ing ongoing surveillance to ensure that these lesions are detected. Whilst the incidence of life-threatening lesions iden- tified in musculoskeletal imaging is low, the onus is on the investigator to ensure that any abnormalities present are iden- tified when imaging is performed for research purposes. This is the first study to examine the prevalence of unsus- pected, potentially clinically significant abnormalities identified by either musculoskeletal MRI or another imaging modality in a healthy population. Previous studies have reported case series of all identified bone and cartilaginous tumours identi- fied by clinically indicated plain radiographs for non-muscu- loskeletal indications, such as sinus radiography . In contrast, many of our participants were asymptomatic. This study is limited in that subjects underwent diagnostic imaging using more limited sequences than would be used in a clinically indicated scan and an abnormality was defined as one a trained MRI radiologist deemed to require further inves- tigation. Although use of more extensive sequences in the studies may have better characterized the identified abnormal- ities, they may also have identified additional abnormalities, so that the true prevalence of such lesions may be underesti- mated. However, further sequences would be neither finan- cially viable nor optimal for research purposes although this may reduce the need for contacting the subjects to perform further investigation to confirm the nature of detected lesions. Conversely, it is possible that we have overestimated the prev- alence of incidental findings in an asymptomatic population since the 'healthy' participants may self-select on the basis of knee pain or prior trauma. However, since we excluded sub- jects experiencing significant pain, requiring therapy, and those with a history of significant knee trauma, this is unlikely: these subjects would not have otherwise undergone knee imaging. Subjects with knee OA had already undergone radi- ography for study inclusion, which had not identified these lesions. It might be expected that the prevalence of lesions in studies of symptomatic OA will be higher since, for study inclu- sion, participants are often required to have knee pain. It is possible that pain may not be due to knee OA but to a coex- isting, new, alternative pathology. Although we did not detect a difference between studies of healthy subjects and those involving participants with knee OA, our numbers were small and our power to detect this was limited. Indeed, our numbers were small and are able to give only an estimate of the preva-
It has been suggested that baseline (BL) MRI knee stud- ies can be clinically utilized to prevent injury and improve diagnostic accuracy in athletes, which could reduce loss of playing time. In addition, when symptoms do arise, BL MRI screenings can be compared with those obtained at follow-up to identify new knee abnormalities or lesions more likely to be correlated with symptoms (Walczak et al. 2008). Moreover, MRI screenings may aid in the under- standing of knee abnormalities found in athletes who sub- ject the knee to high loads and are at high risk of subsequent OA. Thus, the aim of this study was to longi- tudinally and cross-sectionally evaluate knee abnormalities by sex and age in adolescent and adult volleyball athletes over 2 years using MRI. These findings can help elucidate the role of MRI in aiding clinical diagnosis and in the pre- vention and treatment of injuries in athletes.
▸ This study introduces Knee Inflammation MRI Scoring System (KIMRISS), a scoring system that uses an electronic overlay to allow readers to record rapid touch-based or click-based binary scoring decisions for many small regions of bone, in a convenient web- based environment. This precise and detailed scoring would be impractical by traditional manual scoring methods. We show that KIMRISS is feasible, has reli- ability equivalent or higher than the current MRI Osteoarthritis Knee Score scoring system, and has higher sensitivity to interval changes. The novel com- bination of electronic overlays and direct on-screen scoring via web-based interface can also be applied in future to other types of image-based scoring, in other body parts and other disease processes. It may be an important tool for external knowledge transfer of newly developed scoring platforms based on imaging.
Results: Radial vascular marks were present in the first axial upper tibial subchondral slice, peaked between 6 and 10 mm depth and were absent by 16 mm depth. There was no association with age, left or right knee, BMI, or weight. There was more K-L graded OA medially and more vascular marks laterally. There was an inverse correlation between the number of marks and early grades of osteoarthritis medially ( p < 0.001) and laterally ( p < 0.002). Conclusion: We demonstrate previously undescribed subchondral vascular marks on axial MRI scans of the tibia and their inverse correlation with the presence and severity of early knee osteoarthritis. Our work offers a new insight into the possible vascular aetiology of osteoarthritis and potentially a means of earlier diagnosis and a therapeutic target.
Interestingly, to the best of our knowledge, this is the first study to demonstrate that a decrease in BML size was associated with an improvement in knee pain. This relationship was seen in those without ROA. There are increasing data to suggest that BMLs are reversible [14,15,17] and using areal measure of BML size, we have found that a decrease is associated with a positive clinical outcome. This has important implications for intervention studies. Currently there is no disease-modi- fying osteoarthritis drugs (DMOADs) available to mod- ify structural progression in OA; therefore, structure modification is now a primary aim in clinical drug trials. We believe there is increasing evidence to suggest that BMLs are a promising target. BMLs predict important disease outcomes such as cartilage loss and knee repla- cement, have the potential to regress and resolve, and are strongly linked to knee pain. Therefore, by targeting BMLs, it may be possible to slow disease progression as well as reduce pain in patients with OA. BMLs are visualised using standard fluid-sensitive sequences; how- ever, new advanced imaging analysis techniques (such as T1rho and T2 relaxation time quantification, and delayed gadolinium-enhanced MRI of cartilage (dGEM- RIC)) have been developed. dGEMRIC measures glyco- saminoglycan (GAG) concentrations in articular cartilage and GAG content can change quickly, there- fore dGEMRIC can be used to determine if altering BML natural history improves cartilage biochemistry. There is no doubt that both standard and advanced MRI techniques will play an important role in guiding future treatments in OA.
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In study I we have proposed an adaptive Rician denoising procedure with edge preserv- ing capabilities. The objective of the proposed method is to provide sufficient denoising with improved contrast to noise ratio of the image without the loss of edge information. Edge preservation has been achieved by a sophisticated statistical method that performs verification of the null hypothesis of the Brown-Forsythe test for the two independent regions across the diagonal of the circular mask. This method has been tested on magni- tude MRI images of the cartilage and synthetic images. We have observed a significant reduction of noise in the image with negligible loss in cartilage tissue due to the edge preservation capability of the filtering method. It also improves the contrast to noise ratio of the cartilage with respect to the surrounding knee structure. The efficiency of the proposed method has been validated, by estimation of the image quality using SNR and CNR index ratios for the denoised MRI images. The proposed method can also be implemented on other magnitude MRI images which are similarly affected by Rician denoising as shown in the simulation study. Future work may include advanced edge de- tection algorithms for more robust edge detection, a more accurate estimation of noise, improved computational cost and extension of the proposed method for 3D denoising.
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Accurate diagnosis is not an end in itself and therapeutic impact also needs to be considered. There are many prospective studies in the literature demonstrating the high accuracy of knee MRI against an arthroscopic standard, but little is being written on whether this accuracy can influence patient management. Reflecting on the experience of MRI over the last decade, Dixon et al. highlight the potential of MRI to influence patient management in cases of uncertain diagnosis, which almost certainly result in diagnostic arthroscopy. 25 In cases where clinical examination provides clear indication of disorder, Dixon et al. argue that the role of MRI is less relevant. Table 9 summarises the results of studies designed to evaluate the impact of MRI on patient management.
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Studies conducted by Shepard have suggested that meniscal injuries of the anterior cornu, which are found through an increase in the MRI signal, commonly do not have apparent clinical signs. 17 This suggests that there is a correlation of interpretations of MRI with the clinical examination. As demonstrated by Kocabey in 2004, there was no statistical significance (P>0.05) in comparing MRI with clinical examination in diagnosing meniscal and ligament injuries of the knee in relation to arthroscopic findings. 18 This suggests that well-trained orthopedic surgeons can safely diagnose ACL injuries and that the routine of indicating MRI before the clinical examination is not recommended. 19
As far as we know, there are seldom longitudinal stu- dies [14–16] investigating the relationship between MRI-detected OPs and clinical changes of OA. Sowers et al. found that large MRI-detected OPs were associated with increased odds of knee pain and reduced physical function . Hakky et al. measured OP volume using MRI and observed significant positive correlation between OP volume and cartilage thickness loss . In the latest study, MRI-detected OPs in a group of pa- tients with end-stage OA scored using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) grading system, those with a MRI-detected OP score of more than 30 have about threefold higher risk of undergoing total knee arthroplasty . Based on the Chingford study, the natural history of radiographic OA is that of very slow progression . However, the natural history of semi-quantitative MRI-detected OPs has not been de- scribed and it is unknown whether knee structural ab- normalities, including cartilage defects, bone marrow lesions (BMLs), meniscal extrusion, infrapatellar fat pad (IPFP), and effusion-synovitis, can predict MRI-detected OP change over time. Hence, the aims of this study were to describe the natural history of knee MRI-detected OP, and to determine if knee structural abnormalities are associated with change of MRI-detected OP in a longitu- dinal study of older adults.
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TGF-β proteins induce osteogenesis and chondrogenesis, and play a role in cell growth, differentiation, and extracel- lular matrix protein synthesis . TGF-β stimulates proteoglycan synthesis and chondrocyte proliferation, and may also have anti-inflammatory and immunosuppressive characteristics . A new treatment approach for knee osteoarthritis (OA) involves intraarticular administration of human chondrocytes transduced with a viral vector containing the gene for TGF-β1 transcription. Recently, a preliminary evaluation of the efficacy of non-transduced allogeneic human chondrocytes and allogeneic human chondrocytes virally transduced to express TGF-β1 (TG- C) was done. TG-C is made of human chondrocytes which has immunosuppressive effect and is grown from tissue obtained from a polydactyly finger of a single infant donor . TG-C represents a cell-mediated cytokine gene ther- apy approach for local intra-articular administration in pa- tients with OA. TG-C showed positive effects on pain levels in patients with moderate to advanced knee OA, as demonstrated by the visual analogue scale (VAS) and International Knee Documentation Committee (IKDC) scores at 1 year follow-up compared to the control cohort . Patients receiving TG-C had less knee pain, and they were less likely to need analgesics compared to placebo. However, effects of TG-C on MRI-assessed structural changes in knee joint tissues have only been assessed in a single study demonstrating mixed results after 12 months, i.e. those who received low-dose TG-C showed worsening mean MRI score of cartilage signal intensity, while those who had high-dose TG-C showed worsening mean MRI scores in bone surface osteophytes and periarticular inflammation .
previously been reported to be indicative of osteoarth- ritis . In the current project, the dGEMRIC analyses used corresponding points on each condyle. The ROIs were manually chosen and standardized at three differ- ent points in each knee condyle, as illustrated in Fig. 1, and the values were reported as the mean and the 95 % CI. Unpaired Student’s t-tests were used for the MRI T2 mapping results because these results were not calcu- lated for the contralateral knee. A linear regression was used to analyze the relationship between the dGEMRIC readings of the injured condyles and both the duration of symptoms and the subscale of KOOS pain. A paired t-test was used to compare the mean of the injured condyle with the contralateral control condyle. The intraclass correlation coefficient (ICC) was calculated to assess the intraobserver reliability of the dGEMRIC assessments.
Successful rabbit models were randomly assi- gned to the high-intensity group (impact from a height of 60 cm), medium-intensity group (im- pact from a height of 45 cm), and low-intensity group (impact from a height of 35 cm) in terms of impact intensity. MRI was performed to examine bilateral knee joints of lower extremi- ties in rabbits using a 1.5T MR scanner (Sie- mens, Germany) at 6 hours, 2 weeks, and 4 weeks after impact. MRI sequences are listed in Table 1 and the signal-noise ratio (SNR) was calculated. Findings of all MRIs were evaluated in a double-blind manner by 3 senior radiolo- gists from our hospital. After each MRI exami- nation, 15 rabbits (5 in each group) were sacri- ficed, from which knee joint specimens were extracted. Extracted specimens were fixed in 10% formaldehyde solution followed by obser- vation of the pathological sections (bone mar- row hemorrhage, edema, and trabecular struc- ture) under a light microscope.
Correlation between cartilage damage and MRI-de- fined OPs has been reported previously . But few other studies have examined the associations of IPFP ab- normality and effusion-synovitis with MRI-detected OP progression. One cross-sectional study suggested, unsur- prisingly, that greater size of MRI-detected OPs related to severity of radiographic OA . Another cross-sectional study revealed that MRI-detected OPs were weakly associated with synovitis or joint effusion but not correlated with Kellgren-Lawrence score . Hill et al. reported that change in synovitis correlated with change in knee pain, but not loss of cartilage . The only longitudinal study to be published revealed sig- nificant associations between MRI-detected OP volume and cartilage thickness loss but did not investigate asso- ciations with other structures . In the current study, baseline BMLs, cartilage defects, meniscal extrusion, IPFP abnormality and effusion-synovitis were associ- ated with worsening MRI-detected OPs over time, but presence of IPFP abnormality, IPFP maximum area, effusion-synovitis in the central portion, posterior femoral recess and subpopliteal recess were not inde- pendently associated with worsening MRI-detected OPs over time. Although the underlying structural mechanisms are largely unknown, these findings reinforce the evolving concept that knee OA is a Table 2 Site-specific association with increase in MRI-detected
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Methods: This was a retrospective case-control study. Following a sample size calculation on pilot data, eighteen sequential patients demonstrating hyper-intense subcutaneous signal changes around the knee on fat-saturated T2- weighted MRI were identified from PACS (18 females, mean age 45, range 31 – 62). Age and gender-matched patients without abnormal T2 MR signal changes were selected. Two observers independently drew regions of interest representing cross-sectional areas of bone and fat. The location of T2 signal hyper-intense lesions was characterized by consensus.
Among middle-aged and older adults who presented to an outpatient orthopedic clinic for evaluation of knee pain, and who later received an MRI (either ordered by the surgeon or independently by our study staff ), about three-quarters had a meniscal tear documented on MRI. This high prevalence of meniscal tear was similar among subjects whom the expert physicians were highly confident had symptomatic meniscal tear (80 % had positive MRI) as well as those for whom the surgeons had medium (87 %) and low levels of confidence (64 %). Meniscal tear prevalence was very high among all pa- tients with radiographic knee OA (79 %) but was also commonly documented among those without radio- graphic knee OA (69 %).
A healthy 27 year-old immunocompetent male was re- ferred for orthopaedic oncology evaluation of a possible neoplasm involving the inferior pole of his left patella. The man described a four month history of progressive anterior knee pain and swelling. Suspecting a knee infec- tion, his orthopaedic surgeon performed two separate aspirations for culture, both of which were negative for any microorganisms including fungus. Radiographs dem- onstrated a lucent lesion in the inferior pole of the pa- tella, and a CT and MRI of the knee were ordered. The
MRI of the knee was performed on SIEMENS Magnetom C! Syngo MR Machine with field of strength 0.35T using an extremity coil. The knee was imaged in three standard planes i.e. coronal, axial & sagittal planes using T1W, T2W, PD, STIR & GRE sequences with 4 mm slice thickness. The patient was placed in supine position with the knee externally rotated 15-20 degree in order to facilitate the visualization of anterior cruciate ligament (ACL) completely on sagittal images.
Published data indicate a large increase during the nine- ties in the use of magnetic resonance imaging (MRI) , including extremity  and specifically knee MRI . The criteria for performing MRI of the knee have broadened considerably . Possible advantages are improved detec- tion of relevant traumatic lesions  and reduced use of invasive diagnostic arthroscopy [2,5], as MRI provides good visualisation of menisci and ligaments [6,7]. The overall clinical benefit of the current use of knee MRI is uncertain, however [8-10], and overuse may exist. Irrel- evant findings such as degenerative rupture of the medial meniscus are frequent, especially in middle and older ages [11-13]. A study  from Wales published 2002 found that 46% of knee MRI requests were not regarded as clin- ically indicated.
Bone is considered an integral structure in the pathogenesis of osteoarthritis (OA) and the role of local and systemic bone mineral density (BMD) is gaining increasing interest. When the knee joint is examined for OA outcomes, local BMD refers to subchondral or periarticular BMD of the tibia and systemic BMD refers to BMD of the hip, lumbar spine, and total body [1, 2]. It has been speculated that OA is more prevalent in people with higher systemic BMD [3, 4] and that there is an inverse relationship be- tween osteoporosis and OA [3, 5, 6]. Higher systemic BMD may not reflect better-quality bone, as higher lumbar spine BMD is associated with lumbar spondyl- osis . Such associations are thought to be due to either higher BMD within sclerotic areas, or generalized increase in subchondral bone, both of which are features that characterize knee OA [8–10]. With the advent of medications that modify bone turnover, a bet- ter understanding of the relationship between systemic BMD and early structural changes in knee OA may have important implications for disease onset and or progression. Indeed, a large radiographic study of 1754 participants demonstrated that high systemic BMD in- creases the risk of incident knee OA, as measured by the onset of joint space narrowing . However, radio- graphic joint space narrowing provides only a surrogate measure of cartilage, with magnetic resonance imaging (MRI) evidence that approximately 11–13% of cartilage volume has been lost prior to radiographic evidence of any diminution of the joint space . Cartilage volume loss and cartilage defects are both clinically significant as they are associated with the important patient outcomes of pain [12, 13] and risk of knee re- placement [14, 15].
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The present investigation was descriptive in nature and was not designed to compare the results of clinical assess- ment and imaging, but rather to compare two imaging modalities. Four different anatomical areas were assessed in the knee and ankle region, respectively, and three differ- ent areas in the wrist region. The objective was to investi- gate whether the US and MRI findings, respectively, occur in the same or in different anatomical locations. The in- clusion criterion was being a child with clinically active arthritis. Patients without focal clinical symptoms were not presented to the US examiner, who was also blinded to other aspects of the children, such as clinical status and subtype. As the examinations on patients and controls were performed at different occasions and at different locations the examiner was not blinded to whether he was evaluating JIA patients or controls. Another experienced musculoskeletal radiologist analyzed all MRI images. He was blinded to the results of US examinations but, as the dates of examination were differing between the two groups, not to the respective subject category (patients or controls), which might have constituted a bias.
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