Degradation of blood clots using microbubbles and acoustic waves is regarded as microbubbles-assisted sonothrombolysis. This process can be monitored using dual modal clinical ultrasound and photoacoustic imaging. A greater understanding is crucial on how different gas cores of microbubbles and whether the presence of saline in the surfactant solution can affect the stability of microbubbles for sonothrombolysis. In this project, a work on using microbubbles with different gas cores and the effect of saline in the external surfactant solution during microbubbles-assisted sonothrombolysis is reported. To understand the stability of the microbubbles, analysis of the number of microbubbles in surfactant solution was conducted using optical microscopy. Two different gases, sulfur hexafluoride (SF6) gas and decafluorobutane (C4F10) gas were used in this study to examine the effects of microbubbles on sonothrombolysis for blood clot removal. Two different bases: deionized (DI) water and saline in the microbubbles’ external surfactant solution were also used in this study to examine the stability of the microbubbles. A high-shear rotor homogenizer was used to synthesize the microbubbles. Porcine blood was used for clot formation in polyurethane tubes. The clot-containing tube was set up and submerged in water tank. It was first subjected to microbubbles treatment and next sonothrombolysis treatment for a total of one hour, with the microbubbles being introduced at the interface of the blood clot simultaneously during the sonothrombolysis treatment. The mass of the treated blood clot was then obtained by weighing it with an analytical balance and the change in mass can be obtained by comparison with the initial mass of blood clot. Percentage change in mass of the blood clot was then calculated and a greater percentage change correlated with a greater sonothrombolysis effect.
Blood clots or thrombi can occlude the blood vessels which may lead to diseases such as ischemic stroke, deep vein thrombosis, etc. Sonothrombolysis is a non-invasive procedure for breaking down the blood clots using focused ultrasound waves. Microbubbles (MBs) have been used as ultrasound (US) contrast agents and are known to increase the sonothrombolysis efficiency. In this work, we explore the use of gold nanorods-coated microbubbles (AuMBs) under a nanosecond-pulsed laser exposure within the maximum permissible energy (MPE) limit for sonothrombolysis. The thrombolysis efficiency needs to be compared using microbubbles alone under ultrasound waves and AuMBs under combined laser exposure and ultrasound waves. A dual modal ultrasound (US) and photoacoustic (PA) imaging clinical system is used to evaluate thrombolysis efficiency. While US imaging can be used to visualize the structure and density of blood clots, PA imaging enables the study of composition of the blood clot. Blood clots may be red, white or mixed due to the higher count of red blood cells (RBCs), white blood cells (WBCs) or it being a combination of RBCs and WBCs, respectively. Each clot type has a different PA signal. Hence, the changes in the composition of the blood clot over time can be monitored using PA imaging. Moreover, gold nanoparticles are widely used as PA contrast agents. It has been reported that AuMBs have a higher PA signal compared to gold nanoparticles alone. Hence, the PA signal from AuMBs can be used to ascertain the population of the microbubbles over the course of the thrombolysis treatment. The US and PA signal-to-noise ratios (SNR) of the blood clot and AuMBs, are measured at fixed time intervals during thrombolysis treatment.
KEYWORDS: Blood, Signal to noise ratio, Imaging systems, Ultrasonography, Photoacoustic imaging, Transducers, Blood vessels, In vitro testing, Absorption, In vivo imaging
Blockage of healthy blood vessels by blood clots can lead to serious or even life-threatening complications. The use of a combined ultrasound (US) and photoacoustic (PA) imaging was explored for blood clot monitoring during microbubble-assisted sonothrombolysis. PA imaging is an emerging hybrid imaging modality that has garnered the attention of the biomedical imaging community in recent years. It enables the study of the composition of a blood clot due to its sensitivity toward optical absorption. Here, in vitro imaging of the side of a blood clot facing the microbubbles was done over time. The US and PA signal-to-noise (SNR) ratio value changes during microbubble-assisted sonothrombolysis were studied for two different local environments: blood clot in deionized water and blood clot in blood. In the first case, US and PA SNR values increased by 4.6% and reduced by 20.8%, respectively after 30 min of sonothrombolysis treatment. After 10 min of sonothrombolysis treatment of the blood clot in blood, the US and PA SNR values increased by 7.7% and 38.3%, respectively. The US and PA SNR value changes were recorded in response to its local environment. This technique can be used to determine the final composition of the blood clot which may, in turn, help in the administration of clot-dissolving drugs.
Deep vein thrombosis (DVT) is a disorder that occurs when a blood clot (thrombus) forms in one or more of the deep veins in your body, usually in your legs. Deep vein thrombosis can cause leg pain or swelling, but also can occur with no symptoms. If the clot moves to the vital organs like lungs, heart, brain etc., it can be very fatal and can cause death to the individual. Diagnosing it at early stages is very crucial to decide the treatment strategy. The most commonly used techniques that are used for the diagnosis includes ultrasound, x-ray, CT, etc. For definitive diagnosis contrast agents are required for better visualization of the blood clots and harmful radiations are used. For label free imaging of the blood clots, photoacoustic imaging can be used. To perform in-vivo photoacoustic imaging, high framerate imaging is needed as the velocity of the blood in the veins is between 3 cm/s to 14 cm/s. In this work, we have shown high framerate photoacoustic imaging at different framerates of 5, 10, 50, 100, 500, 1000, 2000 and 3000 fps using a pulsed laser diode of 7000 Hz frequency. We have demonstrated label free imaging of blood clots at 803 nm. Blood clot has at least 1.5 times higher SNR compared to blood and can be clearly visualized against blood as background. High framerate photoacoustic imaging can be used for label free diagnosis of deep vein thrombosis.
Formation of blood clots or thrombus in healthy blood vessels can lead to serious or even life-threatening complications. Sonothrombolysis is a promising tool for lysing the blood clots non-invasively using focused acoustic waves. Ultrasound (US) imaging is commonly used to detect the blood clots presents in veins. In this work, we explore the use of a combined ultrasound and photoacoustic (PA) imaging clinical system during sonothrombolysis. PA imaging is a hybrid and emerging imaging modality which has garnered the attention of the biomedical imaging community in recent years. While US imaging has been used to visualize the blood clot, PA imaging enables the study of composition of the blood clot due to its optical absorption. Blood clots may be red, white or mixed due to the higher count of red blood cells (RBCs), white blood cells (WBCs) or it being a combination of RBCs and WBCs, respectively. Each clot type has a different photoacoustic signal. In our work, blood clots rich in RBCs are taken in transparent polyurethane tubes for sonothrombolysis. Meanwhile, the ultrasound and photoacoustic signal-to-noise ratios (SNR) are measured at fixed time intervals to evaluate the size and optical properties of the clot. Two cases were taken: blood clot + DI water and blood clot + blood and their US and PA SNR values were compared after 30 mins of sonothrombolysis treatment. The PA signal of the blood clot obtained after performing sonothrombolysis can be used to determine its final composition which may, in turn, help in the administration of clot-dissolving drugs.
Microbubbles stabilized by surfactant shells have been established as ultrasound contrast agents for the past several decades. The microbubbles often get destroyed as these are delivered to the region of interest using catheters with different needle sizes. Optimizing the concentration of the surfactants on its shell is crucial for minimizing microbubble destruction. In terms of shell material for this work; polyoxyethylene glycol 40 (PEG-40) stearate which is a non-ionic surfactant, polypropylene glycol and glycerol were used to stabilize the microbubbles with a nitrogen gas core. Presence of surfactants greatly influence the size and stability of the microbubbles and thus four different surfactant concentrations (2, 5, 10 and 15%) of PEG-40 and two different polypropylene glycol + glycerol (GPW) mixtures (10% and 15%) were examined. Nitrogen microbubbles were synthesized through high-shear rotor homogenizer and pushed through three different needle sizes (23, 27 and 30 gauge) using a syringe pump to examine their sensitivity to needle injection. A sample volume of 100 μl containing microbubbles were collected at a constant flow rate of 43.63 ul/min which is the maximum flow rate of the syringe pump used in our experiments. The microbubbles collected at the outlet of the needles were sandwiched between two glass slides for their stability characterization using optical microscopy. The results demonstrated that solution containing 10% PEG-40, 10% polypropylene glycol and 10% glycerol had the highest concentration of microbubbles post injection for all three needle sizes. Finally, phantom experiments were conducted to calculate the signal-to-noise (SNR) ratios of the microbubbles with the different surfactant concentrations using a clinical ultrasound system.
Contrast agents which can be used for more than one bio-imaging technique has gained a lot of attention from researchers in recent years. In this work, a microfluidic device employing a flow-focusing junction, is used for the continuous generation of monodisperse nitrogen microbubbles in methylene blue, an optically absorbing organic dye, for dual-modal photoacoustic and ultrasound imaging. Using an external phase of polyoxyethylene glycol 40 stearate (PEG 40), a non-ionic surfactant, and 50% glycerol solution at a flow rate of 1 ml/hr and gas pressure at 1.75 bar, monodisperse nitrogen microbubbles of diameter 7 microns were obtained. The external phase also contained methylene blue hydrate at a concentration of 1 gm/litre. The monodisperse microbubbles produced a strong ultrasound signal as expected. It was observed that the signal-to-noise (SNR) ratio of the photoacoustic signal for the methylene blue solution in the presence of the monodisperse microbubbles was 68.6% lower than that of methylene blue solution in the absence of microbubbles. This work is of significance because using microfluidics, we can precisely control the bubbles’ production rate and bubble size which increases ultrasound imaging efficiency. A uniform size distribution of the bubbles will have narrower resonance frequency bandwidth which will respond well to specific ultrasound frequencies.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.