Intravital imaging reveals inflammation as a dominant pathophysiology of age-related hepatovascular changes

Aging is the most significant risk factor for the majority of chronic diseases, including liver disease. The cellular, molecular, and pathophysiological mechanisms that promote age-induced hepatovascular changes are unknown due to our inability to visualize changes in liver pathophysiology in live mice over time. We performed quantitative liver intravital microscopy (qLIM) in live C57BL/6J mice to investigate the impact of aging on the hepatovascular system over a 24-month period. qLIM revealed that age-related hepatic alterations include reduced liver sinusoidal blood flow, increased sinusoidal vessel diameter and loss of small hepatic vessels. The ductular cell structure deteriorates with age, resulting in altered expression of hepatic junctional proteins. Furthermore, qLIM imaging revealed increased inflammation in the aged liver, which was linked to increased expression of proinflammatory macrophages, hepatic neutrophils, liver sinusoidal endothelial cells, and procoagulants. Finally, we detected elevated NF-κB pathway activity in aged livers. Overall, these findings emphasize the importance of inflammation in age-related hepatic vasculo-epithelial alterations and highlight the utility of qLIM in studying age-related effects in organ pathophysiology.

Significance of Rouviere’s Sulcus in Hepatobiliary Surgery: A Cadaveric study

Background: Rouviere’s sulcus (RS) was first identified in 1924 by Henri Rouviere. It lies oblique to the anterior and inferior border of the liver and holds the right portal pedicle. Material and Methods: The study was conducted in the Department of Anatomy of a Medical College in Maharashtra, India, on 45 cadaveric livers. The morphological observations made were: presence/ absence RS; direction of RS (oblique/ horizontal/ vertical); sulcus type ( deep/ slit/ scar); length, width and depth; presence of right hepatic pedicle; distance of the hepatic vessels from edge of the sulcus . Results: 40 livers showed the presence of Rouviere’s Sulcus. It was absent in five specimens. Direction was horizontal in 40%, oblique in 57.5% and vertical in 2.5% .26 livers showed a deep type of sulcus, 12 showed the slit type and 2 showed scar type .29 livers showed the right hepatic pedicle entering the RS. Average length, depth, of the RS was 2.35 cm and1.07 cm respectively. The average width was 0.32cm at medial end, 0.22cm at midpoint and 0.1cm at lateral end. Present study has added the details of depth of vessels from the edge of RS, which was not recorded in earlier studies. Depth of vessels from the edge of the sulcus was average 5mm (0.5cm) for the right branch of the hepatic artery and was 12mm (1.2cm) for the right branch of portal vein. Conclusion: Rouviere’s sulcus is a reference landmark for surgeons during laparoscopic surgeries on gall bladder and during hepatic resection to avoid injuries. This study wishes to provide detailed morphological data of the Rouviere’s Sulcus to hepatobiliary surgeons including depth of hepatic vessels in the RS as an added parameter to aid them in their surgical endeavor. KEY WORDS: Rouviere’s sulcus, Anatomical Landmark, Morphology, Depth, Hepatobiliary Surgery.

Perivascular vital cells in the ablation center after multibipolar radiofrequency ablation in an in vivo porcine model

Multibipolar radiofrequency ablation (RFA) is an advanced ablation technique for early stage hepatocellular carcinoma and liver metastases. Vessel cooling in multibipolar RFA has not been systematically investigated. The objective of this study was to evaluate the presence of perivascular vital cells within the ablation zone after multibipolar RFA. Multibipolar RFA were performed in domestic pigs in vivo. Three internally cooled bipolar RFA applicators were used simultaneously. Three experimental settings were planned: (1) inter-applicator-distance: 15 mm; (2) inter-applicator-distance: 20 mm; (3) inter-applicator-distance: 20 mm with hepatic inflow occlusion (Pringle maneuver). A vitality staining was used to analyze liver cell vitality around all vessels in the ablation center with a diameter > 0.5 mm histologically. 771 vessels were identified. No vital tissue was seen around 423 out of 429 vessels (98.6%) situated within the central white zone. Vital cells could be observed around major hepatic vessels situated adjacent to the ablation center. Vessel diameter (> 3.0 mm; p < 0.05) and low vessel-to-ablation-center distance (< 0.2 mm; p < 0.05) were identified as risk factors for incomplete ablation adjacent to hepatic vessels. The vast majority of vessels, which were localized in the clinically relevant white zone, showed no vital perivascular cells, regardless of vessel diameter and vessel type. However, there was a risk of incomplete ablation around major hepatic vessels situated directly within the ablation center. A Pringle maneuver could avoid incomplete ablations.

Engineering the Vasculature of Stem-Cell-Derived Liver Organoids

The vasculature of stem-cell-derived liver organoids can be engineered using methods that recapitulate embryonic liver development. Hepatic organoids with a vascular network offer great application prospects for drug screening, disease modeling, and therapeutics. However, the application of stem cell-derived organoids is hindered by insufficient vascularization and maturation. Here, we review different theories about the origin of hepatic cells and the morphogenesis of hepatic vessels to provide potential approaches for organoid generation. We also review the main protocols for generating vascularized liver organoids from stem cells and consider their potential and limitations in the generation of vascularized liver organoids.

Conventional ultrasound for diagnosis of hepatic steatosis is better than believed

Background Hepatic steatosis is a condition frequently encountered in clinical practice, with potential progression towards fibrosis, cirrhosis, and hepatocellular carcinoma. Detection and staging of hepatic steatosis are of most importance in nonalcoholic fatty liver disease (NAFLD), a disease with a high prevalence of more than 1 billion individuals affected. Ultrasound (US) is one of the most used noninvasive imaging techniques used in the diagnosis of hepatic steatosis. Detection of hepatic steatosis with US relies on several conventional US parameters, which will be described. US is the first-choice imaging in adults at risk for hepatic steatosis. The use of some scoring systems may add additional accuracy especially in assessing the severity of hepatic steatosis. Summary In the presented paper, we discuss screening and risk stratification, ultrasound features for diagnosing hepatic steatosis, B-mode criteria, focal fatty patterns and Doppler features of the hepatic vessels, and the value of the different US signs for the diagnosis of liver steatosis including classifying the severity of steatosis using different US scores. Limitations of conventional B-mode and Doppler features in the evaluation of hepatic steatosis are also discussed, including those in grading and assessing the complications of steatosis, namely fibrosis and nonalcoholic steatohepatitis. Key Messages Ultrasound is the first-line imaging examination for the screening and follow-up of patients with liver steatosis. The use of some scoring systems may add additional accuracy in assessing the severity of steatosis. Conventional B-mode and Doppler ultrasound have limitations in grading and assessing the complications of steatosis.

Segmentation of Liver Anatomy by Combining 3D U-Net Approaches

Accurate liver vessel segmentation is of crucial importance for the clinical diagnosis and treatment of many hepatic diseases. Recent state-of-the-art methods for liver vessel reconstruction mostly utilize deep learning methods, namely, the U-Net model and its variants. However, to the best of our knowledge, no comparative evaluation has been proposed to compare these approaches in the liver vessel segmentation task. Moreover, most research works do not consider the liver volume segmentation as a preprocessing step, in order to keep only inner hepatic vessels, for Couinaud representation for instance. For these reasons, in this work, we propose using accurate Dense U-Net liver segmentation and conducting a comparison between 3D U-Net models inside the obtained volumes. More precisely, 3D U-Net, Dense U-Net, and MultiRes U-Net are pitted against each other in the vessel segmentation task on the IRCAD dataset. For each model, three alternative setups that allow adapting the selected CNN architectures to volumetric data are tested, namely, full 3D, slab-based, and box-based setups are considered. The results showed that the most accurate setup is the full 3D process, providing the highest Dice for most of the considered models. However, concerning the particular models, the slab-based MultiRes U-Net provided the best score. With our accurate vessel segmentations, several medical applications can be investigated, such as automatic and personalized Couinaud zoning of the liver.

Periportal fields cause stronger cooling effects than veins in hepatic microwave ablation: an in vivo porcine study

Background Vascular cooling effects are a well-known source for tumor recurrence in thermal in situ ablation techniques for hepatic malignancies. Microwave ablation (MWA) is an ablation technique to be considered in the treatment of malignant liver tumors. The impact of vascular cooling in MWA is still controversial. Purpose To evaluate the influence of different intrahepatic vessel types, vessel sizes, and vessel-to-antenna-distances on MWA geometry in vivo. Material and Methods Five MWAs (902–928 MHz) were performed with an energy input of 24.0 kJ in three porcine livers in vivo. MWA lesions were cut into 2-mm slices. The minimum and maximum radius of the ablation area was measured for each slice. Distances were measured from ablation center toward all adjacent hepatic vessels with a diameter of ≥1 mm and within a perimeter of 20 mm around the antenna. The respective vascular cooling effect relative to the maximum ablation radius was calculated. Results In total, 707 vessels (489 veins, 218 portal fields) were detected; 370 (76%) hepatic veins and 185 (85%) portal fields caused a cooling effect. Portal fields resulted in higher cooling effects (37%) than hepatic veins (26%, P < 0.01). No cooling effect could be observed in close proximity of vessels within the central ablation zone. Conclusion Hepatic vessels influenced MWA zones and caused a distinct cooling effect. Portal fields resulted in more pronounced cooling effect than hepatic veins. No cooling effect was observed around vessels situated within the central white zone.