Sevan Harput

The effect of amplitude modulation on subharmonic imaging with chirp excitation

Subharmonic generation from ultrasound contrast agents depends on the spectral and temporal properties of the excitation signal. The subharmonic response can be improved by using wideband and long-duration signals. However, for sinusoidal tone-burst excitation, the effective bandwidth of the signal is inversely proportional to the signal duration. Linear frequency-modulated (LFM) and nonlinear frequencymodulated (NLFM) chirp excitations allow independent control over the signal bandwidth and duration; therefore, in this study LFM and NLFM signals were used for the insonation of microbubble populations. The amplitude modulation of the excitation waveform was achieved by applying different window functions. A customized window was designed for the NLFM chirp excitation by focusing on reducing the spectral leakage at the subharmonic frequency and increasing the subharmonic generation from microbubbles. Subharmonic scattering from a microbubble population was measured for various excitation signals and window functions. At a peak negative pressure of 600 kPa, the generated subharmonic energy by ultrasound contrast agents was 15.4 dB more for NLFM chirp excitation with 40% fractional bandwidth when compared with tone-burst excitation. For this reason, the NLFM chirp with a customized window was used as an excitation signal to perform subharmonic imaging in an ultrasound flow phantom. Results showed that the NLFM waveform with a customized window improved the subharmonic contrast by 4.35 ± 0.42 dB on average over a Hann-windowed LFM excitation.

Diagnostic ultrasound tooth imaging using fractional fourier transform

An ultrasound contact imaging method is proposed to measure the enamel thickness in the human tooth. A delay-line transducer with a working frequency of 15 MHz is chosen to achieve a minimum resolvable distance of 400 μm in human enamel. To confirm the contact between the tooth and the transducer, a verification technique based on the phase shift upon reflection is used. Because of the high attenuation in human teeth, linear frequency-modulated chirp excitation and pulse compression are exploited to increase the penetration depth and improve the SNR. Preliminary measurements show that the enamel-dentin boundary creates numerous internal reflections, which cause the applied chirp signals to interfere arbitrarily. In this work, the fractional Fourier transform (FrFT) is employed for the first time in dental imaging to separate chirp signals overlapping in both time and frequency domains. The overlapped chirps are compressed using the FrFT and matched filter techniques. Micro-computed tomography is used for validation of the ultrasound measurements for both techniques. For a human molar, the thickness of the enamel layer is measured with an average error of 5.5% after compressing with the FrFT and 13.4% after compressing with the matched filter based on the average speed of sound in human teeth.

Increasing the sonoporation efficiency of targeted polydisperse microbubble populations using chirp excitation

The therapeutic use of microbubbles for targeted drug or gene delivery is a highly active area of research. Phospholipid-encapsulated microbubbles typically have a polydisperse size distribution over the 1 to 10 μm range and can be functionalized for molecular targeting and loaded with drug-carrying liposomes. Sonoporation through the generation of shear stress on the cell membrane by microbubble oscillations is one mechanism that results in pore formation in the cell membrane and can improve drug delivery. A microbubble oscillating at its resonant frequency would generate maximum shear stress on a membrane. However, because of the polydisperse nature of phospholipid microbubbles, a range of resonant frequencies would exist in a single population. In this study, the use of linear chirp excitations was compared with equivalent duration and acoustic pressure tone excitations when measuring the sonoporation efficiency of targeted microbubbles on human colorectal cancer cells. A 3 to 7 MHz chirp had the greatest sonoporation efficiency of 26.9 ± 5.6%, compared with 16.4 ± 1.1% for the 1.32 to 3.08 MHz chirp. The equivalent 2.2- and 5-MHz tone excitations have efficiencies of 12.8 ± 2.1% and 15.6 ± 1.1%, respectively, which were all above the efficiency of 4.1 ± 3.1% from the control exposure.

Superharmonic imaging with chirp coded excitation: filtering spectrally overlapped harmonics

Superharmonic imaging improves the spatial resolution by using the higher order harmonics generated in tissue. The superharmonic component is formed by combining the third, fourth, and fifth harmonics, which have low energy content and therefore poor SNR. This study uses coded excitation to increase the excitation energy. The SNR improvement is achieved on the receiver side by performing pulse compression with harmonic matched filters. The use of coded signals also introduces new filtering capabilities that are not possible with pulsed excitation. This is especially important when using wideband signals. For narrowband signals, the spectral boundaries of the harmonics are clearly separated and thus easy to filter; however, the available imaging bandwidth is underused. Wideband excitation is preferable for harmonic imaging applications to preserve axial resolution, but it generates spectrally overlapping harmonics that are not possible to filter in time and frequency domains. After pulse compression, this overlap increases the range side lobes, which appear as imaging artifacts and reduce the Bmode image quality. In this study, the isolation of higher order harmonics was achieved in another domain by using the fan chirp transform (FChT). To show the effect of excitation bandwidth in superharmonic imaging, measurements were performed by using linear frequency modulated chirp excitation with varying bandwidths of 10% to 50%. Superharmonic imaging was performed on a wire phantom using a wideband chirp excitation. Results were presented with and without applying the FChT filtering technique by comparing the spatial resolution and side lobe levels. Wideband excitation signals achieved a better resolution as expected, however range side lobes as high as -23 dB were observed for the superharmonic component of chirp excitation with 50% fractional bandwidth. The proposed filtering technique achieved >50 dB range side lobe suppression and improved the image quality without affecting the axial resolution.

Evolution of ultrasonic impulses in chains of spheres using resonant excitation

It is demonstrated that broad-bandwidth ultrasonic signals containing frequency components in excess of 200 kHz can be created in spherical chains using harmonic excitation at 73 kHz. Multiple reflections created a periodic waveform containing both harmonics and sub-harmonics of the original forcing frequency, due to non-linear Hertzian contact. These discrete frequencies represented some of the many allowed non-linear normal modes of vibration of the whole chain. Excitation at a single fixed frequency could thus be used to produce wide-bandwidth impulses for different lengths of spherical chains. Experimental results were in good agreement with theoretical predictions.

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

The accumulation of 1–10 μm phospholipid-shelled microbubbles was demonstrated by creating an “ultrasonic tap” using acoustic travelling waves. Microbubbles were flowed through a 200 μm cellulose tube at rates ranging between 14–50 ml/h, in order to approximate the velocities and wall shear rates found throughout the human circulatory system. The generated acoustic radiation force directly opposing the flow direction was sufficient to hold microbubbles in a fluid flow up to 28 cm/s. Clusters of microbubbles subject to wall shear rates of up to 9000 s−1 were retained near a pressure null for several seconds.

New performance metrics for ultrasound pulse compression systems

In medical ultrasound, B-mode images are log-compressed and displayed with a grayscale map, typically on a 40-60 dB dynamic range. The image formation process is the same for an ultrasound pulse compression system using coded excitation. Metrics, such as full width at half maximum (FWHM), peak sidelobe level (PSL) and integrated sidelobe level (ISL), used to evaluate pulse compression systems were adopted from radar and communications. These metrics are utilized to evaluate the performance of an auto-correlation function, which is the ideal case. In medical ultrasound imaging however, the combination of frequency and depth dependent attenuation, dispersion, harmonic generation, beamforming errors, and limited transducer bandwidth create a more complicated case for a pulse compressed system that is far from the ideal.

Non-linear harmonic reduction pulse width modulation (HRPWM) for the arbitrary control of transducer-integrated switched excitation electronics

Advances in electronics and transducer fabrication have provided the ultrasound system designer with the opportunity for integrating electronics into the transducer head. Switched mode circuits are miniaturizable, low loss and as such are suited to array excitation. Without careful excitation signal design switched mode waveforms lack combined time varying amplitude and harmonic control. Existing modulation schemes have provided either amplitude or harmonic control. The proposed harmonic reduction pulse width modulation (HRPWM) provides a method of creating a quinary (5-level) switched waveform with both time-varying amplitude control and third harmonic cancellation. HRPWM achieves waveform control through matching the amplitude of energy contained at the fundamental frequency with the desired amplitude, and third harmonic cancellation through the use of a non-linear modulating waveform. The resulting HRPWM excitation signals use multiple bipolar low voltage pulses for the control of signals below 50% magnitude, and a five-level pulse for amplitudes above 50%. In simulations, HRPWM shows an excitation signal third harmonic power of -34.75 dB, a reduction of 19 dB from other 5-level modulation schemes, and a ultrasound pressure waveform third harmonic power of -64.19 dB, a reduction of 19.9 dB from other 5-level modulation schemes, and 25 dB lower than bipolar switched excitation.

The dynamic excitation of a granular chain for biomedical ultrasound applications: contact mechanics finite element analysis and validation

There has been recent interest in the transmission of acoustic signals along granular chains of spherical beads to produce waveforms of relevance to biomedical ultrasound applications. Hertzian contact between adjacent beads can introduce different harmonic content into the signal as it propagates. This transduction mechanism has the potential to be of use in both diagnostic and therapeutic ultrasound applications, and is the object of the study presented here. Although discrete dynamics models of this behaviour exist, a more comprehensive solution must be sought if changes in shape and deformation of individual beads are to be considered. Thus, the finite element method was used to investigate the dynamics of a granular chain of six, 1 mm diameter chrome steel spherical beads excited at one end using a sinusoidal displacement signal at 73 kHz. Output from this model was compared with the solution provided by the discrete dynamics model, and good overall agreement obtained. In addition, it was able to resolve the complex dynamics of the granular chain, including the multiple collisions which occur. It was demonstrated that under dynamic excitation conditions, the inability of discrete mechanics models to account for elastic deformation of the beads when these lose contact, could lead to discrepancies with experimental observations.

Separating the second harmonic response of tissue and microbubbles using bispectral analysis

The second harmonic generation in medical ultrasound is either caused by tissue or ultrasound contrast agents. The conventional signal processing techniques cannot separate the harmonic response from microbubbles and tissue. The second order spectral analysis, commonly known as the frequency analysis, is the most common way of evaluating the microbubble response. Although frequency analysis can estimate the power spectrum effectively, it suppresses the phase relation between the frequency components. In this study, bispectral analysis is used to evaluate the microbubble response and separate the second harmonic generated by tissue and microbubbles via the phase coupling between fundamental and harmonic components.