In vitro mitral chordal cutting by high intensity focused ultrasound.

Mitral regurgitation, when it arises from functional restriction of mitral leaflet closure, can be relieved by surgical cutting of the mitral tendineae chordae. We hypothesized that high intensity focused ultrasound (HIFU) might be useful as a noninvasive extracorporeal technique for cutting mitral chordae. As a pilot study to test this hypothesis, we examined the in vitro feasibility of using HIFU to cut calf mitral chordae with diameters from 0.2 to 1.6 mm. Sixty-seven percent of chordae were completely cut with HIFU, operated at 4.67 MHz and 45 W acoustic power, with up to 120 pulses of 0.3-s duration at 2-s intervals. Forty-five percent were completely cut when the pulse duration was reduced to 0.2 s. The average diameter of those chordae, which were completely cut, was significantly smaller than that of incompletely cut chordae (0.59 +/- 0.30 versus 1.14 +/- 0.30 mm with a pulse duration of 0.2 s, p < 0.0001; 0.68 +/- 0.29 versus 1.32 +/- 0.20 mm with a pulse duration of 0.3 s, p < 0.0001). For each pulse duration, the number of pulses required for complete cutting exhibited a strong positive correlation with the chordae diameter. In conclusion, in vitro feasibility of mitral chordal cutting by HIFU depended on the diameter of chordae but was controllable by HIFU settings. (E-mail: abeyukio@aol.com).

Ultrasonic tissue characterization via 2-D spectrum analysis: theory and in vitro measurements.

A theoretical model is described for application in ultrasonic tissue characterization using a calibrated 2-D spectrum analysis method. This model relates 2-D spectra computed from ultrasonic backscatter signals to intrinsic physical properties of tissue microstructures, e.g., size, shape, and acoustic impedance. The model is applicable to most clinical diagnostic ultrasound systems. Two experiments employing two types of tissue architectures, spherical and cylindrical scatterers, are conducted using ultrasound with center frequencies of 10 and 40 MHz, respectively. Measurements of a tissue-mimicking phantom with an internal suspension of microscopic glass beads are used to validate the theoretical model. Results from in vitro muscle fibers are presented to further elucidate the utility of 2-D spectrum analysis in ultrasonic tissue characterization.

On the statistics of ultrasonic spectral parameters.

Several factors affect the accuracy and precision of ultrasonic spectrum analysis, which is used for characterization of normal and diseased tissue in a variety of organs. For example, averaging procedures and the sequence of operations affect the accuracy and precision of spectrum analysis. Averaging procedures and logarithmic conversion (i.e., conversion to dB) introduce a constant bias that affects spectral amplitudes and the values of intercept and midband fit; the bias depends on the sequencing of the log conversion and averaging as well as the number of independent spectra or spectral parameters that are averaged. We derive expressions that permit correction of such biases. Furthermore, we show that standard deviations for slope and midband-fit estimation can be minimized by averaging spectra before dB conversion and before computing spectral parameters by linear regression. Experimental results using phantoms agree remarkably with theoretical predictions for the data window functions studied in this article, Hamming and rectangular.

Myocardial lesion formation using high-intensity focused ultrasound.

BACKGROUND: The potential therapeutic uses of ultrasound energy in cardiac disease have not been extensively studied. We have developed a means to deliver high-intensity focused ultrasound (HIFU) to myocardial tissue. Unlike other therapy modalities such as radiofrequency catheter ablation, this system has the advantages of not requiring direct tissue contact and the ability to focus intense energy within a small volume. METHODS: Sections of left and right ventricles from freshly excised canine hearts were treated in vitro with HIFU pulses. Lesions were created using 1-second HIFU pulses with ultrasonic powers ranging from 19.8 to 45.8 W. RESULTS: There was a dose-response relationship between the applied HIFU energy and lesion size (r = 0.70, P < .001). Myocardial lesion formation with HIFU was also performed in vivo in a canine open-chest beating heart model. With 200-millisecond HIFU pulses gated to the electrocardiogram, focal myocardial lesions were created ranging in length from 2 to 6 mm depending on the dose used. Furthermore, both in vitro and in vivo, focal lesions were successfully formed in the midmyocardial wall that spared both the endocardial and epicardial surfaces. CONCLUSION: HIFU is a novel means to create focal myocardial lesions without direct tissue contact. HIFU energy delivery can be gated to the electrocardiogram in an in vivo model, and lesions can be formed intramyocardially. Further application of this technology may prove to be useful for the ablation of myocardial lesions such as arrhythmogenic foci and the hypertrophic ventricular septum in hypertrophic cardiomyopathy. The potential therapeutic uses of ultrasound energy in cardiac diseases have not been well studied. We tested a novel system to deliver high-intensity focused ultrasound energy in vitro and in vivo to canine myocardial samples without direct contact with the target tissue. Focal myocardial lesions were formed in a dose-dependent manner, and myocardial lesions were created. This technology may prove useful for ablation of focal intramyocardial lesions such as arrhythmogenic foci and the hypertrophic left ventricular septum in hypertrophic cardiomyopathy.

Design and fabrication of a 40-MHz annular array transducer.

This paper investigates the feasibility of fabricating a five-ring, focused annular array transducer operating at 40 MHz. The active piezoelectric material of the transducer was a 9-microm thick polyvinylidene fluoride (PVDF) film. One side of the PVDF was metallized with gold and forms the ground plane of the transducer. The array pattern of the transducer and electrical traces to each annulus were formed on a copper-clad polyimide film. The PVDF and polyimide were bonded with a thin layer of epoxy, pressed into a spherically curved shape, then back filled with epoxy. A five-ring transducer with equal area elements and 100-microm kerfs between annuli was fabricated and tested. The transducer had a total aperture of 6 mm and a geometric focus of 12 mm. The pulse/echo response from a quartz plate located at the geometric focus, two-way insertion loss (IL), complex impedance, electrical crosstalk, and lateral beamwidth all were measured for each annulus. The complex impedance data from each element were used to perform electrical matching, and the measurements were repeated. After impedance matching; fc approximately equal to 36 MHz and -6-dB bandwidths ranged from 31 to 39%. The ILs for the matched annuli ranged from -28 to -38 dB.

In vitro ablation of cardiac valves using high-intensity focused ultrasound.

The purpose of this study was to evaluate the possibility of using high-intensity focused ultrasound (US), or HIFU, to create lesions in cardiac valves in vitro. Calf mitral valves and aortic valves were examined. Focused US energy was applied with an operating frequency of 4.67 MHz at a nominal acoustic power of 58 W for 0.2, 0.3 and 0.4 s at 4-s intervals. Mitral valve perforation was achieved with 20.8 +/- 3.7 exposures of 0.2 s, 15.4 +/- 2.1 exposures of 0.3 s or 11.2 +/- 2.3 exposures of 0.4 s. Aortic valve perforation was achieved with 13.3 +/- 2.4 exposures of 0.2 s, 10.3 +/- 2.2 exposures of 0.3 s or 8.4 +/- 1.8 exposures of 0.4 s. The mean diameter of the perforated area was 1.09 +/- 0.11 mm. The lesions were slightly discolored and coagulation of tissue around the perforation was observed. HIFU was successful in perforating cardiac valves. With further refinement, HIFU may prove useful for valvulotomy or valvuloplasty.

High-frequency harmonic imaging of the eye.

PURPOSE: Harmonic imaging has become a well-established technique for ultrasonic imaging at fundamental frequencies of 10 MHz or less. Ophthalmology has benefited from the use of fundamentals of 20 MHz to 50 MHz. Our aim was to explore the ability to generate harmonics for this frequency range, and to generate harmonic images of the eye. METHODS: The presence of harmonics was determined in both water and bovine vitreous propagation media by pulse/echo and hydrophone at a series of increasing excitation pulse intensities and frequencies. Hydrophone measurements were made at the focal point and in the near- and far-fields of 20 MHz and 40 MHz transducers. Harmonic images of the anterior segment of the rabbit eye were obtained by a combination of analog filtering and digital post-processing. RESULTS: Harmonics were generated nearly identically in both water and vitreous. Hydrophone measurements showed the maximum second harmonic to be -5 dB relative to the 35 MHz fundamental at the focus, while in pulse/echo the maximum harmonic amplitude was -15dB relative to the fundamental. Harmonics were absent in the near-field, but present in the far-field. Harmonic images of the eye showed improved resolution. CONCLUSION: Harmonics can be readily generated at very high frequencies, and at power levels compliant with FDA guidelines for ophthalmology. This technique may yield further improvements to the already impressive resolutions obtainable in this frequency range. Improved imaging of the macular region, in particular, may provide significant improvements in diagnosis of retinal disease.

Ultrasonic tissue characterization using 2-D spectrum analysis and its application in ocular tumor diagnosis.

We are investigating the utility of a new ultrasonic tissue characterization technique, specifically two-dimensional (2-D) spectrum analysis of radio-frequency backscatter signals, which promises to provide quantitative measures of the physical properties of tissue microstructures. Previously successful 1-D spectrum analysis is expanded to 2-D to more fully characterize diagnostically significant features of biological tissue. Two new spectral functions, radially integrated spectral power (RISP) and angularly integrated spectral power (AISP), are defined to quantitatively characterize tissue properties. This new approach is applied to the diagnosis of in vivo ocular melanomas. Our initial results indicate that 2-D spectrum analysis can provide significant new information on tissue anisotropy that are not apparent in 1-D spectra. Acoustic scattering models are applied to relate the 2-D spectral parameters to the physical properties (e.g., size and shape) of biological tissues.

Noninvasive in vivo detection of prognostic indicators for high-risk uveal melanoma: ultrasound parameter imaging.

PURPOSE: Primary malignant melanoma of the choroid and ciliary body has traditionally been treated without histologic staging, using purely clinical indicators. The presence of extravascular matrix patterns (EMP) in histologic sections of uveal melanoma has been shown to be an independent indicator of metastatic risk. These patterns are of a dimension and physical composition that are likely to be detected with ultrasound backscatter analysis. Our aim was to determine whether ultrasound parameter imaging could detect the presence of EMP at a diagnostically significant level for treatment staging and for planning investigational studies of therapeutic modalities. DESIGN: Prospective, masked ultrasound-pathologic correlative study. PARTICIPANTS: One hundred seventeen patients diagnosed with previously untreated choroidal melanoma were scanned within 2 weeks before enucleation. METHODS: Tumors were evaluated histologically and divided into high-risk and low-risk groups on the basis of the presence of 2% or more histologic cross-sectional area composed of EMP patterns. Digital ultrasound data were processed to generate parameter images representing the size and concentration of ultrasound scatterers. Histologic and ultrasound images and data were correlated, and linear and nonlinear statistical methods were used to create multivariate models for noninvasive differentiation of high-risk and low-risk tumors. MAIN OUTCOME MEASURES: Presence or absence of high-risk EMP and associated ultrasound parameter classification models. RESULTS: Of the 117 tumors, 69 were classified as low risk, and 48 were classified as high-risk with histologic analysis. A classification that used ultrasound parameter image features with linear discriminant analysis could correctly identify 79.5% of cases retrospectively and 75.2% of cases by use of cross-validation, an estimate of prospective classification ability. By use of a more powerful classification technique (support vector machine), 93.1% of cases were correctly classified retrospectively. With a cross-validation procedure, 80.10% of cases were correctly classified. CONCLUSIONS: Ultrasound can be used noninvasively to classify tumors into high-risk and low-risk groups by detecting the presence of EMP patterns. By the use of previous studies that compared the histologic presence of EMP patterns with patient survival, estimates of hazard rates associated with ultrasound risk groups can be made. The noninvasive ultrasound classification is potentially useful as a prognostic variable and as a tool for stratification of patient populations for tumor treatment evaluation.

Adaptive spectral strain estimators for elastography.

In conventional elastography, internal tissue deformations, induced by external compression applied to the tissue surface, are estimated by cross-correlation analysis of echo signals obtained before and after compression. Conventionally, strains are estimated by computing the gradient of estimated displacement. However, gradient-based algorithms are highly susceptible to noise and decorrelation, which could limit their utility. We previously developed strain estimators based on a frequency-domain (spectral) formulation that were shown to be more robust but less precise compared to conventional strain estimators, In this paper, we introduce a novel spectral strain estimator that estimates local strain by maximizing the correlation between the spectra of pre- and postcompression echo signals using iterative frequency-scaling of the latter; we also discuss a variation of this algorithm that may be computationally more efficient but less precise. The adaptive spectral strain estimator combines the advantages of time- and frequency-domain methods and has outperformed conventional estimators in experiments and 2-D finite-element simulations.

Radiation-force technique to monitor lesions during ultrasonic therapy.

This report describes a monitoring technique for high-intensity focused ultrasound (US), or HIFU, lesions, including protein-denaturing lesions (PDLs) and those made for noninvasive cardiac therapy and tumor treatment in the eye, liver and other organs. Designed to sense the increased stiffness of a HIFU lesion, this technique uniquely utilizes the radiation force of the therapeutic US beam as an elastographic push to detect relative stiffness changes. Feasibility was demonstrated with computer simulations (treating acoustically induced displacements, concomitant heating, and US displacement-estimation algorithms) and pilot in vitro experimental studies, which agree qualitatively in differentiating HIFU lesions from normal tissue. Detectable motion can be induced by a single 5 ms push with temperatures well below those needed to form a lesion. Conversely, because the characteristic heat diffusion time is much longer than the characteristic relaxation time following a push, properly timed multiple therapy pulses will form lesions while providing precise control during therapy.

Spectral parameter imaging for detection of prognostically significant histologic features in uveal melanoma.

Specific extracellular matrix patterns in uveal melanoma are associated with metastatic risk. The laminin-rich composition and dimensions (on the order of a wavelength or less) of these structures suggest that acoustic backscatter might be affected by their presence. In this study, 10-MHz radiofrequency (RF) ultrasound (US) data were acquired before surgical removal of 117 eyes with uveal malignant melanoma. Histologic sections were evaluated for the presence of matrix patterns and acoustic backscatter was characterized using calibrated spectrum analysis. Statistical correlations between acoustic and histologic patterns were determined and linear discriminant analysis (LDA) and radial basis networks (RBN) were used to develop classification models for histologically based risk groups. Statistically significant correlations were found between acoustic parameters and the presence of histologic matrix-rich patterns. Retrospective classification accuracies of 74.4% and 78.6% were obtained with LDA and RBN, respectively. Leave-one-out analyses indicated estimated predictive accuracies of 71.8% and 75.0% for LDA and RBN, respectively.

A review of physical phenomena associated with ultrasonic contrast agents and illustrative clinical applications.

Successful clinical applications of contrast agents involve an understanding of the physical interaction of ultrasound (US) with contrast agents. This paper reviews the physical phenomena involved in these interactions and discusses the relevant theoretical background for modeling US-contrast agent interactions. Measurement techniques using US to obtain information regarding contrast agents are summarized. Illustrative clinical applications are given in the second part of the paper. Recent developments in nonlinear imaging techniques and transient techniques are reviewed. New methods, such as depletion perfusion measurement, and high-frequency applications are included.