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Background: Quantitative techniques such as T2 and T1ρ mapping allow evaluating the cartilage and meniscus. We evaluated multi-interleaved X-prepared turbo-spin echo with intuitive relaxometry (MIXTURE) sequences with turbo spin-echo (TSE) contrast and additional parameter maps versus reference TSE sequences in an in situ model of human cartilage defects., Methods: Standardized cartilage defects of 8, 5, and 3 mm in diameter were created in the lateral femora of ten human cadaveric knee specimens (81 ± 10 years old; nine males, one female). MIXTURE sequences providing proton density-weighted fat-saturated images and T2 maps or T1-weighted images and T1ρ maps as well as the corresponding two- and three-dimensional TSE reference sequences were acquired before and after defect creation (3-T scanner; knee coil). Defect delineability, bone texture, and cartilage relaxation times were quantified. Appropriate parametric or non-parametric tests were used., Results: Overall, defect delineability and texture features were not significantly different between the MIXTURE and reference sequences (p ≤ 0.47). After defect creation, relaxation times significantly increased in the central femur (T2 pre = 51 ± 4 ms [mean ± standard deviation] versus T2 post = 56 ± 4 ms; p = 0.002) and all regions combined (T1ρ pre = 40 ± 4 ms versus T1ρ post = 43 ± 4 ms; p = 0.004)., Conclusions: MIXTURE permitted time-efficient simultaneous morphologic and quantitative joint assessment based on clinical image contrasts. While providing T2 or T1ρ maps in clinically feasible scan time, morphologic image features, i.e., cartilage defects and bone texture, were comparable between MIXTURE and reference sequences., Relevance Statement: Equally time-efficient and versatile, the MIXTURE sequence platform combines morphologic imaging using familiar contrasts, excellent image correspondence versus corresponding reference sequences and quantitative mapping information, thereby increasing the diagnostic value beyond mere morphology., Key Points: • Combined morphologic and quantitative MIXTURE sequences are based on three-dimensional TSE contrasts. • MIXTURE sequences were studied in an in situ human cartilage defect model. • Morphologic image features, i.e., defect delineabilty and bone texture, were investigated. • Morphologic image features were similar between MIXTURE and reference sequences. • MIXTURE allowed time-efficient simultaneous morphologic and quantitative knee joint assessment., (© 2024. The Author(s).)

Magnetic resonance imaging (MRI) is commonly used to assess traumatic and non-traumatic conditions of the knee. Due to its complex and variable anatomy, the posterolateral corner (PLC)-often referred to as the joint's dark side-remains diagnostically challenging. We aimed to render the diagnostic evaluation of the PLC more functional by combining MRI, varus loading, and image post-processing in a model of graded PLC injury that used sequential transections of the lateral collateral ligament, popliteus tendon, popliteofibular ligament, and anterior cruciate ligament. Ten human cadaveric knee joint specimens underwent imaging in each condition as above, and both unloaded and loaded using an MR-compatible device that standardized loading (of 147 N) and position (at 30° flexion). Following manual segmentation, 3D joint models were used to computationally measure lateral joint space opening for each specimen, configuration, and condition, while manual measurements provided the reference standard. With more extensive ligament deficiency and loading, lateral joint spaces increased significantly. In conclusion, varus stress MRI allows comprehensive PLC evaluation concerning structural integrity and associated functional capacity. Beyond providing normative values of lateral compartment opening, this study has potential implications for diagnostic and surgical decision-making and treatment monitoring in PLC injuries., (© 2022. The Author(s).)

Magnetic resonance imaging (MRI) under mechanical loading, commonly referred to as stress MRI, allows the evaluation of functional properties of intra- and periarticular tissues non-invasively beyond static assessment. Quantitative MRI can identify physiological and pathological responses to loading as indication of, potentially treatable, early degeneration and load transmission failure. Therefore, we have developed and validated an MRI-compatible pressure-controlled axial loading device to compress human knee specimens under variable loading intensity and axis deviation. Ten structurally intact human knee specimens (mean age 83.2 years) were studied on a 3.0T scanner (Achieva, Philips). Proton density-weighted fat-saturated turbo spin-echo and high-resolution 3D water selective 3D gradient-echo MRI scans were acquired sequentially at 10° joint flexion in seven configurations: unloaded and then at approximately half and full body weight loading in neutral, 10° varus and 10° valgus alignment, respectively. Following manual segmentation in both femorotibial compartments, cartilage thickness (ThC) was determined as well as meniscus extrusion (ExM). These measures were compared to computed tomography scans, histological grading (Mankin and Pauli scores), and biomechanical properties (Instantaneous Young's Modulus). Compartmental, regional and subregional changes in ThC and ExM were reflective of loading intensity and joint alignment, with the greatest changes observed in the medial compartment during varus and in the lateral compartment during valgus loading. These were not significantly associated with the histological tissue status or biomechanical properties. In conclusion, this study explores the physiological in-situ response of knee cartilage and meniscus, based on stress MRI, and as a function of loading intensity, joint alignment, histological tissue status, and biomechanical properties, as another step towards clinical implementation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Water, collagen, and proteoglycans determine articular cartilage functionality. If altered, susceptibility to premature degeneration is increased. This study investigated the effects of enzymatic proteoglycan depletion on cartilage functionality as assessed by advanced Magnetic Resonance Imaging (MRI) techniques under standardized loading. Lateral femoral condylar cartilage-bone samples from patients undergoing knee replacement (n = 29) were serially imaged by Proton Density-weighted and T1, T1ρ, T2, and T2* mapping sequences on a clinical 3.0 T MRI scanner (Achieva, Philips). Using pressure-controlled indentation loading, samples were imaged unloaded and quasi-statically loaded to 15.1 N and 28.6 N, and both before and after exposure to low-concentrated (LT, 0.1 mg/mL, n = 10) or high-concentrated trypsin (HT, 1.0 mg/mL, n = 10). Controls were not treated (n = 9). Responses to loading were assessed for the entire sample and regionally, i.e. sub- and peri-pistonally, and zonally, i.e. upper and lower sample halves. Trypsin effects were quantified as relative changes (Δ), analysed using appropriate statistical tests, and referenced histologically. Histological proteoglycan depletion was reflected by significant sub-pistonal decreases in T1 (p = 0.003) and T2 (p = 0.008) after HT exposure. Loading-induced changes in T1ρ and T2* were not related. In conclusion, proteoglycan depletion alters cartilage functionality and may be assessed using serial T1 and T2 mapping under loading.

Objective: To evaluate whether the response to loading of cartilage samples as assessed ex vivo by quantitative MRI (qMRI) mapping techniques can differentiate intact and early degenerative cartilage., Methods: Upon IRB approval and written informed consent, 59 macroscopically intact osteochondral samples were obtained from the central lateral femoral condyles of patients undergoing total knee replacement. Spatially resolved T1, T2, T2*, and T1ρ maps were generated prior to and during displacement-controlled quasi-static indentation loading to 405 μm (Δ 1/2 ) and 810 μm (Δ 1 ). Upon manual segmentation, absolute qMRI parameters and loading-induced relative changes (δ 1/2 , δ 1 ) were determined for the entire cartilage sample and distinct zones and regions. Based on their histologically determined degeneration as quantified according to Mankin (Mankin sum scores [MSS], range 0-14), samples were dichotomised into intact (int; MSS 0-4, n = 35) and early degenerative (ed, MSS 5-8, n = 24)., Results: For T1ρ, consistent loading-induced increases were found for δ 1/2 and δ 1 . Throughout the entire sample, increases in T1ρ were significantly higher in early degenerative than in intact samples (Δ 1/2 (ed) = 23.8 [q 25  = 18.1, q 75  = 29.0] %; Δ 1/2 (int) = 12.7 [q 25  = 5.9, q 75  = 19.5] %; p < 0.0005), according to Wilcoxon's signed-rank test). Zonal and regional analysis revealed these changes to be most pronounced in the sub-pistonal area. No significant degeneration-dependent loading-induced changes were found for T1, T2, or T2*., Conclusion: Aberrant load-bearing of early degenerative cartilage may be detected using T1ρ mapping as a function of loading. Hence, the diagnostic differentiation of intact versus early degenerative cartilage may allow the reliable identification of early and potentially reversible cartilage degeneration, thereby opening new opportunities for diagnosis and treatment of cartilage pathologies., Key Points: • T1ρ mapping of the cartilage response to loading allows the reliable identification of early degenerative changes ex vivo. • Distinct response-to-loading patterns of cartilage tissue as assessed by functional MRI techniques are associated with biomechanical and histological tissue properties. • Non-invasive functional MR imaging techniques may facilitate the more sensitive monitoring of therapeutic outcomes and treatment strategies.

Objective: To investigate changes in response to sequential pressure-controlled loading and unloading in human articular cartilage of variable histological degeneration using serial T1ρ mapping., Method: We obtained 42 cartilage samples of variable degeneration from the medial femoral condyles of 42 patients undergoing total knee replacement. Samples were placed in a standardized artificial knee joint within an MRI-compatible whole knee-joint compressive loading device and imaged before (δ 0 ), during (δ ld1 , δ ld2 , δ ld3 , δ ld4 , δ ld5 ) and after (δ rl1 , δ rl2 , δ rl3 , δ rl4 , δ rl5 ) pressure-controlled loading to 0.663 ± 0.021 kN (94% body weight) using serial T1ρ mapping (spin-lock multigradient echo sequence; 3.0T MRI system [Achieva, Philips]). Reference assessment included histology (Mankin scoring) and conventional biomechanics (Tangent stiffness). We dichotomized sample into intact (n = 21) and degenerative (n = 21) based on histology and analyzed data using Mann Whitney, Kruskal Wallis, one-way ANOVA tests and Spearman's correlation, respectively., Results: At δ 0 , we found no significant differences between intact and degenerative samples, while the response-to-loading patterns were distinctly different. In intact samples, T1ρ increases were consistent and non-significant, while in degenerative samples, T1ρ increases were significantly higher (P = 0.004, δ0 vs δld1, δ0 vs δld3), yet undulating and variable. With unloading, T1ρ increases subsided, yet were persistently elevated beyond δ0., Conclusion: Cartilage mechanosensitivity is related to histological degeneration and assessable by serial T1ρ mapping. Unloaded, T1ρ characteristics are not significantly different in intact vs degenerative cartilage, while load bearing is organized in intact cartilage and disorganized in degenerative cartilage., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

To assess human articular cartilage tissue functionality by serial multiparametric quantitative MRI (qMRI) mapping as a function of histological degeneration. Forty-nine cartilage samples obtained during total knee replacement surgeries were placed in a standardized artificial knee joint within an MRI-compatible compressive loading device and imaged in situ and at three loading positions, i.e. unloaded, at 2.5 mm displacement (20% body weight [BW]) and at 5 mm displacement (110% BW). Using a clinical 3.0 T MRI system (Achieva, Philips), serial T1, T1ρ, T2 and T2* maps were generated for each sample and loading position. Histology (Mankin scoring) and biomechanics (Young's modulus) served as references. Samples were dichotomized as intact (int, n = 27) or early degenerative (deg, n = 22) based on histology and analyzed using repeated-measures ANOVA and unpaired Student's t-tests after log-transformation. For T1ρ, T2 and T2*, significant loading-induced differences were found in deg (in contrast to int) samples, while for T1 significant decreases in all zones were observed, irrespective of degeneration. In conclusion, cartilage functionality may be visualized using serial qMRI parameter mapping and the response-to-loading patterns are associated with histological degeneration. Hence, loading-induced changes in qMRI parameter maps provide promising surrogate parameters of tissue functionality and status in health and disease.

Objective: To define the physiological response to sequential loading and unloading in histologically intact human articular cartilage using serial T1ρ mapping, as T1ρ is considered to indicate the tissue's macromolecular content., Method: 18 macroscopically intact cartilage-bone samples were obtained from the central lateral femoral condyles of 18 patients undergoing total knee replacement. Serial T1ρ mapping was performed on a clinical 3.0-T MRI system using a modified prostate coil. Spin-lock multiple gradient-echo sequences prior to, during and after standardized indentation loading (displacement controlled, strain 20%) were used to obtain seven serial T1ρ maps: unloaded (δ 0 ), quasi-statically loaded (indentation 1 -indentation 3 ) and under subsequent relaxation (relaxation 1 -relaxation 3 ). After manual segmentation, zonal and regional regions-of-interest were defined. ROI-specific relative changes were calculated and statistically assessed using paired t-tests. Histological (Mankin classification) and biomechanical (unconfined compression) evaluations served as references., Results: All samples were histologically and biomechanically grossly intact (Mankin sum: 1.8 ± 1.2; Young's Modulus: 0.7 ± 0.4 MPa). Upon loading, T1ρ consistently increased throughout the entire sample thickness, primarily subpistonally (indentation 1 [M ± SD]: 9.5 ± 7.8% [sub-pistonal area, SPA] vs 4.2 ± 5.8% [peri-pistonal area, PPA]; P < 0.001). T1ρ further increased with ongoing loading (indentation 3 : 14.1 ± 8.1 [SPA] vs 7.7 ± 5.9% [PPA]; P < 0.001). Even upon unloading (i.e., relaxation), T1ρ persistently increased in time., Conclusion: Serial T1ρ-mapping reveals distinct and complex zonal and regional changes in articular cartilage as a function of loading and unloading. Thereby, longitudinal adaptive processes in hyaline cartilage become evident, which may be used for the tissue's non-invasive functional characterization by T1ρ., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

The response to loading of human articular cartilage as assessed by magnetic resonance imaging (MRI) remains to be defined in relation to histology and biomechanics. Therefore, an MRI-compatible whole-knee joint loading device for the functional in situ assessment of cartilage was developed and validated in this study. A formalin-fixed human knee was scanned by computed tomography in its native configuration and digitally processed to create femoral and tibial bone models. The bone models were covered by artificial femoral and tibial articular cartilage layers in their native configuration using cartilage-mimicking polyvinyl siloxane. A standardized defect of 8 mm diameter was created within the artificial cartilage layer at the central medial femoral condyle, into which native cartilage samples of similar dimensions were placed. After describing its design and specifications, the comprehensive validation of the device was performed using a hydraulic force gauge and digital electronic pressure-sensitive sensors. Displacement-controlled quasi-static uniaxial loading to 2.5 mm [Formula: see text] and 5.0 mm [Formula: see text] of the mobile tibia versus the immobile femur resulted in forces of [Formula: see text] N [Formula: see text] and [Formula: see text] N [Formula: see text] (on the entire joint) and local pressures of [Formula: see text] MPa [Formula: see text] and [Formula: see text] MPa [Formula: see text] (at the site of the cartilage sample). Upon confirming the MRI compatibility of the set-up, the response to loading of macroscopically intact human articular cartilage samples ([Formula: see text]) was assessed on a clinical 3.0-T MR imaging system using clinical standard proton-density turbo-spin echo sequences and T2-weighted multi-spin echo sequences. Serial imaging was performed at the unloaded state [Formula: see text] and at consecutive loading positions (i.e. at [Formula: see text] and [Formula: see text]. Biomechanical unconfined compression testing (Young's modulus) and histological assessment (Mankin score) served as the standards of reference. All samples were histologically intact (Mankin score, [Formula: see text]) and biomechanically reasonably homogeneous (Young's modulus, [Formula: see text] MPa). They could be visualized in their entirety by MRI and significant decreases in sample height [[Formula: see text]: [Formula: see text] mm; [Formula: see text]: [Formula: see text] mm; [Formula: see text]: [Formula: see text] mm; [Formula: see text] (repeated-measures ANOVA)] as well as pronounced T2 signal decay indicative of tissue pressurization were found as a function of compressive loading. In conclusion, our compression device has been validated for the noninvasive response-to-loading assessment of human articular cartilage by MRI in a close-to-physiological experimental setting. Thus, in a basic research context cartilage may be functionally evaluated beyond mere static analysis and in reference to histology and biomechanics.

Objective: To evaluate the usefulness of quantitative parameters obtained by optical coherence tomography (OCT) and magnetic resonance imaging (MRI) in the comprehensive assessment of human articular cartilage degeneration., Materials and Methods: Human osteochondral samples of variable degeneration (n = 45) were obtained from total knee replacements and assessed by MRI sequences measuring T1, T1ρ, T2 and T2* relaxivity and by OCT-based quantification of irregularity (OII, optical irregularity index), homogeneity (OHI, optical homogeneity index]) and attenuation (OAI, optical attenuation index]). Samples were also assessed macroscopically (Outerbridge classification) and histologically (Mankin classification) as grade-0 (Mankin scores 0-4)/grade-I (scores 5-8)/grade-II (scores 9-10)/grade-III (score 11-14). After data normalisation, differences between Mankin grades and correlations between imaging parameters were assessed using ANOVA and Tukey's post-hoc test and Spearman's correlation coefficients, respectively. Sensitivities and specificities in the detection of Mankin grade-0 were calculated., Results: Significant degeneration-related increases were found for T2 and OII and decreases for OAI, while T1, T1ρ, T2* or OHI did not reveal significant changes in relation to degeneration. A number of significant correlations between imaging parameters and histological (sub)scores were found, in particular for T2 and OII. Sensitivities and specificities in the detection of Mankin grade-0 were highest for OHI/T1 and OII/T1ρ, respectively., Conclusion: Quantitative OCT and MRI techniques seem to complement each other in the comprehensive assessment of cartilage degeneration. Sufficiently large structural and compositional changes in the extracellular matrix may thus be parameterized and quantified, while the detection of early degeneration remains challenging.