The assessment of neuronal status in normal and cervical spondylotic myelopathy using diffusion tensor imaging.

STUDY DESIGN: A prospective observational analysis of diffusion tensor imaging (DTI) datametrics collected from control and patients with cervical spondylotic myelopathy (CSM). OBJECTIVE: The aims were to study the use of DTI in CSM and to probe whether DTI datametrics and tractography will correlate with magnetic resonance imaging and clinical findings. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging is the current "gold standard" in the assessment of cord status in CSM; however, various parameters such as extent of compression and presence of signal intensity changes do not correlate well with clinical status. DTI is a novel investigation tool with proven applications in brain pathologies but is not routinely used in spinal cord evaluation. METHODS: Patients with CSM (n = 35) who required surgical decompression (mean age = 48 yr) and 40 normal individuals (mean age = 38 yr) were included. Diffusion Tensor Imaging of the cervical spine was obtained using a 1.5T magnetic resonance image. Apparent diffusion coefficient, fractional anisotropy, and eigenvalues (E1, E2, and E3) were obtained at each cervical level. The DTI datametrics of CSM patients were compared with normal volunteers and correlated with individual and grouped Nurick grades, which indicate the neurological status of patients. RESULTS: There was significant difference in DTI datametrics between patients with myelopathy and control (P < 0.05), with decrease in fractional anisotropy (0.49 ± 0.081 vs. 0.53 ± 0.07) and increase in apparent diffusion coefficient (1.8 ± 0.315 vs. 1.44 ± 0.145) and eigenvalues (E1: 2.82 ± 0.395 vs. 2.37 ± 0.221, E2: 1.64 ± 0.39 vs. 1.18 ± 0.198, E3: 0.956 ± 0.277 vs. 0.76 ± 0.142). There was also a significant difference between increasing grades of myelopathy when individuals were grouped as-control, self-ambulant (Nurick grades 1 and 2), and dependent (Nurick grades 3, 4, and 5). CONCLUSION: The study shows that DTI is a promising and useful investigational tool in evaluation of CSM. There was a significant difference in all DTI values between control and patients with CSM, and there was a significant trend of change in values between control, self-ambulant, and dependent patients. Our results encourage further investigation of this important modality. LEVEL OF EVIDENCE: 3.

Variability of trabecular microstructure is age-, gender-, race- and anatomic site-dependent and affects stiffness and stress distribution properties of human vertebral cancellous bone.

Cancellous bone microstructure is an important determinant of the mechanical integrity of vertebrae. The numerous microstructural parameters that have been studied extensively are generally represented as a single value obtained as an average over a sample. The range of the intra-sample variability of cancellous microstructure and its effect on the mechanical properties of bone are less well-understood. The objectives of this study were to investigate the extent to which human cancellous bone microstructure within a vertebra i) is related to bone modulus and stress distribution properties and ii) changes along with age, gender and locations thoracic 12 (T12) vs lumbar 1 (L1). Vertebrae were collected from 15 male (66±15 years) and 25 female (54±16 years) cadavers. Three dimensional finite element models were constructed using microcomputed tomography images of cylindrical specimens. Linear finite element models were used to estimate apparent modulus and stress in the cylinders during uniaxial compression. The intra-specimen mean, standard deviation (SD) and coefficient of variation (CV) of microstructural variables were calculated. Mixed model statistical analysis of the results demonstrated that increases in the intra-specimen variability of the microstructure contribute to increases in the variability of trabecular stresses and decreases in bone stiffness. These effects were independent from the contribution from intra-specimen average of the microstructure. Further, the effects of microstructural variability on bone stiffness and stress variability were not accounted for by connectivity and anisotropy. Microstructural variability properties (SD, CV) generally increased with age, were greater in females than in males and in T12 than in L1. Significant interactions were found between age, gender, vertebra and race. These interactions suggest that microstructural variability properties varied with age differently between genders, races and vertebral levels. The current results collectively demonstrate that microstructural variability has a significant effect on mechanical properties and tissue stress of human vertebral cancellous bone. Considering microstructural variability could improve the understanding of bone fragility and improve assessment of vertebral fracture risk.

The associations between mineral crystallinity and the mechanical properties of human cortical bone.

It is well known that the amount of mineralization renders bone its stiffness. However, besides the mere amount of the mineral phase, size and shape of carbonated apatite crystals are postulated to affect the mechanical properties of bone tissue as predicted by composite mechanics models. Despite this predictive evidence, there is little experimental insight on the relation between the characteristics of mineral crystals and hard tissue mechanics. In this study, Raman spectroscopy was used to provide information on the crystallinity of bone's mineral phase, a parameter which is an overall indicator of mineral crystal size and stoichiometric perfection. Raman scans and mechanical tests (monotonic and fatigue; n=64 each) were performed on the anterior, medial, lateral and posterior quadrant sections of 16 human cadaveric femurs (52 y.o.-85 y.o.). The reported coefficient of determination values (R(2)) were adjusted for the effects of age to bring out the unbiased contribution of crystallinity. Crystallinity was able to explain 6.7% to 48.3% of the variation in monotonic mechanical properties. Results indicated that the tissue-level strength and stiffness increased with increasing crystallinity while the ductility reduced. Crystallinity explained 11.3% to 63.5% of the variation in fatigue properties. Moduli of specimens with greater crystallinity degraded at a slower rate and, also, they had longer fatigue lives. However, not every anatomical quadrant displayed these relationships. In conclusion, these results acknowledge crystal properties as an important bone quality factor and raise the possibility that aberrations in these properties may contribute to senile osteoporotic fractures.

The compositional and physicochemical homogeneity of male femoral cortex increases after the sixth decade.

The temporal and spatial fluctuations in the dynamics of secondary osteonal remodeling impart heterogeneity to the compositional quality of bone. Bone mineral density (BMD) fails to reflect this heterogeneity as being a single score, and thus it cannot resolve the overlap between healthy individuals and those who experience fractures. Such information on tissue heterogeneity is lacking in the literature. In the current study, specimens were prepared from mid-diaphyseal portions of human femora (N=16, age range 52-85 years old) and grouped based on the anatomical location (anterior, lateral, medial and posterior quadrants). Raman microscopy was used to obtain multiple measurements from each specimen which allowed the construction of histograms of mineralization, crystallinity and carbonation. The coefficient of variation (COV) and skewness were extracted from histograms as measures of heterogeneity. Results demonstrated that average mineralization of the medial quadrant and the data pooled over quadrants significantly increased with age. The mean carbonation increased within the observed age range for the pooled data. The variations of values about the mean became tighter for mineralization, crystallinity and type-B carbonation with age, indicating an overall reduction in compositional heterogeneity of aging femoral cortex. Skewness values indicated that the distributions of histograms were not Gaussian. We conclude that age-related changes in mean tissue composition are confounded with changes in the variation of tissue make-up about the mean. Future studies will establish as to whether compositional heterogeneity correlates with the mechanical strength of bone.