Digital Human Modeling and Medicine: The Digital Twin

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Digital Human Modeling and Medicine
Digital Human Modeling and Medicine The Digital Twin
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Contents
Contributors
1 -
Modeling methods
	1 - From the visible human project to the digital twin
		Introduction
		The visible human project
		Anatomography
		Virtual physiological human
		The digital twin
		References
		Further reading
	2 - Massive data probabilistic framework for parameter estimation in biological problems
		Introduction
		General framework
			About modeling
			About experiments: smart experiments
				Strategy 1: in one stroke
				Strategy 2: divide and conquer
				Strategy 3: the general situation
			Model separability
			Including model uncertainty
		Mathematical tools and concepts
			Managing data uncertainty
			Estimation of probabilistic models
				Parametric methods
					Method of moments
					Method of moments
					Maximum likelihood method
					Maximum likelihood method
				Nonparametric methods
			Design of experiments
			Copulas
				Mathematical definition
				Theorem 1: Sklar's theorem
				Parametric copulas
				Nonparametric copulas
		Methodology
			Model adjustment
			Model analysis and applications
				Parameter estimation
		A case study: GBM evolution
			Mathematical model
			Data generation
			Results
				Model adjustment
				Model validation
				Parameter estimation
				Experimental design
		Conclusions
		References
	3 - Deep learning applied to detection of the vulnerable atherosclerotic plaque
		Introduction
		The atheroma plaque problem
			3D parametric study
			Source data
		Mathematical methods for regression
			Artificial neural network
			Support vector machine
			Assuring the quality of the machine
			Validation with a real geometry
				How the decision support system works
			Finite element models
		Results
		Discussion
		References
	4 - Computational stability of human musculoskeletal systems
		Introduction
		Methods
			Criteria of structural stability
			Stability of human MS systems
		Stability of the human spine
			Role of posture and passive ligamentous stiffness
			Role of load orientation and elevation
			Role of coactivity
			Stability-based multicriteria simulations
		Stability of human knee joint
		Summary
		References
	5 - Techniques for automatic landmark detection of human tissue
		Introduction
		Machine learning techniques
			Artificial neural networks
			Decision trees
			Support vector machines
		Knowledge-based techniques
			Shape analysis
				Approximation to simple shapes
			Curvature analysis
			Template-based approaches
				Atlas-based templates
			Statistical shape modeling
			Patient-specific templates
				Spatial coherence
		Conclusion
		References
	6 - Multibody modeling of the musculoskeletal system
		Introduction
		Fundamentals of multibody modeling
		Motion capture–based model
			Cadaver-based lower extremity model
				Scaling of the template model to subject-specific data
			Linear geometric scaling law
			Parameter identification
			Mass and inertial properties
			Mass-fat muscle strength scaling law
			Over-determinate kinematic analysis
			Inverse dynamic analysis
		Analysis of gait modifications
		Other applications
		Concluding remarks
		References
	7 - AnyBody modeling system
		Background and context
		Software design choices
			AnyScript
			Multibody system formulation
		The model repository
			Structuring principles
		Applications
			Fundamental science applications
			Orthopedic applications
			Industrial product design
			Sports
			Workplace ergonomics
		Digital human models and the digital patient
		References
	8 - The NEUROiD neuromusculoskeletal movement simulation platform
		Introduction
		The NEUROiD movement simulation platform
			Design philosophy and architecture
				Multiscale, multidiscipline, and multifunction platform
				Workflow in NEUROiD
			Model definition, simulation, and visualization
				Curation and definition
					Model specification to the definition
					Model specification to the definition
					Definition across scale and discipline
					Definition across scale and discipline
					Neuromusculoskeletal interface design
					Neuromusculoskeletal interface design
				Experiment and simulation
					Experiment specification to the definition
					Experiment specification to the definition
					Parallelization
					Parallelization
				Visualization
			Integrative model development
			Choosing a musculoskeletal model
		Design and characterization of limbs in silico
			Upper limb
			Lower limb
		Movement training of virtual limbs
			Machine learning setup
		NEUROiD in medicine
			NEUROiD models
			NEUROiD activities
			Twinning in NEUROiD
			Clinical trials and experimentation in silico with NEUROiD
				Clinical triage for spasticity
				Design and test of prostheses
				Diabetic neuropathy–induced diabetic foot
				Stroke: cross-sectional modeling of stroke severity and corticospinal residuum
				Stroke: longitudinal modeling of recovery and computational neurorehabilitation
				Spinal cord stimulation
				Motor neuron disease (amyotrophic lateral Sclerosis, spinal muscular atrophy, familial spastic paraplegia)
				Peripheral neuropathies
				Mechanisms and consequences of aging-induced changes in motor unit structure
				Limitations
				Medical education and training
		Conclusion and future landscapes
		References
	9 - HumMod: a modeling environment for the simulation of integrative human physiology
		Disclosures
		History
			Model content
		HumMod for testing physiological concepts and hypotheses in pathophysiology
			Example 1: salt sensitivity
			Example 2: baroreceptor activation therapy
			Example 3: arteriovenous fistula
			The future of modeling: virtual populations
		Conclusion, limitations, and future considerations
		References
2 - Organs
	10 - Computational biomechanics as a tool to improve surgical procedures for Uterine Prolapse
		Introduction
			Mechanism of the development of POP
		Biomechanical uterine prolapse simulation
		Isotropic constitutive model—simulating the passive behavior
		Computational model of the pelvic cavity
		Computational model of the implant
		Biomechanical properties of the soft tissues and mesh implant
		Uterine prolapse simulation
		Personalized models to repair the uterine prolapse
		Conclusions
		References
	11 - Computational Modeling of aerosol particle transport and deposition in the healthy and stented human airways c ...
		Clinical background
		Materials and methods
			Geometries
			Numerical model and boundary conditions
				Continuous phase: airflow
				Discrete phase: particle transport and deposition modeling
		Results
			Airflow patterns in healthy and stented airways
			Airflow turbulent patterns in healthy and stented airways
			Particle deposition and transport
			Validation of the numerical findings
				Comparison between healthy and stented human upper airways
					Total deposition fractions
					Total deposition fractions
			Regional deposition fractions
		Conclusions and final remarks
		Funding
		References
	12 - Ultrafine particle transport to the lower airways: airway diameter reduction effects
		Introduction
		Geometrical development
		Numerical methods
		Result and discussion
		Velocity functions
		Pressure variations
		Particle deposition fraction
		Escaped particles
		Conclusions
		Limitations of the approach
		References
	13 - Aerosolized airborne bacteria and viruses inhalation: Micro-bioaerosols deposition effects through upper nasal ...
		Introduction
		Materials and method
			Computational model
			Governing equations
		Results
		Discussion
		Conclusion
			Declaration of competing interest
		References
	14 - Numerical simulation of the aortic arch behavior∗
		Nomenclature
		Introduction
		Methods
			Geometry reconstruction and grid generation
			Governing equations
			Boundary conditions and numerical solution
		Results
		Discussion
		Conclusion
		Disclosure of interest
		References
	15 - Modern placental imaging methods
		Introduction
		Ultrasound
		Doppler
		Volume rendering
		Sonoelastography
		Placental elastography
		Magnetic resonance imaging
		Conclusion
		References
3 - Body parts
	16 - Foot digital twin and in silico clinical applications
		Where a foot digital twin can help
			Key aspects of foot biomechanics
			Main foot pathologies by volume
			Foot digital twin—scope of interest
			The potential of foot CM&S
		How to build a foot digital twin
			Anatomy reconstruction
			Loading and boundary conditions
			Tissue properties
			Verification and validation
			Initiatives to improve model credibility in healthcare
		Foot digital twin: a look into the future
			In silico trials
			What level of anatomical detail is required for clinical applications?
			Foot CM&S for clinical applications
			Foot CM&S for the footwear industry
			Why foot and ankle CM&S is not yet in the clinic
		References
	17 - Flow processes occurring within the body but still external to the body's epithelial layer (gastrointestinal a ...
		Introduction
		Computational methods
			SPH for fluids and foods
			DEM for motion and collisions of particles
			Collisions and rigid body dynamics in SPH
			DEM-SPH coupling for slurry simulation
			Flexible and deformable surfaces
			Specialized intestinal models
				Genome-scale metabolic models
				0D model of microbial fermentation
				Reduced 1D models
				A potentially powerful multiscale approach: hierarchical 3D-1D-0D model
		Ingestion and oral digestion
			Background
			Example simulation scenario: melting of chocolate on the tongue
		Stomach
		Small intestine
			Solute/nutrient diffusion and absorption
			Spatially varying multiphase digesta rheology
		Large intestine
		Liquid transport and droplet formation in the respiratory tract
		Conclusions
		References
	18 - Digital modeling of the jaws for the evaluation of mandibular reconstruction techniques
		Introduction
		Anatomy and biomechanics of the mandible
		The finite element method
			Performing finite element analysis of the mandible
		Alloplastic mandibular reconstruction methods: evaluating the implant design using finite element analysis
			Computer-aided design of mandibular models
		Design and plan of endoprostheses
		Stress and magnitude of displacement of stem and wing design in unilateral loading conditions
		Conclusion
		References
	19 - Cornea digital twins for studying the critical role of mechanics in physiology, pathology and surgical repair
		Introduction
		Corneal biomechanics
		In silico biomechanical models of cornea
			Toward accurate models of corneal collagen fibrils
			Multiphasic and multiphysics computational models of cornea
			Simulation-based subject-specific surgical planning
		Concluding remarks
		References
	20 - Influence of fluid–structure interaction on human corneal biomechanics under air puff non-contact tonometry
		Introduction
			Corneal biomechanics
				In vivo nondestructive testing
				Ex vivo destructive testing
			Glaucoma
			Aeroelasticity
			Classification of fluid–structure interaction problems
		Numerical methods
			Three-dimensional eye model
			Three-dimensional CFD turbulence model of the air puff
		Air puff traverses and pressure on cornea
		Parametric study statistics
			Clinical dataset
		Intraocular pressure algorithm (fIOP)
		Corneal material stress–strain index (fSSI)
		Conclusions
		References
4 -
Biomedicine
	21 - Digital twins for understanding the mechanical adaptation of bone in disease and postsurgery
		Introduction—the basics of bone remodeling
		Computational models of bone remodeling in response to mechanical stimuli
			Strain energy density as a mechanical stimulus for bone remodeling
			Incorporation of stress, strain, and damage as remodeling stimuli
			Fluid flow as a mechanical stimulus for bone remodeling
		Effects of implants and pharmaceuticals on bone remodeling
		Alternative or complementary numerical approaches to FE for in silico bone remodeling
		Conclusion
		References
	22 - Bone strength, bone remodeling, and Biomechanics of fracture
		Bone physiology
		Bone cells
		Bone modeling and remodeling
		Bone mechanical properties and fracture
			Bone elasticity
			Bone post-elastic behavior
			Bone time-dependent properties
		Predictions of bone strength with finite element models
			DXA-based models
			CT-based FE models
			HR-pQCT-based FE models
			MicroCT-based FE models
		Model validation
			Standard mechanical tests
			Local deformation with strain gauges
			Full field tests DIC and DVC
			Examples of validation studies for FE models
		Predictions of bone remodeling
			Mechanoregulation
			Bone adaptation algorithm and implementation in FE framework
			Validation for murine studies
			Morphometric and densitometric analysis
			Spatial analysis and biomarkers for bone formation
		References
	23 - Single-cell based models for cell–cell and cell–extracellular matrix interactions
		Introduction
		Methodology
			Cell motility
			Cell mechanotaxis
			Cell electrotaxis
			Drag force
			Cell–cell interaction
			Cell–cell contact
			Cell–cell adhesion
			Cell fate decision
			Cell maturation
			Cell differentiation
			Cell proliferation
			Model parameters and experiment setup
			ECM discretization
			Boundary conditions
			Assumptions
		Numerical implementation and applications
			Cell–cell contact forces
			Cell differentiation modulated by ECM stiffness
			Cell adhesions modulated by ECM stiffness
			Mechanically stimulated ECMs
			Electrically stimulated ECM
			Advanced materials for mechanoelectrical stimulation coupling
		Conclusions
		References
	24 - Flow and remodeling processes occurring within the body proper
		Introduction
		Computational methods
			SPH method for fluids and solids
			Continuity equation
			Momentum equation for fluid (Navier–Stokes)
			Momentum equation for solid deformation
			Pressure solution
			Solid boundary conditions
			Soft bodies with flexible surfaces (such as cell membranes)
			Species concentration and diffusion
			Integration of the SPH ordinary differential equations
		Models for biological processes
			Adhesion modeling for cells
				Elastic regime
				Viscous regime
			Simple model for thrombin-controlled coagulation
			SPH solid evolution for remodeling processes
		Hemodynamics of vascular disease
			Explicit modeling of cell mechanics at capillary scale
			White blood cell rolling adhesion
			Arterial scale flow
		Blood coagulation and clot formation modeling
			Background
			Simple SPH coagulation model and predictions
		Plaque rupture in an artery
			Background
			SPH model for plaque rupture
		Bone remodeling
		Conclusions
		References
5 -
Medical devices
	25 - Digital co-creation: an early-stage product individualization framework to bridge the customer–designer void
		Introduction
		Background
			The transition from mass customization to mass individualization
			The lack of customer participation in conventional product development
		Methodology
			Theoretical bases of the co-creation framework
			Stages of the co-creation framework
				Ideation
				Modeling
				Analysis
				Visualization
		Case study
			Step 1: ideation and configure
			Step 2: modeling and modify
			Step 3: analysis and revise
			Step 4: visualization and experience
		Discussion and conclusions
		References
	26 - Implant design on virtual digital human skull models for the creation of customized Patient-specific regenerat ...
		Introduction
		Regenerative craniofacial surgery—current state of the art
		Customized implant design—design considerations
		Customized implant design—biomechanics
		Commercialization considerations—a balancing act between design and regulation through in vivo tissue engineering
		Future outlook
		References
	27 - Virtual reality–assisted treatment planning, patient management, and educational approaches in dentistry
		Introduction
		Implant treatment planning
		Digital workflow in dental implantology
			Software-guided implant surgery
			Digital smile design
			Virtual reality and dental anxiety
			Virtual reality and dental education
		Future directions
		References
		Further reading
6 -
Medical application
	28 - Whole-body movement modeling in realistic environments for understanding performance and injury
		Introduction
		Markerless motion capture for digital human model construction
			Background
			Overview of MMC pipeline
				Two-dimensional pose estimation models
				Three-dimensional pose reconstruction
				Joint angles from inverse kinematics
			Benefits and future applications
		Computational methods
			Biomechanical methods
				Introduction
				Kinematic definitions and theory
				Kinetics
				Dynamics
			SPH method for simulating the external environment
				SPH method for fluids
				SPH method for elastic and elastoplastic solids
				SPH boundary modeling
				Integration of SPH equations
		Using digital twins to understand performance and injury: sports examples
			Swimming
			Diving
			Snow skiing
		Realtime digital human applications: workplace injury example
		Creating software products based on human digital twins
		Conclusions
		References
	29 - Digital human modeling in cleft care
		Introduction
		Presurgical infant orthopedics
		Cleft lip and cleft lip nasal deformity repair
		Cleft palate repair
		Alveolar bone cleft reconstruction
		Orthognathic surgery in cleft care
		Conclusion
		References
	30 - The virtual patient model for correction of facial deformity and accuracy of simulation and surgical guide con ...
		Historical methods of planning
			Overview
			Orthognathic surgery
			Postablative reconstructive jaw surgery
			Craniofacial surgery
			Limitations of traditional planning
		3D imaging and biomechanical soft tissue simulation
			Introduction
			Multislice computed tomography
			Applications
			Cone beam computed tomography
			Dental records
			Stereophotogrammetry
			Biosimulations
		Virtual surgical planning, customized surgical guide, and fixation plates
			Introduction
			VSP in orthognathic surgery
			Integration of digital information
			Virtual operating theater
			Designing and printing of surgical aids, guides, or implants
			VSP in reconstructive surgery of the jaw
			VSP in craniofacial surgery
			VSP in posttraumatic deformities
			VSP in temporomandibular joint surgery
		Comparison between traditional and modern planning
			Traditional versus modern planning
			Accuracy of surgical plan transfer
			Cost and time
			Surgical outcome/patient satisfaction
		References
	31 - Patient-specific modeling of pain progression: a use case on knee osteoarthritis patients using machine learni ...
		Introduction
		Dataset description
		Methods
			Grouping/labeling
			Data preprocessing
			Feature selection
			Machine learning
			Validation
		Results and discussion
			Predictive capacity of the binary classifiers without pain-related variables
			Predictive capacity of the binary classifiers with pain variables
			Feature selection results
			Data fusion results
			Comparative analysis
		Conclusions
		References
	32 - A design procedure for the development of VR platforms for the rehabilitation of patients after stroke
		Introduction
		Scientific background
		Methods and tools
			Definition of the rehabilitation exercise and related devices
			Identification of ICT tools
			Medical data management
		Use cases
			VR platform for the evaluation of the extra-personal neglect
			VR platform for the recovery of severe memory loss
				3D scanning acquisition
				Development of the serious game
			Motor-skills tele-rehabilitation of hands
		Evaluation
		Conclusion
		References
	33 - Personalization for surgical implants
		Introduction to personalization of surgical implants
		Personalized medical device definitions
		Adoption of personalization in surgery
			Orthopedic surgery
			Craniomaxillofacial surgery
			Spinal surgery
			Vascular surgery
			Urology surgery
		Regulation
		Summary and future perspectives
		References
Index
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	R
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	U
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	X
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