A Systematized Review of Quantitative Ultrasound Based on First-Order Speckle Statistics.

Since the late 1970s, the speckle interference patterns ubiquitous in pulse-echo ultrasound images have been used to characterize subresolution tissue structures. During this time, new models, estimation methods, and processing techniques have proliferated, offering a wealth of recommendations for the task of tissue characterization. A literature review was performed to draw attention to these various methods and to critically track assumptions and gaps in knowledge. A total of 388 articles were collected from a systematic search for first-order speckle statistics in diagnostic ultrasound in the NIH PubMed database and Elsevier's Scopus database. Articles were grouped by basic characteristics and evaluated for addressing fundamental assumptions. A sampling of models and methods is presented to reveal the state of the art in speckle statistics as well as sources of measurement error and other important considerations. While this body of literature emphasizes the value of speckle analysis in diagnostic ultrasound, it is shown that relatively little attention is devoted to basic assumptions such as the linearity of system response and scatterer geometry. Additionally, several areas of investigation are available to improve upon speckle statistics analysis, potentially leading to the advancement of this unique tool.

Comparing the clinical applicability of wavefront phase imaging in keratoconus versus normal eyes.

The aim of this work is to quantitatively assess the wavefront phase of keratoconic eyes measured by the ocular aberrometer t·eyede (based on WaveFront Phase Imaging Sensor), characterized by a lateral resolution of 8.6 µm without requiring any optical element to sample the wavefront information. We evaluated the parameters: root mean square error, Peak-to-Valley, and amplitude of the predominant frequency (Fourier Transform analysis) of a section of the High-Pass filter map in keratoconic and healthy cohorts. Furthermore, we have analyzed keratoconic eyes that presented dark-light bands in this map to assess their period and orientation with the Fourier Transform. There are significant statistical differences (p value < 0.001) between healthy and keratoconic eyes in the three parameters, demonstrating a tendency to increase with the severity of the disease. Otherwise, the quantification of the bands reveals that the width is independent of eye laterality and keratoconic stage as orientation, which tends to be oblique. In conclusion, the quantitative results obtained with t·eyede could help to diagnose and monitor the progression of keratoconus.

Diagnostic Accuracy of the Triglyceride-Glucose Index (TyG), TyG Body Mass Index, and TyG Waist Circumference Index for Liver Steatosis Detection.

BACKGROUND: The triglyceride-glucose index (TyG) and a combination of body mass index (BMI) and waist circumference (WC) have been proposed as predictive scores for liver steatosis (LS). The aim of this study was to determine the diagnostic accuracy of these indices compared with controlled attenuation parameters (CAPs) and other predictive scores of LS. METHODS: A retrospective analysis of patients who attended a check-up unit in 2021 was performed. LS was determined by CAP. Anthropometric and biochemical parameters for calculating TyG, TyG-BMI, TyG-WC, fatty liver index, and hepatic steatosis index were obtained. ROC curve was used to establish the best cut-off point of each TyG index for LS detection. The accuracy was determined for all patients, as well as for overweight and diabetic patients. RESULTS: Medical records of 855 patients with a median age of 48 [IQR, 44-54] years and a BMI of 25.7 [IQR 23.4-28.1] kg/m2 were included. According to CAP, LS prevalence was 31.8% (n = 272). TyG-BMI and TyG-WC show better AUCs compared with CAP (0.82, 0.81), FLI (0.96, both), and HSI (0.93, 0.85). For diabetic patients, TyG-WC shows an AUC of 0.70. Meanwhile, TyG-BMI shows better accuracy (0.75) compared with CAP. CONCLUSIONS: TyG-BMI and TyG-WC showed a superior predictive accuracy for detecting LS compared with the TyG index.

Simulation of ultrasonic scattering from scatterer size distributions using Field II.

Quantitative analysis of radio frequency (RF) signals obtained from ultrasound scanners can yield objective parameters that are gaining clinical relevance as imaging biomarkers. These include the backscatter coefficient (BSC) and the effective scatterer diameter (ESD). Biomarker validation is typically performed in phantoms which do not provide the flexibility of systematic variation of scattering properties. Computer simulations, such as those from the ultrasound simulator Field II, can allow more flexibility. However, Field II does not allow simulation of RF data from a distribution of scatterers with finite size. In this work, a simulation method is presented which builds upon previous work by including Faran theory models representative of distributions of scatterer size. These are systematically applied to RF data simulated in Field II. The method is validated by measuring the root mean square error of the estimated BSC and percent bias of the ESD and comparing to experimental results. The results indicate the method accurately simulates distributions of scatterer sizes and provides scattering similar to that seen in data from clinical scanners. Because Field II is widely used by the ultrasound community, this method can be adopted to aid in validation of quantitative ultrasound imaging biomarkers.

Homodyned K-Distribution Parameter Estimation in Quantitative Ultrasound: Autoencoder and Bayesian Neural Network Approaches.

Quantitative ultrasound (QUS) analyzes the ultrasound (US) backscattered data to find the properties of scatterers that correlate with the tissue microstructure. Statistics of the envelope of the backscattered radio frequency (RF) data can be utilized to estimate several QUS parameters. Different distributions have been proposed to model envelope data. The homodyned K-distribution (HK-distribution) is one of the most comprehensive distributions that can model US backscattered envelope data under diverse scattering conditions (varying scatterer number density and coherent scattering). The scatterer clustering parameter ( α ) and the ratio of the coherent to diffuse scattering power ( k ) are the parameters of this distribution that have been used extensively for tissue characterization in diagnostic US. The estimation of these two parameters (which we refer to as HK parameters) is done using optimization algorithms in which statistical features such as the envelope point-wise signal-to-noise ratio (SNR), skewness, kurtosis, and the log-based moments have been utilized as input to such algorithms. The optimization methods minimize the difference between features and their theoretical value from the HK model. We propose that the true value of these statistical features is a hyperplane that covers a small portion of the feature space. In this article, we follow two approaches to reduce the effect of sample features' error. We propose a model projection neural network based on denoising autoencoders to project the noisy features into this space based on this assumption. We also investigate if the noise distribution can be learned by the deep estimators. We compare the proposed methods with conventional methods using simulations, an experimental phantom, and data from an in vivo animal model of hepatic steatosis. The network weight and a demo code are available online at ht.tp://code.sonography.ai.

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.

Physics-Inspired Regularized Pulse-Echo Quantitative Ultrasound: Efficient Optimization With ADMM.

Pulse-echo quantitative ultrasound (PEQUS), which estimates the quantitative properties of tissue microstructure, entails estimating the average attenuation and the backscatter coefficient (BSC). Growing recent research has focused on the regularized estimation of these parameters. Herein, we make two contributions to this field: first, we consider the physics of the average attenuation and backscattering to devise regularization terms accordingly. More specifically, since the average attenuation gradually alters in different parts of the tissue, while BSC can vary markedly from tissue to tissue, we apply L2 and L1 norms for the average attenuation and the BSC, respectively. Second, we multiply different frequencies and depths of the power spectra with different weights according to their noise levels. Our rationale is that the high-frequency contents of the power spectra at deep regions have a low signal-to-noise ratio (SNR). We exploit the alternating direction method of multipliers (ADMM) for optimizing the cost function. The qualitative and quantitative evaluations of bias and variance exhibit that our proposed algorithm improves the estimations of the average attenuation and the BSC up to about 100%.

Hunger & satiety signals: another key mechanism involved in the NAFLD pathway.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disease, although prevalence could change according to region, nowadays is considered a public health problem whose real impact on the health system is unknown. NAFLD has a multifactorial and complex pathophysiology, due to this, developing a unique and effective pharmacological treatment has not been successful in reverting or avoiding the progression of this liver disease. Even though NAFLD pathophysiology is known, all actual treatments are focused on modifying or regulating the metabolic pathways, some of which interplay with obesity. It has been known that impairments in hunger and satiety signals are associated with obesity, however, abnormalities in these signals in patients with NAFLD and obesity are not fully elucidated. To describe these mechanisms opens an additional option as a therapeutic target sharing metabolic pathways with NAFLD, therefore, this review aims to describe the hormones and peptides implicated in both hunger-satiety in NAFLD. It has been established that NAFLD pharmacological treatment cannot be focused on a single purpose; hence, identifying interplays that lead to adding or modifying current treatment options could also have an impact on another related outcome such as hunger or satiety signals.

TOR complex 1 negatively regulates NDR kinase Cbk1 to control cell separation in budding yeast.

The target of rapamycin (TOR) signalling pathway plays a key role in the coordination between cellular growth and the cell cycle machinery in eukaryotes. The underlying molecular mechanisms by which TOR might regulate events after anaphase remain unknown. We show for the first time that one of the 2 TOR complexes in budding yeast, TORC1, blocks the separation of cells following cytokinesis by phosphorylation of a member of the NDR (nuclear Dbf2-related) protein-kinase family, the protein Cbk1. We observe that TORC1 alters the phosphorylation pattern of Cbk1 and we identify a residue within Cbk1 activation loop, T574, for which a phosphomimetic substitution makes Cbk1 catalytically inactive and, indeed, reproduces TORC1 control over cell separation. In addition, we identify the exocyst component Sec3 as a key substrate of Cbk1, since Sec3 activates the SNARE complex to promote membrane fusion. TORC1 activity ultimately compromises the interaction between Sec3 and a t-SNARE component. Our data indicate that TORC1 negatively regulates cell separation in budding yeast by participating in Cbk1 phosphorylation, which in turn controls the fusion of secretory vesicles transporting hydrolase at the site of division.

Accuracy of Narrow-Band Imaging International Colorectal Endoscopic Classification for Predicting the Histology of Colon Polyps by Experienced Endoscopists and Trainees.

BACKGROUND/AIMS: Digital chromoendoscopy has proven to be useful in the histological prediction of premalignant lesions in the colon. The aim of the study was to describe the diagnostic performance of Narrow-Band Imaging International Colorectal Endoscopic Classification in the histological differentiation of colonic lesions, applied by expert endoscopists and trainees. MATERIALS AND METHODS: Cross-sectional study that includes high-definition endoscopic images and histopathological reports of 94 patients over 50 years. Images were evaluated and classified as Narrow-Band Imaging International Colorectal Endoscopic 1, 2, or 3 by 2 experts and 2 trainee endoscopists, all of them blinded to histological results. Diagnostic accuracy for each Narrow-Band Imaging International Colorectal Endoscopic category was calculated for trainees and expert endoscopists. Intra-observer agreement was evaluated by means of Cohen's kappa coefficient; meanwhile, inter-observer agreement was calculated by means of Fleiss' kappa. RESULTS: Evaluations performed by expert and trainee endoscopists showed a performance for Narrow-Band Imaging International Colorectal Endoscopic category 1: sensitivity 62%, specificity 85%, area under receiver operator characteristic 0.73; Narrow-Band Imaging International Colorectal Endoscopic category 2: sensitivity 61%, specificity 73%, area under receiver operator characteristic 0.66; and Narrow-Band Imaging International Colorectal Endoscopic category 3: sensitivity 88%, specificity 91%, area under receiver operator characteristic 0.86. The total agreement of the evaluations was 72.5%, with an inter-observer variability of K 0.60 (95% CI 0.52-0.74). When the diagnostic performance for non-dysplastic lesions and dysplastic lesions (Narrow-Band Imaging International Colorectal Endoscopic 1 vs 2 and 3) was compared, we observed an increase in sensitivity for differentiated adenomas (Narrow-Band Imaging International Colorectal Endoscopic 2). CONCLUSION: Narrow-Band Imaging International Colorectal Endoscopic Classification applied in the histological prediction of static images of colonic lesions has a good diagnostic performance for Narrow-Band Imaging International Colorectal Endoscopic category 3, as well as an acceptable performance for Narrow-Band Imaging International Colorectal Endoscopic category 1, with a moderate agreement among observers.

Recent Advances in Attenuation Estimation.

This chapter reviews some of the recent advances in the estimation of the local and the total attenuation, with an emphasis on reducing the bias and variance of the estimates. A special focus is put on describing the effect of power spectrum estimation on bias and variance, the introduction of regularization strategies, as well as on eliminating the need to use reference phantoms for compensating for system dependent effects.

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.

Low-Normal Thyroid Function Is Not Associated with Either Non-Alcoholic Fatty Liver Disease or with Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND: The association of low-normal thyroid function (LNTF) with non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated fatty liver disease (MAFLD) is controversial; thus, the aim of this study is to determine this association. METHODS: NAFLD was evaluated by controlled attenuation parameter of transient elastography. Patients were classified by MAFLD criteria. LNTF was defined as TSH levels of 2.5 to 4.5 mIU/L and were divided into three different cut-off points (>4.5 to 5.0, >3.1, and >2.5 mIU/L). Associations between LNTF, NAFLD, and MAFLD were evaluated by univariate and multivariate logistic regression analyses. RESULTS: A total of 3697 patients were included; 59% (n = 2179) were male, and median age and body mass index were 48 (43-55) years and 25.9 (23.6-28.5) kg/m2, respectively, and 44% (n = 1632) were diagnosed with NAFLD. THS levels of 2.5 and 3.1 showed significant associations with the presence of NAFLD and MAFLD; however, LNTF did not show an independent association with the presence of NAFLD or MAFLD in multivariate analysis. According to different cut-off points, patients with LNTF presented similar risks for NAFLD as the general population. CONCLUSION: LNTF is not associated with NAFLD or MAFLD. Patients with high LNTF are equally at risk for NAFLD as the general population.

A Geometric Model of Ultrasound Backscatter to Describe Microstructural Anisotropy of Tissue.

Methods to assess ultrasound backscatter anisotropy from clinical array transducers have recently been developed. However, they do not provide information about the anisotropy of microstructural features of the specimens. This work develops a simple geometric model, referred to as the secant model, of backscatter coefficient anisotropy. Specifically, we evaluate anisotropy of the frequency dependence of the backscatter coefficient parameterized in terms of effective scatterer size. We assess the model in phantoms with known scattering sources and in a skeletal muscle, a well-known anisotropic tissue. We demonstrate that the secant model can determine the orientation of the anisotropic scatterers, as well as accurately determining effective scatterer sizes, and it may classify isotropic versus anisotropic scatterers. The secant model may find utility in monitoring disease progression as well as characterizing normal tissue architectures.

Arsenic may be a carcinogenic determinant of a subset of gallbladder cancer: A pilot study.

Gallbladder cancer (GBC) is one of the deadliest malignancy and treatment options are deplorably limited. Better strategies of prevention are urgently needed but knowledge on risk factors remains scarce. Recent data suggested that arsenic (As) may be involved in GBC carcinogenesis but the question remains debated. To date, there are no data on As measurement in GBC samples. This pilot study aimed to measure As concentrations in tissue samples from patients with GBC compared to non-cancerous gallbladder (NCGB). Included patients underwent cholecystectomy at Hospital Clinico Universidad de Chile, Santiago in Chile, a country with high As exposure, between 2001 and 2020. Tissue samples were preserved in formalin-fixed, paraffin-embedded blocks. Selected samples were retrieved, processed and submitted to inductively coupled plasma mass spectrometry (ICP-MS) to determine As concentrations. A total of 77 patients were included, including 35 GBC and 42 NCGB. The two groups were comparable, except for age (68 vs. 49 years, p < 0.001). Measured in 11 GBC and 38 NCGB, total As was detected in 5 GBC (14%) compared to 0 NCGB samples (p < 0.001). GBC group also showed higher median values of As compared to NCGB (p < 0.001). This pilot study provided a proof-of-concept to measure As concentrations in gallbladder samples and showed higher level of As in GBC samples compared to NCGB, paving the way for future studies aiming to investigate the impact of As on GBC, which may contribute to the prevention of this deadly disease.

Multiscale Label-Free Imaging of Fibrillar Collagen in the Tumor Microenvironment.

With recent advances in cancer therapeutics, there is a great need for improved imaging methods for characterizing cancer onset and progression in a quantitative and actionable way. Collagen, the most abundant extracellular matrix protein in the tumor microenvironment (and the body in general), plays a multifaceted role, both hindering and promoting cancer invasion and progression. Collagen deposition can defend the tumor with immunosuppressive effects, while aligned collagen fiber structures can enable tumor cell migration, aiding invasion and metastasis. Given the complex role of collagen fiber organization and topology, imaging has been a tool of choice to characterize these changes on multiple spatial scales, from the organ and tumor scale to cellular and subcellular level. Macroscale density already aids in the detection and diagnosis of solid cancers, but progress is being made to integrate finer microscale features into the process. Here we review imaging modalities ranging from optical methods of second harmonic generation (SHG), polarized light microscopy (PLM), and optical coherence tomography (OCT) to the medical imaging approaches of ultrasound and magnetic resonance imaging (MRI). These methods have enabled scientists and clinicians to better understand the impact collagen structure has on the tumor environment, at both the bulk scale (density) and microscale (fibrillar structure) levels. We focus on imaging methods with the potential to both examine the collagen structure in as natural a state as possible and still be clinically amenable, with an emphasis on label-free strategies, exploiting intrinsic optical properties of collagen fibers.

Bariatric endoscopic-surgical therapies for NAFLD. Should they be considered viable options among current treatments?

Nowadays, non-alcoholic fatty liver disease is one of the first causes of liver transplant worldwide; many efforts have been done to find the perfect drug for this multifactorial disease. Presently we just have a few drugs that could be used in specific and limited clinical scenarios. Current evidence suggests that bariatric endoscopic and surgical therapies could be strategies with optimal outcomes, with high impact in quality of life, decrease of cardiovascular risk, and improvement in metabolic profile, despite being considered expensive procedures. This review proposes to consider these therapies early together with liver fibrosis evaluation, with long term cost-effectiveness benefits in the absence of response to lifestyle modifications and pharmacological treatments.

¿Cuándo el patólogo debe solicitar inmunomarcación con B-Catenina?: una revisión de la literatura a propósito de dos casos / When should the pathologist request immunostaining with B-catenin?: a review of the literature on two cases

For more than 20 years, immunohistochemistry has represented an auxiliary test of great relevance to support pathological work, however, it should be noted that the pillar of diagnosis continues and will continue to be the classic morphological description based on hematoxylin eosin and the trained eye of the specialist. In neoplastic pathologies, whether benign or malignant, it is becoming increasingly necessary to incorporate new tissue biomarkers that help objectify or confirm the diagnosis of each patient, in order to provide better treatment or a more precise diagnosis about the biological nature of their illness. In this line, there has been intense research in relation to the participation of the Wnt/ß-catenin pathway in the development of various types of tumors, including colon adenocarcinoma, some pancreatic neoplasms and even some tumors of mesenchymal origin, as will be seen. in this work. In this context and based on two clinical cases of special interest, we have prepared a brief review of the literature considering the biological aspects of ß-catenin, tumors where there is currently a true relative consensus that its immunolabeling offers a real contribution to the confirmation of the entity and finally a limited exposition regarding the future of this biomarker in the pathology discipline.

Desde hace más de 20 años la inmunohistoquímica ha representado una prueba auxiliar de gran relevancia para apoyar el trabajo anatomopatológico, no obstante, cabe señalar que, aún el pilar del diagnóstico sigue y seguirá siendo la descripción morfológica clásica basada en hematoxilina eosina y el ojo entrenado del especialista. En las patologías neoplásicas, ya sea benignas, como malignas, se hace cada vez más necesario la incorporación de nuevos biomarcadores tisulares que ayuden a objetivar o confirmar el diagnóstico de cada paciente, con objeto de entregar un mejor tratamiento o un diagnóstico más preciso de la naturaleza biológica de su enfermedad. En esta línea, ha habido intensa investigación en relación con la participación de la vía Wnt/ß-catenina en el desarrollo de varios tipos de cáncer, entre ellos el adenocarcinoma de colon, algunas neoplasias pancreáticas e incluso algunos tumores de origen mesenquimal como se verá en este trabajo. En este contexto y partir de dos casos clínicos de especial interés, hemos preparado una breve revisión de la literatura considerando los aspectos biológicos de la ß-catenina, los tumores donde en la actualidad existe verdadero consenso de que su inmunomarcación ofrece un aporte real a la confirmación de la entidad y finalmente una exposición acotada respecto al futuro de este biomarcador en la disciplina de la anatomía patológica.

Impact on Prevalence of the Application of NAFLD/MAFLD Criteria in Overweight and Normal Weight Patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Recently, the term metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed and adapted to body mass index (BMI). This study describes the impact on prevalence of the application of both criteria in overweight and lean patients. METHODS: Patients who were evaluated for liver steatosis by transient elastography were included and divided according to BMI (≥25 kg/m2 and <25 kg/m2) and classified as NAFLD or MAFLD, according to metabolic abnormalities. Differences in prevalence were evaluated applying both criteria. A multivariate analysis was performed to evaluate independent associations of metabolic abnormalities and liver steatosis in lean patients. RESULTS: 3847 patients were included. In overweight patients (61%), the prevalence NAFLD was 63.6% and 65.3% for MAFLD (p = 0.22). In contrast, the prevalence of MAFLD was lower (7.9% vs. 18.3%, p ≤ 0.001) in lean patients. In this group, higher age, fasting glucose, triglycerides, and waist circumference showed independent association with liver steatosis. CONCLUSION: The application of NAFLD/MAFLD criteria did not show prevalence differences in overweight patients. With MAFLD criteria, the prevalence is lower in lean patients, but patients with high risk of progression of liver disease for steatosis were identified, according to their metabolic abnormalities.