Effect of ultrasound on adherent microbubble contrast agents

Loughran, Jonathan; Sennoga, Charles A.; Eckersley, Robert J.; Tang, Meng‐Xing

doi:10.1088/0031-9155/57/21/6999

Cited by 7 publications

(6 citation statements)

References 41 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been shown that ultrasound pulses with even medium amplitude are able to detach targeted microbubbles (Loughran, et al 2012). Unlike imaging vascular endothelial targets where shear stress from blood flow can detach the microbubbles from their bound sites, reducing ultrasound signal, the flow is very limited outside the vasculature and any detached bubbles could potentially stay in position and continue to contribute to ultrasound signal.…”

Section: Ultrasound Pulses On Detachmentmentioning

confidence: 99%

Quantification of Vaporised Targeted Nanodroplets Using High-Frame-Rate Ultrasound and Optics

Zhang

Lin

Leow

et al. 2019

Ultrasound in Medicine & Biology

Self Cite

View full text Add to dashboard Cite

Molecular targeted nanodroplets, promising to extravasate beyond the vascular space, have great potential to improve tumor detection and characterization. High frame rate ultrasound, on the other hand, is an emerging tool for imaging at a frame rate 1-2 orders of magnitude higher than common existing ultrasound operating systems. In this study, we used high frame rate ultrasound combined with optics to study the acoustic response and size distribution of Folate Receptor (FR) -targeted versus Non-Targeted (NT)-nanodroplets in vitro with MDA-MB-231 breast cancer cells immediately after ultrasound activation. A flow velocity mapping technique, Stokes' theory, and optical microscopy were used to estimate the size of both floating and attached vaporized nanodroplets immediately after activation. It was found that the size of floating vaporized nanodroplets was on average more than 7 times larger than the size of vaporized nanodroplets attached to the cells. The results also showed that the acoustic signal of vaporized FR-nanodroplets was persistent after activation, with 70% of the acoustic signals still present 1 second after activation, compared to the vaporized NT-nanodroplets where only 40% of the acoustic signal remains. The optical microscopic images showed on average 6 times more vaporized FR-nanodroplets generated with a wider range of diameters (from 4 to 68 µm) that still attach to the cells compared to vaporized NTnanodroplets (from 1 to 7 µm) with non-specific binding after activation. It was also found that the mean size of attached vaporized FR-nanodroplets was on average about 3-fold larger than that of attached vaporized NT-nanodroplets. The study offers an improved understanding of the vaporization of the targeted nanodroplets in terms of their sizes and acoustic response in comparison with non-targeted ones, taking advantage of high-frame-rate contrast-enhanced ultrasound and optical microscopy. Such understanding would help design optimized methodology for imaging and therapeutic applications.

show abstract

Section: Ultrasound Pulses On Detachmentmentioning

confidence: 99%

Quantification of Vaporised Targeted Nanodroplets Using High-Frame-Rate Ultrasound and Optics

Zhang

Lin

Leow

et al. 2019

Ultrasound in Medicine & Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…It has also been found that as ARF insonation pressure increases, secondary radiation force can overcome molecular binding forces, and allow bound microbubbles to dislodge or cluster 48–50 . Loughran and colleagues determined that the peak negative pressure necessary for secondary radiation forces to overcome the molecular binding forces of adherent microbubbles was approximately 150 kPa 49 . In the imaging sequence employed in this study, PI, B-mode, and ARF transmissions had peak negative pressures of 286 kPa, 115 kPa, and 255 kPa, respectively without accounting for attenuation.…”

Section: Discussionmentioning

confidence: 99%

The Use of Acoustic Radiation Force Decorrelation-Weighted Pulse Inversion for Enhanced Ultrasound Contrast Imaging

Herbst¹,

Unnikrishnan²,

Wang³

et al. 2017

Invest Radiol

View full text Add to dashboard Cite

Objectives The use of ultrasound imaging for cancer diagnosis and screening can be enhanced with the use of molecularly targeted microbubbles. Nonlinear imaging strategies such as pulse inversion (PI) and “contrast pulse sequences” (CPS) can be used to differentiate microbubble signal, but often fail to suppress highly echogenic tissue interfaces. This failure results in false positive detection and potential misdiagnosis. In this study, a novel Acoustic Radiation Force (ARF) based approach was developed for superior microbubble signal detection. The feasibility of this technique, termed ARF-decorrelation-weighted PI (ADW-PI), was demonstrated in vivo using a subcutaneous mouse tumor model. Materials and Methods Tumors were implanted in the hindlimb of C57BL/6 mice by subcutaneous injection of MC38 cells. Lipid-shelled microbubbles were conjugated to anti-VEGFR2 antibody and administered via bolus injection. An image sequence using ARF pulses to generate microbubble motion was combined with PI imaging on a Verasonics Vantage programmable scanner. ADW-PI images were generated by combining PI images with inter-frame signal decorrelation data. For comparison, CPS images of the same mouse tumor were acquired using a Siemens Sequoia clinical scanner. Results Microbubble-bound regions in the tumor interior exhibited significantly higher signal decorrelation than static tissue (n = 9, p < 0.001). The application of ARF significantly increased microbubble signal decorrelation (n = 9, p < 0.01). Using these decorrelation measurements, ADW-PI imaging demonstrated significantly improved microbubble contrast-to-tissue ratio (CTR) when compared to corresponding CPS or PI images (n = 9, p < 0.001). CTR improved with ADW-PI by approximately 3 dB compared to PI images and 2 dB compared to CPS images. Conclusions Acoustic radiation force can be used to generate adherent microbubble signal decorrelation without microbubble bursting. When combined with pulse inversion, measurements of the resulting microbubble signal decorrelation can be used to reconstruct images that exhibit superior suppression of highly echogenic tissue interfaces when compared to PI or CPS alone.

show abstract

“…Additionally, bound microbubbles are subject to secondary Bjerknes forces which may cause detachment of bound microbubbles at low MI (Garbin et al 2011; Gessner et al 2012b; Loughran et al 2012). These forces may induce microbubble unbinding in this method due to lower pressure pulses acting on a microbubble before the dual focus is aligned with the microbubble, potentially reducing sensitivity if detached microbubbles flow out of plane before being detected.…”

Section: Discussionmentioning

confidence: 99%

Molecular Acoustic Angiography: A New Technique for High-resolution Superharmonic Ultrasound Molecular Imaging

Shelton

Lindsey

Tsuruta

et al. 2016

Ultrasound in Medicine & Biology

View full text Add to dashboard Cite

Ultrasound molecular imaging utilizes targeted microbubbles to bind to vascular targets such as integrins, selectins, and other extracellular binding domains. After binding, these microbubbles are typically imaged using low pressures and multi-pulse imaging sequences. In this article, we present an alternative approach for molecular imaging using ultrasound which relies on superharmonic signals produced by microbubble contrast agents. Bound bubbles were insonified near resonance using a low frequency (4 MHz) and superharmonic echoes were received at high frequencies (25–30 MHz). While this approach was observed to produce declining image intensity during repeated imaging in both in vitro and in vivo experiments due to bubble destruction, the feasibility of superharmonic molecular imaging was demonstrated for transmit pressures which are sufficiently high to induce shell disruption in bound microbubbles. This approach was validated using microbubbles targeted to the αvβ3 integrin in a rat fibrosarcoma model (n=5), and combined with superharmonic images of free microbubbles to produce high contrast, high resolution 3D volumes of both microvascular anatomy and molecular targeting. Image intensity over repeated scans and the effect of microbubble diameter were also assessed in vivo, indicating that larger microbubbles yield increased persistence in image intensity. Using ultrasound-based acoustic angiography images rather than conventional B-mode ultrasound to provide the underlying anatomical information facilitates anatomical localization of molecular markers. Quantitative analysis of relationships between microvasculature and targeting information indicated that most targeting occurred within 50 µm of a resolvable vessel (>100 µm diameter). The combined information provided by these scans may present new opportunities for analyzing relationships between microvascular anatomy and vascular targets, subject only to limitations of the current mechanically-scanned system and microbubble persistence to repeated imaging at moderate mechanical indices.

show abstract

Effect of ultrasound on adherent microbubble contrast agents

Cited by 7 publications

References 41 publications

Quantification of Vaporised Targeted Nanodroplets Using High-Frame-Rate Ultrasound and Optics

Quantification of Vaporised Targeted Nanodroplets Using High-Frame-Rate Ultrasound and Optics

The Use of Acoustic Radiation Force Decorrelation-Weighted Pulse Inversion for Enhanced Ultrasound Contrast Imaging

Molecular Acoustic Angiography: A New Technique for High-resolution Superharmonic Ultrasound Molecular Imaging

Contact Info

Product

Resources

About