stiffer than usual benign lesions (p = 0.002) but tended to be softer than DCIS (p = 0.14). Fat necrosis and abscesses were relatively stiff. Conclusions were similar for both small and large masses. CONCLUSION: Despite overlap in Emax values, maximum stiffness measured by SWE is a highly effective predictor of the histopathologic severity of sonographically depicted breast masses.

Role of US Contrast Agents in the Assessment of Indeterminate Solid and Cystic Lesions in Native and Transplant Kidneys.

Ultrasonography (US) is often the initial imaging modality employed in the evaluation of renal diseases. Despite improvements in B-mode and Doppler imaging, US still faces limitations in the assessment of focal renal masses and complex cysts as well as the microcirculation. The applications of contrast-enhanced US (CEUS) in the kidneys have dramatically increased to overcome these shortcomings with guidelines underlining their importance. This article describes microbubble contrast agents and their role in renal imaging. Microbubble contrast agents consist of a low solubility complex gas surrounded by a phospholipid shell. Microbubbles are extremely safe and well-tolerated pure intravascular agents that can be used in renal failure and obstruction, where computed tomographic (CT) and magnetic resonance (MR) imaging contrast agents may have deleterious effects. Their intravascular distribution allows for quantitative perfusion analysis of the microcirculation, diagnosis of vascular problems, and qualitative assessment of tumor vascularity and enhancement patterns. Low acoustic power real-time prolonged imaging can be performed without exposure to ionizing radiation and at lower cost than CT or MR imaging. CEUS can accurately distinguish pseudotumors from true tumors. CEUS has been shown to be more accurate than unenhanced US and rivals contrast material-enhanced CT in the diagnosis of malignancy in complex cystic renal lesions and can upstage the Bosniak category. CEUS can demonstrate specific enhancement patterns allowing the differentiation of benign and malignant solid tumors as well as focal inflammatory lesions. In conclusion, CEUS is useful in the characterization of indeterminate renal masses and cysts.

Safety of contrast-enhanced ultrasound in children for non-cardiac applications: a review by the Society for Pediatric Radiology (SPR) and the International Contrast Ultrasound Society (ICUS).

The practice of contrast-enhanced ultrasound in children is in the setting of off-label use or research. The widespread practice of pediatric contrast-enhanced US is primarily in Europe. There is ongoing effort by the Society for Pediatric Radiology (SPR) and International Contrast Ultrasound Society (ICUS) to push for pediatric contrast-enhanced US in the United States. With this in mind, the main objective of this review is to describe the status of US contrast agent safety in non-cardiac applications in children. The five published studies using pediatric intravenous contrast-enhanced US comprise 110 children. There is no mention of adverse events in these studies. From a European survey 948 children can be added. In that survey six minor adverse events were reported in five children. The intravesical administration of US contrast agents for diagnosis of vesicoureteric reflux entails the use of a bladder catheter. Fifteen studies encompassing 2,951 children have evaluated the safety of intravesical US contrast agents in children. A European survey adds 4,131 children to this group. No adverse events could be attributed to the contrast agent. They were most likely related to the bladder catheterization. The existing data on US contrast agent safety in children are encouraging in promoting the widespread use of contrast-enhanced US.

Shear-wave elastography improves the specificity of breast US: the BE1 multinational study of 939 masses.

PURPOSE: To determine whether adding shear-wave (SW) elastographic features could improve accuracy of ultrasonographic (US) assessment of breast masses. MATERIALS AND METHODS: From September 2008 to September 2010, 958 women consented to repeat standard breast US supplemented by quantitative SW elastographic examination in this prospective multicenter institutional review board-approved, HIPAA-compliant protocol. B-mode Breast Imaging Reporting and Data System (BI-RADS) features and assessments were recorded. SW elastographic evaluation (mean, maximum, and minimum elasticity of stiffest portion of mass and surrounding tissue; lesion-to-fat elasticity ratio; ratio of SW elastographic-to-B-mode lesion diameter or area; SW elastographic lesion shape and homogeneity) was performed. Qualitative color SW elastographic stiffness was assessed independently. Nine hundred thirty-nine masses were analyzable; 102 BI-RADS category 2 masses were assumed to be benign; reference standard was available for 837 category 3 or higher lesions. Considering BI-RADS category 4a or higher as test positive for malignancy, effect of SW elastographic features on area under the receiver operating characteristic curve (AUC), sensitivity, and specificity after reclassifying category 3 and 4a masses was determined. RESULTS: Median participant age was 50 years; 289 of 939 (30.8%) masses were malignant (median mass size, 12 mm). B-mode BI-RADS AUC was 0.950; eight of 303 (2.6%) BI-RADS category 3 masses, 18 of 193 (9.3%) category 4a lesions, 41 of 97 (42%) category 4b lesions, 42 of 57 (74%) category 4c lesions, and 180 of 187 (96.3%) category 5 lesions were malignant. By using visual color stiffness to selectively upgrade category 3 and lack of stiffness to downgrade category 4a masses, specificity improved from 61.1% (397 of 650) to 78.5% (510 of 650) (P<.001); AUC increased to 0.962 (P=.005). Oval shape on SW elastographic images and quantitative maximum elasticity of 80 kPa (5.2 m/sec) or less improved specificity (69.4% [451 of 650] and 77.4% [503 of 650], P<.001 for both), without significant improvement in sensitivity or AUC. CONCLUSION: Adding SW elastographic features to BI-RADS feature analysis improved specificity of breast US mass assessment without loss of sensitivity.

Shear wave elastography for breast masses is highly reproducible.

OBJECTIVES: To evaluate intra- and interobserver reproducibility of shear wave elastography (SWE) for breast masses. METHODS: For intraobserver reproducibility, each observer obtained three consecutive SWE images of 758 masses that were visible on ultrasound. 144 (19%) were malignant. Weighted kappa was used to assess the agreement of qualitative elastographic features; the reliability of quantitative measurements was assessed by intraclass correlation coefficients (ICC). For the interobserver reproducibility, a blinded observer reviewed images and agreement on features was determined. RESULTS: Mean age was 50 years; mean mass size was 13 mm. Qualitatively, SWE images were at least reasonably similar for 666/758 (87.9%). Intraclass correlation for SWE diameter, area and perimeter was almost perfect (ICC ≥ 0.94). Intraobserver reliability for maximum and mean elasticity was almost perfect (ICC = 0.84 and 0.87) and was substantial for the ratio of mass-to-fat elasticity (ICC = 0.77). Interobserver agreement was moderate for SWE homogeneity (κ = 0.57), substantial for qualitative colour assessment of maximum elasticity (κ = 0.66), fair for SWE shape (κ = 0.40), fair for B-mode mass margins (κ = 0.38), and moderate for B-mode mass shape (κ = 0.58), orientation (κ = 0.53) and BI-RADS assessment (κ = 0.59). CONCLUSIONS: SWE is highly reproducible for assessing elastographic features of breast masses within and across observers. SWE interpretation is at least as consistent as that of BI-RADS ultrasound B-mode features. KEY POINTS: • Shear wave ultrasound elastography can measure the stiffness of breast tissue • It provides a qualitatively and quantitatively interpretable colour-coded map of tissue stiffness • Intraobserver reproducibility of SWE is almost perfect while intraobserver reproducibility of SWE proved to be moderate to substantial • The most reproducible SWE features between observers were SWE image homogeneity and maximum elasticity.

Renal transplants: what ultrasound can and cannot do.

Renal transplantation has emerged as the most cost-effective and patient-supportive way to treat chronic renal failure, with excellent graft survival rates thanks to improved surgical techniques and rejection management. Its success has placed a heavy burden on imaging, especially ultrasound, which is used in the selection of live donors and in monitoring each stage of the postoperative care of the recipient. Ultrasound is particularly useful for detecting vascular complications such as early occlusions and arterial stenosis. It can detect and monitor perinephric complications and transplant hydronephrosis, all clinically significant complications that affect management. Ultrasound can detect many of the late acquired diseases, especially intercurrent tumors that require surgery. It is the best method to guide interventions such as aspiration of collections and insertion of nephrostomy drains. It can also detect postbiopsy arteriovenous shunts and the end-stage kidney of chronic rejection. These, however, are of no great clinical significance, and the findings rarely affect clinical decisions. Ultrasound fails to discriminate between the important causes of early graft dysfunction, especially acute tubular necrosis, rejection, and drug toxicity: these important distinctions still rely on biopsy. There is hope that some of the newer ultrasound methods, especially the functional data from microbubble contrast agent dynamics, might supply useful information for their detection and differentiation.

Measurement of the reflectivity of the intima-medial layer of the common carotid artery improves the discriminatory value of intima-medial thickness measurement as a predictor of risk of atherosclerotic disease.

Our aim was to assess the predictive value of a measurement of intima-medial layer (IML) reflectivity in the differentiation of pathological from physiological increases in intima-medial thickness (IMT). Both common carotid arteries (CCA) of familial hypercholesterolemia (FH) patients and age- and sex-matched controls (no cardiovascular risk factors) were imaged using a 10- to 15-MHz linear array transducer (n = 30). Images of the CCA far wall were analyzed in the IMT "plug-in" of "HDI Lab." The IML reflectivity, averaged over an 8- to 12-mm length of arterial wall, was expressed as a ratio of reflectivity at a point 0.21-mm deep to the intima-medial interface divided by the reflectivity at the intima-medial interface, termed the intima-medial reflectivity index (IMRI). The risk of atherosclerosis was assessed in terms of IMT alone and IMT coupled with IMRI. Defining high risk of atherosclerosis in FH, in terms of both IMT alone and IMT coupled with IMRI, produced an appropriate, when compared with cholesterol-years score, statistically significant stratification (p < 0.01 and p < 0.005). Analysis of the low-risk subjects revealed a tendency to define a subject as "high risk" based on a physiological increase in IMT, but when IMRI is included in the assessment, all controls are correctly identified as low risk. This method of quantifying the reflectivity of the IML improved the discriminatory performance of IMT increase as an indicator of atherosclerotic risk by enabling a smaller, therefore earlier, increase in IMT to be considered pathologic when accompanied by an increase in IMRI.

Differential Intensity Projection for Visualisation and Quantification of Plaque Neovascularisation in Contrast-Enhanced Ultrasound Images of Carotid Arteries.

Studies have reported that intraplaque neovascularisation (IPN) is closely correlated with plaque vulnerability. In this study, a new image processing approach, differential intensity projection (DIP), was developed to visualise and quantify IPN in contrast-enhanced non-linear ultrasound image sequences of carotid arteries. DIP used the difference between the local temporal maximum and the local temporal average signals to identify bubbles against tissue non-linear artefact and noise. The total absolute and relative areas occupied by bubbles within each plaque were calculated to quantify IPN. In vitro measurements on a laboratory phantom were made, followed by in vivo measurements in which 24 contrast-enhanced non-linear ultrasound image sequences of carotid arteries from 48 patients were selected and motion corrected. The results using DIP were compared with those obtained by maximum intensity projection (MIP) and visual assessment. The results indicated that DIP can significantly reduce non-linear propagation tissue artefacts and is much more specific in detecting bubble signals than MIP, being able to reveal microbubble signals that are buried in tissue artefacts in the corresponding MIP image. A good correlation was found between microvascular area (MVA) (r = 0.83, p < 0.001)/microvascular density (r = 0.77, p < 0.001) obtained using DIP and the corresponding expert visual grades, comparing favourably to r = 0.26 and 0.23 obtained using MIP on the same data. In conclusion, the proposed method exhibits great potential in quantification of IPN in contrast-enhanced ultrasound images of carotid arteries.

Colour doppler ultrasound of the lumbar arteries: a novel application and reproducibility study in healthy subjects.

Lumbar arteries are important because they are the main source of blood supply to the lumbar spine structures. However, these vessels and their flow characteristics have received little attention and their role in conditions such as low back pain remains unclear. The present study 1. describes the application of duplex ultrasonography in the assessment of lumbar artery blood flow and 2. evaluates the interobserver and intraobserver reproducibility of lumbar artery Doppler velocimetry. A total of 13 healthy volunteers were evaluated by two different examiners successively on the same day and measurements repeated by the same examiners 1 week later. Peak systolic velocities of lumbar arteries were recorded at an optimal angle below 60 degrees . Overall mean peak systolic velocity (+/-SD) for lumbar arteries was 0.158 +/- 0.051 m/s, and mean Doppler angle (+/-SD) was 24.6 +/- 14.5 degrees . For interobserver variability, the coefficient of variation was 23.4% and SD of differences 0.037 m/s. Reliable results of lumbar artery Doppler velocimetry demonstrate its applicability in future clinical investigations in patients with low back disorders. (E-mail: ).

A novel technique to measure splanchnic transit time using microbubble ultrasound.

OBJECTIVE: The objective of this study was to measure splanchnic transit time by intravenous injection of a microbubble. MATERIALS AND METHODS: Ten volunteers were examined before and after eating. After Doppler indices of splanchnic circulation were obtained, the superior mesenteric artery (SMA) and vein (SMV) were simultaneously interrogated using power Doppler ultrasound after intravenous injection of a microbubble. Contrast arrival in the SMA and subsequently the SMV was recorded and splanchnic transit time calculated from differences in the time-intensity curves. RESULTS: Splanchnic transit time decreased significantly after eating (mean 11 vs. 6.9 seconds; P = 0.007), reflecting splanchnic hemodynamics. Between-subject variability attributable to repeated measurements was least for the SMA resistive index (17%) but 56% for the new index, suggesting poor reproducibility. CONCLUSION: Splanchnic transit time may be measured by microbubble injection but is subject to considerable measurement error. Newer microbubbles and imaging methods may allow more reproducible measurements.

Attenuation Correction and Normalisation for Quantification of Contrast Enhancement in Ultrasound Images of Carotid Arteries.

An automated attenuation correction and normalisation algorithm was developed to improve the quantification of contrast enhancement in ultrasound images of carotid arteries. The algorithm first corrects attenuation artefact and normalises intensity within the contrast agent-filled lumen and then extends the correction and normalisation to regions beyond the lumen. The algorithm was first validated on phantoms consisting of contrast agent-filled vessels embedded in tissue-mimicking materials of known attenuation. It was subsequently applied to in vivo contrast-enhanced ultrasound (CEUS) images of human carotid arteries. Both in vitro and in vivo results indicated significant reduction in the shadowing artefact and improved homogeneity within the carotid lumens after the correction. The error in quantification of microbubble contrast enhancement caused by attenuation on phantoms was reduced from 55% to 5% on average. In conclusion, the proposed method exhibited great potential in reducing attenuation artefact and improving quantification in contrast-enhanced ultrasound of carotid arteries.

Heterogeneous delayed enhancement of the liver after ultrasound contrast agent injection--a normal variant.

We report a characteristic heterogeneous delayed liver enhancement pattern that we have encountered in a total of 6 of approximately 1500 subjects who underwent contrast-enhanced liver ultrasonography. The heterogeneous enhancement occurred several min after contrast injection and persisted for up to 1 h. It was seen in diseased as well as healthy livers and appears to represent a "normal variant" of liver enhancement. It was observed with two different contrast agents. The cause of the described effect is unknown; it may be related to the formation of large bubbles and vascular entrapment of these bubbles in the liver.

Optimisation of ultrasound-mediated gene transfer (sonoporation) in skeletal muscle cells.

Ultrasound (US) is a promising tool for facilitating direct gene transfer to skeletal muscle, but no systematic optimisation study has been performed. We exposed H2K myoblast cells to US with varying intensity of exposure and duration to evaluate its effect on cell viability and transfection efficiency using as endpoints transfection rate, average fluorescence intensity (fluorescence normalised by the number of transfected cells) and overall expression (the product of transfection rate and average fluorescence intensity) as indices. Cell viability decreased with exposure time and intensity, consistent with previous findings. Optimal setting of US was observed at the range of 0.5 to 1 W cm(-2) with duration of 20 s, producing maximum efficiency (transfection = 4.5%) in gene transfection with minimum cell toxicity (cell viability = 83%). Higher intensity alone or in combination with low intensity and long duration did not improve cell viability and transfection. The increase of eGFP (enhanced green fluorescence protein) plasmid concentration up to 200 microg per mL was related to an increase in average fluorescence intensity and overall expression. However, transfection rate saturated when DNA concentration reached 50 microg per mL despite initial increase with DNA concentration. The average fluorescence intensity was linearly proportional to the logarithm of DNA concentration, suggesting a diffusion-based model for DNA uptake under sonoporation. We conclude that low-intensity US irradiation provides a safe and effective alternative for gene delivery.

Enhancement characteristics of the microbubble agent Levovist: reproducibility and interaction with aspirin.

We investigated the reproducibility of Doppler enhancement indices following intravenous bolus injections of Levovist (Schering AG, Berlin) microbubbles. We also aimed to determine whether observations from animal studies suggesting that aspirin potentiates microbubble enhancement were reproducible in humans. In five healthy volunteers, time enhancement profiles of Doppler intensity following repeated bolus injections of Levovist were acquired from the common carotid artery, hepatic vein and kidney using spectral and power Doppler before and after oral aspirin (600 mg). Peak enhancement (PE), area under the curve (AUC) and decay slopes (lambda) were calculated. Hepatic vein contrast arrival time (AT) was determined subjectively. Well-defined carotid enhancement was seen in 19/20 injections. Reproducibility was high (r > 0.8). PE and AUG were unaffected by aspirin, but lambda was slightly reduced (P = 0.02). Renal power Doppler profiles were well defined (10/10) with no significant changes of AUC, PE or lambda after aspirin. Our study demonstrates good reproducibility of carotid spectral Doppler time intensitometry with Levovist in man. Aspirin does not have a significant effect on enhancement indices except carotid spectral Doppler decay. We conclude that aspirin is unlikely to potentiate microbubble enhancement, as seen in animal studies.

Which continuous US scanning mode is optimal for the detection of vascularity in liver lesions when enhanced with a second generation contrast agent?

OBJECTIVES: Microbubble echo-enhancers help in the assessment of focal liver masses by enhancing the signal from blood vessels. A variety of linear and nonlinear scanning modes are now available, but it is unclear which is optimal. A controlled comparison was performed during the infusion of such an agent (SonoVue: Bracco, Milan, Italy). METHODS AND MATERIALS: Ten patients with known focal liver lesions were studied. The diagnoses, confirmed on dual phase helical computed tomography (CT) at the same attendance were metastasis (n = 7), haemangioma (n = 2) and focal nodular hyperplasia FNH (n = 1). A dose of 12 ml SonoVue concentrated at 5 mg/ml was infused intravenously at a rate of 1 ml/min. The enhancement level was monitored with a continuous wave (CW) Doppler probe over the right radial artery and the intensity of the signal was registered at 1 s intervals. When a plateau of enhancement was reached, a single lesion in each patient was imaged using five different continuous scanning modes, fundamental grey scale (FGS); fundamental colour Doppler (FCD); fundamental power Doppler (FPD); second harmonic grey scale (HGS); and pulse inversion mode (Pim) using an HDI5000 scanner and C5-2 probe (ATL, Bothell, WA). The order of scanning modes was varied between patients using a predefined randomisation protocol. The videos (super video home system (SVHS)) were analysed offsite by two blinded readers, both experienced in contrast ultrasound of the liver. The readers were asked to score each mode in terms of its ability to detect vessels within/around the lesion at optimal enhancement. This was done using a ranking system (1, worst; 5, best) for each patient. RESULTS: Both observers scored FPD as the optimal imaging method, followed by Pim. (Scores summed across all patients, observer 1: FPD 48, Pim 42, FCD 37, HGS 21, FGS 10; observer 2: FPD 49, Pim 40, FCD 38, HGS 21, FGS 10). The differences from FPD were significant for FCD, HGS and FGS using a unpaired analysis of variance (ANOVA) comparison, with Bonferroni multiple corrections, (P<0.01, both observers). The differences between FPD and Pim were also significant both for observer 2 and for both observers combined (P<0.01), but did not reach significance for observer 1 (P = 0.19). CONCLUSIONS: In this study, FPD performed best, and the non-linear modes, performed continuously (pulse inversion and second HGS), showed no clear advantage.

Initial observations on the effect of irradiation on the liver-specific uptake of Levovist.

The aim of this pilot study was to see if the biodistribution of the microbubble Levovist (SHU 508 A; Schering AG, Berlin) during its liver specific phase is altered by radiotherapy. The mechanism of this liver-specific phase of this agent remains poorly understood. One way of investigating this is to see what effect radiotherapy has on liver uptake, as both Kupffer cell function and vascular endothelial integrity are selectively damaged by irradiation. The regional liver specific uptake of Levovist was evaluated in eight patients undergoing radiotherapy to the hepatic area. Ultrasound (US) sweeps were made 4 min after Levovist injection using the phase inversion mode (PIM) which is specific for microbubbles. Differences between irradiated and non-irradiated areas were observed in 2/8 subjects completing the study. Both subjective and objective evaluations in these subjects showed a significantly reduced grey scale unit in non-irradiated versus irradiated liver regions (average values 99 vs. 89, P < 0.0045 and 75 vs. 62, P < 0.0001). These findings are somewhat inconclusive, but given the difficulty in defining areas of irradiated and non-irradiated liver, because multiple radiotherapy portals were used in all patients, tentatively suggests a radiotherapy induced effect in at least some patients. The two likely mechanisms would be damage to the Kupffer cells and or the vascular endothelium, although the relative contribution of these is unclear.

Can contrast-enhanced ultrasound distinguish malignant from reactive lymph nodes in patients with head and neck cancers?

The purpose of this study was to investigate the utility of contrast-enhanced ultrasound in differentiating benign from malignant cervical lymph nodes in patients with squamous cell carcinoma of the head and neck. A consecutive series of 17 patients with known head and neck malignancy scheduled for neck surgery and lymph node clearance were recruited for contrast-enhanced ultrasound evaluation. Sonographic signal intensity as a function of time, comparing features of time to peak, time to arrival and time to wash-out, was quantified. The selected node was removed surgically and submitted for histology. Contrast-enhanced ultrasound examination had 100% sensitivity and 85.7% specificity for lymph node involvement. Functional analysis revealed contrast peaks significantly earlier in the malignant nodes (mean ± standard deviation) of 24.14 ± 2.7 s compared with 29.33 ± 3.4 s (p = 0.0128). Contrast-enhanced ultrasound holds promise in the detection and characterization of metastatic nodes that would not be diagnosed as abnormal on the basis of conventional ultrasound criteria.