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Microbubble-Facilitated Ultrasound Catheter Ablation Causes Microvascular Damage and Fibrosis.

ABSTRACT: High-intensity ultrasound (US) ablation produces deeper myocardial lesions than radiofrequency ablation. The presence of intravascular microbubble (MB) contrast agents enhances pulsed-wave US ablation via cavitation-related histotripsy, potentially facilitating ablation in persistently perfused/conducting myocardium. US ablation catheters were developed and tested in the presence of MBs using ex vivo and in vivo models. High-frame-rate videomicroscopy and US imaging of gel phantom models confirmed MB destruction by inertial cavitation. MB-facilitated US ablation in an ex vivo perfused myocardium model generated shallow (2 mm) lesions and, in an in vivo murine hindlimb model, reduced perfusion by 42% with perivascular hemorrhage and inflammation, but no myonecrosis.

SUBMITTER: Nazer B

PROVIDER: S-EPMC8211318 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Microbubble-Facilitated Ultrasound Catheter Ablation Causes Microvascular Damage and Fibrosis.

Nazer Babak B Giraud David D Zhao Yan Y Qi Yue Y Mason O'Neil O Jones Peter D PD Diederich Chris J CJ Gerstenfeld Edward P EP Lindner Jonathan R JR

Ultrasound in medicine & biology 20201020 1

High-intensity ultrasound (US) ablation produces deeper myocardial lesions than radiofrequency ablation. The presence of intravascular microbubble (MB) contrast agents enhances pulsed-wave US ablation via cavitation-related histotripsy, potentially facilitating ablation in persistently perfused/conducting myocardium. US ablation catheters were developed and tested in the presence of MBs using ex vivo and in vivo models. High-frame-rate videomicroscopy and US imaging of gel phantom models confirm ...[more]

PMID: 33092899

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Project description:RationaleMicrobubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld.ObjectiveTo develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging.Methods and resultsMicrobubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab')2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification.ConclusionsTargeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)-(iii) desired for clinical applications.

Project description:BackgroundMicroFlow imaging (MFI) is a novel noninvasive ultrasound (US) technique that depicts microcirculatory blood vessels in the kidney while filtering out tissue motion and enhancing blood flow signals. We aimed to investigate the value of MFI for the detection of renal microvascular perfusion in chronic kidney disease caused by stage I-II membranous nephropathy (MN).MethodsSeventy-six participants including biopsy-proven MN (n=38) and healthy volunteers (n=38) were prospectively examined using MFI from March 2020 to December 2020. In addition, patients with MN were subdivided into a mild group, a moderate group, and a severe group based on the results of vascular pathology evaluation. All MFI images were analyzed by Image Pro Plus to obtain a cortical vascular index (VI). Basic patient information, relative US parameters and laboratory results were then acquired for each participant. Finally, after the univariate analysis among multiple groups, binary logistic regression (forward LR) and ordered logistic regression were used for multivariate analysis. Significance was set at P<0.05.ResultsVI was significantly lower in MN patients compared with that of healthy controls (0.65±0.09 vs. 0.35±0.18, P<0.001). After multivariate analysis, we found that the exploratory diagnostic performance of VI [area under the curve (AUC): 0.94; 95% confidence interval (CI): 0.89-0.99] outperformed that of serum creatinine (Scr) (AUC: 0.87; 95% CI: 0.79-0.95) in identifying MN. We also observed considerable differences among MN groups in parameters including VI (P=0.006), estimated glomerular filtration rate (eGFR) (P=0.037), shape (P=0.013), and impression (P=0.007). In addition, in the group with mild vascular damage, the exploratory diagnostic performance of VI (AUC: 0.79; 95% CI: 0.64-0.94) was better than other parameters, such as eGFR (AUC: 0.63; 95% CI: 0.43-0.84).ConclusionsMFI detected abnormal renal microvascular perfusion in patients with MN (particularly in those with early vascular damage or preserved renal function) without the use of a contrast agent. Combining MFI with B-mode US can improve the predictive performance of traditional kidney US.

Dataset Information

Microbubble-Facilitated Ultrasound Catheter Ablation Causes Microvascular Damage and Fibrosis.

Publications

Microbubble-Facilitated Ultrasound Catheter Ablation Causes Microvascular Damage and Fibrosis.

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