Experimental validation of the use of Kramers-Kronig relations to eliminate the phase sheet ambiguity in broadband phase spectroscopy.

The technique of broadband phase spectroscopy proposed in 1978 by Sachse and Pao [J. Appl. Phys. 49, 4320-4327 (1978)] determines the phase velocity as a function of frequency from the Fourier transforms of a received reference and through-sample signal. Although quite successful, this approach can be influenced by an ambiguity in the phase velocity calculation which stems from the boundedness of the inverse tangent operation used to calculate phase. Several empirical approaches to resolve the phase ambiguity have been reported. An alternative approach that has not previously been considered appeals to the causal nature of the measurements. This article experimentally validates a method which uses the causally consistent Kramers-Kronig relations to eliminate the ambiguity in phase spectroscopy-derived phase velocity calculations. Broadband pulse and narrow-band tone burst measurements were performed on three gelatin-based phantoms containing different concentrations of graphite particles (0%, 10%, and 20% by volume). The phantoms were constructed to have attenuation coefficients which vary approximately linear-with-frequency, a dependence exhibited by many soft tissues. The narrow-band phase velocity measurements do not suffer from a phase ambiguity, and thus they serve as a "gold standard" against which the broadband phase velocity measurements are compared. The experimental results illustrate that using the Kramers-Kronig dispersion relations in conjunction with phase spectroscopy-derived phase velocity measurements is an effective means by which to resolve the phase sheet ambiguity in broadband phase spectroscopy.

In vitro characterization of a novel, tissue-targeted ultrasonic contrast system with acoustic microscopy.

Targeted ultrasonic contrast systems are designed to enhance the reflectivity of selected tissues in vivo [Lanza et al., Circulation 94, 3334 (1996)]. In particular, these agents hold promise for the minimally invasive diagnosis and treatment of a wide array of pathologies, most notably tumors, thromboses, and inflamed tissues. In the present study, acoustic microscopy was used to assess the efficacy of a novel, perfluorocarbon based contrast agent to enhance the inherent acoustic reflectivity of biological and synthetic substrates. Data from these experiments were used to postulate a simple model describing the observed enhancements. Frequency averaged reflectivity (30-55 MHz) was shown to increase 7.0 +/- 1.1 dB for nitrocellulose membranes with targeted contrast. Enhancements of 36.0 +/- 2.3 dB and 8.5 +/- 0.9 dB for plasma and whole blood clots, respectively, were measured between 20 and 35 MHz. A proposed acoustic transmission line model predicted the targeted contrast system would increase the acoustic reflectivity of the nitrocellulose membrane, whole blood clot, and fibrin plasma clot by 2.6, 8.0, and 31.8 dB, respectively. These predictions were in reasonable agreement with the experimental results of this paper. In conclusion, acoustic microscopy provides a rapid and sensitive approach for in vitro chracterization, development, and testing of mathematical models of targeted contrast systems. Given the current demand for targeted contrast systems for medical diagnostic and therapeutic use, the use of acoustic microscopy may provide a useful tool in the development of these agents.

High-frequency ultrasonic detection of thrombi with a targeted contrast system.

Site-targeted acoustic contrast agents used in conjunction with high-frequency intravascular ultrasound have the potential to localize and characterize intravascular pathology. The present study quantifies the utility of a novel, site-targeted ultrasonic contrast agent with high-frequency ultrasound (30 to 50 MHz) and demonstrates the feasibility of the new agent for augmenting detection of targeted pathology with intravascular ultrasonic catheters. High-frequency acoustic microscopy was used to image avidinconjugated nitrocellulose membranes after exposure to a control or biotinylated contrast agent. Increases (p < 0.05) in backscattered power of approximately 66 dB (4-fold) were found for the biotinylated, but not the control contrast agent. Intravascular ultrasonic images (30 MHz nominal center frequency) of plasma clots after exposure to the targeted contrast agent were brighter (p < 0.05) than in controls. These results demonstrate high-frequency acoustic enhancement with a novel targeted contrast agent and may extend the potential diagnostic spectrum of intravascular ultrasound.

Frequency dependence of acoustic backscatter from 5 to 65 MHz (0.06 < ka < 4.0) of polystyrene beads in agarose.

Attenuation and compensated backscatter from suspensions of random distributions of polystyrene beads in agarose are reported across a broad, continuous range of frequencies including frequencies which are currently of interest in the emerging fields of acoustic backscatter microscopy and intravascular imaging. Data are reported over the range of ka from 0.06 to 4, where k is the magnitude of the ultrasonic wave vector and a is the radius of the beads. The attenuation coefficient exhibits a linear dependence on frequency for ka < < 1 and more complex behaviour at larger values of ka. The measured frequency dependence of the compensated backscatter was consistent with the frequency dependence of the differential backscatter cross section for a single polystyrene sphere throughout the range of ka investigated.