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).

High resolution ultrasound elastomicroscopy imaging of soft tissues: system development and feasibility.

Research in elasticity imaging typically relies on 1-10 MHz ultrasound. Elasticity imaging at these frequencies can provide strain maps with a resolution in the order of millimetres, but this is not sufficient for applications to skin, articular cartilage or other fine structures. We developed a prototype high resolution elastomicroscopy system consisting of a 50 MHz ultrasound backscatter microscope system and a calibrated compression device using a load cell to measure the pressure applied to the specimen, which was installed between a rigidly fixed face-plate and a specimen platform. Radiofrequency data were acquired in a B-scan format (10 mm wide x 3 mm deep) in specimens of mouse skin and bovine patellar cartilage. The scanning resolution along the B-scan plane direction was 50 microm, and the ultrasound signals were digitized at 500 MHz to achieve a sensitivity better than 1 microm for the axial displacement measurement. Because of elevated attenuation of ultrasound at high frequencies, special consideration was necessary to design a face-plate permitting efficient ultrasound transmission into the specimen and relative uniformity of the compression. Best results were obtained using a thin plastic film to cover a specially shaped slit in the face-plate. Local tissue strain maps were constructed by applying a cross-correlation tracking method to signals obtained at the same site at different compression levels. The speed of sound in the tissue specimen (1589.8+/-7.8 m s(-1) for cartilage and 1532.4+/-4.4 m s(-1) for skin) was simultaneously measured during the compression test. Preliminary results demonstrated that this ultrasound elastomicroscopy technique was able to map deformations of the skin and articular cartilage specimens to high resolution, in the order of 50 microm. This system can also be potentially used for the assessment of other biological tissues, bioengineered tissues or biomaterials with fine structures.

Quantification of ultrasound contrast agent response: comparison of continuous wave Doppler and power Doppler to backscattered radiofrequency data.

Our goal was to compare two quantification methods of ultrasound contrast agents available in clinical practice [continuous wave Doppler intensity (CWDI) and power Doppler intensity (PWDI)] to the reference technique (radio-frequency analysis) with a simple recirculating flow phantom using a renal dialysis cartridge. Measurements were made at different doses of perflenapent emulsion and BR1. Cineloops of power Doppler images were recorded using a clinically available ultrasound unit (HDI 3000). Simultaneously, integrated backscatter (IBS) was measured by analysis of radiofrequency signals, whereas Doppler signal intensity was measured with a continuous wave Doppler device. A linear relationship was found between CWDI and IBS and between PWDI and IBS when R(2) was calculated for each pair of parameters injection-by-injection. Results are summarized by the average R(2) for all injections between CWDI and IBS (BR1: R(2) = 0.93 +/- 0.05, perflenapent emulsion: R(2) = 0.94 +/- 0.03) and between PWDI and IBS (BR1: R(2) = 0.88 +/- 0.07, perflenapent emulsion: R(2) = 0.79 +/- 0.09). However, for all data obtained from all different injected doses and for both contrast agents, there was considerable variation of CWDI and PWDI values measured for a given value of IBS. In conclusion, for a fixed microbubble population, CWDI and PWDI can be proposed for quantification of USCA. However, their important variations observed at each dose make it difficult to link a single value of PWDI or CWDI or IBS to a single microbubble distribution composition.

Reproducibility of skin characterization with backscattered spectra (12--25 MHz) in healthy subjects.

Ultrasonic techniques were developed for quantitative in vivo analysis of skin composition based on measurements of apparent integrated backscatter (IBS) and its frequency dependence (n) between 12.5 and 25 MHz. Parameters were measured at five depths in healthy dermis of the midforearm of 29 volunteers (13 women, 16 men, 20 to 76 years old) on three different days. Reproducibility of measurements was evaluated (standardized coefficients of variation: 7% to 11% for IBS and 9% to 20% for n). Parameter values were significantly influenced by pressure of the ultrasonic probe on the skin, and both room and skin-surface temperatures were correlated to IBS measured in a single subject on 28 days. More precise control of these factors could further improve measurement reproducibility and sensitivity to skin composition. Significant (p < 0.05) differences of parameter values with respect to region of interest depth, age and gender of subjects were discussed in comparison with dermal composition and offer promise that these parameters could be used to characterize skin modifications.

Multiparametric attenuation and backscatter images for characterization of carotid plaque.

The goal of this study was to develop methods for quantitative ultrasound imagery suitable for noninvasive assessment of carotid plaque composition prior to the selection of the technique for revascularization. Using two broadband transducers (5-12 MHz and 12-28 MHz), backscattered radio frequency signals were acquired from entire lengths of 15 carotid endarterectomy specimens. Spectral analysis methods with correction for system response and beam diffraction were applied to radio frequency signals from local volumes of plaque having a 2 mm slice thickness, 1 mm width and axial depth of 480 microm and 240 microm at 10 MHz and 20 MHz, respectively. From these spectra, local values of four ultrasound parameters (integrated backscatter, frequency dependence of backscatter, integrated attenuation and slope of attenuation) were estimated and used to construct quantitative images. To combine information from these different parameter images, a two-step approach was followed. First, in 59 independent quantitative images of highly stenotic plaque, the average parameter values in a central five-by-three pixel region were correlated with plaque composition as assessed by histology to investigate the relationship between parameter values, frequency bandwidth and plaque composition. Discriminant analysis of parameter values vs. plaque composition was made to find a set of predictive equations to classify sets of measurements. Correct classification was obtained for 100% of calcified, 75% of intraplaque hemorrhage and 71% of lipidic plaques of the input data set. Second, each set of pixels from different parameter images was classified using the predictive equations, and a single, local tissue composition image was constructed. Examples of tissue composition images are presented in comparison with corresponding histologic sections. Both agreement and disagreement between image pairs are discussed.

[Non-invasive imaging of atherosclerosis by MRI and ultrasonography]. / Imagerie non invasive de l'athérosclérose en IRM et échographie.

The concept of the unstable, so-called "high risk" or vulnerable atheromatous plaque has been accepted for several years and its biological, mechanical and cellular features (collagen top, lipid core with macrophages, metalloproteinases...) have been determined. However, the means of investigating these lesions remain limited. A description of their composition has become essential as the prognosis of coronary, aortic and carotid artery disease is no longer evaluated only by morphometric data (degree of stenosis). MRI with T1 or T2 contrast sequences, density of spin, chemical shift, diffusion, magnetisation transfer or spectroscopy provides a non-invasive tool for their study. This method, based on the detection of magnetic atomic nuclei (such as proton H1, carbon 13, sodium 23, potassium 49) enables tissue characterisation by means of the variations in chemical environment and their consequences on the degree of magnetisation of the nuclei studied. High frequency ultrasound could also be used to this end by measuring the coefficients of attenuation and back-scattering. These methods, used clinically and in different animal models, should improve our understanding of the physiopathology, facilitate diagnosis and improve the prognostic accuracy in patients with atherosclerosis.

Characterization of atherosclerotic plaque components by high resolution quantitative MR and US imaging.

High resolution MRI at 3 T and US imaging at 50 MHz were used for atherosclerotic plaque characterization. For 14 excised segments of human arteries, conventional MR and US images, quantitative MR T2 maps, US integrated attenuation (IA) maps, and histologic sections were produced and compared. The MR T2 and US attenuation mean values estimated in selected regions of interest were related with tissue type as identified on histologic sections. Significant distinction between media or collagen and lipid or collagen lipidic plaque was achieved with both techniques (MR: P < .001; US: P < .01). Significant distinction was obtained between media and collagen (P < .0001) and between iliac and aortic media (P < .05) with MR T2 but not with IA. MR and US native and parametric images, with different sensitivities to tissue type, provide complementary information useful for quantitative plaque characterization.

US backscatter and attenuation 30 to 50 MHz and MR T2 at 3 Tesla for differentiation of atherosclerotic artery constituents in vitro.

This study compares quantitative characterization of atherosclerotic artery constituents by high resolution estimates of ultrasonic attenuation, ultrasonic attenuation-compensated backscatter, and magnetic resonance transverse relaxation time. Atherosclerotic human arteries were studied in vitro at 37°C. Backscattered radio frequency signals were acquired with a 50 MHz backscatter acoustic microscope. Ultrasonic parametric images were constructed from the integrated (30 to 50 MHz) backscatter and attenuation obtained using FFT methods with diffraction correction and a multinarrow-band attenuation algorithm. Parametric magnetic resonance images were constructed from calculated values of the transverse relaxation time T2 determined from an 8 echo-single-slice sequence at 3 Tesla. In a total of 54 regions of interest, average values of integrated attenuation, integrated backscatter compensated for the attenuation between the artery surface and the scattering volume, and the transverse relaxation time were correlated with local tissue composition as assessed by histology. Results show that ultrasound and magnetic resonance techniques offer complementary approaches for characterization of plaque composition.

Correlation of ultrasonic attenuation (30 to 50 MHz and constituents of atherosclerotic plaque.

The ultrasonic integrated attenuation and the slope of attenuation (30-50 MHz) were measured in vitro at 20 degrees +/- 2 degrees C using radio frequency signals backscattered from human aortae. Ultrasonic measurements and histologic classifications were made in a total of 124 local regions from 58 independent segments of aortae. Values of the integrated attenuation were significantly higher in collagen-lipidic (142 +/- 51 dB cm-1, n = 18), and lipidic regions (139 +/- 53 dB cm-1, n = 11) compared to regions of normal media (97 +/- 20 dB cm-1, n = 44) and dense collagen (107 +/- 33 dB cm-1, n = 43). The most elevated integrated attenuation values were observed in calcified regions (245 +/- 93 dB cm-1, n = 8). The slope of attenuation was significantly higher in lipidic than in normal media (p = 0.002), dense collagen (p = 0.0007) or collagenlipidic (p = 0.04) regions. The correlation between attenuation and local tissue composition was used to establish ranges of values of integrated attenuation that are most likely to indicate specific tissue types. Images of the local tissue type were constructed. Comparison of these quantitative images with the corresponding histologic sections demonstrates that attenuation measurements offer promise for the in vivo characterization of plaque structure and composition.

Parametric (integrated backscatter and attenuation) images constructed using backscattered radio frequency signals (25-56 MHz) from human aortae in vitro.

Quantitative ultrasonic tissue characterization using backscattered high-frequency intravascular ultrasound could provide a basis for the objective identification of lesions in vivo. Representation of local measurements of quantitative ultrasonic parameters in a conventional image format should facilitate their interpretation and thus increase their clinical utility. Toward this goal, the apparent integrated backscatter, the slope of attenuation (25-56 MHz) and the value of the attenuation on the linear fit at 37.5 MHz were measured using the backscattered radio frequency signals from in vitro human aortae. Local estimations of these ultrasonic parameters from both normal and atherosclerotic aortic segments were displayed in a B-scan format. The morphological features of these parametric images corresponded well to features of histological images of the same regions. The attenuation from 25-56 MHz of seven segments of the medial layer (both with and without overlying atheroma) were measured using the multinarrow-band backscatter method. The average attenuation in the media at 24 degrees C +/- 3 degrees C was 45 +/- 16 dB/cm at 25 MHz and 102 +/- 13 dB/cm at 50 MHz. This work represents progress toward the development of quantitative imaging methods for intravascular applications.

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.