Thresholding approaches for estimating paraspinal muscle fat infiltration using T1- and T2-weighted MRI: Comparative analysis using water-fat MRI.

Background: Paraspinal muscle fat infiltration is associated with spinal degeneration and low back pain, however, quantifying muscle fat using clinical magnetic resonance imaging (MRI) techniques continues to be a challenge. Advanced MRI techniques, including chemical-shift encoding (CSE) based water-fat MRI, enable accurate measurement of muscle fat, but such techniques are not widely available in routine clinical practice. Methods: To facilitate assessment of paraspinal muscle fat using clinical imaging, we compared four thresholding approaches for estimating muscle fat fraction (FF) using T1- and T2-weighted images, with measurements from water-fat MRI as the ground truth: Gaussian thresholding, Otsu's method, K-mean clustering, and quadratic discriminant analysis. Pearson's correlation coefficients (r), mean absolute errors, and mean bias errors were calculated for FF estimates from T1- and T2-weighted MRI with water-fat MRI for the lumbar multifidus (MF), erector spinae (ES), quadratus lumborum (QL), and psoas (PS), and for all muscles combined. Results: We found that for all muscles combined, FF measurements from T1- and T2-weighted images were strongly positively correlated with measurements from the water-fat images for all thresholding techniques (r = 0.70-0.86, p < 0.0001) and that variations in inter-muscle correlation strength were much greater than variations in inter-method correlation strength. Conclusion: We conclude that muscle FF can be quantified using thresholded T1- and T2-weighted MRI images with relatively low bias and absolute error in relation to water-fat MRI, particularly in the MF and ES, and the choice of thresholding technique should depend on the muscle and clinical MRI sequence of interest.

Radiation-induced changes in load-sharing and structure-function behavior in murine lumbar vertebrae.

In this study, we used micro-CT-based finite element analysis to investigate the biomechanical effects of radiation on the microstructure and mechanical function of murine lumbar vertebrae. Specifically, we evaluated vertebral microstructure, whole-bone stiffness, and cortical-trabecular load sharing in the L5 vertebral body of mice exposed to ionizing radiation 11 days post exposure (5 Gy total dose; n = 13) and controls (n = 14). Our findings revealed the irradiated group exhibited reduced trabecular bone volume and microstructure (p < 0.001) compared to controls, while cortical bone volume remained unchanged (p = 0.91). Axially compressive loads in the irradiated group were diverted from the trabecular centrum and into the vertebral cortex, as evidenced by a higher cortical load-fraction (p = 0.02) and a higher proportion of cortical tissue at risk of initial failure (p < 0.01). Whole-bone stiffness was lower in the irradiated group compared to the controls, though the difference was small and non-significant (2045 ± 142 vs. 2185 ± 225 vs. N/mm, irradiated vs. control, p = 0.07). Additionally, the structure-function relationship between trabecular bone volume and trabecular load fraction differed between groups (p = 0.03), indicating a less biomechanically efficient trabecular network in the irradiated group. We conclude that radiation can decrease trabecular bone volume and result in a less biomechanically efficient trabecular structure, leading to increased reliance on the vertebral cortex to resist axially compressive loads. These findings offer biomechanical insight into the effects of radiation on structure-function behavior in murine lumbar vertebrae independent of possible tissue-level material effects.

Deep-learning-based biomarker of spinal cartilage endplate health using ultra-short echo time magnetic resonance imaging.

Background: T2* relaxation times in the spinal cartilage endplate (CEP) measured using ultra-short echo time magnetic resonance imaging (UTE MRI) reflect aspects of biochemical composition that influence the CEP's permeability to nutrients. Deficits in CEP composition measured using T2* biomarkers from UTE MRI are associated with more severe intervertebral disc degeneration in patients with chronic low back pain (cLBP). The goal of this study was to develop an objective, accurate, and efficient deep-learning-based method for calculating biomarkers of CEP health using UTE images. Methods: Multi-echo UTE MRI of the lumbar spine was acquired from a prospectively enrolled cross-sectional and consecutive cohort of 83 subjects spanning a wide range of ages and cLBP-related conditions. CEPs from the L4-S1 levels were manually segmented on 6,972 UTE images and used to train neural networks utilizing the u-net architecture. CEP segmentations and mean CEP T2* values derived from manually- and model-generated segmentations were compared using Dice scores, sensitivity, specificity, Bland-Altman, and receiver-operator characteristic (ROC) analysis. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated and related to model performance. Results: Compared with manual CEP segmentations, model-generated segmentations achieved sensitives of 0.80-0.91, specificities of 0.99, Dice scores of 0.77-0.85, area under the receiver-operating characteristic curve values of 0.99, and precision-recall (PR) AUC values of 0.56-0.77, depending on spinal level and sagittal image position. Mean CEP T2* values and principal CEP angles derived from the model-predicted segmentations had low bias in an unseen test dataset (T2* bias =0.33±2.37 ms, angle bias =0.36±2.65°). To simulate a hypothetical clinical scenario, the predicted segmentations were used to stratify CEPs into high, medium, and low T2* groups. Group predictions had diagnostic sensitivities of 0.77-0.86 and specificities of 0.86-0.95. Model performance was positively associated with image SNR and CNR. Conclusions: The trained deep learning models enable accurate, automated CEP segmentations and T2* biomarker computations that are statistically similar to those from manual segmentations. These models address limitations with inefficiency and subjectivity associated with manual methods. Such techniques could be used to elucidate the role of CEP composition in disc degeneration etiology and guide emerging therapies for cLBP.

ISSLS Prize in Bioengineering Science 2023: Age- and sex-related differences in lumbar intervertebral disc degeneration between patients with chronic low back pain and asymptomatic controls.

PURPOSE: Clinical management of disc degeneration in patients with chronic low back pain (cLBP) is hampered by the challenge of distinguishing pathologic changes relating to pain from physiologic changes related to aging. The goal of this study was to use imaging biomarkers of disc biochemical composition to distinguish degenerative changes associated with cLBP from normal aging. METHODS: T1ρ MRI data were acquired from 133 prospectively enrolled subjects for this observational study (80 cLBP, 53 controls; mean ± SD age = 43.9 ± 13.4 years; 61 females, 72 males). The mean T1ρ relaxation time in the nucleus pulposus (NP-T1ρ; n = 650 discs) was used as a quantitative biomarker of disc biochemical composition. Linear regression was used to assess associations between NP-T1ρ and age, sex, spinal level, and study group, and their interactions. RESULTS: NP-T1ρ values were lower in cLBP patients than controls (70.8 ± 22.8 vs. 76.4 ± 22.2 ms, p = 0.009). Group differences were largest at L5-S1 (ΔT1ρcLBP-control = -11.3 ms, p < 0.0001), representing biochemical deterioration typically observed over a 9-12 year period (NP-T1ρ declined by 0.8-1.1 ms per year [95% CI]). Group differences were large in younger patients and diminished with age. Finally, the age-dependence of disc degeneration was stronger in controls than cLBP patients. CONCLUSION: Aging effects on the biochemical composition of the L5-S1 disc may involve a relatively uniform set of factors from which many cLBP patients deviate. NP-T1ρ values at L5-S1 may be highly relevant to clinical phenotyping, particularly in younger individuals.

The contributions of cartilage endplate composition and vertebral bone marrow fat to intervertebral disc degeneration in patients with chronic low back pain.

PURPOSE: The composition of the subchondral bone marrow and cartilage endplate (CEP) could affect intervertebral disc health by influencing vertebral perfusion and nutrient diffusion. However, the relative contributions of these factors to disc degeneration in patients with chronic low back pain (cLBP) have not been quantified. The goal of this study was to use compositional biomarkers derived from quantitative MRI to establish how CEP composition (surrogate for permeability) and vertebral bone marrow fat fraction (BMFF, surrogate for perfusion) relate to disc degeneration. METHODS: MRI data from 60 patients with cLBP were included in this prospective observational study (28 female, 32 male; age = 40.0 ± 11.9 years, 19-65 [mean ± SD, min-max]). Ultra-short echo-time MRI was used to calculate CEP T2* relaxation times (reflecting biochemical composition), water-fat MRI was used to calculate vertebral BMFF, and T1ρ MRI was used to calculate T1ρ relaxation times in the nucleus pulposus (NP T1ρ, reflecting proteoglycan content and degenerative grade). Univariate linear regression was used to assess the independent effects of CEP T2* and vertebral BMFF on NP T1ρ. Mixed effects multivariable linear regression accounting for age, sex, and BMI was used to assess the combined relationship between variables. RESULTS: CEP T2* and vertebral BMFF were independently associated with NP T1ρ (p = 0.003 and 0.0001, respectively). After adjusting for age, sex, and BMI, NP T1ρ remained significantly associated with CEP T2* (p = 0.0001) but not vertebral BMFF (p = 0.43). CONCLUSION: Poor CEP composition plays a significant role in disc degeneration severity and can affect disc health both with and without deficits in vertebral perfusion.

Paraspinal Muscle in Chronic Low Back Pain: Comparison Between Standard Parameters and Chemical Shift Encoding-Based Water-Fat MRI.

BACKGROUND: Paraspinal musculature (PSM) is increasingly recognized as a contributor to low back pain (LBP), but with conventional MRI sequences, assessment is limited. Chemical shift encoding-based water-fat MRI (CSE-MRI) enables the measurement of PSM fat fraction (FF), which may assist investigations of chronic LBP. PURPOSE: To investigate associations between PSM parameters from conventional MRI and CSE-MRI and between PSM parameters and pain. STUDY TYPE: Prospective, cross-sectional. POPULATION: Eighty-four adults with chronic LBP (44.6 ± 13.4 years; 48 males). FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted fast spin-echo and iterative decomposition of water and fat with echo asymmetry and least squares estimation sequences. ASSESSMENT: T1-weighted images for Goutallier classification (GC), muscle volume, lumbar indentation value, and muscle-fat index, CSE-MRI for FF extraction (L1/2-L5/S1). Pain was self-reported using a visual analogue scale (VAS). Intra- and/or interreader agreement was assessed for MRI-derived parameters. STATISTICAL TESTS: Mixed-effects and linear regression models to 1) assess relationships between PSM parameters (entire cohort and subgroup with GC grades 0 and 1; statistical significance α = 0.0025) and 2) evaluate associations of PSM parameters with pain (α = 0.05). Intraclass correlation coefficients (ICCs) for intra- and/or interreader agreement. RESULTS: The FF showed excellent intra- and interreader agreement (ICC range: 0.97-0.99) and was significantly associated with GC at all spinal levels. Subgroup analysis suggested that early/subtle changes in PSM are detectable with FF but not with GC, given the absence of significant associations between FF and GC (P-value range: 0.036 at L5/S1 to 0.784 at L2/L3). Averaged over all spinal levels, FF and GC were significantly associated with VAS scores. DATA CONCLUSION: In the absence of FF, GC may be the best surrogate for PSM quality. Given the ability of CSE-MRI to detect muscle alterations at early stages of PSM degeneration, this technique may have potential for further investigations of the role of PSM in chronic LBP. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

The Role of Vertebral Porosity and Implant Loading Mode on Bone-Tissue Stress in the Human Vertebral Body Following Lumbar Total Disc Arthroplasty.

STUDY DESIGN: Micro-computed tomography- (micro-CT-) based finite element analysis of cadaveric human lumbar vertebrae virtually implanted with total disc arthroplasty (TDA) implants. OBJECTIVE: (1) Assess the relationship between vertebral porosity and maximum levels of bone-tissue stress following TDA; (2) determine whether the implant's loading mode (axial compression vs. sagittal bending) alters the relationship between vertebral porosity and bone-tissue stress. SUMMARY OF BACKGROUND DATA: Implant subsidence may be related to the bone biomechanics in the underlying vertebral body, which are poorly understood. For example, it remains unclear how the stresses that develop in the supporting bone tissue depend on the implant's loading mode or on typical inter-individual variations in vertebral morphology. METHODS: Data from micro-CT scans from 12 human lumbar vertebrae (8 males, 4 females; 51-89 years of age; bone volume fraction [BV/TV] = 0.060-0.145) were used to construct high-resolution finite element models (37 µm element edge length) comprising disc-vertebra-implant motion segments. Implants were loaded to 800 N of force in axial compression, flexion-, and extension-induced impingement. For comparison, the same net loads were applied via an intact disc without an implant. Linear regression was used to assess the relationship between BV/TV, loading mode, and the specimen-specific change in stress caused by implantation. RESULTS: The increase in maximum bone-tissue stress caused by implantation depended on loading mode (P < 0.001), increasing more in bending-induced impingement than axial compression (for the same applied force). The change in maximum stress was significantly associated with BV/TV (P = 0.002): higher porosity vertebrae experienced a disproportionate increase in stress compared with lower porosity vertebrae. There was a significant interaction between loading mode and BV/TV (P = 0.002), indicating that loading mode altered the relationship between BV/TV and the change in maximum bone-tissue stress. CONCLUSION: Typically-sized TDA implants disproportionately increase the bone-tissue stress in more porous vertebrae; this affect is accentuated when the implant impinges in sagittal bending.Level of Evidence: N/A.

Oxidized Zirconium Components Maintain a Smooth Articular Surface Except Following Hip Dislocation.

BACKGROUND: Oxidized zirconium (OxZr) offers theoretical advantages in total hip and knee arthroplasty (THA and TKA, respectively) relative to other biomaterials by combining the tribological benefits of ceramics with the fracture toughness of metals. Yet, some studies have found that OxZr does not improve outcomes or wear rates relative to traditional bearing materials such as cobalt-chromium (CoCr). Separately, effacement of the thin ceramic surface layer has been reported for OxZr components, though the prevalence and sequelae are unclear. METHODS: To elucidate the in vivo behavior of OxZr implants, the articular surfaces of 94 retrieved THA and TKA femoral components (43 OxZr TKA, 21 OxZr THA, 30 CoCr THA) were analyzed using optical microscopy, non-contact profilometry, and scanning electron microscopy. RESULTS: We found that OxZr components maintain a smooth articular surface except following hip dislocation. Three of four OxZr femoral heads revised following dislocation exhibited severe damage to the articular surface, including macroscopic regions of ceramic-layer effacement and exposure of the underlying metal substrate; these components were 23-32 times rougher than pristine OxZr controls. When revised for dislocation, OxZr femoral heads were substantially rougher than CoCr femoral heads (median Sa = 0.431 v. 0.020 µm, P = .03). In contrast, CoCr femoral heads exhibited low overall roughness values regardless of whether they dislocated (median Sa = 0.020 v. 0.008 µm, P = .09, CoCr dislocators v. non-dislocators). CONCLUSIONS: Effacement of the ceramic surface layer and substantial articular surface roughening is not atypical following dislocation of OxZr femoral heads, making OxZr much less tolerant than CoCr to hip dislocation.

Load-transfer in the human vertebral body following lumbar total disc arthroplasty: Effects of implant size and stiffness in axial compression and forward flexion.

Adverse clinical outcomes for total disc arthroplasty (TDA), including subsidence, heterotopic ossification, and adjacent-level vertebral fracture, suggest problems with the underlying biomechanics. To gain insight, we investigated the role of size and stiffness of TDA implants on load-transfer within a vertebral body. Uniquely, we accounted for the realistic multi-scale geometric features of the trabecular micro-architecture and cortical shell. Using voxel-based finite element analysis derived from a micro-computed tomography scan of one human L1 vertebral body (74-µm-sized elements), a series of generic elliptically shaped implants were analyzed. We parametrically modeled three implant sizes (small, medium [a typical clinical size], and large) and three implant materials (metallic, E = 100 GPa; polymeric, E = 1 GPa; and tissue-engineered, E = 0.01 GPa). Analyses were run for two load cases: 800 N in uniform compression and flexion-induced anterior impingement. Results were compared to those of an intact model without an implant and loaded instead via a disc-like material. We found that TDA implantation increased stress in the bone tissue by over 50% in large portions of the vertebra. These changes depended more on implant size than material, and there was an interaction between implant size and loading condition. For the small implant, flexion increased the 98th-percentile of stress by 32 ± 24% relative to compression, but the overall stress distribution and trabecular-cortical load-sharing were relatively insensitive to loading mode. In contrast, for the medium and large implants, flexion increased the 98th-percentile of stress by 42 ± 9% and 87 ± 29%, respectively, and substantially re-distributed stress within the vertebra; in particular overloading the anterior trabecular centrum and cortex. We conclude that TDA implants can substantially alter stress deep within the lumbar vertebra, depending primarily on implant size. For implants of typical clinical size, bending-induced impingement can substantially increase stress in local regions and may therefore be one factor driving subsidence in vivo.