Combined passive acoustic mapping and magnetic resonance thermometry for monitoring phase-shift nanoemulsion enhanced focused ultrasound therapy.

Focused ultrasound (FUS) has the potential to enable precise, image-guided noninvasive surgery for the treatment of cancer in which tumors are identified and destroyed in a single integrated procedure. However, success of the method in highly vascular organs has been limited due to heat losses to perfusion, requiring development of techniques to locally enhance energy absorption and heating. In addition, FUS procedures are conventionally monitored using MRI, which provides excellent anatomical images and can map temperature, but is not capable of capturing the full gamut of available data such as the acoustic emissions generated during this inherently acoustically-driven procedure. Here, we employed phase-shift nanoemulsions (PSNE) embedded in tissue phantoms to promote cavitation and hence temperature rise induced by FUS. In addition, we incorporated passive acoustic mapping (PAM) alongside simultaneous MR thermometry in order to visualize both acoustic emissions and temperature rise, within the bore of a full scale clinical MRI scanner. Focal cavitation of PSNE could be resolved using PAM and resulted in accelerated heating and increased the maximum elevated temperature measured via MR thermometry compared to experiments without nanoemulsions. Over time, the simultaneously acquired acoustic and temperature maps show translation of the focus of activity towards the FUS transducer, and the magnitude of the increase in cavitation and focal shift both increased with nanoemulsion concentration. PAM results were well correlated with MRI thermometry and demonstrated greater sensitivity, with the ability to detect cavitation before enhanced heating was observed. The results suggest that PSNE could be beneficial for enhancement of thermal focused ultrasound therapies and that PAM could be a critical tool for monitoring this process.

High-resolution renal perfusion mapping using contrast-enhanced ultrasonography in ischemia-reperfusion injury monitors changes in renal microperfusion.

Alterations in renal microperfusion play an important role in the development of acute kidney injury with long-term consequences. Here we used contrast-enhanced ultrasonography as a novel method for depicting intrarenal distribution of blood flow. After infusion of microbubble contrast agent, bubbles were collapsed in the kidney and postbubble destruction refilling was measured in various regions of the kidney. Local perfusion was monitored in vivo at 15, 30, 45, 60 minutes and 24 hours after 28 minutes of bilateral ischemia in 12 mice. High-resolution, pixel-by-pixel analysis was performed on each imaging clip using customized software, yielding parametric perfusion maps of the kidney, representing relative blood volume in each pixel. These perfusion maps revealed that outer medullary perfusion decreased disproportionately to the reduction in the cortical and inner medullary perfusion after ischemia. Outer medullary perfusion was significantly decreased by 69% at 60 minutes postischemia and remained significantly less (40%) than preischemic levels at 24 hours postischemia. Thus, contrast-enhanced ultrasonography with high-resolution parametric perfusion maps can monitor changes in renal microvascular perfusion in space and time in mice. This novel technique can be translated to clinical use in man.

Multi-planar dynamic contrast-enhanced ultrasound assessment of blood flow in a rabbit model of testicular torsion.

To assess correlation between multi-planar, dynamic contrast-enhanced ultrasound (US) blood flow measurements and radiolabeled microsphere blood flow measurements, five groups of six rabbits underwent unilateral testicular torsion of 0°, 180°, 360°, 540° or 720°. Five US measurements per testis (three transverse/two longitudinal) were obtained pre-operatively and immediately and 4 and 8 h post-operatively using linear transducers (7-4 MHz/center frequency 4.5 MHz/10 rabbits; 9-3 MHz/center frequency 5.5 MHz/20 rabbits). Björck's linear least-squares method fit the rise phase of mean pixel intensity over a 7-s period for each time curve. Slope of fit and intervention/control US pixel intensity ratios were calculated. Means of transverse, longitudinal and combined transverse/longitudinal US ratios as a function of torsion degree were compared with radiolabeled microsphere ratios using Pearson's correlation coefficient, ρ. There was high correlation between the two sets of ratios (ρ ≥ 0.88, p ≤ 0.05), except for the transverse US ratio in the immediate post-operative period (ρ = 0.79, p = 0.11). These results hold promise for future clinical applications.

Two-dimensional image reconstruction with spectrally-randomized ultrasound signals.

An ultrasound imaging method using unfocused frequency-randomized transmissions and image reconstruction from data received by a single element is experimentally demonstrated. The elements of an ultrasound imaging array are randomly assigned different frequencies and driven by a multicycle sinusoidal burst. The resulting acoustic field is spectrally unique and target localization is possible based on the a priori knowledge of this field. A 64-element phased array driven by arbitrary waveform generators is used in the experiments. Transmission frequencies range from 2.00 to 2.64 MHz with 10 kHz resolution. One element of the array is reserved for receiving backscattered signals and an image is reconstructed from the signals received by this single element. Reconstruction is based on cross-correlation of the received data with transmitted bursts to obtain radial elliptical projections. Multiple projections are obtained from single received data, which are back-projected to obtain an image. Successful target localization is made possible through multiple frequency-randomized acquisitions. The performance of the method is measured using images of a single point target. These images are quantified and analyzed in terms of their point spread function (PSF) and SNR. Optimum imaging parameters, such as the number of acquisitions, transmit burst length, and number of possible receivers, are obtained through further analysis of SNR. Images obtained with the frequency-randomized transmission method compared well with the performance measurements of a typical B-mode acquisition. It is demonstrated that the frequency-randomized method provides images superior to B-mode images in terms of PSF. The two-point discrimination threshold is measured to be 2 mm in the lateral and azimuth directions.

Time-reversal transcranial ultrasound beam focusing using a k-space method.

This paper proposes the use of a k-space method to obtain the correction for transcranial ultrasound beam focusing. Mirroring past approaches, a synthetic point source at the focal point is numerically excited, and propagated through the skull, using acoustic properties acquired from registered computed tomography of the skull being studied. The received data outside the skull contain the correction information and can be phase conjugated (time reversed) and then physically generated to achieve a tight focusing inside the skull, by assuming quasi-plane transmission where shear waves are not present or their contribution can be neglected. Compared with the conventional finite-difference time-domain method for wave propagation simulation, it will be shown that the k-space method is significantly more accurate even for a relatively coarse spatial resolution, leading to a dramatically reduced computation time. Both numerical simulations and experiments conducted on an ex vivo human skull demonstrate that precise focusing can be realized using the k-space method with a spatial resolution as low as only 2.56 grid points per wavelength, thus allowing treatment planning computation on the order of minutes.

Reconstruction algorithm for improved ultrasound image quality.

A new algorithm is proposed for reconstructing raw RF data into ultrasound images. Previous delay-and-sum beamforming reconstruction algorithms are essentially one-dimensional, because a sum is performed across all receiving elements. In contrast, the present approach is two-dimensional, potentially allowing any time point from any receiving element to contribute to any pixel location. Computer-intensive matrix inversions are performed once, in advance, to create a reconstruction matrix that can be reused indefinitely for a given probe and imaging geometry. Individual images are generated through a single matrix multiplication with the raw RF data, without any need for separate envelope detection or gridding steps. Raw RF data sets were acquired using a commercially available digital ultrasound engine for three imaging geometries: a 64-element array with a rectangular field-of- view (FOV), the same probe with a sector-shaped FOV, and a 128-element array with rectangular FOV. The acquired data were reconstructed using our proposed method and a delay- and-sum beamforming algorithm for comparison purposes. Point spread function (PSF) measurements from metal wires in a water bath showed that the proposed method was able to reduce the size of the PSF and its spatial integral by about 20 to 38%. Images from a commercially available quality-assurance phantom had greater spatial resolution and contrast when reconstructed with the proposed approach.

Rayleigh-Lamb wave propagation on a fractional order viscoelastic plate.

A previous study of the authors published in this journal focused on mechanical wave motion in a viscoelastic material representative of biological tissue [Meral et al., J. Acoust. Soc. Am. 126, 3278-3285 (2009)]. Compression, shear and surface wave motion in and on a viscoelastic halfspace excited by surface and sub-surface sources were considered. It was shown that a fractional order Voigt model, where the rate-dependent damping component that is dependent on the first derivative of time is replaced with a component that is dependent on a fractional derivative of time, resulted in closer agreement with experiment as compared with conventional (integer order) models, such as those of Voigt and Zener. In the present study, this analysis is extended to another configuration and wave type: out-of-plane response of a viscoelastic plate to harmonic anti-symmetric Lamb wave excitation. Theoretical solutions are compared with experimental measurements for a polymeric tissue mimicking phantom material. As in the previous configurations the fractional order modeling assumption improves the match between theory and experiment over a wider frequency range. Experimental complexities in the present study and the reliability of the different approaches for quantifying the shear viscoelastic properties of the material are discussed.

Surface response of a fractional order viscoelastic halfspace to surface and subsurface sources.

Previous studies by the second author published in this journal focused on low audible frequency (40-400 Hz) shear and surface wave motion in and on a viscoelastic material representative of biological tissue. Specific cases considered were that of surface wave motion on a halfspace caused by a finite rigid circular disk located on the surface and oscillating normal to it [Royston et al., J. Acoust. Soc. Am. 106, 3678-3686 (1999)] and compression, shear, and surface wave motion in a halfspace generated by a subsurface finite dipole [Royston et al., J. Acoust. Soc. Am. 113, 1109-1121 (2003)]. In both studies, a Voigt model of viscoelasticity was assumed in the theoretical treatment, which resulted in agreement between theoretical predictions and experimental measurements over a limited frequency range. In the present article, the linear viscoelastic assumption in these two prior works is revisited to consider a (still linear) fractional order Voigt model, where the rate-dependent damping component that is dependent on the first derivative of time is replaced with a component that is dependent on a fractional derivative of time. It is shown that in both excitation source configurations, the fractional order Voigt model assumption improves the match of theory to experiment over a wider frequency range (in some cases up to the measured range of 700 Hz).