Contrast Harmonic Imaging Research Articles

Nonlinear Frequency Mixing Ultrasound Imaging of Nanoscale Contrast Agents.

Nanoscale ultrasound contrast agents show promise as alternatives for diagnostics and therapies due to their enhanced stability and ability to traverse blood vessels. Nonetheless, their reduced size limits echogenicity. This study introduces an enhanced nanobubble frequency mixing ultrasound imaging method, by capitalizing on their nonlinear acoustic response to dual-frequency excitation. A single broadband transducer (L12-3v) controlled by a programmable ultrasound system was used to transmit a dual-frequency single-cycle wavefront. The frequency mixing effect enabled simultaneous transducer capture of nanobubble-generated sum and difference frequencies in real time without the need for additional hardware or post-processing, by substituting the single-frequency wavefront in a standard contrast harmonic pulse inversion imaging protocol, with the dual-frequency wavefront. Optimization experiments were conducted in tissue mimicking phantoms. Among the dual-frequency combinations that were tested, the highest contrast was obtained using 4&8 MHz. The nanobubble contrast improved with increased mechanical index, and achieved a maximal contrast improvement of 8.4 ± 0.5 dB compared to 4 MHz pulse inversion imaging. In imaging of a breast cancer tumor mouse model, after a systemic nanobubble injection, the contrast was improved by 3.4 ± 1.7, 4.8 ± 1.8, and 6.3 ± 1.6 dB for mechanical indices of 0.04, 0.08, and 0.1, respectively. Nonlinear frequency mixing significantly improved the nanobubble contrast, which facilitated their imaging in-vivo. This study offers a new avenue to enhance ultrasound imaging utilizing nanobubbles, potentially leading to advancements in other diagnostic applications.

Identification of sentinel lymph nodes in esophageal cancer patients using contrast-enhanced EUS with peritumoral injections.

The objective of this pilot study was to compare the performance of contrast-enhanced EUS (CE-EUS)-guided fine-needle aspiration (FNA) with EUS-FNA for lymph node (LN) staging in esophageal cancer. Thirty-seven subjects with esophageal cancer undergoing EUS staging were enrolled, and 30 completed this institutional review board-approved study. A Prosound F75 US system (Hitachi Medical Systems, Tokyo, Japan) with harmonic contrast imaging software and GF-UCT180 curvilinear endoscope (Olympus, Tokyo, Japan) was utilized. All LNs identified by standard EUS were first noted. Sonazoid (dose: 1 mL; GE Healthcare, Oslo, Norway) was administered peritumorally, and all enhanced LNs were recorded. Fine-needle aspiration was performed on LNs considered suspicious by EUS alone, as well as LNs enhanced on CE-EUS. Performance of each modality was compared using FNA cytology as reference standard. A total of 132 LNs were detected with EUS, of which 59 showed enhancement on CE-EUS. Fifty-three LNs underwent FNA, and 22 LNs were determined to be malignant. Among the latter, 10 were considered suspicious by EUS, whereas the other 12 LNs underwent FNA only because of CE-EUS enhancement. Contrast-enhanced EUS showed enhancement in 19 of the 22 malignant LNs. The rate of metastatic node identification from EUS was 45% (10/22), and it was 86% (19/22; P = 0.008) for CE-EUS. Eight subjects (8/30 [27% of study total]) had nodal status upgraded by the addition of CE-EUS, which influenced LN staging and clinical management. Fine-needle aspiration of LNs identified by CE-EUS may increase metastasis positive rate by ruling out LNs not associated with the tumor drainage pattern. In addition, CE-EUS seems to identify more metastatic LNs that would not be biopsied under the standard EUS criteria.

Ultrasound Frequency Mixing for Enhanced Contrast Harmonic Imaging of Microbubbles.

Microbubbles (MBs) serve as contrast agents in diagnostic ultrasound (US) imaging. Contrast harmonic imaging (CHI) of MBs takes advantage of their nonlinear properties that generate additional harmonic frequencies in the received spectrum. However, CHI suffers from limitations in terms of contrast, the signal-to-noise ratio, and artifacts. This article presents an enhanced, real-time, nonlinear imaging technique based on the excitation of MBs with a dual frequency waveform. The MBs trigger a frequency mixing effect that generates additional frequency components in the received spectrum; i.e., difference and sum frequencies, in addition to the standard harmonics, thus amplifying the MB's nonlinear response and enhancing image contrast. In this real-time approach, two single frequency waveforms are superpositioned into a dual frequency transmission. The dual frequency waveform is incorporated into a standard pulse-inversion (PI) sequence and is transmitted by an array transducer using an arbitrary waveform generator (AWG) in a programmable US system. Upon receive, standard dynamic receive beamforming is used, without additional post processing. Numerical simulations using the Marmottant model are used to confirm the generation of the difference frequency in the MB's backscattered echoes. The resulting image quality enhancement is demonstrated in a tissue-mimicking phantom containing MBs' suspension. A maximal contrast improvement of 3.43 dB compared to standard PI was achieved, along with a reduction by 4.5 fold in the mechanical index (MI).

Gastric Cancer Angiogenesis Assessment by Dynamic Contrast Harmonic Imaging Endoscopic Ultrasound (CHI-EUS) and Immunohistochemical Analysis-A Feasibility Study.

Tumor vascular perfusion pattern in gastric cancer (GC) may be an important prognostic factor with therapeutic implications. Non-invasive methods such as dynamic contrast harmonic imaging endoscopic ultrasound (CHI-EUS) may provide details about tumor perfusion and could also lay out another perspective for angiogenesis assessment. Methods: We included 34 patients with GC, adenocarcinoma, with CHI-EUS examinations that were performed before any treatment decision. We analyzed eighty video sequences with a dedicated software for quantitative analysis of the vascular patterns of specific regions of interest (ROI). As a result, time-intensity curve (TIC) along with other derived parameters were automatically generated: peak enhancement (PE), rise time (RT), time to peak (TTP), wash-in perfusion index (WiPI), ROI area, and others. We performed CD105 and CD31 immunostaining to calculate the vascular diameter (vd) and the microvascular density (MVD), and the results were compared with CHI-EUS parameters. Results: High statistical correlations (p < 0.05) were observed between TIC analysis parameters MVD and vd CD31. Strong correlations were also found between tumor grade and 7 CHI-EUS parameters, p < 0.005. Conclusions: GC angiogenesis assessment by CHI-EUS is feasible and may be considered for future studies based on TIC analysis.

ID: 3523607 TUMOR ANGIOGENESIS ASSESSED BY DYNAMIC CONTRAST HARMONIC IMAGING ENDOSCOPIC ULTRASOUND AND IMMUNOHISTOCHEMICAL ANALYSIS IN GASTRIC CANCER - A FEASIBILITY STUDY

Background and Objectives: The aim of this feasibility study was to assess the vascular perfusion pattern in gastric cancer (GC) using dynamic contrast harmonic imaging endoscopic ultrasound (CHI-EUS) and compare it to immunohistochemical markers of angiogenesis and clinico-pathological parameters.

Diagnostic Value of High Frame Rate Contrast-enhanced Ultrasonography and Post-processing Contrast Vector Imaging for Evaluation of Focal Liver Lesions: A Feasibility Study

This study evaluated the feasibility of contrast vector imaging (CVI) to characterize focal liver lesions. From July to October 2019, we prospectively enrolled 30 patients with focal liver lesions (hepatocellular carcinoma [HCC] [n = 19], metastasis [n = 8], combined HCC-cholangiocarcinoma [CC] [n = 1], intra-hepatic CC [n = 1] and sclerosed hemangioma [n = 1]). Contrast-enhanced ultrasound (CEUS) was performed with high frame rate contrast harmonic imaging technique by one radiologist, and post-processing CVI was obtained and analyzed by two radiologists. On combined CVI with CEUS, the staining pattern was significantly predominant in HCCs (9/11, 81.8%), while peripheral rim was frequent in non-HCCs (5/8, 62.5%) (p = 0.020). HCCs exhibited feeding arteries (8/11, 45.5%) and high velocity variance (10/11, 90.9 %), whereas non-HCCs showed detour pattern (4/8, 50.0%) with either a high or low velocity variance (4/8, 50.0%, both), with no significant inter-group differences (p = 0.052 and 0.080, respectively). In conclusion, CVI was feasible and provided quantitative and multi-parametric information of different types of hepatic tumors.

Endoscopic ultrasonography in pancreatic diseases: advances in tissue acquisition.

Background and study aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) improved the diagnostic performance and upgraded the role of endoscopic ultrasonography (EUS) into an interventional modality, able to guide patient management and treatment.This review aimed to highlight the advances, emerging practices, procedural techniques and technological innovations in EUS tissue acquisition in pancreatic diseases. Methods A thorough review of the literature was performed using PubMed to identify articles that describe techniques, advances, and practices in EUS tissue acquisition in gastrointestinal diseases. Conclusion Since the first EUS-FNA procedure, EUS guided-tissue acquisition has been evolving continuously. Development of needles with innovative tip design enabled procurement of larger samples with preserved histological architecture. Moreover, sampling techniques and complementary methods, such as contrast harmonic imaging and EUS-elastography, have been introduced in an effort to improve diagnostic performance and sample adequacy.

Identification of two distinct hereditary hemorrhagic telangiectasia patient subsets with different hepatic perfusion properties by combination of contrast-enhanced ultrasound (CEUS) with perfusion imaging quantification.

BackgroundHereditary hemorrhagic telangiectasia (HHT) is marked by arteriovenous fusion comprising hepatic vascular malformations (HVaMs) with the chance of bleeding.AimsWe investigated HVaMs in HHT patients by combination of contrast-enhanced ultrasound (CEUS) with perfusion imaging quantification to be able to sub-classify a high risk cohort of asymptomatic HHT patients.MethodsThe imaging characteristics on CEUS in 34 patients (aged 21–84 years; mean 58.9) with HHT were retrospectively evaluated. Real-time contrast harmonic imaging, sulfur hexafluoride-filled microbubbles and motion adjustment were utilized. Cine loops of the liver were digital stored, perfusion was quantified using a software reading DICOM data`s.ResultsHVaMs were diagnosed in 31 out of 34 patients. Significant uppermost peak enhancement (PE), wash-in area under the curve (WiAUC) and wash-in perfusion index (WiPI) were identified in the shunt region (100%), next in the hilar region (PE 32.6%; WiAUC 33.9%; WiPI 34.1%), and the lowest in the hepatic parenchyma (PE 10.2%; WiAUC 12.0%; WiPI 9.5%). The perfusion parameters in the shunt region compared to the other regions were significantly increased in one subgroup of patients. Consistent with this, the intrahepatic portal vein diameter and Buscarini grading was significantly higher, while portal vein peak velocity was significantly lower in this patient subset. By statistical analysis, we could correlate PE and WiPI to these clinical parameters, while WiAUC showed no clinical association.ConclusionsFor the first time we combined CEUS findings with motion adjustment software to quantitative determine perfusion parameters of a cohort of HHT patients. Hereby, we could identify a subset of HHT patients with two markedly increased parameter values in the shunt region compared to the hilus/hepatic parenchyma. This could contribute to sub-classify a high-risk group of HHT patients with therapeutic indication.

Quantitative, noninvasive assessment of intra- and extraocular perfusion by contrast-enhanced ultrasonography and its clinical applicability in healthy dogs.

ObjectiveTo assess quantitative perfusion of intra‐ and extraocular regions of interest (ROIs) in conscious, healthy dogs utilizing contrast‐enhanced ultrasonography (CEUS); to compare varying enhancement with the first and second bolus injection and in the right and left eye; and to determine the most appropriate examination time.ProceduresGray scale ultrasonography and contrast harmonic imaging using sulfur hexafluoride were performed randomly assigned in both eyes in 10 university‐owned beagles. Perfusion parameters including slope time, time to peak (TTP), peak intensity (PI), and area under the curve (AUC) were measured at individually drawn ROIs (retrobulbar cone = ROI 1, choroid‐retina complex = ROI 2, medial = ROI 3, and lateral anterior uvea = ROI 4).ResultsTime‐intensity curve parameters revealed no significant differences in eyes examined by the first or second bolus injection (P > 0.05) or in the right or left eye (P > 0.05). Pooled data from all eyes were analyzed. Peak intensity of ROI 2 was significantly higher compared to all other ROIs (P < 0.001). Area under the curve at ROI 2 was significantly higher compared to all other ROIs (P < 0.05), and AUC at ROI 1 was significantly higher than at ROI 4 (P < 0.05). No significant differences in TTP were observed between different ROIs (P > 0.05). Ratios relative to different ROI sizes showed fastest enhancement in the retrobulbar cone and most intense perfusion in the anterior uveal regions. The first minute after contrast injection provided the highest diagnostic value.ConclusionQuantitative perfusion in nondiseased canine eyes revealed consistent parameters. Application of standardized CEUS protocols may be a promising diagnostic tool to differentiate ocular lesions.

Diagnosis of gallbladder polypoid lesions using contrast enhanced ultrasound

Purpose Effectiveness of differential diagnosis of gallbladder polypoid lesions using contrast enhanced ultrasound (CEUS) examination by perflubutane (Sonazoid®:Daiichi-Sankyo, Tokyo). Material & Methods CEUS was performed on 183 patients with gallbladder polypoid lesions.It consists of 10 adenocarcinomas, 2 adenomas, 129 benign polyps and 42 adenomyomatosis (fundal type). For benigndiseases, we examined cases where the size was 6 mm or more and could be observed for more than one year. Ultrasound was performed using TUS-A500 (Aplio 500) (Canon MedicalSystems. Tokyo) and prosound alpha10 (Hitachi Aloka Medical,Ltd.Tokyo). First, the largest cross section of a lesion was visualized using B-mode and infusion of Sonazoid. The characteristics and behavior of blood flow in the lesion in the early vascular phase were examined over approximately 30 sec. Thereafter, observation was continued accordingly for about 3 min. Sonazoid infusion using contrast harmonic imaging and real-time perfusion Imaging. Results Gallbladder carcinoma showed hypervascular staining and “eruption sign” was apparent in 60%. The “eruption sign” showed an image of a vigorously boiling water that was splashing up from the entire lesion. Blood flow imaging revealed irregular size and buckling, including tortuous vessels and erratic blood flow in 70%. Gallbladder adenoma showed “eruption sign” was apparent in 50%. The irregular size, tortuous vessels and eruption signs of blood flow imaging were 83.3% as an index of neoplastic. Gallbladder benign polyp, staining was scattered within them, and “flicker sign” was observed in 93.8%. The “flicker sign” showed an image of bubbling pre-boiled hot water. Five cases (3.9%) showed a diffused and hypervascular staining pattern. The staining time was shorter than gallbladder carcinoma. Blood flow image showed normal vessels without buckling. Linear blood flow of the stalk of gallbladder polyp was also characteristic. Gallbladder adenomyomatosis (fundal type), staining was scattered and mild flicker signs were observed in 85.7%. Blood flow at the surface of the prominence and internal Rokitansky-Aschoff sinus was observed clearity. Conclusions CEUS can clarify the hemodynamics and blood flow images and are useful for the differential diagnosis of gallbladder polypoid lesions.

Dual frequency contrast ultrasound angiography

Acoustic angiography is a contrast imaging approach in which the superharmonics associated with low frequency excitation of microbubbles are received and processed over a broad bandwidth at a much higher frequency. As demonstrated by Dayton and colleagues, this technique facilitates the visualization of the microvasculature with a resolution typical of micro computed tomography and with superior contrast-to tissue-ratios than conventional nonlinear processing. To date dual frequency contrast imaging has been performed with a 2- 4 MHz annulus coaligned with 25-30MHz single element focused transducer operated by a Vevo770 (Visualsonics) scanner. This technology has limitations (mechanical scanning, single focus, limited focal depth) which hinder its clinical use but which could be alleviated using dualfrequency arrays (DFA). In this presentation we first describe the performance and applications of mechanical acoustic angiography and early results from the development of dual frequency array devices for acoustic angiography. The logical extension to array based designs is then explored. We built prototype dual frequency devices in both a vertical and horizonal topology. The horizonal topography consisted of a central 256 element high frequency array (HF, 20 MHz) flanked by two single element low frequency transducers(LF, 2 MHz) that extended for the length of the HF array. The vertical topography consisted of a 32-element LF transmitter array positioned behind a 256-element HF receiver array. Both arrays were built from piezoelectric composites. The HF backing material, between the two piezoelectric layers in the vertical design is weakly and highly attenuating at 2 MHz and 20 MHz, respectively. Two matching layers on the LF array and 4 matching layers on the HF array were used to improve transmission throughout the whole array structure. An elevation lens was added to focus the receive component at around 9 mm. Impedance and hydrophone measurements were performed to evaluate both configurations. Examples of super harmonic contrast imaging for each of the above configurations will be shown for phantom studies and preliminary in vivo images of animal models will be presented.

Can different regions of interest influence the diagnosis of benign and malignant breast lesions using quantitative parameters of contrast-enhanced sonography?

ObjectivesTo evaluate the diagnostic utility of quantitative parameters which generated in different regions of interests (ROIs) of benign and malignant breast lesions using contrast-enhanced sonography(CEUS). Materials and methods130 patients were evaluated with contrast harmonic imaging after the injection of a bolus dose of 4.8 ml SonoVue (Bracco Sp A, Milan, Italy). Quantitative analyses using the TIC were performed in two types of ROI (manually tracing the whole lesions and using 3-mm rectangular sampling frames to depict local lesions).Wash in slope (WIS), rise time (RT), time to peak (TTP),peak intensity (PI),strengthening intensity (SI),wash out slope(WOS) and mean transit time(MTT) were investigated in each ROI, SI includes the strengthening intensity of the lesion itself(SIs) and its strengthening intensity relative to the reference area(SIr). ResultsPathologic analysis showed 52 benign and 78 malignant lesions. There were significant differences in the quantitative parameters obtained by the two ROI types (P < 0.05). There were significant differences between benign and malignant lesions in the WIS-e(P < 0.05), TTP-e(P < 0.05), and SIr-e (P < 0.05) for the manual ROI. Significant differences were found between benign and malignant lesions in the WIS-l(P < 0.05), TTP-l(P < 0.05), PI-l(P < 0.05), SIs-l(P < 0.05), and SIr-l (P < 0.05) for the 3-mm ROI. The regression equation obtained by ROI-e was P = 1/[1 + e−(2.65−0.184TTP-e)]. The regression equation obtained by ROI-l was P = 1/[1 + e-(2.472+0.024SIr-l-0.279TTP-l)]. There was statistically significant difference in the diagnostic efficacy between the two ROI types (P < 0.05). ConclusionsCEUS quantitative analysis has a certain value in the diagnosis of benign and malignant breast lesions. The ROI type which depicts local lesions can better reflect the hemodynamic characteristics of the lesions.

Visibility of the graft hepatic artery using superb microvascular imaging in liver transplantation recipients: initial experience.

Background Hepatic artery (HA) obstruction is one of the most threatening complications following liver transplantation (LT); however, conventional color Doppler imaging (CDI) suffers from technical limitations regarding the visualization of fine vessels and low-velocity blood flow. Purpose To test the visibility of HA in postoperative evaluation of LT using a superb microvascular imaging (SMI). Material and Methods This retrospective study was approved by our institutional review board. Fifty-five consecutive patients (58 grafts; mean age = 56 years) who underwent LT with Doppler ultrasonography (US) on postoperative day 1 were included. We compared the subjective visibility of HA and objective measurements of HA caliber, visible HA length on CDI, monochrome SMI (mSMI), contrast-enhanced mSMI (CE-mSMI), and contrast harmonic imaging (CHI). Reproducibility of HA caliber measurements on SMI techniques were also evaluated by using intraclass correlation coefficients (ICCs). Results The subjective image quality for visibility of HA tended to be graded higher with mSMI than CDI, and with CE-mSMI than mSMI ( P < 0.001). The overall reproducibility of HA caliber measurements was good to excellent for both mSMI and CE-mSMI (ICC = 0.674-0.855). HA caliber measurements on mSMI and CE-mSMI strongly correlated with CHI ( R = 0.785, 0.798, P < 0.001), while mean HA length on mSMI was significantly longer than on CDI (1.88 ± 0.83 vs. 1.42 ± 1.01cm, P = 0.004), and even longer on CE-mSMI (vs. 3.28 ± 1.11 cm, P < 0.001). Conclusion The mSMI technique shows good reproducibility and correlates well with currently used methods for postoperative evaluation of HA in LT recipients. It is further improved by administration of an US contrast agent.

Su1333 Clinical Impact of Strain Histogram Real-Time Elastography in Combination With Contrast Harmonic Imaging Eus for the Differential Diagnosis of Focal Pancreatic Masses: A Multicentric Trial

Su1333 Clinical Impact of Strain Histogram Real-Time Elastography in Combination With Contrast Harmonic Imaging Eus for the Differential Diagnosis of Focal Pancreatic Masses: A Multicentric Trial

Potential role of imaging in assessing harmful effects on spermatogenesis in adult testes with varicocele.

Varicocele is characterized by an abnormal dilatation and retrograde blood flow in the spermatic veins. Varicocele is the leading correctable cause of male infertility. Although it is highly prevalent in infertile men, it is also observed in individuals with normal fertility. Determining which men are negatively affected by varicocele would enable clinicians to better select those men who will benefit from treatment. To assess the functional status of the testes in men with varicocele, color Doppler sonographic parameters were evaluated. Testicular arterial blood flow was significantly reduced in men with varicocele, reflecting an impairment of spermatogenesis. An improvement in the testicular blood supply was found after varicocelectomy on spectral Doppler analysis. Testicular contrast harmonic imaging and elastography might improve our knowledge about the influence of varicocele on intratesticular microcirculation and tissue stiffness, respectively, providing possible information on the early damage of testicular structure by varicocele. Magnetic resonance imaging (MRI), with measurement of apparent diffusion coefficient has been used to assess the degree of testicular dysfunction and to evaluate the effectiveness of varicocele repair. Large prospective studies are needed to validate the possible role of functional sonography and MRI in the assessment of early defects of spermatogenesis in testes with varicocele.

Macro- and microcirculation patterns of intrahepatic blood flow changes in patients with hereditary hemorrhagic telangiectasia.

AIMTo evaluated vascular dynamic processes in the liver of hereditary hemorrhagic telangiectasia (HHT) patients by ultrasound (US) considering quantitative analytic methods.METHODSThe imaging features on US and contrast-enhanced ultrasound (CEUS) in 18 patients diagnosed with HHT were retrospectively analyzed. Regarding CEUS, real-time contrast harmonic imaging and sulfur hexafluoride-filled microbubbles were used.RESULTSHVaMs were identified in all 18 patients. By US, the two major Caselitz criteria could be detected in 55.6% patients. "Color spots" were detected in 72.2% of the cases. Respecting sonographic grading criteria by Buscarini, grade 3 could be demonstrated most frequent (40%). By CEUS, all the patients showed quick and early hyperenhancement during the arterial phase. Significant lowest time to peak (TTP) and highest area under the curve (AUC) values were identified in the hepatic artery (TTP: 69.8%; AUC: 100%) and highest TTP and lowest AUC in the hepatic parenchyma and the portal vein.CONCLUSIONFor the first time we analyzed CEUS findings of a group of HHT patients regarding macro- and microcirculation. Our data demonstrate significant differences in TTP and AUC values in the four selected regions: hepatic artery, shunt region, portal vein and hepatic parenchyma.

Contrast-Enhanced Tissue Harmonic Imaging versus Phase Inversion Harmonic Sonographic Imaging for the Delineation of Hepatocellular Carcinomas

Objective: To compare contrast tissue harmonic imaging (THI) with low mechanical index (MI) and conventional contrast harmonic imaging (CHI) with respect to lesion visibility of hepatocellular carcinoma (HCC). Methods: One hundred and twenty-five patients (84 men and 41 women, age range 39-94 years, mean age 74 years) with 100 naïve HCCs and 30 lesions after radiofrequency ablation (RFA) for HCC were evaluated. One hundred and four patients had liver cirrhosis of Child-Pugh class A, and the remaining 21 had Child-Pugh class B cirrhosis. The lesion conspicuity and intratumoral echogenicity during the postvascular phase were compared using conventional CHI and contrast THI with low MI. Results: The MI values ranged from 0.20 to 0.30 on conventional CHI and from 0.30 to 0.35 on contrast THI. Regarding HCC lesion conspicuity, contrast THI with low MI was clearer in 79 lesions (60.8%), equal in 34 lesions (26.2%), and less clear in 17 lesions (13.1%) when compared with conventional CHI. The lesion conspicuity with contrast THI was significantly better than that with conventional CHI (p < 0.01). All of the postablative lesions were well delineated in patients who received RFA. Conclusion: Low-MI contrast THI was superior to conventional CHI with respect to lesion visibility of HCCs and might offer good imaging for the guiding of RFA.

Contrast-enhanced ultrasound using real-time contrast harmonic imaging in invasive breast cancer: comparison of enhancement dynamics with three different doses of contrast agent

In the last few years new potential applications have been developed for contrast-enhanced ultrasound (CEUS) and the management of breast diseases, but there is still some debate concerning the optimal dose to evaluate breast lesions, especially as a diagnostic tool. To compare different CEUS doses of injected contrast agent in order to establish an optimal dose for the diagnosis of invasive breast cancer. In Group A we compared the bolus dose of 1.2 mL vs. 2.4 mL and in Group B we compared the bolus dose of 2.4 mL vs. 4.8 mL (26 and 25 invasive carcinomas, respectively). CEUS was performed in real-time contrast harmonic imaging (CHI) using a L9-3 MHz probe. All examinations were recorded in a contrast side/side imaging mode loop for 120 s. Wash-in and wash-out patterns of the contrast agent were analyzed with advanced US quantification software and kinetic curves were used for statistical analysis. In Group B (2.4 mL vs. 4.8 mL), more and stronger correlation was found among kinetic parameters (area under the curve, P < 0.00001; lognormal model parameters, μ, P = 0.0007 and σ, P < 0.0001; mean transit time, P < 0.0001; model-based wash-out ratios, W21m, P = 0.0002; W50m, P = 0.0001; time-to-peak, P = 0.005) as compared to Group A (1.2 mL vs. 2.4 mL). The optimal way to evaluate kinetic features of invasive breast tumors using real-time CEUS is with an injection of contrast agent of either 2.4 mL or 4.8 mL.

Evaluation with contrast ultrasound of the prevalence of splenic infarction in left-sided infective endocarditis.

To prospectively evaluate the prevalence of the embolization of the spleen in patients with definite left-sided infective endocarditis (IE) using a contrast-enhanced ultrasound (CEUS). From March 2012 through September 2013, 18 consecutive patients (9 females and 9 males, aged 21-83years) evaluated at our hospital and with definite left-sided IE according to the revised Duke criteria were enrolled. All of the patients gave informed written consent and the study was performed in conformity with the ethical guidelines of the Declaration of Helsinki. All of the patients were submitted to a CEUS of the spleen within 10days after the definite diagnosis of IE. For the CEUS, a blood pool second-generation contrast agent and an ultrasound machine with a contrast harmonic imaging technology were used. The splenic CEUS showed infarctions in 11 patients (61%) and resulted positive in the 2 patients with negative echocardiography. In this study, CEUS of the spleen, a repeatable and low-cost imaging technique, easily allowed the bedside detection of asymptomatic and even tiny infarctions and showed a high rate of embolization in patients with definite left-sided IE. Therefore, in the setting of IE (possible or definite), CEUS of the spleen has the potential to better define or accelerate the diagnosis itself.

Contrast-Enhanced Harmonic Endoscopic Ultrasonography in the Differential Diagnosis of Gallbladder Wall Thickening

Differentiation of gallbladder (GB) carcinoma from benign GB wall thickening is challenging. The recent introduction of second-generation ultrasonic contrast agents has made contrast harmonic imaging with EUS possible. The aim of our study was to evaluate the utility of contrast-enhanced harmonic EUS (CH-EUS) for the differential diagnosis of GB wall thickening. Thirty-six consecutive patients with GB wall thickening imaged by CH-EUS and then underwent surgery were enrolled in this study. After the lesions were observed with conventional harmonic EUS (H-EUS), CH-EUS was performed with intravenous injection of 0.015 ml/kg of Sonazoid. Three reviewers with various levels of experience of EUS (Reviewer A: experienced endosonographer, B: EUS trainee, C: experienced gastroenterologist with expertise in transabdominal ultrasound but no EUS experience) were blinded to findings of recorded video of H-EUS and CH-EUS. The diagnostic accuracy of H-EUS and CH-EUS for malignant GB wall thickening was compared. Final diagnoses based on surgical histology were GB carcinoma in 16, cholecystitis in 11, adenomyomatosis in 6 and cholesterolosis in 3. Overall sensitivity, specificity and accuracy for diagnosing malignant GB wall thickening of H-EUS and CH-EUS were 83.3 versus 89.6, 65 versus 98% (p < 0.001) and 73.1 versus 94.4% (p < 0.001). The inter-observer agreement for H-EUS was moderate (κ = 0.51), whereas that for CH-EUS was substantial (κ = 0.77). The inhomogeneous enhanced pattern on CH-EUS was a strong predictive factor of malignant GB wall thickening. CH-EUS has the potential to improve the preoperative diagnostic accuracy and inter-observer agreement in the differential diagnosis of GB wall thickening.