Dawn M. Elliott

Background: The spinal endplate region consists of the cartilage endplate (CEP), bony endplate (BEP), and subchondral trabecular bone (STB). Although this region is often involved in vertebral fractures and disrupted with disc degeneration, the biomechanics of these tissues are incompletely understood. The goal of this study was to characterize the mechanical, structural, and compositional properties of the spinal endplate region across aging and disc degeneration. Methods: Cadaveric human lumbar spine segments ( n = 45) were imaged with magnetic resonance imaging to assess disc degeneration. BEP and STB microstructure were analyzed with micro‐computed tomography. BEP specimens were subjected to four‐point‐bend testing, and CEP specimens to confined compression testing. BEP and STB composition was measured with ash analysis. Results: Several BEP mechanical properties, including flexural modulus, were associated with structural measures such as bone volume fraction, but showed few correlations to composition. Measures of structure and composition were generally different but correlated between the BEP and STB. Superior and inferior endplates differed from each other in structure but not composition. Apart from the STB microstructure, which became sparser with age in superior endplates, none of the endplate region properties correlated with age or disc degeneration, despite large ranges in values observed for many of these properties, particularly, BEP fracture strain (1%–52% strain). Conclusions: Structural measures are more reliable indicators of endplate region properties than are compositional measures, age, or disc degeneration. The BEP may play an important, independent role in spine function, due to its range in ductility and limited correspondence in properties to those of neighboring tissues.

Aging musculoskeletal tissues have a progressively declining ability to maintain homeostasis, increasing the risk of tendinopathy and tendon rupture. In young rats (3 months old), in vivo mechanical overload induced adaptive changes at 8 weeks, where load-bearing ability increased, which transitioned to degenerative changes at 16-weeks, where mechanical properties declined. It is unknown how maturation will influence the timeline of tendon outcomes to overload. The primary objective of this study was to evaluate mechanical and structural responses to overload in “middle-aged” (12-month-old) rats, representing an age when human tendon injuries become more prevalent, using a synergist ablation (SynAb) model. 12-month-old rats demonstrated adaptive changes in structural properties after 8-weeks of overload and no alterations in material properties, similar to prior findings in 3-month-old rats. Contrary to our findings in young animals, middle-age animals did not exhibit mechanical degeneration but rather they returned to control levels. MRI and μCT revealed no overload-dependent differences in tissue-scale structure, tendon cellularity, and collagen organization at either timepoint. A secondary objective was to evaluate natural age-related changes in untreated tendons. Twelve-month-old tendons, compared to 3-month-old tendons, exhibited greater load bearing-capacity, reduced extensibility, increased linear modulus, more heterotopic ossification, and a shift toward rounder nuclear morphology. These findings indicate that maturation still induces an initial adaptive response but does not lead to degeneration at later timepoints, differing from younger rats.

Background: T2 relaxation time is a widely used quantitative MRI measure of intervertebral disc degeneration, correlated with water and biochemical composition. T2 time is dependent on many factors, including scan parameters, signal decay model, and region(s) of interest, such that quantification of T2 time repeatability is necessary for interpreting T2 study outcomes. Further, the sensitivity of T2 time to factors such as time of day and unloaded rest has not been sufficiently quantified. The objective of this study was to evaluate repeatability, as well as time of day and unloaded rest effects on lumbar disc T2 relaxation time. Methods: Young asymptomatic participants underwent MRI. Part 1 assessed intra‐rater, inter‐rater, and inter‐scan Repeatability. Part 2 evaluated effects of Time of Day across four time points spanning 8 am to 5 pm, and 45 min unloaded Rest. T2 time was evaluated using a noise‐corrected exponential decay model for a circular region of interest (ROI) in the nucleus pulposus (NP) and for 5 regions across a mid‐sagittal line spanning the annulus fibrosus (AF), NP, and transition regions. Results: Intra‐ and inter‐rater repeatability was good‐excellent (ICC = 0.76–0.99) across all regions. Inter‐scan repeatability was good‐excellent (ICC = 0.89–0.93) for the NP, while the AF had moderate‐poor repeatability (ICC = 0.17–0.53). The minimal detectable change (MDC) for the NP ROI was 31 ms. Time of Day and Rest did not significantly affect NP T2 time. Across regions, all measured changes for Time of Day and Rest were less than corresponding MDCs. Conclusions: T2 time variability is primarily driven by acquisition factors, not rater subjectivity. Time of Day and Rest T2 time changes did not exceed within‐subject variability (by MDC) and therefore are not critical considerations for some study designs. The reported MDCs provide practical thresholds for interpreting individual T2 time differences.

Meniscus tears compromise its mechanical function, leading to impaired joint loading and, if left untreated, increase the risk of further joint degeneration. Surgical repair can be successful for certain tear patterns. Establishing new methods for quantifying In vivo meniscus mechanics under weightbearing facilitates improvements in surgical techniques and postoperative care. The goal of this study was to establish a method for quantifying meniscus mechanics under loading in vivo using magnetic resonance imaging (MRI). A custom MRI-compatible knee loading device was instrumented with the capability of applying loads up to 700 N at variable flexion angles. To evaluate the device, the medial and lateral menisci of healthy young participants and participants with knee pathologies were evaluated. MRI was acquired when the knees were loaded under 10% and 50% body weight at 0 deg extension and 30 deg flexion. Displacements were quantified in both menisci and articular cartilage. All participants completed the knee loading protocol without issue or discomfort. The participants with knee pathologies exhibited greater amounts of displacement compared to the healthy participants. Cartilage strain was consistent and within the expected physiological range among all participant groups. This study demonstrated the safety and effectiveness of using an in vivo MRI-compatible knee loading device that can apply axial compressive loads at varying knee flexion angles. Our results provide proof-of-concept of this technique to quantify altered joint kinematics in surgical patients with meniscus or cartilage pathologies. The novel methodology substantiates further study on patients who receive meniscus surgical procedures.

Low back pain (LBP) is the leading cause of disability worldwide, yet clinical imaging remains largely limited to anatomical assessment, providing little insight into the spinal tissue mechanics underlying most idiopathic cases. This review highlights emerging noninvasive imaging technologies that enable in vivo quantification of intervertebral disc and spinal muscle mechanics, including radiography, ultrasound imaging, ultrasound elastography, magnetic resonance imaging, and magnetic resonance elastography. These approaches move beyond static morphology to capture spinal kinematics, load-dependent deformation, and tissue material properties under physiologically relevant conditions. Despite substantial technical progress, translation is hindered by inter-individual variability, limited symptomatic cohorts, and challenges in separating age-related changes from pathology. We discuss opportunities to accelerate clinical impact through development of normative mechanical datasets, dynamic and load-dependent imaging paradigms, and integration of imaging-derived mechanical biomarkers with computational modeling and machine learning. Together, these innovations position mechanics-based imaging to enable objective diagnosis, improved patient stratification, and mechanism-driven treatment of low back pain.

Osteoarthritis (OA) of the knee is a leading cause of pain and disability. Large animal models that accurately reflect the human OA phenotype are essential for evaluating new therapeutics. This study sought to evaluate a porcine model of knee injury using an enhanced destabilization of the medial meniscus (DMM+) approach in which a 5 mm portion of the medial meniscus anterior (cranial) attachment (cranial medial meniscotibial ligament) was resected. A series of quantitative and semi‐quantitative measures of joint‐wide structure and function were used to assess joint degeneration at 6 weeks and 6 months postoperatively, including cartilage mechanical testing, subchondral bone analysis, osteochondral and synovial histology and gait analysis. Results showed that early degenerative changes were localized to regions experiencing a change in mechanical loading, with changes including decreased cartilage mechanics and subchondral bone sclerosis. By 6 months, despite resolution of the subchondral bone changes, other features of degeneration became more diffuse, with cartilage softening, synovial inflammation, and altered gait being apparent at this time point, indicating a transition from acute mechanical insult to chronic joint pathology. This large animal model results in OA‐like changes to cartilage mechanics and synovium, mimicking some key aspects of human OA, making it a potentially valuable platform in which to test disease‐modifying treatments and regenerative strategies.

Mechanical loading is essential for tendon homeostasis. Increases in the duration and magnitude of load can promote tendon adaptation; however, excessive or prolonged overloading can surpass the tendon's adaptive capacity, leading to pathological degeneration. While the adaptive and degenerative responses of tendons to mechanical loading are well accepted, the threshold and mechanisms that distinguish adaptation from degeneration remain unknown. This study evaluated longitudinal mechanical, structural and cellular responses due to plantaris tendon overload using the synergistic ablation model (SynAb). Female Long–Evans rats either received bilateral SynAb surgery (Achilles tendon resected), or bilateral sham surgery, or were age‐matched intact control. Animal activity was measured before surgery and then bi‐weekly. Rats were euthanized at either 3 days, 8 weeks, or 16 weeks post‐intervention. Each leg was randomly assigned for mechanical tests, histology, or gene expression. A subset of legs was also assessed for 3D tissue structure using magnetic resonance imaging. We observed time‐dependent mechanical, structural, and cellular responses. While overload initially induced adaptive remodelling evidenced by increased tendon cross‐sectional area and ultimate load, prolonged overload led to degenerative changes, including reduced mechanical properties (modulus and ultimate stress) and a transcriptomic profile showing elevated inflammatory and matrix degradation markers. These findings suggest that between 8 and 16 weeks, an adaptive‐to‐degenerative threshold was crossed, where repair mechanisms could no longer keep up with accumulated overload, triggering extracellular matrix breakdown. image Key points: Mechanical loading is essential for tendon homeostasis and adaptive remodelling. However prolonged overload can lead to degeneration. The mechanisms driving adaptive remodelling or pathological degeneration in response to mechanical loading remain unknown. This study evaluated the longitudinal response to plantaris tendon overload using the synergist ablation model (SynAb). We observed time‐dependent mechanical, structural and cellular changes to overload. Overload initially produced an adaptive response; however, prolonged overload eventually led to degeneration. These findings highlight a critical transition from adaptation to degeneration, opening important new opportunities to investigate mechanisms driving this progression. Understanding early changes is essential for identifying key factors that determine whether tendons adapt or develop pathology in response to increased loading.

Introduction: Intervertebral disc degeneration is strongly implicated as a cause of low back pain. Although the precise pathophysiological mechanisms remain elusive, perturbations in nutrition that adversely impact the cellular microenvironment of the central nucleus pulposus (NP) may be contributing factors. A comprehensive understanding of this microenvironment, including changes in nutrient availability as a function of degeneration, is critical for the development of effective cell‐based treatments. The goal of this study was to adapt brain tissue oxygen probes and microdialysis catheters for in situ determination of relative NP oxygen, glucose, and lactate levels in a preclinical goat model of disc degeneration.Methods: Following ex vivo technical refinement in bovine caudal discs, baseline metabolite measurements were performed in vivo in the lumbar discs of 3 large frame goats. Degeneration was then induced via injection of chondroitinase ABC (ChABC) into the NP, and measurements were repeated after 12 weeks. Degeneration severity was graded using magnetic resonance imaging (MRI) and histology, and vertebral endplate porosity was assessed using microcomputed tomography.Results: Oxygen and lactate levels in goat NPs were significantly higher in degenerate compared to healthy discs, while glucose levels were not significantly different. ChABC‐injected discs exhibited higher vertebral endplate porosity, worse histological and MRI grades, and a spectrum of cartilage endplate damage compared to healthy discs. There were significant positive correlations between MRI grade and both NP oxygen and lactate levels.Discussion: We successfully adapted techniques including surgical placement, equilibration time, flow rate, and detection method for in situ measurement of oxygen, glucose, and lactate in a goat model of disc degeneration. Interestingly, while increased lactate with degeneration was expected, increased oxygen levels were unexpected. Our findings may, in part, be explained by associated alterations in disc and endplate structure, and motivate future studies to comprehensively establish the underlying mechanisms in this model.

Age is an important factor to consider with Achilles tendon injury, as variability in tendon structure during developmental growth and aging influence lower limb function and mobility. However, the overlap in structural alterations with aging and Achilles tendon injury makes it unclear which structural changes are related to age separate from tendon pathology. The objective of this study was to determine the relationship between structure and age in healthy Achilles tendons. Healthy Achilles tendons from 389 children and adults (8–79 years) were included in this retrospective analysis. Achilles tendon morphology was assessed via B‐mode ultrasound of Achilles tendon length, cross‐sectional area (CSA), and thickness. Mechanical properties of Achilles tendon shear modulus and viscosity were assessed via continuous shear wave elastography. The relationship between Achilles tendon structure and age was determined using General Linear Models and White's test of heteroscedasticity (to assess for unequal variance across the age span), controlling for sex, weight, and physical activity level. Healthy free Achilles tendon length (p = 0.002), thickness (p < 0.001), CSA (p < 0.001), and viscosity (p = 0.009) increased with age, supporting age‐related changes in tendon structure that may limit its capacity to store and transfer energy in older adults. Full Achilles tendon length and CSA varied across the age span (p < 0.05), suggesting the Achilles tendon undergoes natural aging processes seen with most musculoskeletal tissue. Normative data on Achilles tendon structure with age will contribute to our understanding and interpretation of Achilles tendon injury pathogenesis; aiding in the design of injury prevention and treatment strategies.

Purpose: Intervertebral disc degeneration progresses with normal aging; yet common disc grading schemes do not account for age. Degeneration progression also varies between spine levels and is similarly not accounted for by current grading schemes. These limitations inhibit differentiation between discs with normal and expected aging (non-pathological) and discs with accelerated degeneration (which may be pathological). We sought to develop a statistical model to quantify normal age and spine level dependent disc degeneration. Methods: Eighty-four asymptomatic adult subjects ranging evenly from 18 to 83 years old underwent magnetic resonance imaging (MRI) of the lumbar spine. Subject traits, MRI-derived disc geometry, and MRI biomarkers of T2 relaxation time were evaluated and used to develop a statistical model to predict effective disc age, the age at which normal aging would produce a disc’s observed phenotype. Results: After evaluating several models, a 4-predictor model utilizing 1) subject height, 2) nucleus pulposus T2 relaxation time, 3) disc mid-sagittal area and 4) disc 3D volume, optimally estimated effective disc age. The effective age closely tracked true age for spine levels L1-L5 (R² ≈ 0.7, RMSE ≈ 10 years) and moderately tracked true age for L5-S1 (R² = 0.4, RMSE = 14 years). The uncertainty in the effective disc age prediction was ± 3 years as assessed by fivefold cross validation. Conclusion: We offer a data-driven, quantitative tool to quantify normal, expected intervertebral disc aging. This effective age model allows future research to target discs with accelerated degeneration.