Development of subject specific finite element models of the mouse knee joint for preclinical applications

Osteoarthritis is the most common musculoskeletal disabling disease worldwide. Preclinical studies on mice are commonly performed to test new interventions. Finite element (FE) models can be used to study joint mechanics, but usually simplified geometries are used. The aim of this project was to create a realistic subject specific FE model of the mouse knee joint for the assessment of joint mechanical properties. Four different FE models of a C57Bl/6 female mouse knee joint were created based on micro-computed tomography images of specimens stained with phosphotungstic acid in order to include different features: individual cartilage layers with meniscus, individual cartilage layers without meniscus, homogeneous cartilage layers with two different thickness values, and homogeneous cartilage with same thickness for both condyles. They were all analyzed under compressive displacement and the cartilage contact pressure was compared at 0.3 N reaction force. Peak contact pressure in the femur cartilage was 25% lower in the model with subject specific cartilage compared to the simpler model with homogeneous cartilage. A much more homogeneous pressure distribution across the joint was observed in the model with meniscus, with cartilage peak pressure 5–34% lower in the two condyles compared to that with individual cartilage layers. In conclusion, modeling the meniscus and individual cartilage was found to affect the pressure distribution in the mouse knee joint under compressive load and should be included in realistic models for assessing the effect of interventions preclinically

PTH(1–34) treatment and/or mechanical loading have different osteogenic effects on the trabecular and cortical bone in the ovariectomized C57BL/6 mouse

In preclinical mouse models, a synergistic anabolic response to PTH(1–34) and tibia loading was shown. Whether combined treatment improves bone properties with oestrogen deficiency, a cardinal feature of osteoporosis, remains unknown. This study quantified the individual and combined longitudinal effects of PTH(1–34) and loading on the bone morphometric and densitometric properties in ovariectomised mice. C57BL/6 mice were ovariectomised at 14-weeks-old and treated either with injections of PTH(1–34); compressive loading of the right tibia; both interventions concurrently; or both interventions on alternating weeks. Right tibiae were microCT-scanned from 14 until 24-weeks-old. Trabecular metaphyseal and cortical midshaft morphometric properties, and bone mineral content (BMC) in 40 different regions of the tibia were measured. Mice treated only with loading showed the highest trabecular bone volume fraction at week 22. Cortical thickness was higher with co-treatment than in the mice treated with PTH alone. In the mid-diaphysis, increases in BMC were significantly higher with loading than PTH. In ovariectomised mice, the osteogenic benefits of co-treatment on the trabecular bone were lower than loading alone. However, combined interventions had increased, albeit regionally-dependent, benefits to cortical bone. Increased benefits were largest in the mid-diaphysis and postero-laterally, regions subjected to higher strains under compressive loads

Estimation of in vivo inter-vertebral loading during motion using fluoroscopic and magnetic resonance image informed finite element models

Finite element (FE) models driven by medical image data can be used to estimate subject-specific spinal biomechanics. This study aimed to combine magnetic resonance (MR) imaging and quantitative fluoroscopy (QF) in subject-specific FE models of upright standing, flexion and extension. Supine MR images of the lumbar spine were acquired from healthy participants using a 0.5 T MR scanner. Nine 3D quasi-static linear FE models of L3 to L5 were created with an elastic nucleus and orthotropic annulus. QF data was acquired from the same participants who performed trunk flexion to 60o and trunk extension to 20o. The displacements and rotations of the vertebrae were calculated and applied to the FE model. Stresses were averaged across the nucleus region and transformed to the disc co-ordinate system (S1 = mediolateral, S2 = anteroposterior, S3 = axial). In upright standing S3 was predicted to be -0.7 ± 0.6 MPa (L3L4) and -0.6 ± 0.5 MPa (L4L5). S3 increased to -2.0 ± 1.3 MPa (L3L4) and -1.2 ± 0.6 MPa (L4L5) in full flexion and to -1.1 ± 0.8 MPa (L3L4) and -0.7 ± 0.5 MPa (L4L5) in full extension. S1 and S2 followed similar patterns; shear was small apart from S23. Disc stresses correlated to disc orientation and wedging. The results demonstrate that MR and QF data can be combined in a participant-specific FE model to investigate spinal biomechanics in vivo and that predicted stresses are within ranges reported in the literature

An in-vivo study exploring correlations between early-to-moderate disc degeneration and flexion mobility in the lumbar spine

Purpose: Early disc degeneration (DD) has been thought to be associated with loss of spine 6 stability. However, before this can be understood in relation to back pain, it is necessary to 7 know the relationship between DD and intervertebral motion in people without pain. This 8 study aimed to find out if early to moderate DD is associated with intervertebral motion in 9 people without back pain. 10 Methods: Ten pain free adults, aged 51-71 received recumbent and weight bearing MRI 11 scans and quantitative fluoroscopy (QF) screenings during recumbent and upright lumbar 12 flexion. Forty individual level and 10 composite (L2-S1) radiographic and MRI DD gradings 13 were recorded and correlated with intervertebral flexion ROM, translation, laxity, and 14 motion sharing inequality and variability for both positions. 15 Results: Kinematic values were similar to previous control studies. DD was evidenced up to 16 moderate levels by both radiographic and MRI grading. Disc height loss correlated slightly, 17 but negatively with flexion during weight bearing flexion (R=-0.356, p=0.0.025). Composite 18 MRI DD and T2 signal loss evidenced similar relationships (R= -0.305, R= -0.267) but did not 19 reach statistical significance (p=0.056, p=0.096). No significant relationships between any 20 other kinematic variables and DD were found. 21 Conclusion: This study found only small, indefinite associations between early-to-moderate 22 DD and intervertebral motion in healthy controls. Motion sharing in the absence of pain 23 was also not related to early DD, consistent with previous control studies. Further research 24 is needed to investigate these relationships in patients. 25 Key words: back pain, disc degeneration, instability, imagin