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Elevated Microdamage Spatially Correlates with Stress in Metastatic Vertebrae

  • Ayelet Atkins
  • Mikhail Burke
  • Saeid Samiezadeh
  • Margarete K. Akens
  • Michael Hardisty
  • Cari M. WhyneEmail author
Article
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Abstract

Metastasis of cancer to the spine impacts bone quality. This study aims to characterize vertebral microdamage secondary to metastatic disease considering the pattern of damage and its relationship to stress and strain under load. Osteolytic and mixed osteolytic/osteoblastic vertebral metastases were produced in athymic rats via HeLa cervical or canine Ace-1 prostate cancer cell inoculation, respectively. After 21 days, excised motion segments (T12–L2) were µCT scanned, stained with BaSO4 and re-imaged. T13–L2 motion segments were loaded in axial compression to induce microdamage, re-stained and re-imaged. L1 (loaded) and T12 (unloaded) vertebrae were fixed, sample blocks cut, polished and BSE imaged. µFE models were generated of all L1 vertebrae with displacement boundary conditions applied based on the loaded µCT images. µCT stereological analysis, BSE analysis and µFE derived von Mises stress and principal strains were quantitatively compared (ANOVA), spatial correlations determined and patterns of microdamage assessed qualitatively. BaSO4 identified microdamage was found to be spatially correlated with regions of high stress in µFEA. Load-induced microdamage was shown to be elevated in the presence of osteolytic and mixed metastatic disease, with diffuse, crossed hatched areas of microdamage present in addition to linear microdamage and microfractures in metastatic tissue, suggesting diminished bone quality.

Keywords

Microdamage Vertebral metastasis Bone quality Barium sulfate staining Micro computed tomography Backscatter electron imaging Finite element analysis 

Abbreviations

µCT

Micro computed tomography

T12, L1

12th thoracic and 1st lumbar vertebrae

N

Newtons

SREs

Skeletal related events

BaSO4

Barium sulfate

BSE imaging

Backscatter electron imaging

µFE(A)

Micro finite element (analysis)

ANOVA

Analysis of variance

RPMI

Roswell Park Memorial Institute (RPMI) 1640 Medium

DMEM/F-12

Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12

CO2

Carbon dioxide

TBV

Trabecular bone volume

TMD

Tissue mineral density

BMD

Bone mineral density

TbN

Trabecular number

TbS

Trabecular spacing

TbTh

Trabecular thickness

FHWM

Full width half maximum

GLMax

Grey level at the max intensity

GLAve

Average grey level

GPa, MPa

GigaPascal, MegaPascal

\(\varvec{\varepsilon}_{1}\) and \(\varvec{\varepsilon}_{3}\)

Maximum and minimum principal strain

\(\varvec{\sigma}_{1}\) and \(\varvec{\sigma}_{3}\)

Maximum and minimum principal stress

\(\varvec{\sigma}_{vm}\)

Von Mises stress

SD

Standard deviation

g(r)

Spatial correlation

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Copyright information

© Biomedical Engineering Society 2019

Authors and Affiliations

  • Ayelet Atkins
    • 1
  • Mikhail Burke
    • 1
    • 3
  • Saeid Samiezadeh
    • 1
  • Margarete K. Akens
    • 2
    • 4
    • 5
  • Michael Hardisty
    • 1
  • Cari M. Whyne
    • 1
    • 2
    • 3
    Email author
  1. 1.Orthopaedics Biomechanics LaboratorySunnybrook Research InstituteTorontoCanada
  2. 2.Division of Orthopaedics, Department of SurgeryUniversity of TorontoTorontoCanada
  3. 3.Institute of Biomaterials and Biomedical EngineeringUniversity of TorontoTorontoCanada
  4. 4.Techna InstituteUniversity Health NetworkTorontoCanada
  5. 5.Department of Medical BiophysicsUniversity of TorontoTorontoCanada

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