Alexander Haak

Interlaboratory comparison of backscatter coefficient estimates for tissue-mimicking phantoms.

Utrasonic backscatter is useful for characterizing tissues and several groups have reported methods for estimating backscattering properties. Previous interlaboratory comparisons have been made to test the ability to accurately estimate the backscatter coefficient (BSC) by different laboratories around the world. Results of these comparisons showed variability in BSC estimates but were acquired only for a relatively narrow frequency range, and, most importantly, lacked reference to any independent predictions from scattering theory. The goal of this study was to compare Faran-scattering-theory predictions with cooperatively-measured backscatter coefficients for low-attenuating and tissue-like attenuating phantoms containing glass sphere scatterers of different sizes for which BSCs can independently be predicted. Ultrasonic backscatter measurements were made for frequencies from 1 to 12 MHz. Backscatter coefficients were estimated using two different planar-reflector techniques at two laboratories for two groups of phantoms. Excellent agreement was observed between BSC estimates from both laboratories. In addition, good agreement with the predictions of Farans theory was obtained, with average fractional (bias) errors ranging from 8–14%. This interlaboratory comparison demonstrates the ability to accurately estimate parameters derived from the BSC, including an effective scatterer size and the acoustic concentration, both of which may prove useful for diagnostic applications of ultrasound tissue characterization.

Determination of postexcitation thresholds for single ultrasound contrast agent microbubbles using double passive cavitation detection

This work presents experimental responses of single ultrasound contrast agents to short, large amplitude pulses, characterized using double passive cavitation detection. In this technique, two matched, focused receive transducers were aligned orthogonally to capture the acoustic response of a microbubble from within the overlapping confocal region. The microbubbles were categorized according to a classification scheme based on the presence or absence of postexcitation signals, which are secondary broadband spikes following the principle oscillatory response of the ultrasound contrast agent and are indicative of the transient collapse of the microbubble. Experiments were conducted varying insonifying frequencies (0.9, 2.8, 4.6, and 7.1 MHz) and peak rarefactional pressures (200 kPa to 6.2 MPa) for two types of contrast agents (Definity and Optison). Results were fit using logistic regression analysis to define pressure thresholds where at least 5% and 50% of the microbubble populations collapsed for each frequency. These thresholds were found to occur at lower pressures for Definity than for Optison over the range of frequencies studied; additionally, the thresholds occurred at lower pressures with lower frequencies for both microbubble types in most cases, though this trend did not follow a mechanical index scaling.

Ultrasonic backscatter coefficients for weakly scattering, agar spheres in agar phantoms.

Applicability of ultrasound phantoms to biological tissue has been limited because most phantoms have generally used strong scatterers. The objective was to develop very weakly scattering phantoms, whose acoustic scattering properties are likely closer to those of tissues and then compare theoretical simulations and experimental backscatter coefficient (BSC) results. The phantoms consisted of agar spheres of various diameters (nominally between 90 and 212 microm), containing ultrafiltered milk, suspended in an agar background. BSC estimates were performed at two institutions over the frequency range 1-13 MHz, and compared to three models. Excellent agreement was shown between the two laboratory results as well as with the three models.

Cross-imaging platform comparison of ultrasonic backscatter coefficient measurements of live rat tumors

Objective. To translate quantitative ultrasound (QUS) from the laboratory into the clinic, it is necessary to demonstrate that the measurements are platform independent. Because the backscatter coefficient (BSC) is the fundamental estimate from which additional QUS estimates are calculated, agreement between BSC results using different systems must be demonstrated. This study was an intercomparison of BSCs from in vivo spontaneous rat mammary tumors acquired by different groups using 3 clinical array systems and a single‐element laboratory scanner system. Methods. Radio frequency data spanning the 1‐ to 14‐MHz frequency range were acquired in 3 dimensions from all animals using each system. Each group processed their radio frequency data independently, and the resulting BSCs were compared. The rat tumors were diagnosed as either carcinoma or fibroadenoma. Results. Carcinoma BSC results exhibited small variations between the multiple slices acquired with each transducer, with similar slopes of BSC versus frequency for all systems. Somewhat larger variations were observed in fibroadenomas, although BSC variations between slices of the same tumor were of comparable magnitude to variations between transducers and systems. The root mean squared (RMS) errors between different transducers and imaging platforms were highly variable. The lowest RMS errors were observed for the fibroadenomas between 4 and 5 MHz, with an average RMS error of 4 × 10−5 cm−1Sr−1 and an average BSC value of 7.1 × 10−4 cm−1Sr−1, or approximately 5% error. The highest errors were observed for the carcinoma between 7 and 8 MHz, with an RMS error of 1.1 × 10−1 cm−1Sr−1 and an average BSC value of 3.5 × 10−2 cm−1Sr−1, or approximately 300% error. Conclusions. This technical advance shows the potential for QUS technology to function with different imaging platforms.

Techniques and evaluation from a cross-platform imaging comparison of quantitative ultrasound parameters in an in vivo rodent fibroadenoma model

This contribution demonstrates that quantitative ultrasound (QUS) capabilities are platform independent, using an in vivo model. Frequency-dependent attenuation estimates, backscatter coefficient, and effective scatterer diameter estimates are shown to be comparable across four different ultrasound imaging systems with varied processing techniques. The backscatter coefficient (BSC) is a fundamental material property from which several QUS parameters are estimated; therefore, consistent BSC estimates among different systems must be demonstrated. This study is an intercomparison of BSC estimates acquired by three research groups (UIUC, UW, ISU) from four in vivo spontaneous rat mammary fibroadenomas using three clinical array systems and a single-element laboratory scanner system. Because of their highly variable backscatter properties, fibroadenomas provided an extreme test case for BSC analysis, and the comparison is across systems for each tumor, not across the highly heterogeneous tumors. RF echo data spanning the 1 to 12 MHz frequency range were acquired in three dimensions from all animals using each system. Each research group processed their RF data independently, and the resulting attenuation, BSC, and effective scatterer diameter (ESD) estimates were compared. The attenuation estimates across all systems showed the same trends and consistently fit the power-law dependence on frequency. BSCs varied among the multiple slices of data acquired by each transducer, with variations between transducers being of a similar magnitude as those from slice to slice. Variation between BSC estimates was assessed via functional signal-to-noise ratios derived from backscatter data. These functional signal-to-noise ratios indicated that BSC versus frequency variations between systems ranged from negligible compared with the noise level to roughly twice the noise level. The corresponding functional analysis of variance (fANOVA) indicated statistically significant differences between BSC curves from different systems. However, root mean squared difference errors of the BSC values (in decibels) between different transducers and imaging platforms were less than half of the BSC magnitudes in most cases. Statistical comparison of the effective scatterer diameter (ESD) estimates resulted in no significant differences in estimates from three of the four transducers used for those estimates, demonstrating agreement among estimates based on the BSC. This technical advance demonstrates that these in vivo measurements can be made in a system-independent manner; the necessary step toward clinical implementation of the technology.

Encapsulated contrast microbubble radial oscillation associated with postexcitation pressure peaks

This work combines modeling and experiment to assess encapsulated microbubble oscillations associated with broadband pressure peaks detected after microbubble excitation (postexcitation signals). Data were acquired from albumin-shelled and phospholipid-shelled microbubbles using a passive cavitation detector consisting of a confocally aligned 2.8-MHz transmitter and 13-MHz receiver. Microbubbles in weak solutions were insonified with a 5-cycle pulse at a peak rarefactional pressure of 2.0+/-0.2 MPa. For each microbubble type, at least 100 received signals were identified as individual-microbubble responses. The average broadband noise from signals with postexcitation response was 4.2-7.2 dB higher than from signals without postexcitation. Pressure-time responses for each microbubble type were simulated using the model by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)], with insonification conditions matching the experiment. Increased broadband noise predicted for microbubbles with postexcitation response was consistent with that observed experimentally (4.0-8.9 dB). The model predicted that postexcitation signals occur only when the radial oscillation exceeds both the shell break-up threshold and twice the initial radius (free bubble inertial cavitation threshold).

Contrast ultrasound imaging of the aorta alters vascular morphology and circulating von Willebrand factor in hypercholesterolemic rabbits.

Ultrasound contrast agents (UCAs) are intravenously infused microbubbles that add definition to ultrasonic images. Ultrasound contrast agents continue to show clinical promise in cardiovascular imaging, but their biological effects are not known with confidence. We used a cholesterol‐fed rabbit model to evaluate these effects when used in conjunction with ultrasound (US) to image the descending aorta.

8B-6 Semiautomatic Detection of Microbubble Ultrasound Contrast Agent Destruction Applied to Definity® Using Support Vector Machines

For different applications such as imaging, drug delivery, and tissue perfusion measurement, it is necessary to know the inertial cavitation (IC) threshold of ultrasonic contrast agent (UCA) microbubbles. Even though the influence of the incident acoustical pressure, frequency and pulse duration (PD) in the regime of the microbubbles response is well established, the investigation of the IC threshold is essential for the accuracy of some measurement techniques and for ultrasound safety. The goal of our work was to find the IC threshold for the FDA-approved UCA Definity. The dependency of the threshold on the peak rarefactional pressure and PD of an incident tone- burst was investigated. The experiments performed to estimate IC thresholds yield a large amount of data to be classified in the five following classes: Noise, Oscillation, Collapse, Multiple Bubbles and Unknown. A reduction of the manually to classified data was reduced by using a semiautomatic algorithm in order to achieve a low variance in the IC estimates. Further more significant features to distinguish between classes were found and tested. The development of a heuristic algorithm to detect events of thee class Collapse was not successful due to the fact that the classes were overlapping and some signals could not be classified to a single class. Therefore, a semiautomatic algorithm using support vector machines was developed.

Algorithm for estimating the attenuation slope from backscattered ultrasonic signals

In vivo attenuation slope measurements usually utilize the backscattered signal from pulse/echo ultrasound. In this work the down shift of the center frequency of an emitted ultrasound pulse with penetration depth is utilized to estimate the attenuation slope. A diffraction correction of the focused ultrasound source is performed by measuring the reflection from a planar surface positioned throughout the depth of focus. A focused single element transducer with a measured center frequency of 8.2 MHz and a fractional band width of 72% was used to interrogate four tissue mimicking phantoms. The scatterers in the tissue mimicking phantoms were glass spheres embedded in a gelatin/milk matrix. In one set of the phantoms, the backscattering strength was varied; in the other set of phantoms the attenuation slope was varied. The attenuation slope (ASBS) was estimated using pulse/echo data obtained by scanning the phantoms. The “true” attenuation slope (ASThru) was obtained from two independent insertion loss measurements performed at two different laboratories. The relative error of ASBS was investigated for different regions of interest (ROI) for all phantoms. Three different axial and lateral ROI sizes were tested. It was observed that the average relative error (average over all four phantoms) changed by less than three percent when the lateral size of the ROI was decreased by seventy percent. The axial size of the ROI was changed by thirty percent whereas the average error changed by less then three percent.

Spectral and temporal signal modifications occuring between stable and transient inertial cavitation

The goal of this work is to investigate temporal and spectral modifications in passive cavitation detection (PCD) measurements from ultrasound contrast microbubbles (MBs) related to MB rupture. Contrast MB pressure-time responses are modelled with the Marmottant model. Results demonstrate that post-excitation signals occur on simulated pressure-time traces for MBs only when radial oscillations exceed the modelled breakup radius within a range of sizes near the resonant size. PCD signals are acquired from MBs of Optison, Definity and Sonovue (acoustic excitation at 2.8-MHz, 5-cycle transmit; confocal 13-MHz receiver). Although data are acquired at relatively high incident acoustic pressures (peak rarefactional pressure of 1.6, 2.0 and 2.4 plusmn 0.2 MPa), subsets of data with and without post-excitation signals are identified for each MB type and pressure range. Post-excitation signals are used to identify which PCD signals indicate MB break-up [1] then average values of peak-to-peak voltage, 2nd harmonic, 3rd and 4th harmonic and broadband noise are calculated for responses from groups of ruptured and nonruptured MBs for each pressure range and MB type. The signal to noise ratio (SNR) is high (10 to 49 dB) both for ruptured (with post-excitation signals) and nonruptured (no post-excitation signals) MBs for all pressures and MBs. The average parameter values from ruptured MBs are approximately 3 to 8 dB higher than for nonruptured MBs although differences vary with the type of MB. Results contribute to better understand the link between PCD spectral and temporal modifications and MB break-up.