Dual Frequency Method for Simultaneous Translation and Real-Time Imaging of Ultrasound Contrast Agents Within Large Blood Vessels

Abstract

A dual frequency excitation method for simultaneous translation and selective real-time imaging of microbubbles is presented. The method can distinguish signals originating from free flowing and static microbubbles. This method is implemented on a programmable scanner with a broadband linear array. The programmable interface allows for dynamic variations in the acoustic parameters and aperture attributes, enabling application of this method to large blood vessels located at varying depths. The performance of the method was evaluated in vitro (vessel diameter 2 mm) by quantifying the sensitivity of the method to various acoustic, microbubble, and fluid flow parameters. It was observed that the static microbubble response maximized at the approximate resonance frequency of the microbubble population (estimated from a coulter counter measurement), thus signifying the need for dual frequency excitation. The static microbubble signal declined from 25 to 12 dB with increasing centerline flow velocities (2.65-15.9 cm/s); indicating applicable range of flow velocities. The maximum intensity of the static microbubbles signal scaled with variations in the microbubble concentration. The rate of increment of static microbubble signal was independent of microbubble concentration. It was deduced that the rate of increment of the static microbubble signal is primarily a function of the pulse frequency, whereas the maximum static microbubble signal intensity is dependent on three parameters: a) the pulse frequency, b) the flow velocity, and c) the microbubble concentration. The proposed dual frequency sequence may enable application of radiation force for optimizing the effect of targeted imaging and modulating drug delivery in large blood vessels with high flow velocities.

The capture of flowing microbubbles with an ultrasonic tap using acoustic radiation force

“…Applying radiation force orthogonal to the flow in large arteries to stop flowing MB remains a challenge as mean velocities can reach several cm/s. Patil et al 17 reported that, even when excited near resonance, a mechanical index of 0.15 was required to halt MB for a wall shear rate of 52 s −1 . Moreover, flowing MB clusters can impede accumulation by engulfing already bound targeted MB.…”

Quantitative Ultrasound Molecular Imaging in Large Blood Vessel Environments

“…Low-pass filtering in slow-time dimension is designed to suppress highfrequency circulating microbubble signals while retaining low-frequency adherent microbubble signals [45]- [48]. Similarly, slow-time averaging is designed to cancel out more random signals derived from circulating microbubbles while retaining stationary signals from adherent microbubbles [49], [50]. "Dwell time" is another threshold-determined parameter used to quantify the inter-frame signature of microbubbles.…”

“…tumor) has been demonstrated, studies were performed in large blood vessel environments with application of ARF in vitro and ex vivo [23], [45], [49], [50], [64]. Due to the high flow rate and shear forces, ARF is essential in large vessels to push microbubbles towards the distal vessel wall.…”

“…Current methods for separating signals arising from molecularly bound adherent microbubbles, versus tissue and freely circulating microbubbles, are primarily designed for small vessels and generally rely on frequency domain filtering schemes [46], [47], [49], [50], [114]. For example, Gessner et al achieved high contrast-to-tissue ratio imaging using a dual-frequency transducer [114].…”

“…consisted of harmonic imaging and slow-time filtering with a wideband customized transducer to enhance sensitivity [47]. In addition, Patil et al demonstrated molecular imaging in large vessels in vitro and ex vivo using the combination of pulse inversion and a slow-time averaging strategy [49], [50]. In each of these methods, the elimination of tissue signal is attempted by first using non-linear extraction methods (e.g.…”