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.

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.

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.

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. SUMMARY BACKGROUND DATA / BACKGROUND: The use of surgical video data has become 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 dataset 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 post-processing step to enhance the performance and test a low-cost setup for real-time anonymization during live surgery streaming. RESULTS: Framewise anonymization yielded an ROC AUC-score of 99.46% on unseen procedures, increasing to 99.89% after post-processing. Our Robotic Anonymization Network (ROBAN) 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 ROBAN 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.

Surgical Phase Duration in Robot-Assisted Partial Nephrectomy: A Surgical Data Science Exploration for Clinical Relevance.

(1) Background: Surgical phases form the basic building blocks for surgical skill assessment, feedback, and teaching. The phase duration itself and its correlation with clinical parameters at diagnosis have not yet been investigated. Novel commercial platforms provide phase indications but have not been assessed for accuracy yet. (2) Methods: We assessed 100 robot-assisted partial nephrectomy videos for phase durations based on previously defined proficiency metrics. We developed an annotation framework and subsequently compared our annotations to an existing commercial solution (Touch Surgery, Medtronic™). We subsequently explored clinical correlations between phase durations and parameters derived from diagnosis and treatment. (3) Results: An objective and uniform phase assessment requires precise definitions derived from an iterative revision process. A comparison to a commercial solution shows large differences in definitions across phases. BMI and the duration of renal tumor identification are positively correlated, as are tumor complexity and both tumor excision and renorrhaphy duration. (4) Conclusions: The surgical phase duration can be correlated with certain clinical outcomes. Further research should investigate whether the retrieved correlations are also clinically meaningful. This requires an increase in dataset sizes and facilitation through intelligent computer vision algorithms. Commercial platforms can facilitate this dataset expansion and help unlock the full potential, provided that the phase annotation details are disclosed.

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 Fåhræs-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.

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.

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.

A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment.

BACKGROUND: Long-term drug evaluation heavily relies upon rodent models. Drug discovery methods to reduce animal models in oncology may include three-dimensional (3D) cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties. METHODS: In this study we reconstructed a 3D tumor using an elastic polymer (acrylate-endcapped urethane-based poly(ethylene glycol) (AUPPEG)) with clinical relevant stiffness. Single cell suspensions from low-grade serous ovarian cancer (LGSOC) patient-derived early passage cultures of cancer cells and cancer-associated fibroblasts (CAF) embedded in a collagen gel were introduced to the AUPPEG scaffold. After self-organization in to a 3D tumor, this model was evaluated by a long-term (> 40 days) exposure to a drug combination of MEK and HSP90 inhibitors. The drug-response results from this long-term in vitro model are compared with drug responses in an orthotopic LGSOC xenograft mouse model. RESULTS: The in vitro 3D scaffold LGSOC model mimics the growth ratio and spatial organization of the LGSOC. The AUPPEG scaffold approach allows to test new targeted treatments and monitor long-term drug responses. The results correlate with those of the orthotopic LGSOC xenograft mouse model. CONCLUSIONS: The mechanically-tunable scaffolds colonized by a three-dimensional LGSOC allow long-term drug evaluation and can be considered as a valid alternative to reduce, replace and refine animal models in drug discovery.

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.

Improving Augmented Reality Through Deep Learning: Real-time Instrument Delineation in Robotic Renal Surgery.

Several barriers prevent the integration and adoption of augmented reality (AR) in robotic renal surgery despite the increased availability of virtual three-dimensional (3D) models. Apart from correct model alignment and deformation, not all instruments are clearly visible in AR. Superimposition of a 3D model on top of the surgical stream, including the instruments, can result in a potentially hazardous surgical situation. We demonstrate real-time instrument detection during AR-guided robot-assisted partial nephrectomy and show the generalization of our algorithm to AR-guided robot-assisted kidney transplantation. We developed an algorithm using deep learning networks to detect all nonorganic items. This algorithm learned to extract this information for 65 927 manually labeled instruments on 15 100 frames. Our setup, which runs on a standalone laptop, was deployed in three different hospitals and used by four different surgeons. Instrument detection is a simple and feasible way to enhance the safety of AR-guided surgery. Future investigations should strive to optimize efficient video processing to minimize the 0.5-s delay currently experienced. General AR applications also need further optimization, including detection and tracking of organ deformation, for full clinical implementation.

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.

Interstitial fluid pressure as an emerging biomarker in solid tumors.

The physical microenvironment of cancer is characterized by elevated stiffness and tissue pressure, the main component of which is the interstitial fluid pressure (IFP). Elevated IFP is an established negative predictive and prognostic parameter, directly affecting malignant behavior and therapy response. As such, measurement of the IFP would allow to develop strategies aimed at engineering the physical microenvironment of cancer. Traditionally, IFP measurement required the use of invasive methods. Recent progress in dynamic and functional imaging methods such as dynamic contrast enhanced (DCE) magnetic resonance imaging and elastography, combined with numerical models and simulation, allows to comprehensively assess the biomechanical landscape of cancer, and may help to overcome physical barriers to drug delivery and immune cell infiltration. Here, we provide a comprehensive overview of the origin of elevated IFP, and its role in the malignant phenotype. Also, we review the methods used to measure IFP using invasive and imaging based methods, and highlight remaining obstacles and potential areas of progress in order to implement IFP measurement in clinical practice.

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.

Rigorous mathematical optimization of synthetic hepatic vascular trees.

In this paper, we introduce a new framework for generating synthetic vascular trees, based on rigorous model-based mathematical optimization. Our main contribution is the reformulation of finding the optimal global tree geometry into a nonlinear optimization problem (NLP). This rigorous mathematical formulation accommodates efficient solution algorithms such as the interior point method and allows us to easily change boundary conditions and constraints applied to the tree. Moreover, it creates trifurcations in addition to bifurcations. A second contribution is the addition of an optimization stage for the tree topology. Here, we combine constrained constructive optimization (CCO) with a heuristic approach to search among possible tree topologies. We combine the NLP formulation and the topology optimization into a single algorithmic approach. Finally, we attempt the validation of our new model-based optimization framework using a detailed corrosion cast of a human liver, which allows a quantitative comparison of the synthetic tree structure with the tree structure determined experimentally down to the fifth generation. The results show that our new framework is capable of generating asymmetric synthetic trees that match the available physiological corrosion cast data better than trees generated by the standard CCO approach.

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.

A Hybrid Particle-Flow CFD Modeling Approach in Truncated Hepatic Arterial Trees for Liver Radioembolization: A Patient-specific Case Study.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. At its intermediate, unresectable stage, HCC is typically treated by local injection of embolizing microspheres in the hepatic arteries to selectively damage tumor tissue. Interestingly, computational fluid dynamics (CFD) has been applied increasingly to elucidate the impact of clinically variable parameters, such as injection location, on the downstream particle distribution. This study aims to reduce the computational cost of such CFD approaches by introducing a novel truncation algorithm to simplify hepatic arterial trees, and a hybrid particle-flow modeling approach which only models particles in the first few bifurcations. A patient-specific hepatic arterial geometry was pruned at three different levels, resulting in three trees: Geometry 1 (48 outlets), Geometry 2 (38 outlets), and Geometry 3 (17 outlets). In each geometry, 1 planar injection and 3 catheter injections (each with different tip locations) were performed. For the truncated geometries, it was assumed that, downstream of the truncated outlets, particles distributed themselves proportional to the blood flow. This allowed to compare the particle distribution in all 48 "outlets" for each geometry. For the planar injections, the median difference in outlet-specific particle distribution between Geometry 1 and 3 was 0.21%; while the median difference between outlet-specific flow and particle distribution in Geometry 1 was 0.40%. Comparing catheter injections, the maximum median difference in particle distribution between Geometry 1 and 3 was 0.24%, while the maximum median difference between particle and flow distribution was 0.62%. The results suggest that the hepatic arterial tree might be reliably truncated to estimate the particle distribution in the full-complexity tree. In the resulting hybrid particle-flow model, explicit particle modeling was only deemed necessary in the first few bifurcations of the arterial tree. Interestingly, using flow distribution as a surrogate for particle distribution in the entire tree was considerably less accurate than using the hybrid model, although the difference was much higher for catheter injections than for planar injections. Future work should focus on replicating and experimentally validating these results in more patient-specific geometries.

Optimization of intraperitoneal aerosolized drug delivery using computational fluid dynamics (CFD) modeling.

Intraperitoneal (IP) aerosolized anticancer drug delivery was recently introduced in the treatment of patients with peritoneal metastases. However, little is known on the effect of treatment parameters on the spatial distribution of the aerosol droplets in the peritoneal cavity. Here, computational fluid dynamics (CFD) modeling was used in conjunction with experimental validation in order to investigate the effect of droplet size, liquid flow rate and viscosity, and the addition of an electrostatic field on the homogeneity of IP aerosol. We found that spatial distribution is optimal with small droplet sizes (1-5 µm). Using the current clinically used technology (droplet size of 30 µm), the optimal spatial distribution of aerosol is obtained with a liquid flow rate of 0.6 mL s-1. Compared to saline, nebulization of higher viscosity liquids results in less homogeneous aerosol distribution. The addition of electrostatic precipitation significantly improves homogeneity of aerosol distribution, but no further improvement is obtained with voltages higher than 6.5 kV. The results of the current study will allow to choose treatment parameters and settings in order to optimize spatial distribution of IP aerosolized drug, with a potential to enhance its anticancer effect.

Exploring high pressure nebulization of Pluronic F127 hydrogels for intraperitoneal drug delivery.

Peritoneal metastasis is an advanced cancer type which can be treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Here, chemotherapeutics are nebulized under high pressure in the intraperitoneal (IP) cavity to obtain a better biodistribution and tumor penetration. To prevent the fast leakage of chemotherapeutics from the IP cavity, however, nebulization of controlled release formulations is of interest. In this study, the potential of the thermosensitive hydrogel Pluronic F127 to be applied by high pressure nebulization is evaluated. Therefore, aerosol formation is experimentally examined by laser diffraction and theoretically simulated by computational fluid dynamics (CFD) modelling. Furthermore, Pluronic F127 hydrogels are subjected to rheological characterization after which the release of fluorescent model nanoparticles from the hydrogels is determined. A delicate equilibrium is observed between controlled release properties and suitability for aerosolization, where denser hydrogels (20% and 25% w/v Pluronic F127) are able to sustain nanoparticle release up to 30 h, but cannot effectively be nebulized and vice versa. This is demonstrated by a growing aerosol droplet size and exponentially decreasing aerosol cone angle when Pluronic F127 concentration and viscosity increase. Novel nozzle designs or alternative controlled release formulations could move intraperitoneal drug delivery by high pressure nebulization forward.