Influences of Variability in Attenuation Compensation on the Estimation of Backscatter Coefficient of Median Nerves in Vivo.

OBJECTIVE: Peripheral nerves remain a challenging target for medical imaging, given their size, anatomical complexity, and structural heterogeneity. Quantitative ultrasound (QUS) applies a set of techniques to estimate tissue acoustic parameters independent of the imaging platform. Many useful medical and laboratory applications for QUS have been reported, but challenges remain for deployment in vivo, especially for heterogeneous tissues. Several phenomena introduce variability in attenuation estimates, which may influence the estimation of other QUS parameters. For example, estimating the backscatter coefficient (BSC) requires compensation for the attenuation of overlying tissues between the transducer and the underlying tissue of interest. The purpose of this study is to extend prior studies by investigating the efficacy of several analytical methods of estimating attenuation compensation on QUS outcomes in the human median nerve. METHODS: Median nerves were imaged at the volar wrist in vivo and beam-formed radiofrequency (RF) data were acquired. Six analytical approaches for attenuation compensation were compared: 1-2) attenuation estimated by applying spectral difference method (SDM) and spectral log difference method (SLDM) independently to regions of interest (ROIs) overlying the nerve and to the nerve ROI itself; 3-4) attenuation estimation by applying SDM and SLDM to ROIs overlying the nerve, and transferring these properties to the nerve ROI; and 5-6) methods that apply previously published values of tissue attenuation to the measured thickness of each overlying tissue. Mean between-subject estimates of BSC-related outcomes as well as within-subject variability of these outcomes were compared among the 6 methods. RESULTS: Compensating for attenuation using SLDM and values from the literature reduced variability in BSC-based outcomes, compared to SDM. Variability in attenuation coefficients contributes substantially to variability in backscatter measurements. CONCLUSION: This work has implications for the application of QUS to in vivo diagnostic assessments in peripheral nerves and possibly other heterogeneous tissues.

Evaluation of Scatterer Parameters From Ultrasound Scattering Models Taking Into Account Scattering From Nuclei and Cells of Cell-Pellet Biophantoms and Ex Vivo Tumors.

The Quantitative Ultrasound backscatter coefficient provides the capability to evaluate tissue microstructure parameters. Tissue-based scatterer parameters are extracted using ultrasound scattering models. It is challenging to correlate ultrasound scatterer parameters of tissue structures from optical-measured histology, possibly because of inappropriate scattering models or the presence of multiple scatterers. The objective of this study is to pursue the quantification of pertinent scatterer parameters with scattering models that consider ultrasound scattering from nuclei and cells. The concentric sphere model (CSM) and the structure factor model adapted for two types of scatterers (SFM2) are evaluated for cell-pellet biophantoms and ex vivo tumors of four cell lines: 4T1, JC, LMTK, and MAT. The structure factor model (SFM) was used for comparison. CSM and SFM2 provided scatterer parameters closer to histology (lower relative errors) for nucleus and cell radii and volume fractions than SFM but were not always accompanied by lower dispersion of the scatterer distribution (lower coefficient of variation). CSM and SFM2 quantified cell and nucleus radius and volume fraction parameters with lower relative error compared to SFM. For tumors, CSM provided better results than SFM2.

Spectral-based Quantitative Ultrasound Imaging Processing Techniques: Comparisons of RF Versus IQ Approaches.

Quantitative ultrasound (QUS) is an imaging technique which includes spectral-based parameterization. Typical spectral-based parameters include the backscatter coefficient (BSC) and attenuation coefficient slope (ACS). Traditionally, spectral-based QUS relies on the radio frequency (RF) signal to calculate the spectral-based parameters. Many clinical and research scanners only provide the in-phase and quadrature (IQ) signal. To acquire the RF data, the common approach is to convert IQ signal back into RF signal via mixing with a carrier frequency. In this study, we hypothesize that the performance, that is, accuracy and precision, of spectral-based parameters calculated directly from IQ data is as good as or better than using converted RF data. To test this hypothesis, estimation of the BSC and ACS using RF and IQ data from software, physical phantoms and in vivo rabbit data were analyzed and compared. The results indicated that there were only small differences in estimates of the BSC between when using the original RF, the IQ derived from the original RF and the RF reconverted from the IQ, that is, root mean square errors (RMSEs) were less than 0.04. Furthermore, the structural similarity index measure (SSIM) was calculated for ACS maps with a value greater than 0.96 for maps created using the original RF, IQ data and reconverted RF. On the other hand, the processing time using the IQ data compared to RF data were substantially less, that is, reduced by more than a factor of two. Therefore, this study confirms two things: (1) there is no need to convert IQ data back to RF data for conducting spectral-based QUS analysis, because the conversion from IQ back into RF data can introduce artifacts. (2) For the implementation of real-time QUS, there is an advantage to convert the original RF data into IQ data to conduct spectral-based QUS analysis because IQ data-based QUS can improve processing speed.

High-frequency Quantitative Ultrasound Imaging of Human Rotator Cuff Muscles: Assessment of Repeatability and Reproducibility.

This study evaluated the repeatability and reproducibility of using high-frequency quantitative ultrasound (QUS) measurement of backscatter coefficient (BSC), grayscale analysis, and gray-level co-occurrence matrix (GLCM) textural analysis, to characterize human rotator cuff muscles. The effects of varying scanner settings across two different operators and two US systems were investigated in a healthy volunteer with normal rotator cuff muscles and a patient with chronic massive rotator cuff injury and substantial muscle degeneration. The results suggest that BSC is a promising method for assessing rotator cuff muscles in both control and pathological subjects, even when operators were free to adjust system settings (depth, level of focus, and time-gain compensation). Measurements were repeatable and reproducible across the different operators and ultrasound imaging platforms. In contrast, grayscale and GLCM analyses were found to be less reliable in this setting, with significant measurement variability. Overall, the repeatability and reproducibility measurements of BSC indicate its potential as a diagnostic tool for rotator cuff muscle evaluation.

Extracting Quantitative Ultrasonic Parameters from the Backscatter Coefficient.

The ultrasonic backscatter coefficient (BSC) is a fundamental quantitative ultrasound (QUS) parameter that contains rich information about the underlying tissue. Deriving parameters from the BSC is essential for fully utilizing the information contained in BSC for tissue characterization. In this chapter, we review two primary approaches for extracting parameters from the BSC versus frequency curve: the model-based approach and the model-free approach, focusing on the model-based approach, where a scattering model is fit to the observed BSC to yield model parameters. For this approach, we will attempt to unite commonly used models under a coherent theoretical framework. We will focus on the underlying assumptions and conditions for various BSC models. Computer code is provided to facilitate the use of some of the models. The strengths and weaknesses of various models are also discussed.

Inter- and Intra-Operator Variability of Regularized Backscatter Quantitative Ultrasound for the Characterization of Breast Masses.

OBJECTIVES: Here we report on the intra- and inter-operator variability of the backscatter coefficient (BSC) estimated with a new low-variance quantitative ultrasound (QUS) approach applied to breast lesions in vivo. METHODS: Radiofrequency (RF) echo signals were acquired from 29 BIRADS 4 and 5 breast lesions in 2 sequential cohorts following 2 imaging protocols: cohort 1) radial and antiradial views, and cohort 2) short- and long-axis views. Protocol 2 was implemented after retraining and discussion on how to improve reproducibility. Each patient was scanned by at least 2 of 3 radiologists; each performed 3 acquisitions with transducer and patient repositioning in between acquisitions. BSC was estimated using a low-variance QUS approach based on regularization. Intra- and inter-operator variability of the intra-lesion median BSC was evaluated with a multifactorial ANOVA test (P-values) and the intraclass correlation coefficient (ICC). RESULTS: Inter-operator variability was only significant in the first protocol (P < .007); ICCinter = .77 (95% CI .71-.82), indicating good inter-operator agreement. In the second protocol, the inter-operator variability was not significant (P > .05) and agreement was excellent (ICCinter = .92 [.89-.94]). In both protocols, the intra-operator variability was not significant. CONCLUSIONS: Our findings demonstrate the need for standardizing image acquisition protocols for backscatter-based QUS to reduce inter-operator variability and ensure its successful translation to the characterization of suspicious breast masses.

Quantitative Ultrasound: Scattering Theory.

The radio-frequency ultrasound backscattered data from tissue is rich in information and can provide important information about tissue state that is not obtained through traditional B-mode imaging. To parameterize the ultrasound backscattered data, the frequency spectrum, i.e., the backscatter coefficient, can be modeled using scattering theory. Models of tissue scattering are often represented by simple discrete geometric shapes, i.e., discrete scattering model. The discrete scattering model provides important insights into how the spatial arrangement of scatterers contributes to the signal spectrum. Another competing model is the continuum scattering model. In this model, the tissue is described as a continuous tissue construct with scatterers that have a continuous impedance change from the background. The continuous model provides a form factor description of the underlying tissue scatterers such as an effective scatterer diameter. In this chapter, we will compare and contrast the two underlying tissue scattering models and how they provide insights into ultrasonic scattering from soft tissues.

Phantoms for Quantitative Ultrasound.

Tissue-mimicking materials and phantoms have an important role in quantitative ultrasound. These materials allow for investigation of new techniques with the ability to design materials with properties that are stable over time and available for repeated measurements to refine techniques and analysis algorithms. This chapter presents an overview of the history of phantoms, methods of creation of materials with a variety of acoustic properties, and methods of measurement of those properties. It includes a section addressing the measurement of variance in those techniques using interlaboratory comparisons. There is a wide range of existing tissue-mimicking materials that exhibit properties similar to those of most soft tissues. Ongoing work is part of the expansion of QUS as materials are developed to better mimic specific tissues, geometries, or pathologies.

Improved the Impact of SST for HY-2A Scatterometer Measurements by Using Neural Network Model.

The variation of sea surface temperature (SST) can change the backscatter coefficient measured by a scatterometer, resulting in a decrease in the accuracy of the sea surface wind measurement. This study proposed a new approach to correct the effect of SST on the backscatter coefficient. The method focuses on the Ku-band scatterometer HY-2A SCAT, which is more sensitive to SST than C-band scatterometers, can improve the wind measurement accuracy of the scatterometer without relying on reconstructed geophysical model function (GMF), and is more suitable for operational scatterometers. Through comparisons to WindSat wind data, we found that the Ku-band scatterometer HY-2A SCAT wind speeds are systemically lower under low SST and higher under high SST conditions. We trained a neural network model called the temperature neural network (TNNW) using HY-2A data and WindSat data. TNNW-corrected backscatter coefficients retrieved wind speed with a small systematic deviation from WindSat wind speed. In addition, we also carried out a validation of HY-2A wind and TNNW wind using European Center for Medium-Range Weather Forecasts (ECMWF) reanalysis data as a reference, and the results showed that the retrieved TNNW-corrected backscatter coefficient wind speed is more consistent with ECMWF wind speed, indicating that the method is effective in correcting SST impact on HY-2A scatterometer measurements.

Analysis of Onboard Verification Flight Test for the Salinity Satellite Scatterometer.

The upcoming Salinity Satellite, scheduled for launch in 2024, will feature the world's first phased array radar scatterometer. To validate its capability in measuring ocean surface backscatter coefficients, this paper conducts an in-depth analysis of the onboard verification flight test for the Salinity Satellite scatterometer. This paper provides a detailed introduction to the system design of the Salinity Satellite scatterometer, which utilizes phased array radar technology and digital beamforming techniques to achieve accurate measurements of sea surface scattering characteristics. The paper elaborates on the derivation of backscatter coefficients, system calibration, and phase amplitude correction for the phased array scatterometer. Furthermore, it describes the process of the onboard calibration flight test. By analyzing internal noise signals, onboard calibration signals, and external noise signals, the stability and reliability of the scatterometer system are validated. The experiment covers both land and ocean observations, with a particular focus on complex sea surface conditions in nearshore areas. Through the precise analysis of backscatter coefficients, the paper successfully distinguishes the different backscatter coefficient characteristics between ocean and land. The research results effectively demonstrate the feasibility of the Salinity Satellite scatterometer for measuring backscatter coefficients in a phased array configuration, as well as its outstanding performance in complex marine environments.

Effect of Clutter Filter in High-Frame-Rate Ultrasonic Backscatter Coefficient Analysis.

High-frame-rate imaging with a clutter filter can clearly visualize blood flow signals and provide more efficient discrimination with tissue signals. In vitro studies using clutter-less phantom and high-frequency ultrasound suggested a possibility of evaluating the red blood cell (RBC) aggregation by analyzing the frequency dependence of the backscatter coefficient (BSC). However, in in vivo applications, clutter filtering is required to visualize echoes from the RBC. This study initially evaluated the effect of the clutter filter for ultrasonic BSC analysis for in vitro and preliminary in vivo data to characterize hemorheology. Coherently compounded plane wave imaging at a frame rate of 2 kHz was carried out in high-frame-rate imaging. Two samples of RBCs suspended by saline and autologous plasma for in vitro data were circulated in two types of flow phantoms without or with clutter signals. The singular value decomposition was applied to suppress the clutter signal in the flow phantom. The BSC was calculated using the reference phantom method, and it was parametrized by spectral slope and mid-band fit (MBF) between 4-12 MHz. The velocity distribution was estimated by the block matching method, and the shear rate was estimated by the least squares approximation of the slope near the wall. Consequently, the spectral slope of the saline sample was always around four (Rayleigh scattering), independently of the shear rate, because the RBCs did not aggregate in the solution. Conversely, the spectral slope of the plasma sample was lower than four at low shear rates but approached four by increasing the shear rate, because the aggregations were presumably dissolved by the high shear rate. Moreover, the MBF of the plasma sample decreased from -36 to -49 dB in both flow phantoms with increasing shear rates, from approximately 10 to 100 s-1. The variation in the spectral slope and MBF in the saline sample was comparable to the results of in vivo cases in healthy human jugular veins when the tissue and blood flow signals could be separated.

Novel Method for Ultrasound-Derived Fat Fraction Using an Integrated Phantom.

OBJECTIVES: The purpose of this study was to demonstrate the clinical feasibility of an integrated reference phantom method for quantitative ultrasound by creating an ultrasound-derived fat fraction (UDFF) tool. This tool was evaluated with respect to its diagnostic performance as a biomarker for assessing histologic hepatic steatosis and its agreement with the magnetic resonance imaging (MRI) proton density fat fraction (PDFF). METHODS: Adults (n = 101) with known or suspected nonalcoholic fatty liver disease consented to participate in this prospective cross-sectional study. All patients underwent MRI-PDFF and ultrasound scans, whereas 90 underwent liver biopsy. A linear least-squares analysis used the attenuation coefficient and backscatter coefficient to create the UDFF model for predicting MRI-PDFF. RESULTS: The area under the receiver operating characteristic curve values were 0.94 (95% confidence interval [CI], 0.85-0.98) for histologic steatosis grade 0 (n = 6) versus 1 or higher (n = 84), 0.88 (95% CI, 0.8-0.94) for grade 1 or lower (n = 45) versus 2 or higher (n = 45), and 0.83 (95% CI, 0.73-0.9) for grade 2 or lower (n = 78) versus 3 (n = 12). The Pearson correlation coefficient between UDFF and PDFF was ρ = 0.87 with 95% limits of agreement of ±8.5%. Additionally, the diagnosis of steatosis, defined as MRI-PDFF higher than 5% and 10%, had area under the receiver operating characteristic curve values of 0.97 (95% CI, 0.93-0.99) and 0.95 (95% CI, 0.9-0.98), respectively. The body mass index was not correlated with either UDFF or PDFF. CONCLUSIONS: An on-system, integrated UDFF tool provides a simple, noninvasive, accessible, low-cost, and commercially viable clinical tool for quantifying the hepatic fat fraction with a high degree of agreement with histologic biopsy or the MRI-PDFF biomarker.

Quantitative Ultrasound and the Pancreas: Demonstration of Early Detection Capability.

OBJECTIVES: To show that quantitative ultrasound biomarkers attenuation (AC) and backscatter (BSC) coefficients are effective tools to detect early changes in acute pancreatitis, using a cerulein-induced pancreatitis rat model. METHODS: Sprague-Dawley rats (n = 68) were divided into 8 groups: uninjected cage controls, saline-injected controls, and cerulein-injected rats euthanized at 2, 4, 15, 24, 48, and 60 hours after injection. Pancreatic AC and BSC (25-55 MHz) were estimated in vivo (Vevo 2100, VisualSonics, Toronto, CA) and ex vivo (40-MHz transducer). The pancreas of each rat was evaluated histopathologically. RESULTS: Changes in both in vivo and ex vivo AC and BSC relative to controls reflected temporal histomorphologic changes. Overall, there were decreased AC and BSC at early time points and then rebound toward control values over time. Maximal in vivo AC and BSC decreases occurred at 2 hours after cerulein injection. Attenuation coefficient changes corresponded well with early pancreatic edema and acinar cell vacuolation, with rebound as edema decreased, autophagy/cellular death occurred, and histiocytic infiltrates and fibrosis manifested. Backscatter coefficient decreased early but rebounded as autophagy and apoptosis increased, only to fall as acinar atrophy peaked, and fibrosis and histiocytic infiltration increased. CONCLUSIONS: Cerulein-induced pancreatitis is an excellent model for studying ultrasonic AC and BSC biomarkers during the early stages of acute pancreatitits, reflecting microscopic structural changes. Edema followed by cell shrinkage and apoptosis, then histiocytic infiltration and fibrosis, has certain similarities with the morphologies of some forms of pancreatic carcinoma. This suggests that quantitative ultrasound may be very useful for early detection of disease onset or response to therapy for not only acute pancreatitis but also pancreatic cancer.

Repeatability and Reproducibility of the Ultrasonic Attenuation Coefficient and Backscatter Coefficient Measured in the Right Lobe of the Liver in Adults With Known or Suspected Nonalcoholic Fatty Liver Disease.

OBJECTIVES: To assess the repeatability and reproducibility of the ultrasonic attenuation coefficient (AC) and backscatter coefficient (BSC) measured in the livers of adults with known or suspected nonalcoholic fatty liver disease (NAFLD). METHODS: The Institutional Review Board approved this Health Insurance Portability and Accountability Act-compliant prospective study; informed consent was obtained. Forty-one research participants with known or suspected NAFLD were recruited and underwent same-day ultrasound examinations of the right liver lobe with a clinical scanner by a clinical sonographer. Each participant underwent 2 scanning trials, with participant repositioning between trials. Two transducers were used in each trial. For each transducer, machine settings were optimized by the sonographer but then kept constant while 3 data acquisitions were obtained from the liver without participant repositioning and then from an external calibrated phantom. Raw RF echo data were recorded. The AC and BSC were measured within 2.6 to 3.0 MHz from a user-defined hepatic field of interest from each acquisition. The repeatability and reproducibility were analyzed by random-effects models. RESULTS: The mean AC and log-transformed BSC (logBSC) were 0.94 dB/cm-MHz and -27.0 dB, respectively. Intraclass correlation coefficients were 0.88 to 0.94 for the AC and 0.87 to 0.95 for the logBSC acquired without participant repositioning. For between-trial repeated scans with participant repositioning, the intraclass correlation coefficients were 0.80 to 0.84 for the AC and 0.69 to 0.82 for the logBSC after averaging results from 3 within-trial images. The variability introduced by the transducer was less than the repeatability error. CONCLUSIONS: Hepatic AC and BSC measures using a reference phantom technique on a clinical scanner are repeatable and reproducible between transducers in adults with known or suspected NAFLD.

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.

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.

Backscatter coefficient estimation using tapers with gaps.

When using the backscatter coefficient (BSC) to estimate quantitative ultrasound parameters such as the effective scatterer diameter (ESD) and the effective acoustic concentration (EAC), it is necessary to assume that the interrogated medium contains diffuse scatterers. Structures that invalidate this assumption can affect the estimated BSC parameters in terms of increased bias and variance and decrease performance when classifying disease. In this work, a method was developed to mitigate the effects of echoes from structures that invalidate the assumption of diffuse scattering, while preserving as much signal as possible for obtaining diffuse scatterer property estimates. Backscattered signal sections that contained nondiffuse signals were identified and a windowing technique was used to provide BSC estimates for diffuse echoes only. Experiments from physical phantoms were used to evaluate the effectiveness of the proposed BSC estimation methods. Tradeoffs associated with effective mitigation of specular scatterers and bias and variance introduced into the estimates were quantified. Analysis of the results suggested that discrete prolate spheroidal (PR) tapers with gaps provided the best performance for minimizing BSC error. Specifically, the mean square error for BSC between measured and theoretical had an average value of approximately 1.0 and 0.2 when using a Hanning taper and PR taper respectively, with six gaps. The BSC error due to amplitude bias was smallest for PR (Nω = 1) tapers. The BSC error due to shape bias was smallest for PR (Nω = 4) tapers. These results suggest using different taper types for estimating ESD versus EAC.

In Vivo Validation of an In Situ Calibration Bead as a Reference for Backscatter Coefficient Calculation.

OBJECTIVE: The study described here was aimed at assessing the capability of quantitative ultrasound (QUS) based on the backscatter coefficient (BSC) for classifying disease states, such as breast cancer response to neoadjuvant chemotherapy and quantification of fatty liver disease. We evaluated the effectiveness of an in situ titanium (Ti) bead as a reference target in calibrating the system and mitigating attenuation and transmission loss effects on BSC estimation. METHODS: Traditional BSC estimation methods require external references for calibration, which do not account for ultrasound attenuation or transmission losses through tissues. To address this issue, we used an in situ Ti bead as a reference target, because it can be used to calibrate the system and mitigate the attenuation and transmission loss effects on estimation of the BSC. The capabilities of the in situ calibration approach were assessed by quantifying consistency of BSC estimates from rabbit mammary tumors (N = 21). Specifically, mammary tumors were grown in rabbits and when a tumor reached ≥1 cm in size, a 2 mm Ti bead was implanted in the tumor as a radiological marker and a calibration source for ultrasound. Three days later, the tumors were scanned with an L-14/5 38 array transducer connected to a SonixOne scanner with and without a slab of pork belly placed on top of the tumors. The pork belly acted as an additional source of attenuation and transmission loss. QUS parameters, specifically effective scatterer diameter (ESD) and effective acoustic concentration (EAC), were calculated using calibration spectra from both an external reference phantom and the Ti bead. RESULTS: For ESD estimation, the 95% confidence interval between measurements with and without the pork belly layer was 6.0, 27.4 using the in situ bead and 114, 135.1 with the external reference phantom. For EAC estimation, the 95% confidence intervals were -8.1, 0.5 for the bead and -41.5, -32.2 for the phantom. These results indicate that the in situ bead method has reduced bias in QUS estimates because of intervening tissue losses. CONCLUSION: The use of an in situ Ti bead as a radiological marker not only serves its traditional role but also effectively acts as a calibration target for QUS methods. This approach accounts for attenuation and transmission losses in tissue, resulting in more accurate QUS estimates and offering a promising method for enhanced disease state classification in clinical settings.

In vivo validation of an in situ calibration bead as a reference for backscatter coefficient calculation.

Objectives: The study aims to assess the capability of Quantitative Ultrasound (QUS) based on the backscatter coefficient (BSC) for classifying disease states, such as breast cancer response to neoadjuvant chemotherapy and quantifying fatty liver disease. We evaluate the effectiveness of an in situ titanium (Ti) bead as a reference target in calibrating the system and mitigating attenuation and transmission loss effects on BSC estimation. Methods: Traditional BSC estimation methods require external references for calibration, which do not account for ultrasound attenuation or transmission losses through tissues. To address this issue, we use an in situ titanium (Ti) bead as a reference target, because it can be used to calibrate the system and mitigate the attenuation and transmission loss effects on estimation of the BSC. The capabilities of the in situ calibration approach were assessed by quantifying consistency of BSC estimates from rabbit mammary tumors (N=21). Specifically, mammary tumors were grown in rabbits and when a tumor reached 1 cm or greater in size, a 2-mm Ti bead was implanted into the tumor as a radiological marker and a calibration source for ultrasound. Three days later, the tumors were scanned with a L-14/5 38 array transducer connected to a SonixOne scanner with and without a slab of pork belly placed on top of the tumors. The pork belly acted as an additional source of attenuation and transmission loss. QUS parameters, specifically effective scatterer diameter (ESD) and effective acoustic concentration (EAC), were calculated using calibration spectra from both an external reference phantom and the Ti bead. Results: For ESD estimation, the 95% confidence interval between measurements with and without the pork belly layer was (6.0,27.4) using the in situ bead and (114, 135.1) with the external reference phantom. For EAC estimation, the 95% confidence interval were (-8.1, 0.5) for the bead and (-41.5, -32.2) for the phantom. These results indicate that the in situ bead method shows reduced bias in QUS estimates due to intervening tissue losses. Conclusions: The use of an in situ Ti bead as a radiological marker not only serves its traditional role but also effectively acts as a calibration target for QUS methods. This approach accounts for attenuation and transmission losses in tissue, resulting in more accurate QUS estimates and offering a promising method for enhanced disease state classification in clinical settings.

Simulation of ultrasound backscatter coefficient measurement using the finite element method.

Ultrasound backscatter coefficient (BSC) measurement is a method for assessing tissue morphology that can inform on pathologies such as cancer. The BSC measurement is, however, limited by the accuracy with which the investigator can normalise their results to account for frequency dependent effects of diffraction and attenuation whilst performing such measurements. We propose a simulation-based approach to investigate the potential sources of error in assessing the BSC. Presented is a tool for the 2D Finite Element (FE) simulation mimicking a BSC measurement using the planar reflector substitution method in reduced dimensionality. The results of this are verified against new derivations of BSC equations also in reduced dimensionality. These new derivations allow computation of BSC estimates based on the scattering from a 2D scattering area, a line reference reflector and a theoretical value for the BSC of a 2D distribution of scatterers. This 2D model was designed to generate lightweight simulations that allow rapid investigation of the factors associated with BSC measurement, allowing the investigator to generate large data sets in relatively short time scales. Under the conditions for an incoherent scattering medium, the simulations produced BSC estimates within 6% of the theoretical value calculated from the simulation domain, a result reproduced across a range of source f-numbers. This value of error compares well to both estimated errors from other simulation based approaches and to physical experiments. The mathematical and simulation models described here provide a theoretical and experimental framework for continued investigation into factors affecting the accuracy of BSC measurements.