The Reliability of Ultrasound in the Assessment of Hyaline Cartilage in Rheumatoid Arthritis and Healthy Metacarpal Heads.

PURPOSE: i) To assess the inter- and intra-observer reliability of ultrasound (US) in the evaluation of the hyaline cartilage (HC) of the metacarpal head (MH) in patients with rheumatoid arthritis (RA) and in healthy subjects (HS) both qualitatively and quantitatively. ii) To calculate the smallest detectable difference (SDD) of the MH cartilage thickness measurement. iii) To correlate the qualitative scoring system and the quantitative assessment. MATERIALS AND METHODS: US examination was performed on 280 MHs of 20 patients with RA and 15 HS using a very high frequency probe (up to 22 MHz). HC status was evaluated both qualitatively (using a five-grade scoring system) and quantitatively (using the average value of the longitudinal and transverse measures). The HC of MHs from II to V metacarpophalangeal joint of both hands were scanned independently on the same day by two rheumatologists to assess inter-observer reliability. All subjects were re-examined using the same scanning protocol and the same US setting by one sonographer after a week to assess intra-observer reliability. RESULTS: The inter-observer agreement and intra-observer agreement were moderate to substantial (k = 0.66 and k = 0.73) for the qualitative scoring system and high (ICC = 0.93 and ICC = 0.94) for the quantitative assessment. The SDD of the MH cartilage thickness measurement was 0.09 mm. A significant correlation between the two scoring systems was found (r = -0.35; p < 0.001). CONCLUSION: The present study describes the main methodological issues of HC assessment. Using a standardized protocol, both the qualitative and the quantitative scoring systems can be reliable.

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

OBJECTIVE: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard. METHODS: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings. RESULTS: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation. CONCLUSION: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.

Prospective Multiparametric Magnetic Resonance Monitoring of Changes in Lesions of Hyaline Cartilage of the Knee Joint After Treatment by Microfractures and Implantation of Biological Collagen Type I Matrix Implants .

RATIONALE AND OBJECTIVES: This study's aims were to depict changes in cartilage quality after surgical intervention using magnetic resonance (MR) examination and in content of glycosaminoglycans chains (GAGs) after two types of surgeries - chondral defect treatment by microfractures and scaffold implantation in combination with microfractures. MATERIALS AND METHODS: Twenty-five patients were studied: 14 with implants, 11 with microfractures. MR examination was made before surgery and 6, 12, and 18 months thereafter. Qualitative changes in cartilage were observed by means of delayed gadolinium enhanced magnetic resonance imaging of cartilage sequence using Gd-DTPA2- and Gd-DOTA. In each examination, GAGs content was determined at three locations: the defect, its surroundings, and a non-load-bearing reference area. RESULTS: Measured indices showed no statistically significant differences in changes within the defect area when comparing the two treatment types at individual time points of 6, 12, and 18 months. In the case of microfracture treatment, more substantial decrease in GAGs concentration occurred at month 6, whereas the greatest decline occurred at month 12 when using an implant. Change in GAGs content and decline in cartilage quality were substantial also in the reference area and close surroundings. CONCLUSIONS: Hyaline cartilage behaves as a unified whole, and change in GAGs content was marked also in locations with no morphological damage. Over the monitored period, no statistically significant difference between treatment types was noted as measured by GAGs content in the defect or its close surroundings. dGEMRIC is suitable for monitoring cartilage quality even if use of Gd-DTPA2- is not possible, because comparable results were achieved using Gd-DOTA.

Spectrum of common and uncommon causes of knee joint hyaline cartilage degeneration and their key imaging features.

Hyaline cartilage lining the surfaces of diarthrodial joints is an important construct for transmission of load and to reduce friction between the bones. Normal wear and tear accounts for about 3-5 percent knee cartilage loss ever year in otherwise healthy people after the age of 30 years. Several conditions and diseases lead to premature cartilage degeneration. Standardized description of cartilage loss, detailed evaluation of the joint health and determining the underlying etiology of cartilage loss are important for effective reporting, multidisciplinary communications and patient management. In this article, the authors discuss normal and abnormal imaging appearances of the hyaline cartilage of knee with focus on using controlled terminology and MRI classifications. The reader will benefit and learn key MR imaging features of a spectrum of common and uncommon conditions and diseases affecting the knee cartilage, such as trauma, secondary injury associated with meniscus and ligament injury related instability, arthritis, ischemia, idiopathic, and hereditary conditions including Matrix metalloproteinase-2 (MMP-2) mutations and mucopolysaccharidosis type IX disease with illustrative case examples.

High-field (3 Tesla) MRI of the navicular apparatus of sound horses shows good agreement to histopathology.

Magnetic resonance imaging and the correlation to histopathological findings of the equine palmar foot of lame horses have been described previously, using 0.27 and 1.5 T systems. Compared to these, 3 T systems provide superior spatial resolution and imaging contrast. The aim of our prospective anatomic study was to characterize the imaging anatomy of the navicular region on 3 T MRI in comparison to histopathological findings. We hypothesized that 3 T MRI allows a good visualization of the entire navicular apparatus and reliable measurements of navicular cartilage and cortical bone thickness. Twenty front feet of sound horses were examined using a 3 T MRI system. For histopathological examination, sagittal tissue sections of the navicular bones and adjacent ligaments were prepared. Alterations in magnetic resonance signal were graded for each region and compared to corresponding histological slices. Overall, there was good visualization of the anatomical detail and a very good agreement between MRI and histology for compact bone and spongiosa, good agreement for the fibrocartilage and the distal sesamoidean impar ligament, but only moderate agreement for the hyaline cartilage and the collateral sesamoidean ligament. A comparative measurement of cartilage and cortical bone thickness on magnetic resonance images and histological sections was performed. In MRI, the hyaline cartilage of the articular surface appeared significantly thinner and the fibrocartilage of the flexor surface appeared significantly thicker compared to histology. Findings indicated that MRI at a field strength of 3 T allows reliable depiction of anatomic details of the navicular apparatus.

Tenosynovial Giant Cell Tumor, Localized Type With Extensive Chondroid Metaplasia: A Case Report With Immunohistochemical and Molecular Genetic Analysis.

Tenosynovial giant cell tumor (TSGCT) of localized type is a common disease occurring mostly in the hands. Diagnosis of this tumor is relatively easy to render with hematoxylin-eosin-stained sections as compared with that of TSGCT of diffuse type. However, very rare cases with chondroid metaplasia that have recently been reported mainly in diffuse type can make pathological differentiation from soft tissue cartilaginous tumors extremely difficult. In this article, the authors present the second reported case of TSGCT of localized type showing extensive chondroid metaplasia. Pathological interpretation was difficult without utilizing immunohistochemistry and fluorescence in situ hybridization. One must be careful not to misdiagnose this lesion as cartilaginous tumors of soft tissue, and we suspect at least some chondroblastoma-like chondroma could be reclassified as TSGCT of localized type with extensive chondroid metaplasia. Morphological, immunohistochemical, and molecular genetic characteristics are presented and discussed.

Diagnostic value of ultrasound in calcium pyrophosphate deposition disease of the knee joint.

OBJECTIVE: To assess the diagnostic performance of ultrasound (US) for calcium pyrophosphate deposition (CPPD) at the level of menisci, hyaline cartilage (HC), tendons, and synovial fluid (SF) of the knee, and to examine inter- and intra-observer reliability. DESIGN: We consecutively included patients with knee effusion over a 2-year period (43 patients with CPPD and 131 controls). All patients underwent SF analysis, conventional radiography (CR), and US examination using the Outcome Measures in Rheumatology (OMERACT) definition of the US characteristics of CPPD. Two independent operators performed the US, and inter-observer agreement was calculated. Intra-observer agreement was examined with static images obtained for all enrolled patients. RESULTS: US revealed calcium pyrophosphate (CPP) deposits in menisci, HC, and tendon more frequently in patients with CPPD than in control patients. The presence of US CPP deposits in SF was not significantly different between the two groups. Combined US evaluation of the three components (menisci, HC, and tendon) showed the best diagnostic performance. The sensitivity and specificity for US evaluation of the three components were 74.4% and 77.1%, respectively, while for CR evaluation, the sensitivity and specificity were 44.2% and 96.9%, respectively. Inter- and intra-observer agreement were excellent for medial (κ = 0.930, 0.972) and lateral menisci (κ = 0.905, 0.942), HC (κ = 0.844, 0.957), and SF (κ = 0.817, 0.925). Tendon showed fair inter-observer (κ = 0.532) and good intra-observer reliability (κ = 0.788). CONCLUSIONS: Based on the OMERACT definition, US demonstrated better diagnostic capacity than CR to diagnose CPPD, with excellent reliability. Combined evaluation of menisci, HC, and tendon showed the best diagnostic accuracy.

[Current Options and Importance of Imaging of the Hyaline Articular Cartilage of the Knee Prior to the Surgery - a Different Perspective of an Orthopaedic Surgeon and a Radiologist]. / Soucasné moznosti a význam zobrazování hyalinní chrupavky kolenního kloubu pred operacním zákrokem ­ rozdílný pohled ortopeda a radiologa.

The authors present an overview of the commonly used techniques and new trends of the cartilage imaging, especially postoperatively, and also discuss the potential of MRI imaging of the cartilage from the perspective of an experienced orthopaedic surgeon. In conclusion, the authors propose possible explanations for the potential discrepancies between the MRI and the arthroscopic findings. Hyaline cartilage damage and subsequent reparation of this tissue is one of the topical issues of orthopaedics and traumatology. Due to the expanding possibilities of treatment of this tissue and a relatively good effect of the surgery, the number of patients indicated for magnetic resonance imaging prior to the surgery has been on an increase. To make a decision concerning the subsequent type of treatment, it is necessary to get an idea of the cartilage cover condition, articular surfaces and also of the associated pathologies. The degree of cartilage damage can be assessed by arthroscopy or magnetic resonance imaging, which provides also the possibility of the subchondral lesion detection. Thanks to the noninvasive nature of the MRI examination, it has become the most important method in full imaging of the articular cartilage. The MRI of the cartilage has many options and at present the evaluation of the hyaline cartilage should be an integral part of each MRI examination of joints. For a more accurate assessment of the cartilage there are several advanced techniques available that can be used not only for preoperative diagnostics, but also for monitoring after the surgery. Key words: hyaline cartilage, magnetic resonance, arthroscopy.

Influence of meniscus on cartilage and subchondral bone features of knees from older individuals: A cadaver study.

OBJECTIVE: Cartilage and subchondral bone form a functional unit. Here, we aimed to examine the effect of meniscus coverage on the characteristics of this unit in knees of older individuals. METHODS: We assessed the hyaline cartilage, subchondral cortical plate (SCP), and subchondral trabecular bone in areas covered or uncovered by the meniscus from normal cadaver knees (without degeneration). Bone cores harvested from the medial tibial plateau at locations uncovered (central), partially covered (posterior), and completely covered (peripheral) by the meniscus were imaged by micro-CT. The following were measured on images: cartilage volume (Cart.Vol, mm3) and thickness (Cart.Th, mm); SCP thickness (SCP.Th, µm) and porosity (SCP.Por, %); bone volume to total volume fraction (BV/TV, %); trabecular thickness (Tb.Th, µm), spacing (Tb.Sp, µm), and number (Tb.N, 1/mm); structure model index (SMI); trabecular pattern factor (Tb.Pf); and degree of anisotropy (DA). RESULTS: Among the 28 specimens studied (18 females) from individuals with mean age 82.8±10.2 years, cartilage and SCP were thicker at the central site uncovered by the meniscus than the posterior and peripheral sites, and Cart.Vol was greater. SCP.Por was highest in posterior samples. In the upper 1-5 mm of subchondral bone, central samples were characterized by higher values for BV/TV, Tb.N, Tb.Th, and connectivity (Tb.Pf), a more plate-like trabecular structure and lower anisotropy than with other samples. Deeper down, at 6-10 mm, the differences were slightly higher for Tb.Th centrally, DA peripherally and SMI posteriorly. CONCLUSIONS: The coverage or not by meniscus in the knee of older individuals is significantly associated with Cart.Th, SCP.Th, SCP.Por and trabecular microarchitectural parameters in the most superficial 5 mm and to a lesser extent the deepest area of subchondral trabecular bone. These results suggest an effect of differences in local loading conditions. In subchondral bone uncovered by the meniscus, the trabecular architecture resembles that of highly loaded areas.

SMD Kozlowski type caused by p.Arg594His substitution in TRPV4 reveals abnormal ossification and notochordal remnants in discs and vertebrae.

Spondylometaphyseal dysplasia Kozlowski type (SMDK) is a monogenic disorder within the TRPV4 dysplasia spectrum and has characteristic spinal and metaphyseal changes. We report skeletal MR imaging in a two-year-old patient who manifested typical clinical and radiographic features of SMDK. The diagnosis was confirmed by molecular analysis which revealed a mutation NM_021625.4:c.1781G > A - p.(Arg594His) in exon 11 of the TRPV4 gene. We have documented abnormalities in endochondral formation of the long and short tubular bones as well as round bones of the wrists and feet. The vertebral bodies had increased thickness of hyaline cartilage which enveloped ossification centers. The vertebrae and discs also had abnormalities in size, shape and structure. These anomalies were most likely the consequence of notochordal remnants presence within the intervertebral discs and in the vertebral bodies. The advantages of MR imaging in bone dysplasias caused by TRPV4 mutations are emphasized in this article.

MRI magic-angle effect in femorotibial cartilages of the red kangaroo.

OBJECTIVE: Kangaroo knee cartilages are robust tissues that can support knee flexion and endure high levels of compressive stress. This study aimed to develop a detailed understanding of the collagen architecture in kangaroo knee cartilages and thus obtain insights into the biophysical basis of their function. DESIGN: Cylindrical/square plugs from femoral and tibial hyaline cartilage and tibial fibrocartilage were excised from the knees of three adult red kangaroos. Multi-slice, multi-echo MR images were acquired at the sample orientations 0° and 55° ("magic angle") with respect to the static magnetic field. Maps of the transverse relaxation rate constant (R2) and depth profiles of R2 and its anisotropic component (R2A) were constructed from the data. RESULTS: The R2A profiles confirmed the classic three-zone organisation of all cartilage samples. Femoral hyaline cartilage possessed a well-developed, thick superficial zone. Tibial hyaline cartilage possessed a very thick radial zone (80% relative thickness) that exhibited large R2A values consistent with highly ordered collagen. The R2A profile of tibial fibrocartilage exhibited a unique region near the bone (bottom 5-10%) consistent with elevated proteoglycan content ("attachment sub-zone"). CONCLUSIONS: Our observations suggest that the well-developed superficial zone of femoral hyaline cartilage is suitable for supporting knee flexion; the thick and well-aligned radial zone of tibial hyaline cartilage is adapted to endure high compressive stress; while the innermost part of the radial zone of tibial fibrocartilage may facilitate anchoring of the collagen fibres to withstand high shear deformation. These findings may inspire new designs for cartilage tissue engineering.

Definition and Reliability Assessment of Elementary Ultrasonographic Findings in Calcium Pyrophosphate Deposition Disease: A Study by the OMERACT Calcium Pyrophosphate Deposition Disease Ultrasound Subtask Force.

OBJECTIVE: To define the ultrasonographic characteristics of calcium pyrophosphate crystal (CPP) deposits in joints and periarticular tissues and to evaluate the intra- and interobserver reliability of expert ultrasonographers in the assessment of CPP deposition disease (CPPD) according to the new definitions. METHODS: After a systematic literature review, a Delphi survey was circulated among a group of expert ultrasonographers, who were members of the CPPD Ultrasound (US) Outcome Measures in Rheumatology (OMERACT) subtask force, to obtain definitions of the US characteristics of CPPD at the level of fibrocartilage (FC), hyaline cartilage (HC), tendon, and synovial fluid (SF). Subsequently, the reliability of US in assessing CPPD at knee and wrist levels according to the agreed definitions was tested in static images and in patients with CPPD. Cohen's κ was used for statistical analysis. RESULTS: HC and FC of the knee yielded the highest interobserver κ values among all the structures examined, in both the Web-based (0.73 for HC and 0.58 for FC) and patient-based exercises (0.55 for the HC and 0.64 for the FC). Kappa values for the other structures were lower, ranging from 0.28 in tendons to 0.50 in SF in the static exercise and from 0.09 (proximal patellar tendon) to 0.27 (triangular FC of the wrist) in the patient-based exercise. CONCLUSION: The new OMERACT definitions for the US identification of CPPD proved to be reliable at the level of the HC and FC of the knee. Further studies are needed to better define the US characteristics of CPPD and optimize the scanning technique in other anatomical sites.

Using synchrotron X-ray phase-contrast micro-computed tomography to study tissue damage by laser irradiation.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine if X-ray micro-computed tomography could be used to locate and characterize tissue damage caused by laser irradiation and to describe its advantages over classical histology for this application. STUDY DESIGN/MATERIALS AND METHODS: A surgical CO2 laser, operated in single pulse mode (100 milliseconds) at different power settings, was used to ablate different types of cadaveric animal tissues. Tissue samples were then harvested and imaged with synchrotron X-ray phase-contrast and micro-computed tomography to generate stacks of virtual sections of the tissues. Subsequently, Fiji (ImageJ) software was used to locate tissue damage, then to quantify volumes of laser ablation cones and thermal coagulation damage from 3D renderings of tissue image stacks. Visual comparisons of tissue structures in X-ray images with those visible by classic light microscopy histology were made. RESULTS: We demonstrated that micro-computed tomography could be used to rapidly identify areas of surgical laser ablation, vacuolization, carbonization, and thermally coagulated tissue. Quantification and comparison of the ablation crater, which represents the volume of ablated tissue, and the thermal coagulation zone volumes were performed faster than we could by classical histology. We demonstrated that these procedures can be performed on fresh hydrated and non-sectioned plastic embedded tissue. CONCLUSION: We demonstrated that the application of non-destructive micro-computed tomography to the visualization and analysis of laser induced tissue damage without tissue sectioning is possible. This will improve evaluation of new surgical lasers and their corresponding effect on tissues. Lasers Surg. Med. 48:866-877, 2016. © 2016 Wiley Periodicals, Inc.

Species-Independent Modeling of High-Frequency Ultrasound Backscatter in Hyaline Cartilage.

Apparent integrated backscatter (AIB) is a common ultrasound parameter used to assess cartilage matrix degeneration. However, the specific contributions of chondrocytes, proteoglycan and collagen to AIB remain unknown. To reveal these relationships, this work examined biopsies and cross sections of human, ovine and bovine cartilage with 40-MHz ultrasound biomicroscopy. Site-matched estimates of collagen concentration, proteoglycan concentration, collagen orientation and cell number density were employed in quasi-least-squares linear regression analyses to model AIB. A positive correlation (R(2) = 0.51, p < 10(-4)) between AIB and a combination model of cell number density and collagen concentration was obtained for collagen orientations approximately perpendicular (>70°) to the sound beam direction. These findings indicate causal relationships between AIB and cartilage structural parameters and could aid in more sophisticated future interpretations of ultrasound backscatter.

A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study.

In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.

Ultrasound imaging for the rheumatologist. XLVII. Ultrasound of the shoulder in patients with gout and calcium pyrophosphate deposition disease.

OBJECTIVES: This study was aimed at determining the prevalence of ultrasound (US) morpho-structural changes in the shoulders of patients with crystal-related arthropathies, and at investigating the relationship between them and the clinical findings. METHODS: Eighty-eight patients with a crystal proven diagnosis of gout or calcium pyrophosphate dihydrate (CPPD) disease attending the in-patient and the out-patient clinics of four Italian Rheumatology Departments were consecutively enrolled in this multi-centre study. All patients were clinically examined by an expert rheumatologist who recorded clinical and laboratory data in addition to the presence/absence of spontaneous shoulder pain and performed the Hawkins, Jobe, Patte, Gerber, and Speed tests. In each centre, US examinations were carried out by a rheumatologist expert in musculoskeletal US blinded to clinical data, using a MyLab TWICE XVG machine (Esaote SpA, Genoa, Italy) equipped with a linear probe operating at 4-13 MHz, and a Logiq 9 machine (General Electrics Medical Systems, Milwaukee, WI, USA) with a linear probe operating at 9-14 MHz. Shoulders were scanned to detect peri-articular inflammation, rotator cuff pathology and joint involvement, and to reveal US signs indicative of crystal deposits. RESULTS: A total of 88 patients, 39 with gout, 46 with CPPD disease, and 3 with both gout and CPPD disease, were enrolled. In total, 176 shoulders were clinically assessed, of which 54/176 (30%) were painful and 74/176 (42%) were clinically normal shoulders. All US findings indicative of peri-articular synovial inflammation were more frequently detected in patients with CPPD disease than in gouty patients. In 50 out of 176 (28.4%) shoulders, US allowed the detection of at least one finding indicative of synovial inflammation. Chronic tendinopathy was a frequent US finding both in gout patients and in patients with CPPD disease and the supraspinatus tendon was the most frequently involved one. In CPPD disease the supraspinatus tendon was found ruptured in a number of shoulders seven times higher than in gouty patients. The osteophytes were found at acromion-clavicular joint in nearly 80% of the shoulders in CPPD disease and in 60% in the gouty patients. CONCLUSIONS: The results of this study confirm the high specificity of US findings indicative of crystal deposits at hyaline cartilage level and indicate that the supraspinatus tendon and the fibrocartilage of the acromion-clavicular joint are the most frequently affected structures of the shoulders in patients with crystal-related arthropathies.

Contrast-enhanced nanofocus computed tomography images the cartilage subtissue architecture in three dimensions.

We describe a non-destructive imaging method, named contrast-enhanced nanofocus X-ray computed tomography (CE-nanoCT), that permits simultaneously imaging and quantifying in 3D the (sub)tissue architecture and (biochemical) composition of cartilage and bone in small animal models at a novel contrast and spatial resolution. To demonstrate the potential of this novel methodology, a newborn mouse was scanned using CE-nanoCT. This allowed simultaneously visualising the bone and cartilage structure much like the traditional alcian blue-alizarin red skeletal stain. Additionally, it enabled a 3D visualisation at such a high spatial image resolution that internal, micro-scale structures could be digitally dissected and evaluated for size, structure and composition. Ex vivo treatment with papain, that is known to specifically remove the non-calcified cartilage layer but keep the calcified cartilage intact, proved CE-nanoCT to be applicable to visualise the subdivisions within the hyaline cartilage of the articular joint of mice. The quantitative power of CE-nanoCT in vivo was evaluated using a mouse model for osteoarthritis (OA), where OA-like cartilage lesions are induced by meniscus destabilisation surgery. The thickness of both the non-calcified and calcified cartilage layer in the knee joint of such mice was visualised and quantified in 3D and compared to unaffected mice. Finally, to show that different forms of cartilage and tissue combinations can be distinguished using CE-nanoCT, different cartilaginous body parts of the mouse were imaged. In conclusion, CE-nanoCT can provide novel insights in preclinical research by quantifying in a non-destructive 3D manner pathological differences, in particular in developing mice, newborns or adults.

Tips and tricks to recognize microcrystalline arthritis.

US plays a useful role in diagnosing and monitoring therapy in microcrystalline arthritis, as it may detect both monosodium urate and calcium pyrophosphate crystal aggregates. The knowledge of some tips and tricks in the identification of these findings can play a key role in exploiting the relevant potential of US in microcrystalline arthritis, avoiding errors and misinterpretations. This review provides an in-depth description of simple technical and methodological issues to guide the rheumatologist in daily clinical practice.

Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration.

INTRODUCTION: Adipose stem cells (ASCs) secrete many trophic factors that can stimulate tissue repair, including angiogenic factors, but little is known about how ASCs and their secreted factors influence cartilage regeneration. Therefore, the aim of this study was to determine the effects ASC-secreted factors have in repairing chondral defects. METHODS: ASCs isolated from male Sprague Dawley rats were cultured in monolayer or alginate microbeads supplemented with growth (GM) or chondrogenic medium (CM). Subsequent co-culture, conditioned media, and in vivo cartilage defect studies were performed. RESULTS: ASC monolayers and microbeads cultured in CM had decreased FGF-2 gene expression and VEGF-A secretion compared to ASCs cultured in GM. Chondrocytes co-cultured with GM-cultured ASCs for 7 days had decreased mRNAs for col2, comp, and runx2. Chondrocytes treated for 12 or 24 hours with conditioned medium from GM-cultured ASCs had reduced sox9, acan, and col2 mRNAs; reduced proliferation and proteoglycan synthesis; and increased apoptosis. ASC-conditioned medium also increased endothelial cell tube lengthening whereas conditioned medium from CM-cultured ASCs had no effect. Treating ASCs with CM reduced or abolished these deleterious effects while adding a neutralizing antibody for VEGF-A eliminated ASC-conditioned medium induced chondrocyte apoptosis and restored proteoglycan synthesis. FGF-2 also mitigated the deleterious effects VEGF-A had on chondrocyte apoptosis and phenotype. When GM-grown ASC pellets were implanted in 1 mm non-critical hyaline cartilage defects in vivo, cartilage regeneration was inhibited as evaluated by radiographic and equilibrium partitioning of an ionic contrast agent via microCT imaging. Histology revealed that defects with GM-cultured ASCs had no tissue ingrowth from the edges of the defect whereas empty defects and defects with CM-grown ASCs had similar amounts of neocartilage formation. CONCLUSIONS: ASCs must be treated to reduce the secretion of VEGF-A and other factors that inhibit cartilage regeneration, which can significantly influence how ASCs are used for repairing hyaline cartilage.