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1.
Catheter Cardiovasc Interv ; 103(6): 924-933, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38597297

RESUMO

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) is a non-surgical treatment for right ventricular outflow tract (RVOT) dysfunction. During PPVI, a stented valve, delivered via catheter, replaces the dysfunctional pulmonary valve. Stent oversizing allows valve anchoring within the RVOT, but overexpansion can intrude on the surrounding structures. Potentially dangerous outcomes include aortic valve insufficiency (AVI) from aortic root (AR) distortion and myocardial ischemia from coronary artery (CA) compression. Currently, risks are evaluated via balloon angioplasty/sizing before stent deployment. Patient-specific finite element (FE) analysis frameworks can improve pre-procedural risk assessment, but current methods require hundreds of hours of high-performance computation. METHODS: We created a simplified method to simulate the procedure using patient-specific FE models for accurate, efficient pre-procedural PPVI (using balloon expandable valves) risk assessment. The methodology was tested by retrospectively evaluating the clinical outcome of 12 PPVI candidates. RESULTS: Of 12 patients (median age 14.5 years) with dysfunctional RVOT, 7 had native RVOT and 5 had RV-PA conduits. Seven patients had undergone successful RVOT stent/valve placement, three had significant AVI on balloon testing, one had left CA compression, and one had both AVI and left CA compression. A model-calculated change of more than 20% in lumen diameter of the AR or coronary arteries correctly predicted aortic valve sufficiency and/or CA compression in all the patients. CONCLUSION: Agreement between FE results and clinical outcomes is excellent. Additionally, these models run in 2-6 min on a desktop computer, demonstrating potential use of FE analysis for pre-procedural risk assessment of PPVI in a clinically relevant timeframe.


Assuntos
Cateterismo Cardíaco , Análise de Elementos Finitos , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Desenho de Prótese , Valva Pulmonar , Humanos , Valva Pulmonar/fisiopatologia , Valva Pulmonar/cirurgia , Valva Pulmonar/diagnóstico por imagem , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/efeitos adversos , Medição de Risco , Adolescente , Resultado do Tratamento , Fatores de Risco , Masculino , Criança , Estudos Retrospectivos , Feminino , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Adulto Jovem , Valor Preditivo dos Testes , Hemodinâmica , Stents , Insuficiência da Valva Pulmonar/fisiopatologia , Insuficiência da Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Obstrução do Fluxo Ventricular Externo/etiologia , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Tomada de Decisão Clínica , Adulto
2.
Comput Biol Med ; 171: 108033, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38430739

RESUMO

BACKGROUND AND OBJECTIVE: Atrioventricular valve disease is a common cause of heart failure, and successful surgical or interventional outcomes are crucial. Patient-specific fluid-structure interaction (FSI) modeling may provide valuable insights into valve dynamics and guidance of valve repair strategies. However, lack of validation has kept FSI modeling from clinical implementation. Therefore, this study aims to validate FSI simulations against in vitro benchmarking data, based on clinically relevant parameters for evaluating heart valve disease. METHODS: An FSI model that mimics the left heart was developed. The domain included a deformable mitral valve of different stiffnesses run with different inlet velocities. Five different cases were simulated and compared to in vitro data based on the pressure difference across the valve, the valve opening, and the velocity in the flow domain. RESULTS: The simulations underestimate the pressure difference across the valve by 6.8-14 % compared to catheter measurements. Evaluation of the valve opening showed an underprediction of 5.4-7.3 % when compared to cine MRI, 2D Echo, and 3D Echo data. Additionally, the simulated velocity through the valve showed a 7.9-8.4 % underprediction in relation to Doppler Echo measurements. Qualitative assessment of the velocity profile in the ventricle and the streamlines of the flow in the domain showed good agreement of the flow behavior. CONCLUSIONS: Parameters relevant to the diagnosis of heart valve disease estimated by FSI simulations showed good agreement when compared to in vitro benchmarking data, with differences small enough not to affect the grading of heart valve disease. The FSI model is thus deemed good enough for further development toward patient-specific cases.


Assuntos
Doenças das Valvas Cardíacas , Modelos Cardiovasculares , Humanos , Modelagem Computacional Específica para o Paciente , Ultrassonografia Doppler , Valva Mitral/diagnóstico por imagem , Doenças das Valvas Cardíacas/diagnóstico por imagem , Hemodinâmica/fisiologia , Simulação por Computador
4.
IEEE Trans Med Imaging ; 43(1): 203-215, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37432807

RESUMO

Automated volumetric meshing of patient-specific heart geometry can help expedite various biomechanics studies, such as post-intervention stress estimation. Prior meshing techniques often neglect important modeling characteristics for successful downstream analyses, especially for thin structures like the valve leaflets. In this work, we present DeepCarve (Deep Cardiac Volumetric Mesh): a novel deformation-based deep learning method that automatically generates patient-specific volumetric meshes with high spatial accuracy and element quality. The main novelty in our method is the use of minimally sufficient surface mesh labels for precise spatial accuracy and the simultaneous optimization of isotropic and anisotropic deformation energies for volumetric mesh quality. Mesh generation takes only 0.13 seconds/scan during inference, and each mesh can be directly used for finite element analyses without any manual post-processing. Calcification meshes can also be subsequently incorporated for increased simulation accuracy. Numerous stent deployment simulations validate the viability of our approach for large-batch analyses. Our code is available at https://github.com/danpak94/Deep-Cardiac-Volumetric-Mesh.


Assuntos
Aprendizado Profundo , Humanos , Fenômenos Biomecânicos , Simulação por Computador , Modelagem Computacional Específica para o Paciente , Coração/diagnóstico por imagem
5.
Comput Methods Programs Biomed ; 244: 107963, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38064956

RESUMO

BACKGROUND AND OBJECTIVE: Rupture of small intracranial aneurysm (IA) often leads to the development of highly fatal clinical syndromes such as subarachnoid hemorrhage. Due to the patient specificity of small IA, there are many difficulties in evaluating the rupture risk of small IA such as multiple influencing factors, high clinical experience requirements and poor reusability. METHODS: In this study, clinical methods such as transcranial doppler (TCD) and magnetic resonance imaging (MRI) are used to obtain patient-specific parameters, and the fluid-structure interaction method (FSI) is used to model and evaluate the biomechanics and hemodynamics of patient-specific small IA. RESULTS: The results show that a spiral vortex stably exists in the patient-specific small IA. Due to the small size of the patient-specific small IA, the blood flow velocity still maintains a high value with maximum reaching 3 m/s. The inertial impact of blood flow and vortex convection have certain influence on hemodynamic and biomechanics parameters. They cause three high value areas of WSSM on the patient-specific small IA with maximum of 180 Pa, 130 Pa and 110 Pa, respectively. They also cause two types of WSS concentration points, positive normal stress peak value areas and negative normal stress peak value areas to appear. CONCLUSION: This paper found that the factors affecting hemodynamic parameters and biomechanical parameters are different. Unlike hemodynamic parameters, biomechanical parameters are also affected by blood pressure in addition to blood flow velocity. This study reveals the relationship between the flow field distribution and changes of patient-specific small IA, biomechanics and hemodynamics.


Assuntos
Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Fenômenos Biomecânicos , Hemodinâmica/fisiologia , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Ruptura , Modelagem Computacional Específica para o Paciente , Estresse Mecânico
6.
Artigo em Inglês | MEDLINE | ID: mdl-38083458

RESUMO

In the condition of anemia, kidneys produce less erythropoietin hormone to stimulate the bone marrow to make red blood cells (RBC) leading to a reduced hemoglobin (Hgb) level, also known as chronic kidney disease (CKD). External recombinant human erythropoietin (EPO) is administrated to maintain a healthy level of Hgb, i.e., 10 - 12 g/dl. The semi-blind robust model identification method is used to obtain a personalized patient model using minimum dose-response data points. The identified patient models are used as predictive models in the model predictive control (MPC) framework. The simulation results of MPC for different CKD patients are compared with those obtained from the existing clinical method, known as anemia management protocol (AMP), used in hospitals. The in-silico results show that MPC outperforms AMP to maintain healthy levels of Hgb without over-or-under- shoots. This offers a considerable performance improvement compared to AMP which is unable to stabilize EPO dosage and shows oscillations in Hgb levels throughout the treatment.Clinical Relevance-This research work provides a framework to help clinicians in decision-making for personalized EPO dose guidance using MPC with semi-blind robust model identification using minimum clinical patient dose-response data.


Assuntos
Anemia , Eritropoetina , Insuficiência Renal Crônica , Humanos , Anemia/tratamento farmacológico , Modelagem Computacional Específica para o Paciente , Eritropoetina/uso terapêutico , Rim
7.
Sci Rep ; 13(1): 19911, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964071

RESUMO

The assessment of carotid plaque vulnerability is a relevant clinical information that can help prevent adverse cerebrovascular events. To this aim, in this study, we propose a patient-specific computational workflow to quantify the stress distribution in an atherosclerotic carotid artery, by means of geometric modeling and structural simulation of the plaque and vessel wall. Ten patients were involved in our study. Starting with segmentation of the lumen, calcific and lipid plaque components from computed tomography angiography images, the fibrous component and the vessel wall were semi-automatically reconstructed with an ad-hoc procedure. Finite element analyses were performed using local pressure values derived from ultrasound imaging. Simulation outputs were analyzed to assess how mechanical factors influence the stresses within the atherosclerotic wall. The developed reconstruction method was first evaluated by comparing the results obtained using the automatically generated fibrous component model and the one derived from image segmentation. The high-stress regions in the carotid artery wall around plaques suggest areas of possible rupture. In mostly lipidic and heterogeneous plaques, the highest stresses are localized at the interface between the lipidic components and the lumen, in the fibrous cap.


Assuntos
Aterosclerose , Estenose das Carótidas , Placa Aterosclerótica , Humanos , Análise de Elementos Finitos , Modelagem Computacional Específica para o Paciente , Angiografia por Tomografia Computadorizada , Artérias Carótidas/diagnóstico por imagem , Aterosclerose/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Estresse Mecânico , Estenose das Carótidas/diagnóstico por imagem
8.
J Appl Biomech ; 39(5): 304-317, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37607721

RESUMO

In this narrative review, we explore developments in the field of computational musculoskeletal model personalization using the Physiome and Musculoskeletal Atlas Projects. Model geometry personalization; statistical shape modeling; and its impact on segmentation, classification, and model creation are explored. Examples include the trapeziometacarpal and tibiofemoral joints, Achilles tendon, gastrocnemius muscle, and pediatric lower limb bones. Finally, a more general approach to model personalization is discussed based on the idea of multiscale personalization called scaffolds.


Assuntos
Tendão do Calcâneo , Modelagem Computacional Específica para o Paciente , Humanos , Criança , Músculo Esquelético/fisiologia , Articulação do Joelho , Modelos Estatísticos
9.
Artif Organs ; 47(8): 1326-1341, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36995361

RESUMO

BACKGROUND: Parametric multipool kinetic models were used to describe the intradialytic trends of electrolytes, breakdown products, and body fluids volumes during hemodialysis. Therapy customization can be achieved by the identification of parameters, allowing patient-specific modulation of mass and fluid balance across dialyzer, capillary, and cell membranes. This study wants to evaluate the possibility to use this approach to predict the patient's intradialytic response. METHODS: 6 sessions of 68 patients (DialysIS© project) were considered. Data from the first three sessions were used to train the model, identifying the patient-specific parameters, that, together with the treatment settings and the patient's data at the session start, could be used for predicting the patient's specific time course of solutes and fluids along the sessions. Na+ , K+ , Cl- , Ca2+ , HCO3 - , and urea plasmatic concentrations and hematic volume deviations from clinical data were evaluated. RESULTS: nRMSE predictive error is on average equal to 4.76% when describing the training sessions, and only increases by 0.97 percentage points on average in independent sessions of the same patient. CONCLUSIONS: The proposed predictive approach represents a first step in the development of tools to support the clinician in tailoring the patient's prescription.


Assuntos
Modelagem Computacional Específica para o Paciente , Diálise Renal , Humanos , Equilíbrio Hidroeletrolítico , Sódio
10.
Expert Rev Med Devices ; 20(3): 233-244, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36860182

RESUMO

INTRODUCTION: While 3D printing of bone models for preoperative planning or customized surgical templating has been successfully implemented, the use of patient-specific additively manufactured (AM) implants is a newer application not yet well established. To fully evaluate the advantages and shortcomings of such implants, their follow-up results need to be evaluated. AREA COVERED: This systematic review provides a survey of the reported follow-ups on AM implants used for oncologic reconstruction, total hip arthroplasty both primary and revision, acetabular fracture, and sacrum defects. EXPERT OPINION: The review shows that Titanium alloy (Ti4AL6V) is the most common type of material system used due to its excellent biomechanical properties. Electron beam melting (EBM) is the predominant AM process for manufacturing implants. In almost all cases, porosity at the contact surface is implemented through the design of lattice or porous structures to enhance osseointegration. The follow-up evaluations show promising results, with only a small number of patients suffering from aseptic loosening, wear, or malalignment. The longest reported follow-up length was 120 months for acetabular cages and 96 months for acetabular cups. The AM implants have proven to serve as an excellent option to restore premorbid skeletal anatomy of the pelvis.


Assuntos
Ossos Pélvicos , Próteses e Implantes , Desenho de Prótese , Sacro , Humanos , Acetábulo/cirurgia , Seguimentos , Osseointegração , Porosidade , Ossos Pélvicos/cirurgia , Modelagem Computacional Específica para o Paciente , Sacro/cirurgia , Fenômenos Biomecânicos
11.
Appl Biochem Biotechnol ; 195(11): 6441-6464, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36870026

RESUMO

Sustainable remediation of arsenic-fluoride from rice fields through efficient bio-extraction is the need of the hour, since these toxicants severely challenge safe cultivation of rice and food biosafety. In the present study, we screened an arsenic-fluoride tolerant strain AB-ARC of Acinetobacter indicus from the soil of a severely polluted region of West Bengal, India, which was capable of efficiently removing extremely high doses of arsenate and fluoride from the media. The strain also behaved as a plant growth-promoting rhizobacterium, since it could produce indole-3-acetic acid and solubilize phosphate, zinc, and starch. Due to these properties of the identified strain, it was used for bio-priming the seeds of the arsenic-fluoride susceptible rice cultivar, Khitish for testing the efficacy of the AB-ARC strain to promote combined arsenic-fluoride tolerance in the rice genotype. Bio-priming with AB-ARC led to accelerated uptake of crucial elements like iron, copper, and nickel which behave as co-factors of physiological and antioxidative enzymes. Thus, the activation of superoxide dismutase, catalase, guaiacol peroxidase, glutathione peroxidase, and glutathione-S-transferase enabled detoxification of reactive oxygen species (ROS) and reduction of the oxidative injuries like malondialdehyde and methylglyoxal generation. Overall, due to ameliorated molecular damages and low uptake of the toxic xenobiotics, the plants were able to maintain improved growth vigor and photosynthesis, as evident from the elevated levels of Hill activity and chlorophyll content. Hence, bio-priming with the A. indicus AB-ARC strain may be advocated for sustainable rice cultivation in arsenic-fluoride co-polluted fields.


Assuntos
Arsênio , Oryza , Oligoelementos , Fluoretos/toxicidade , Oryza/metabolismo , Micronutrientes , Modelagem Computacional Específica para o Paciente , Antioxidantes/metabolismo , Estresse Oxidativo , Homeostase
12.
Sci Rep ; 13(1): 3172, 2023 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-36823433

RESUMO

The location of the instantaneous centre of rotation (ICR) of a lumbar unit has a considerable clinical importance as a spinal health estimator. Consequently, many studies have been conducted to measure or estimate the ICR during rotations in the three anatomical planes; however the results reported are widely scattered. Even if some inter-subjects variability is to be expected, such inconsistencies are likely explained by the differences in methods and experiments. Therefore, in this paper we seek to model three behaviours of the ICR during lateral bending and axial rotation based on results published in the literature. In order to assess the metabolic and mechanical sensibility to the assumption made on the ICR kinematics, we used a previously validated three dimensional non-linear poroelastic model of a porcine intervertebral disc to simulate physiological lateral and axial rotations. The impact of the geometry was also briefly investigated by considering a 11[Formula: see text] wedge angle. From our simulations, it appears that the hypothesis made on the ICR location does not significantly affect the critical nutrients concentrations but gives disparate predictions of the intradiscal pressure at the centre of the disc (variation up to 0.7 MPa) and of the displacement fields (variation up to 0.4 mm). On the contrary, the wedge angle does not influence the estimated intradiscal pressure but leads to minimal oxygen concentration decreased up to 33% and increased maximal lactate concentration up to 13%. While we can not settle on which definition of the ICR is more accurate, this work suggests that patient-specific modeling of the ICR is required and brings new insights that can be useful for the development of new tools or the design of surgical material such as total lumbar disc prostheses.


Assuntos
Disco Intervertebral , Vértebras Lombares , Animais , Suínos , Fenômenos Biomecânicos/fisiologia , Vértebras Lombares/cirurgia , Amplitude de Movimento Articular/fisiologia , Disco Intervertebral/cirurgia , Modelagem Computacional Específica para o Paciente
13.
Ann Biomed Eng ; 51(1): 58-70, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36042099

RESUMO

Bicuspid aortic valve (BAV), the most common congenital heart malformation, is characterized by the presence of only two valve leaflets with asymmetrical geometry, resulting in elliptical systolic opening. BAV often leads to early onset of calcific aortic stenosis (AS). Following the rapid expansion of transcatheter aortic valve replacement (TAVR), designed specifically for treating conventional tricuspid AS, BAV patients with AS were initially treated "off-label" with TAVR, which recently gained FDA and CE regulatory approval. Despite its increasing use in BAV, pathological BAV anatomy often leads to complications stemming from mismatched anatomical features. To mitigate these complications, a novel eccentric polymeric TAVR valve incorporating asymmetrical leaflets was designed specifically for BAV anatomies. Computational modeling was used to optimize its asymmetric leaflets for lower functional stresses and improved hemodynamic performance. Deployment and flow were simulated in patient-specific BAV models (n = 6) and compared to a current commercial TAVR valve (Evolut R 29 mm), to assess deployment and flow parameters. The novel eccentric BAV-dedicated valve demonstrated significant improvements in peak systolic orifice area, along with lower jet velocity and wall shear stress (WSS). This feasibility study demonstrates the clinical potential of the first known BAV-dedicated TAVR design, which will foster advancement of patient-dedicated valvular devices.


Assuntos
Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Doenças das Valvas Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Valva Aórtica , Doenças das Valvas Cardíacas/cirurgia , Modelagem Computacional Específica para o Paciente , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
14.
Int J Numer Method Biomed Eng ; 39(2): e3665, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36448192

RESUMO

Estimating a patient-specific computational model's parameters relies on data that is often unreliable and ill-suited for a deterministic approach. We develop an optimization-based uncertainty quantification framework for probabilistic model tuning that discovers model inputs distributions that generate target output distributions. Probabilistic sampling is performed using a surrogate model for computational efficiency, and a general distribution parameterization is used to describe each input. The approach is tested on seven patient-specific modeling examples using CircAdapt, a cardiovascular circulatory model. Six examples are synthetic, aiming to match the output distributions generated using known reference input data distributions, while the seventh example uses real-world patient data for the output distributions. Our results demonstrate the accurate reproduction of the target output distributions, with a correct recreation of the reference inputs for the six synthetic examples. Our proposed approach is suitable for determining the parameter distributions of patient-specific models with uncertain data and can be used to gain insights into the sensitivity of the model parameters to the measured data.


Assuntos
Modelos Estatísticos , Modelagem Computacional Específica para o Paciente , Humanos , Incerteza , Modelos Cardiovasculares
15.
ASAIO J ; 68(11): e179-e187, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36326700

RESUMO

Institution of extracorporeal membrane oxygenation (ECMO) results in unique blood flow characteristics to the end-organ vascular beds. We studied the interplay between cardiac-driven and extracorporeal membrane oxygenation (ECMO)-driven flow to vascular beds in different ECMO configurations using a patient-specific computational fluid dynamics (CFD) analysis. A computational ECMO model (femoral artery cannulation [FAC]) was constructed using patient-specific imaging and hemodynamic data. Following model calibration, we augmented the 3D geometrical model to represent alternative ECMO configurations (ascending aorta cannulation [AAC] and subclavian artery cannulation [SAC]). We performed CFD analyses, including a novel virtual color-dye analysis to compare global and regional blood flow and pressure characteristics as well as contributions of cardiac and ECMO-derived flow to the various vascular beds. Flow waveforms at all the aortic branch vessels were pulsatile, despite low cardiac output and predominant nonpulsatile ECMO-driven hemodynamics. Virtual color-dye analysis revealed differential contribution of cardiac and ECMO-derived flow to the end-organ vascular beds in the FAC model, while this was more evenly distributed in the AAC and SAC models. While global hemodynamics were relatively similar between various ECMO configurations, several distinct hemodynamic indices, in particular wall shear stress and oscillatory shear patterns, as well as differential contribution of ECMO-derived flow to various vascular beds, showed remarkable differences. The clinical impact of this study highlighting the relevance of CFD modeling in assessment of complex hemodynamics in ECMO warrants further evaluation.


Assuntos
Oxigenação por Membrana Extracorpórea , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Modelagem Computacional Específica para o Paciente , Hemodinâmica/fisiologia , Cateterismo , Aorta
16.
PLoS Comput Biol ; 18(10): e1010541, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36215228

RESUMO

Reliable and robust simulation of individual patients using patient-specific models (PSMs) is one of the next frontiers for modeling and simulation (M&S) in healthcare. PSMs, which form the basis of digital twins, can be employed as clinical tools to, for example, assess disease state, predict response to therapy, or optimize therapy. They may also be used to construct virtual cohorts of patients, for in silico evaluation of medical product safety and/or performance. Methods and frameworks have recently been proposed for evaluating the credibility of M&S in healthcare applications. However, such efforts have generally been motivated by models of medical devices or generic patient models; how best to evaluate the credibility of PSMs has largely been unexplored. The aim of this paper is to understand and demonstrate the credibility assessment process for PSMs using patient-specific cardiac electrophysiological (EP) modeling as an exemplar. We first review approaches used to generate cardiac PSMs and consider how verification, validation, and uncertainty quantification (VVUQ) apply to cardiac PSMs. Next, we execute two simulation studies using a publicly available virtual cohort of 24 patient-specific ventricular models, the first a multi-patient verification study, the second investigating the impact of uncertainty in personalized and non-personalized inputs in a virtual cohort. We then use the findings from our analyses to identify how important characteristics of PSMs can be considered when assessing credibility with the approach of the ASME V&V40 Standard, accounting for PSM concepts such as inter- and intra-user variability, multi-patient and "every-patient" error estimation, uncertainty quantification in personalized vs non-personalized inputs, clinical validation, and others. The results of this paper will be useful to developers of cardiac and other medical image based PSMs, when assessing PSM credibility.


Assuntos
Coração , Modelagem Computacional Específica para o Paciente , Estudos de Coortes , Simulação por Computador , Coração/fisiologia , Humanos , Incerteza
17.
J Exp Clin Cancer Res ; 41(1): 312, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273171

RESUMO

BACKGROUND: Cancer-associated fibroblasts (CAFs) are considered to play a fundamental role in pancreatic ductal adenocarcinoma (PDAC) progression and chemoresistance. Patient-derived organoids have demonstrated great potential as tumor avatars for drug response prediction in PDAC, yet they disregard the influence of stromal components on chemosensitivity. METHODS: We established direct three-dimensional (3D) co-cultures of primary PDAC organoids and patient-matched CAFs to investigate the effect of the fibroblastic compartment on sensitivity to gemcitabine, 5-fluorouracil and paclitaxel treatments using an image-based drug assay. Single-cell RNA sequencing was performed for three organoid/CAF pairs in mono- and co-culture to uncover transcriptional changes induced by tumor-stroma interaction. RESULTS: Upon co-culture with CAFs, we observed increased proliferation and reduced chemotherapy-induced cell death of PDAC organoids. Single-cell RNA sequencing data evidenced induction of a pro-inflammatory phenotype in CAFs in co-cultures. Organoids showed increased expression of genes associated with epithelial-to-mesenchymal transition (EMT) in co-cultures and several potential receptor-ligand interactions related to EMT were identified, supporting a key role of CAF-driven induction of EMT in PDAC chemoresistance. CONCLUSIONS: Our results demonstrate the potential of personalized PDAC co-cultures models not only for drug response profiling but also for unraveling the molecular mechanisms involved in the chemoresistance-supporting role of the tumor stroma.


Assuntos
Antineoplásicos , Fibroblastos Associados a Câncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Técnicas de Cocultura , Organoides/metabolismo , Resistencia a Medicamentos Antineoplásicos , Modelagem Computacional Específica para o Paciente , Ligantes , Células Estromais/metabolismo , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Paclitaxel/farmacologia , Fluoruracila/farmacologia , Antineoplásicos/farmacologia , Neoplasias Pancreáticas
18.
J Neuroimmunol ; 372: 577959, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36095861

RESUMO

BACKGROUND/AIMS: The psycho-immune-neuroendocrine (PINE) network is a predominantly physiological (metabolomic) model constructed from the literature, inter-linking multiple biological processes associated with major depressive disorder (MDD), thereby integrating putative mechanistic pathways for MDD into a single network. MATERIAL AND METHODS: Previously published metabolomic pathways for the PINE network based on literature searches conducted in 1991-2021 were used to construct an edge table summarizing all physiological pathways in pairs of origin nodes and target nodes. The Gephi software program was used to calculate network metrics from the edge table, including total degree and centrality measures, to ascertain key network nodes and construct a directed network graph. RESULTS: An edge table and directional network graph of physiological relationships in the PINE network is presented. The network has properties consistent with complex biological systems, with analysis yielding key network nodes comprising pro-inflammatory cytokines (TNF- α, IL6 and IL1), glucocorticoids and corticotropin releasing hormone (CRH). These may represent central structural and regulatory elements in the context of MDD. CONCLUSION: The identified hubs have a high degree of connection and are known to play roles in the progression from health to MDD. These nodes represent strategic targets for therapeutic intervention or prevention. Future work is required to build a weighted and dynamic simulation of the network PINE.


Assuntos
Transtorno Depressivo Maior , Hormônio Liberador da Corticotropina , Transtorno Depressivo Maior/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Interleucina-6 , Modelagem Computacional Específica para o Paciente , Biologia de Sistemas
19.
Front Endocrinol (Lausanne) ; 13: 888429, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909562

RESUMO

Objective: A personalized simulation tool, p-THYROSIM, was developed (1) to better optimize replacement LT4 and LT4+LT3 dosing for hypothyroid patients, based on individual hormone levels, BMIs, and gender; and (2) to better understand how gender and BMI impact thyroid dynamical regulation over time in these patients. Methods: p-THYROSIM was developed by (1) modifying and refining THYROSIM, an established physiologically based mechanistic model of the system regulating serum T3, T4, and TSH level dynamics; (2) incorporating sex and BMI of individual patients into the model; and (3) quantifying it with 3 experimental datasets and validating it with a fourth containing data from distinct male and female patients across a wide range of BMIs. For validation, we compared our optimized predictions with previously published results on optimized LT4 monotherapies. We also optimized combination T3+T4 dosing and computed unmeasured residual thyroid function (RTF) across a wide range of BMIs from male and female patient data. Results: Compared with 3 other dosing methods, the accuracy of p-THYROSIM optimized dosages for LT4 monotherapy was better overall (53% vs. 44%, 43%, and 38%) and for extreme BMI patients (63% vs. ~51% low BMI, 48% vs. ~36% and 22% for high BMI). Optimal dosing for combination LT4+LT3 therapy and unmeasured RTFs was predictively computed with p-THYROSIM for male and female patients in low, normal, and high BMI ranges, yielding daily T3 doses of 5 to 7.5 µg of LT3 combined with 62.5-100 µg of LT4 for women or 75-125 µg of LT4 for men. Also, graphs of steady-state serum T3, T4, and TSH concentrations vs. RTF (range 0%-50%) for untreated patients showed that neither BMI nor gender had any effect on RTF predictions for our patient cohort data. Notably, the graphs provide a means for estimating unmeasurable RTFs for individual patients from their hormone measurements before treatment. Conclusions: p-THYROSIM can provide accurate monotherapies for male and female hypothyroid patients, personalized with their BMIs. Where combination therapy is warranted, our results predict that not much LT3 is needed in addition to LT4 to restore euthyroid levels, suggesting opportunities for further research exploring combination therapy with lower T3 doses and slow-releasing T3 formulations.


Assuntos
Hipotireoidismo , Modelagem Computacional Específica para o Paciente , Tiroxina , Tri-Iodotironina , Índice de Massa Corporal , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Masculino , Hormônios Tireóideos/administração & dosagem , Hormônios Tireóideos/sangue , Hormônios Tireóideos/farmacologia , Hormônios Tireóideos/uso terapêutico , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangue , Tiroxina/farmacologia , Tiroxina/uso terapêutico , Tri-Iodotironina/administração & dosagem , Tri-Iodotironina/sangue , Tri-Iodotironina/farmacologia , Tri-Iodotironina/uso terapêutico
20.
Clin Oral Investig ; 26(8): 5117-5128, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35687196

RESUMO

The dental practice has largely evolved in the last 50 years following a better understanding of the biomechanical behaviour of teeth and its supporting structures, as well as developments in the fields of imaging and biomaterials. However, many patients still encounter treatment failures; this is related to the complex nature of evaluating the biomechanical aspects of each clinical situation due to the numerous patient-specific parameters, such as occlusion and root anatomy. In parallel, the advent of cone beam computed tomography enabled researchers in the field of odontology as well as clinicians to gather and model patient data with sufficient accuracy using image processing and finite element technologies. These developments gave rise to a new precision medicine concept that proposes to individually assess anatomical and biomechanical characteristics and adapt treatment options accordingly. While this approach is already applied in maxillofacial surgery, its implementation in dentistry is still restricted. However, recent advancements in artificial intelligence make it possible to automate several parts of the laborious modelling task, bringing such user-assisted decision-support tools closer to both clinicians and researchers. Therefore, the present narrative review aimed to present and discuss the current literature investigating patient-specific modelling in dentistry, its state-of-the-art applications, and research perspectives.


Assuntos
Inteligência Artificial , Cirurgia Bucal , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Modelagem Computacional Específica para o Paciente , Medicina de Precisão
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