Congestive Hepatopathy: Pathophysiology, Workup, and Imaging Findings with Pathologic Correlation.

Liver congestion is increasingly encountered in clinical practice and presents diagnostic pitfalls of which radiologists must be aware. The complex altered hemodynamics associated with liver congestion leads to diffuse parenchymal changes and the development of benign and malignant nodules. Distinguishing commonly encountered benign hypervascular lesions, such as focal nodular hyperplasia (FNH)-like nodules, from hepatocellular carcinoma (HCC) can be challenging due to overlapping imaging features. FNH-like lesions enhance during the hepatic arterial phase and remain isoenhancing relative to the background liver parenchyma but infrequently appear to wash out at delayed phase imaging, similar to what might be seen with HCC. Heterogeneity, presence of an enhancing capsule, washout during the portal venous phase, intermediate signal intensity at T2-weighted imaging, restricted diffusion, and lack of uptake at hepatobiliary phase imaging point toward the diagnosis of HCC, although these features are not sensitive individually. It is important to emphasize that the Liver Imaging Reporting and Data System (LI-RADS) algorithm cannot be applied in congested livers since major LI-RADS features lack specificity in distinguishing HCC from benign hypervascular lesions in this population. Also, the morphologic changes and increased liver stiffness caused by congestion make the imaging diagnosis of cirrhosis difficult. The authors discuss the complex liver macro- and microhemodynamics underlying liver congestion; propose a more inclusive approach to and conceptualization of liver congestion; describe the pathophysiology of liver congestion, hepatocellular injury, and the development of benign and malignant nodules; review the imaging findings and mimics of liver congestion and hypervascular lesions; and present a diagnostic algorithm for approaching hypervascular liver lesions. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Detection of Cannabinoids in Oral Fluid Specimens as the Preferred Biological Matrix for a Point-of-Care Biosensor Diagnostic Device.

An increasing number of countries have started to decriminalize or legalize the consumption of cannabis for recreational and medical purposes. The active ingredients in cannabis, termed cannabinoids, affect multiple functions in the human body, including coordination, motor skills, memory, response time to external stimuli, and even judgment. Cannabinoids are a unique class of terpeno-phenolic compounds, with 120 molecules discovered so far. There are certain situations when people under the influence of cannabis may be a risk to themselves or the public safety. Over the past two decades, there has been a growing research interest in detecting cannabinoids from various biological matrices. There is a need to develop a rapid, accurate, and reliable method of detecting cannabinoids in oral fluid as it can reveal the recent intake in comparison with urine specimens, which only show a history of consumption. Significant improvements are continuously made in the analytical formats of various technologies, mainly concerning improving their sensitivity, miniaturization, and making them more user-friendly. Additionally, sample collection and pretreatment have been extensively studied, and specific devices for collecting oral fluid specimens have been perfected to allow rapid and effective sample collection. This review presents the recent findings regarding the use of oral fluid specimens as the preferred biological matrix for cannabinoid detection in a point-of-care biosensor diagnostic device. A critical review is presented, discussing the findings from a collection of review and research articles, as well as publicly available data from companies that manufacture oral fluid screening devices. Firstly, the various conventional methods used to detect cannabinoids in biological matrices are presented. Secondly, the detection of cannabinoids using point-of-care biosensors is discussed, emphasizing oral fluid specimens. This review presents the current pressing technological challenges and highlights the gaps where new technological solutions can be implemented.

l-Cysteine-Tuned the Hierarchical Structure Based on Benzimidazole: Synthesis, Characterization, and Application in Ratiometric Electrochemiluminescence Immunoassay.

Efficient and robust electrochemiluminescence (ECL) emitters are crucial for enhancing the ECL immunosensor sensitivity. This study introduces a novel ECL emitter, CoBIM/Cys, featuring a hierarchical core-shell structure. The core of the structure is created through the swift coordination between the sulfhydryl and carboxyl groups of l-cysteine (l-Cys) and cobalt ions (Co2+), while the shell is constructed by sequentially coordinating benzimidazole (BIM) with Co2+. This design yields a greater specific surface area and a more intricate porous structure compared to CoBIM, markedly enhancing mass transfer and luminophore accessibility. Moreover, the l-Cys and Co2+ core introduces Co-S and Co-O catalytic sites, which improve the catalytic decomposition of H2O2, leading to an increased production of hydroperoxyl radicals (OOH•). This mechanism substantially amplifies the ECL performance. Leveraging the competitive interaction between isoluminol and BIM for OOH• during ECL emission, we developed a ratiometric immunosensor for cardiac troponin I (cTnI) detection. This immunosensor demonstrates a remarkably broad detection range (1 pg mL-1 to 10 ng mL-1), a low detection limit (0.4 pg mL-1), and exceptional reproducibility and specificity.

Additive Manufacturing Applications in Biosensors Technologies.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the additive manufacturing applications in biosensor technologies with a particular emphasis on extrusion-based 3D printing modalities. We highlight the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis is placed on the approach by which the sensing molecules are introduced during the fabrication process. Finally, future perspectives are provided.

Fine tuning of porphyrin based-paddlewheel framework by imidazole derivative to boost electrochemiluminescence performance.

Precise tuning the structure of catalytic center is of great importance for the construction of enhanced electrochemiluminescence (ECL) emitters and the development of ECL amplification strategies, which is a key factor in improving the sensitivity of biosensors. In this work, we report the enhanced ECL emitters based on the porphyrin-based paddlewheel framework (PPF) with axial coordinated imidazole-like ligands (PPF/X, X = 2-methylimidazole (MeIm), imidazole (Im), benzimidazole (BIM)). In this system, the electron-donating ability of the axial ligands is positively correlated to its coordination ability to the paddlewheel units and the catalytic ability of the axially coordinated paddlewheel units. In addition, the electrochemical and ECL behavior of PPF/X (X = MeIm, Im, BIM) with different axial coordinated ligands are explored.

Micelle-Assisted Confined Coordination Spaces for Benzimidazole: Enhanced Electrochemiluminescence for Nitrite Determination.

Selective and sensitive detection of nitrite has important medical and biological implications. In the present work, to obtain an enhanced electrochemiluminescence (ECL) determination of nitrite, a novel nano-ECL emitter CoBIM/cetyltrimethylammonium bromide (CTAB) was prepared via a micelle-assisted, energy-saving, and ecofriendly method based on benzimidazole (BIM) and CTAB. Unlike conventional micelle assistance, the deprotonated BIM (BIM-) preferential placement was in the palisade layer of cationic CTAB-based micelles. Enriching the original CTAB micelle with BIM- disrupted its stability and resulted in the formation of considerably smaller BIM/CTAB-based micelles, providing a confined coordination environment for BIM- and Co2+. As a result, the growth of CoBIM/CTAB was also limited. Owing to the unusual nitration reaction between BIM and nitrite, the prepared CoBIM/CTAB was successfully applied as a novel ECL probe for the detection of nitrite with a wide linear range of 1-1500 µM and a low detection limit of 0.67 µM. This work also provides a promising ECL platform for ultrasensitive monitoring of nitrite and it was applied with sausages and pickled vegetables.

Cost-Effectiveness Analysis of Hepatocellular Carcinoma Surveillance in Nonalcoholic Fatty Liver Disease Cirrhosis Using US Visualization Score C-Triggered Abbreviated MRI.

INTRODUCTION: Ultrasound (US) is associated with severe visualization limitations (US Liver Imaging Reporting and Data System visualization score C) in one-third of patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis undergoing hepatocellular carcinoma (HCC) screening. Data suggest abbreviated MRI (aMRI) may improve HCC screening efficacy. This study analyzed the cost-effectiveness of HCC screening strategies, including an US visualization score-based approach with aMRI, in patients with NAFLD cirrhosis. METHODS: We constructed a Markov model simulating adults with compensated NAFLD cirrhosis in the United States undergoing HCC screening, comparing strategies of US plus visualization score, US alone, or no surveillance. We modeled aMRI in patients with visualization score C and negative US, while patients with scores A/B did US alone. We performed a sensitivity analysis comparing US plus visualization score with US plus alpha fetoprotein or no surveillance. The primary outcome was the incremental cost-effectiveness ratio (ICER), with a willingness-to-pay threshold of $100,000 per quality-adjusted life-year. Sensitivity analyses were performed for all variables. RESULTS: US plus visualization score was the most cost-effective strategy, with an ICER of $59,005 relative to no surveillance. The ICER for US alone to US plus visualization score was $822,500. On sensitivity analysis, screening using US plus visualization score remained preferred across several parameters. Even with alpha fetoprotein added to US, the US plus visualization score strategy remained cost-effective, with an ICER of $62,799 compared with no surveillance. DISCUSSION: HCC surveillance using US visualization score-based approach, using aMRI for visualization score C, seems to be the most cost-effective strategy in patients with NAFLD cirrhosis.

Understanding the role of radiologists in complex treatment decisions for patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and represents a significant global health burden. Management of HCC can be challenging due to multiple factors, including variable expectations for treatment outcomes. Several treatment options are available, each with specific eligibility and ineligibility criteria, and are provided by a multidisciplinary team of specialists. Radiologists should be aware of the types of treatment options available, as well as the criteria guiding the development of individualized treatment plans. This awareness enables radiologists to contribute effectively to patient-centered multidisciplinary tumor boards for HCC and play a central role in reassessing care plans when the treatment response is deemed inadequate. This comprehensive review aims to equip radiologists with an overview of HCC staging systems, treatment options, and eligibility criteria. The review also discusses the significance of imaging in HCC diagnosis, treatment planning, and monitoring treatment response. Furthermore, we highlight the crucial branch points in the treatment decision-making process that depend on radiological interpretation.

The Rise and Fall of Omicron BA.1 Variant as Seen in Wastewater Supports Epidemiological Model Predictions.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has inflicted significant mortality and morbidity worldwide. Continuous virus mutations have led to the emergence of new variants. The Omicron BA.1 sub-lineage prevailed as the dominant variant globally at the beginning of 2022 but was subsequently replaced by BA.2 in numerous countries. Wastewater-based epidemiology (WBE) offers an efficient tool for capturing viral shedding from infected individuals, enabling early detection of potential pandemic outbreaks without relying solely on community cooperation and clinical testing resources. This study integrated RT-qPCR assays for detecting general SARS-CoV-2 and its variants levels in wastewater into a modified triple susceptible-infected-recovered-susceptible (SIRS) model. The emergence of the Omicron BA.1 variant was observed, replacing the presence of its predecessor, the Delta variant. Comparative analysis between the wastewater data and the modified SIRS model effectively described the BA.1 and subsequent BA.2 waves, with the decline of the Delta variant aligning with its diminished presence below the detection threshold in wastewater. This study demonstrates the potential of WBE as a valuable tool for future pandemics. Furthermore, by analyzing the sensitivity of different variants to model parameters, we are able to deduce real-life values of cross-variant immunity probabilities, emphasizing the asymmetry in their strength.

Imaging Findings in Cirrhotic Liver: Pearls and Pitfalls for Diagnosis of Focal Benign and Malignant Lesions.

Cirrhosis is the end stage of chronic liver disease and causes architectural distortion and perfusional anomalies. It is a major risk factor for developing hepatocellular carcinoma (HCC). Common disease entities in noncirrhotic livers, such as hemangiomas, can be rare in cirrhotic livers, and benign entities such as confluent hepatic fibrosis and focal nodular hyperplasia-like lesions may mimic the appearance of malignancies,. HCC usually has typical imaging characteristics, such as the major features established by the Liver Imaging Reporting and Data System. However, HCC can also have a spectrum of atypical or uncommon appearances, such as cystic HCC, hypovascular HCC, or macroscopic fat-containing HCC. HCCs with certain genetic mutations such as CTNNB-1-mutated HCC can harbor unique imaging features not seen in other types of HCC. In addition, malignancies that are less common than HCC, such as cholangiocarcinoma and metastases, which can be difficult to differentiate, can still occur in cirrhotic livers. Atypical imaging features of benign and malignant lesions can be challenging to accurately diagnose. Therefore, familiarity with these features and an understanding of the prevalence of disease entities in cirrhotic livers are key in the daily practice of radiologists for evaluation of cirrhotic livers. The authors illustrate the typical and atypical features of benign and malignant lesions in cirrhosis and discuss the technical pitfalls and unique advantages associated with various imaging modalities in assessing cirrhotic livers, including noncontrast and contrast-enhanced US, CT, and MRI. Work of the U.S. Government published under an exclusive license with the RSNA. Quiz questions for this article are available in the supplemental material.

Post-synthetic modification-driven ZIF reconstruction and functionalization for efficient SARS-CoV-2 ECL detection.

The emergence of novel pathogens, as well as their frequent variants, raises the significance of developing superior and versatile sensing materials and techniques. Herein, a post-modified zeolitic imidazolate framework (pm-ZIF) was synthesized by using ZIF-67 as a parent MOF, and zinc(II) meso-tetra (4-carboxyphenyl) porphine (ZnTCPP) as a successive exchange ligand. Due to the preservation of the tetrahedral Co-N4 units from the ZIF precursor and the introduced porphyrin luminophores, this hybrid material pm-ZIF/P(Zn) enables the linear electrochemiluminescence (ECL) signal conversion of the target DNA concentration. An efficient biosensor that can be used to quantitatively detect SARS-CoV-2 was therefore constructed. The linear range of the sensor was 10-12-10-8 M, with a limit of detection (LOD) reaching 158 pM. Compared with the traditional amplification-based methods, the duration time of our method is significantly shortened and the quantitation of the SARS-Cov-2 RdRp gene can be completed within twenty minutes at room temperature.

3,3'-Diindolylmethane (DIM): A Potential Therapeutic Agent against Cariogenic Streptococcus mutans Biofilm.

Indole, a metabolite of the amino acid tryptophan, has been proven to act as a signal molecule in bacteria, acting in different aspects of biofilm formation. The oral biofilm is a type of biofilm that has consequences for human health. It is a complex, three-dimensional structure that develops on the surface of teeth via the attachment of primary microbial colonizers. Many oral infections are caused by an imbalance occurring in the microorganisms naturally found in oral biofilms and are considered major public health concerns. In this study, we test the effect of a natural bis-indole, 3,3'-Diindolylmethane (DIM), in mitigating the pathogenicity of the oral biofilm inhabiting bacterium Streptococcus mutans, a bacterium that is considered to be a principal etiological agent in dental caries. Our study found that DIM was able to attenuate S. mutans biofilm formation by 92%. Additionally, treatment with DIM lowered extracellular polymeric substance (EPS) production and decreased its durability significantly under acidic conditions. Therefore, the anti-biofilm and anti-virulence properties of DIM against S. mutans bacteria in an "oral setting" provides evidence for its usefulness in reducing biofilm formation and potentially for caries attenuation.

A Multicenter Assessment of Interreader Reliability of LI-RADS Version 2018 for MRI and CT.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

The adoption of LI-RADS: a survey of non-academic radiologists.

PURPOSE: To understand the practice and determinants of non-academic radiologists regarding LI-RADS and the four current LI-RADS algorithms: CT/MRI, contrast-enhanced ultrasound (CEUS), ultrasound (US), and CT/MRI Treatment Response. MATERIALS AND METHODS: Seven themes were covered in this international survey, as follows: (1) demographics of participants and sub-specialty, (2) HCC practice and interpretation, (3) reporting practice, (4) screening and surveillance, (5) HCC imaging diagnosis, (6) treatment response, and (7) CT and MRI technique. RESULTS: Of the 232 participants, 69.4% were from the United States, 25.0% from Canada, and 5.6% from other countries and 45.9% were abdominal/body imagers. During their radiology training or fellowship, no formal HCC diagnostic system was used by 48.7% and LI-RADS was used by 44.4% of participants. In their current practice, 73.6% used LI-RADS, 24.7% no formal system, 6.5% UNOS-OPTN, and 1.3% AASLD. Barriers to LI-RADS adoption included lack of familiarity (25.1%), not used by referring clinicians (21.6%), perceived complexity (14.5%), and personal preference (5.3%). The US LI-RADS algorithm was used routinely by 9.9% of respondents and CEUS LI-RADS was used by 3.9% of the respondents. The LI-RADS treatment response algorithm was used by 43.5% of the respondents. 60.9% of respondents thought that webinars/workshops on LI-RADS Technical Recommendations would help them implement these recommendations in their practice. CONCLUSION: A majority of the non-academic radiologists surveyed use the LI-RADS CT/MR algorithm for HCC diagnosis, while nearly half use the LI-RADS TR algorithm for assessment of treatment response. Less than 10% of the participants routinely use the LI-RADS US and CEUS algorithms.

Conversations in the Gut: The Role of Quorum Sensing in Normobiosis.

An imbalance in gut microbiota, termed dysbiosis, has been shown to affect host health. Several factors, including dietary changes, have been reported to cause dysbiosis with its associated pathologies that include inflammatory bowel disease, cancer, obesity, depression, and autism. We recently demonstrated the inhibitory effects of artificial sweeteners on bacterial quorum sensing (QS) and proposed that QS inhibition may be one mechanism behind such dysbiosis. QS is a complex network of cell-cell communication that is mediated by small diffusible molecules known as autoinducers (AIs). Using AIs, bacteria interact with one another and coordinate their gene expression based on their population density for the benefit of the whole community or one group over another. Bacteria that cannot synthesize their own AIs secretly "listen" to the signals produced by other bacteria, a phenomenon known as "eavesdropping". AIs impact gut microbiota equilibrium by mediating intra- and interspecies interactions as well as interkingdom communication. In this review, we discuss the role of QS in normobiosis (the normal balance of bacteria in the gut) and how interference in QS causes gut microbial imbalance. First, we present a review of QS discovery and then highlight the various QS signaling molecules used by bacteria in the gut. We also explore strategies that promote gut bacterial activity via QS activation and provide prospects for the future.

Universal Liver Imaging Lexicon: Imaging Atlas for Research and Clinical Practice.

The use of standardized terms in assessing and reporting disease processes has well-established benefits, such as clear communication between radiologists and other health care providers, improved diagnostic accuracy and reproducibility, and the enhancement and facilitation of research. Recently, the Liver Imaging Reporting and Data System (LI-RADS) Steering Committee released a universal liver imaging lexicon. The current version of the lexicon includes 81 vetted and precisely defined terms that are relevant to acquisition of images using all major liver imaging modalities and contrast agents, as well as lesion- and organ-level features. Most terms in the lexicon are applicable to all patients undergoing imaging of the liver, and only a minority of the terms are strictly intended to be used for patients with high risk factors for hepatocellular carcinoma. This pictorial atlas familiarizes readers with the liver imaging lexicon and includes discussion of general concepts, providing sample definitions, schematics, and clinical examples for a subset of the terms in the liver imaging lexicon. The authors discuss general, technical, and imaging feature terms used commonly in liver imaging, with the goal of illustrating their use for clinical and research applications. Work of the U.S. Government published under an exclusive license with the RSNA. Online supplemental material is available for this article.

Methodology for clinical research.

A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Indeed, selecting an inappropriate study type, an error that cannot be corrected after the beginning of a study, results in flawed methodology. The results of clinical research studies enhance the repertoire of knowledge regarding a disease pathogenicity, an existing or newly discovered medication, surgical or diagnostic procedure or medical device. Medical research can be divided into primary and secondary research, where primary research involves conducting studies and collecting raw data, which is then analysed and evaluated in secondary research. The successful deployment of clinical research methodology depends upon several factors. These include the type of study, the objectives, the population, study design, methodology/techniques and the sampling and statistical procedures used. Among the different types of clinical studies, we can recognize descriptive or analytical studies, which can be further categorized in observational and experimental. Finally, also pre-clinical studies are of outmost importance, representing the steppingstone of clinical trials. It is therefore important to understand the types of method for clinical research. Thus, this review focused on various aspects of the methodology and describes the crucial steps of the conceptual and executive stages.

Ethical considerations regarding animal experimentation.

Animal experimentation is widely used around the world for the identification of the root causes of various diseases in humans and animals and for exploring treatment options. Among the several animal species, rats, mice and purpose-bred birds comprise almost 90% of the animals that are used for research purpose. However, growing awareness of the sentience of animals and their experience of pain and suffering has led to strong opposition to animal research among many scientists and the general public. In addition, the usefulness of extrapolating animal data to humans has been questioned. This has led to Ethical Committees' adoption of the 'four Rs' principles (Reduction, Refinement, Replacement and Responsibility) as a guide when making decisions regarding animal experimentation. Some of the essential considerations for humane animal experimentation are presented in this review along with the requirement for investigator training. Due to the ethical issues surrounding the use of animals in experimentation, their use is declining in those research areas where alternative in vitro or in silico methods are available. However, so far it has not been possible to dispense with experimental animals completely and further research is needed to provide a road map to robust alternatives before their use can be fully discontinued.