In Vivo Imaging of Liver Spheroids Engrafted in the Anterior Chamber of the Mouse Eye.

Biomedical studies of the liver in mammals are hindered by the lack of methods for in vivo noninvasive longitudinal imaging at cellular resolution. Until now, optical imaging of the liver in situ is possible by intravital imaging, which offers high-resolution imaging at the cellular level but cannot be performed multiple times and, therefore, longitudinally in the same animal. Noninvasive imaging methods, such as bioluminescence, allow repeated imaging sessions on the same animal but do not achieve cell resolution. To address this methodology gap, we have developed a platform for noninvasive in vivo imaging of liver spheroids engrafted in the anterior chamber of the mouse eye. In the workflow described in this study, primary mouse liver spheroids are generated in vitro and transplanted into the anterior chamber of the eye of recipient mice, where they engraft on the iris. The cornea acts as a natural body window through which we can image the engrafted spheroids by conventional confocal microscopy. The spheroids survive for months in the eye, during which the cells can be studied in contexts of health and disease, as well as being monitored in response to different stimuli over repeated imaging sessions using appropriate fluorescent probes. In this protocol, we provide a breakdown of the necessary steps to implement this imaging system and explain how to best harness its potential.

Arterial embolization in the treatment of multiple renal and hepatic hamartomas with spontaneous hemorrhage and 2-year follow-up: a case report.

BACKGROUND: Hamartoma is a common benign tumor that usually occurs in the kidney, liver, lung, and pancreas. Large renal hamartomas may spontaneously rupture and hemorrhage, which is potentially life-threatening. CASE PRESENTATION: This report describes a 46-year-old Han Chinese female patient with multiple renal and hepatic hamartomas with rupture and hemorrhage of giant hamartoma in the left kidney. She underwent arterial embolization three times successively, and her condition was stable during the 2-year follow-up. This report includes a review of the relevant literature CONCLUSIONS: the findings in this report and previous literature suggest that arterial embolization can not only rapidly treat hamartoma hemorrhage in the acute phase but can also effectively control multiple lesions in the long term after repeated multisite arterial embolization.

Ultrasound diagnosis of cystic echinococcosis: updates and implications for clinical management.

The diagnosis of cystic echinococcosis (CE) is based on imaging. Detection of a focal lesion with morphological characteristics of Echinococcus granulosus sensu lato metacestode is the starting point for the diagnostic workup. In organs explorable with ultrasound (US), this is the method of choice for both aetiological diagnosis of CE and staging of the CE cyst. Staging in terms of lesion morphology is also needed when serology is added to the diagnostic workflow when imaging alone is inconclusive. Finally, staging guides the clinical management of uncomplicated CE, especially in the liver. This commentary provides an overview of the most up-to-date evidence backing the above-mentioned role of US in the diagnosis and clinical management of CE. Finally, we outline future perspectives for the improvement of CE diagnosis.

Impact of Age-Related Change in Caval Flow Ratio on Hepatic Flow Distribution in the Fontan Circulation.

BACKGROUND: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac conduit or a lateral tunnel connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. The effect of age-related changes in caval inflows on HFD was evaluated using cardiac magnetic resonance data and patient-specific computational fluid dynamics modeling. METHODS: SVC and IVC flow from 414 patients with Fontan were collected to establish a relationship between SVC:IVC flow ratio and age. Computational fluid dynamics modeling was performed in 60 (30 extracardiac and 30 lateral tunnel) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. RESULTS: SVC:IVC flow ratio inverted at ≈8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC, 2, 1, and 0.5 corresponded to ages, 3, 8, and 15+, respectively) was not significant for extracardiac but statistically significant for lateral tunnel cohorts. For all 3 caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2 to 0.5 (age, 3-15+) years, the correlation's strength decreased from 0.87 to 0.64, due to potential flow perturbation as IVC flow momentum increased. CONCLUSIONS: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of SVC:IVC variations over time on Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes.

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.

EBER-negative inflammatory pseudotumor-like follicular dendritic cell sarcoma of liver: A case report.

RATIONALE: Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) of the liver is rare. It was previously believed that Epstein-Barr virus (EBV) positivity was a necessary criterion for pathological diagnosis. However, we found that there were also cases of EBV negativity. Therefore, clinicians and pathologists are reminded that EBV positivity is not a necessary condition for diagnosis. PATIENT CONCERNS: A 70-year-old female underwent computed tomography (CT) examination for upper abdominal discomfort, which revealed the presence of a liver tumor. Follow-up revealed that the tumor had progressively increased in size. DIAGNOSIS: The final diagnosis was an IPT-like follicular cell sarcoma, based on CT, MRI, HE staining, and immunohistochemical staining. INTERVENTIONS: The patient underwent a laparoscopic left hemihepatectomy. OUTCOMES: The patient has not undergone any special treatment, such as radiotherapy and chemotherapy, and has been followed up for over 3 years without experiencing any recurrence. LESSONS: IPT-like FDCS is a rare tumor that lacks definitive criteria, and its diagnosis mainly relies on pathological findings. Previously, it was believed that being EBV-positive was an important condition for diagnosis. Primary IPT-like FDCS in the liver is even rarer, and the patient in this case tested negative for EBV. It may be necessary for pathologists to consider the role of EBV in the diagnosis of IPT-like FDCS.

Multiscale transport and 4D time-lapse imaging in precision-cut liver slices (PCLS).

Background: Monitoring cellular processes across different levels of complexity, from the cellular to the tissue scale, is important for understanding tissue structure and function. However, it is challenging to monitor and estimate these structural and dynamic interactions within three-dimensional (3D) tissue models. Objective: The aim of this study was to design a method for imaging, tracking, and quantifying 3D changes in cell morphology (shape and size) within liver tissue, specifically a precision-cut liver slice (PCLS). A PCLS is a 3D model of the liver that allows the study of the structure and function of liver cells in their native microenvironment. Methods: Here, we present a method for imaging liver tissue during anisosmotic exposure in a multispectral four-dimensional manner. Three metrics of tissue morphology were measured to quantify the effects of osmotic stress on liver tissue. We estimated the changes in the volume of whole precision cut liver slices, quantified the changes in nuclei position, and calculated the changes in volumetric responses of tissue-embedded cells. Results: During equilibration with cell-membrane-permeating and non-permeating solutes, the whole tissue experiences shrinkage and expansion. As nuclei showed a change in position and directional displacement under osmotic stress, we demonstrate that nuclei could be used as a probe to measure local osmotic and mechanical stress. Moreover, we demonstrate that cells change their volume within tissue slices as a result of osmotic perturbation and that this change in volume is dependent on the position of the cell within the tissue and the duration of the exposure. Conclusion: The results of this study have implications for a better understanding of multiscale transport, mechanobiology, and triggered biological responses within complex biological structures.

Non-operative Management - The First Option in the Treatment of Blunt Liver and Spleen Trauma in Pediatric Patients.

AIM: The aim of the present study is to assess some characteristics of blunt hepatic and splenic injuries in children, the non-operative management (NOM) procedures and efficiency, over a 5-year period in a tertiary hospital for children. Materials and Methods: We conducted a retrospective study on 32 patients with blunt liver and/or spleen injuries. Age, gender, mechanism of injury, hemoglobin and hematocrit levels, lenght of stay and bedrest, imaging diagnosis, hemostatics and transfusions, treatment, and discharge status were evaluated. Results: 58% of patients were males. Mean age was 10.7 years. The main mechanism of injury was motor vehicle accident. Ultrasound (US) and Computed Tomography (CT) found 56.2% patients with spleen injury and 43.8% with liver injuries. On US the most frequent injuries were lacerations, and on CT were splenic-grade III and hepatic-grade II. 84.4% of patients were hospitalized in Intensive Care Unit and 15.6% in the surgical unit. The mean hemoglobin and hematocrit were 10.91g/l and 33%, respectively.The treatment was non-operative for 84.4%, and operative for 15.6%. When discharged, 56.2% of patients were cured and 43.8% were improved. CONCLUSION: With a performing multidisciplinary team of surgeons, intensive care therapists and radiologists, NOM in pediatric patients with blunt liver and spleen injuries is safe and effective, may be conducted depending on the hemodynamic stability rather than the lesions' extension, and reduces the ICU lenght of stay, as well as the need for hemostatics and transfusion.

Algorithms for Liver Segmentation in Computed Tomography Scans: A Historical Perspective.

Oncology has emerged as a crucial field of study in the domain of medicine. Computed tomography has gained widespread adoption as a radiological modality for the identification and characterisation of pathologies, particularly in oncology, enabling precise identification of affected organs and tissues. However, achieving accurate liver segmentation in computed tomography scans remains a challenge due to the presence of artefacts and the varying densities of soft tissues and adjacent organs. This paper compares artificial intelligence algorithms and traditional medical image processing techniques to assist radiologists in liver segmentation in computed tomography scans and evaluates their accuracy and efficiency. Despite notable progress in the field, the limited availability of public datasets remains a significant barrier to broad participation in research studies and replication of methodologies. Future directions should focus on increasing the accessibility of public datasets, establishing standardised evaluation metrics, and advancing the development of three-dimensional segmentation techniques. In addition, maintaining a collaborative relationship between technological advances and medical expertise is essential to ensure that these innovations not only achieve technical accuracy, but also remain aligned with clinical needs and realities. This synergy ensures their applicability and effectiveness in real-world healthcare environments.

Effect of repeated prolonged exercise on liver fat content and visceral adipose tissue in well-trained older men.

INTRODUCTION: Liver fat (LF) and visceral adipose tissue (VAT) content decreases with training, however, this has mainly been investigated in sedentary obese or healthy participants. The aim of this study was to investigate the effects of repeated prolonged exercise on LF and VAT content in well-trained older men and to compare baseline LF and VAT content to recreationally active older men. METHOD: A group of five well-trained older men were tested before and after cycling a total distance of 2558 km in 16 consecutive days. VAT content and body composition was measured using DXA before a bicycle ergometer test was performed to determine maximal fat oxidation (MFO), maximal oxygen consumption ( VO 2 max $$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ ), and the relative intensity at which MFO occurred (Fatmax). LF content was measured on a separate day using MRI. For comparison of baseline values, a control group of eight healthy age- and BMI-matched recreationally active men were recruited. RESULTS: The well-trained older men had lower VAT (p = 0.02), and a tendency toward lower LF content (p = 0.06) compared with the control group. The intervention resulted in decreased LF content (p = 0.02), but VAT, fat mass, and lean mass remained unchanged. VO 2 max $$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ , MFO, and Fatmax were not affected by the intervention. CONCLUSION: The study found that repeated prolonged exercise reduced LF content, but VAT and VO 2 max $$ {\mathrm{VO}}_{2_{\mathrm{max}}} $$ remained unchanged. Aerobic capacity was aligned with lower LF and VAT in older active men.

Adjacent object distorts the organ-of-interest in filtered back-projection tomographic image reconstruction: 'ramp filter' or 'reconstruction' artifact revisited.

OBJECTIVE: To simulate the artifact caused by an adjacent object on organ-of-interest during filtered back-projection (FBP) tomographic reconstruction (the so-called "ramp filter" artifact) and to demonstrate the extent to which an organ-of-interest is influenced by such adjacent hot spot or attenuating object. METHODS AND MATERIALS: Two simulations are conducted with two simplified phantoms: "hot spot" and "cardiac." First one is used to visualize effect of hot spot on its periphery. Second one is used to evaluate effect of nearby object (liver) on left ventricle (LV) as organ-of-interest. To generate sinograms, forward projection process is done with and without modeling radiation attenuation. FBP using windowed ramp filter is done. All slices are analyzed by plotting intensity profiles. RESULTS: In tomographic slices, there is a hypo-intense halo around presumed edge of object when compared to background intensity, more noticeable in phantoms with less blurring. Even with ramp filter applied, no halo is visible in FBP without attenuation for cardiac phantom. In contrast, in slices with considering attenuation, zones with different levels of count suppression on both sides of object are visualized instead. The most prominent one is between liver and LV in simulation with higher-attenuating object and higher activity. CONCLUSION: A single hot spot with sufficient amount of blurring does not distort its surroundings. Hot spots and attenuating objects near organ-of-interest, however, distort myocardial perfusion imaging. Artifactual defects are thus only created when attenuation is modeled during FBP, producing zones of count suppression between organ-of-interest and nearby object or hot spot.

Noninvasive assessment of liver fibrosis and portal hypertension.

PURPOSE OF REVIEW: The result of ongoing liver injury - and disease, regardless of cause - is fibrosis, and fibrosis appears to be a critically important result of ongoing injury. Further, in a number of different liver diseases, the presence of fibrosis has prognostic value. Therefore, the assessment of fibrosis is of critical clinical importance. Given the importance of fibrosis, there has been a rapid evolution in the use of noninvasive liver tests. This review highlights a number of the core principles surrounding. RECENT FINDINGS: The use of noninvasive test has progressed rapidly over the last decade and data are rapidly accumulating. New terminology has been adapted by the American Association for the Study of Liver Disease (AASLD) for noninvasive assessment of liver disease and termed 'NILDA' (Non-Invasive Liver Disease Assessment). Blood based such as APRI and or FIB-4 and imaging tests such as liver stiffness measurement (LSM) have moderate to high degrees of accuracy for detection of advanced liver fibrosis (≥ F2) and even higher accuracy for detection of severe fibrosis (F4 or cirrhosis). NILDA are particularly effective at the ends of the liver disease spectrum. For example, a very low LSM (less than 7 kPa) essentially excludes significant fibrosis or portal hypertension, and a very high LSM (> 25 kPa) makes significant fibrosis with portal hypertension (cirrhosis) highly likely. SUMMARY: NILDA are currently front and center in terms of assessment of the severity of liver disease. In all patients with known or suspected liver disease, noninvasive blood tests, including APRI and or FIB-4, should be the initial choice to assess the severity of liver fibrosis and/or portal hypertension. In most patients, these tests should be followed with imaging evaluation. The most commonly available imaging is LSM, which appears to be more accurate in predicting fibrosis severity, and is superior to blood tests in the assessment of portal hypertension. In situations in which there is diagnostic uncertainly, liver biopsy with or without HVPG remains an important consideration.

Multiple ultrasonic parametric imaging for the detection and monitoring of high-intensity focused ultrasound ablation.

Numerous quantitative ultrasound imaging techniques have demonstrated superior monitoring performance for thermal ablation when compared to conventional ultrasonic B-mode imaging. However, the absence of comparative studies involving various quantitative ultrasound imaging techniques hinders further clinical exploration. In this study, we simultaneously reconstructed ultrasonic Nakagami imaging, ultrasonic horizontally normalized Shannon entropy (hNSE) imaging, and ultrasonic differential attenuation coefficient intercept (DACI) imaging from ultrasound backscattered envelope data collected during high-intensity focused ultrasound ablation treatment. We comprehensively investigated their performance differences through qualitative and quantitative analyses, including the calculation of contrast-to-noise ratios (CNR) for ultrasonic images, receiver operating characteristic (ROC) analysis with corresponding indicators, the analysis of lesion area fitting relationships, and computational time consumption comparison. The mean CNR of hNSE imaging was 10.98 ± 4.48 dB, significantly surpassing the 3.82 ± 1.40 dB (p < 0.001, statistically significant) of Nakagami imaging and the 2.45 ± 0.74 dB (p < 0.001, statistically significant) of DACI imaging. This substantial difference underscores that hNSE imaging offers the highest contrast resolution for lesion recognition. Furthermore, we evaluated the ability of multiple ultrasonic parametric imaging to detect thermal ablation lesions using ROC curves. The area under the curve (AUC) for hNSE was 0.874, exceeding the values of 0.848 for Nakagami imaging and 0.832 for DACI imaging. Additionally, hNSE imaging exhibited the strongest linear correlation coefficient (R = 0.92) in the comparison of lesion area fitting, outperforming Nakagami imaging (R = 0.87) and DACI imaging (R = 0.85). hNSE imaging also performs best in real-time monitoring with each frame taking 6.38 s among multiple ultrasonic parametric imaging. Our findings unequivocally demonstrate that hNSE imaging excels in monitoring HIFU ablation treatment and holds the greatest potential for further clinical exploration.

OA-GAN: organ-aware generative adversarial network for synthesizing contrast-enhanced medical images.

Contrast-enhanced computed tomography (CE-CT) images are vital for clinical diagnosis of focal liver lesions (FLLs). However, the use of CE-CT images imposes a significant burden on patients due to the injection of contrast agents and extended shooting. Deep learning-based image synthesis models offer a promising solution that synthesizes CE-CT images from non-contrasted CT (NC-CT) images. Unlike natural images, medical image synthesis requires a specific focus on certain organs or localized regions to ensure accurate diagnosis. Determining how to effectively emphasize target organs poses a challenging issue in medical image synthesis. To solve this challenge, we present a novel CE-CT image synthesis model called, Organ-Aware Generative Adversarial Network (OA-GAN). The OA-GAN comprises an organ-aware (OA) network and a dual decoder-based generator. First, the OA network learns the most discriminative spatial features about the target organ (i.e. liver) by utilizing the ground truth organ mask as localization cues. Subsequently, NC-CT image and captured feature are fed into the dual decoder-based generator, which employs a local and global decoder network to simultaneously synthesize the organ and entire CECT image. Moreover, the semantic information extracted from the local decoder is transferred to the global decoder to facilitate better reconstruction of the organ in entire CE-CT image. The qualitative and quantitative evaluation on a CE-CT dataset demonstrates that the OA-GAN outperforms state-of-the-art approaches for synthesizing two types of CE-CT images such as arterial phase and portal venous phase. Additionally, subjective evaluations by expert radiologists and a deep learning-based FLLs classification also affirm that CE-CT images synthesized from the OA-GAN exhibit a remarkable resemblance to real CE-CT images.