EPIC-μCT Imaging of Articular Cartilage

Lin, Angela; Salazar-Noratto, Giuliana E.; Guldberg, Robert E.

doi:10.1007/978-1-4939-1619-1_11

Cited by 6 publications

(7 citation statements)

References 16 publications

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“…were not correlated, in agreement with a recent in vivo study which found no association between disc and facet biomechanics under diurnal loading. 39 Future studies may need to quantify whole facet cartilage volumes (using contrast enhanced µCT 40 ) to improve such correlations.…”

Section: Resultsmentioning

confidence: 99%

Level dependent alterations in human facet cartilage mechanics and bone morphometry with spine degeneration

Gupta

Xiao

Fainor

et al. 2022

Journal Orthopaedic Research

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The zygapophyseal joints of the spine, also known as the facet joints, are paired diarthrodial joints posterior to the intervertebral disc and neural elements. The pathophysiology of facet osteoarthritis (OA), as well as crosstalk between the disc and facets, remains largely understudied compared to disc degeneration. The purpose of this study was to characterize alterations to human facet cartilage and subchondral bone across a spectrum of degeneration and to investigate correlations between disc and facet degeneration. Human lumbar facet articular surfaces from six independent donors were subject to creep indentation mechanical testing to quantify cartilage mechanical properties, followed by microcomputed tomography (µCT) analyses for subchondral bone morphometry.The degenerative state of each articular surface was assessed via macroscopic scoring and via Osteoarthritis Research Society International histopathology scoring. Our data suggest reduced facet cartilage compressive and tensile moduli and increased permeability with increasing degenerative grade, particularly at the lower levels of the spine. µCT analyses revealed spinal level-dependent alterations to the subchondral bone, with an increase in trabecular bone at the L4−L5 level, but a decrease at the upper levels of the lumbar spine with increasing degenerative grade. Cortical bone volume fraction was generally decreased with increasing degenerative grade across spinal levels. Correlation analysis revealed several associations between quantitative measures of disc degeneration and facet OA. This study showed that alterations in the mechanical properties of facet cartilage and in the structural properties of facet subchondral bone correlated with aspects of disc degeneration and were highly dependent on spinal level.

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Section: Resultsmentioning

confidence: 99%

Level dependent alterations in human facet cartilage mechanics and bone morphometry with spine degeneration

Gupta

Xiao

Fainor

et al. 2022

Journal Orthopaedic Research

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“…These correlations were all relatively weak with the greatest r value being 0.41. Previous studies in rodents with cartilage that is even thinner in dogs have shown stronger correlations . There may be some degree of limitation with regard to the depth of penetration of the contrast with the thicker cartilage that is seen in dogs.…”

Section: Discussionmentioning

confidence: 90%

“…While the development of effective antemortem methods for assessing cartilage health is a priority, methods of improving post‐mortem cartilage assessments in the canine would also be beneficial to translational studies. Acquisition of biochemical data, including the proteoglycan and collagen content of cartilage, requires removal of cartilage samples . This process is destructive and inhibits histologic assessment of those same areas.…”

mentioning

confidence: 99%

“…Equilibrium partitioning of an ionic contrast agent (EPIC) via µCT is a non‐destructive method of assessing articular cartilage proteoglycan concentration post‐mortem, which allows for evaluation of all joints surfaces and does not impede subsequent histologic evaluations. Joints are incubated with a negatively charged, ionic, and iodinated contrast agent that is repelled by negatively charged proteoglycans in healthy cartilage . The amount of contrast that permeates the articular cartilage can be assessed using µCT and has been shown to provide reproducible topography of the joint surfaces and to correlate closely with biochemical analyses of proteoglycan content and histologic assessment of cartilage health in rodent and bovine tissues .…”

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confidence: 99%

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T1ρ, T2 mapping, and EPIC‐µCT Imaging in a Canine Model of Knee Osteochondral Injury

Franklin

Stoker

Lin

et al. 2019

Journal Orthopaedic Research

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The dog is the most commonly used large animal model for the study of osteoarthritis. Optimizing methods for assessing cartilage health would prove useful in reducing the number of dogs needed for a valid study of osteoarthritis and cartilage repair. Twelve beagles had critical-sized osteochondral defects created in the medial femoral condyle of both knees. Eight dogs had T1ρ and T2 magnetic resonance imaging (MRI) performed approximately 6 months after defect creation. Following MRI evaluations, all 12 dogs were humanely euthanatized and cartilage samples were obtained from the medial and lateral femoral condyles, medial and lateral tibial plateaus, trochlear groove, and patella for proteoglycan and collagen quantification. Equilibrium partitioning of an ionic contrast (EPIC)-µCT was then performed followed by the histologic assessment of the knees. Correlations between T1ρ, T2, EPIC-µCT and proteoglycan, collagen, and histology scores were assessed using a multivariate analysis accounting for correlations from samples within the same knee and in the same dog. Pearson's correlation coefficients were calculated to assess the strength of significant relationships. Correlations between µCT values and biochemical or histologic assessment were weak to moderately strong (0.09-0.41; p < 0.0001-0.66). There was a weak correlation between the T2 values and cartilage proteoglycan (−0.32; p = 0.04). The correlation between T1ρ values and cartilage proteoglycan were moderately strong (−0.38; p < 0.05) while the strongest correlation was between the T1ρ values and histological assessment of cartilage with a correlation coefficient of 0.58 (p < 0.0001). These data suggest that T1ρ shows promise for possible utility in the translational study of cartilage health and warrants further development in this species.

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“…Images regionally evaluated in the medial third of the medial tibial plateau ( Figure 1A ). Direct distance transformation algorithms were used to quantify 3D cartilage thickness measures ( Xie et al, 2009 ; Hildebrand and Rüegsegger, 1997 ; Laib et al, 2000 ; Lin et al, 2015 ). Consistent volumes of cartilaginous tissue excluding margins were annotated for evaluation based on image processing standards previously established ( Reece et al, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Intra-articular delivery of micronized dehydrated human amnion/chorion membrane reduces degenerative changes after onset of post-traumatic osteoarthritis

Lin,

Reece,

Thote

et al. 2023

Front. Bioeng. Biotechnol.

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Background: Micronized dehydrated human amnion/chorion membrane (mdHACM) has reduced short term post-traumatic osteoarthritis (PTOA) progression in rats when delivered 24 h after medial meniscal transection (MMT) and is being investigated for clinical use as a disease modifying therapy. Much remains to be assessed, including its potential for longer-term therapeutic benefit and treatment effects after onset of joint degeneration.Objectives: Characterize longer-term effects of acute treatment with mdHACM and determine whether treatment administered to joints with established PTOA could slow or reverse degeneration. Hypotheses: Acute treatment effects will be sustained for 6 weeks, and delivery of mdHACM after onset of joint degeneration will attenuate structural osteoarthritic changes.Methods: Rats underwent MMT or sham surgery (left leg). mdHACM was delivered intra-articularly 24 h or 3 weeks post-surgery (n = 5–7 per group). Six weeks post-surgery, animals were euthanized and left tibiae scanned using equilibrium partitioning of an ionic contrast agent microcomputed tomography (EPIC-µCT) to structurally quantify joint degeneration. Histology was performed to examine tibial plateau cartilage.Results: Quantitative 3D µCT showed that cartilage structural metrics (thickness, X-ray attenuation, surface roughness, exposed bone area) for delayed mdHACM treatment limbs were significantly improved over saline treatment and not significantly different from shams. Subchondral bone mineral density and thickness for the delayed treatment group were significantly improved over acute treated, and subchondral bone thickness was not significantly different from sham. Marginal osteophyte degenerative changes were decreased with delayed mdHACM treatment compared to saline. Acute treatment (24 h post-surgery) did not reduce longer-term joint tissue degeneration compared to saline. Histology supported µCT findings and further revealed that while delayed treatment reduced cartilage damage, chondrocytes displayed qualitatively different morphologies and density compared to sham.Conclusion: This study provides insight into effects of intra-articular delivery timing relative to PTOA progression and the duration of therapeutic benefit of mdHACM. Results suggest that mdHACM injection into already osteoarthritic joints can improve joint health, but a single, acute mdHACM injection post-injury does not prevent long term osteoarthritis associated with meniscal instability. Further work is needed to fully characterize the durability of therapeutic benefit in stable osteoarthritic joints and the effects of repeated injections.

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EPIC-μCT Imaging of Articular Cartilage

Cited by 6 publications

References 16 publications

Level dependent alterations in human facet cartilage mechanics and bone morphometry with spine degeneration

Level dependent alterations in human facet cartilage mechanics and bone morphometry with spine degeneration

T1ρ, T2 mapping, and EPIC‐µCT Imaging in a Canine Model of Knee Osteochondral Injury

Intra-articular delivery of micronized dehydrated human amnion/chorion membrane reduces degenerative changes after onset of post-traumatic osteoarthritis

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