Exvivo ultrasound attenuation coefficient for human cervical and uterine tissue from 5 to 10 MHz

Attenuation estimation and imaging in the cervix has been utilized to evaluate the onset of cervical ripening during pregnancy. This feature has also been utilized for the acoustic characterization of leiomyomas and myometrial tissue. In this paper, we present direct narrowband substitution measurement values of the variation in the ultrasonic attenuation coefficient in ex vivo human uterine and cervical tissue, in the 5-10 MHz frequency range. At 5 MHz, the attenuation coefficient values are similar for the different orientations of uterine tissue with values of 4.1-4.2 dB/cm, 5.1 dB/cm for the leiomyoma, and 6.3 dB/cm for the cervix. As the frequency increases, the attenuation coefficient values increase and are also spread out, with a value of approximately 12.6 dB/cm for the uterus (both parallel and perpendicular), 16.0 for the leiomyoma, and 26.8 dB/cm for the cervix at 10 MHz. The attenuation coefficient measured increases monotonically over the frequency range measured following a power law.     

Ultrasound attenuation estimation using backscattered echoes from multiple sources

The objective of this study was to devise an algorithm that can accurately estimate the attenuation along the propagation path (i.e., the total attenuation) from backscattered echoes. It was shown that the downshift in the center frequency of the backscattered ultrasound echoes compared to echoes obtained in a water bath was calculated to have the form Deltaf=mf(o)+b after normalizing with respect to the source bandwidth where m depends on the correlation length, b depends on the total attenuation, and f(o) is the center frequency of the source as measured from a reference echo. Therefore, the total attenuation can be determined independent of the scatterer correlation length by measuring the downshift in center frequency from multiple sources (i.e., different f(o)) and fitting a line to the measured shifts versus f(o). The intercept of the line gives the total attenuation along the propagation path. The calculations were verified using computer simulations of five spherically focused sources with 50% bandwidths and center frequencies of 6, 8, 10, 12, and 14 MHz. The simulated tissue had Gaussian scattering structures with effective radii of 25 mum placed at a density of 250 mm(3). The attenuation of the tissue was varied from 0.1 to 0.9 dB / cm-MHz. The error in the attenuation along the propagation path ranged from -3.5+/-14.7% for a tissue attenuation of 0.1 dB / cm-MHz to -7.0+/-3.1% for a tissue attenuation of 0.9 dB / cm-MHz demonstrating that the attenuation along the propagation path could be accurately determined using backscattered echoes from multiple sources using the derived algorithm.     

Estimate of the attenuation coefficient using a clinical array transducer for the detection of cervical ripening in human pregnancy

Premature delivery is the leading cause of infant mortality in the United States. Currently, premature delivery cannot be prevented and new treatments are difficult to develop due to the inability to diagnose symptoms prior to uterine contractions. Cervical ripening is a long period that precedes the active phase of uterine contractions and cervical dilation. The changes in the microstructure of the cervix during cervical ripening suggest that the ultrasonic attenuation should decrease. The objective of this study is to use the reference phantom algorithm to estimate the ultrasonic attenuation in the cervix of pregnant human patients. Prior to applying the algorithm to in vivo human data, two homogeneous phantoms with known attenuation coefficients were used to validate the algorithm and to find the length and the width of the region of interest (ROI) that achieves the smallest error in the attenuation coefficient estimates. In the phantom data, we found that the errors in the attenuation coefficients estimates are less than 12% for ROIs that contain 40 wavelengths or more axially and 30 echo lines or more laterally. The reference phantom algorithm was then used to obtain attenuation maps of the echoes from two human pregnant cervices at different gestational ages. It was observed that the mean of the attenuation coefficient estimates in the cervix of the patient at a more advanced gestational age is smaller than the mean of the attenuation coefficient estimates in the cervix of the patient at an earlier gestational age which suggests that ultrasonic attenuation decreases with increasing gestational age. We also observed a large variance between the attenuation coefficient estimates in the different regions of the cervix due to the natural variation in tissue micro-structures across the cervix. The preliminary results indicate that the algorithm could potentially provide an important diagnostic tool for diagnosing the risk of premature delivery.     

Time and frequency parameters of bottlenose dolphin whistles as predictors of surface behavior in the Mississippi Sound

In this study, an algorithm previously developed for estimating the total ultrasonic attenuation along the propagation path from the surface of the transducer to a region of interest (ROI) in tissue, was modified to make it more practical for use in clinical settings. Specifically, the algorithm was re-derived for when a tissue mimicking phantom rather than a planar reflector is used to obtain the reference power spectrum. The reference power spectrum is needed to compensate for the transfer function of the transmitted pulse, the transfer function of transducer, and the diffraction effects that result from focusing/beam forming. The modified algorithm was tested on simulated radio frequency (RF) echo lines obtained from two samples that have different scatterer sizes and different attenuation coefficient slopes, one of which was used as a reference. The mean and standard deviation of the percent errors in the attenuation coefficient estimates (ACEs) were less than 5% and 10%, respectively, for ROIs that contain more than 10 pulse lengths and more than 25 independent echo lines. The proposed algorithm was also tested on two tissue mimicking phantoms that have attenuation coefficient slopes of 0.7 dB/cm-MHz and 0.5 dB/cm-MHz respectively, the latter being the reference phantom. When a single element spherically focused source was used, the mean and standard deviation of the percent errors in the ACEs were less than 5% and 10% respectively for windows that contain more than 10 pulse lengths and more than 17 independent echo lines. When a clinical array transducer was used, the mean and standard deviation of the percent errors in the ACEs were less than 5% and 25%, respectively, for windows that contain more than 12 pulse lengths and more than 45 independent echo lines.     

Impact of local attenuation approximations when estimating correlation length from backscattered ultrasound echoes

Estimating the characteristic correlation length of tissue microstructure from the backscattered power spectrum could improve the diagnostic capability of medical ultrasound. Previously, size estimates were obtained after compensating for source focusing, the frequency-dependent attenuation along the propagation path (total attenuation), and the frequency-dependent attenuation in the scattering region (local attenuation). In this study, the impact of approximations of the local attenuation on the scatterer size estimate was determined using computer simulations and theoretical analysis. The simulations used Gaussian impedance distributions with an effective radius of 25 microm randomly positioned in a homogeneous half-space sonified by a spherically focused source (f/1 to f/4). The approximations of the local attenuation that were assessed neglected local attenuation (i.e., assume 0 dB/cm-MHz) neglected frequency dependence of the local attenuation, and assumed a finite frequency dependence (i.e., 0.5 dB/cm-MHz) independent of the true attenuation of the medium. Errors in the scatterer size estimate due to the local attenuation approximations increased with increasing window length, increasing true local attenuation and increasing f number. The most robust estimates were obtained when the local attenuation was approximated by a tissue-independent attenuation value that was greater than 70% of the largest attenuation expected in the tissue region of interest.     

Improved algorithm for estimation of attenuation along propagation path using backscattered echoes from multiple sources

Accurately determining the attenuation along the propagation path leading to a region of interest could significantly improve diagnostic ultrasound tissue characterization since tissue characterization requires exact compensation for the frequency-dependent attenuation along the propagation path. In a previous study (JASA, 124:1367, 2008), it was shown that the total attenuation can be determined by using the backscattered echoes from multiple sources. The preliminary computer simulation results, had an average error between ?0.3 and +0.2 dB/MHz for the cases tested with a trend towards increasing error with increasing correlation length (i.e., characteristic size of the tissue microstructure of the scattering medium) and attenuation along the propagation path. Therefore, the goal of this study was to improve the accuracy of previously derived algorithm and reduce the dependence of the algorithm on correlation length and attenuation. In this study, the previous derivations were redone and the assumptions made by the algorithm regarding the scattering properties of the medium and the shape of the backscattered power spectrum were relaxed. The revised algorithm was then verified using computer simulations of five sources (6, 8, 10, 12, and 14 MHz, 50% bandwidth) exposing a homogeneous tissue region. The simulated tissue had microstructure following a Gaussian spatial correlation function (i.e., exp (?0.827(ka_eff)²) where k is the wavenumber) with effective radii, a_eff, of 5–55 μm (one size per simulated case) placed at a density of 250/mm³ (～5 scatterers/resolution cell for 14 MHz transducer). The attenuation of the tissue was also varied from 0.1 to 0.9 dB/cm-MHz. The computer simulations demonstrated that the modifications significantly improved the accuracy of the algorithm resulting in average errors between ?0.04 and 0.1 dB/MHz which is three times better than the error performance of the original algorithm.     

High frequency ultrasonic characterization of human vocal fold tissue

Recently, endolaryngeal sonography at frequencies ranging from 10 to 30 MHz has been found to be useful in diagnosing diseases of the vocal folds (VFs). However, image resolution can be further improved by ultrasound at higher frequencies, necessitating the measurement of high-frequency acoustic properties of VF tissue. The ultrasonic parameters of integrated backscatter, sound velocity, and frequency-dependent attenuation coefficient were measured in both the lamina propria (LP) and vocalis muscle (VM) of human VFs using a 47 MHz high-frequency ultrasonic transducer. The integrated backscatter was -173.44+/-6.14 (mean+/-s.d.) and -195.13+/-3.58 dB in the LP and VM, respectively, the sound velocity was 1667.68+/-44.9 and 1595.07+/-39.33 ms, and the attenuation coefficient at 47 MHz was 8.28+/-1.72 and 7.17+/-1.30 dBmm. The difference between these ultrasonic parameters may be attributed to variations in the structure and fiber concentrations in VF tissue. These results could serve as a useful clinical reference for the further development of high-frequency ultrasound devices for endolarynx sonography applications.     

Identification of human myocardial infarction in vitro based on the frequency dependence of ultrasonic backscatter.

It has been reported previously that acute and mature myocardial infarction in dogs can be differentiated in vitro and in vivo by ultrasonic tissue characterization based on measurement of the frequency dependence of ultrasonic backscatter. To characterize human infarction with an index of the frequency dependence of backscatter that could be obtained in patients, cylindrical biopsy specimens from 7 normal regions and 12 regions of infarction of 6 fixed, explanted human hearts in 2-deg steps around their entire circumference with a 5-MHz broadband transducer were insonified. One to six consecutive transmural levels were studied for each specimen. The dependence of apparent (uncompensated for attenuation or beam width) backscatter, /B(f)/2, on frequency (f) was computed from spectral analyses of radio-frequency data as /B(f)/2 = afn, where from theoretical considerations the magnitude of n decreases as scatterer size increases. Apparent integrated backscatter was computed as the average of /B(f)/2 from 3 to 7 MHz. The average value for n for normal tissue (0.9 +/- 0.1) exceeded that for tissue from regions of infarction (0.6 +/- 0.1; p less than 0.05). Infarct manifested a significant decrease of n from epicardial to endocardial levels (epi----mid----endo: 0.9----0.7----0.2; p less than 0.05) whereas normal tissue manifested similar values for n at each transmural level (0.8----1.1----0.9; p = NS). Average integrated backscatter across all transmural levels for infarct was significantly greater than for normal tissue (-48.3 +/- 0.5 vs -53.4 +/- 0.4 dB, infarct versus normal; p less than 0.05). The presence of fibrosis was associated with smaller values of n and greater integrated backscatter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bulk ablation of soft tissue with intense ultrasound: modeling and experiments

Methods for the bulk ablation of soft tissue using intense ultrasound, with potential applications in the thermal treatment of focal tumors, are presented. An approximate analytic model for bulk ablation predicts the progress of ablation based on tissue properties, spatially averaged ultrasonic heat deposition, and perfusion. The approximate model allows the prediction of threshold acoustic powers required for ablation in vivo as well as the comparison of cases with different starting temperatures and perfusion characteristics, such as typical in vivo and ex vivo experiments. In a full three-dimensional numerical model, heat deposition from array transducers is computed using the Fresnel approximation and heat transfer in tissue is computed by finite differences, accounting for heating changes caused by boiling and thermal dose-dependent absorption. Similar ablation trends due to perfusion effects are predicted by both the simple analytic model and the full numerical model. Comparisons with experimental results show the efficacy of both models in predicting tissue ablation effects. Phenomena illustrated by the simulations and experiments include power thresholds for in vivo ablation, differences between in vivo and ex vivo lesioning for comparable source conditions, the effect of tissue boiling and absorption changes on ablation depth, and the performance of a continuous rotational scanning method suitable for interstitial bulk ablation of soft tissue.     

Simultaneous estimation of attenuation and structure parameters of aggregated red blood cells from backscatter measurements

The analysis of the ultrasonic frequency-dependent backscatter coefficient of aggregating red blood cells reveals information about blood structural properties. The difficulty in applying this technique in vivo is due to the frequency-dependent attenuation caused by intervening tissue layers that distorts the spectral content of backscattering properties from blood microstructures. An optimization method is proposed to simultaneously estimate tissue attenuation and blood structure factor. With in vitro experiments, the method gave satisfactory estimates with relative errors below 22% for attenuations between 0.101 and 0.317 dBcmMHz, signal-to-noise ratios>28 dB and kR<2.7 (k being the wave number and R the aggregate radius).     

Time domain attenuation estimation method from ultrasonic backscattered signals

Ultrasonic attenuation is important not only as a parameter for characterizing tissue but also for compensating other parameters that are used to classify tissues. Several techniques have been explored for estimating ultrasonic attenuation from backscattered signals. In the present study, a technique is developed to estimate the local ultrasonic attenuation coefficient by analyzing the time domain backscattered signal. The proposed method incorporates an objective function that combines the diffraction pattern of the source/receiver with the attenuation slope in an integral equation. The technique was assessed through simulations and validated through experiments with a tissue mimicking phantom and fresh rabbit liver samples. The attenuation values estimated using the proposed technique were compared with the attenuation estimated using insertion loss measurements. For a data block size of 15 pulse lengths axially and 15 beamwidths laterally, the mean attenuation estimates from the tissue mimicking phantoms were within 10% of the estimates using insertion loss measurements. With a data block size of 20 pulse lengths axially and 20 beamwidths laterally, the error in the attenuation values estimated from the liver samples were within 10% of the attenuation values estimated from the insertion loss measurements.     

Determination of avocado and mango fruit properties by ultrasonic technique

A nondestructive ultrasonic measurement system was developed for the assessment of some transmission parameters which might have quantitative relations with the maturity, firmness and other quality-related properties of avocado and mango fruits. The system utilizes a set of low-frequency probes arranged to measure the ultrasonic signal transmitted and received over a short distance across the peel. The attenuation of the ultrasonic waves, transmitted through the peel and the attached fruit tissue, changes as a result of the progressive ripening and softening of the fruit during the fruiting season and in the course of storage. The present study quantitatively addressed the linkage between the ultrasonic attenuation and the physiological parameters of the flesh of the fruits. Results were obtained in the time and frequency domain, and the data set was analyzed statistically to identify the relations between the major physiological indices and the ultrasonic parameters. Quantitative relations were developed to describe the linkage between ultrasonic parameters and the maturity, firmness and other quality-related properties in mango and avocado fruits.     

A plane layered model to estimate in situ ultrasound exposures

Determination of in situ ultrasound exposures in experimental animals and patients is necessary to assess any potential hazard of ultrasound implied by reported biological effects in animals. A layered model was used to calculate total attenuation of ultrasound pulses as they passed through tissue layers to an organ site, thus enabling calculation of in situ intensities from free-field transducer emissions. The model assumes plane homogeneous layers of tissue of known thickness, attenuation and acoustic impedance. Calculations based on the model, compared with in situ measurements in a human cadaver specimen, were accurate to within approximately +/- 3 dB. We then calculated in situ clinical exposures using published obstetric B-scans. Total attenuation to the fetus averaged approximately 11 dB at 3.5 MHz.     

Ultrasound speed and attenuation in homogenates of bovine skeletal muscle

The attenuation and speed of ultrasound were measured in homogenates of post-rigor bovine skeletal muscle, and found to increase in proportion to the concentration of muscle. Extrapolation of the data to tissue concentrations yielded an attenuation of 7.5 dB cm-1 at pH 5.7, 20 degrees C and 7.3 MHz. This was close to that measured in the minced tissue, 8.3 dB cm-1, and between values previously recorded across and along the fibres of intact muscle. Corresponding measurements for the speed of ultrasound in homogenates, extrapolated to the native tissue concentration, were: 1555 +/- 9 m s-1 at 0 degree C, 1592 +/- 10 m s-1 at 20 degrees C and 1616 +/- 9 m s-1 at 37 degrees C. These were not significantly different from measurements of minced muscle at the same temperatures. Measurements of the attenuation of 7.3 MHz ultrasound in suspensions of myofibrils indicated that attenuation by the myofibrils caused at least 64% of the attenuation in muscle homogenates at pH 5.7. Re-analysis of the viscous loss arising from relative movement of the myofibrils in their surrounding fluid, indicated that this mechanism could account for no more than 15% of the attenuation in muscle homogenates. Attenuation due to scattering was calculated to be at least two orders of magnitude smaller than that observed in either homogenates or suspensions of myofibrils. It was concluded that the contribution of scattering to the attenuation was small, and that the attenuation was caused by processes involving an absorption of energy.(ABSTRACT TRUNCATED AT 250 WORDS)     

A theoretical comparison of attenuation measurement techniques from backscattered ultrasound echoes

Accurate characterization of tissue pathologies using ultrasonic attenuation is strongly dependent on the accuracy of the algorithm that is used to obtain the attenuation coefficient estimates. In this paper, computer simulations were used to compare the accuracy and the precision of the three methods that are commonly used to estimate the local ultrasonic attenuation within a region of interest (ROI) in tissue; namely, the spectral log difference method, the spectral difference method, and the hybrid method. The effects of the inhomgeneities within the ROI on the accuracy of the three algorithms were studied, and the optimal ROI size (the number of independent echoes laterally and the number of pulse lengths axially) was quantified for each method. The three algorithms were tested for when the ROI was homogeneous, the ROI had variations in scatterer number density, and the ROI had variations in effective scatterer size. The results showed that when the ROI was homogeneous, the spectral difference method had the highest accuracy and precision followed by the spectral log difference method and the hybrid method, respectively. Also, when the scatterer number density varied, the spectral difference method completely failed, while the log difference method and hybrid method still gave good results. Lastly, when the scatterer size varied, all of the methods failed.     

Time evolution of enhanced ultrasonic reflection using a fibrin-targeted nanoparticulate contrast agent

Complex molecular signaling heralds the early stages of pathologies such as angiogenesis, inflammation, unstable atherosclerotic plaques, and areas of remote thrombi. In previous studies, acoustic enhancement of blood clot morphology was demonstrated with the use of a nongaseous, fibrin-targeted acoustic nanoparticle emulsion delivered to areas of thrombosis both in vitro and in vivo. In this study, a system was designed and constructed that allows visualization of the evolution of acoustic contrast enhancement. To evaluate the system, two targets were examined: avidin-complexed nitrocellulose membrane and human plasma clots. The time evolution of enhancement was visualized in 10-min increments for 1 h. A monotonic increase was observed in ultrasonic reflection enhancement from specially treated nitrocellulose membranes for targeted emulsions containing perfluorooctylbromide (1.30+/-0.3 dB) and for perfluorooctane (2.64+/-0.5 dB) within the first 60 min of imaging. In comparison, the inherently nonechogenic plasma clots showed a substantial increase of 12.0+/-0.9 dB when targeted with a perfluoro-octane emulsion. This study demonstrates the concept of molecular imaging and provides the first quantifiable time-evolution report of the binding of a site-targeted ultrasonic contrast agent. Moreover, with the incorporation of specific drug treatments into the nanoparticulate contrast agent, ultrasonic molecular imaging may yield reliable detection and quantification of nascent pathologies and facilitate targeted drug therapy.     

Ultrasonic attenuation estimation in-vivo using the difference ratio correction method.

In recent years, B scanners have been widely used clinically. Obviously, it is of particular importance to use the commercial B scanners to characterize tissue by estimating its ultrasonic attenuation in vivo. However, there are a lot of difficulties in doing so because the output of a B scanner is affected by many unknown factors. In this paper, a time domain method named the difference ratio correction (DRC) method is proposed to estimate the ultrasonic attenuation of tissue in vivo. In this method, three tissue-mimicking phantoms with known acoustical properties were employed to eliminate the instrumentation errors of the B scanner and the measuring system and to correct beam diffraction for correct attenuation estimation. Other advantages of this method are that it is very convenient to apply this method clinically and there is no need to change the inner construction of the B scanner because this method only utilizes the video output. Experimental and clinical results have proved the validity of this method.     

Model-based PRFS thermometry using fat as the internal reference and the extended Prony algorithm for model fitting

A model-based proton resonance frequency shift (PRFS) thermometry method was developed to significantly reduce the temperature quantification errors encountered in the conventional phase mapping method and the spatiotemporal limitations of the spectroscopic thermometry method. Spectral data acquired using multi-echo gradient echo (GRE) is fit into a two-component signal model containing temperature information and fat is used as the internal reference. The noniterative extended Prony algorithm is used for the signal fitting and frequency estimate. Monte Carlo simulations demonstrate the advantages of the method for optimal water-fat separation and temperature estimation accuracy. Phantom experiments demonstrate that the model-based method effectively reduces the interscan motion effects and frequency disturbances due to the main field drift. The thermometry result of ex vivo goose liver experiment with high intensity focused ultrasound (HIFU) heating was also presented in the paper to indicate the feasibility of the model-based method in real tissue.     

Ultrasonic propagation properties (@ 100 MHz) in excessively fatty rat liver

The effects on the ultrasonic propagation properties of livers of the addition of 1% orotic acid to rat diets were examined. In rats, dietary orotic acid exerts several effects on lipid metabolism; its overall consequence is that excessively high hepatic fat concentrations are built up over a short period of time, thus making this an ideal model to study the ultrasonic propagation properties as a function of sequential development of fatty liver. Over a 16-day period on the orotic acid diet, the supplemented rat liver lipid concentrations increased from a normal range of 2%-4% to the lower 20's%; hepatic water concentration decreased from a normal value of approximately 70% to approximately 50%; total protein concentration decreased slightly from a normal range of 17%-20% to 11%-16%; and rat liver weight increased from approximately 11 g to around 20 g. Ultrasonic attenuation coefficient and speed were assessed in liver tissue with the scanning laser acoustic microscope at 100 MHz. As hepatic lipid increased, ultrasonic attenuation at 100 MHz increased temporally from a normal range of 12-14 dB/mm to a maximum of 54 dB/mm and ultrasonic speed decreased from a normal range of 1553-1584 m/s to a minimum of 1507 m/s. Multivariant linear regression was used in the analysis of covariance to fit the least-squares estimates to the linear regression model. Strong correlates of ultrasonic speed with both water concentration and fat concentration in the liver were observed.     

Shaping the Wavefront of Incident Light with a Strong Robustness Particle Swarm Optimization Algorithm

We demonstrate a modified particle swarm optimization(PSO) algorithm to effectively shape the incident light with strong robustness and short optimization time. The performance of the modified PSO algorithm and genetic algorithm(GA) is numerically simulated. Then, using a high speed digital micromirror device, we carry out light focusing experiments with the modified PSO algorithm and GA. The experimental results show that the modified PSO algorithm has greater robustness and faster convergence speed than GA. This modified PSO algorithm has great application prospects in optical focusing and imaging inside in vivo biological tissue, which possesses a complicated background.