Contrast-enhanced Doppler Research Articles

Spleen Transient Elastography and Damping Index Identify a Subgroup of Patients Without an Acute or Chronic Response to Beta-Blockers.

Background and AimsMonitoring of acute or chronic response to beta-blockers in patients with liver cirrhosis is based on the measurement of the HVPG. Our aim was to evaluate the response to beta-blockers with non-invasive techniques.Patients and MethodsThis is a prospective observational study. Consecutive patients with an indication of primary or secondary prophylaxis of variceal bleeding who did not meet exclusion criteria were included. Acute response and chronic response were evaluated. Baseline and after acute and chronic response hepatosplenic measurements of TE and ARFI were obtained. Contrast-enhanced Doppler ultrasound was performed before and after acute and chronic responses.ResultsFrom June 2015 to May 2018, 55 patients (14 with exclusion criteria) were included. We analyzed 41 patients, mean age 57 (SD: 8), 82.9% men, alcohol 43.9%, children A/B/C 78%/17.1%/4.9%, and 87.8% on primary prophylaxis. In all, the acute response was performed and was positive in 68.3% (CI 95: 55–85%). The chronic response was performed in 30 (73.2%) and was positive in 36.7% (CI 95: 18–55%). Basal measurements significantly related to acute response were spleen TE [responders 58.4 (SD: 23.0) KPa vs. non-responders 75 (SD: 0) KPa; p = 0.02] and damping index [non-responders 0.96 (0.8) vs. responders 0.44 (0.4), p = 0.01], and with chronic response, the spleen TE [responders 58.1 (SD: 21.4) KPa vs. non-responders 73.2 (SD: 5.5) KPa; p = 0.02], and damping index [non-chronic responders 0.8 (0.7) vs. chronic responders 0.4 (0.4), p = 0.04]. A spleen TE ≥ 74 KPa had a high sensitivity of 100% and specificity of 60% and a high NPV100% for predicting poor acute response to beta-blockers. The damping index > 0.6 showed moderate sensitivity of 67% and specificity of 69% with a high NPV of 82% for predicting poor acute response to beta-blockers. The combination of both measurements for predicting poor acute response to beta-blockers had an AUC of 0.8 (CI 95: 0.5–0.9). A spleen TE ≥ 74 KPa had a high sensitivity of 87% and specificity of 71% with a high NPV of 71% for predicting poor chronic response to beta-blockers. A damping index > 0.6 had moderate sensitivity of 60%, specificity of 82%, and NPV of 56% for predicting poor chronic response to beta-blockers. The combination of both measurements for predicting poor chronic response to beta-blockers had an AUC of 0.8 (CI 95: 0.7–0.9).ConclusionSpleen TE and damping index can identify a subgroup of patients with poor acute or chronic response to beta-blockers.

Abstract 117: Contrast-enhanced Transcranial Doppler Ultrasonography Versus Transesophageal Echocardiography As Screening Tool In Embolic Stroke

Introduction: Right-to-left (RtL) intracardiac and intrapulmonary shunts are associated with embolic stroke. Although contrast-enhanced transcranial doppler ultrasonography (ceTCD) and transesophageal echocardiography (TEE) are used in embolic stroke work up, there are no standardized guidelines as to which test should be considered as ‘gold standard’. Our objective is to evaluate the sensitivity of contrast-enhanced TCD and TEE in detecting right-to-left shunt to determine respective utilities as screening tools. Methods: Electronic medical records of subjects presenting with acute neurological symptoms who had ceTCD and TEE were evaluated. Sensitivity and specificity were calculated. Based on the respective prevalence of intracardiac and intrapulmonary shunts, positive predictive value, negative predictive value, and test accuracy were determined for ceTCD and TEE. Social Science Statistics was used for data analysis. Results: From June 2016 to August 2021, of 7,498 ischemic stroke patients, 260 patients were suspected of having strokes related to right to left shunts and underwent ceTCD and TEE for detection of cardioembolic sources for stroke. A positive right-to-left shunt was detected in 83 subjects. Detection by ceTCD was confirmed by the operator for 81 patients while 2 were considered false positive results (delayed sporadic High Intensity Transient Signals (HITS)). Sensitivity of ceTCD was 97.65% (95% CI [91.76%, 99.71%]). No safety concerns were identified in patients undergoing ceTCD. Of those with positive ceTCD (68.57%, n=35) were detected by Valsalva, and all of those 35 patients had negative TEE. TEE had sensitivity of 70.34% (95% CI [61.23%, 78.39%]). Conclusion: Contrast-enhanced TCD has superior sensitivity, is cost-effective, practical, and a safe alternative to TEE in identifying intracardiac or intrapulmonary shunts. Screening superiority of ceTCD may lie in ability to elicit shunts during Valsalva maneuvers. To our knowledge this is the largest single center series confirming ceTCD as a gold standard tool for screening of right to left shunts.

Ultrasound‐Responsive Nanopeptisomes Enable Synchronous Spatial Imaging and Inhibition of Clot Growth in Deep Vein Thrombosis

Deep vein thrombosis (DVT) is a life-threatening blood clotting condition that, if undetected, can cause deadly pulmonary embolisms. Critical to its clinical management is the ability to rapidly detect, monitor, and treat thrombosis. However, current diagnostic imaging modalities lack the resolution required to precisely localize vessel occlusions and enable clot monitoring in real time. Here, we rationally design fibrinogen-mimicking fluoropeptide nanoemulsions, or nanopeptisomes (NPeps), that allow contrast-enhanced ultrasound imaging of thrombi and synchronous inhibition of clot growth. The theranostic duality of NPeps is imparted via their intrinsic binding to integrins overexpressed on platelets activated during coagulation. The platelet-bound nanoemulsions can be vaporized and oscillate in an applied acoustic field to enable contrast-enhanced Doppler ultrasound detection of thrombi. Concurrently, nanoemulsions bound to platelets competitively inhibit secondary platelet-fibrinogen binding to disrupt further clot growth. Continued development of this synchronous theranostic platform may open new opportunities for image-guided, non-invasive, interventions for DVT and other vascular diseases.

Effects of contrast-enhanced ultrasound treatment on neoadjuvant chemotherapy in breast cancer.

Purpose: Preclinical and clinical data indicate that contrast-enhanced ultrasound can enhance tumor perfusion and vessel permeability, thus, improving chemotherapy accumulation and therapeutic outcome. Therefore, we investigated the effects of high mechanical index (MI) contrast-enhanced Doppler ultrasound (CDUS) on tumor perfusion in breast cancer.Methods: In this prospective study, breast cancer patients were randomly assigned to receive either 18 minutes of high MI CDUS during chemotherapy infusion (n = 6) or chemotherapy alone (n = 5). Tumor perfusion was measured before and after at least six chemotherapy cycles using motion-model ultrasound localization microscopy. Additionally, acute effects of CDUS on vessel perfusion and chemotherapy distribution were evaluated in mice bearing triple-negative breast cancer (TNBC).Results: Morphological and functional vascular characteristics of breast cancer in patients were not significantly influenced by high MI CDUS. However, complete clinical tumor response after neoadjuvant chemotherapy was lower in high MI CDUS-treated (1/6) compared to untreated patients (4/5) and size reduction of high MI CDUS treated tumors tended to be delayed at early chemotherapy cycles. In mice with TNBC high MI CDUS decreased the perfused tumor vessel fraction (p < 0.01) without affecting carboplatin accumulation or distribution. Higher vascular immaturity and lower stromal stabilization may explain the stronger vascular response in murine than human tumors.Conclusion: High MI CDUS had no detectable effect on breast cancer vascularization in patients. In mice, the same high MI CDUS setting did not affect chemotherapy accumulation although strong effects on the tumor vasculature were detected histologically. Thus, sonopermeabilization in human breast cancers might not be effective using high MI CDUS protocols and future applications may rather focus on low MI approaches triggering microbubble oscillations instead of destruction. Furthermore, our results show that there are profound differences in the response of mouse and human tumor vasculature to high MI CDUS, which need to be further explored and considered in clinical translation.

An investigation of the detection capability of pulsed wave duplex Doppler of low grade stenosis using ultrasound contrast agent microbubbles – An in-vitro study

ObjectiveThe objective of the study was to investigate whether clinically used ultrasonic contrast agents improved the accuracy of spectral Doppler ultrasound in the detection of low grade (<50%) renal artery stenosis. Low grade stenoses in the renal artery are notoriously difficult to reliably detect using Doppler ultrasound due to difficulties such as overlying fat and bowel gas. MethodsA range of anatomically-realistic renal artery phantoms with varying low degrees of stenosis (0, 30 and 50%) were constructed and peak velocity data was measured from within the pre-stenotic and mid-stenotic regions in each phantom, for both unenhanced and contrast-enhanced spectral Doppler data acquisitions. The effect of a 20 mm overlying fat layer on the ultrasound beam distortion and phase aberration, and hence on the measured peak velocity data, was also investigated. ResultsThe overlying fat layer produced a statistically significant underestimation (p < 0.01) in both the peak velocity and peak velocity ratio [Stenotic Region(Vmax)/Pre-stenotic Region(Vmax)] for the 0% and 30% stenosis models, but not the 50% model. A statistically significant increase (p < 0.01) in the peak velocity was found in the contrast-enhanced Doppler spectra; however, no significant difference was found between the unenhanced and contrast enhanced peak velocity ratio data, which suggests that the ratio metric has better diagnostic accuracy. The peak velocity ratios determined for each of the contrast-enhanced phantoms correctly predicted if the phantom had a stenosis and furthermore correctly classified the degree of stenosis. ConclusionContrast-enhanced Doppler ultrasound could significantly assist in the early detection of renal artery disease.

Modeling of the Acoustic Field Produced by Diagnostic Ultrasound Arrays in Plane and Diverging Wave Modes.

Recent advances in ultrafast contrast imaging have facilitated innovations, such as superresolution imaging and ultrafast contrast-enhanced Doppler imaging. Combining plane and diverging wave imaging (PWI/DWI) with tissue harmonic imaging (THI) may offer improvements in image quality in applications such as 3-D THI and harmonic color flow. However, no studies have reported simulations of the nonlinear acoustic fields produced by diagnostic arrays in either plane or diverging wave mode. The aim of this study is to model three typical diagnostic arrays that are used in clinical practice and research, Verasonics L11-4v linear array, C5-2v convex array, and P4-2v phased array with the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation. We have two specific objectives: first, to investigate whether there is increased bubble destruction due to the nature of the plane and diverging fields in contrast imaging; and second, to investigate the feasibility of combining PWI/DWI and THI by quantifying the second harmonic generated by these fields. We showed in linear simulations that using such arrays for ultrafast contrast imaging produced pressures that are greater in the near field and lower in the far field than those of focused beams and thus may induce more near-field bubble destruction. In nonlinear simulations, the second harmonic produced by ultrafast THI was found to be 2-16 dB lower than that of focused beams for all arrays considered when operated at the same MI. This moderate difference of the second harmonic between PWI/DWI and focused ultrasound suggests that it is feasible to combine PWI/DWI and THI.

3-D Perfusion Imaging Using Principal Curvature Detection Rendering.

Three-dimensional contrast-enhanced ultrasound (CEUS) imaging presents a clear advantage over its 2-D counterpart in detecting and characterizing suspicious lesions as it properly surveys the inherent heterogeneity of tumors. However, 3-D CEUS is also slow compared to 2-D CEUS and tends to undersample the microbubble wash-in. This makes it difficult to resolve the feeding vessels, an important oncogenic marker, from the background perfusion cloud. Contrast-enhanced Doppler is helpful in isolating this conduit flow, but requires too many pulses in conventional line-by-line beamforming design. Recent breakthroughs in plane-wave imaging have greatly accelerated the volumetric imaging frame rate, but volumetric Doppler angiography still remains challenging when considering real-time limitations on the Doppler ensemble length. In this work, we demonstrate the feasibility of volumetric CEUS angiography subjected to real-time imaging constraints. Namely, we show how principal curvature detection can significantly improve 3-D rendering of relatively noisy ultrasound angiograms without degrading the spatial resolution while subjected to a reasonable Doppler ensemble size. Singular value decomposition is also shown to be capable of identifying the quasi-stationary capillary perfusion.

Right-to-Left Shunt Detected Using Contrast-Enhanced Transcranial Doppler: A Comparison of Provocation Manoeuvres between Cough and a Modified Valsalva Manoeuvre

Right-to-Left Shunt Detected Using Contrast-Enhanced Transcranial Doppler: A Comparison of Provocation Manoeuvres between Cough and a Modified Valsalva Manoeuvre

Concepts and Tradeoffs in Velocity Estimation With Plane-Wave Contrast-Enhanced Doppler.

While long Doppler ensembles are, in principle, beneficial for velocity estimates, short acoustic pulses must be used in microbubble contrast-enhanced (CE) Doppler to mitigate microbubble destruction. This introduces inherent tradeoffs in velocity estimates with autocorrelators, which are studied here. A model of the autocorrelation function adapted to the microbubble Doppler signal accounting for transit time, the echo frequency uncertainty, and contrast-agent destruction is derived and validated in vitro. It is further demonstrated that a local measurement of the center frequency of the microbubble echo is essential in order to avoid significant bias in velocity estimates arising from the linear and nonlinear frequency-dependent scattering of microbubbles and compensate for the inherent speckle nature of the received echo frequency. For these reasons, broadband Doppler estimators (2-D autocorrelator and Radon projection) are better suited than simpler narrow-band estimators (1-D autocorrelator and 1-D Fourier transform) for CE flow assessment. A case study of perfusion in a VX-2 carcinoma using CE plane-wave Doppler is also shown. We demonstrate that even when considering all uncertainties associated with microbubble-related decorrelation (destruction, pulse bandwidth, transit time, and flow gradient) and the need for real-time imaging, a coefficient of variation of 4% on the axial velocity is achievable with plane-wave imaging.

Safety and Efficacy of Cardiac Ultrasound Contrast in Children and Adolescents for Resting and Stress Echocardiography

Small pilot studies of ultrasound contrast (UC) echocardiography in children have suggested that it is safe; therefore, larger scale evaluation of safety and efficacy in this population is of particular interest. This was a retrospective study (January 2005 to June 2014). Known intracardiac shunt was the only exclusion criterion. UC echocardiography was performed on commercially available ultrasound systems using Definity (3% infusion). When indicated, real-time myocardial contrast echocardiography was performed at rest and stress, with examination of myocardial contrast replenishment, plateau intensity, and wall motion. The primary outcome was short-term safety and efficacy (<24hours). In all, 113 patients (55% male; mean age, 17.8±3years; age range, 5-21 years) underwent UC echocardiography for left ventricular opacification or stress wall motion and perfusion analysis. Diagnosis categories were congenital heart disease (30%), acquired heart disease (21%), and other (suspected cardiac complications of disease of other organ systems; 49%). Twelve patients (11%) with right ventricular systolic pressures>40mmHg received UC without complications; four of these (33%) had the highest right ventricular-right atrial gradient recorded with ultrasound contrast-enhanced Doppler. Myocardial perfusion and/or UC echocardiography-detected wall motion abnormalities were seen in 13 patients (12%); four had confirmed correlations by angiography or magnetic resonance imaging. There were 13 instances of adverse events or reported symptoms during UC echocardiography. All symptoms and events were transient, all patients completed protocols, and there were no immediate sequelae. These data demonstrate the usefulness and safety of UC echocardiography in children and adolescents for a wide variety of indications. UC echocardiography provided myocardial perfusion and wall motion information important in clinical decision making.

Current status and future applications of contrast-enhanced endoscopic ultrasonography.

Endoscopic ultrasonography (EUS) is currently an integral investigation of many gastrointestinal disorders. It has been shown to have a higher efficacy than conventional computed tomography in detection and characterization of small lesions especially in the pancreas. Much effort has been put to further improve the sensitivity, specificity and overall accuracy of EUS. One of the major advances is the utilization of contrast agents for better delineation of the vascularity and tissue perfusion of the target lesion. This article describes the basic principles of ultrasound contrast agents and the different modalities used in contrast-enhanced EUS (CE-EUS) including contrast-enhanced Doppler EUS (CED-EUS) and contrast-enhanced harmonic EUS (CEH-EUS). In addition, the current applications of contrast enhanced EUS in different gastrointestinal conditions were discussed. Furthermore, the future development of hybrid approaches combining CE-EUS with other imaging modalities and the potential therapeutic aspect of using it as a vector for drug delivery were also discussed.

Cognitive impairment and antiphospholipid syndrome: is paradoxical embolism the rule?

Objective: Although cognitive decline (CD) is described in antiphospholipid syndrome (APS), its physiopathology is unknown. Paradoxical embolization (PE) is related to CD in Alzheimer disease. The objective of this study was to determine whether PE plays a role in CD in APS patients through a significant right-to-left shunt (sRLS).Methods: A total of 27 patients diagnosed with APS without a history of stroke were tested for the presence of an sRLS using a contrast-enhanced transcranial Doppler (cTCD) ultrasound. Cognitive decline was assessed using the mini mental state examination (MMSE), the Montreal cognitive assessment (MoCA), and a battery of neuropsychological tests.Results: Of the 27 patients, 19 (70%) had a non-sRLS condition (≤10 high-intensity transient signs [HITS] on cTCD), and 8 (30%) had an sRLS. Patients with more than 10 years of scholarship performed significantly better on both the MMSE (P = 0·048) and MoCA (P = 0·03). Individuals of the non-sRLS group with more than 10 years of scholarship had better performances on the five-point test (FPT) when compared with the sRLS group (P = 0·01).Conclusions: Patients without sRLS and with more years of education exhibited a better performance in cognitive tests than sRLS patients.

Contrast‐enhanced endoscopic ultrasound

Compared to other imaging modalities, endoscopic ultrasound (EUS) has limitations in terms of image enhancement. However, with the availability of contrast agents in ultrasonography, EUS has evolved. Contrast-enhanced Doppler EUS (CD-EUS) enhances Doppler signals from vessels and is useful for characterizing lesions detected by EUS. Moreover, contrast-enhanced harmonic EUS (CH-EUS) with second-generation ultrasound contrast agents and a broad band transducer allows microvessels and parenchymal perfusion to be visualized. Vascularity can also be quantitatively analyzed during CH-EUS by generating a time-intensity curve. CE-EUS is useful for characterizing pancreatic lesions and can detect pancreatic adenocarcinomas with a sensitivity of 94%and a specificity of 89% as a result of the hypo-enhancement of these lesions. Indeed, CH-EUS is superior to multiple detector-computed tomography in terms of the differential diagnosis of small lesions that are ≤2 cm. CH-EUS complements EUS-guided fine-needle aspiration (EUS-FNA) as it identifies the EUS-FNA target and lesions with false-negative EUS-FNA findings. CH-EUS is also used to estimate the malignant potential of gastrointestinal stromal tumors and helps to differentiate between malignant and benign lymphadenopathy.

A phase II study of sorafenib in combination with cisplatin and 5-fluorouracil in the treatment of recurrent or metastatic nasopharyngeal carcinoma.

5538 Background: Nasopharyngeal carcinoma (NPC) is a disease with distinctive epidemiology and clinical behavior compared with Head and neck cancer (HNC) and more common in South-East Asia. Sorafenib monotherapy has been shown modest anticancer activity in HNC and NPC (C Elser et al; JCO 2007). This study was to evaluate the efficacy and tolerability of sorafenib combined with cisplatin and 5-fluorouracil (5-FU) for patients with recurrent or metastatic NPC. Methods: A phase II, single arm clinical trial was conducted in three centers in China. Chemotherapy-naive histologically confirmed NPC patients with recurrent or metastatic disease were enrolled. Patients received oral sorafenib 400mg bid continuously until disease progression or unacceptable toxicity, cisplatin 80mg/m2 intravenously (iv) on day 1-5, and 5-FU 400mg/m2 iv infusion for 96 hours on day 1. Treatment was repeated every 21 days for a maximum of 6 cycles. Results: 54 patients were enrolled. Most patients were with bone metastases (70.0%), followed by liver (56%) and lung metastases (56%). The median chemotherapy administrated was 4.0 cycles (range, 2 - 6 cycles). The disease control rate (DCR) reached 90.7%, including one complete response (CR), 41 partial responses (PR) and 7 stable diseases (SD). Median PFS was 7.2 months (95% CI 6.8-8.4 months) and median OS was 11.8 months (95% CI 10.6-18.7 months). Tumor cavitation after treatment was observed in 32.1% of patients with lung metastases. Decreased percentage of contrast update in responder patients (PR and CR) with liver metastases was also observed by Contrast-Enhanced Doppler ultrasound. The major toxicities include hand foot syndrome (HFS), myelo-suppression and gastrointestinal reaction.Dose reduction of sorafenib was required in 22 patients (40.7%) and dose interruption in 14 patients (25.9%) because of toxicity. Conclusions: Sorafenib combined with cisplatin and 5-FU has an encouraging efficacy profile with tolerable toxicity. Further randomized studies are needed to confirm the clinical benefit of sorafenib combined with chemotherapy in recurrent or metastatic NPC.

Imaging of ankylosing spondylitis

Conventional radiography can visualize bone erosion, sclerosis, joint space narrowing and new bone formation in sacroiliac joints and the spine, but is unfortunately not very sensitive in early disease. Diagnosis of ankylosing spondylitis (AS) is dependent on presence of bilateral moderate or unilateral severe radiographic sacroiliitis, as part of the modified New York criteria for AS. This has, until recently (see MRI below), delayed the diagnosis by 7-10 years. Furthermore, the modified Stokes ankylosing spondylitis spine score (mSASSS), which is the most sensitive radiographic method for monitoring structural damage in AS, is not very reproducible or sensitive to change, so improved methods for structural damage assessment are highly needed. MRI has resulted in a major improvement in the evaluation and management of patients with SpA. Firstly, it permits earlier diagnosis, as MRI findings of active sacroiliitis form part of the recent ASAS criteria for axial spondyloarthritis. Secondly, MRI can provide objective evidence of currently active inflammation in patients with SpA. MRI is by far the best available method for detecting and monitoring inflammation in the spine and sacroiliac joints, and several validated assessment systems exist. Until the introduction of MRI, disease activity assessment was restricted to patient-reported outcomes, such as the Bath ankylosing spondylitis disease activity index (BASDAI) and functional index (BASFI), because disease activity could not be assessed in a sensitive manner by biochemical (mainly C- reactive protein (CRP)) or physical evaluation. Furthermore, MRI can visualize structural damage (erosion, fat infiltration, syndesmophytes and ankylosis) in the sacroiliac joint and spine, but the clinical role of MRI for monitoring structural damage remains to be established. Finally, certain MRI findings (inflammation at the vertebral corners) have predictive value with respect to subsequent development of radiographic syndesmophytes. However, clarification of the prognostic value of MRI in clinical practice requires further research. Despite contrast-enhanced Doppler US has been reported to have a high negative predictive value for the detection of sacroiliitis, the role of US in assessment of sacroiliac and spine involvement in AS and other types of axial SpA is minimal.

Evaluation of high frequency ultrasound methods and contrast agents for characterising tumor response to anti-angiogenic treatment

PurposeTo compare non-enhanced and contrast-enhanced high-frequency 3D Doppler ultrasound with contrast-enhanced 2D and 3D B-mode imaging for assessing tumor vascularity during antiangiogenic treatment using soft-shell and hard-shell microbubbles. Materials and methodsAntiangiogenic therapy effects (SU11248) on vascularity of subcutaneous epidermoid-carcinoma xenografts (A431) in female CD1 nude mice were investigated longitudinally using non-enhanced and contrast-enhanced 3D Doppler at 25MHz. Additionally, contrast-enhanced 2D and 3D B-mode scans were performed by injecting hard-shell (poly-butyl-cyanoacrylate-based) and soft-shell (phospholipid-based) microbubbles. Suitability of both contrast agents for high frequency imaging and the sensitivity of the different ultrasound methods to assess early antiangiogenic therapy effects were investigated. Ultrasound data were validated by immunohistology. ResultsHard-shell microbubbles induced higher signal intensity changes in tumors than soft-shell microbubbles in 2D B-mode measurements (424±7 vs. 169±8A.U.; p<0.01). In 3D measurements, signals of soft-shell microbubbles were hardly above the background (5.48±4.57 vs. 3.86±2.92A.U.), while signals from hard-shell microbubbles were sufficiently high (30.5±8.06A.U). Using hard-shell microbubbles 2D and 3D B-mode imaging depicted a significant decrease in tumor vascularity during antiangiogenic therapy from day 1 on. Using soft-shell microbubbles significant therapy effects were observed at day 4 after therapy in 2D B-mode imaging but could not be detected in the 3D mode. With non-enhanced and contrast-enhanced Doppler imaging significant differences between treated and untreated tumors were found from day 2 on. ConclusionHard-shell microbubble-enhanced 2D and 3D B-mode ultrasound achieved highest sensitivity for assessing therapy effects on tumor vascularisation and were superior to B-mode ultrasound with soft-shell microbubbles and to Doppler imaging.

Endoscopic Ultrasonography and Contrast-Enhanced Endoscopic Ultrasonography

Endoscopic ultrasonography (EUS) is superior to all other imaging modalities in detecting small pancreatic cancers. However, its ability to characterize hypoechoic pancreatic masses is limited: most carcinomas, neuroendocrine tumors, and inflammatory pseudotumors are simply depicted as hypoechoic masses. Contrast enhancement helps EUS to characterize such hypoechoic masses. Intravenous ultrasound (US) agents increase the signal from the blood and, thus, act as amplifiers and improve visualization of blood flow in small vessels using Doppler US. Contrast-enhanced Doppler EUS can differentiate small pancreatic carcinomas that cannot be detected by other imaging modalities. The development of second-generation US contrast agents and an EUS system with a broad-band transducer enabled the visualization of microvessels and the parenchymal perfusion in the pancreas. This contrast-enhanced harmonic EUS has shown that most pancreatic cancers exhibit hypovascular heterogeneous enhancement with irregular network-like microvessels. Moreover, it can diagnose pancreatic cancers with a high sensitivity (89–92%).

Haemodynamic evaluation by Doppler ultrasonography in patients with portal hypertension: a review

Doppler ultrasonography (US) has an advantage of being non-invasive; therefore, several attempts have been made to investigate the haemodynamic alterations in cirrhosis and the response to medical treatment of portal hypertension. Doppler indices, which have been commonly used for the evaluation of portal hypertension, include the measurement of portal and splenic venous blood velocity and flows, and the resistive and pulsatility index at hepatic, splenic, renal, superior mesenteric artery. Although many positive evidences have been suggested, its clinical usefulness in portal hypertension remains unsettled because of being plagued by lack of reproducibility and accuracy characterized by intra- and interobserver variation. However, recently, Doppler's usefulness in assessment of severity of portal hypertension in terms of reproducibility, technical ease and accuracy and response to drugs that reduce the portal pressure has been proposed. In addition, because most of the patients with cirrhosis and portal hypertension have intrahepatic shunts, they show a decrease in intrahepatic circulatory time (IHCT). Doppler US using microbubble contrast agents allows measurement of IHCT. Therefore, application of contrast-enhanced Doppler US can be prospective for the assessment of the severity of portal hypertension. Several reports have demonstrated that colour Doppler endoscopic US enable haemodynamic study to assess the portal hypertension and has a role of guidance to measure the imaging-based variceal pressure. We have reviewed briefly the clinical usefulness of Doppler US in assessing the severity of portal hypertension and its response to treatment.

Non-invasive investigations of potential renal artery stenosis in renal insufficiency

The diagnostic value of non-invasive methods for diagnosing renal artery stenosis in patients with renal insufficiency is incompletely known. Forty-seven consecutive patients with moderately impaired renal function and a clinical suspicion of renal artery stenosis were investigated with computed tomography angiography (CTA), gadolinium-enhanced magnetic resonance angiography (MRA), contrast-enhanced Doppler ultrasound and captopril renography. The primary reference standard was stenosis reducing the vessel diameter by at least 50% on CTA, and an alternative reference standard ('morphological and functional stenosis') was defined as at least 50% diameter reduction on CTA or MRA, combined with a positive finding from ultrasound or captopril renography. The frequency of positive findings, calculated on the basis of individual patients, was 70% for CTA, 60% for MRA, 53% for ultrasound and 30% for captopril renography. Counting kidneys rather than patients, corresponding frequencies were 53%, 41%, 29% and 15%, respectively. In relation to the CTA standard, the sensitivity (and specificity) at the patient level was 0.81 (0.79) for MRA, 0.70 (0.89) for ultrasound and 0.42 (1.00) for captopril renography, and at the kidney level 0.76 (0.82), 0.53 (0.81) and 0.30 (0.86), respectively. Relative to the alternative reference standard, corresponding values at the patient level were 1.00 (0.62) for CTA, 0.90 (0.69) for MRA, 0.91 (1.00) for ultrasound and 0.67 (1.00) for captopril renography, and at the kidney level 0.96 (0.76), 0.85 (0.79), 0.71 (0.97) and 0.50 (0.97), respectively. CTA and MRA are superior to ultrasound and captopril renography at diagnosing morphological stenosis, but ultrasound may be useful as a screening method and captopril renography for verifying renin-dependent hypertension.

Contrast‐Enhanced Power and Color Doppler Ultrasonography of the Pancreas in Healthy and Diseased Cats

The diagnosis of feline pancreatic disease is difficult, because clinical abnormalities and routine noninvasive diagnostic tests are unreliable. The purpose of this study was to investigate by Doppler ultrasonography if vascularity and blood volume differs in the otherwise ultrasonographically normal and diseased feline pancreas. Thirty-six client owned cats. The pancreas was examined with B-mode and contrast-enhanced color and power Doppler ultrasonography. Doppler images were analyzed with a computer program: parameter fractional area represents a vascularity index and color-weighted fractional area assesses blood volume. Based on the B-mode findings, the pancreas was considered normal in 11 clinically healthy cats and diseased in 25 cats of which 4 were clinically healthy and 21 had clinical signs consistent with pancreatic disease. Histologic or cytologic samples were taken in all diseased pancreata. Fifteen samples were of diagnostic quality: purulent or mixed cellular inflammation (8), nodular hyperplasia (4), and neoplasia (3) were identified. Vascularity and blood volume for all Doppler methods was significantly higher in cats with pancreatic disease. Significantly higher Doppler values were detected with power Doppler than with color Doppler, and with postcontrast color and power Doppler than with precontrast Doppler technologies. Contrast-enhanced Doppler ultrasonography appears feasible in the feline pancreas. Significant differences were found between normal cats and those with evidence of pancreatic pathology. Further studies are needed to evaluate its use for the differentiation of pancreatic disorders and in cats suspected to have pancreatic disease but without B-mode ultrasonographic changes of the pancreas.