Computational Modelling of the Trabecular Bone

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influence of age, osteoporosis status and other variables on bone fracture. • biomaterial development and scaffold engineering. • intersticial transport of drugs for ...
Computational Modelling of the Trabecular Bone Network from the GB-µFEA Technique Gustavo Peixoto de Oliveira, Dr. Waldir Leite Roque, Dr. [email protected]

*

Graduate Program in Computational and Mathematical Modelling Center of Informatics Federal University of Paraíba

João Pessoa, March 10th, 2016 @PGMEC-UFPB

Outline • • • • • •

Introduction µFEA Overview Mathematical Formulation Some Simulations Future Research Questions

Introduction

Motivation

Hip fractures






Men 310% 
 Women 240%

From: http://www.iofbonehealth.org/epidemiology

Bone fragility • • • • • •

Osteoporosis in elderly people Public health issue High costs of treatment Socio-economical impact Possible to grade? How to model?

Bone architecture (hierarchical view)

Donelly, Clin Orthop Relat Res (2011) 469:2128–2138

Focus: microscale cortical bone + trabecular bone

• •

Stages of degradation Bone mass loss

Bone cell population and remodelling

• •

Integrity of the skeletal system maintained 
 by continuous remodelling Roles of the Basic Multicellular Units
 Osteoclasts: removers of “old” bone 
 (compromised mechanical integrity)
 Osteoblasts: synthesizers of “new” bone
 (bone matrix mineralization)
 Osteocytes: network “designers” 
 (remodelling control)

Check this out —> http://youtu.be/inqWoakkiTc

Oftadeh et al., J. of Biomech. Eng. (2015) 137(1)
 doi: 10.1115/1.4029176

Trabecular bone as load-bearing struts Forth Road Bridge, Scotland

• •

Ability to rapidly adapt to the mechanical loading environment Optimizes its mass and structure to bear high loads with as little bone tissue as possible

“Trabecular Bone: Light as a Feather, Stiff as a Board” Christiansen, J. of Biomech. Eng. (2015) 137, Editorial

From: http://billharvey.typepad.com/

The Mechanical Competence Parameter • •

Measure the load-bearing capacity of trabecular bone is crucial for assessing fracture risk A proposed MCP to assess the characterization of trabecular bone fragility from high spatial resolution images connectivity

morphometry

MCP tortuosity

elastic properties

MCP M CP = 0.52BV /T V trabecular volume fraction

EP CV = 12 (#I

0.49EP CV + 0.51Ez Euler-Poincaré characteristic

#B + #H)

#I

number of objects (isolated parts)

#B

number of tunnels (redundant connections)

#H

number of enclosed cavities (holes)

Roque et al., IEEE Transactions on Biomed. Eng. (2013), (60),5

Young modulus of elasticity

Ez =

✏z

⌧+z =

LG,z LE,z

0.48⌧+z vertical tortuosity

isotropy + 1D

Normalized MCP • •

MCP was verified to be similar with both µCT and MRI A normalized MCP per sample M CPN,k =

M CPk M CPmin,k M CPmax,k M CPmin,k ,

spectrum 1: low fracture risk 0: high fracture risk 0  M CPN,k  1 Roque & Bayarri (2015), 
 DOI 10.1007/978-3-319-13407-9_11

k = 1, 2, . . . , nk

Image acquisition µCT / MRI images 3D reconstruction

(Brief mathematics of images) I(0, 0)

I(0, N )

continuous signal

I(x, y)

discretization (pixels)

I(m, n) m = 1, 2, . . . , M n = 1, 2, . . . , N

I(M, 0)

I(M, N )

color spaces I(M, N ) ⇥ C

H S V

Image segmentation and binarization Segmentation: generic process by which an image is subdivided into regions or constituent objects (Solomon & Breckon, Wiley, 2011) z

⌦ =

z ⌦bone

[

z ⌦marrow ,

z = 1, 2, . . . , Z

I(m, n, C)z ; C = {0, 1} binarization

region of interest (ROI)

µFEA Overview

Aspects of µFEA • •



• •

Micro-Finite Element analysis (µFEA) have been widely used to derive bone mechanical properties Under loading condition, can be used to derive stiffness, strength of the bone, as well as the stresses and strains in the bone tissue Some assumptions over the years: 
 µFE better predicts bone stiffness and strength?
 µFE better reflects bone fracture risk? Several validation tests with different imaging techniques Other applications: effect of diseases, treatments, activities and growth
 Van Ritbergen, Journal of Biomechanics 48 (2015) 832–841

Two main approaches •



Geometry-based (GB): defines a geometric model comprised of curves and surfaces that is finally discretized into finite elements Voxel-based (VB): each group of voxels (base unit of 3D imaging) is directly converted into hexahedral elements weaknesses GB VB





strengths

complex geometries may require extreme computational cost contact problems require smoothing techniques

• •



possibility of creating smooth surfaces simulates any kind of interface direct conversion of elements

Bocaccio et al, Int. J. Biol. Sci. (2011), 7

Example: VB x GB VB brick elements

GB tetrahedral elements

Clinic Rev Bone Miner Metab (2016) 14:26–37

3D reconstruction + FE meshing trabecular bone region

unhealthy individual

healthy individual

⌦U bone

⌦H bone

(What about the full FE meshing?)

• •

see also Metzger (2015), 137; 011006-1



multimaterial meshing mechanobiology of
 bone/marrow interface:
 - homogeneous fluid hypothesis
 - FSI simulations to appear…

Behind the scenes… Image processing: • multithresholding • “de-islanding” (hole removal) • filtering • smoothing 3D Meshing: • CGAL • iso2Mesh • adaptivity

d Tbone

:=

S Jb

d j=1 Tj ,

d Tp

\

d Tq

6= ; d = 2, 3

(Effective area) @⌦bone,top

@⌦bone @⌦bone,bot Aef f = A(@⌦bone )

2 A(Tbone )

Aef f = PJb 1 = j=1 2 ||(x3

=

P Jb

2 T j=1 j =

x1 )j ⇥ (x2

x1 )j ||

Mathematical Formulation

Classical displacement problem

“Determine the distribution of displacements, strains and stresses in the interior of an elastic body in equilibrium when body forces are given and the distribution of the displacements are prescribed over the surface of the body.” (Saad, 2011) u(x@⌦bone ) = g(x@⌦bone )

FEBio software Nonlinear finite element solver that is specifically designed for biomechanical applications Open-source and multi-platform (Windows, OS-X and Linux platforms available) Maintenance: Original: Musculoskeletal Research Laboratories - University of Utah 
 Current: University of Utah / Musculoskeletal Biomechanics Laboratory - Columbia University

Weak form for solid mechanics Virtual work equation W = W d v f t

R

⌦bone

: d d⌦

R

⌦bone

: virtual work : Cauchy's stress tensor : virtual rate of deformation tensor : virtual velocity : body force : traction force

f · v d⌦

R

@⌦bone

t · v d@⌦ = 0

Linearization and discrete form In FEBio, virtual work is solved using an incremental-iterative strategy based on Newton’s method, which requires linearization W ( k , v) + D W ( k , v) · u = 0 directional derivative

: deformation

k : trial function

For more details on the derivation, see: Maas, Steve A., et al. "FEBio: finite elements for biomechanics." 
 J. of biomechanical eng. 134.1 (2012): 011005. Bonet, J., and Wood, R. D., 1997, Nonlinear Continuum Mechanics for Finite Element Analysis, 
 Cambridge University Press, Cambridge, NY.

à la Ritz position, displacement deform. grad. tensor real and virtual velocity real rate of deformation virtual rate of deformation linear strain tensor

Na

element shape functions

rNa =

@Na grad. init. config. @X

l.h.s. e

W ( , Na v a ) = R f · (Na va ) dTj Tj

R

: ( va ⌦ rNa ) dTj t · (Na va ) d@Tj = 0, @Tj

TRj

W e ( , Na v a ) = v a ·

⇣R

: (u ⌦ v) ⌘ u · v Tj

rNa dTj

internal

e

W ( , Na v a ) = v a ·

e (Ta

R

Tj

f Na dTj

j = 1, 2, . . . , J1 R

@Tj

tNa d@Tj = 0

external

e Fa )

= va ·



e Ra

r.h.s. D W e ( , Na va )[Nb ub ] = D( va · (Tea va · D(Tea Fea ))[Nb ub ] = va · Keab ub tangent stiffness matrix

Element assembly

e Kab

Fea ))[Nb ub ] =

= Kec,ab + Ke ,ab + Kep,ab constitutive
 component

stress

arbitrary 
 virtual 
 velocity

vT Ku =

vT R ) Ku =

R

external
 forces

Linear system solution K(xk )u = xk =

R(xk ), k (X),

xk+1 = xk + u P X= Na Xa

iterative quasi-Newton BFGS method

Constitutive equations linear elasticity =c:✏ c ✏

: Cauchy's stress tensor : elasticity tensor : small strain tensor

nonlinear neo-Hookean solid =

µ J (b T

b = FF b F µ,

I) + J (ln J)I J = det F

: left Cauchy-Green deformation tensor : deformation gradient tensor : Lamé’s constants

uniaxial extension ≈ linear for 
 small strains

1: linear
 2: neo-Hookean
 3: Mooney-Rivlin From: Wikipedia (rheology tests)

Febio theory manual C. W. Macosko, 1994, Rheology: principles, 
 measurement and applications, 
 VCH Publishers, p. 47

Some Simulations

Bone compression test Material elastic properties Young's modulus (E)= 10GPa Poisson ratio (ν)= 0.3 Imposed strain = 1%

µ=

E 2(1+⌫) ,

=

E⌫ (1+⌫)(1 2⌫)

u(@⌦bone,top ) =

u z ez

Bayarri et al, 2010, IntechOpen

u(@⌦bone,bot ) = 0

Computational simulations

Outside…

Some considerations • • • •

Warm-up results Limited computational resources 
 Thousands —> millions of elements Verification and validation MCP parameters

Future Research

State-of-art and future research •

@CI validate MCP through µFE and establish MCPn-based biomarkers



@world



mechanobiology of the interaction between bone and marrow



FSI simulations & poroelastic theory



rigorous validation of µFE methods



standardisation of biomarkers for fracture risk



influence of age, osteoporosis status and other variables on bone fracture



biomaterial development and scaffold engineering



intersticial transport of drugs for bone treatment See cited refs.

Thanks for listening!

QUESTIONS?

[email protected]

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