Automated Field of Interest Determination for Quantitative Ultrasound Analyses of Cervical Tissues: Toward Real-time Clinical Translation in Spontaneous Preterm Birth Risk Assessment.

OBJECTIVE: Quantitative ultrasound (QUS) analysis of the human cervix is valuable for predicting spontaneous preterm birth risk. However, this approach currently requires an offline processing step wherein a medically trained analyst manually draws a free-hand field of interest (Manual FOI) for QUS computation. This offline step hinders the clinical adoption of QUS. To address this challenge, we developed a method to determine automatically the cervical FOI (Auto FOI). This study's objective is to evaluate the agreement between QUS results obtained from the Auto and Manual FOIs and assess the feasibility of using the Auto FOI to replace the Manual FOI for cervical QUS computation. METHODS: The auto FOI method was developed and evaluated using cervical ultrasound data from 527 pregnant women, using Manual FOIs as the reference. A deep learning model was developed using the cervical B-mode image as the input to determine automatically the FOI. RESULTS: Quantitative comparison between the Auto and Manual FOIs yielded a high pixel accuracy of 97% and a Dice coefficient of 87%. Further, the Auto FOI yielded QUS biomarker values that were highly correlated with those obtained from the Manual FOIs. For example, the Pearson correlation coefficient was 0.87 between attenuation coefficient values obtained using Auto and Manual FOIs. Further, Bland-Altman analyses showed negligible bias between QUS biomarker values computed using the Auto and Manual FOIs. CONCLUSION: The results support the feasibility of using Auto FOIs to replace Manual FOIs in QUS computation, an important step toward the clinical adoption of QUS technology.

Trajectory of Postpartum Cervical Remodeling in Women Delivering Full-Term and Spontaneous Preterm: Sensitivity to Quantitative Ultrasound Biomarkers.

OBJECTIVE: Women with a history of spontaneous preterm birth (sPTB) face an increased risk of recurrence. Yet, the factors contributing to the increased risk are unknown, hampering the development of targeted interventions. Noninvasive quantitative ultrasound (QUS) has been validated in the characterization of cervical tissue and has the potential to provide information about postpartum cervical remodeling. The objective of this study was to determine the postpartum cervical remodeling trajectories of women over 12 mo post-delivery and to determine whether there were differences between women who delivered full-term and spontaneous preterm that were sensitive to QUS biomarkers. METHODS: Data were collected prospectively from 55 women: 41 who delivered full-term and 14 who delivered spontaneously preterm at 6 wk, 3, 6, 9 and 12 mo (±2 wk) postpartum. Data from QUS biomarkers: Attenuation Coefficient; Backscatter Coefficient; Shear Wave Speed; and Lizzi-Feleppa Slope, Intercept and Midband were analyzed from the acquired radiofrequency data using a Siemens S2000 ultrasound system with a transvaginal MC 9-4 MHz probe. The biomarkers were analyzed using descriptive statistics and linear mixed-effects models. RESULTS: QUS biomarkers, Backscatter Coefficient and Lizzi-Feleppa Intercept showed significant differences during the year after delivery between women who had a full-term birth and sPTB (p < 0.05), suggesting that there are differences in the cervical remodeling trajectories between the two groups. All QUS biomarkers demonstrated significant variations between the full-term birth and sPTB groups over time (p < 0.05), indicating ongoing cervical remodeling for both groups during the 12-mo postpartum period. CONCLUSION: QUS biomarkers identified cervical microstructure differences and trajectories in the year after delivery between women who delivered full-term and spontaneous preterm.

Post-mortem Tissue Degassing Using Positive Pressure Is Superior to Negative Pressure.

OBJECTIVE: To compare the effectiveness of positive pressure (PP) and negative pressure (NP) for reducing gas inclusions in biological tissues in preparation for acoustic imaging. METHODS: Eighteen pieces of porcine liver in degassed saline were included in this study. For the PP group (n = 9 samples), a wristwatch waterproof tester was used to pressurize samples to 0.41 MPa (59 psi) for 10 min. For the NP group (n = 9 samples), a desiccator at -0.08 MPa (-12 psi) was used for 30 min. Backscatter coefficients (BSCs) were calculated over the central frequency range of the backscattered spectra and paired-samples t-tests were performed. RESULTS: Utilization of PP resulted in a decrease in BSC for all samples, indicating less gas post-PP (pre-PP -13.0 ± 4.3 dB [mean ± SD], post-PP -18.9 ± 5.0 dB, p = .001). Utilization of NP resulted in an increase in BSC for the majority of samples (pre-NP -14.6 ± 6.0 dB, post-NP -13.1 ± 5.3 dB, p = .177). CONCLUSION: Utilization of a simple PP chamber consistently resulted in a decrease in tissue gas, at lower pressures than previously reported. The vacuum method is ineffective, may result in a paradoxical increase in tissue gas, and may not be recommended for tissue degassing.

Sticky Hard-Sphere Model for Characterizing Tumor Microstructure via Quantitative Ultrasound.

The use of the structure function (SF) to model interscatterer contribution to ultrasonic scattering is a major step to improve the capability and accuracy of quantitative ultrasound (QUS) and tissue characterization. However, existing QUS-based SF models rely on the hard-sphere (HS) model, which is limited in its applicability for complex scatterer distributions in real tissue. This article introduces the sticky HS (SHS) model for QUS and tissue characterization, which considers a very short-range attractive potential that accounts for the adhesive nature of biological cells and yields a new parameter called stickiness. Herein, the analytical SF expression is presented for monodisperse scatterer size and validated using simulations of scatterer distributions with varying degrees of grouping and volume fractions (0.16, 0.32, and 0.40) over the frequency range from 15 to 110 MHz. The SHS model is applied to three mammary tumor types with differing spatial distributions of tumor cells. The histology-derived SF is computed by considering the nuclei as the main sources of scattering. The results show that the SHS model provides more accurate scatterer radius and volume fraction estimates than the HS model when fit to histology-derived SF versus frequency curves. Furthermore, the new stickiness parameter provided by SHS is sensitive to the grouping structure in tumor cell distribution. This stickiness parameter, combined with the radius and volume fraction estimated from the SHS model, enables better differentiation between different tumor types than using the radius and volume fraction obtained from the HS model. This study demonstrates the potential of the SHS model to improve the QUS tissue characterization.

A "solo-solvent de novo liquid-phase" method for synthesizing sulfide solid electrolyte Li6PS5Cl.

We report a "solo-solvent de novo liquid-phase" method of synthesizing a highly-favored sulfide electrolyte (Li6PS5Cl) for developing all-solid-state lithium batteries. The key chemistry for such a successful method is that tetrahydropyrrole enables in situ synthesis of the critical precursor Li2S from cheap and air-stable precursors of lithium chloride and sodium sulfide.

Enhanced identification of women at risk for preterm birth via quantitative ultrasound: a prospective cohort study.

BACKGROUND: Historically, clinicians have relied on medical risk factors and clinical symptoms for preterm birth risk assessment. In nulliparous women, clinicians may rely solely on reported symptoms to assess for the risk of preterm birth. The routine use of ultrasound during pregnancy offers the opportunity to incorporate quantitative ultrasound scanning of the cervix to potentially improve assessment of preterm birth risk. OBJECTIVE: This study aimed to investigate the efficiency of quantitative ultrasound measurements at relatively early stages of pregnancy to enhance identification of women who might be at risk for spontaneous preterm birth. STUDY DESIGN: A prospective cohort study of pregnant women was conducted with volunteer participants receiving care from the University of Illinois Hospital in Chicago, Illinois. Participants received a standard clinical screening followed by 2 research screenings conducted at 20±2 and 24±2 weeks. Quantitative ultrasound scans were performed during research screenings by registered diagnostic medical sonographers using a standard cervical length approach. Quantitative ultrasound features were computed from calibrated raw radiofrequency backscattered signals. Full-term birth outcomes and spontaneous preterm birth outcomes were included in the analysis. Medically indicated preterm births were excluded from the analysis. Using data from each visit, logistic regression with Akaike information criterion feature selection was conducted to derive predictive models for each time frame based on historical clinical and quantitative ultrasound features. Model evaluations included a likelihood ratio test of quantitative ultrasound features, cross-validated receiver operating characteristic curve analysis, sensitivity, and specificity. RESULTS: On the basis of historical clinical features alone, the best predictive model had an estimated receiver operating characteristic area under the curve of 0.56±0.03. By the time frame of Visit 1, a predictive model using both historical clinical and quantitative ultrasound features provided a modest improvement in the area under the curve (0.63±0.03) relative to that of the predictive model using only historical clinical features. By the time frame of Visit 2, the predictive model using historical clinical and quantitative ultrasound features provided significant improvement (likelihood ratio test, P<.01), with an area under the curve of 0.69±0.03. CONCLUSION: Accurate identification of women at risk for spontaneous preterm birth solely through historical clinical features has been proven to be difficult. In this study, a history of preterm birth was the most significant historical clinical predictor of preterm birth risk, but the historical clinical predictive model performance was not statistically significantly better than the no-skill level. According to our study results, including quantitative ultrasound yields a statistically significant improvement in risk prediction as the pregnancy progresses.

Transcranial Phase Correction Using Pulse-Echo Ultrasound and Deep Learning: A 2-D Numerical Study.

Phase aberration caused by human skulls severely degrades the quality of transcranial ultrasound images, posing a major challenge in the practical application of transcranial ultrasound techniques in adults. Aberration can be corrected if the skull profile (i.e., thickness distribution) and speed of sound (SOS) are known. However, accurately estimating the skull profile and SOS using ultrasound with a physics-based approach is challenging due to the complexity of the interaction between ultrasound and the skull. A deep learning approach is proposed herein to estimate the skull profile and SOS using ultrasound radiofrequency (RF) signals backscattered from the skull. A numerical study was performed to test the approach's feasibility. Realistic numerical skull models were constructed from computed tomography (CT) scans of five ex vivo human skulls in this numerical study. Acoustic simulations were performed on 3595 skull segments to generate array-based ultrasound backscattered signals. A deep learning model was developed and trained to estimate skull thickness and SOS from RF channel data. The trained model was shown to be highly accurate. The mean absolute error (MAE) was 0.15 mm (2% error) for thickness estimation and 13 m/s (0.5% error) for SOS estimation. The Pearson correlation coefficient between the estimated and ground-truth values was 0.99 for thickness and 0.95 for SOS. Aberration correction performed using deep-learning-estimated skull thickness and SOS values yielded significantly improved beam focusing (e.g., narrower beams) and transcranial imaging quality (e.g., improved spatial resolution and reduced artifacts) compared with no aberration correction. The results demonstrate the feasibility of the proposed approach for transcranial phase aberration correction.

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.

Toward High-Quality Sulfide Solid Electrolytes: A Liquid-Phase Approach Featured with an Interparticle Coupled Unification Effect.

Sulfide solid electrolytes (SSEs) are highly wanted for solid-state batteries (SSBs). While their liquid-phase synthesis is advantageous over their solid-phase strategy in scalable production, it confronts other challenges, such as low-purity products, user-unfriendly solvents, energy-inefficient solvent removal, and unsatisfactory performance. This article demonstrates that a suspension-based solvothermal method using single oxygen-free solvents can solve those problems. Experimental observations and theoretical calculations together show that the basic function of suspension-treatment is "interparticle-coupled unification", that is, even individually insoluble solid precursors can mutually adsorb and amalgamate to generate uniform composites in nonpolar solvents. This anti-intuitive concept is established when investigating the origins of impurities in SSEs electrolytes made by the conventional tetrahydrofuran-ethanol method and then searching for new solvents. Its generality is supported by four eligible alkane solvents and four types of SSEs. The electrochemical assessments on the former three SSEs show that they are competitive with their counterparts in the literature. Moreover, the synthesized SSEs presents excellent battery performance, showing great potential for practical applications.

Quantitative evaluation of rat sciatic nerve degeneration using high-frequency ultrasound.

In this study, we evaluated the utility of using high-frequency ultrasound to non-invasively track the degenerative process in a rat model of peripheral nerve injury. Primary analyses explored spatial and temporal changes in quantitative backscatter coefficient (BSC) spectrum-based outcomes and B-mode textural outcomes, using gray level co-occurrence matrices (GLCMs), during the progressive transition from acute to chronic injury. As secondary analyses, correlations among GLCM and BSC spectrum-based parameters were evaluated, and immunohistochemistry were used to suggest a structural basis for ultrasound outcomes. Both mean BSC spectrum-based and mean GLCM-based measures exhibited significant spatial differences across presurgical and 1-month/2-month time points, distal stumps enclosed proximity to the injury site being particularly affected. The two sets of parameters sensitively detected peripheral nerve degeneration at 1-month and 2-month post-injury, with area under the receiver operating charactersitic curve > 0.8 for most parameters. The results also indicated that the many BSC spectrum-based and GLCM-based parameters significantly correlate with each other, and suggested a common structural basis for a diverse set of quantitative ultrasound parameters. The findings of this study suggest that BSC spectrum-based and GLCM-based analysis are promising non-invasive techniques for diagnosing peripheral nerve degeneration.

Synthesis of Deliquescent Lithium Sulfide in Air.

In the field of lithium-sulfur batteries (LSBs) and all-solid-state batteries, lithium sulfide (Li2S) is a critical raw material. However, its practical application is greatly hindered by its high price due to its deliquescent property and production at high temperatures (above 700 °C) with carbon emission. Hereby, we report a new method of preparing Li2S, in air and at low temperatures (∼200 °C), which presents enriched and surprising chemistry. The synthesis relies on the solid-state reaction between inexpensive and air-stable raw materials of lithium hydroxide (LiOH) and sulfur (S), where lithium sulfite (Li2SO3), lithium thiosulfate (Li2S2O3), and water are three major byproducts. About 57% of lithium from LiOH is converted into Li2S, corresponding to a material cost of ∼$64.9/kg_Li2S, less than 10% of the commercial price. The success of conducting this water-producing reaction in air lies in three-fold: (1) Li2S is stable with oxygen below 220 °C; (2) the use of excess S can prevent Li2S from water attack, by forming lithium polysulfides (Li2Sn); and (3) the byproduct water can be expelled out of the reaction system by the carrier gas and also absorbed by LiOH to form LiOH·H2O. Two interesting and beneficial phenomena, i.e., the anti-hydrolysis of Li2Sn and the decomposition of Li2S2O3 to recover Li2S, are explained with density functional theory computations. Furthermore, our homemade Li2S (h-Li2S) is at least comparable with the commercial Li2S (c-Li2S), when being tested as cathode materials for LSBs.

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.

"One Stone Two Birds" Strategy of Synthesizing the Battery Material Lithium Sulfide: Aluminothermal Reduction of Lithium Sulfate.

Lithium sulfide (Li2S) is a critical material for clean energy technologies, i.e., the cathode material in lithium-sulfur batteries and the raw material for making sulfide solid electrolytes in all-solid-state batteries. However, its practical application at a large scale is hindered by its industrial production method of reducing lithium sulfate with carbon materials at high temperatures, which emits carbon dioxide and is time-consuming. We hereby report a method of synthesizing Li2S by thermally reducing lithium sulfate with aluminum. Compared with the carbothermal method, this aluminothermal approach has several advantages, such as operation at lower temperatures, completion in minutes, no emission of greenhouse gases, and valuable byproducts of aluminum oxide (Al2O3). The home-made Li2S demonstrates competitive performance in battery tests versus the commercial counterpart. Moreover, using the byproduct Al2O3 to coat the cathode side of the separator can enhance the battery's capacity without influencing its rate capability. Thus, this "one stone two birds" method has great potential for practical applications of developing Li-S batteries.

Predicting Spontaneous Pre-term Birth Risk Is Improved When Quantitative Ultrasound Data Are Included With Historical Clinical Data.

OBJECTIVE: Predicting women at risk for spontaneous pre-term birth (sPTB) has been medically challenging because of the lack of signs and symptoms of pre-term birth until interventions are too late. We hypothesized that prediction of the sPTB risk level is enhanced when using both historical clinical (HC) data and quantitative ultrasound (QUS) data compared with using only HC data. HC data defined herein included birth history prior to that of the current pregnancy as well as, from the current pregnancy, a clinical cervical length assessment and physical examination data. METHODS: The study population included 248 full-term births (FTBs) and 26 sPTBs. QUS scans (Siemens S2000 and MC9-4) were performed by registered diagnostic medical sonographers using a standard cervical length approach. Two cervical QUS scans were conducted at 20 ± 2 and 24 ± 2 wk of gestation. Multiple QUS features were evaluated from calibrated raw radiofrequency backscattered ultrasonic signals. Two statistical models designed to determine sPTB risk were compared: (i) HC data alone and (ii) combined HC and QUS data. Model comparisons included a likelihood ratio test, cross-validated receiver operating characteristic area under the curve, sensitivity and specificity. The study's birth outcomes were only FTBs and sPTBs; medically induced pre-term births were not included. DISCUSSION: Combined HC and QUS data identified women at risk of sPTB with better AUC (0.68, 95% confidence interval [CI]: 0.57-0.78) compared with HC data alone (0.53, 95% CI: 0.40-0.66) and HC data + cervical length at 18-20 wk of gestation (average AUC = 0.51, 95% CI: 0.38-0.64). A likelihood ratio test for significance of QUS features in the classification model was highly statistically significant (p < 0.01). CONCLUSION: Even with only 26 sPTBs among 274 births, value was added in predicting sPTB when QUS data were included with HC data.

Pulse-Echo Technique to Compensate for Laminate Membrane Transmission Loss in Phantom-Based Ultrasonic Attenuation Coefficient Measurements.

OBJECTIVES: Accurately measuring the attenuation coefficient (AC) of reference phantoms is critical in clinical applications of quantitative ultrasound. Phantom AC measurement requires proper compensation of membrane transmission loss. Conventional methods require separate membrane samples to obtain membrane transmission loss. Unfortunately, separate membrane samples are often unavailable. A pulse-echo approach is proposed herein to compensate for membrane transmission loss without requiring separate membrane samples. METHODS: The proposed method consists of the following steps. First, the insertion loss, caused by phantom attenuation and membrane transmission loss, is measured. Second, the membrane reflection coefficient is measured. Third, the unknown acoustic parameters of the membrane and phantom material are estimated by fitting theoretical reflection coefficient to the measured one. Finally, the fitted parameters are used to estimate membrane transmission loss and phantom AC. The proposed method was validated through k-Wave simulations and phantom experiments. Experimental AC measurements were repeated on 5 distinct phantoms by 2 operators to assess the repeatability and reproducibility of the proposed method. Five transducers were used to cover a broad bandwidth (0.7-16 MHz). RESULTS: The acquired AC in the simulations had a maximum error of 0.06 dB/cm-MHz for simulated phantom AC values ranging from 0.5 to 1 dB/cm-MHz. The acquired AC in the experiments had a maximum error of 0.045 dB/cm-MHz for phantom AC values ranging from 0.28 to 1.48 dB/cm-MHz. Good repeatability and cross-operator reproducibility were observed with a mean coefficient of variation below 0.054. CONCLUSION: The proposed method simplifies phantom AC measurement while providing satisfactory accuracy and precision.

Repeatability, Reproducibility and Sources of Variability in the Assessment of Backscatter Coefficient and Texture Parameters from High-Frequency Ultrasound Acquisitions in Human Median Nerve.

Ultrasound (US) is an increasingly prevalent and effective diagnostic modality for neuromuscular imaging. Gray-scale B-mode imaging has been the dominant US approach to evaluating nerves qualitatively or making morphometric measurements of nerves, providing important insights into pathological changes for conditions such as carpal tunnel syndrome. Among more recent ultrasound strategies, high-frequency ultrasound (often defined as >15 MHz for clinical applications), quantitative ultrasound and image textural analysis offer promising enhancements for improved and more objective approaches to nerve imaging. In this study, we evaluated the repeatability and reproducibility of backscatter coefficient (BSC) and imaging texture features extracted by gray-level co-occurrence matrices (GLCMs) in homogeneous tissue-mimicking reference phantoms and in median nerves in the wrists of healthy participants. We also investigated several practical sources of variability in the assessment of quantitative parameters, including influences of operators, and participant-to-participant variability. Overall, BSC- and GLCM-based outcomes are highly repeatable and reproducible after operator training, based on measurement of descriptive statistics, repeatability coefficient (RC) and reproducibility coefficient recommended by Quantitative Imaging Biomarker Alliance (QIBA RDC). GLCM parameters appear more reproducible and repeatable than BSC-based parameters in healthy participants in vivo. However, such variability noted here must be compared with the value ranges and variability of the results in pathological nerves, including median nerves afflicted by trauma, overuse syndromes such as carpal tunnel syndrome and after surgical repair.

Green Synthesis for Battery Materials: A Case Study of Making Lithium Sulfide via Metathetic Precipitation.

For some future clean-energy technologies (such as advanced batteries), the concept of green chemistry has not been exercised enough for their material synthesis. Herein, we report a waste-free method of synthesizing lithium sulfide (Li2S), a critical material for both lithium-sulfur batteries and sulfide-electrolyte-based all-solid-state lithium batteries. The key novelty lies in directly precipitating crystalline Li2S out of an organic solution after the metathetic reaction between a lithium salt and sodium sulfide. Compared with conventional methods, this method is advantageous in operating at ambient temperatures, releasing no hazardous wastes, and being economically more competitive. To collect the valuable byproduct out of the liquid phases, a "solventing-out crystallization" technique is employed by adding an antisolvent (AS) of low boiling point. The subsequent distillation of the new solution under vacuum evaporates off the AS rather than the high-boiling-point reaction solvent (RS), saving a lot of energy. Consequently, the separated AS and RS containing the unreacted lithium salt can be directly reused. For industrial production, the entire process may be operated continuously in a closed loop without discharging any wastes. Moreover, Li2S cathodes and sulfide-electrolyte Li6PS5Cl derived from the synthesized Li2S show impressive battery performance, displaying the great potential of this method for practical applications.

US Backscatter for Liver Fat Quantification: An AIUM-RSNA QIBA Pulse-Echo Quantitative Ultrasound Initiative.

Nonalcoholic fatty liver disease (NAFLD) is believed to affect one-third of American adults. Noninvasive methods that enable detection and monitoring of NAFLD have the potential for great public health benefits. Because of its low cost, portability, and noninvasiveness, US is an attractive alternative to both biopsy and MRI in the assessment of liver steatosis. NAFLD is qualitatively associated with enhanced B-mode US echogenicity, but visual measures of B-mode echogenicity are negatively affected by interobserver variability. Alternatively, quantitative backscatter parameters, including the hepatorenal index and backscatter coefficient, are being investigated with the goal of improving US-based characterization of NAFLD. The American Institute of Ultrasound in Medicine and Radiological Society of North America Quantitative Imaging Biomarkers Alliance are working to standardize US acquisition protocols and data analysis methods to improve the diagnostic performance of the backscatter coefficient in liver fat assessment. This review article explains the science and clinical evidence underlying backscatter for liver fat assessment. Recommendations for data collection are discussed, with the aim of minimizing potential confounding effects associated with technical and biologic variables.