3D Model Research Articles

DDDR-27. BMP SIGNALING MODULATES APOPTOTIC AND NON-APOPTOTIC CELL DEATH IN GLIOBLASTOMA

Abstract Recurrence occurs in approximately 90% of glioblastoma (GBM) patients, in part due to the tumors becoming resistant to cell death in response to existing therapies. These therapies often trigger apoptosis; however, apoptosis is only one of several different forms of cell death. We hypothesize that activating non-canonical death mechanisms could provide a back door to killing treatment-resistant GBM cells. To test this hypothesis, we first developed a new imaging-based high-throughput method to directly quantify cell death in 3D models. Using this method, we find patient-derived GBM spheroids to be resistant to the induction of cell death in response to various standard-of-care and experimental therapeutic compounds. To further investigate mechanisms underlying this resistance, we screened a panel of extracellular protein ligands for the modulation of cell death response. We find that bone morphogenic protein (BMP) signaling increases resistance to several apoptosis-inducing compounds, including temozolomide and tyrosine kinase inhibitors. Intriguingly, BMP signaling simultaneously enhanced sensitivity to a novel non-apoptotic cell death pathway triggered by the small molecule CIL56. Efforts are ongoing to further understand how BMP signaling governs apoptotic and non-apoptotic cell death mechanisms. Nevertheless, our results suggest a novel approach to treating GBM, centered upon the modulation of BMP signaling combined with the use of agents that induce non-apoptotic cell death.

Molecular dynamics simulations of a multicellular model with cell-cell interactions and Hippo signaling pathway.

The transcriptional coactivator Yes-associated protein (YAP)/transcriptional co-activator with PDZ binding motif (TAZ) induces cell proliferation through nuclear localization at low cell density. Conversely, at extremely high cell density, the Hippo pathway, which regulates YAP/TAZ, is activated. This activation leads to the translocation of YAP/TAZ into the cytoplasm, resulting in cell cycle arrest. Various cancer cells have several times more YAP/TAZ than normal cells. However, it is not entirely clear whether this several-fold increase in YAP/TAZ alone is sufficient to overcome proliferation inhibition (contact inhibition) under high-density conditions, thereby allowing continuous proliferation. In this study, we construct a three-dimensional (3D) mathematical model of cell proliferation incorporating the Hippo-YAP/TAZ pathway. Herein, a significant innovation in our approach is the introduction of a novel modeling component that inputs cell density, which reflects cell dynamics, into the Hippo pathway and enables the simulation of cell proliferation as the output response. We assume such 3D model with cell-cell interactions by solving reaction and molecular dynamics (MD) equations by applying adhesion and repulsive forces that act between cells and frictional forces acting on each cell. We assume Lennard-Jones (12-6) potential with a softcore character so that each cell secures its exclusive domain. We set cell cycles composed of mitotic and cell growth phases in which cells divide and grow under the influence of cell kinetics. We perform mathematical simulations at various YAP/TAZ levels to investigate the extent of YAP/TAZ increase required for sustained proliferation at high density. The results show that a twofold increase in YAP/TAZ levels of cancer cells was sufficient to evade cell cycle arrest compared to normal cells, enabling cells to continue proliferating even under high-density conditions. Finally, this mathematical model, which incorporates cell-cell interactions and the Hippo-YAP/TAZ pathway, may be applicable for evaluating cancer malignancy based on YAP/TAZ levels, developing drugs to suppress the abnormal proliferation of cancer cells, and determining appropriate drug dosages. The source codes are freely available.

Optimization Design of Hull Compartment Structure Based on 3D Modeling

Optimization Design of Hull Compartment Structure Based on 3D Modeling

“Jia you (Add oil, let’s go!)”: A Speech’s Critical Discourse Analysis on the Use of Metaphors to Empower the Asian Community Against Hate Amid Covid-19

Following Fairclough’s three-dimensional model, this paper presents a critical discourse analysis of the speech “We are GOLDEN” delivered at a Stop Asian Hate rally held in the U.S. in 2021.The analysis focuses on the use of adjectives and metaphors at the text, discursive practice and social practice levels, which demonstrate the speaker’s strong criticism and opposition to violence, systemic racism, hegemony, and the power of white supremacy that became evermore present amid COVID-19. The results unveil the use of cultural and historical intertextuality from a resilient perspective to empower the Asian American and Pacific Islander community to promote social change and stand against hate.

TMOD-28. MODELING MICROENVIRONMENTAL DYNAMICS: A NOVEL 3D GLIOMA-NEURON FUSION MODEL

Abstract Gliomas engage in bidirectional interactions with their microenvironment, wherein neuronal activity influences glioma proliferation and gliomas induce neuronal hyperexcitability. Although various models elucidate this complex interplay, a preference for a three-dimensional (3D) cell culture model has emerged to mimic intra-tumoral heterogeneity and microenvironmental interactions influencing glioma invasion, resistance, and recurrence. This study introduces an in vitro, self-assembled, scaffold-free, neuron-glioma spheroid fusion model to investigate the electrophysiological and functional interplay between glioma and its microenvironment. Primary mouse cortical neurons (MCN) were isolated from prenatal brain tissues and were cultured at 500,000 cells/spheroid on ultra-low attachment plates. Glioma organoids (WHO Grade 2-4) were developed from primary patient-derived tissue samples and were allowed to self-assemble for at least two weeks. After spontaneous spiking activity was detected in MCN spheroids, they were combined with glioma organoids in culture and allowed to fuse. A multielectrode array (MEA) was used to characterize the electrophysiological properties of the fusion model. Structural and functional characterizations were performed using immunofluorescence staining of proliferation, microglial, astrocytic, synaptic, and tumor markers. Additionally, the electrophysiological effects of the dual-IDH-mutant inhibitor, Vorasidenib, were assessed in WHO grade 2-4 IDH-mutant gliomas. Electrophysiological analysis of glioma-neuron co-cultures using MEA demonstrated a significantly increased network synchrony and firing rate in the fusion model when compared with the neuron-only condition, consistent with 2D models in the past. In correlation, the fusion model also demonstrated a significant increase in the Ki67 proliferation index across WHO grade 2-4 gliomas when compared to the glioma organoid-only condition. Vorasidenib treatment decreased neuronal firing rate and synchrony. Together, these results offer a high-throughput 3D model for recapitulating the tumor-brain microenvironment for both low and high-grade gliomas. Future studies will focus on the use of this model for drug screening and the exploration of malignant transformation in gliomas.

Energy absorption characteristics and auxetic effect of novel elliptic-arc re-entrant honeycomb structures

The novel elliptical-arc re-entrant honeycomb (ERH) is designed by substituting the straight inclined struts within the re-entrant honeycomb with elliptical-arc struts. To assess its performance effectively, the study established the 3D equivalent Cauchy model (3D-ECM) and 2D equivalent Kirchhoff–Love model (2D-EKM) using the variational asymptotic method. The equivalent properties derived from the unit-cell constitutive model were integrated into the equivalent models for macroscopic analysis. Through 3D printing experiments and numerical simulations, the model’s accuracy in predicting the compression behaviors and auxetic effects of various uni- and multi-cellular ERHs under uniaxial compression, as well as the three-point bending behaviors of ERH panels were confirmed. In addition, this model substantially simplifies the modeling process, leading to a 8-fold increase in computational efficiency. Parametric analyses demonstrated that the ERH structure can uphold a beneficial auxetic effect while achieving lightweight and high strength characteristics when the axial ratio of the ellipse equals 1.25. Furthermore, ERH structures outperform arc-shaped re-entrant and regular re-entrant honeycombs in energy absorption and specific energy absorption capacity. These findings offer valuable insights for the preliminary design and optimization of ERH structures.

Estimating Cooling Energy Demand from Building Attributes and Environmental Parameters using 3D City Models

Abstract. Most of the global population have shifted to urbanization with advancements in technology. With this transition comes the responsibility of applying these technologies to promote sustainable development practice. Since energy demand is highest in the urbanized areas, it is important that proper assessment and management of energy resource is considered in policy-making and urban planning. This study investigated the estimation of cooling energy demand in Iloilo City Proper, Philippines using a 3D city model integrated with building attributes including building functions and year of construction, while also taking into consideration meteorological factors in the area. The proposed method used the application SimStadt2.0, following the German computation standard DINV18599. Building functions and year of construction were extracted from available building attributes data and satellite images respectively, using the free and open-source software QGIS. A CityGML Level of Detail 1 was generated from 3Dfier using building footprints and LiDAR point cloud data, along with the extracted building attributes of the 5,426 buildings. Meteorological data from INSEL 8 were also considered in the estimation of cooling energy demand in SimStadt2.0. Results showed a monthly energy demand of 12.33 kWh to 313,530.08 kWh in the study area. The estimated energy demand values were higher than the standard mean for different building functions in the country, but within the expected range of values for each season. Urban Heat Islands (UHIs), analyzed using Land Surface Temperature (LST) values, also have significant correlation to areas with higher cooling energy demands. However, inconsistencies can imply the need for further investigation.

Nonlinear Stress-Induced Transformations in Collagen Fibrillar Organization, Disorder and Strain Mechanisms in the Bone-Cartilage Unit.

By developing a 3D X-ray modeling and spatially correlative imaging method for fibrous collagenous tissues, this study provides a comprehensive mapping of nanoscale deformation in the collagen fibril network across the intact bone-cartilage unit (BCU), whose healthy functioning is critical for joint function and preventing degeneration. Extracting the 3D fibril structure from 2D small-angle X-ray scattering before and during physiological compression reveals of dominant deformation modes, including crystallinity transitions, lateral fibril compression, and reorientation, which vary in a coupled, nonlinear, and correlated manner across the cartilage-bone interface. A distinct intermolecular arrangement of collagen molecules, and enhanced molecular-level disorder, is found in the cartilage (sliding) surface region. Just below, fibrils accommodate tissue strain by reorientation, which transitions molecular-level kinking or loss of crystallinity in the deep zone. Crystalline fibrils laterally shrink far more (20×) than they contract, possibly by water loss from between tropocollagen molecules. With the calcified plate acting as an anchor for surrounding tissue, a qualitative switch occurs in fibrillar deformation between the articular cartilage and calcified regions. These findings significantly advance this understanding of the complex, nonlinear ultrastructural dynamics at this critical interface, and opens avenues for developing targeted diagnostic and therapeutic strategies for musculoskeletal disorders.

LociPARSE: A Locality-aware Invariant Point Attention Model for Scoring RNA 3D Structures.

A scoring function that can reliably assess the accuracy of a 3D RNA structural model in the absence of experimental structure is not only important for model evaluation and selection but also useful for scoring-guided conformational sampling. However, high-fidelity RNA scoring has proven to be difficult using conventional knowledge-based statistical potentials and currently available machine learning-based approaches. Here, we present lociPARSE, a locality-aware invariant point attention architecture for scoring RNA 3D structures. Unlike existing machine learning methods that estimate superposition-based root-mean-square deviation (RMSD), lociPARSE estimates Local Distance Difference Test (lDDT) scores capturing the accuracy of each nucleotide and its surrounding local atomic environment in a superposition-free manner, before aggregating information to predict global structural accuracy. Tested on multiple datasets including CASP15, lociPARSE significantly outperforms existing statistical potentials (rsRNASP, cgRNASP, DFIRE-RNA, and RASP) and machine learning methods (ARES and RNA3DCNN) across complementary assessment metrics. lociPARSE is freely available at https://github.com/Bhattacharya-Lab/lociPARSE.

Relative facial width, and its association with canine size and body mass among chimpanzees and bonobos: Implications for understanding facial width-to-height ratio expression among human populations.

Facial width-to-height ratio (fWHR) has been widely investigated in the context of its role in visual communication, though there is a lack of consensus about how fWHR serves as a social signal. To better understand fWHR variation in a comparative context, we investigate the associations between fWHR and canine crown height (CCH) and body mass, respectively, among two chimpanzee subspecies (Pan troglodytes schweinfurthii, Pan troglodytes troglodytes) and bonobos (Pan paniscus). We collected landmark data from 3D surface models of 86 Pan cranial specimens to quantify fWHR and upper CCH, and to estimate body mass. We used Spearman's r and Kruskal-Wallis tests to test for significant relationships among variables, and to assess sexual dimorphism. There is an inverse relationship between fWHR and CCH in both sexes of Pan, however there are interpopulation differences in the relationship between fWHR and CCH among Pan taxa. Pan paniscus have relatively wide faces and small canine crowns, and wide faces in Pan t. schweinfurthii males may be driven by body size constraints. Pan troglodytes and Pan paniscus show fWHR dimorphism, and Pan paniscus have significantly higher fWHRs than do either Pan troglodytes subspecies. Our findings indicate that CCH and facial breadth may serve subtly different signaling functions among Pan taxa. Further research into the circumstances in which wide faces evolved among chimpanzees and bonobos will likely afford deeper insights into the function of relatively wide faces in the context of visual signaling among humans and our extinct hominin relatives.

Scalp condition improvement with botanical extracts possessing chemical and physical antioxidant activity.

Oxidative stress is implicated in scalp and hair health manifesting in several ways, including skin barrier, hair retention, healthy hair appearance and scalp sensation. We previously linked markers of oxidative damage to dandruff and skin barrier impairment and have linked key anti-dandruff technologies to the resolution of these issues. Here we expand the therapeutic space demonstrating many botanical extracts offer protective benefits against ROS stress via both chemical and biological antioxidant mechanisms. Chemical antioxidant activity of 10 botanical extracts was measured using oxygen radical absorbance capacity (ORAC) and biological antioxidant activity was measured using a Nrf-2 cell assay. A three-dimensional human keratinocyte skin equivalent model from MatTek was used to measure efficacy of reducing reactive oxygen species (ROS) from both the botanicals added as a solution and from a shampoo product. A 4-week consumer study with 56 panels was conducted with a leave-on treatment containing a botanical extract. Measurement of the oxidized lipids (9 and 13-Hydroxy-10E 12Z-octadecadienoic acid, HODE) extracted from scalp tape strips was made using gradient reversed-phase high-performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS). We demonstrated invitro that many botanical extracts exert antioxidant activity by quenching radicals in ORAC testing as well as activating biological antioxidant pathways via nrf-2 up-regulation in a cellular reporter system. Furthermore, we demonstrate these antioxidant activities for these botanicals in 3D skin models and ultimately show the reduction of lipid oxidation products in a consumer use context with a rosemary extract. Improved scalp condition can be achieved with incorporation of botanicals having the potential to exert antioxidant activity in hair/scalp care products.

EXTH-61. TOWARDS A QUANTUM THERAPY FOR GLIOBLASTOMA: A NEW THERAPEUTIC PARADIGM IN MEDICINE

Abstract BACKGROUND A cell operates as an interconnected bioelectrical circuit, utilising electron transfer processes for intracellular communication, with cytochrome c (Cyt c) playing a pivotal role. The redox processes of Cyt c, occurring via electron tunnelling, are essential for its translocation into the cytosol and modulation of its conformation to bind apoptotic protease activating factor 1. This highlights the need for novel technologies capable of interacting with these processes at the atomic scale to control downstream effects and induce apoptosis in cancer cells. METHODS We demonstrate that ‘bio-nanoantennae’, when supplied with an electrical current, enable quantum biological tunnelling for electron transfer (QBET) and facilitate cellular apoptosis in patient-derived IDH wild-type glioblastoma from both the infiltrative tumour margin and proliferative core. The bio-nanoantennae were constructed from gold nanoparticles functionalised with reduced Cyt c and zinc porphyrin as a redox couple. RESULTS Electrical polarisation of these bio-nanoantennae via resonant alternating currents in preclinical glioblastoma cells led to decreased metabolic activity and reduced cell viability by oxidizing Cyt c, thus inducing cellular stress. No significant effect was observed in healthy human astrocyte counterparts. The cytosol localised bio-nanoantennae induced differential gene expression related to ion channels, apoptosis, cancer proliferation and tumour suppression upon activation, in tumour relative to astrocyte cell populations. The bio-nanoantennae were also tested in 3D glioblastoma spheroid models, showing similar effects, and in vivo studies demonstrated a significant reduction in glioblastoma xenograft tumour size. CONCLUSION We propose that bio-nanoantennae modulate the redox state of Cyt c under an electrical field through QBET. To validate this, we investigated the tunnel junction energy and plasmon resonance scattering, and developed a mathematical model to explain the system’s behaviour. This innovative wireless electrical–molecular nanodevice, capable of inducing cancer cell apoptosis, paves the way for further applications of quantum signalling as a new (non-pharmacological) therapeutic paradigm.

3D bioprinted in vitro epilepsy models for pharmacological evaluation in temporal lobe epilepsy

This study introduces a novelin vitromodel for intractable temporal lobe epilepsy (TLE) utilizing 3D bioprinting technology, aiming to replicate the complex neurobiological characteristics of TLE more accurately. Primary neural cell constructs were fabricated and subjected to epileptiform-inducing conditions, fostering synaptic proliferation and neuronal loss. Systematically electrophysiological and immunofluorescent analyses indicated that significant synaptic connectivity and sustained epileptiform activities within the constructs akin to those observed in human epilepsy models. Notably, the model responded to treatments with phenytoin and tetrodotoxin, illustrating its potential utility in drug response kinetics studies. Furthermore, we performed drug permeability simulations using COMSOL Multiphysics to analyze the diffusion characteristics of these drugs within the constructs. These results confirm that our 3D bioprinted neural model provides a physiologically relevant and ethically sustainable platform, which is beneficial for studying TLE mechanisms and developing therapeutic strategies with high accuracy and clinical relevance.

DNAR-05. VALIDATING THE ERK5 PROTAC OS11 AS A POTENTIAL NOVEL THERAPEUTIC INEX VIVO GLIOMA STEM CELL MODELS OF INTRATUMOURAL HETEROGENEITY AND RESIDUAL DISEASE

Abstract Glioblastoma is a grade IV brain tumour with poor survival rates of 15 months post-diagnosis, and 5-year survival rates of 10%. Limited progress over the past 40 years to improve the current treatment regimen of surgery and chemo-/radio-therapy are mainly due to tumour heterogeneity that drive resistance mechanisms. The persistence of glioma stem-like cells (GSCs) sub-populations, particularly within post-surgical residual tumour tissue. ERK5 is an emerging oncology drug target that we previously highlighted as a potential target for combined therapy with temozolomide (TMZ) in glioblastoma due to heightened ERK5 expression, which is associated with poor survival. This current project aims to expand on our previous findings by establishing whether targeting ERK5 can sensitise glioblastoma cells to TMZ using primary derived ex vivo GSC models of intratumor heterogeneity and residual disease. Primary GSC models were derived from patients at the Royal Hallamshire Hospital. The PROTAC OS11 (CRUK & University of Manchester) was used to degrade ERK5. DNA damage and cell survival were evaluated following treatment of TMZ alone and in combination with OS11. Consistent with our findings in established glioma cell lines, OS11 was able to robustly degrade ERK5 in a 3D GSC model for at least 72hrs. Combining OS11 and TMZ in GSCs led to a significant increase in DNA damage, with MGMT negative cells exhibiting a greater increase in DNA damage compared to MGMT positive cells. However, unlike our previous findings in established cell lines, this did not lead to reduced cell survival in combination with TMZ. These findings further support the preclinical use of ex vivo models that better represent intratumoural heterogeneity and post-surgical GCS niches. Overall, these data highlight the value of preclinical validation in more clinically relevant models to identify the best possible novel therapeutic approaches to pursue further towards clinical delivery.

3D WCSPH modelling of landslide-water dynamics during 1963 Vajont disaster.

This study illustrates the full-scale 3D numerical simulation of the coupled water-landslide dynamics of the 1963 Vajont catastrophic event. The focus is given to the early phase of the event when about 270million cubic meters of rock fell into the reservoir within an estimated runout time of about 25s. A complex surge wave system developed throughout the basin in the first 40-55s, producing maximum run-up of 270m above the dam crowning. The mesh-free Lagrangian Weakly Compressible Smoothed Particle Hydrodynamics (WCSPH) method is adopted to discretize and solve the coupled system of governing equations for the landslide and water dynamics. The adopted model, which is based on SPHERA v.9.0.0 (Amicarelli et al. Comput Phys Commun, 2020), has been derived by introducing relevant modifications in the research code SPHERA (RSE SpA). The derived model is validated and the influence of water saturated soil on prediction of surge wave run-up is analysed. The average values from technical literature are assigned to mechanical parameters without tuning or calibration. The maximum flooding on the opposite side of the valley and the peak flow rate of the discharge hydrograph through the dam section show good agreement with reference data and improvements with respect to published results. The validated derived model proves to be a promising engineering tool for quantifying the level of risk in analogous applications.

NIMG-05. ARTIFICIAL INTELLIGENCE-BASED RESPONSE ASSESSMENT FOR PATIENTS RECEIVING LASER INTERSTITIAL THERMAL THERAPY

Abstract BACKGROUND Laser interstitial thermal therapy (LITT) is a minimally invasive option for tissue diagnosis, cytoreduction, and rapid post-operative return to systemic therapies for patients with brain tumors or radiation necrosis. As ablated tissue remains in situ, post-LITT edema may be associated with apparent increased lesion size and transient clinical worsening, complicating assessment of progression. METHODS All patients receiving LITT at a single center for tumors or radiation necrosis from 2015 – 2023 with ≥ 9 months of MRI follow-up were retrospectively reviewed. A 3D U-net segmentation model implemented in nnU-Net was developed for automated segmentation of Contrast-enhancing Lesion Volume (CeLV) of LITT-treated lesions on T1-weighted post-contrast MR images. CeLVs were analyzed to establish volumetric post-LITT response assessments. RESULTS Across 384 unique MRI exams, 61LITT-treated lesions and 6 control cases of medically-managed radiation necrosis were analyzed. Automated segmentation was qualitatively accurate in 367/384 (95.6%) images. CeLV increased to a median of 68.3% (IQR 35.1 – 109.2%) from baseline at 1 – 3 months from LITT (P = 0.0012) and returned to baseline thereafter. Based on established criteria, volumetric disease progression was defined as lesion expansion 40% from volumetric nadir or baseline. Twenty-one of 56 (37.5%) patients experienced volumetric progression with a progression-free survival of 21.4 (6.0 – 93.4) months. Patients experiencing volumetric progression had lower mOS (17.3 vs 62.1 months, P = 0.0015). CONCLUSIONS We observed a stereotyped increase in CeLV at 1 – 3 months post-LITT, which resolved within 6 months of the procedure. Post-LITT disease response can be reliably and feasibly assessed with criteria that account for this transient CeLV expansion. Automated lesion segmentation may speed adoption of volumetric response assessment criteria to clinical practice.

Impact of Geometric Attributes on Abdominal Aortic Aneurysm Rupture Risk: An InVivo FSI-Based Study.

Reported in this paper is a cutting-edge computational investigation into the influence of geometric characteristics on abdominal aortic aneurysm (AAA) rupture risk, beyond the traditional measure of maximum aneurysm diameter. A Comprehensive fluid-structure interaction (FSI) analysis was employed to assess risk factors in a range of patient scenarios, with the use of three-dimensional (3D) AAA models reconstructed from patient-specific aortic data and finite element method. Wall shear stress (WSS), and its derivatives such as time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT) and transverse WSS (transWSS) offer insights into the force dynamics acting on the AAA wall. Emphasis is placed on these WSS-based metrics and seven key geometric indices. By correlating these geometric discrepancies with biomechanical phenomena, this study highlights the novel and profound impact of geometry on risk prediction. This study demonstrates the necessity of a multidimensional assessment approach, future efforts should complement these findings with experimental validations for an applicable approach for clinical use.

Multi-Time Scale Energy Storage Optimization of DC Microgrid Source-Load Storage Based on Virtual Bus Voltage Control

The energy storage adjustment strategy of source and load storage in a DC microgrid is very important to the economic benefits of a power grid. Therefore, a multi-timescale energy storage optimization method for direct current (DC) microgrid source-load storage based on a virtual bus voltage control is studied. It uses a virtual damping compensation strategy to control the stability of virtual bus voltage and establishes a virtual energy storage model by combining different types of distributed capability units. The design of an optimization process for upper-level daily energy storage has the objective function of maximizing the economic benefits of microgrids to cope with unplanned fluctuations in power. A real-time energy-adjustment scheme for the lower level is introduced, and a real-time energy-adjustment scheme based on virtual energy storage for the short-term partition of the source-load storage is designed to improve the reliability of microgrid operations. The experiment shows that, in response to the constant amplitude oscillation of the power grid after a sudden increase in power, this method introduces a virtual damping compensation strategy at 20 s, which can stabilize the virtual bus voltage. From 00:00 to 09:00, the battery power remains at around 4 MW, and from 12:00 to 21:00, the battery exits the discharge state. The economic benefits from applying this method are significantly higher than before. This method can effectively adjust the source-load energy storage in real time. During peak electricity price periods, the SOC value of supercapacitors is below 0.4, and during normal electricity price periods, the SOC value of supercapacitors can reach up to 1.0, which can make the state of the charge value of supercapacitors meet economic requirements.

DDEL-06. CONVECTION-ENHANCED DELIVERY OF SEVEN DIFFERENT MOLECULES SHOW LARGE DIFFERENCES IN CONVECTIVE PROPERTIES BETWEEN MOLECULES. INFORMED DECISION MAKING FOR OPTIMIZED CATHETER PLACEMENT AND SUBSEQUENT INFUSION STRATEGIES

Abstract INTRODUCTION Glioblastoma (GBM) trials based on convection-enhanced drug delivery (CED) bypassing the blood-brain barrier have failed to prove efficient until now. Many factors influence CED. In this study we evaluated CED of seven different molecules using dynamic PET/MRI during infusion. This enabled in-depth evaluation of drug distribution and concentration gradients providing a more precise understanding of the Vd/Vi ratio and the extent of efficacy level across the Vd zone. Novel surgical catheter placement software algorithms, results in more informed-decision-making for catheter positioning and subsequent infusion planning strategies. METHODS Pigs were implanted with neuroinfuse™ drug delivery systems enabling intermittent drug infusions. Gadolinium, [124I]-UdR, [55Co]Co-DOTA-hEGF, [55Co]Co-DOTA-SP4, [18F]PSMA-1007 and three differently sized [64Cu]-labelled nanocarriers were evaluated in both pigs with and without a brain resection cavity. Gadolinium distribution was followed by MRI. PET imaging was used for the rest. To inform clinical trial design, strategic catheter placement and volumes to be infused, planning was investigated on several historical GBM cases. RESULTS Vd/Vi ratios ranged between 1.00 – 3.77. where large-sized liposomes performed best. Catheters stayed patent during weeks of repeated infusions. In the resected animals no leakage of drugs into the brain resection cavity was observed. Effective 3D modelling of novel catheter infusion planning aids provided visualized representations of tailor-made infusion plumes, capable of being suitably positioned to optimize surgical planning of catheters and transcutaneous reaccess port. CONCLUSION Large differences in convective properties between different molecules were observed. Large-sized liposomes as drug-carrier system showed superior performance to all other molecules. Vd/Vi ratios for promising drugs should be determined before initiating future clinical CED trials. Infusion concentration gradients to facilitate more precise Vd/Vi ratios provided important performance metrics for visualised infusion planning aids of a novel chronic drug delivery system, illustrating informed decision making for optimised catheter placement and subsequent infusion strategies is clinically translatable for GBM indications.

TMOD-36. NANOGLIOS: A MINIATURIZED PATIENT AVATAR ENABLING RAPID AND HIGH-THROUGHPUT PHENOTYPIC SCREENING FOR GLIOMAS

Abstract BACKGROUND Establishing pre-clinical patient derived orthtopical xenograft models for IDH-mutant and H3K27M-mutant gliomas has presented significant histological challenges. There is increasing interest in developing faithful patient-derived ex vivo 3D models to replicate these type of gliomas, aiming to accelerate drug screening efforts. METHOD We developed a rapid approach for establishing nanoliter-sized miniature glioma organoids, termed NanoGlios, by leveraging emulsion microfluidics. We tested the robustness of NanoGlios for neurosphere culture, glioma xenografts, and primary patient samples, focusing on H3K27M-mutant diffuse midline gliomas (DMGs) and IDH-mutant gliomas. We compared the morphological features of NanoGlios to their counterparts using high-content imaging, H&E staining, and histological analysis. Additionally, we evaluated the mutation and gene expression profiles of NanoGlios relative to their counterparts. Furthermore, we conducted proof-of-concept drug screening of NanoGlios with various inhibitors and established an AI-enhanced high-throughput phenotypic imaging-based screening platform. RESULTS We successfully established NanoGlios from various sample sources, including neurospheres, xenografts, and primary tissues harboring H3K27M or IDH1/2 mutations. NanoGlios derived from xenografts or primary tissues captured more heterogeneous patterns as compared to the neuropsheres. We were able to generate thousands of NanoGlios and perform drug assays for hundreds of conditions at passage 0 within two weeks from both resected glioma tissues and xenografts. The AI phenotypic screening enabled us to identify differential responses of NanoGlios to ONC-201 treatment and drug responses to mutant IDH inhibitors Vorasidenib and Ivosidenib, which was not able to be detected by conventional cell viability bulk assays.