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Meniscal lesions in vascularized regions are known to regenerate while lack of vascular supply leads to poor healing. Here, we developed and validated a novel methodology for three‐dimensional structural analysis of meniscal vascular structures with high‐resolution microcomputed tomography (µCT). We collected porcine medial menisci from 10 neonatal (not‐developed meniscus, n‐) and 10 adults (fully developed meniscus, a‐). The menisci were cut into anatomical regions (anterior horn (n‐AH and a‐AH), central body (n‐CB and a‐CB), and posterior horn (n‐PH and a‐PH). Specimens were cut in half, fixed, and one specimen underwent critical point drying and µCT imaging, while other specimen underwent immunohistochemistry and vascularity biomarker CD31 staining for validation of µCT. Parameters describing vascular structures were calculated from µCT. The vascular network in neonatal spread throughout meniscus, while in adult was limited to a few vessels in outer region, mostly on femoral side. n‐AH, n‐CB, and n‐PH had 20, 17, and 11 times greater vascular volume fraction than adult, respectively. Moreover, thickness of blood vessels, in three regions, was six times higher in adults than in neonatal. a‐PH appeared to have higher vascular fraction, longer and thicker blood vessels than both a‐AH and a‐CB. Overall, neonatal regions had a higher number of blood vessels, more branching, and higher tortuosity compared to adult regions. For the first time, critical point drying‐based µCT imaging allowed detailed three‐dimensional visualization and quantitative analysis of vascularized meniscal structures. We showed more vascularity in neonatal menisci, while adult menisci had fewer and thicker vascularity especially limited to the femoral surface. [ABSTRACT FROM AUTHOR]

In this study, we investigated the discriminative capacity of knee morphology in automatic detection of osteophytes defined by the Osteoarthritis Research Society International atlas, using X‐ray and magnetic resonance imaging (MRI) data. For the X‐ray analysis, we developed a deep learning (DL) based model to segment femur and tibia. In case of MRIs, we utilized previously validated segmentations of femur, tibia, corresponding cartilage tissues, and menisci. Osteophyte detection was performed using DL models in four compartments: medial femur (FM), lateral femur (FL), medial tibia (TM), and lateral tibia (TL). To analyze the confounding effects of soft tissues, we investigated their morphology in combination with bones, including bones+cartilage, bones+menisci, and all the tissues. From X‐ray‐based 2D morphology, the models yielded balanced accuracy of 0.73, 0.69, 0.74, and 0.74 for FM, FL, TM, TL, respectively. Using 3D bone morphology from MRI, balanced accuracy was 0.80, 0.77, 0.71, and 0.76, respectively. The performance was higher than in 2D for all the compartments except for TM, with significant improvements observed for femoral compartments. Adding menisci or cartilage morphology consistently improved balanced accuracy in TM, with the greatest improvement seen for small osteophyte. Otherwise, the models performed similarly to bones‐only. Our experiments demonstrated that MRI‐based models show higher detection capability than X‐ray based models for identifying knee osteophytes. This study highlighted the feasibility of automated osteophyte detection from X‐ray and MRI data and suggested further need for development of osteophyte assessment criteria in addition to OARSI, particularly, for early osteophytic changes. [ABSTRACT FROM AUTHOR]

Objective: Mandibular condylar cartilage (MCC) of the rat was examined with the Fourier‐transform infrared (FITR) spectroscopic imaging to study the effects of ageing, oestrogen level and altered dietary loading on the structure of MCC. Materials and Methods: The Sprague–Dawley rats (n = 96) aged 5 and 14 months were divided into 12 subgroups according to age, oestrogen status (ovariectomized [OVX], non‐ovariectomized [non‐OVX)]) and diet (hard, normal, soft). Specimens of the MCC were examined with FTIR spectroscopic imaging to quantify the distribution of collagens and proteoglycans. MCC was divided sagittally into three segments: anterior, most superior and posterior. From each segment, the collagen and proteoglycan contents at different depths of cartilage were statistically compared between the groups using an N‐way analysis of variance (ANOVA). Results: The amount of collagen content was significantly associated with old age in the deep layer of the anterior segment and in the middle layer of the posterior segment of MCC. In the deep layer of the most superior segment, the collagen content also increased with ageing. The amount of proteoglycan content increased significantly when dietary loading increased, and the oestrogen level decreased in the deep layer of the most superior segment of MCC. Conclusion: Ageing, oestrogen level and altered dietary loading have a significant effect on the location and content of collagens and proteoglycans of rat MCC. Ageing significantly increased the amount of collagen content in the superior and posterior segments, being highest in the older soft‐diet rats. Decreased oestrogen levels and increased dietary loading increased the amount of proteoglycan content. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state‐of‐the‐art microfocus small‐angle X‐ray scattering with a 5‐μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well‐defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading‐related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Morphological changes in knee cartilage subregions are valuable imaging‐based biomarkers for understanding progression of osteoarthritis, and they are typically detected from magnetic resonance imaging (MRI). So far, accurate segmentation of cartilage has been done manually. Deep learning approaches show high promise in automating the task; however, they lack clinically relevant evaluation. We introduce a fully automatic method for segmentation and subregional assessment of articular cartilage, and evaluate its predictive power in context of radiographic osteoarthritis progression. Two data sets of 3D double‐echo steady‐state (DESS) MRI derived from the Osteoarthritis Initiative were used: first, n = 88; second, n = 600, 0‐/12‐/24‐month visits. Our method performed deep learning‐based segmentation of knee cartilage tissues, their subregional division via multi‐atlas registration, and extraction of subregional volume and thickness. The segmentation model was developed and assessed on the first data set. Subsequently, on the second data set, the morphological measurements from our and the prior methods were analyzed in correlation and agreement, and, eventually, by their discriminative power of radiographic osteoarthritis progression over 12 and 24 months, retrospectively. The segmentation model showed very high correlation (r > 0.934) and agreement (mean difference < 116 mm3) in volumetric measurements with the reference segmentations. Comparison of our and manual segmentation methods yielded r = 0.845–0.973 and mean differences = 262–501 mm3 for weight‐bearing cartilage volume, and r = 0.770–0.962 and mean differences = 0.513–1.138 mm for subregional cartilage thickness. With regard to osteoarthritis progression, our method found most of the significant associations identified using the manual segmentation method, for both 12‐ and 24‐month subregional cartilage changes. The method may be effectively applied in osteoarthritis progression studies to extract cartilage‐related imaging biomarkers. [ABSTRACT FROM AUTHOR]

Objectives: To determine the diagnostic performance of ultrasonography (US) for evaluation of the ankle joint osteoarthritic (OA) changes. Cone‐beam computed tomography (CT) was used as the gold standard and US performance was compared with conventional radiography (CR). As a secondary aim, associations between the imaging findings and ankle symptoms were assessed. Methods: US was performed to 51 patients with ankle OA. Every patient had prior ankle CR and underwent cone‐beam CT during the same day as US examination. On US, effusion/synovitis, osteophytes, talar cartilage damage, and tenosynovitis were evaluated. Comparison to respective imaging findings on CR and cone‐beam CT was then performed. Single radiologist blinded to other modalities assessed all the imaging studies. Symptoms questionnaire, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), was available for 48 patients. Results: US detected effusion/synovitis of the talocrural joint with 45% sensitivity and 90% specificity. For the detection of anterior talocrural osteophytes, US sensitivity was 78% and specificity 79%. For the medial talocrural osteophytes, they were 39 and 83%, and for the lateral talocrural osteophytes 54 and 100%, respectively. Considering cartilage damage of the talus, US yielded a low sensitivity of 18% and high specificity of 97%. Overall, the performance of US was only moderate and comparable to CR. The imaging findings showed only weak associations with ankle symptoms. Conclusions: The ability of US to detect ankle OA is only moderate. Interestingly, performance of CR also remained moderate. The associations between imaging findings and WOMAC score seem to be weak in ankle OA. [ABSTRACT FROM AUTHOR]

Concurrent osteoarthritic (OA) manifestations in bone and cartilage are poorly known. To shed light on this issue, this study aims to investigate changes in subchondral bone and articular cartilage at two time points after anterior cruciate ligament transection (ACLT) in a rabbit model. 2 (N = 16) and 8 (N = 10) weeks after ACLT, the subchondral bone structure, cartilage thickness, Osteoarthritis Research Society International (OARSI) score, fixed charged density (FCD), and collagen orientation angle were analyzed. OA related changes were evaluated by comparing the ACLT to the contralateral (C‐L) and control knees. Already 2 weeks after ACLT, higher trabecular number in the medial femoral condyle and femoral groove, greater OARSI score in the femoral condyles, and thinner trabeculae in the lateral tibial plateau and femoral groove were observed in ACLT compared to C‐L knees. Only minor changes of cartilage collagen orientation in the femoral condyles and femoral groove and smaller FCD in the femoral condyles, medial tibial plateau, femoral groove and patella were observed. 8 weeks post‐ACLT, the surgical knees had thinner subchondral plate and trabeculae, and smaller trabecular bone volume fraction in most of the knee locations. OARSI score was greater in the femoral condyle and lateral tibial plateau cartilage. FCD loss was progressive only in the femoral condyle, femoral groove, and patellar cartilage, and minor changes of cartilage collagen orientation angle were present in the femoral condyles, femoral groove, and lateral tibial plateau. We conclude that ACLT induces progressive subchondral bone loss, during which proteoglycan loss occurs followed by their partly recovery, as indicated by FCD results. [ABSTRACT FROM AUTHOR]

Structural dynamics of calcified cartilage (CC) are poorly understood. Conventionally, CC structure is analyzed using histological sections. Micro‐computed tomography (µCT) allows for three‐dimensional (3D) imaging of mineralized tissues; however, the segmentation between bone and mineralized cartilage is challenging. Here, we present state‐of‐the‐art deep learning segmentation for µCT images to assess 3D CC morphology. The sample includes 16 knees from 12 New Zealand White rabbits dissected into osteochondral samples from six anatomical regions: lateral and medial femoral condyles, lateral and medial tibial plateaus, femoral groove, and patella (n = 96). The samples were imaged with µCT and processed for conventional histology. Manually segmented CC from the images was used to train segmentation models with different encoder–decoder architectures. The models with the greatest out‐of‐fold evaluation Dice score were selected. CC thickness was compared across 24 regions, co‐registered between the imaging modalities using Pearson correlation and Bland–Altman analyses. Finally, the anatomical CC thickness variation was assessed via a Linear Mixed Model analysis. The best segmentation models yielded average Dice of 0.891 and 0.807 for histology and µCT segmentation, respectively. The correlation between the co‐registered regions was strong (r = 0.897, bias = 21.9 µm, standard deviation = 21.5 µm). Finally, both methods could separate the CC thickness between the patella, femoral, and tibial regions (p < 0.001). As a conclusion, the proposed µCT analysis allows for ex vivo 3D assessment of CC morphology. We demonstrated the biomedical relevance of the method by quantifying CC thickness in different anatomical regions with a varying mean thickness. CC was thickest in the patella and thinnest in the tibial plateau. Our method is relatively straightforward to implement into standard µCT analysis pipelines, allowing the analysis of CC morphology. In future research, µCT imaging might be preferable to histology, especially when analyzing dynamic changes in cartilage mineralization. It could also provide further understanding of 3D morphological changes that may occur in mineralized cartilage, such as thickening of the subchondral plate in osteoarthritis and other joint diseases. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is promising in vivo tool in various biomedical applications; moreover, in recent years, its use for characterizing articular cartilage degeneration has been developing. It has also shown potential for scoring the severity of cartilage lesions, which could be useful in determining the optimal treatment strategy during cartilage repair surgery. However, the effect of different cartilage injury types on Raman spectra is unknown. This study aims to investigate the potential of Raman spectroscopy for detecting changes in cartilage due to different injury types. Artificial injuries were induced in cartilage samples using established mechanical and enzymatic approaches to mimic trauma‐induced and natural degeneration. Mechanical damage was induced using surface abrasion (ABR, n = 12) or impact loading (IMP, n = 12), while enzymatic damage was induced using three different treatments: 30 min trypsin digestion (T30, n = 12), 90 min collagenase digestion (C90, n = 12), and 24 h collagenase digestion (C24, n = 12). Raman spectra were obtained from all specimens, and partial least squares discriminant analysis (PLS‐DA) was used to distinguish cartilage injury types from their respective controls. PLS‐DA cross‐validation accuracies were higher for C24 (88%) and IMP (79%) than for C90 (67%), T30 (63%), and ABR (58%) groups. This study indicates that Raman spectroscopy, combined with multivariate analysis, can discern different cartilage injury types. This knowledge could be useful in clinical decision‐making, for example, selecting the optimal treatment remedy during cartilage repair surgery. [ABSTRACT FROM AUTHOR]

In this study, we aimed to precisely localize the hyperintense signal that is generated at the osteochondral junction when using ultrashort echo time magnetic resonance imaging (MRI) and to investigate the osteochondral junction using sweep imaging with Fourier transformation (SWIFT) MRI. Furthermore, we seek to evaluate what compositional properties of the osteochondral junction are the sources of this signal. In the study, we obtained eight samples from a tibial plateau dissected from a 68‐year‐old male donor, and one additional osteochondral sample of bovine origin. The samples were imaged using high‐resolution ultrashort echo time SWIFT MRI and microcomputed tomography (μCT) scans. Localization of the bright signal in the osteochondral junction was performed using coregistered data sets. Potential sources of the signal feature were examined by imaging the bovine specimen with variable receiver bandwidths and by performing variable flip angle T1 relaxation time mapping. The results of the study showed that the hyperintense signal was found to be located entirely in the deep noncalcified articular cartilage. The intensity of this signal at the interface varied between the specimens. Further tests with bovine specimens indicated that the imaging bandwidth and T1 relaxation affect the properties of the signal. Based on the present results, the calcified cartilage has low signal intensity even in SWIFT imaging. Concomitantly, it appears that the bright signal seen in ultrashort echo time imaging resides within the noncalcified cartilage. Furthermore, the most likely sources of this signal are the rapid T1 relaxation of the deep cartilage and the susceptibility‐induced effects arising from the calcified tissues. [ABSTRACT FROM AUTHOR]

In this study, the rabbit model with anterior cruciate ligament transection (ACLT) was used to investigate early degenerative changes in cartilage using multiparametric quantitative magnetic resonance imaging (qMRI). ACLT was surgically induced in the knees of skeletally mature New Zealand White rabbits (n = 14). ACL transected and contralateral knee compartments—medial femur, lateral femur, medial tibia, and lateral tibia—were harvested 2 (n = 8) and 8 weeks (n = 6) postsurgery. Twelve age‐matched nonoperated rabbits served as control. qMRI was conducted at 9.4 T and included relaxation times T1, T2, continuous‐wave T1ρ (CWT1ρ), adiabatic T1ρ (AdT1ρ), adiabatic T2ρ (AdT2ρ), and relaxation along a fictitious field (TRAFF). For reference, quantitative histology and biomechanical measurements were carried out. Posttraumatic changes were primarily noted in the superficial half of the cartilage. Prolonged T1, T2, CWT1ρ, and AdT1ρ were observed in the lateral femur 2 and 8 weeks post‐ACLT, compared with the corresponding control and contralateral groups (P <.05). Collagen orientation was significantly altered in the lateral femur at 2 weeks post‐ACLT compared with the corresponding control group. In the medial femur, all the studied relaxation time parameters, except TRAFF, were increased 8 weeks post‐ACLT, as compared with the corresponding contralateral and control groups (P <.05). Similarly, significant proteoglycan loss was observed in the medial femur at 8 weeks following surgery (P <.05). Multiparametric MRI demonstrated early degenerative changes primarily in the superficial cartilage with T1, T2, CWT1ρ, and AdT1ρ sensitive to cartilage changes at 2 weeks after surgery. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether ultrasonographic (US) findings associate with clinical findings in severe knee osteoarthritis (OA). Association of US findings with side-of-knee pain and inter-reader agreement of knee US were also evaluated.Methods: One-hundred-two patients (in total 123 knees) with severe knee OA were recruited for this cross-sectional study. US was performed by a single observer, and on 53 knees by two independent observers to assess inter-reader reliability. Preoperative clinical data was available for 69 knees. Cutoff values were applied to dichotomize US and clinical findings. The Chi-square test, Mann-Whitney test, and prevalence- and bias-adjusted kappa (PABAK) were applied for statistical analyses.Results: Seven of 99 associations tested were statistically significant. Associations were observed between range of flexion and lateral femoral (P = .009) and tibial (P = .001) osteophytes, mediolateral instability and damage to the lateral femoral cartilage (P = .014) and damage to the lateral meniscus (P = .031), and alignment and damage to the lateral femoral cartilage (P < .001), lateral tibial osteophytes (P = .037), and damage to the lateral meniscus (P < .001). A strong association was observed between medial-sided pain and same-sided cartilage damage and osteophytes (P < .001). That inter-reader agreement was excellent on the medial side of the knee joint (PABAK = 0.811-0.887).Conclusions: US findings show a rather poor association with clinical OA findings. Inter-reader agreement of knee US is excellent on the medial side. [ABSTRACT FROM AUTHOR]

One of the earliest changes in osteoarthritis (OA) is a surface discontinuity of the articular cartilage (AC), and these surface changes become gradually more complex with OA progression. We recently developed a contrast enhanced micro‐computed tomography (μCT) method for visualizing AC surface in detail. The present study aims to introduce a μCT analysis technique to parameterize these complex AC surface features and to demonstrate the feasibility of using these parameters to quantify degenerated AC surface. Osteochondral plugs (n = 35) extracted from 19 patients undergoing joint surgery were stained with phosphotungstic acid and imaged using μCT. The surface micro‐topography of AC was analyzed with developed method. Standard root mean square roughness (Rq) was calculated as a reference, and the Area Under Curve (AUC) for receiver operating characteristic analysis was used to compare the acquired quantitative parameters with semi‐quantitative visual grading of μCT image stacks. The parameters quantifying the complex micro‐topography of AC surface exhibited good sensitivity and specificity in identifying surface continuity (AUC: 0.93, [0.80 0.99]), fissures (AUC: 0.94, [0.83 0.99]) and fibrillation (AUC: 0.98, [0.88 1.0]). Standard Rq was significantly smaller compared with the complex roughness (CRq) already with mild surface changes with all surface reference parameters − continuity, fibrillation, and fissure sum. Furthermore, only CRq showed a significant difference when comparing the intact surface with lowest fissure sum score. These results indicate that the presented method for evaluating complex AC surfaces exhibit potential to identify early OA changes in superficial AC and is dynamic throughout OA progression. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. Society. 9999:1–12, 2019. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the feasibility of quantitative susceptibility mapping (QSM) for assessing degradation of articular cartilage by measuring ex vivo bovine cartilage samples subjected to different degradative treatments. Specimens were scanned at several orientations to study if degradation affects the susceptibility anisotropy. T2*‐mapping, histological stainings, and polarized light microscopy were used as reference methods. Additionally, simulations of susceptibility in layered geometry were performed. Methods: Samples (n = 9) were harvested from the patellae of skeletally mature bovines. Three specimens served as controls, and the rest were artificially degraded. MRI was performed at 9.4T using a 3D gradient echo sequence. QSM and T2* images and depth profiles through the centers of the samples were compared with each other and the histological findings. A planar isotropic model with depth‐wise susceptibility variation was used in the simulations. Results: A strong diamagnetic contrast was seen in the deep and calcified layers of cartilage, while T2* maps reflected the typical trilaminar structure of the collagen network. Anisotropy of susceptibility in cartilage was observed and was found to differ from the T2* anisotropy. Slight changes were observed in QSM and T2* following the degradative treatments. In simulations, anisotropy was observed. Conclusions: The results suggest that QSM is not sensitive to cartilage proteoglycan content, but shows sensitivity to the amount of calcification and to the integrity of the collagen network, providing potential for assessing osteoarthritis. The simulations suggested that the anisotropy of susceptibility might be partially explained by the layered geometry of susceptibility in cartilage. [ABSTRACT FROM AUTHOR]

Background: Texture analysis methods based on gray level co‐occurrence matrices (GLCM) can be optimized to probe the spatial correspondence information from knee MRI T2 maps and the changes caused by osteoarthritis, and thus possibly leading to a more sensitive characterization of osteoarthritic cartilage. Curvature of the cartilage surfaces combined with the low image resolution in relation to cartilage thickness set special requirements for an effective texture analysis tool. Purpose/Hypothesis: To introduce a novel implementation of GLCM algorithm optimized for cartilage texture analysis; to evaluate the performance of the designed algorithm against mean T2 relaxation time analysis; and to identify the most suitable texture features for discerning osteoarthritic subjects and asymptomatic controls. Study Type: Case control. Population/Subjects/Phantom/Specimen/animal Model: Eighty symptomatic osteoarthritis patients and 64 asymptomatic controls. Field Strength/Sequence: Multislice multiecho spin echo sequence on a 3T MRI system. Assessment: The T2 relaxation time maps were manually segmented by an operator trained for the task. Texture analysis was performed using an in‐house algorithm developed in MATLAB. Statistical Tests: Symptomatic and asymptomatic subjects were compared using Mann–Whitney U‐test. Repeatability of different features was addressed using the concordance correlation coefficient (CCC). Spearman's correlations between the features were determined. Results: The algorithm displayed excellent performance in discerning symptomatic and asymptomatic subjects. Fifteen features provided a significant difference between the groups (P ≤ 0.05) and 12 of those had P values smaller than the mean T2 differences. Most of the studied texture features were highly repeatable with CCC over 90%. For the features with significant differences, correlation with mean T2 was low or moderate (|r| ≤ 0.5). Data Conclusion: With careful parameter and feature selection and algorithm optimization, texture analysis provides a powerful tool for assessing knee osteoarthritis with more sensitive detection of cartilage degeneration compared to the mean value of the T2 relaxation times in an identical region of interest. Level of Evidence: 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018;47:1316–1327. [ABSTRACT FROM AUTHOR]

ABSTRACT: The structural integrity and mechanical environment of the articular cartilage matrix directly affect chondrocyte deformations. Rabbit models of early osteoarthritis at 9 weeks following anterior cruciate ligament transection (ACLT) have been shown to alter the deformation behavior of superficial zone chondrocytes in mechanically loaded articular cartilage. However, it is not fully understood whether these changes in cell mechanics are caused by changes in structural macromolecules in the extracellular matrix. Therefore, the purpose of this study was to characterize the proteoglycan content, collagen content, and collagen orientation at 9 weeks post ACLT using microscopic techniques, and relate these changes to the altered cell mechanics observed upon mechanical loading of cartilage. At 9 weeks following ACLT, collagen orientation was significantly (p < 0.05) altered and proteoglycan content was significantly (p < 0.05) reduced in the superficial zone cartilage matrix. These structural changes either in the extracellular or pericellular matrix (ECM and PCM) were also correlated significantly (p < 0.05) with chondrocyte width and height changes, thereby suggesting that chondrocyte deformation response to mechanical compression in early OA changes primarily because of alterations in matrix structure. However, compared to the normal group, proteoglycan content in the PCM from the ACLT group decreased less than that in the surrounding ECM. Therefore, PCM could play a key role to protect excessive chondrocyte deformations in the ACLT group. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:342–350, 2018. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate adiabatic T1ρ and T2ρ of articular cartilage in symptomatic osteoarthritis (OA) patients and asymptomatic volunteers, and to determine their association with magnetic resonance imaging (MRI)-based structural abnormalities in cartilage and bone.Materials and Methods: A total of 24 subjects (age range: 50-68 years; 12 female) were enrolled, including 12 early OA patients and 12 volunteers with normal joint function. Patients and volunteers underwent 3T MRI. T2 , adiabatic T1ρ , and T2ρ relaxation times of knee articular cartilage were measured. Proton density (PD)- and T1 -weighted MR image series were also obtained and separately evaluated for morphological changes using the MRI OA Knee Scoring (MOAKS) system. Comparisons using the Mann-Whitney nonparametric test were performed after dividing the study participants according to physical symptoms as determined by Western Ontario and McMaster Universities (WOMAC) score or presence of cartilage lesions, bone marrow lesions, or osteophytes.Results: Elevated adiabatic T1ρ and T2ρ relaxation times of articular cartilage were associated with cartilage loss (P = 0.024-0.047), physical symptoms (0.0068-0.035), and osteophytes (0.0039-0.027). Elevated adiabatic T1ρ was also associated with bone marrow lesions (0.033).Conclusion: Preliminary data suggest that elevated adiabatic T1ρ and T2ρ of cartilage are associated with morphological abnormalities of cartilage and bone, and thus may be applicable for in vivo OA research and diagnostics.Level Of Evidence: 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:678-689. [ABSTRACT FROM AUTHOR]

NMR experiments carried out at magnetic fields below 1 T provide new relaxation parameters unavailable with conventional clinical scanners. Contrast of T1 generally becomes larger towards low fields, as slow molecular reorientation processes dominate relaxation at the corresponding Larmor frequencies. This advantage has to be considered in the context of lower sensitivity and frequently reduced spatial resolution. The layered structure of cartilage is one example where a particularly strong variation of T1 across the tissue occurs, being affected by degenerative diseases such as osteoarthritis (OA). Furthermore, the presence of 1H-14 N cross-relaxation, leading to so-called quadrupolar dips in the 1H relaxation time dispersion, provide insight into the concentration and mobility of proteoglycans and collagen in cartilage, both being affected by OA. In this study, low-field imaging and variable-field NMR relaxometry were combined for the first time for tissue samples, employing unidirectional load to probe the mechanical properties. 20 human knee cartilage samples were placed in a compression cell, and studied by determining relaxation profiles without and with applied pressure (0.6 MPa) at 50 μm in-plane resolution, and comparing with volume-averaged T1 dispersion. Samples were subsequently stored in formalin, prepared for histology and graded according to the Mankin score system. Quadrupolar dips and thickness change under load showed the strongest correlation with Mankin grade. Average T1 and change of maximum T1 under load, as well as its position, correlate with thickness and thickness change. Furthermore, T1( ω) above 25 mT was found to correlate with thickness change. While volume-averaged T1 is not a suitable indicator for OA, its change due to mechanical load and its extreme values are suggested as biomarkers available in low-field MRI systems. The shape of the dispersion T1( ω) represents a promising access to understanding and quantifying molecular dynamics in tissue, pointing toward future in vivo tissue studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Despite increasing evidence that subchondral bone contributes to osteoarthritis (OA) pathogenesis, little is known about local changes in bone structure compared to cartilage degeneration. This study linked structural adaptation of subchondral bone with histological OA grade. Twenty-five osteochondral samples of macroscopically different degeneration were prepared from tibiae of 14 patients. Samples were scanned with micro-computed tomography (μCT) and both conventional structural parameters and novel 3D parameters based on local patterns were analyzed from the subchondral plate and trabecular bone. Subsequently, samples were processed for histology and evaluated for OARSI grade. Each bone parameter and OARSI grade was compared to assess structural adaptation of bone with OA severity. In addition, thicknesses of cartilage, calcified cartilage, and subchondral plate were analyzed from histological sections and compared with subchondral bone plate thickness from μCT. With increasing OARSI grade, the subchondral plate became thicker along with decreased specific bone surface, while there was no change in tissue mineral density. Histological analysis showed that subchondral plate thickness from μCT also includes calcified cartilage. Entropy of local patterns increased with OA severity, reflecting higher tissue heterogeneity. In the trabecular compartment, bone volume fraction and both trabecular thickness and number increased with OARSI grade while trabecular separation and structure model index decreased. Also, elevation of local patterns became longitudinal in the subchondral plate and axial transverse in trabecular bone with increasing OARSI grade. This study demonstrates the possibility of radiological assessment of OA severity by structural analysis of bone. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 35:785-792, 2017. [ABSTRACT FROM AUTHOR]

Optical clearing is an effective method to reduce light scattering of biological tissues that provides significant enhancement of light penetration into the biological tissues making non-invasive diagnosis more feasible. In current report Optical Coherence Tomography (OCT) in conjunction with optical clearing is applied for assessment of deep cartilage layers and cartilage-bone interface. The solution of Iohexol in water has been used as an optical clearing agent. The cartilage-bone boundary becomes visible after 15 min of optical clearing that enabling non-invasive estimation of its roughness: Sa = 10 ± 1 µm. The results show that for 0.9 mm thick cartilage optical clearing is stopped after 50 min with an increase of refractive index from 1.386 ± 0.008 to 1.510 ± 0.009. Current approach enables more reliable detection of arthroscopically inaccessible regions, including cartilage-bone boundary and subchondral bone, and potentially improves accuracy of the osteoarthritis diagnosis. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the sensitivity of quantitative MRI techniques (T1, T1,Gd, T2, continous wave (CW) T1ρ dispersion, adiabatic T1ρ, adiabatic T2ρ, RAFF and inversion-prepared magnetization transfer (MT)) for assessment of human articular cartilage with varying degrees of natural degeneration. Methods Osteochondral samples (n = 14) were obtained from the tibial plateaus of patients undergoing total knee replacement. MRI of the specimens was performed at 9.4T and the relaxation time maps were evaluated in the cartilage zones. For reference, quantitative histology, OARSI grading and biomechanical measurements were performed and correlated with MRI findings. Results All MRI parameters, except T1,Gd, showed statistically significant differences in tangential and full-thickness regions of interest (ROIs) between early and advanced osteoarthritis (OA) groups, as classified by OARSI grading. CW-T1ρ showed significant dispersion in all ROIs and featured classical laminar structure of cartilage with spin-lock powers below 1000 Hz. Adiabatic T1ρ, T2ρ, CW-T1ρ, MT, and RAFF correlated strongly with OARSI grade and biomechanical parameters. Conclusion MRI parameters were able to differentiate between early and advanced OA. Furthermore, rotating frame methods, namely adiabatic T1ρ, adiabatic T2ρ, CW-T1ρ, and RAFF, as well as MT experiment correlated strongly with biomechanical parameters and OARSI grade, suggesting high sensitivity of the parameters for cartilage degeneration. Magn Reson Med 74:249-259, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Radiographic texture analysis has been developed lately to improve the assessment of bone architecture as a determinant of bone quality. We validate here an algorithm for the evaluation of trabecular homogeneity index (HI) in the proximal femur from hip radiographs, with a focus on the impact of the principal compressive system of the trabecular bone, and evaluate its correlation with femoral strength, bone mineral density (BMD), and volumetric trabecular structure parameters. A semiautomatic custom-made algorithm was applied to calculate the HI in the femoral neck and trochanteric areas from radiographs of 178 femoral bone specimens (mean age 79.3 ± 10.4 years). Corresponding neck region was selected in CT scans to calculate volumetric parameters of trabecular structure. The site-specific BMDs were assessed from dual-energy X-ray absorptiometry (DXA), and the femoral strength was experimentally tested in side-impact configuration. Regression analysis was performed between the HI and biomechanical femoral strength, BMD, and volumetric parameters. The correlation between HI and failure load was R2 = 0.50; this result was improved to R2 = 0.58 for cervical fractures alone. The discrimination of bones with high risk of fractures (load <3000 N) was similar for HI and BMD (AUC = 0.87). Regression analysis between the HIs versus site-specific BMDs yielded R2 = 0.66 in neck area, R2 = 0.60 in trochanteric area, and an overall of R2 = 0.66 for the total hip. Neck HI and BMD correlated significantly with volumetric structure parameters. We present here a method to assess HI that can explain 50% of an experimental failure load and determines bones with high fracture risk with similar accuracy as BMD. The HI also had good correlation with DXA and computed tomography-derived data. © 2013 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The organization and composition of the collagen matrix of cortical bone changes as the bone matures due to growth and mechanical loading. We aimed to investigate the composition and organization of the collagen matrix in rabbit cortical bone during maturation using Fourier transform infrared (FTIR) microspectroscopy and polarized light microscopy (PLM). FTIR and PLM findings were compared to biochemical analysis from an earlier study. Mid-diaphyseal samples from left femora of female New Zealand White rabbits were used. The animal age ranged from newborn to 18-month old (5 age groups, n = 10 per group). The bones had earlier been decalcified and evaluated with biochemistry. In this study, collagen content, orientation, collagen cross-linking and spatial heterogeneity of all parameters was evaluated. Similar results were obtained when collagen content was evaluated with FTIR and PLM compared to the collagen content assessed with BA. Collagen content, orientation and collagen maturity increased significantly until the age of 3 months and remained similar thereafter. Simultaneously, spatial heterogeneity of the measured parameters decreased. Based on these findings, it seems that the collagen matrix of rabbit bone attains its mature state around 3 months of age, which is before the overall skeletal maturity is reached. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:435-442, 2012 [ABSTRACT FROM AUTHOR]

The article presents a study that characterized bone composition in high-turnover renal osteodystrophy patients using Fourier transform infrared spectroscopic imaging (FTIRI). The results of the study showed that there were linear correlations found between histomorphometric parameters and number of bone cells which were considered to be statistically significant. The data gathered from the study suggest that parameters of FTIRI which are related to carbonate could indicate the turnover and rate of remodeling of bone.

Background: Texture analysis methods based on gray level co-occurrence matrices (GLCM) can be optimized to probe the spatial correspondence information from knee MRI T2 maps and the changes caused by osteoarthritis, and thus possibly leading to a more sensitive characterization of osteoarthritic cartilage. Curvature of the cartilage surfaces combined with the low image resolution in relation to cartilage thickness set special requirements for an effective texture analysis tool.Purpose/hypothesis: To introduce a novel implementation of GLCM algorithm optimized for cartilage texture analysis; to evaluate the performance of the designed algorithm against mean T2 relaxation time analysis; and to identify the most suitable texture features for discerning osteoarthritic subjects and asymptomatic controls.Study Type: Case control.Population/subjects/phantom/specimen/animal Model: Eighty symptomatic osteoarthritis patients and 64 asymptomatic controls.Field Strength/sequence: Multislice multiecho spin echo sequence on a 3T MRI system.Assessment: The T2 relaxation time maps were manually segmented by an operator trained for the task. Texture analysis was performed using an in-house algorithm developed in MATLAB.Statistical Tests: Symptomatic and asymptomatic subjects were compared using Mann-Whitney U-test. Repeatability of different features was addressed using the concordance correlation coefficient (CCC). Spearman's correlations between the features were determined.Results: The algorithm displayed excellent performance in discerning symptomatic and asymptomatic subjects. Fifteen features provided a significant difference between the groups (P ≤ 0.05) and 12 of those had P values smaller than the mean T2 differences. Most of the studied texture features were highly repeatable with CCC over 90%. For the features with significant differences, correlation with mean T2 was low or moderate (|r| ≤ 0.5).Data Conclusion: With careful parameter and feature selection and algorithm optimization, texture analysis provides a powerful tool for assessing knee osteoarthritis with more sensitive detection of cartilage degeneration compared to the mean value of the T2 relaxation times in an identical region of interest.Level Of Evidence: 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2018;47:1316-1327. [ABSTRACT FROM AUTHOR]