Subharmonic scattering of ultrasound contrast agent microbubbles may be an effective and promising tool for portal vein pressure estimation.
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ABSTRACT:
SUBMITTER: Pang M
PROVIDER: S-EPMC10432296 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Publications
Subharmonic scattering of ultrasound contrast agent microbubbles may be an effective and promising tool for portal vein pressure estimation.
Hepatobiliary surgery and nutrition 20230717 4
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Project description:Noninvasive, accurate measurement of pressures within the human body has long been an important but elusive clinical goal. Contrast agents for ultrasound imaging are gas-filled, encapsulated microbubbles (diameter < 10 μm) that traverse the entire vasculature and enhance signals by up to 30 dB. These microbubbles also produce nonlinear oscillations at frequencies ranging from the subharmonic (half of the transmit frequency) to higher harmonics. The subharmonic amplitude has an inverse linear relationship with the ambient hydrostatic pressure. Here an ultrasound system capable of performing real-time, subharmonic aided pressure estimation (SHAPE) is presented. During ultrasound contrast agent infusion, an algorithm for optimizing acoustic outputs is activated. Following this calibration, subharmonic microbubble signals (i.e., SHAPE) have the highest sensitivity to pressure changes and can be used to noninvasively quantify pressure. The utility of the SHAPE procedure for identifying portal hypertension in the liver is the emphasis here, but the technique has applicability across many clinical scenarios.
| S-EPMC8327282 | biostudies-literature
Project description:Background The current standard for assessing the severity of portal hypertension is the invasive acquisition of hepatic venous pressure gradient (HVPG). A noninvasive US-based technique called subharmonic-aided pressure estimation (SHAPE) could reduce risk and enable routine acquisition of these pressure estimates. Purpose To compare quantitative SHAPE to HVPG measurements to diagnose portal hypertension in participants undergoing a transjugular liver biopsy. Materials and Methods This was a prospective cross-sectional trial conducted at two hospitals between April 2015 and March 2019 (ClinicalTrials.gov identifier, NCT02489045). This trial enrolled participants who were scheduled for transjugular liver biopsy. After standard-of-care transjugular liver biopsy and HVPG pressure measurements, participants received an infusion of a US contrast agent and saline. During infusion, SHAPE data were collected from a portal vein and a hepatic vein, and the difference was compared with HVPG measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity of SHAPE. Results A total of 125 participants (mean age ± standard deviation, 59 years ± 12; 80 men) with complete data were included. Participants at increased risk for variceal hemorrhage (HVPG ≥12 mm Hg) had a higher mean SHAPE gradient compared with participants with lower HVPGs (0.79 dB ± 2.53 vs -4.95 dB ± 3.44; P < .001), which is equivalent to a sensitivity of 90% (13 of 14; 95% CI: 88, 94) and a specificity of 80% (79 of 99; 95% CI: 76, 84). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the HVPG measurements (r = 0.68). Conclusion Subharmonic-aided pressure estimation is an accurate noninvasive technique for detecting clinically significant portal hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kiessling in this issue.
| S-EPMC7771992 | biostudies-literature
Project description:Purpose To investigate if the right ventricular (RV) systolic and left ventricular (LV) diastolic pressures can be obtained noninvasively using the subharmonic-aided pressure estimation (SHAPE) technique with Sonazoid microbubbles. Materials and Methods Individuals scheduled for a left and/or right heart catheterization were prospectively enrolled in this institutional review board-approved clinical trial from 2017 to 2020. A standard-of-care catheterization procedure was performed by advancing fluid-filled pressure catheters into the LV and aorta (n = 25) or RV (n = 22), and solid-state high-fidelity pressure catheters into the LV and aorta in a subset of participants (n = 18). Study participants received an infusion of Sonazoid microbubbles (GE HealthCare), and SHAPE data were acquired using a validated interface developed on a SonixTablet (BK Medical) US scanner, synchronously with the pressure catheter data. A conversion factor, derived using cuff-based pressure measurements with a SphygmoCor XCEL PWA (ATCOR) and subharmonic signal from the aorta, was used to convert the subharmonic signal into pressure values. Errors between the pressure measurements obtained using the SHAPE technique and pressure catheter were compared. Results The mean errors in pressure measurements obtained with the SHAPE technique relative to those of the fluid-filled pressure catheter were 1.6 mm Hg ± 1.5 [SD] (P = .85), 8.4 mm Hg ± 6.2 (P = .04), and 7.4 mm Hg ± 5.7 (P = .09) for RV systolic, LV minimum diastolic, and LV end-diastolic pressures, respectively. Relative to the measurements with the solid-state high-fidelity pressure catheter, the mean errors in LV minimum diastolic and LV end-diastolic pressures were 7.2 mm Hg ± 4.5 and 6.8 mm Hg ± 3.3 (P ≥ .44), respectively. Conclusion These results indicate that SHAPE with Sonazoid may have the potential to provide clinically relevant RV systolic and LV diastolic pressures. Keywords: Ultrasound-Contrast, Cardiac, Aorta, Left Ventricle, Right Ventricle ClinicalTrials.gov registration no.: NCT03245255 © RSNA, 2024.
| S-EPMC10912883 | biostudies-literature
Project description:Six models of contrast microbubbles are investigated to determine the excitation threshold for subharmonic generation. The models are applied to a commercial contrast agent; its characteristic parameters according to each model are determined using experimentally measured ultrasound attenuation. In contrast to the classical perturbative result, the minimum threshold for subharmonic generation is not always predicted at excitation with twice the resonance frequency; instead it occurs over a range of frequencies from resonance to twice the resonance frequency. The quantitative variation of the threshold with frequency depends on the model and the bubble radius. All models are transformed into a common interfacial rheological form, where the encapsulation is represented by two radius dependent surface properties-effective surface tension and surface dilatational viscosity. Variation of the effective surface tension with radius, specifically having an upper limit (resulting from strain softening or rupture of the encapsulation during expansion), plays a critical role. Without the upper limit, the predicted threshold is extremely large, especially near the resonance frequency. Having a lower limit on surface tension (e.g., zero surface tension in the buckled state) increases the threshold value at twice the resonance frequency, in some cases shifting the minimum threshold toward resonance.
| S-EPMC3259666 | biostudies-other
Project description:Photoacoustic (PA) imaging is an emerging diagnostic technology that combines the penetration depth of ultrasound (US) imaging and the contrast resolution of optical imaging. Although PA imaging can visualize several endogenous chromophores to obtain clinically-relevant information, multiple applications require the administration of external contrast agents. Metal phthalocyanines have strong PA properties and chemical stability, but their extreme hydrophobicity requires their encapsulation in delivery systems for biomedical applications. Hence, we developed hybrid US/PA contrast agents by encapsulating metal phthalocyanines in poly(butyl cyanoacrylate) microbubbles (PBCA MB), which display acoustic response and ability to efficiently load hydrophobic drugs. Six different metal chromophores were loaded in PBCA MB, showing greater encapsulation efficiency with higher chromophore hydrophobicity. Notably, while the US response of the MB was unaffected by the loading of the chromophores, the PA characteristics varied greatly. Among the different formulations, MB loaded with zinc and cobalt naphthalocyanines showed the strongest PA contrast, as a result of high encapsulation efficiencies and tunable optical properties. The strong US and PA contrast signals of the formulations were preserved in biological environment, as demonstrated by in vitro imaging in serum and whole blood, and ex vivo imaging in deceased mice. Taken together, these findings highlight the advantages of combining highly hydrophobic PA contrast agents and polymeric MB for the development of contrast agents for hybrid US/PA imaging, where different types of information (structural, functional, or potentially molecular) can be acquired by combining both imaging modalities.
| S-EPMC10916536 | biostudies-literature
Project description:PURPOSE:Cavernous transformation of the portal vein can be missed on color Doppler exam or arterial phase cross-sectional imaging due to their slow flow and delayed enhancement. Contrast-enhanced ultrasound (CEUS) offers many advantages over other imaging techniques and can be used to successfully detect cavernous transformations of the portal vein. METHODS:A 10-month-old female was followed for repeat episodes of hematemesis. Computed tomography angiography (CTA) and magnetic resonance arteriogram (MRA) and portal venography were performed. Color Doppler exam of the portal vein was performed followed by administration of Lumason, a microbubble US contrast agent. RESULTS:Magnetic resonance arteriogram, CTA, and color Doppler exam at the time of initial presentation was unremarkable without obvious vascular malformation within the limits of motion degraded exam. At 8-month follow-up, esophagogastroduodenoscopy revealed a vascular malformation in the distal esophagus which was sclerosed. At 6 month after sclerosis of the lesion, portal venography revealed occlusion of the portal vein with extensive collateralization. Color Doppler revealed subtle hyperarterialization and periportal collaterals. CEUS following color Doppler exam demonstrated extensive enhancement of periportal collaterals. Repeat color Doppler after contrast administration demonstrated extensive Doppler signal in the collateral vessels, suggestive of cavernous transformation. CONCLUSIONS:We describe a case of cavernous transformation of the portal vein missed on initial color Doppler, CTA and MRA, but detected with contrast-enhanced ultrasound technique.
| S-EPMC5972103 | biostudies-literature
Project description:Stroke is closely associated with carotid plaques. The assessment of carotid plaque is still the key issue of stroke prevention in clinical practice. This prospective cross-sectional study included patients with carotid plaque evaluated by ultrasonography (US). The intima-media thickness (IMT), lumen stenosis severity, thickness, and length of carotid plaque were measured by the routine US, and the amplitudes of subharmonics in the upstream shoulder, top, and downstream shoulder of all plaques and corresponding lumens were observed by Subharmonic Aided Pressure Estimation (SHAPE) US examination from the US contrast agent perflubutane microbubbles (Sonazoid), which analyzed the clinical parameters of patients, the subharmonic amplitude characteristics of all plaques and lumens, and the parameter differences between the ischemic stroke (IS) group and control group. From May 2021 to February 2022, 46 carotid plaques of 23 patients were included. For plaques, the subharmonic amplitude in the plaque (-60.52 ± 4.46) was lower than that in the opposing level lumen (-56.82 ± 5.68 dB), the subharmonic gradient across the plaque cap was negatively correlated with plaque thickness (r = -0.51, p < 0.001), and with the lumen stenosis severity (r = -0.42, p = 0.003). The median IMT of the IS group was thicker than the control group. The subharmonic gradient of the intraplaque of the IS group was larger than the control group (p = 0.004). In this analysis, we use the receiver operating characteristic (ROC) curve to establish the cutoff value of the difference to predict a new monitoring method for plaque without invasion to predict IS. It still needs a large-scale study with long-term follow-up to validate these findings.
| S-EPMC10014698 | biostudies-literature
Project description:Lipid-coated microbubbles are widely used as an ultrasound contrast agent, as well as drug delivery carriers. However, the two main limitations in ultrasound diagnosis and drug delivery using microbubbles are the short half-life in the blood system, and the difficulty of surface modification of microbubbles for active targeting. The exosome, a type of extracellular vesicle, has a preferentially targeting ability for its original cell. In this study, exosome-fused microbubbles (Exo-MBs) were developed by embedding the exosome membrane proteins into microbubbles. As a result, the stability of Exo-MBs is improved over the conventional microbubbles. On the same principle that under the exposure of ultrasound, microbubbles are cavitated and self-assembled into nano-sized particles, and Exo-MBs are self-assembled into exosome membrane proteins-embedded nanoparticles (Exo-NPs). The Exo-NPs showed favorable targeting properties to their original cells. A photosensitizer, chlorin e6, was loaded into Exo-MBs to evaluate therapeutic efficacy as a drug carrier. Much higher therapeutic efficacy of photodynamic therapy was confirmed, followed by cancer immunotherapy from immunogenic cell death. We have therefore developed a novel ultrasound image-guided drug delivery platform that overcomes the shortcomings of the conventional ultrasound contrast agent and is capable of simultaneous photodynamic therapy and cancer immunotherapy.
| S-EPMC10692476 | biostudies-literature
Project description:For contrast ultrasound imaging, the most efficient contrast agents comprise highly compressible gas-filled microbubbles. These micrometer-sized particles are typically filled with low-solubility perfluorocarbon gases, and coated with a thin shell, often a lipid monolayer. These particles circulate in the bloodstream for several minutes; they demonstrate good safety and are already in widespread clinical use as blood pool agents with very low dosage necessary (sub-mg per injection). As ultrasound is an ubiquitous medical imaging modality, with tens of millions of exams conducted annually, its use for molecular/targeted imaging of biomarkers of disease may enable wider implementation of personalised medicine applications, precision medicine, non-invasive quantification of biomarkers, targeted guidance of biopsy and therapy in real time. To achieve this capability, microbubbles are decorated with targeting ligands, possessing specific affinity towards vascular biomarkers of disease, such as tumour neovasculature or areas of inflammation, ischaemia-reperfusion injury or ischaemic memory. Once bound to the target, microbubbles can be selectively visualised to delineate disease location by ultrasound imaging. This review discusses the general design trends and approaches for such molecular ultrasound imaging agents, which are currently at the advanced stages of development, and are evolving towards widespread clinical trials.
| S-EPMC6319889 | biostudies-literature
Project description:Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features: such as non-toxicity, intravenous injectability, ability to cross the pulmonary capillary bed, and significant enhancement of echo signals for the duration of the examination, resulting in essential preclinical and clinical applications. The use of microbubbles functionalized with targeting ligands to bind to specific targets in the bloodstream has further enabled ultrasound molecular imaging. Nevertheless, it is very challenging to utilize targeted microbubbles for molecular imaging of extravascular targets due to their size. A series of acoustic nanomaterials have been developed for breaking free from this constraint. Especially, biogenic gas vesicles, gas-filled protein nanostructures from microorganisms, were engineered as the first biomolecular ultrasound contrast agents, opening the door for more direct visualization of cellular and molecular function by ultrasound imaging. The ordered protein shell structure and unique gas filling mechanism of biogenic gas vesicles endow them with excellent stability and attractive acoustic responses. What's more, their genetic encodability enables them to act as acoustic reporter genes. This article reviews the upgrading progresses of ultrasound contrast agents from microbubbles to biogenic gas vesicles, and the opportunities and challenges for the commercial and clinical translation of the nascent field of biomolecular ultrasound.
| S-EPMC10471104 | biostudies-literature