Privacy-proof Live Surgery Streaming: Development and Validation of a Low-cost, Real-time Robotic Surgery Anonymization Algorithm.

OBJECTIVE: Develop a pioneer surgical anonymization algorithm for reliable and accurate real-time removal of out-of-body images validated across various robotic platforms. BACKGROUND: The use of surgical video data has become a common practice in enhancing research and training. Video sharing requires complete anonymization, which, in the case of endoscopic surgery, entails the removal of all nonsurgical video frames where the endoscope can record the patient or operating room staff. To date, no openly available algorithmic solution for surgical anonymization offers reliable real-time anonymization for video streaming, which is also robotic-platform and procedure-independent. METHODS: A data set of 63 surgical videos of 6 procedures performed on four robotic systems was annotated for out-of-body sequences. The resulting 496.828 images were used to develop a deep learning algorithm that automatically detected out-of-body frames. Our solution was subsequently benchmarked against existing anonymization methods. In addition, we offer a postprocessing step to enhance the performance and test a low-cost setup for real-time anonymization during live surgery streaming. RESULTS: Framewise anonymization yielded a receiver operating characteristic area under the curve score of 99.46% on unseen procedures, increasing to 99.89% after postprocessing. Our Robotic Anonymization Network outperforms previous state-of-the-art algorithms, even on unseen procedural types, despite the fact that alternative solutions are explicitly trained using these procedures. CONCLUSIONS: Our deep learning model, Robotic Anonymization Network, offers reliable, accurate, and safe real-time anonymization during complex and lengthy surgical procedures regardless of the robotic platform. The model can be used in real time for surgical live streaming and is openly available.

Assessment of hepatic arterial hemodynamics with 4D flow MRI: in vitro analysis of motion and spatial resolution related error and in vivo feasibility study in 20 volunteers.

OBJECTIVES: To assess the ability of four-dimensional (4D) flow MRI to measure hepatic arterial hemodynamics by determining the effects of spatial resolution and respiratory motion suppression in vitro and its applicability in vivo with comparison to two-dimensional (2D) phase-contrast MRI. METHODS: A dynamic hepatic artery phantom and 20 consecutive volunteers were scanned. The accuracies of Cartesian 4D flow sequences with k-space reordering and navigator gating at four spatial resolutions (0.5- to 1-mm isotropic) and navigator acceptance windows (± 8 to ± 2 mm) and one 2D phase-contrast sequence (0.5-mm in -plane) were assessed in vitro at 3 T. Two sequences centered on gastroduodenal and hepatic artery branches were assessed in vivo for intra - and interobserver agreement and compared to 2D phase-contrast. RESULTS: In vitro, higher spatial resolution led to a greater decrease in error than narrower navigator window (30.5 to -4.67% vs -6.64 to -4.67% for flow). In vivo, hepatic and gastroduodenal arteries were more often visualized with the higher resolution sequence (90 vs 71%). Despite similar interobserver agreement (κ = 0.660 and 0.704), the higher resolution sequence had lower variability for area (CV = 20.04 vs 30.67%), flow (CV = 34.92 vs 51.99%), and average velocity (CV = 26.47 vs 44.76%). 4D flow had lower differences between inflow and outflow at the hepatic artery bifurcation (11.03 ± 5.05% and 15.69 ± 6.14%) than 2D phase-contrast (28.77 ± 21.01%). CONCLUSION: High-resolution 4D flow can assess hepatic artery anatomy and hemodynamics with improved accuracy, greater vessel visibility, better interobserver reliability, and internal consistency. KEY POINTS: • Motion-suppressed Cartesian four-dimensional (4D) flow MRI with higher spatial resolution provides more accurate measurements even when accepted respiratory motion exceeds voxel size. • 4D flow MRI with higher spatial resolution provides substantial interobserver agreement for visualization of hepatic artery branches. • Lower peak and average velocities and a trend toward better internal consistency were observed with 4D flow MRI as compared to 2D phase-contrast.

Multicentric exploration of tool annotation in robotic surgery: lessons learned when starting a surgical artificial intelligence project.

BACKGROUND: Artificial intelligence (AI) holds tremendous potential to reduce surgical risks and improve surgical assessment. Machine learning, a subfield of AI, can be used to analyze surgical video and imaging data. Manual annotations provide veracity about the desired target features. Yet, methodological annotation explorations are limited to date. Here, we provide an exploratory analysis of the requirements and methods of instrument annotation in a multi-institutional team from two specialized AI centers and compile our lessons learned. METHODS: We developed a bottom-up approach for team annotation of robotic instruments in robot-assisted partial nephrectomy (RAPN), which was subsequently validated in robot-assisted minimally invasive esophagectomy (RAMIE). Furthermore, instrument annotation methods were evaluated for their use in Machine Learning algorithms. Overall, we evaluated the efficiency and transferability of the proposed team approach and quantified performance metrics (e.g., time per frame required for each annotation modality) between RAPN and RAMIE. RESULTS: We found a 0.05 Hz image sampling frequency to be adequate for instrument annotation. The bottom-up approach in annotation training and management resulted in accurate annotations and demonstrated efficiency in annotating large datasets. The proposed annotation methodology was transferrable between both RAPN and RAMIE. The average annotation time for RAPN pixel annotation ranged from 4.49 to 12.6 min per image; for vector annotation, we denote 2.92 min per image. Similar annotation times were found for RAMIE. Lastly, we elaborate on common pitfalls encountered throughout the annotation process. CONCLUSIONS: We propose a successful bottom-up approach for annotator team composition, applicable to any surgical annotation project. Our results set the foundation to start AI projects for instrument detection, segmentation, and pose estimation. Due to the immense annotation burden resulting from spatial instrumental annotation, further analysis into sampling frequency and annotation detail needs to be conducted.

Calibration of an Electrical Analog Model of Liver Hemodynamics in Fontan Patients.

Fontan associated liver disease is a common complication in patients with Fontan circulation, who were born with a single functioning heart ventricle. The hepatic venous pressure gradient (HVPG) is used to assess liver health and is a surrogate measure of the pressure gradient across the entire liver (portal pressure gradient (PPG)). However, it is thought to be inaccurate in Fontan patients. The main objectives of this study were (1) to apply an existing detailed lumped parameter model (LPM) of the liver to Fontan patients using patient-specific clinical data and (2) to determine whether HVPG is a suitable measurement of PPGs in these patients. An existing LPM of the liver blood circulation was applied and tuned to simulate patient-specific liver hemodynamics. Geometries were collected from seven adult Fontan patients and used to evaluate model parameters. The model was solved and tuned using waveform measurements of flows, inlet and outlet pressures. The predicted ratio of portal to hepatic venous pressures is comparable to in vivo measurements. The results confirmed that HVPG is not suitable for Fontan patients, as it would underestimate the portal pressures gradient by a factor of 3 to 4. Our patient-specific liver model provides an estimate of the pressure drop across the liver, which differs from the clinically used metric HVPG. This work represents a first step toward models suitable to assess liver health in Fontan patients and improve its long-term management.

Angiopoietin-2 Promotes Pathological Angiogenesis and Is a Therapeutic Target in Murine Nonalcoholic Fatty Liver Disease.

Angiogenesis contributes to the development of nonalcoholic steatohepatitis (NASH) and promotes inflammation, fibrosis, and progression to hepatocellular carcinoma (HCC). Angiopoietin-2 (Ang-2) is a key regulator of angiogenesis. We aimed to investigate the role of Ang-2 and its potential as a therapeutic target in NASH using human samples, in vivo mouse models, and in vitro assays. Serum Ang-2 levels were determined in 104 obese patients undergoing bariatric surgery and concomitant liver biopsy. The effect of the Ang-2/Tie2 receptor inhibiting peptibody L1-10 was evaluated in the methionine-choline deficient (MCD) and streptozotocin-western diet nonalcoholic fatty liver disease mouse models, and in vitro on endothelial cells and bone marrow-derived macrophages. The hepatic vasculature was visualized with µCT scans and scanning electron microscopy of vascular casts. Serum Ang-2 levels were increased in patients with histological NASH compared with patients with simple steatosis and correlated with hepatic CD34 immunoreactivity as a marker of hepatic angiogenesis. Serum and hepatic Ang-2 levels were similarly increased in mice with steatohepatitis. Both preventive and therapeutic L1-10 treatment reduced hepatocyte ballooning and fibrosis in MCD diet-fed mice and was associated with reduced hepatic angiogenesis and normalization of the vascular micro-architecture. Liver-isolated endothelial cells and monocytes from MCD-fed L1-10-treated mice showed reduced expression of leukocyte adhesion and inflammatory markers, respectively, compared with cells from untreated MCD diet-fed mice. In the streptozotocin-western diet model, therapeutic Ang-2 inhibition was able to reverse NASH and attenuate HCC progression. In vitro, L1-10 treatment mitigated increased cytokine production in lipopolysaccharide-stimulated endothelial cells but not in macrophages. Conclusion: Our findings provide evidence for Ang-2 inhibition as a therapeutic strategy to target pathological angiogenesis in NASH.

Quantitative analysis of hepatic macro- and microvascular alterations during cirrhogenesis in the rat.

Cirrhosis represents the end-stage of any persistent chronically active liver disease. It is characterized by the complete replacement of normal liver tissue by fibrosis, regenerative nodules, and complete fibrotic vascularized septa. The resulting angioarchitectural distortion contributes to an increasing intrahepatic vascular resistance, impeding liver perfusion and leading to portal hypertension. To date, knowledge on the dynamically evolving pathological changes of the hepatic vasculature during cirrhogenesis remains limited. More specifically, detailed anatomical data on the vascular adaptations during disease development is lacking. To address this need, we studied the 3D architecture of the hepatic vasculature during induction of cirrhogenesis in a rat model. Cirrhosis was chemically induced with thioacetamide (TAA). At predefined time points, the hepatic vasculature was fixed and visualized using a combination of vascular corrosion casting and deep tissue microscopy. Three-dimensional reconstruction and data-fitting enabled cirrhogenic features to extracted at multiple scales, portraying the impact of cirrhosis on the hepatic vasculature. At the macrolevel, we noticed that regenerative nodules severely compressed pliant venous vessels from 12 weeks of TAA intoxication onwards. Especially hepatic veins were highly affected by this compression, with collapsed vessel segments severely reducing perfusion capabilities. At the microlevel, we discovered zone-specific sinusoidal degeneration, with sinusoids located near the surface being more affected than those in the middle of a liver lobe. Our data shed light on and quantify the evolving angioarchitecture during cirrhogenesis. These findings may prove helpful for future targeted invasive interventions.

A multilevel framework to reconstruct anatomical 3D models of the hepatic vasculature in rat livers.

The intricate (micro)vascular architecture of the liver has not yet been fully unravelled. Although current models are often idealized simplifications of the complex anatomical reality, correct morphological information is instrumental for scientific and clinical purposes. Previously, both vascular corrosion casting (VCC) and immunohistochemistry (IHC) have been separately used to study the hepatic vasculature. Nevertheless, these techniques still face a number of challenges such as dual casting in VCC and limited imaging depths for IHC. We have optimized both techniques and combined their complementary strengths to develop a framework for multilevel reconstruction of the hepatic circulation in the rat. The VCC and micro-CT scanning protocol was improved by enabling dual casting, optimizing the contrast agent concentration, and adjusting the viscosity of the resin (PU4ii). IHC was improved with an optimized clearing technique (CUBIC) that extended the imaging depth for confocal microscopy more than five-fold. Using in-house developed software (DeLiver), the vascular network - in both VCC and IHC datasets - was automatically segmented and/or morphologically analysed. Our methodological framework allows 3D reconstruction and quantification of the hepatic circulation, ranging from the major blood vessels down to the intertwined and interconnected sinusoids. We believe that the presented framework will have value beyond studies of the liver, and will facilitate a better understanding of various parenchymal organs in general, in physiological and pathological circumstances.

A multilevel modeling framework to study hepatic perfusion characteristics in case of liver cirrhosis.

Liver cirrhosis represents the end-stage of different liver disorders, progressively affecting hepatic architecture, hemodynamics, and function. Morphologically, cirrhosis is characterized by diffuse fibrosis, the conversion of normal liver architecture into structurally abnormal regenerative nodules and the formation of an abundant vascular network. To date, the vascular remodeling and altered hemodynamics due to cirrhosis are still poorly understood, even though they seem to play a pivotal role in cirrhogenesis. This study aims to determine the perfusion characteristics of the cirrhotic circulation using a multilevel modeling approach including computational fluid dynamics (CFD) simulations. Vascular corrosion casting and multilevel micro-CT imaging of a single human cirrhotic liver generated detailed datasets of the hepatic circulation, including typical pathological characteristics of cirrhosis such as shunt vessels and dilated sinusoids. Image processing resulted in anatomically correct 3D reconstructions of the microvasculature up to a diameter of about 500 µm. Subsequently, two cubic samples (150 × 150 × 150 µm³) were virtually dissected from vascularized zones in between regenerative nodules and applied for CFD simulations to study the altered cirrhotic microperfusion and permeability. Additionally, a conceptual 3D model of the cirrhotic macrocirculation was developed to reveal the hemodynamic impact of regenerative nodules. Our results illustrate that the cirrhotic microcirculation is characterized by an anisotropic permeability showing the highest value in the direction parallel to the central vein (kd,zz = 1.68 × 10-13 m² and kd,zz = 7.79 × 10⁻¹³ m² for sample 1 and 2, respectively) and lower values in the circumferential (kd,ϑϑ = 5.78 × 10⁻¹4 m² and kd,ϑϑ = 5.65 × 10⁻¹³ m² for sample 1 and 2, respectively) and radial (kd,rr = 9.87 × 10⁻¹4 m² and kd,rr = 5.13 × 10⁻¹³ m² for sample 1 and 2, respectively) direction. Overall, the observed permeabilities are markedly higher compared to a normal liver, implying a locally decreased intrahepatic vascular resistance (IVR) probably due to local compensation mechanisms (dilated sinusoids and shunt vessels). These counteract the IVR increase caused by the presence of regenerative nodules and dynamic contraction mechanisms (e.g., stellate cells, NO-concentration, etc.). Our conceptual 3D model of the cirrhotic macrocirculation indicates that regenerative nodules severely increase the IVR beyond about 65 vol. % of regenerative nodules. Numerical modeling allows quantifying perfusion characteristics of the cirrhotic macro- and microcirculation, i.e., the effect of regenerative nodules and compensation mechanisms such as dilated sinusoids and shunt vessels. Future research will focus on the development of models to study time-dependent degenerative adaptation of the cirrhotic macro- and microcirculation.

Analyzing the human liver vascular architecture by combining vascular corrosion casting and micro-CT scanning: a feasibility study.

Although a full understanding of the hepatic circulation is one of the keys to successfully perform liver surgery and to elucidate liver pathology, relatively little is known about the functional organization of the liver vasculature. Therefore, we materialized and visualized the human hepatic vasculature at different scales, and performed a morphological analysis by combining vascular corrosion casting with novel micro-computer tomography (CT) and image analysis techniques. A human liver vascular corrosion cast was obtained by simultaneous resin injection in the hepatic artery (HA) and portal vein (PV). A high resolution (110 µm) micro-CT scan of the total cast allowed gathering detailed macrovascular data. Subsequently, a mesocirculation sample (starting at generation 5; 88 × 68 × 80 mm³) and a microcirculation sample (terminal vessels including sinusoids; 2.0 × 1.5 × 1.7 mm³) were dissected and imaged at a 71-µm and 2.6-µm resolution, respectively. Segmentations and 3D reconstructions allowed quantifying the macro- and mesoscale branching topology, and geometrical features of HA, PV and hepatic venous trees up to 13 generations (radii ranging from 13.2 mm to 80 µm; lengths from 74.4 mm to 0.74 mm), as well as microvascular characteristics (mean sinusoidal radius of 6.63 µm). Combining corrosion casting and micro-CT imaging allows quantifying the branching topology and geometrical features of hepatic trees using a multiscale approach from the macro- down to the microcirculation. This may lead to novel insights into liver circulation, such as internal blood flow distributions and anatomical consequences of pathologies (e.g. cirrhosis).

Simplification strategies for a patient-specific CFD model of particle transport during liver radioembolization.

BACKGROUND: Patient-specific 3D computational fluid dynamics (CFD) simulations have been used previously to identify the impact of injection parameters (e.g. injection location, velocity, etc.) on the particle distribution and the tumor dose during transarterial injection of radioactive microspheres for treatment of hepatocellular carcinoma. However, these simulations are computationally costly, so we aim to evaluate whether these can be reliably simplified. METHODS: We identified and applied five simplification strategies (i.e. truncation, steady flow modelling, moderate and severe grid coarsening, and reducing the number of cardiac cycles) to a patient-specific CFD setup. Subsequently, we evaluated whether these strategies can be used to (1) accurately predict the CFD output (i.e. particle distribution and tumor dose) and (2) quantify the sensitivity of the model output to a specific injection parameter (injection flow rate). RESULTS: For both accuracy and sensitivity purposes, moderate grid coarsening is the most reliable simplification strategy, allowing to predict the tumor dose with only a maximal deviation of 1.4 %, and a similar sensitivity (deviation of 0.7 %). The steady strategy performs the worst, with a maximal deviation in the tumor dose of 20 % and a difference in sensitivity of 10 %. CONCLUSION: The patient-specific 3D CFD simulations of this study can be reliably simplified by coarsening the grid, decreasing the computational time by roughly 45 %, which works especially well for sensitivity studies.

Adaptive design of experiments to fit surrogate Gaussian process regression models allows fast sensitivity analysis of the input waveform for patient-specific 3D CFD models of liver radioembolization.

BACKGROUND AND OBJECTIVE: Patient-specific 3D computational fluid dynamics (CFD) models are increasingly being used to understand and predict transarterial radioembolization procedures used for hepatocellular carcinoma treatment. While sensitivity analyses of these CFD models can help to determine the most impactful input parameters, such analyses are computationally costly. Therefore, we aim to use surrogate modelling to allow relatively cheap sensitivity analysis. As an example, we compute Sobol's sensitivity indices for three input waveform shape parameters. METHODS: We extracted three characteristic shape parameters from our input mass flow rate waveform (peak systolic mass flow rate, heart rate, systolic duration) and defined our 3D input parameter space by varying these parameters within 75 %-125 % of their nominal values. To fit our surrogate model with a minimal number of costly CFD simulations, we developed an adaptive design of experiments (ADOE) algorithm. The ADOE uses 100 Latin hypercube sampled points in 3D input space to define the initial design of experiments (DOE). Subsequently, we re-sample input space with 10,000 Latin Hypercube sampled points and cheaply estimate the outputs using the surrogate model. In each of 27 equivolume bins which divide our input space, we determine the most uncertain prediction of the 10,000 points, compute the true outputs using CFD, and add these points to the DOE. For each ADOE iteration, we calculate Sobol's sensitivity indices, and we continue to add batches of 27 samples to the DOE until the Sobol indices have stabilized. RESULTS: We tested our ADOE algorithm on the Ishigami function and showed that we can reliably obtain Sobol's indices with an absolute error <0.1. Applying ADOE to our waveform sensitivity problem, we found that the first-order sensitivity indices were 0.0550, 0.0191 and 0.407 for the peak systolic mass flow rate, heart rate, and the systolic duration, respectively. CONCLUSIONS: Although the current study was an illustrative case, the ADOE allows reliable sensitivity analysis with a limited number of complex model evaluations, and performs well even when the optimal DOE size is a priori unknown. This enables us to identify the highest-impact input parameters of our model, and other novel, costly models in the future.

Branching Exponents of Synthetic Vascular Trees Under Different Optimality Principles.

OBJECTIVE: The branching behavior of vascular trees is often characterized using Murray's law. We investigate its validity using synthetic vascular trees generated under global optimization criteria. METHODS: Our synthetic tree model does not incorporate Murray's law explicitly. Instead, we show that its validity depends on properties of the optimization model and investigate the effects of different physical constraints and optimization goals on the branching exponent that is now allowed to vary locally. In particular, we include variable blood viscosity due to the Fåhræus-Lindqvist effect and enforce an equal pressure drop between inflow and the micro-circulation. Using our global optimization framework, we generate vascular trees with over one million terminal vessels and compare them against a detailed corrosion cast of the portal venous tree of a human liver. RESULTS: Murray's law is fulfilled when no additional constraints are enforced, indicating its validity in this setting. Variable blood viscosity or equal pressure drop lead to different optima but with the branching exponent inside the experimentally predicted range between 2.0 and 3.0. The validation against the corrosion cast shows good agreement from the portal vein down to the venules. CONCLUSION: Not enforcing Murray's law increases the predictive capabilities of synthetic vascular trees, and in addition reduces the computational cost. SIGNIFICANCE: The ability to study optimal branching exponents across different scales can improve the functional assessment of organs.

Hydraulic conductivity of human cancer tissue: A hybrid study.

Background: Elevated tumor tissue interstitial fluid pressure (IFP) is an adverse biomechanical biomarker that predicts poor therapy response and an aggressive phenotype. Advances in functional imaging have opened the prospect of measuring IFP non-invasively. Image-based estimation of the IFP requires knowledge of the tissue hydraulic conductivity (K), a measure for the ease of bulk flow through the interstitium. However, data on the magnitude of K in human cancer tissue are not available. Methods: We measured the hydraulic conductivity of tumor tissue using modified Ussing chambers in surgical resection specimens. The effect of the tumor microenvironment (TME) on K was investigated by quantifying the collagen content, cell density, and fibroblast density of the tested samples using quantitative immune histochemistry. Also, we developed a computational fluid dynamics (CFD) model to evaluate the role of K on interstitial fluid flow and drug transport in solid tumors. Results: The results show that the hydraulic conductivity of human tumor tissues is very limited, ranging from approximately 10-15 to 10-14 m2/Pa∙s. Moreover, K values varied significantly between tumor types and between different samples from the same tumor. A significant inverse correlation was found between collagen fiber density and hydraulic conductivity values. However, no correlation was detected between K and cancer cell or fibroblast densities. The computational model demonstrated the impact of K on the interstitial fluid flow and the drug concentration profile: higher K values led to a lower IFP and deeper drug penetration. Conclusions: Human tumor tissue is characterized by a very limited hydraulic conductivity, representing a barrier to effective drug transport. The results of this study can inform the development of realistic computational models, facilitate non-invasive IFP estimation, and contribute to stromal targeting anticancer therapies.

Spatiotemporal Analysis of Particle Spread to Assess the Hybrid Particle-Flow CFD Model of Radioembolization of HCC Tumors.

OBJECTIVE: Computational fluid dynamics (CFD) models can potentially aid in pre-operative planning of transarterial radioactive microparticle injections to treat hepatocellular carcinoma, but these models are computationally very costly. Previously, we introduced the hybrid particle-flow model as a surrogate, less costly modelling approach for the full particle distribution in truncated hepatic arterial trees. We hypothesized that higher cross-sectional particle spread could increase the match between flow and particle distribution. Here, we investigate whether truncation is still reliable for selective injection scenarios, and if spread is an important factor to consider for reliable truncation. METHODS: Moderate and severe up- and downstream truncation for selective injection served as input for the hybrid model to compare downstream particle distributions with non-truncated models. In each simulation, particle cross-sectional spread was quantified for 5-6 planes. RESULTS: Severe truncation gave maximum differences in particle distribution of ∼4-11% and ∼8-9% for down- and upstream truncation, respectively. For moderate truncation, these differences were only ∼1-1.5% and ∼0.5-2%. Considering all particles, spread increased downstream of the tip to 80-90%. However, spread was found to be much lower at specific timepoints, indicating high time-dependency. CONCLUSION: Combining domain truncation with hybrid particle-flow modelling is an effective method to reduce computational complexity, but moderate truncation is more reliable than severe truncation. Time-dependent spread measures show where differences might arise between flow and particle modelling. SIGNIFICANCE: The hybrid particle-flow model cuts down computational time significantly by reducing the physical domain, paving the way towards future clinical applications.

Effect of interstitial fluid pressure on shear wave elastography: an experimental and computational study.

Objective. An elevated interstitial fluid pressure (IFP) can lead to strain-induced stiffening of poroelastic biological tissues. As shear wave elastography (SWE) measures functional tissue stiffness based on the propagation speed of acoustically induced shear waves, the shear wave velocity (SWV) can be used as an indirect measurement of the IFP. The underlying biomechanical principle for this stiffening behavior with pressurization is however not well understood, and we therefore studied how IFP affects SWV through SWE experiments and numerical modeling.Approach. For model set-up and verification, SWE experiments were performed while dynamically modulating IFP in a chicken breast. To identify the confounding factors of the SWV-IFP relationship, we manipulated the material model (linear poroelastic versus porohyperelastic), deformation assumptions (geometric linearity versus nonlinearity), and boundary conditions (constrained versus unconstrained) in a finite element model mimicking the SWE experiments.Main results. The experiments demonstrated a statistically significant positive correlation between the SWV and IFP. The model was able to reproduce a similar SWV-IFP relationship by considering an unconstrained porohyperelastic tissue. Material nonlinearity was identified as the primary factor contributing to this relationship, whereas geometric nonlinearity played a smaller role. The experiments also highlighted the importance of the dynamic nature of the pressurization procedure, as indicated by a different observed SWV-IFP for pressure buildup and relaxation, but its clinical relevance needs to be further investigated.Significance. The developed model provides an adaptable framework for SWE of poroelastic tissues and paves the way towards non-invasive measurements of IFP.

First-in-human real-time AI-assisted instrument deocclusion during augmented reality robotic surgery.

The integration of Augmented Reality (AR) into daily surgical practice is withheld by the correct registration of pre-operative data. This includes intelligent 3D model superposition whilst simultaneously handling real and virtual occlusions caused by the AR overlay. Occlusions can negatively impact surgical safety and as such deteriorate rather than improve surgical care. Robotic surgery is particularly suited to tackle these integration challenges in a stepwise approach as the robotic console allows for different inputs to be displayed in parallel to the surgeon. Nevertheless, real-time de-occlusion requires extensive computational resources which further complicates clinical integration. This work tackles the problem of instrument occlusion and presents, to the authors' best knowledge, the first-in-human on edge deployment of a real-time binary segmentation pipeline during three robot-assisted surgeries: partial nephrectomy, migrated endovascular stent removal, and liver metastasectomy. To this end, a state-of-the-art real-time segmentation and 3D model pipeline was implemented and presented to the surgeon during live surgery. The pipeline allows real-time binary segmentation of 37 non-organic surgical items, which are never occluded during AR. The application features real-time manual 3D model manipulation for correct soft tissue alignment. The proposed pipeline can contribute towards surgical safety, ergonomics, and acceptance of AR in minimally invasive surgery.

Drug transport modeling in solid tumors: A computational exploration of spatial heterogeneity of biophysical properties.

Inadequate uptake of therapeutic agents by tumor cells is still a major barrier in clinical cancer therapy. Mathematical modeling is a powerful tool to describe and investigate the transport phenomena involved. However, current models for interstitial flow and drug delivery in solid tumors have not yet embedded the existing heterogeneity of tumor biomechanical properties. The purpose of this study is to introduce a novel and more realistic methodology for computational models of solid tumor perfusion and drug delivery accounting for these regional heterogeneities as well as lymphatic drainage effects. Several tumor geometries were studied using an advanced computational fluid dynamics (CFD) modeling approach of intratumor interstitial fluid flow and drug transport. Hereby, the following novelties were implemented: (i) the heterogeneity of tumor-specific hydraulic conductivity and capillary permeability; (ii) the effect of lymphatic drainage on interstitial fluid flow and drug penetration. Tumor size and shape both have a crucial role on the interstitial fluid flow regime as well as drug transport illustrating a direct correlation with interstitial fluid pressure (IFP) and an inverse correlation with drug penetration, except for large tumors having a diameter larger than 50 mm. The results also suggest that the interstitial fluid flow and drug penetration in small tumors depend on tumor shape. A parameter study on the necrotic core size illustrated that the core effect (i.e. fluid flow and drug penetration alteration) was only profound in small tumors. Interestingly, the impact of a necrotic core on drug penetration differs depending on the tumor shape from having no effect in ideally spherical tumors to a clear effect in elliptical tumors with a necrotic core. A realistic presence of lymphatic vessels only slightly affected tumor perfusion, having no substantial effect on drug delivery. In conclusion, our findings illustrated that our novel parametric CFD modeling strategy in combination with accurate profiling of heterogeneous tumor biophysical properties can provide a powerful tool for better insights into tumor perfusion and drug transport, enabling effective therapy planning.

Calf health veterinary services: Making them work for calves, farmers and veterinarians.

BACKGROUND: Despite an appetite among UK veterinarians (vets) and farmers to improve calf health, vets face challenges in delivering and sustaining proactive calf health services. METHODS: Forty-six vets and 10 veterinary technicians (techs) participated in a project to determine what makes calf health services successful while improving their own services. In four facilitated workshops and two seminars, carried out between August 2021 and April 2022, participants described their approaches to calf work, discussed measures of success, identified challenges and success factors, and addressed knowledge gaps. RESULTS: Many approaches to calf health services were described, and these could be categorised into three overlapping models. Success involved enthusiastic, knowledgeable vets/techs, supported by their practice team, fostering positive attitudes among farmers by providing the services they need, creating a tangible return on investment for farmers and the practice. Lack of time was identified as the most prominent challenge to achieving success. LIMITATIONS: Participants were self-selected from one nationwide group of practices. CONCLUSION: Successful calf health services depend on identifying the needs of calves, farmers and veterinary practices, and delivering measurable benefits to each. More calf health services embedded as a core part of farm veterinary practice could bring wide ranging benefits to calves, farmers and vets.

Robot-assisted Partial Nephrectomy Using Intra-arterial Renal Hypothermia for Highly Complex Endophytic or Hilar Tumors: Case Series and Description of Surgical Technique.

Background: In partial nephrectomy for highly complex tumors with expected long ischemia time, renal hypothermia can be used to minimize ischemic parenchymal damage. Objective: To describe our case series, surgical technique, and early outcomes for robot-assisted partial nephrectomy (RAPN) using intra-arterial cold perfusion through arteriotomy. Design setting and participants: A retrospective analysis was conducted of ten patients with renal tumors (PADUA score 9-13) undergoing RAPN between March 2020 and March 2023 with intra-arterial cooling because of expected arterial clamping times longer than 25 min. Surgical procedure: Multiport transperitoneal RAPN with full renal mobilization and arterial, venous, and ureteral clamping was performed. After arteriotomy and venotomy, 4°C heparinized saline is administered intravascular through a Fogarty catheter to maintain renal hypothermia while performing RAPN. Measurements: Demographic data, renal function, console and ischemia times, surgical margin status, hospital stay, estimated blood loss, and complications were analyzed. Results and limitations: The median warm and cold ischemia times were 4 min (interquartile range [IQR] 3-7 min) and 60 min (IQR 33-75 min), respectively. The median rewarming ischemia time was 10.5 min (IQR 6.5-23.75 min). The median pre- and postoperative estimated glomerular filtration rate values at least 1 mo after surgery were 90 ml/min (IQR 78.35-90 ml/min) and 86.9 ml/min (IQR 62.08-90 ml/min), respectively. Limitations include small cohort size and short median follow-up (13 [IQR 9.1-32.4] mo). Conclusions: We demonstrate the feasibility and first case series for RAPN using intra-arterial renal hypothermia through arteriotomy. This approach broadens the scope for minimal invasive nephron-sparing surgery in highly complex renal masses. Patient summary: We demonstrate a minimally invasive surgical technique that reduces kidney infarction during complex kidney tumor removal where surrounding healthy kidney tissue is spared. The technique entails arterial cold fluid irrigation, which temporarily decreases renal metabolism and allows more kidneys to be salvaged.

A Novel Three-dimensional Planning Tool for Selective Clamping During Partial Nephrectomy: Validation of a Perfusion Zone Algorithm.

BACKGROUND: Selective clamping during robot-assisted partial nephrectomy (RAPN) requires extensive knowledge on patient-specific renal vasculature, obtained through imaging. OBJECTIVE: To validate an in-house developed perfusion zone algorithm that provides patient-specific three-dimensional (3D) renal perfusion information. DESIGN, SETTING, AND PARTICIPANTS: Between October 2020 and June 2022, 25 patients undergoing RAPN at Ghent University Hospital were included. Three-dimensional models, based on preoperative computed tomography (CT) scans, showed the clamped artery's ischemic zone, as calculated by the algorithm. SURGICAL PROCEDURE: All patients underwent selective clamping during RAPN. Indocyanine green (ICG) was administered to visualize the true ischemic zone perioperatively. Surgery was recorded for a postoperative analysis. MEASUREMENTS: The true ischemic zone of the clamped artery was compared with the ischemic zone predicted by the algorithm through two metrics: (1) total ischemic zone overlap and (2) tumor ischemic zone overlap. Six urologists assessed metric 1; metric 2 was assessed objectively by the authors. RESULTS AND LIMITATIONS: In 92% of the cases, the algorithm was sufficiently accurate to plan a selective clamping strategy. Metric 1 showed an average score of 4.28 out of 5. Metric 2 showed an average score of 4.14 out of 5. A first limitation is that ICG can be evaluated only at the kidney surface. A second limitation is that mainly patients with impaired renal function are expected to benefit from this technology, but contrast-enhanced CT is required at present. CONCLUSIONS: The proposed new tool demonstrated high accuracy when planning selective clamping for RAPN. A follow-up prospective study is needed to determine the tool's clinical added value. PATIENT SUMMARY: In partial nephrectomy, the surgeon has no information on which specific arterial branches perfuse the kidney tumor. We developed a surgeon support system that visualizes the perfusion zones of all arteries on a three-dimensional model and indicates the correct arteries to clamp. In this study, we validate this tool.