First-in-human imaging using a MR-compatible e4D ultrasound probe for motion management of radiotherapy.

PURPOSE: Respiration-induced tumor or organ positional changes can impact the accuracy of external beam radiotherapy. Motion management strategies are used to account for these changes during treatment. The authors report on the development, testing, and first-in-human evaluation of an electronic 4D (e4D) MR-compatible ultrasound probe that was designed for hands-free operation in a MR and linear accelerator (LINAC) environment. METHODS: Ultrasound components were evaluated for MR compatibility. Electromagnetic interference (EMI) shielding was used to enclose the entire probe and a factory-fabricated cable shielded with copper braids was integrated into the probe. A series of simultaneous ultrasound and MR scans were acquired and analyzed in five healthy volunteers. RESULTS: The ultrasound probe led to minor susceptibility artifacts in the MR images immediately proximal to the ultrasound probe at a depth of <10 mm. Ultrasound and MR-based motion traces that were derived by tracking the salient motion of endogenous target structures in the superior-inferior (SI) direction demonstrated good concordance (Pearson correlation coefficients of 0.95-0.98) between the ultrasound and MRI datasets. CONCLUSION: We have demonstrated that our hands-free, e4D probe can acquire ultrasound images during a MR acquisition at frame rates of approximately 4 frames per second (fps) without impacting either the MR or ultrasound image quality. This use of this technology for interventional procedures (e.g. biopsies and drug delivery) and motion compensation during imaging are also being explored.

Effects of ultrasound technology advances on measurement of carotid intima-media thickness: A review.

In this review, we describe how technological advances in ultrasound imaging related to transducer construction and image processing fundamentally alter generation of ultrasound images to produce better quality images with higher resolution. However, carotid intima-media thickness (IMT) measurements made from images acquired on modern ultrasound systems are not comparable to historical population nomograms that were used to determine wall thickness thresholds that inform atherosclerotic cardiovascular disease risk. Because it is nearly impossible to replicate instrumentation settings that were used to create the reference carotid IMT nomograms and to place an individual's carotid IMT value in or above a clinically relevant percentile, carotid IMT measurements have a very limited role in clinical medicine, but remain a useful research tool when instrumentation, presets, image acquisition, and measurements can be standardized. In addition to new validation studies, it would be useful for the ultrasound imaging community to reach a consensus regarding technical aspects of ultrasound imaging acquisition, processing, and display for blood vessels so standard presets and imaging approaches could reliably yield the same measurements.

Three-dimensional US for Quantification of Volumetric Blood Flow: Multisite Multisystem Results from within the Quantitative Imaging Biomarkers Alliance.

Background Quantitative blood flow (QBF) measurements that use pulsed-wave US rely on difficult-to-meet conditions. Imaging biomarkers need to be quantitative and user and machine independent. Surrogate markers (eg, resistive index) fail to quantify actual volumetric flow. Standardization is possible, but relies on collaboration between users, manufacturers, and the U.S. Food and Drug Administration. Purpose To evaluate a Quantitative Imaging Biomarkers Alliance-supported, user- and machine-independent US method for quantitatively measuring QBF. Materials and Methods In this prospective study (March 2017 to March 2019), three different clinical US scanners were used to benchmark QBF in a calibrated flow phantom at three different laboratories each. Testing conditions involved changes in flow rate (1-12 mL/sec), imaging depth (2.5-7 cm), color flow gain (0%-100%), and flow past a stenosis. Each condition was performed under constant and pulsatile flow at 60 beats per minute, thus yielding eight distinct testing conditions. QBF was computed from three-dimensional color flow velocity, power, and scan geometry by using Gauss theorem. Statistical analysis was performed between systems and between laboratories. Systems and laboratories were anonymized when reporting results. Results For systems 1, 2, and 3, flow rate for constant and pulsatile flow was measured, respectively, with biases of 3.5% and 24.9%, 3.0% and 2.1%, and -22.1% and -10.9%. Coefficients of variation were 6.9% and 7.7%, 3.3% and 8.2%, and 9.6% and 17.3%, respectively. For changes in imaging depth, biases were 3.7% and 27.2%, -2.0% and -0.9%, and -22.8% and -5.9%, respectively. Respective coefficients of variation were 10.0% and 9.2%, 4.6% and 6.9%, and 10.1% and 11.6%. For changes in color flow gain, biases after filling the lumen with color pixels were 6.3% and 18.5%, 8.5% and 9.0%, and 16.6% and 6.2%, respectively. Respective coefficients of variation were 10.8% and 4.3%, 7.3% and 6.7%, and 6.7% and 5.3%. Poststenotic flow biases were 1.8% and 31.2%, 5.7% and -3.1%, and -18.3% and -18.2%, respectively. Conclusion Interlaboratory bias and variation of US-derived quantitative blood flow indicated its potential to become a clinical biomarker for the blood supply to end organs. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Forsberg in this issue.

Optimization of Ultrasound Backscatter Spectroscopy to Assess Neurotoxic Effects of Anesthesia in the Newborn Non-human Primate Brain.

Studies in animal models have revealed that long exposures to anesthetics can induce apoptosis in the newborn and young developing brain. These effects have not been confirmed in humans because of the lack of a non-invasive, practical in vivo imaging tool with the ability to detect these changes. Following the successful use of ultrasound backscatter spectroscopy (UBS) to monitor in vivo cell death in breast tumors, we aimed to use UBS to assess the neurotoxicity of the anesthetic sevoflurane (SEVO) in a non-human primate (NHP) model. Sixteen 2- to 7-day-old rhesus macaques were exposed for 5 h to SEVO. Ultrasound scanning was done with a phased array transducer on a clinical ultrasound scanner operated at 10 MHz. Data consisting of 10-15 frames of radiofrequency (RF) echo signals from coronal views of the thalamus were obtained 0.5 and 6.0 h after initiating exposure. The UBS parameter "effective scatterer size" (ESS) was estimated by fitting a scattering form factor (FF) model to the FF measured from RF echo signals. The approach involved analyzing the frequency dependence of the measured FF to characterize scattering sources and selecting the FF model based on a χ2 goodness-of-fit criterion. To assess data quality, a rigorous acceptance criterion based on the analysis of prevalence of diffuse scattering (an assumption in the estimation of ESS) was established. ESS changes after exposure to SEVO were compared with changes in a control group of five primates for which ultrasound data were acquired at 0 and 10 min (no apoptosis expected). Over the entire data set, the average measured FF at 0.5 and 6.0 h monotonically decreased with frequency, justifying fitting a single FF over the analysis bandwidth. χ2 values of a (inhomogeneous continuum) Gaussian FF model were one-fifth those of the discrete fluid sphere model, suggesting that a continuum scatterer model better represents ultrasound scattering in the young rhesus brain. After application of the data quality criterion, only 5 of 16 subjects from the apoptotic group and 5 of 5 subjects from the control group fulfilled the acceptance criteria. All subjects in the apoptotic group that passed the acceptance criterion exhibited a significant ESS reduction at 6.0 h. These changes (-6.4%, 95% Interquartile Range: -14.3% to -3.3%) were larger than those in the control group (-0.8%, 95% Interquartile Range: -2.0% to 1.5%]). Data with a low prevalence of diffuse scattering corresponded to possibly biased results. Thus, ESS has the potential to detect changes in brain microstructure related to anesthesia-induced apoptosis.

A Quantitative Ultrasound-Based Multi-Parameter Classifier for Breast Masses.

This manuscript reports preliminary results obtained by combining estimates of two or three (among seven) quantitative ultrasound (QUS) parameters in a model-free, multi-parameter classifier to differentiate breast carcinomas from fibroadenomas (the most common benign solid tumor). Forty-three patients scheduled for core biopsy of a suspicious breast mass were recruited. Radiofrequency echo signal data were acquired using clinical breast ultrasound systems equipped with linear array transducers. The reference phantom method was used to obtain system-independent estimates of the specific attenuation (ATT), the average backscatter coefficients, the effective scatterer diameter (ESD) and an effective scatterer diameter heterogeneity index (ESDHI) over regions of interest within each mass. In addition, the envelope amplitude signal-to-noise ratio (SNR), the Nakagami shape parameter, m, and the maximum collapsed average (maxCA) of the generalized spectrum were also computed. Classification was performed using the minimum Mahalanobis distance to the centroids of the training classes and tested against biopsy results. Classification performance was evaluated with the area under the receiver operating characteristic (ROC) curve. The best performance with a two-parameter classifier used the ESD and ESDHI and resulted in an area under the ROC curve of 0.98 (95% confidence interval [CI]: 0.95-1.00). Classification performance improved with three parameters (ATT, ESD and ESDHI) yielding an area under the ROC curve of 0.999 (0.995-1.000). These results suggest that system-independent QUS parameters, when combined in a model-free classifier, are a promising tool to characterize breast tumors. A larger study is needed to further test this idea.

Quantitative ultrasound and apoptotic death in the neonatal primate brain.

Apoptosis is triggered in the developing mammalian brain by sedative, anesthetic or antiepileptic drugs during late gestation and early life. Whether human children are vulnerable to this toxicity mechanism remains unknown, as there are no imaging techniques to capture it. Apoptosis is characterized by distinct structural features, which affect the way damaged tissue scatters ultrasound compared to healthy tissue. We evaluated whether apoptosis, triggered by the anesthetic sevoflurane in the brains of neonatal rhesus macaques, can be detected using quantitative ultrasound (QUS). Neonatal (n = 15) rhesus macaques underwent 5 h of sevoflurane anesthesia. QUS images were obtained through the sagittal suture at 0.5 and 6 h. Brains were collected at 8 h and examined immunohistochemically to analyze apoptotic neuronal and oligodendroglial death. Significant apoptosis was detected in white and gray matter throughout the brain, including the thalamus. We measured a change in the effective scatterer size (ESS), a QUS biomarker derived from ultrasound echo signals obtained with clinical scanners, after sevoflurane-anesthesia in the thalamus. Although initial inclusion of all measurements did not reveal a significant correlation, when outliers were excluded, the change in the ESS between the pre- and post-anesthesia measurements correlated strongly and proportionally with the severity of apoptotic death. We report for the first time in vivo changes in QUS parameters, which may reflect severity of apoptosis in the brains of infant nonhuman primates. These findings suggest that QUS may enable in vivo studies of apoptosis in the brains of human infants following exposure to anesthetics, antiepileptics and other brain injury mechanisms.

Accuracy of Liver Fat Quantification With Advanced CT, MRI, and Ultrasound Techniques: Prospective Comparison With MR Spectroscopy.

OBJECTIVE: The purpose of this study was to prospectively evaluate the accuracy of proton-density fat-fraction, single- and dual-energy CT (SECT and DECT), gray-scale ultrasound (US), and US shear-wave elastography (US-SWE) in the quantification of hepatic steatosis with MR spectroscopy (MRS) as the reference standard. SUBJECTS AND METHODS: Fifty adults who did not have symptoms (23 men, 27 women; mean age, 57 ± 5 years; body mass index, 27 ± 5) underwent liver imaging with un-enhanced SECT, DECT, gray-scale US, US-SWE, proton-density fat-fraction MRI, and MRS for this prospective trial. MRS voxels for the reference standard were colocalized with all other modalities under investigation. For SECT (120 kVp), attenuation values were recorded. For rapid-switching DECT (80/140 kVp), monochromatic images (70-140 keV) and fat density-derived material decomposition images were reconstructed. For proton-density fat fraction MRI, a quantitative chemical shift-encoded method was used. For US, echogenicity was evaluated on a qualitative 0-3 scale. Quantitative US shear-wave velocities were also recorded. Data were analyzed by linear regression for each technique compared with MRS. RESULTS: There was excellent correlation between MRS and both proton-density fat-fraction MRI (r2 = 0.992; slope, 0.974; intercept, -0.943) and SECT (r2 = 0.856; slope, -0.559; intercept, 35.418). DECT fat attenuation had moderate correlation with MRS measurements (r2 = 0.423; slope, 0.034; intercept, 8.459). There was good correlation between qualitative US echogenicity and MRS measurements with a weighted kappa value of 0.82. US-SWE velocity did not have reliable correlation with MRS measurements (r2 = 0.004; slope, 0.069; intercept, 6.168). CONCLUSION: Quantitative MRI proton-density fat fraction and SECT fat attenuation have excellent linear correlation with MRS measurements and can serve as accurate noninvasive biomarkers for quantifying steatosis. Material decomposition with DECT does not improve the accuracy of fat quantification over conventional SECT attenuation. US-SWE has poor accuracy for liver fat quantification.

Post-Procedure Evaluation of Microwave Ablations of Hepatocellular Carcinomas Using Electrode Displacement Elastography.

Microwave ablation has been used clinically as an alternative to surgical resection. However, lack of real-time imaging to assess treated regions may compromise treatment outcomes. We previously introduced electrode displacement elastography (EDE) for strain imaging and verified its feasibility in vivo on porcine animal models. In this study, we evaluated EDE on 44 patients diagnosed with hepatocellular carcinoma, treated using microwave ablation. The ablated region was identified on EDE images for 40 of the 44 patients. Ablation areas averaged 13.38 ± 4.99 cm2 on EDE, compared with 7.61 ± 3.21 cm2 on B-mode imaging. Contrast and contrast-to-noise ratios obtained with EDE were 232% and 98%, respectively, significantly higher than values measured on B-mode images (p < 0.001). This study indicates that EDE is feasible in patients and provides improved visualization of the ablation zone compared with B-mode ultrasound.

Analysis of Coherent and Diffuse Scattering Using a Reference Phantom.

The estimation of many spectral-based quantitative ultrasound parameters assumes that backscattered echo signals are from a stationary, incoherent scattering process. The accuracy of these assumptions in real tissue can limit the diagnostic value of these parameters and the physical insight about tissue microstructure they can convey. This work presents an empirical decision test to determine the presence of significant coherent contributions to echo signals and whether they are caused by low scatterer number densities or the presence of specular reflectors or scatterers with periodic spacing. This is achieved by computing parameters from echo signals that quantify stationary or nonstationary features related to coherent scattering, and then comparing their values to thresholds determined from a reference material providing diffuse scattering. The paper first presents a number of parameters with demonstrated sensitivity to coherent scattering and describes criteria to select those with the highest sensitivity using simulated and phantom-based echo data. Results showed that the echo amplitude signal-to-noise ratio and the multitaper-generalized spectrum were the parameters with the highest sensitivity to coherent scattering with stationary and nonstationary features, respectively. These parameters were incorporated into the reference-based decision test, which successfully identified regions in simulated and tissue-mimicking phantoms with different incoherent and coherent scattering conditions. When scatterers with periodic organization were detected, the combination of stationary and nonstationary analysis permitted the estimation of the mean spacing below and above the resolution limit imposed by the pulse size. Preliminary applications of this algorithm to human cervical tissue ex vivo showed correspondence between regions of B-mode images showing bright reflectors, tissue interfaces, and hypoechoic regions with regions classified as specular reflectors and low scatterer number density. These results encourage further application of the algorithm to more structurally complex phantoms and tissue.

Acoustic Properties of Breast Fat.

OBJECTIVES: The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) atlas for ultrasound (US) qualitatively describes the echogenicity and attenuation of a mass, where fat lobules serve as a standard for comparison. This study aimed to estimate acoustic properties of breast fat under clinical imaging conditions to determine the degree to which properties vary among patients. METHODS: Twenty-four women with solid breast masses scheduled for biopsy were scanned with a Siemens S2000 scanner and 18L6 linear array transducer (Siemens Medical Solutions, Malvern, PA). Offline analysis estimated the attenuation coefficient and backscatter coefficients (BSCs) from breast fat using the reference phantom method. The average BSC was calculated over 6 to 12 MHz to objectively quantify the BI-RADS US echo pattern descriptor, and effective scatterer diameters were also estimated. RESULTS: A power law fit to the attenuation coefficient versus frequency yielded an attenuation coefficient of 1.28 dB·cm(-1) MHz(-0.73). The mean attenuation coefficient versus frequency slope ± SD at 7 MHz was 0.73 ± 0.23 dB·cm(-1) MHz(-1), in agreement with previously reported values. The BSC versus frequency showed close agreement among all patients, both in magnitude and frequency dependence, with a power law fit of (0.6 ± 0.25) ×10(-4) sr(-1) cm(-1) MHz(-2.49). The average backscatter in the 6-12-MHz range was 0.004 ± 0.002 sr(-1) cm(-1). The mean effective scatterer diameter for fat was 60.2 ± 9.5 µm. CONCLUSIONS: The agreement in parameter estimates for breast fat among these patients supports the use of fat as a standard for comparison with tumors. Results also suggest that objective quantification of these BI-RADS US descriptors may reduce subjectivity when interpreting B-mode image data.

Quantitative Ultrasound Comparison of MAT and 4T1 Mammary Tumors in Mice and Rats Across Multiple Imaging Systems.

OBJECTIVES: Quantitative ultrasound estimates such as the frequency-dependent backscatter coefficient (BSC) have the potential to enhance noninvasive tissue characterization and to identify tumors better than traditional B-mode imaging. Thus, investigating system independence of BSC estimates from multiple imaging platforms is important for assessing their capabilities to detect tissue differences. METHODS: Mouse and rat mammary tumor models, 4T1 and MAT, respectively, were used in a comparative experiment using 3 imaging systems (Siemens, Ultrasonix, and VisualSonics) with 5 different transducers covering a range of ultrasonic frequencies. RESULTS: Functional analysis of variance of the MAT and 4T1 BSC-versus-frequency curves revealed statistically significant differences between the two tumor types. Variations also were found among results from different transducers, attributable to frequency range effects. At 3 to 8 MHz, tumor BSC functions using different systems showed no differences between tumor type, but at 10 to 20 MHz, there were differences between 4T1 and MAT tumors. Fitting an average spline model to the combined BSC estimates (3-22 MHz) demonstrated that the BSC differences between tumors increased with increasing frequency, with the greatest separation above 15 MHz. Confining the analysis to larger tumors resulted in better discrimination over a wider bandwidth. CONCLUSIONS: Confining the comparison to higher ultrasonic frequencies or larger tumor sizes allowed for separation of BSC-versus-frequency curves from 4T1 and MAT tumors. These constraints ensure that a greater fraction of the backscattered signals originated from within the tumor, thus demonstrating that statistically significant tumor differences were detected.

Task-oriented comparison of power spectral density estimation methods for quantifying acoustic attenuation in diagnostic ultrasound using a reference phantom method.

Reported here is a phantom-based comparison of methods for determining the power spectral density (PSD) of ultrasound backscattered signals. Those power spectral density values are then used to estimate parameters describing α(f), the frequency dependence of the acoustic attenuation coefficient. Phantoms were scanned with a clinical system equipped with a research interface to obtain radiofrequency echo data. Attenuation, modeled as a power law α(f)= α0 f (ß), was estimated using a reference phantom method. The power spectral density was estimated using the short-time Fourier transform (STFT), Welch's periodogram, and Thomson's multitaper technique, and performance was analyzed when limiting the size of the parameter-estimation region. Errors were quantified by the bias and standard deviation of the α0 and ß estimates, and by the overall power-law fit error (FE). For parameter estimation regions larger than ~34 pulse lengths (~1 cm for this experiment), an overall power-law FE of 4% was achieved with all spectral estimation methods. With smaller parameter estimation regions as in parametric image formation, the bias and standard deviation of the α0 and ß estimates depended on the size of the parameter estimation region. Here, the multitaper method reduced the standard deviation of the α0 and ß estimates compared with those using the other techniques. The results provide guidance for choosing methods for estimating the power spectral density in quantitative ultrasound methods.

Positron emission tomography imaging of angiogenesis in a murine hindlimb ischemia model with 64Cu-labeled TRC105.

The goal of this study was to assess ischemia-induced angiogenesis with (64)Cu-NOTA-TRC105 positron emission tomography (PET) in a murine hindlimb ischemia model of peripheral artery disease (PAD). CD105 binding affinity/specificity of NOTA-conjugated TRC105 (an anti-CD105 antibody) was evaluated by flow cytometry, which exhibited no difference from unconjugated TRC105. BALB/c mice were anesthetized, and the right femoral artery was ligated to induce hindlimb ischemia, with the left hindlimb serving as an internal control. Laser Doppler imaging showed that perfusion in the ischemic hindlimb plummeted to ∼ 20% of the normal level after surgery and gradually recovered to near normal level on day 24. Ischemia-induced angiogenesis was noninvasively monitored and quantified with (64)Cu-NOTA-TRC105 PET on postoperative days 1, 3, 10, 17, and 24. (64)Cu-NOTA-TRC105 uptake in the ischemic hindlimb increased significantly from the control level of 1.6 ± 0.2 %ID/g to 14.1 ± 1.9 %ID/g at day 3 (n = 3) and gradually decreased with time (3.4 ± 1.9 %ID/g at day 24), which correlated well with biodistribution studies performed on days 3 and 24. Blocking studies confirmed the CD105 specificity of tracer uptake in the ischemic hindlimb. Increased CD105 expression on days 3 and 10 following ischemia was confirmed by histology and reverse transcription polymerase chain reaction (RT-PCR). This is the first report of PET imaging of CD105 expression during ischemia-induced angiogenesis. (64)Cu-NOTA-TRC105 PET may play multiple roles in future PAD-related research and improve PAD patient management by identifying the optimal timing of treatment and monitoring the efficacy of therapy.

Quantitative assessment of in vivo breast masses using ultrasound attenuation and backscatter.

Clinical analysis of breast ultrasound imaging is done qualitatively, facilitated with the ultrasound breast imaging-reporting and data system (US BI-RADS) lexicon, which helps to standardize imaging assessments. Two descriptors in that lexicon, "posterior acoustic features" and the "echo pattern" within a mass, are directly related to quantitative ultrasound (QUS) parameters, namely, ultrasound attenuation and the average backscatter coefficient (BSC). The purpose of this study was to quantify ultrasound attenuation and backscatter in breast masses and to investigate these QUS properties as potential differential diagnostic markers. Radio frequency (RF) echo signals were from patients with breast masses during a special ultrasound imaging session prior to core biopsy. Data were also obtained from a well characterized phantom using identical system settings. Masses include 14 fibroadenomas and 10 carcinomas. Attenuation for the acoustic path lying proximal to the tumor was estimated offline using a least squares method with constraints. BSCs were estimated using a reference phantom method (RPM). The attenuation coefficient within each mass was assessed using both the RPM and a hybrid method, and effective scatterer diameters (ESDs) were estimated using a Gaussian form factor model. Attenuation estimates obtained with the RPM were consistent with estimates done using the hybrid method in all cases except for two masses. The mean slope of the attenuation coefficient versus frequency for carcinomas was 20% greater than the mean slope value for the fibroadenomas. The product of the attenuation coefficient and anteroposterior dimension of the mass was computed to estimate the total attenuation for each mass. That value correlated well with the BI-RADS assessment of "posterior acoustic features" judged qualitatively from gray scale images. Nearly all masses were described as "hypoechoic," so no strong statements could be made about the correlation of echo pattern findings in BI-RADS with the averaged BSC values. However, most carcinomas exhibited lower values for the frequency-average BSC than fibroadenomas. The mean ESD alone did not differentiate the mass type, but fibroadenomas had greater variability in ESDs within the ROI than that found for invasive ductal carcinomas. This study demonstrates the potential to use attenuation and QUS parameters associated with the BSC as quantitative descriptors.

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.

Comparison of ultrasound attenuation and backscatter estimates in layered tissue-mimicking phantoms among three clinical scanners.

Backscatter and attenuation coefficient estimates are needed in many quantitative ultrasound strategies. In clinical applications, these parameters may not be easily obtained because of variations in scattering by tissues overlying a region of interest (ROI). The goal of this study is to assess the accuracy of backscatter and attenuation estimates for regions distal to nonuniform layers of tissue-mimicking materials. In addition, this work compares results of these estimates for "layered" phantoms scanned using different clinical ultrasound machines. Two tissue-mimicking phantoms were constructed, each exhibiting depth-dependent variations in attenuation or backscatter. The phantoms were scanned with three ultrasound imaging systems, acquiring radio frequency echo data for offline analysis. The attenuation coefficient and the backscatter coefficient (BSC) for sections of the phantoms were estimated using the reference phantom method. Properties of each layer were also measured with laboratory techniques on test samples manufactured during the construction of the phantom. Estimates of the attenuation coefficient versus frequency slope, α(0), using backscatter data from the different systems agreed to within 0.24 dB/cm-MHz. Bias in the α(0) estimates varied with the location of the ROI. BSC estimates for phantom sections whose locations ranged from 0 to 7 cm from the transducer agreed among the different systems and with theoretical predictions, with a mean bias error of 1.01 dB over the used bandwidths. This study demonstrates that attenuation and BSCs can be accurately estimated in layered inhomogeneous media using pulse-echo data from clinical imaging systems.

In vivo classification of breast masses using features derived from axial-strain and axial-shear images.

Breast cancer is currently the second leading cause of cancer deaths in women. Early detection and accurate classification of suspicious masses as benign or malignant is important for arriving at an appropriate treatment plan. In this article, we present classification results for features extracted from ultrasound-based, axial-strain and axial-shear images of breast masses. The breast-mass stiffness contrast, size ratio, and a normalized axial-shear strain area feature are evaluated for the classification of in vivo breast masses using a leave-one-out classifier. Radiofrequency echo data from 123 patients were acquired using Siemens Antares or Elegra clinical ultrasound systems during freehand palpation. Data from four different institutions were analyzed. Axial displacements and strains were estimated using a multilevel, pyramid-based two-dimensional cross-correlation algorithm, with final processing block dimensions of 0.385 mm × 0.507 mm (three A-lines). Since mass boundaries on B-mode images for 21 patients could not be delineated (isoechoic), the combined feature analysis was only performed for 102 patients. Results from receiver operating characteristic (ROC) demonstrate that the area under the curve was 0.90, 0.84, and 0.52 for the normalized axial-shear strain, size ratio, and stiffness contrast, respectively. When these three features were combined using a leave-one-out classifier and support vector machine approach, the overall area under the curve improved to 0.93.

Cross-imaging system comparison of backscatter coefficient estimates from a tissue-mimicking material.

A key step toward implementing quantitative ultrasound techniques in a clinical setting is demonstrating that parameters such as the ultrasonic backscatter coefficient (BSC) can be accurately estimated independent of the clinical imaging system used. In previous studies, agreement in BSC estimates for well characterized phantoms was demonstrated across different laboratory systems. The goal of this study was to compare the BSC estimates of a tissue mimicking sample measured using four clinical scanners, each providing RF echo data in the 1-15 MHz frequency range. The sample was previously described and characterized with single-element transducer systems. Using a reference phantom for analysis, excellent quantitative agreement was observed across the four array-based imaging systems for BSC estimates. Additionally, the estimates from data acquired with the clinical systems agreed with theoretical predictions and with estimates from laboratory measurements using single-element transducers.