The Future Is Beyond Bright: The Evolving Role of Quantitative US for Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a common cause of morbidity and mortality. Nonfocal liver biopsy is the historical reference standard for evaluating NAFLD, but it is limited by invasiveness, high cost, and sampling error. Imaging methods are ideally situated to provide quantifiable results and rule out other anatomic diseases of the liver. MRI and US have shown great promise for the noninvasive evaluation of NAFLD. US is particularly well suited to address the population-level problem of NAFLD because it is lower-cost, more available, and more tolerable to a broader range of patients than MRI. Noninvasive US methods to evaluate liver fibrosis are widely available, and US-based tools to evaluate steatosis and inflammation are gaining traction. US techniques including shear-wave elastography, Doppler spectral imaging, attenuation coefficient, hepatorenal index, speed of sound, and backscatter-based estimation have regulatory clearance and are in clinical use. New methods based on channel and radiofrequency data analysis approaches have shown promise but are mostly experimental. This review discusses the advantages and limitations of clinically available and experimental approaches to sonographic liver tissue characterization for NAFLD diagnosis as well as future applications and strategies to overcome current limitations.

Assessment of the added value of intravenous gadolinium for knee osteosarcoma resection planning in pediatric and young adult patients.

BACKGROUND AND OBJECTIVES: To assess the impact of Gadolinium-enhanced magnetic resonance imaging (MRI) sequences on Preoperative imaging evaluation and surgical planning parameters for osteosarcoma (OS) of the knee in pediatric and young adult patients. METHODS: Thirty MRI scans of patients with OS about the knee were reviewed by five orthopedic oncologists. Key preoperative parameters (neurovascular bundle involvement, intra-articular tumor extension, extent of intramedullary extension) and surgical plans were evaluated based on non-contrast versus Gd contrast enhanced sequences. Assessment agreement, inter-rater agreement, and intrarater agreement between pre and postcontrast images were evaluated via Kappa statistics. RESULTS: Moderate agreement was seen between non and contrast-enhanced assessment of neurovascular involvement and intra-articular tumor extension. Intrarater reproducibility was substantial for neurovascular bundle involvement (precontrast Kappa: 0.63, postcontrast Kappa: 0.69). Intrarater reproducibility was also substantial for precontrast (Kappa: 0.70) and moderate for postcontrast (Kappa: 0.50) assessment of intra-articular tumor extension. Planned resection length and choice of surgical approach were similar between sequences. The addition of Gd-enhanced sequences improved the inter-rater agreement across collected parameters. CONCLUSIONS: While some findings suggest that contrast enhanced sequences may not significantly alter the assessment of key preoperative planning parameters by orthopedic oncologists, they may help reduce variability among providers with differing experience levels.

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

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an estimated prevalence of up to 30% in the general population and higher in people with type 2 diabetes. The assessment of liver fat content is essential to help identify patients with or who are at risk for NAFLD and to follow their disease over time. The American Institute of Ultrasound in Medicine-RSNA Quantitative Imaging Biomarkers Alliance Pulse-Echo Quantitative Ultrasound Initiative was formed to help develop and standardize acquisition protocols and to better understand confounding factors of US-based fat quantification. The three quantitative US parameters explored by the initiative are attenuation, backscatter coefficient, and speed of sound. The purpose of this review is to present the current state of attenuation imaging for fat quantification and to provide expert opinion on examination performance and interpretation. US attenuation methods that need further study are outlined.

Pulse-Echo Quantitative US Biomarkers for Liver Steatosis: Toward Technical Standardization.

Excessive liver fat (steatosis) is now the most common cause of chronic liver disease worldwide and is an independent risk factor for cirrhosis and associated complications. Accurate and clinically useful diagnosis, risk stratification, prognostication, and therapy monitoring require accurate and reliable biomarker measurement at acceptable cost. This article describes a joint effort by the American Institute of Ultrasound in Medicine (AIUM) and the RSNA Quantitative Imaging Biomarkers Alliance (QIBA) to develop standards for clinical and technical validation of quantitative biomarkers for liver steatosis. The AIUM Liver Fat Quantification Task Force provides clinical guidance, while the RSNA QIBA Pulse-Echo Quantitative Ultrasound Biomarker Committee develops methods to measure biomarkers and reduce biomarker variability. In this article, the authors present the clinical need for quantitative imaging biomarkers of liver steatosis, review the current state of various imaging modalities, and describe the technical state of the art for three key liver steatosis pulse-echo quantitative US biomarkers: attenuation coefficient, backscatter coefficient, and speed of sound. Lastly, a perspective on current challenges and recommendations for clinical translation for each biomarker is offered.

Variation of Shear Wave Elastography With Preload in the Thyroid: Quantitative Validation.

OBJECTIVES: Thyroid shear wave elastography (SWE) has been shown to have advantages compared to biopsy or other imaging modalities in the evaluation of thyroid nodules. However, studies show variability in its assessment. The objective of this study was to evaluate whether stiffness measurements of the normal thyroid, as estimated by SWE, varied due to preload force or the pressure applied between the transducer and the patient. METHODS: In this study, a measurement system was attached to the ultrasound transducer to measure the applied load. Shear wave elastographic measurements were obtained from the left lobe of the thyroid at applied transducer forces between 2 and 10 N. A linear mixed-effects model was constructed to quantify the association between the preload force and stiffness while accounting for correlations between repeated measurements within each participant. The preload force effect on elasticity was modeled by both linear and quadratic terms to account for a possible nonlinear association between these variables. RESULTS: Nineteen healthy volunteers without known thyroid disease participated in the study. The participants had a mean age ± SD of 36 ± 8 years; 74% were female; 74% had a normal body mass index; and 95% were white non-Hispanic/Latino. The estimated elastographic value at a 2-N preload force was 16.7 kPa (95% confidence interval, 14.1-19.3 kPa), whereas the value at 10 N was 29.9 kPa (95% confidence interval, 24.9-34.9 kPa). CONCLUSIONS: The preload force was significantly and nonlinearly associated with SWE estimates of thyroid stiffness. Quantitative standardization of preload forces in the assessment of thyroid nodules using elastography is an integral factor for improving the accuracy of thyroid nodule evaluation.

Radiological Society of North America/Quantitative Imaging Biomarker Alliance Shear Wave Speed Bias Quantification in Elastic and Viscoelastic Phantoms.

OBJECTIVES: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms. METHODS: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz. RESULTS: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a - 0.27 ± 0.027-m/s (-12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source. CONCLUSIONS: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

Normal Liver Stiffness Measured with MR Elastography in Children.

Background Stiffness thresholds for liver MR elastography in children vary between studies and may differ from thresholds in adults. Normative liver stiffness data are needed to optimize diagnostic thresholds for children. Purpose To determine normal liver stiffness, and associated normal ranges for children, as measured with MR elastography across vendors and field strengths. Materials and Methods This was a prospective multicenter cohort study (ClinicalTrials.gov identifier: NCT03235414). Volunteers aged 7-17.9 years without a known history of liver disease were recruited at four sites for a research MRI and blood draw between February 2018 and October 2019. MRI was performed on three vendor platforms and at two field strengths (1.5 T and 3.0 T). All MRI scans were centrally analyzed; stiffness, proton density fat fraction (PDFF), and R2* values were expressed as means of means. Mean and 95% confidence intervals (CIs) for liver stiffness were calculated. Pearson correlation coefficient (r), two-sample t test, or analysis of variance was used to assess univariable associations. Results Seventy-one volunteers had complete data and no documented exclusion criterion (median age, 12 years; interquartile range [IQR], 10-15 years; 39 female participants). Median body mass index percentile was 54% (IQR, 32.5%-69.5%). Mean liver stiffness was 2.1 kPa (95% CI: 2.0, 2.2 kPa) with mean ± 1.96 kPa standard deviation of 1.5-2.8 kPa. Median liver PDFF was 2.0% (IQR, 1.7%-2.6%). There was no association between liver stiffness and any patient variable or MRI scanner factor. Conclusion Mean liver stiffness measured with MR elastography in children without liver disease was 2.1 kPa (similar to that in adults). The 95th percentile of normal liver stiffness was 2.8 kPa. Liver stiffness was independent of sex, age, or body mass index and did not vary with MRI scanner vendor or field strength. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Yin in this issue.

Liver fibrosis imaging: A clinical review of ultrasound and magnetic resonance elastography.

Liver fibrosis is a histological hallmark of most chronic liver diseases, which can progress to cirrhosis and liver failure, and predisposes to hepatocellular carcinoma. Accurate diagnosis of liver fibrosis is necessary for prognosis, risk stratification, and treatment decision-making. Liver biopsy, the reference standard for assessing liver fibrosis, is invasive, costly, and impractical for surveillance and treatment response monitoring. Elastography offers a noninvasive, objective, and quantitative alternative to liver biopsy. This article discusses the need for noninvasive assessment of liver fibrosis and reviews the comparative advantages and limitations of ultrasound and magnetic resonance elastography techniques with respect to their basic concepts, acquisition, processing, and diagnostic performance. Variations in clinical contexts of use and common pitfalls associated with each technique are considered. In addition, current challenges and future directions to improve the diagnostic accuracy and clinical utility of elastography techniques are discussed. Level of Evidence: 5 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:25-42.

Portal Venous Pulsatility Index: A Novel Biomarker for Diagnosis of High-Risk Nonalcoholic Fatty Liver Disease.

OBJECTIVE. The purpose of this study was to assess the accuracy of portal vein pulsatility for noninvasive diagnosis of high-risk nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS. This retrospective study included patients with biopsy-proven diagnosis of NAFLD who underwent duplex Doppler ultrasound assessment of the main portal vein within 1 year of liver biopsy (January 2014 to February 2018). Doppler ultrasound images were reviewed. The spectral waveform was used to measure the maximum (Vmax) and minimum (Vmin) velocity of blood in the portal veins. Venous pulsatility index (VPI) defined as (Vmax - Vmin) / Vmax was calculated. ROC curve analysis was used to calculate AUC as a measure of accuracy to determine the value of this index for diagnosis of high-risk NAFLD and compared with that of the following four clinical decision aids: NAFLD fibrosis score (FS), fibrosis-4 index (FIB-4), BARD score (body mass index, aspartate aminotransferase [AST]-to-alanine aminotransferase ratio, diabetes mellitus), and AST-to-platelet ratio index (APRI). The value of adding VPI to these indexes was also investigated. RESULTS. Of 123 study subjects, 33 (26.8%) had high-risk NAFLD and were found to have a lower VPI than the other 90 subjects (0.19 vs 0.32; p < 0.001). VPI, NAFLD FS, FIB-4, and APRI had statistically significant diagnostic values for high-risk NAFLD. VPI had the highest optimism-corrected AUC (VPI, 0.84 [95% CI, 0.77-0.91]; NAFLD FS, 0.74 [95% CI, 0.63-0.83]; FIB-4, 0.81 [95% CI, 0.72-0.89]; APRI, 0.73 [95% CI, 0.61-0.82]). Addition of VPI to any of the four scoring systems significantly improved the diagnostic value of the score for high-risk NAFLD. CONCLUSION. VPI may be an accurate noninvasive biomarker for diagnosis of high-risk NAFLD.

Memory-efficient low-compute segmentation algorithms for bladder-monitoring smart ultrasound devices.

Post-operative urinary retention is a medical condition where patients cannot urinate despite having a full bladder. Ultrasound imaging of the bladder is used to estimate urine volume for early diagnosis and management of urine retention. Moreover, the use of bladder ultrasound can reduce the need for an indwelling urinary catheter and the risk of catheter-associated urinary tract infection. Wearable ultrasound devices combined with machine-learning based bladder volume estimation algorithms reduce the burdens of nurses in hospital settings and improve outpatient care. However, existing algorithms are memory and computation intensive, thereby demanding the use of expensive GPUs. In this paper, we develop and validate a low-compute memory-efficient deep learning model for accurate bladder region segmentation and urine volume calculation. B-mode ultrasound bladder images of 360 patients were divided into training and validation sets; another 74 patients were used as the test dataset. Our 1-bit quantized models with 4-bits and 6-bits skip connections achieved an accuracy within [Formula: see text] and [Formula: see text], respectively, of a full precision state-of-the-art neural network (NN) without any floating-point operations and with an [Formula: see text] and [Formula: see text] reduction in memory requirements to fit under 150 kB. The means and standard deviations of the volume estimation errors, relative to estimates from ground-truth clinician annotations, were [Formula: see text] ml and [Formula: see text] ml, respectively. This lightweight NN can be easily integrated on the wearable ultrasound device for automated and continuous monitoring of urine volume. Our approach can potentially be extended to other clinical applications, such as monitoring blood pressure and fetal heart rate.

Liver fibrosis assessment: MR and US elastography.

Elastography has emerged as a preferred non-invasive imaging technique for the clinical assessment of liver fibrosis. Elastography methods provide liver stiffness measurement (LSM) as a surrogate quantitative biomarker for fibrosis burden in chronic liver disease (CLD). Elastography can be performed either with ultrasound or MRI. Currently available ultrasound-based methods include strain elastography, two-dimensional shear wave elastography (2D-SWE), point shear wave elastography (pSWE), and vibration-controlled transient elastography (VCTE). MR Elastography (MRE) is widely available as two-dimensional gradient echo MRE (2D-GRE-MRE) technique. US-based methods provide estimated Young's modulus (eYM) and MRE provides magnitude of the complex shear modulus. MRE and ultrasound methods have proven to be accurate methods for detection of advanced liver fibrosis and cirrhosis. Other clinical applications of elastography include liver decompensation prediction, and differentiation of non-alcoholic steatohepatitis (NASH) from simple steatosis (SS). In this review, we briefly describe the different elastography methods, discuss current clinical applications, and provide an overview of advances in the field of liver elastography.

HaTU-Net: Harmonic Attention Network for Automated Ovarian Ultrasound Quantification in Assisted Pregnancy.

Antral follicle Count (AFC) is a non-invasive biomarker used to assess ovarian reserves through transvaginal ultrasound (TVUS) imaging. Antral follicles' diameter is usually in the range of 2-10 mm. The primary aim of ovarian reserve monitoring is to measure the size of ovarian follicles and the number of antral follicles. Manual follicle measurement is inhibited by operator time, expertise and the subjectivity of delineating the two axes of the follicles. This necessitates an automated framework capable of quantifying follicle size and count in a clinical setting. This paper proposes a novel Harmonic Attention-based U-Net network, HaTU-Net, to precisely segment the ovary and follicles in ultrasound images. We replace the standard convolution operation with a harmonic block that convolves the features with a window-based discrete cosine transform (DCT). Additionally, we proposed a harmonic attention mechanism that helps to promote the extraction of rich features. The suggested technique allows for capturing the most relevant features, such as boundaries, shape, and textural patterns, in the presence of various noise sources (i.e., shadows, poor contrast between tissues, and speckle noise). We evaluated the proposed model on our in-house private dataset of 197 patients undergoing TransVaginal UltraSound (TVUS) exam. The experimental results on an independent test set confirm that HaTU-Net achieved a Dice coefficient score of 90% for ovaries and 81% for antral follicles, an improvement of 2% and 10%, respectively, when compared to a standard U-Net. Further, we accurately measure the follicle size, yielding the recall, and precision rates of 91.01% and 76.49%, respectively.

AI-Enabled, Ultrasound-Guided Handheld Robotic Device for Femoral Vascular Access.

Hemorrhage is a leading cause of trauma death, particularly in prehospital environments when evacuation is delayed. Obtaining central vascular access to a deep artery or vein is important for administration of emergency drugs and analgesics, and rapid replacement of blood volume, as well as invasive sensing and emerging life-saving interventions. However, central access is normally performed by highly experienced critical care physicians in a hospital setting. We developed a handheld AI-enabled interventional device, AI-GUIDE (Artificial Intelligence Guided Ultrasound Interventional Device), capable of directing users with no ultrasound or interventional expertise to catheterize a deep blood vessel, with an initial focus on the femoral vein. AI-GUIDE integrates with widely available commercial portable ultrasound systems and guides a user in ultrasound probe localization, venous puncture-point localization, and needle insertion. The system performs vascular puncture robotically and incorporates a preloaded guidewire to facilitate the Seldinger technique of catheter insertion. Results from tissue-mimicking phantom and porcine studies under normotensive and hypotensive conditions provide evidence of the technique's robustness, with key performance metrics in a live porcine model including: a mean time to acquire femoral vein insertion point of 53 ± 36 s (5 users with varying experience, in 20 trials), a total time to insert catheter of 80 ± 30 s (1 user, in 6 trials), and a mean number of 1.1 (normotensive, 39 trials) and 1.3 (hypotensive, 55 trials) needle insertion attempts (1 user). These performance metrics in a porcine model are consistent with those for experienced medical providers performing central vascular access on humans in a hospital.

Image Processing Pipeline for Liver Fibrosis Classification Using Ultrasound Shear Wave Elastography.

The purpose of this study was to develop an automated method for classifying liver fibrosis stage ≥F2 based on ultrasound shear wave elastography (SWE) and to assess the system's performance in comparison with a reference manual approach. The reference approach consists of manually selecting a region of interest from each of eight or more SWE images, computing the mean tissue stiffness within each of the regions of interest and computing a resulting stiffness value as the median of the means. The 527-subject database consisted of 5526 SWE images and pathologist-scored biopsies, with data collected from a single system at a single site. The automated method integrates three modules that assess SWE image quality, select a region of interest from each SWE measurement and perform machine learning-based, multi-image SWE classification for fibrosis stage ≥F2. Several classification methods were developed and tested using fivefold cross-validation with training, validation and test sets partitioned by subject. Performance metrics were area under receiver operating characteristic curve (AUROC), specificity at 95% sensitivity and number of SWE images required. The final automated method yielded an AUROC of 0.93 (95% confidence interval: 0.90-0.94) versus 0.69 (95% confidence interval: 0.65-0.72) for the reference method, 71% specificity with 95% sensitivity versus 5% and four images per decision versus eight or more. In conclusion, the automated method reported in this study significantly improved the accuracy for ≥F2 classification of SWE measurements as well as reduced the number of measurements needed, which has the potential to reduce clinical workflow.

Diagnostic Accuracy of Shear Wave Elastography as a Non-invasive Biomarker of High-Risk Non-alcoholic Steatohepatitis in Patients with Non-alcoholic Fatty Liver Disease.

In this study, we evaluated the diagnostic accuracy of shear wave elastography (SWE) for differentiating high-risk non-alcoholic steatohepatitis (hrNASH) from non-alcoholic fatty liver and low-risk non-alcoholic steatohepatitis (NASH). Patients with non-alcoholic fatty liver disease scheduled for liver biopsy underwent pre-biopsy SWE. Ten SWE measurements were obtained. Biopsy samples were reviewed using the NASH Clinical Research Network Scoring System and patients with hrNASH were identified. Receiver operating characteristic curves for SWE-based hrNASH diagnosis were charted. One hundred sixteen adult patients underwent liver biopsy at our institution for the evaluation of non-alcoholic fatty liver disease. The area under the receiver operating characteristic curve of SWE for hrNASH diagnosis was 0.73 (95% confidence interval: 0.61-0.84, p < 0.001). The Youden index-based optimal stiffness cutoff value for hrNASH diagnosis was calculated as 8.4 kPa (1.67 m/s), with a sensitivity of 77% and specificity of 66%. SWE may be useful for the detection of NASH patients at risk of long-term liver-specific morbidity and mortality.

Principles of ultrasound elastography.

Tissue stiffness has long been known to be a biomarker of tissue pathology. Ultrasound elastography measures tissue mechanical properties by monitoring the response of tissue to acoustic energy. Different elastographic techniques have been applied to many different tissues and diseases. Depending on the pathology, patient-based factors, and ultrasound operator-based factors, these techniques vary in accuracy and reliability. In this review, we discuss the physical principles of ultrasound elastography, discuss differences between different ultrasound elastographic techniques, and review the advantages and disadvantages of these techniques in clinical practice.

Quantitative Hepatic Fat Quantification in Non-alcoholic Fatty Liver Disease Using Ultrasound-Based Techniques: A Review of Literature and Their Diagnostic Performance.

Non-alcoholic fatty liver disease is a condition that is characterized by the presence of >5% fat in the liver and affects more than one billion people worldwide. If adequate and early precautions are not taken, non-alcoholic fatty liver disease can progress to cirrhosis and death. The current reference standard for detecting hepatic steatosis is a liver biopsy. However, because of the potential morbidity associated with liver biopsies, non-invasive imaging biomarkers have been extensively investigated. Magnetic resonance imaging-based methods have proven accuracy in quantifying liver steatosis; however, these techniques are costly and have limited availability. Ultrasound-based quantitative imaging techniques are increasingly utilized because of their widespread availability, ease of use and relative cost-effectiveness. Several ultrasound-based liver fat quantification techniques have been investigated, including techniques that measure changes in the acoustic properties of the liver caused by the presence of fat. In this review, we focus on quantitative ultrasound approaches and their diagnostic performance in the realm of non-alcoholic fatty liver disease.