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Quantitative ultrasound estimates based on the backscatter coefficient (BSC) have demonstrated the ability to detect and classify disease beyond the capabilities of traditional B-mode imaging. Quantitative ultrasound has been able to differentiate live from apoptotic cells or oncotic cells in vitro with high-frequency ultrasound,1,2 monitor changes in tissue microstructure due to high-intensity focused ultrasound at high frequencies in a preclinical model,3 and monitor changes due to chemotherapy clinically at 6 MHz.4 Tumors have been characterized and differentiated using quantitative ultrasound at high frequencies in preclinical models of thyroid cancer,5 at high frequencies in clinical applications for ocular tumors,6,7 and at clinical frequencies in human patients for breast tumors8 and prostate cancers.9,10 Also, the BSC has been proven valuable for diagnosing fatty liver disease clinically11 and for monitoring physiologic and pharmacologic responses in renal function at clinical frequencies in an animal model.12,13 One of the BSC features that is often cited as an advantage is its system independence; ie, the same BSC value for a given tissue can be estimated from any imaging platform. Previous studies have demonstrated system independence of BSC estimates in well-characterized phantoms.14–17 These investigations applied single-element imaging systems measuring backscatter levels for strong glass bead scatterer phantoms (1–12 MHz),14,15 single-element imaging systems for probing weakly scattering agar-in-agar phantoms (1–13 MHz),16 and clinical array imaging systems for estimating BSC for phantoms with glass bead scatterers (1–15 MHz).17 Parametric estimates based on the BSC have demonstrated the ability to differentiate different types of orthotopic mouse tumors ex vivo (16–24 MHz),18 to identify regions of micrometastases within resected lymph nodes clinically (26.5 MHz center),19 and to identify dominant sources of backscattering in the renal cortex (frequencies covering 2.5–15 MHz).12,13,20,21 The frequency ranges in these studies cover the range being investigated in this study: namely, from the clinical frequencies to the lower end of the small-animal pre-clinical imaging frequencies, covering, for example, 1 to 21 MHz. This study addresses the need for demonstrating that in vivo interlaboratory measurements can be used to distinguish different types of tumors, while being able to obtain consistent BSC results from all systems. Previous studies22,23 examined BSC agreement across single-element and clinical imaging systems for an in vivo rodent fibroadenoma model over a frequency range of 1 to 14 MHz. The heterogeneity of the benign fibroadenomas provided a near worst-case scenario to evaluate quantitative ultrasound performance. The study presented herein seeks to expand on this work using clinical and preclinical array imaging systems to test their capability to detect known tissue differences while maintaining good agreement in BSC values across all systems. Mouse (4T1) and rat (MAT) mammary tumor models were used in a comparative experiment with 3 array-based ultrasound imaging systems (Siemens, Ultrasonix, and VisualSonics) and 5 different transducers covering a range of frequency bandwidths. Backscatter coefficient agreement between systems was assessed, as well as the ability to differentiate the two tumor types.

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.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.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 x 10(-5) cm(-1)Sr(-1) and an average BSC value of 7.1 x 10(-4) cm(-1)Sr(-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 x 10(-1) cm(-1)Sr(-1) and an average BSC value of 3.5 x 10(-2) cm(-1)Sr(-1), or approximately 300% error.This technical advance shows the potential for QUS technology to function with different imaging platforms.

Objective Estimates of ultrasonic attenuation (the loss of energy as an ultrasonic wave propagates through tissue) have been used to evaluate the structure and function of tissues in health and disease. The purpose of this research was to develop a method to estimate ultrasonic cervical attenuation during human pregnancy using a clinical ultrasound system. Methods Forty women underwent a cervical scan once during pregnancy with the Zonare® z.one clinical ultrasound system using a 4–9-MHz endovaginal transducer. This ultrasound system provides access to radiofrequency (RF) image data for processing and analysis. In addition, a scan of a tissue-mimicking phantom with a known attenuation coefficient was acquired and used as a reference. The same settings and transducer used in the clinical scan were used in the reference scan. Digital data of the beam-formed image were saved in Digital Imaging and Communications in Medicine (DICOM) format on a flash drive and converted to RF data on a personal computer using a Matlab® program supplied by Zonare. Attenuation estimates were obtained using an algorithm that was independently validated using tissue-mimicking ultrasonic phantoms. Results RF data were acquired and analyzed to estimate attenuation of the human pregnant cervix. Regression analysis revealed that attenuation was: a predictor of the interval from ultrasound examination to delivery (β = 0.43, P = 0.01); not a predictor of gestational age at time of examination (β = − 0.23, P = 0.15); and not a predictor of cervical length (β = 0.077, P = 0.65). Conclusions Ultrasonic attenuation estimates have the potential to be an early and objective non-invasive method to detect interval between examination and delivery. We hypothesize that a larger sample size and a longitudinal study design will be needed to detect gestational age-associated changes in cervical attenuation. Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.

OBJECTIVE The purpose of this research was to detect cervical ripening with a new quantitative ultrasound technique. METHODS Cervices of 13 nonpregnant and 65 timed pregnant (days 15, 17, 19, 20, and 21 of pregnancy) Sprague Dawley rats were scanned ex vivo with a 70-MHz ultrasound transducer. Ultrasound scatterer property estimates (scatterer diameter [SD], acoustic concentration [AC], and scatterer strength factor [SSF]) from the cervices were quantified and then compared to hydroxyproline and water content. Insertion loss (attenuation) was measured in 3 rats in each of the 6 groups. Discriminant analysis was used to predict gestational age group (cervical ripening) from the ultrasound variables SD, SSF, and AC. RESULTS Differences were observed between the groups (SD, AC, and SSF; P < .0001). Quantitative ultrasound measures changed as the cervix ripened: (1) SD increased from days 15 to 21; (2) AC decreased from days 15 to 21; and (3) SSF was the greatest in the nonpregnant group and the least in the day 21 group. Cervix hydroxyproline content increased as pregnancy progressed (P < .003) and correlated with group, SD, AC, and SSF (P < .001). Discriminant analysis of ultrasound variables predicted 56.4% of gestational group assignment (P < .001) and increased to 77% within 2 days of the predicted analysis. Cervix insertion loss was greatest for the nonpregnant group and least for the day 21 group. CONCLUSIONS Quantitative ultrasound predicted cervical ripening in the rat cervix, but before use in humans, quantitative ultrasound will need to predict gestational age in the later days of gestation with more precision.

Objective As are the attenuation coefficient and sound speed, the backscatter coefficient is a fundamental ultrasonic property that has been used to characterize many tissues. Unfortunately, there is currently far less standardization for the ultrasonic backscatter measurement than for the other two, as evidenced by a previous American Institute of Ultrasound in Medicine (AIUM)-sponsored interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements (J Ultrasound Med 1999; 18:615-631). To explore reasons for these disparities, the AIUM Endowment for Education and Research recently supported this second interlaboratory comparison, which extends the upper limit of the frequency range from 7 to 9 MHz. Methods Eleven laboratories were provided with standard test objects designed and manufactured at the University of Wisconsin (Madison, WI). Each laboratory was asked to perform ultrasonic measurements of sound speed, attenuation coefficients, and backscatter coefficients. Each laboratory was blinded to the values of the ultrasonic properties of the test objects at the time the measurements were performed. Results Eight of the 11 laboratories submitted results. The range of variation of absolute magnitude of backscatter coefficient measurements was about 2 orders of magnitude. If the results of 1 outlier laboratory are excluded, then the range is reduced to about 1 order of magnitude. Agreement regarding frequency dependence of backscatter was better than reported in the previous interlaboratory comparison. For example, when scatterers were small compared with the ultrasonic wavelength, experimental frequency-dependent backscatter coefficient data obtained by the participating laboratories were usually consistent with the expected Rayleigh scattering behavior (proportional to frequency to the fourth power). Conclusions Greater standardization of backscatter measurement methods is needed. Measurements of frequency dependence of backscatter are more consistent than measurements of absolute magnitude.

The measurement of the roughness of soil surfaces on centimeter scales is important to modeling local soil erodibility. An acoustic backscatter technique was examined for its ability to quantify the roughness of porous soil on centimeter scales. Acoustic backscatter offers the possibility of an inexpensive, mobile, and rapid means of estimating statistical properties of soil surfaces. Four soil plots were constructed with varying amounts of roughness. Surface roughness of the four soil plots was measured with the acoustic backscatter technique and a laser microreliefmeter. The roughness power spectra for the surface plots were obtained from surface profiles measured by the laser microreliefmeter and by the acoustic backscatter technique. Statistical values of the RMS (root mean square) height and correlation length of surface roughness for each plot were calculated from the acoustic backscatter power spectra and laser microreliefmeter power spectra and compared. Agreement between the two techniques for estimating roughness statistics was shown to be good (

Objective. To estimate the average scatterer properties from ultrasonic backscatter in tissues for evaluating differences between neoplastic and healthy tissues. Methods. Parametric images of 8 retired breeder rats in which spontaneous mammary tumors had developed were created by superimposing color-coded pixels related to the estimated average scatterer properties on conventional gray scale B-mode images. Results. The images showed a distinct difference between the tumors and surrounding healthy tissues. Analysis of the average scatterer diameters and acoustic concentrations showed a statistically significant difference (P

The potential application of this work is the detection and imaging of buried objects using acoustic methodology. To image buried artifacts, it is vital to know speed and attenuation of sound in the particular soil being examined because they vary in different soil types and at different moisture contents. To that end, our research involved six soils representing a range of properties expected to influence acoustic response. Clay ranged from 2 to 38%, silt from 1 to 82%, sand from 2 to 97%, and organic matter from 0.1 to 11.7%. Signals from an acoustic source were passed through soil samples and detected by an acoustically coupled hydrophone. From a total of 231 evaluations, we determined the acoustic attenuation coefficient and the propagation speed of sound in the soil samples as a function of four levels of soil moisture and two levels of compaction. Attenuation coefficients determined over frequencies of 2 to 6 kHz ranged from 0.12 to 0.96 dB cm -1 kHz -1 . Lower attenuation tended to be in loose dry samples. Correlation coefficients were 0.35 (P = 0.01) and 0.31 (P = 0.03) between attenuation and soil water content and soil bulk density, respectively. Propagation speeds ranged from 86 to 260 m s -1 . The correlation coefficient with speed was -0.28 (P = 0.05) for soil water content and -0.42 (P = 0.002) for total porosity. Given the acoustic properties, it is theoretically possible to detect an object down to ∼40 cm below the soil surface.

A reliable means of detecting metastases in lymph nodes is essential for accurate staging of cancer and effective planning of therapy. The standard means of detecting metastases in nodes is histopathologic evaluation of surgically dissected nodes; however, because examinations tend to be limited to thin sections derived from the center of the node, this time‐consuming procedure appears to have high false‐negative rates for metastases that are 2 mm or smaller. We have been investigating high‐frequency (HF) quantitative ultrasound (QUS) methods as a more‐effective means of providing a rapid and reliable detection of metastases in dissected nodes based on their ultrasound‐scattering properties. We acquired HF ultrasound and histological data from dissected lymph nodes of patients with colorectal, gastric, breast, and other cancers. Freshly dissected nodes were scanned in a saline bath using a raster pattern to acquire 3D RF echo‐signal data. Scans utilized a broadband, F‐2, 25.6‐MHz, single‐element transducer with scan vectors separated by 25 μm in X and Y directions. Scanned nodes were color inked to provide references for subsequent orientation, then fixed and serially‐sectioned in their entire volume at 50‐μm intervals. The presence of metastatic foci was determined histologically in every section; evaluation of node status in the center section provided a basis for comparison with conventional methods. To date, we have analyzed the echo signals of more than 240 nodes including abdominal nodes of colorectal and gastric cancer patients and axillary nodes of breast‐cancer patients. 3D images generated from RF data were segmented semi‐automatically to select nodal tissue for analysis. Echo signals from nodal tissue were processed to yield QUS estimates, which included spectral parameters, scatterer‐property estimates, and B‐mode envelope‐signal statistical features. Different histological node architectures were observed and different QUS results were obtained for abdominal compared to axillary nodes. Linear discriminant analysis and ROC‐curve methods were applied to assess the ability of QUS estimates to distinguish cancerous from non‐cancerous nodes. Classification performance was assessed for individual estimates and various linear combinations of estimates. ROC results for axillary as well as abdominal nodes showed excellent classification. For abdominal nodes, the best area under the ROC curve exceeded 0.95. For axillary nodes, the best area approached 0.90. Images based on QUS parameters showed an excellent ability to depict metastatic foci. Results to date strongly suggest that HF QUS methods may provide a clinically valuable means of detecting small metastatic cancers in dissected lymph nodes and significantly improving the sensitivity for metastases that might not be detected using current, standard histopathology procedures. The ability of HF QUS to reveal otherwise missed metastases will enable pathologists to more‐ efficiently focus histological effort on regions of nodes that have a high suspicion of containing cancer and minimizing wasted time evaluating actually cancer‐free nodes. Future studies will investigate the applicability of these methods to detection of nodal metastases in situ.

Purpose: Previous studies have provided the observation that the ultrasonic backscattered energy from a tissue region will change due to a change of temperature. The mechanism responsible for the changes in backscattered energy (CBE) with temperature has been hypothesized to be from the changes in scattering properties of local aqueous and lipid scatterers. An alternative mechanism is hypothesized here to be capable of producing similar CBE curves, i.e., changes in speckle resulting from changes in summation of scattered wavelets. Methods: Both simulations and experiments were conducted with a 5.5 MHz, 128-element linear array and synthetic and physical phantoms containing randomly spaced scatterers. The speckle pattern resulting from summation of scattered wavelets was changed in simulations and experiments by directly increasing the background sound speed from 1520 to 1540 m/s, and changing the temperature from 37 °C to 48 °C, respectively. Shifts in the backscattered signal were compensated using 2D cross-correlation techniques. Results: Excellent agreement between simulations and experiments was observed, with each pixel in the CBE images on average undergoing either a monotonic increase (up to 3.2 dB) or a monotonic decrease (down to −1.9 dB) with increasing sound speed or temperature. Similar CBE curves were also produced by shifting the image plane in the elevational and axial directions even after correcting for apparent motion. Conclusions: CBE curves were produced by changing the sound speed or temperature in tissue mimicking phantoms or by shifting the image plane in the elevational and axial directions and the production of these CBE curves did not require the presence of lipid and aqueous scatterers.