Microbubble Contrast Research Articles

Targeted microbubbles combined with low-power focused ultrasound promote the thrombolysis of acute deep vein thrombosis.

Introduction: The side effects of conventional therapy for acute deep vein thrombosis (DVT) are severe, with inflammatory reactions playing a pivotal role. It is particularly important to explore new ways of treatment thrombosis by targeting inflammatory factors. Methods: A targeted microbubble contrast agent was prepared using the biotin-avidin method. The 40 DVT model rabbits were established and divided into four groups according to different treatment regimens. The four coagulation indexes, TNF-α, and D-dimer content of experimental animals were measured before modeling and before and after treatment, and the thrombolysis was assessed by ultrasound imaging. Finally, the results were verified by pathology. Results and Discussion: Fluorescence microscopy verified the successful preparation of targeted microbubbles. Among the groups, PT, APTT, and TT in Group II-IV were longer than those in Group I (all p < 0.05). FIB and D-dimer content were lower than those in Group I (all p < 0.05), and TNF-α content in Group IV was lower than that in Group I-III (all p < 0.05). Pairwise comparison before modeling and before treatment and after treatment showed that, after treatment, the PT, APTT, and TT in Group II-IV were longer than those before modeling (all p < 0.05). The contents of FIB and D-dimer were lower than those before modeling and before treatment (all p < 0.05). The content of TNF-α decreased significantly only in Group IV, but increased in the other three groups. Targeted microbubbles combined with Low-power focused ultrasound can reduce inflammation, significantly promote thrombolysis, and provide new ideas and methods for the diagnosis and treatment of acute DVT.

Viability of contrast-enhanced voiding urosonography as an alternative to fluoroscopy during video urodynamics.

Pediatric urodynamic studies are performed to evaluate bladder function, commonly in conjunction with a voiding cystourethrogram (VCUG). Contrast-enhanced voiding urosonography (CeVUS) has been approved in the evaluation of vesicoureteral reflux and has been shown to have equal or superior diagnostic value to VCUG. In this technical innovation, we have shown that ultrasound contrast agent microbubbles are compatible with the equipment used for urodynamic evaluation. We have also shown that it is feasible to use contrast ultrasound in pediatric urodynamic examinations.The purpose of our study was to assess the technical feasibility of CeVUS during urodynamics with an in vitro test followed by a vivo evaluation.This single-center prospective study enrolled 25 patients aged 0-18years who underwent CeVUS instead of VCUG at their regularly scheduled appointment.During the in vitro saline experiment, the radiologic and urologic equipment were found to be compatible. Microbubbles were observed at flow rates of 10 and 20 ml/min.

Localization with deep learning networks for super-resolution ultrasound imaging

OBJECTIVE: The objective was to optimize an acquisition methodology and deep learning network to localize a microbubble (MB) contrast agent on a preclinical ultrasound (US) platform with the goal of moving super-resolution ultrasound (SRUS) imaging towards clinical adoption. METHODS: A deep learning network was optimized based on the latest advances in computer vision, convolutional neural networks, and transformer architectures. Synthetic data were produced in an US simulation of tissue with MB at various concentrations flowing in a vascular model. The network was programmed in PyTorch and trained on 12 000 synthetic images. US data were collected with a Vevo 3100 (FUJIFILM VisualSonics Inc) using an MX201 linear transducer. In vivo testing images were obtained from hepatocellular carcinoma (HCC) rat liver tumors. After MB injection (Definity), 3000 frames were collected at 90 Hz. RESULTS: The SRUS in vivo results reveal a high level of detail. The smallest vessel measured 34 μm in diameter. Compared to conventional methods, the network improved performance by 10x on a CPU. A GPU platform could give an additional boost, by as much 100x. CONCLUSIONS: Deep networks for localization show potential for improving performance of SR-US towards a real-time imaging modality. The use of a pre-clinical focused US platform demonstrates that localization can improve the visualization of vascular detail and aid clinical understanding.

Tracking macrophages with ultrasound

Macrophages play a key role among the immune cells in host defense. They are also known to be involved in various complex processes like angiogenesis and can infiltrate disease environments like in the case of cancer and atherosclerosis. Hence, imaging macrophages and their trafficking patterns could provide important prognostic and diagnostic markers of various human diseases. Previous attempts at imaging macrophages have been limited in depth of penetration, spatial resolution, and sensitivity. We hypothesize that labelling macrophages with microbubble (MB) contrast agents could render them visible to ultrasound and potentially overcome these limitations to enable imaging of macrophage trafficking at high resolution and sensitivity deep into tissues. Here, we show that macrophages can be labeled with MB to make them echogenic. Subsequently, we demonstrate that there are ultrasound exposure settings where these macrophages can retain high echogenicity and viability without affecting their functionality. We also confirmed that these MB-labeled macrophages can be imaged invivo (7-fold increase in CNR as compared to unlabeled macrophages) following intratumoral injection into subcutaneous tumors. In summary, our research findings demonstrate a highly sensitive approach to study macrophage interactions with disease environments that may lead to novel biomarkers for disease diagnosis.

Super-resolution cellular ultrasound imaging via localization of nanodroplets

Ultrasound localization microscopy (ULM) had made it possible to differentiate microbubble contrast agents that are separated only by a few micrometers and, thus, opening the path for super-resolution imaging. However, due to the innate limits of acoustic waves and microbubble imaging, similar levels of resolution to optical imaging (i.e., submicron resolution) are still very challenging. In this paper, we utilize ULM to achieve cellular imaging by using phase-change perfluorocarbon nanodroplets (PFCnDs) as a contrast agent that were fabricated with spontaneous nucleation method. To identify the point spread function (PSF) of a single nanodroplet, gaussian fit function was applied for reconstruction. Nanodroplets were injected into cells through patch clamping and later captured with two transducers: a single element transducer for focused ultrasound and linear array transducer for imaging. Nonlinear imaging (NLO) was used to maximize the sound to noise ratio (SNR), which enables optimal amplitude. With the PSF of a phase-transitioned nanodroplet known, stochastic activation of multiple nanodroplets within a cell was accumulated to image a full cell morphology. These findings can lead researchers to develop effective ultrasound imaging paradigms that can visualize intracellular level of organs in deep tissue invivo.

Time evolution of ambient pressure sensitivity of microbubbles subharmonic response as a function of hydrostatic pressure and the filling gas

The ultrasound contrast microbubbles have shown a great ability to produce nonlinear oscillations in response to acoustic excitation which results in the generation of harmonics and subharmonics of the excitation. The subharmonic response of ½ order changes significantly with a change in hydrostatic pressure in the physiological range. This property is being investigated for subharmonic aided pressure estimation (SHAPE), a noninvasive alternative to current methods for vascular pressure measurement in critical organs. In this study, the ambient pressure sensitivity of the subharmonic response of microbubbles with different gas cores and shells was investigated over 25–700 kPa acoustic pressure and the hydrostatic pressure range of 0–25 kPa. The subharmonic showed different trends of increase and decrease with hydrostatic pressure. The sensitivity has shown gradual change over time which was observed to be related to the hydrostatic pressure magnitude and the gas core. These findings could help to calibrate the SHAPE.

Barrier-breaking effects of ultrasonic cavitation for drug delivery and biomarker release

Recently, emerging evidence has demonstrated that cavitation actually creates important bidirectional channels on biological barriers for both intratumoral drug delivery and extratumoral biomarker release. To promote the barrier-breaking effects of cavitation for both therapy and diagnosis, we first reviewed recent technical advances of ultrasound and its contrast agents (microbubbles, nanodroplets, and gas-stabilizing nanoparticles) and then reported the newly-revealed cavitation physical details. In particular, we summarized five types of cellular responses of cavitation in breaking the plasma membrane (membrane retraction, sonoporation, endocytosis/exocytosis, blebbing and apoptosis) and compared the vascular cavitation effects of three different types of ultrasound contrast agents in breaking the blood-tumor barrier and tumor microenvironment. Moreover, we highlighted the current achievements of the barrier-breaking effects of cavitation in mediating drug delivery and biomarker release. We emphasized that the precise induction of a specific cavitation effect for barrier-breaking was still challenged by the complex combination of multiple acoustic and non-acoustic cavitation parameters. Therefore, we provided the cutting-edge in-situ cavitation imaging and feedback control methods and suggested the development of an international cavitation quantification standard for the clinical guidance of cavitation-mediated barrier-breaking effects.

Modified contrast-enhanced ultrasonography with the new high-resolution examination technique of high frame rate contrast-enhanced ultrasound (HiFR-CEUS) for characterization of liver lesions: First results.

To examine to what extent the high frame rate contrast-enhanced ultrasound (HiFR) diagnostic enables the conclusive diagnosis of liver changes with suspected malignancy. Ultrasound examinations were performed by an experienced examiner using a multifrequency probe (SC6-1) on a high-end ultrasound system (Resona 7, Mindray) to clarify liver changes that were unclear on the B-scan. A bolus of 1-2.4 ml of the Sulphur hexafluoride ultrasound microbubbles contrast agent SonoVue™ (Bracco SpA, Italy) was administered with DICOM storage of CEUS examinations from the early arterial phase (5-15 s) to the late phase (5-6 min). Based on the image files stored in the PACS, an independent reading was performed regarding image quality and finding-related diagnostic significance (0 not informative/non-diagnostic to 5 excellent image quality/confident diagnosis possible). References were clinical follow-up, if possible, comparison to promptly performed computed tomography or magnetic resonance imaging, in some cases also to histopathology. We examined 100 patients (42 women, 58 men, from 18 years to 90 years, mean 63±13 years) with different entities of focal and diffuse liver parenchymal changes, which could be detected in all cases with sufficient image quality with CEUS and with high image quality with HiFR-CEUS. Proportionally septate cysts were found in n = 19 cases, scars after hemihepatectomy with local reduced fat in n = 5 cases, scars after microwave ablation in n = 19 cases, hemangiomas in n = 9 cases, focal nodular hyperplasia in n = 8 cases, colorectal metastases in n = 15 cases, hepatocellular carcinoma (HCC) in n = 11 cases, Osler disease in n = 8 cases. The size of lesions ranged from 5 mm to 200 mm with a mean value of 33.1±27.8 mm. Conclusive diagnoses could be made by the experienced investigator in 97/100 cases with CEUS, confirmed by reference imaging, in parts by histopathology or follow-up. The image quality for HiFR CEUS was rated with a score of 3 to 5; 62 cases were assessed with an average of good (4 points), 27 cases with very good (5 points), and in 11 cases (3 points) still satisfactory despite aggravated acoustic conditions. The specificity of HIFR-CEUS was 97%, the sensitivity 97%, the positive predictive value 94%, the negative predictive value 99% and the accuracy 97%. HIFR-CEUS has demonstrated has demonstrated an improved image quality resulting in a high diagnostic accuracy. In the hands of an experienced investigator, HiFR-CEUS allows the assessment of focal and diffuse unclear liver parenchymal changes on B-scan and dynamic assessment of microcirculation in solid and vascular changes.

The use of contrast-enhanced ultrasound for the evaluation of benign focal liver lesions: a literature review

Ugnė Kulnickaitė1, Klaudijus Baranauskas1 , Domantas Vingrys2 1Hospital of Lithuanian University of Health Science Kauno Klinikos, Radiology department, Kaunas, Lithuania 2Hospital of Lithuanian University of Health Science Kauno Klinikos, Internal medicine department, Kaunas, Lithuania Abstract Background. Contrast-enhanced ultrasound (CEUS) is a low-risk, low-cost imaging technique that uses dedicated imaging ultrasound sequences and FDA-approved contrast microbubbles. […]

Risk Factors of Contrast Agent Intravasation With Sulfur Hexafluoride Microbubble During Hysterosalpingo-Contrast Sonography.

To analyze the risk factors of sulfur hexafluoride microbubble contrast agent intravasation during hysterosalpingo-contrast sonography (HyCoSy), and to explore a simple prediction model by the obvious clinical history. This was a retrospective study included 299 infertility women who had undergone HyCoSy examination from July 1, 2018 to June 31, 2019. The factors were recorded, including age, endometrial thickness, balloon length, infertility type, history of intrauterine surgery, history of pelvic surgery, and tubal patency. The method of multivariate logistic regression analysis was adopted to analyze the risk factors affecting the contrast agent intravasation, and the receiver operating characteristic curves were plotted to test their efficacy. Secondary infertility, a history of intrauterine surgery, thin endometrial thickness, and tubal obstruction were all risk factors of the occurrence of intravasation (P < .05). And the area under the receiver operating characteristic curves of the multifactor-combined prediction model of the intravasation was significantly larger than that of single-factor. Sonographers and gynecologists should be familiar with the risk factors of intravasation and select the appropriate timing of HyCoSy toward reducing the occurrence of intravasation and other complications after thoroughly explaining and communicating with the patients.

Effect of pulse duty ratio on temperature rise induced by focused ultrasound combined with magnetic microbubbles

Development of acoustic/magnetic contrast agent microbubbles with various diagnostic and therapeutic functions has attracted more and more attention in medical ultrasound, biomedical engineering and clinical applications. Superparamagnetic iron oxide nanoparticles (SPIO) have unique magnetic characteristics and wonderful biocompatibility, so they can be used as MRI contrast agents to improve image contrast, spatial resolution and diagnostic accuracy. Our previous work shows that the multimodal diagnostic and therapeutic microbubble agents can be successfully constructed by embedding SPIO particles into the coating shell of conventional ultrasound contrast agent (UCA) microbubbles, which in turn changes the size distribution and shell properties of UCA microbubbles, thereby affecting their acoustic scattering, cavitation and thermal effects. However, previous studies only considered the influence factors such as acoustic pressure and microbubble concentration. The relevant investigation regarding the influence of ultrasound temporal characteristics on the dynamic response of magnetic microbubbles is still lacking. This work systematically measures the temperature enhancement effect of the SPIO-albumin microbubble solution flowing in the vascular gel phantom exposed to pulsed ultrasound with various temporal settings (e.g. duty cycle, PRF and single pulse length). Meanwhile, a two-dimensional finite element model is developed to simulate and verify the experimental observations. The results show that the increase of duty cycle of pulse signal should be the crucial factor affecting the temperature enhancement effect of flowing SPIO-albumin microbubble solution under the exposure to high-intensity focused ultrasound. The current results help us to better understand the influence of different acoustic setting parameters on the thermal effect of dual-modal magnetic UCA microbubbles, and provide useful guidance for ensuring the safety and effectiveness of the application of SPIO-albumin microbubbles in clinics.

Aneurisma de septo interatrial associado a forame oval patente em cão - relato de caso

ABSTRACT Atrial septal aneurysm (ASA) is a rare congenital deformity of variable clinical relevance, often reported in association with patent foramen ovale (PFO). Transthoracic Doppler echocardiography (TTE) is the first choice for diagnosis, but complementary techniques, such as microbubble contrast, should be used. Despite its importance, in Veterinary Medicine, there is little information related to the subject, and the present study is the second report of this condition in dogs. The objective was to report a case of ASA type IV LR associated with PFO in a Shar Pei bitch, diagnosed by a combined approach of transthoracic echocardiography backed by agitated saline solution (microbubbles). During clinical care, the owners reported episodes of seizures as their main complaint. Echocardiographic examination revealed a type 4 LR atrial septal aneurysm and left ventricular systolic dysfunction. The use of microbubble contrast showed right-to-left shunt, confirming PFO. The recommended treatment was medication. It was concluded that the rarity of ASA in dogs may be due to incomplete diagnoses and the transthoracic echocardiographic examination allows its analysis and classification. Furthermore, ASA can be found in animals with or without evidence of heart disease and it should be investigated in patients with neurological alterations.

Correlation Between Portal Vein Pressure and Subharmonic Scattering Signals From SonoVue Microbubbles in Canines.

The current gold standard for the clinical diagnosis of portal hypertension (PH) is an invasive and indirect estimation of portal vein pressure (PVP). Therefore, the need for a non-invasive PVP measurement method is urgent. Subharmonic scattering of ultrasound contrast agent (UCA) microbubbles is under investigation in clinical research as a pressure indicator. However, the driving acoustic pressure must be optimized to improve the ambient pressure sensitivity of the subharmonic amplitude for different UCAs. In this study, for the first time, we obtained the relationship between the PVP and the amplitude of the subharmonic signal scattered from SonoVue microbubbles by using two canines to build the PH model. The results revealed a desirable linear correlation between the subharmonic amplitude and PVP (<20 mmHg) at the incident acoustic pressure of 453 kPa (r=-0.910, p < 0.005; sensitivity: -2.003 dB/mmHg); this was one order of magnitude higher in sensitivity than that of the in vitro case with a detectable pressure variation of approximately 1 mmHg. This indicates the feasibility of using UCA microbubbles to accurately measure low ambient pressures in vivo and further exhibits the potential of the method for non-invasive pressure estimation in clinical applications.

Nanobubble-mediated cancer cell sonoporation using low-frequency ultrasound.

Ultrasound insonation of microbubbles can form transient pores in cell membranes that enable the delivery of non-permeable extracellular molecules to the cells. Reducing the size of microbubble contrast agents to the nanometer range could facilitate cancer sonoporation. This size reduction can enhance the extravasation of nanobubbles into tumors after an intravenous injection, thus providing a noninvasive sonoporation platform. However, drug delivery efficacy depends on the oscillations of the bubbles, the ultrasound parameters and the size of the target compared to the membrane pores. The formation of large pores is advantageous for the delivery of large molecules, however the small size of the nanobubbles limit the bioeffects when operating near the nanobubble resonance frequency at the MHz range. Here, we show that by coupling nanobubbles with 250 kHz low frequency ultrasound, high amplitude oscillations can be achieved, which facilitate low energy sonoporation of cancer cells. This is beneficial both for increasing the uptake of a specific molecule and to improve large molecule delivery. The method was optimized for the delivery of four fluorescent molecules ranging in size from 1.2 to 70 kDa to breast cancer cells, while comparing the results to targeted microbubbles. Depending on the fluorescent molecule size, the optimal ultrasound peak negative pressure was found to range between 300 and 500 kPa. Increasing the pressure to 800 kPa reduced the fraction of fluorescent cells for all molecules sizes. The optimal uptake for the smaller molecule size of 4 kDa resulted in a fraction of 19.9 ± 1.8% of fluorescent cells, whereas delivery of 20 kDa and 70 kDa molecules yielded 14 ± 0.8% and 4.1 ± 1.1%, respectively. These values were similar to targeted microbubble-mediated sonoporation, suggesting that nanobubbles can serve as noninvasive sonoporation agents with a similar potency, and at a reduced bubble size. The nanobubbles effectively reduced cell viability and may thus potentially reduce the tumor burden, which is crucial for the success of cancer treatment. This method provides a non-invasive and low-energy tumor sonoporation theranostic platform, which can be combined with other therapies to maximize the therapeutic benefits of cancer treatment or be harnessed in gene therapy applications.

First experiments with carbon black pigment dispersion acting as a Janus ultrasound contrast agent

Abstract Background: Theranostic ultrasound contrast agents comprise a therapeutic component whose controlled release is triggered by an ultrasound pulse. However, once the therapeutic component has been released from an ultrasound contrast agent microbubble, its intended uptake cannot be monitored, as its acoustically active host has been destroyed. Acoustic Janus particles, whose hydrophobic and hydrophilic properties depend on the external acoustic regime, are of potential use as contrast agents and drug-delivery tracers. The purpose of this study was to evaluate the hypothesis that submicron particles with Janus properties may act as ultrasound contrast agents whose hydrophobicity changes over time. Methods: Fifty samples of carbon black were subjected to 5-minute sonication with pulses with a center frequency of 10 MHz and a 1% duty cycle, after which the optical absorption coefficients were measured in n-octanol and water. These coefficients were compared with those of unsonicated samples. Results: Our preliminary results show that the difference between the linear absorption coefficients of sonicated and unsonicated samples was Δα = 80 ± 13 m−1 immediately after sonication, indicating that the carbon black particles were less hydrophobic after sonication than prior to it. Forty-eight hours after sonication, the difference in linear optical absorption coefficients had lessened to Δα = 16 ± 9 m−1, indicating that the carbon black particles had become more hydrophobic over time, but not equal to the hydrophobicity situation prior to sonication. Conclusion: The experiments confirmed that submicron carbon black particles have acoustic Janus properties.

Shell viscosity estimation of lipid-coated microbubbles.

Understanding the shell rheology of ultrasound contrast agent microbubbles is vital for anticipating their bioeffects in clinical practice. Past studies using sophisticated acoustic and optical techniques have made enormous progress in this direction, enabling the development of shell models that adequately reproduce the nonlinear behaviour of the coated microbubble under acoustic excitation. However, there have also been puzzling discrepancies and missing physical explanations for the dependency of shell viscosity on the equilibrium bubble radius, which demands further experimental investigations. In this study, we aim to unravel the cause of such behaviour by performing a refined characterisation of the shell viscosity. We use ultra-high-speed microscopy imaging, optical trapping and wide-field fluorescence to accurately record the individual microbubble response upon ultrasound driving across a range of bubble sizes. An advanced model of bubble dynamics is validated and employed to infer the shell viscosity of single bubbles from their radial time evolution. The resulting values reveal a prominent variability of the shell viscosity of about an order of magnitude and no dependency on the bubble size, which is contrary to previous studies. We find that the method called bubble spectroscopy, which has been used extensively in the past to determine the shell viscosity, is highly sensitive to methodology inaccuracies, and we demonstrate through analytical arguments that the previously reported unphysical trends are an artifact of these biases. We also show the importance of correct bubble sizing, as errors in this aspect can also lead to unphysical trends in shell viscosity, when estimated through a nonlinear fitting from the time response of the bubble.

Ultrasound Contrast Stability for Urinary Bladder Pressure Measurement.

The goal of this study was to evaluate ultrasound contrast microbubbles(MB) stability during a typical cystometrogram(CMG) for bladder pressure measurement application using the subharmonic-aided pressure estimation technique. A detailed study of MB stability was required given two unique characteristics of this application: first, bulk infusion of MBs into the bladder through the CMG infusion system, and second, duration of a typical CMG which may last up to 30 min. To do so, a series of size measurement and contrast-enhanced ultrasound imaging studies under different conditions were performed and the effects of variables that we hypothesized have an effect on MB stability, namely, i) IV bag air headspace, ii) MB dilution factor, and iii) CMG infusion system were investigated. The results verified that air volume in intravenous(IV) bag headspace was not enough to have a significant effect on MB stability during a CMG. We also showed that higher MB dosage results in a more stable condition. Finally, the results indicated that the CMG infusion system adversely affects MB stability. In summary, to ensure MB stability during the entire duration of a CMG, lower filling rates(limited by estimated bladder capacity in clinical applications) and/or higher MB dosage(limited by FDA regulations and shadowing artifact) and/or the consideration of alternative catheter design may be needed.

Quantitative tissue perfusion imaging using nonlinear ultrasound localization microscopy

Ultrasound localization microscopy (ULM) is a recent advancement in ultrasound imaging that uses microbubble contrast agents to yield vascular images that break the classical diffraction limit on spatial resolution. Current approaches cannot image blood flow at the tissue perfusion level since they rely solely on differences in velocity to separate tissue and microbubble signals; lower velocity microbubble echoes are removed during high pass wall filtering. To visualize blood flow in the entire vascular tree, we have developed nonlinear ULM, which combines nonlinear pulsing sequences with plane-wave imaging to segment microbubble signals independent of their velocity. Bubble localization and inter-frame tracking produces super-resolved images and, with parameters derived from the bubble tracks, a rich quantitative feature set that can describe the relative quality of microcirculatory flow. Using the rat spinal cord as a model system, we showed that nonlinear ULM better resolves some smaller branching vasculature compared to conventional ULM. Following contusion injury, both gold-standard histological techniques and nonlinear ULM depicted reduced in-plane vessel length between the penumbra and contralateral gray matter (−16.7% vs. −20.5%, respectively). Here, we demonstrate that nonlinear ULM uniquely enables investigation and potential quantification of tissue perfusion, arguably the most important component of blood flow.

Microbubble contrast agent SonoVue: An efficient medium for the preoperative lymphatic mapping of thyroid carcinoma.

Objective: To assess the value of microbubble contrast agent SonoVue in the thorough preoperative lymphatic mapping of patients with thyroid carcinoma, including the lymphatic drainage region, the detection of sentinel lymph node (SLN), and the diagnosis of lymph node metastasis (LNM). Materials and methods: 55 patients with 62 thyroid malignancies proved by surgical pathology (59 papillary thyroid carcinomas and three medullary thyroid carcinomas) who underwent preoperative lymphatic contrast-enhanced ultrasound (LCEUS) with microbubble contrast agent SonoVue were enrolled. All LNM were confirmed by pathology. The location of thyroid lesions, ultrasonic features of lymph nodes, lymphatic drainage region, and detection of SLN were assessed. The diagnostic performance (sensitivity, specificity, positive predictive value, negative predictive value and accuracy) of different parameters for the LNM diagnosis was calculated. Results: SonoVue effectively demonstrated the lymphatic drainage region for all enrolled thyroid carcinomas. The most common lymphatic drainage region for thyroid carcinomas was region VI (93.55%), followed by region III (62.90%), region IV (48.39%) and region II (4.84%). When divided by the lesion location, the most common lymphatic drainage regions for the nodule in isthmus, superior lobe and inferior lobe of the thyroid were region VI, region III, and region VI respectively. SLN was detected in 96.77% (60/62) of cases. The two cases without SLN demonstration had pathologically proven LNM. The most common sonographic sign of LNM was perfusion defect (54.17%). The diagnostic accuracy of SonoVue in central and lateral compartment LNM was 86.67% and 91.67%, respectively. Conclusion: Microbubble contrast agent SonoVue is a valuable imaging contrast medium for thorough preoperative lymphatic mapping in patients with thyroid carcinoma, including the lymphatic drainage region, the detection of SLN, and the diagnosis of LNM. LCEUS with SonoVue alone has limitations of false negatives when there is lymphatic vessel obstruction and may need to be combined with other ultrasound modalities.

Noninvasive Evaluation of Cardiac Chamber Pressures Using Subharmonic-Aided Pressure Estimation With Definity Microbubbles

BackgroundNoninvasive and accurate assessment of intracardiac pressures has remained an elusive goal of noninvasive cardiac imaging. ObjectivesThe purpose of this study was to investigate if errors in intracardiac pressures obtained noninvasively using contrast microbubbles and the subharmonic-aided pressure estimation (SHAPE) technique are <5 mm Hg. MethodsIn a nonrandomized institutional review board–approved clinical trial (NCT03243942), patients scheduled for a left-sided and/or right-sided heart catheterization procedure and providing written informed consent were included. A standard-of-care catheterization procedure was performed advancing clinically used pressure catheters into the left and/or right ventricles and/or the aorta. After pressure catheter placement, patients received an infusion of Definity microbubbles (n = 56; 2 vials diluted in 50 mL of saline; infusion rate: 4-10 mL/min) (Lantheus Medical Imaging). Then SHAPE data was acquired using a validated interface developed on a SonixTablet scanner (BK Medical Systems) synchronously with the pressure catheter data. A conversion factor (mm Hg/dB) was derived from SHAPE data and measurements with a SphygmoCor XCEL PWA device (ATCOR Medical) and was combined with SHAPE data from the left and/or the right ventricles to obtain clinically relevant systolic and diastolic ventricular pressures. ResultsThe mean value of absolute errors for left ventricular minimum and end diastolic pressures were 2.9 ± 2.0 and 1.7 ± 1.2 mm Hg (n = 26), respectively, and for right ventricular systolic pressures was 2.2 ± 1.5 mm Hg (n = 11). Two adverse events occurred during Definity infusion; both were resolved. ConclusionsThese results indicate that the SHAPE technique with Definity microbubbles is encouragingly efficacious for obtaining intracardiac pressures noninvasively and accurately. (Noninvasive, Subharmonic Intra-Cardiac Pressure Measurement; NCT03243942)