Microflow imaging: New Doppler technology to detect low-grade inflammation in patients with arthritis.

AIM: To assess the efficacy of microvascular imaging in detecting low-grade inflammation in arthritis compared with Power Doppler ultrasound (PDUS). METHOD AND MATERIALS: Patients presenting for ultrasound with arthralgia were assessed with grey-scale, PDUS and Superb Microvascular Imaging (SMI). Videoclips were stored for analysis at a later date. Three musculoskeletal radiologists scored grey-scale changes, signal on PDUS and/or SMI within these joints. If a signal was detected on both PDUS and SMI, the readers graded the conspicuity of vascular signal from the two Doppler techniques using a visual analogue scale. RESULTS: Eighty-three patients were recruited with 134 small joints assessed. Eighty-nine of these demonstrated vascular flow with both PD and SMI, whilst in five no flow was detected. In 40 joints, vascularity was detected with SMI but not with PDUS (p = 0.007). Out of the 89 joints with vascularity on both SMI and PDUS, 23 were rated as being equal; while SMI scored moderately or markedly better in 45 cases (p <0.001). CONCLUSION: SMI is a new Doppler technique that increases conspicuity of Doppler vascularity in symptomatic joints when compared to PDUS. This allows detection of low grade inflammation not visualised with Power Doppler in patients with arthritis. KEY POINTS: • SMI detects vascularity with improved resolution and sensitivity compared to Power Doppler. • SMI can detect low-grade inflammation not seen with Power Doppler. • Earlier detection of active inflammation could have significant impact on treatment paradigms.

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.

A comparison of 31P magnetic resonance spectroscopy and microbubble-enhanced ultrasound for characterizing hepatitis c-related liver disease.

We compared in vivo hepatic (31) P magnetic resonance spectroscopy ((31) P MRS) and hepatic vein transit times (HVTT) using contrast-enhanced ultrasound with a microbubble agent to assess the severity of hepatitis C virus (HCV)-related liver disease. Forty-six patients with biopsy-proven HCV-related liver disease and nine healthy volunteers had (31) P MRS and HVTT performed on the same day. (31) P MR spectra were obtained at 1.5 T. Peak areas were calculated for metabolites, including phosphomonoesters (PME) and phosphodiesters (PDE). Patients also had the microbubble ultrasound contrast agent, Levovist (2 g), injected into an antecubital vein, and time-intensity Doppler ultrasound signals of the right and middle hepatic veins were measured. The HVTT was calculated as the time from injection to a sustained rise in Doppler signal 10% greater than baseline. The shortest times were used for analysis. Based on Ishak histological scoring, there were 15 patients with mild hepatitis, 20 with moderate/severe hepatitis and 11 with cirrhosis. With increasing severity of disease, the PME/PDE ratio was steadily elevated, while the HVTT showed a monotonic decrease. Both imaging modalities could separate patients with cirrhosis from the mild and moderate/severe hepatitis groups. No statistical difference was observed in the accuracy of each test to denote mild, moderate/severe hepatitis and cirrhosis (Fisher's exact test P =1.00). (31) P MRS and HVTT show much promise as noninvasive imaging tests for assessing the severity of chronic liver disease. Both are equally effective and highly sensitive in detecting cirrhosis.

Hepatic vein transit times of a microbubble agent in assessing response to antiviral treatment in patients with chronic hepatitis C.

Microbubble measurement of hepatic vein transit times (HVTT) may have the potential to assess severity of hepatitis C virus (HCV)-related liver disease, where there is a shorter HVTT with more severe disease. We investigated the utility of this test as a marker of response to antiviral treatment. Thirty-seven patients with biopsy-proven HCV-related disease undergoing antiviral treatment were studied. All had baseline scans and then repeat scans 6 months after the end of treatment. HVTT using Levovist were obtained from the right and middle hepatic veins, and the shorter time was used for analysis. The aspartate aminotransferase to platelet ratio index (APRI) scores were calculated retrospectively. There were seven patients with mild hepatitis, 23 with moderate/severe hepatitis and seven with cirrhosis. The mean baseline HVTT in responders ± SE increased from 27.3 ± 2.29 s to 33.5 ± 2.8 s posttreatment (P = 0.01). In the 10 nonresponders, the HVTT remained the same; 43.3 ± 9 s baseline compared to 44 ± 7.8 s posttreatment (P = 0.84). This trend was also seen with the APRI score where in responders, the mean score decreased from 1.1 ± 0.2 to 0.74 ± 1 (P = 0.03) and in nonresponders, the score remained unchanged; 0.88 ± 0.2 compared to 0.84 ± 0.2 (P = 0.31). HVTT measurement lengthened, while APRI scores decreased in patients who responded to antiviral treatment while both remained the same, shortened (HVTT) or increased (APRI), respectively, in patients who were nonresponders. These results are encouraging and indicate that these tests could be potentially used as markers of response to treatment and could obviate the need for serial biopsies in antiviral future treatment studies.

Can contrast-enhanced sonography distinguish benign from malignant breast masses?

BACKGROUND: We investigated whether microvascular enhancement on contrast-enhanced sonographic (CEUS) imaging can aid in distinguishing between benign and malignant lesions and correlated these findings with histopathological findings. METHOD: Fifteen patients with a palpable breast mass were recruited. Following informed consent, 4.8 mL of the microbubble contrast agent SonoVue was injected intravenously. Digital video clips of lesion enhancement were obtained and reviewed by a consultant radiologist who scored each lesion on the following characteristics: homogeneous versus heterogeneous enhancement, the presence or absence of focal defects, well- versus ill-defined margins and vascular morphology score (VMS). RESULT: Histologically there were 7 malignant and 8 benign lesions. The calculated sensitivity for CEUS in the diagnosis of malignancy was 100%, with a 37.5% specificity. There was no statistically significant difference in overall mean VMS between the malignant and benign lesions. CONCLUSION: The results of our study have not shown any additional benefit in the use of CEUS over conventional triple assessment. The positive trend seen in the higher mean VMS for the malignant tumors needs further investigation with a larger cohort of patients.

Diagnostic efficacy of SonoVue, a second generation contrast agent, in the assessment of extracranial carotid or peripheral arteries using colour and spectral Doppler ultrasound: a multicentre study.

The purpose of this study was to demonstrate the improvement in diagnostic quality and diagnostic accuracy of SonoVue microbubble contrast-enhanced ultrasound (CE-US) versus unenhanced ultrasound imaging during the investigation of extracranial carotid or peripheral arteries. 82 patients with suspected extracranial carotid or peripheral arterial disease received four SonoVue doses (0.3 ml, 0.6 ml, 1.2 ml and 2.4 ml) with Doppler ultrasound performed before and following each dose. Diagnostic quality of the CE-US examinations was evaluated off-site for duration of clinically useful contrast enhancement, artefact effects and percentage of examinations converted from non-diagnostic to diagnostic. Accuracy, sensitivity and specificity were assessed as agreement of CE-US diagnosis evaluated by an independent panel of experts with reference standard modality. The median duration of clinically useful signal enhancement significantly increased with increasing SonoVue doses (p< or =0.002). At the dose of 2.4 ml of SonoVue, diagnostic quality evaluated as number of inconclusive examinations significantly improved, falling from 40.7% at baseline down to 5.1%. Furthermore, SonoVue significantly (p<0.01) increased the accuracy, sensitivity and specificity of assessment of disease compared with baseline ultrasound. SonoVue increases the diagnostic quality of Doppler images and improves the accuracy of both spectral and colour Doppler examinations of extracranial carotid or peripheral arterial disease.

Colour Doppler demonstrates venous flow abnormalities in breast cancer patients with chronic arm swelling.

Chronic arm oedema following breast cancer treatment is traditionally attributed to lymphatic obstruction, with venous obstruction as an infrequent complicating factor. The axillo-subclavian venous systems of 81 patients with arm swelling following breast cancer treatment were examined with colour Doppler, duplex Doppler and grey scale ultrasound. Over half (57%) had evidence of venous outflow obstruction and a further 14% had signs of venous "congestion". Only 30% of the swollen arms had normal venous outflow. The venous systems of the contralateral non-swollen arms were all normal as were both arms in 28 control patients who had similar treatment but had not developed arm swelling. These findings suggest that venous outflow obstruction is an important contributory factor in the pathophysiology of arm swelling following breast cancer treatment.

Increased arterial inflow demonstrated by Doppler ultrasound in arm swelling following breast cancer treatment.

Doppler ultrasound was used to estimate the mean arterial flow in the arms of 50 patients with arm oedema following breast cancer treatment (oedema group). They were compared with 26 treated breast cancer patients with no arm swelling (control group). Flows on the treatment side were expressed as a percentage of the flow in the contralateral normal arm. Mean percentage blood flow was 68% higher in the swollen arms than the contralateral normal arms compared to a mean increase of 38% on the breast cancer treatment side in the control group. In both groups there was a significantly higher proportion of patients with increased (> 150%) rather than decreased (< 50%) flow on the treatment side. The ratio of increased to decreased flow was 27:4 in the oedema group and 6:0 in the control group. A neurological deficit on the treatment side was associated with an increased incidence of higher flow on the same side in the oedema group. These findings demonstrate that breast cancer treatment results in a significant increase in arterial flow in the arm on the treatment side, and that this increase is even higher in those patients with swelling. Increased blood flow is likely to contribute to arm swelling. One explanation for increased flow would be neurological deficit with loss of sympathetic vasoconstrictor control.

The diaphragmatic echo complex: an in vitro study.

The brightly echogenic appearance of the diaphragm on routine clinical scans is not easily reconciled with the well-documented echo-poor appearance of muscle elsewhere in the body. A series of specimens of normal human diaphragm freshly excised at autopsy were suspended in a water bath. Articulated arm scans were done varying the angle of the incident beam to the specimen by 5-degree increments and recording the maximum attenuation which allowed visualization (ie, an extinction point). This was accomplished for intact diaphragm, peritoneal membrane alone, and diaphragmatic muscle alone with both membranes stripped. The bright specular echoes seen are due almost exclusively to the membranes (parietal pleura and peritoneum) and the diaphragmatic muscle itself produces only low-level scattered echoes as elsewhere. However, these scattered echoes account for persistent visualization of the diaphragm at steep angles of the incident beam. A considerable portion of the in vivo thickness of the diaphragmatic echo complex is, therefore, produced by diaphragm-lung interface.

Application of Fourier analysis to clinical study of patterns of tissue movement.

An analysis is made of the kinetics of human liver parenchyma in response to mechanical impulses arising in the heart and aorta, and the results are applied to predicting the time course of the correlation between two time-separated A-scans derived from various regions of the liver. Such predictions are found to correspond well with data derived clinically, both from volunteers and from patients with liver metastases, using a commercial, real-time sector scanner. On the basis of Fourier spectral features of the clinically derived correlation patterns, a clear quantitative separation was demonstrated between the kinetic response of three classes of tissue: normal liver in volunteers, metastatic deposits in liver of cancer patients, and histologically normal liver regions in the same patients.

Quantitative evaluation of real-time ultrasound features of the breast.

Semi-quantitative diagnostic features were extracted by a visual analysis of the echographic images of selected cases of breast disease and the results stored in a computer database. The long term aim is to create an environment suitable for the use of multivariate statistical methods systematically to evaluate ultrasound interpretive criteria and diagnostic performance in relation to factors such as scanning instrumentation and other diagnostic techniques. Eventually it is hoped that it will be possible to generate a system for computer assisted diagnosis and training. The results of this pilot study serve to demonstrate the feasibility of the approach and a univariate analysis is used to provide a preliminary ranking of diagnostic features. Features found to be particularly valuable for distinguishing benign from malignant solid lesions were the regularity and definition of the edge of the tumour, the mobility of the tumour and measures of echo heterogeneity within and posterior to the tumour mass.

Development of three-dimensional power Doppler ultrasound imaging of fetoplacental vasculature.

To develop an off-line system for three-dimensional (3-D) ultrasound (US) reconstruction of fetoplacental vasculature using colour segmentation and reconstruction software and to determine sources of error in fully freehand ultrasound image acquisition. US images were acquired freehand with the Acuson Sequoia (5C 2-MHz transducer) using power Doppler. After digital transfer to a personal computer, CQ Analysis software (Kinetic Imaging Ltd, Liverpool, UK) was used to segment the colour information from these images, and the resulting 8-bit grey-scale images were used for 3-D rendering using commercial software (VoxBlast, Vaytek Inc., Fairfield, IA, USA). 2-D scanning, software and freehand acquisition accuracy were assessed using a linear test rig and distance and volume phantoms (Dansk Phantom Service Ltd); 2-D scanning accuracy was within 1.3%, and software reconstruction accuracy within 1% for x and y planes and up to 3% for the z plane. Fully freehand acquisition was associated with a 12% to 18% mean percentage error in distance measurement in the plane of acquisition. Volumetric reconstruction inaccuracy was between 1.5% and 19.7% for precisely separated images and between 16.2% and 39.2% for fully freehand image acquisition. Rendered 3-D US vascular images clearly delineated vascular anatomy within the placenta and cord. Fully freehand 3-D US does have a role in off-line reconstruction of vascular anatomy, although variability in the z plane precludes its use for volumetric measurement. (E-mail: a.welsh@ic.ac.uk)

Ultrasonic study of in vivo kinetic characteristics of human tissues.

A method is described for quantifying tissue movement in vivo from the computation of correlation coefficient between pairs of A-scans with appropriate time separation. The method yields quantifiable and repeatable secondary patterns of soft tissue movement in response to primary cardiac movement in a given subject, shows consistently different results as between normal livers and a variety of abdominal tumours, and is sensitive to either progress or therapeutically-induced regression of malignant disease. While the results reported here have been obtained using somewhat simple and crude equipment, the method is well suited to implementation on a commercial real-time scanner.

Stimulated acoustic emission to image a late liver and spleen-specific phase of Levovist in normal volunteers and patients with and without liver disease.

Quantitative studies were performed to investigate liver- specific uptake of the microbubble Levovist, using stimulated acoustic emission (SAE), which can detect microbubbles even when stationary or slow-moving. These comprised studies of biodistribution comparing the liver and kidney in five normal volunteers, reproducibility in 34 patients, comparison between cirrhotics and controls (n = 9 each) and maximal depth of effect at different frequencies (180 measurements in 31 patients). Stimulated acoustic emission lasted beyond 30 min, with strongly liver-specific properties in each volunteer and was highly reproducible. No difference in the amount of SAE in the superficial liver was seen between cirrhotic and normal livers, but attenuation was higher in cirrhotics. This demonstrates a frequency-dependent effect on liver SAE penetration. We conclude that the liver uptake of Levovist lasts over 30 min, is reproducible, occurs even where diffuse liver disease is present and can be used to assess tissue attenuation in a novel fashion.

Case report: retroperitoneal varices mimicking a mass: diagnosis on colour Doppler.

Retroperitoneal varices may occasionally resemble retroperitoneal masses on computed tomography and B-mode ultrasound. Biopsy could be disastrous in this situation and angiography has previously been required to establish the diagnosis in suspected cases. This unusual problem can nowadays be readily diagnosed by colour Doppler. We report a case in which retroperitoneal varices were initially misinterpreted on B-mode ultrasound as retroperitoneal masses, but colour Doppler established the diagnosis without the need for further investigations.

Ultrasound features of tumour thrombus in the IVC in retroperitoneal tumours.

Tumour invasion of the inferior vena cava (IVC) is a complication of retroperitoneal tumours that can be identified at the time of ultrasound B scanning. We have recognized nine patients with proven IVC tumour thrombus from such tumours and have noted several common ultrasound features. Six of these cases were associated with renal carcinoma, two with metastatic teratoma and one with rhabdomyosarcoma. The typical appearance included abnormal echogenic solid material in the lumen of the vessel. In sagittal section the anterior wall was domed as it stretched over the thrombus, and on real time scanning there was loss of the normal venous pulsations. Although similar abnormalities occur with non-tumour thrombus, the presence of these typical features in association with a retroperitoneal tumour is likely to represent tumour invasion of the IVC, an important observation for accurate staging and subsequent management.

Case report: cachexia of the kidney--a cause of pseudo-hydronephrosis.

Various pitfalls in diagnosing early hydronephrosis on ultrasound (US) have been recognized. We present a case where the appearances on US mimicked bilateral hydronephrosis in a patient undergoing treatment for recurrent colonic carcinoma. Comparison with a previous ultrasound examination demonstrated marked loss of renal sinus fat. Doppler studies demonstrated normal venous flow within each portion of the "dilated collecting system". In oncology, renal cachexia should be remembered as one of the causes of pseudo-hydronephrosis.

Technical note: appearances on ultrasound of impalpable injection port in a double chamber breast prosthesis.

Breast reconstruction utilizing tissue expansion is being increasingly practised by both plastic and general surgeons. Our current experience for both immediate and delayed reconstruction is with the double chamber Becker prosthesis. The prosthesis with the resulting breast mound has on occasions rendered the injection port difficult to localize by palpation. We have found ultrasound useful in identifying impalpable ports and in facilitating needle insertion into the injection dome.

Case report: diffuse fatty infiltration of the renal parenchyma secondary to bilateral angiomyolipomas--features on ultrasound and computed tomography.

A case is described where ultrasound demonstrated diffusely increased echogenicity in massively enlarged kidneys. Computed tomography confirmed fatty replacement of the renal parenchyma, allowing a confident diagnosis of multiple bilateral angiomyolipomas in a clinical setting of tuberous sclerosis. This is the first ultrasound demonstration of such diffusely echogenic kidneys in angiomyolipoma.