The role of imaging in osteoarthritis




Abstract


Osteoarthritis (OA) is the most prevalent joint disorder with no approved disease-modifying treatment available. The importance of imaging in assessing all joint structures involved in the disease process, including articular cartilage, meniscus, subarticular bone marrow, and synovium for diagnosis, prognostication, and follow-up, has been well recognized. In daily clinical practice, conventional radiography is still the most commonly used imaging technique for the evaluation of a patient with known or suspected OA and radiographic outcome measures are still the only approved end point by regulatory authorities in clinical trials.


The ability of magnetic resonance imaging (MRI) to visualize all joint structures in three-dimensional fashion including tissue ultrastructure has markedly deepened our understanding of the natural history of the disease. This article describes the roles and limitations of different imaging modalities for clinical practice and research in OA, with a focus on radiography and MRI and an emphasis on the knee joint.


Knee osteoarthritis (OA) is a major public health problem that primarily affects the elderly. Almost 10% of the U. S. population suffers from symptomatic knee OA by the age of 60 . Its prevalence is increasing in the aging population and it is a frequent cause of dependency in lower-limb tasks . In total, the health-care expenditures of this condition have been estimated at $US189 billion annually . Despite this, there are no approved interventions that ameliorate structural progression of this disorder.


The increasing importance of imaging in osteoarthritis for diagnosis, prognostication, and follow-up is well recognized by both clinicians and OA researchers. While conventional radiography is the gold standard imaging technique for the evaluation of known or suspected OA in clinical practice and research, it has limitations that have become apparent in the course of large magnetic resonance imaging (MRI)-based knee osteoarthritis studies . Pathological changes may be evident in all structures of a joint with OA, although traditionally researchers have viewed articular cartilage as the central feature and as the primary target for intervention and measurement. Of the commonly employed imaging techniques, only MRI can assess all structures of the joint, including cartilage, meniscus, ligaments, muscle, subarticular bone marrow, and synovium, and thus can show the knee as a whole organ three-dimensionally. In addition, it can directly help in the assessment of cartilage morphology and composition. This imaging modality, therefore, plays a crucial role in increasing our understanding of the natural history of OA and in the development of new therapies. The advantages and limitations of conventional radiography, MRI, and other techniques, such as ultrasound, nuclear medicine, computed tomography (CT), and CT arthrography, in the imaging of OA in both clinical practice and research are described in this review article.


Review criteria


This a nonsystematic, narrative review based on a comprehensive literature search in PubMed, using the following search terms in various combinations: “radiography,” “magnetic resonance imaging”; “computed tomography,” “PET,” “osteoarthritis,” “semi-quantitative scoring”; “morphometry,” “knee”; “hand”; “hip” and “spine.” All articles identified were English-language full-text papers between 2000 and 2013, focusing on recent published research. The reference lists of identified papers were also used to identify further relevant articles, and relevant references published prior to 2000 were included where appropriate. Because of the abundance of publications on the topic over the past years, the authors had to prioritize inclusion of publications based on personal judgment of potential relevance to the readership.




Radiography


Radiography is the simplest, least-expensive, and most widely deployed imaging modality. It enables detection of OA-associated bony features, such as osteophytes, subchondral sclerosis, and cysts . Radiography can also determine joint space width (JSW), a surrogate of cartilage thickness and meniscal integrity, but precise measurement of each of these articular structures is not possible by conventional X-ray-based methods . Despite this limitation, slowing of radiographically detected joint space narrowing (JSN) is the only structural end point currently approved by the U.S. Food and Drug Administration (FDA) to demonstrate efficacy of disease-modifying OA drugs in phase-III clinical trials. Osteoarthritis is radiographically defined by the presence of marginal osteophytes . Progression of JSN is the most commonly used criterion for the assessment of structural OA progression, and the total loss of JSW (“bone-on-bone” appearance) is one of the indicators for joint replacement .


Recent research efforts revealed that cartilage loss is not the only contributor to joint space loss, but that changes in the meniscus, such as meniscal extrusion or subluxation, are also responsible for JSN ( Fig. 1 ) . The lack of sensitivity and specificity of radiography for the detection of OA-associated articular tissue damage and its poor sensitivity to change at follow-up imaging are important limitations of this modality. Variations in semi-flexed knee positioning, which occur during image acquisition despite standardization, can also be problematic. Such variations can affect the quantitative measurement of various radiographic parameters of OA including JSW . Despite these limitations, radiography remains the gold standard for establishing an imaging-based diagnosis of OA and assessment of structural modification in clinical trials of knee OA ( Fig. 2 ).




Fig. 1


Comparison of magnetic resonance imaging (MRI) and radiography for visualization of knee osteoarthritis. A. Baseline posterior–anterior radiograph shows normal medial tibiofemoral joint space width (arrows). B. At 3-year follow-up, definite joint space narrowing is observed. C. Baseline MRI of same knee shows multiple tissues relevant to osteoarthritis not depicted by the radiograph: Cartilage is visualized in a direct fashion as a structure of intermediate signal intensity in this proton-density weighted coronal MRI image (white arrows). The anterior (white arrowhead) and posterior (black arrowhead) cruciate ligaments are clearly depicted as hypointense structures. In addition, the menisci are visualized as hypointense triangular structures in the medial and lateral joint spaces (black arrows). Note that the medial meniscus is aligned with the medial joint margin (white line). D. At the 3-year follow-up, the MRI shows incident meniscal extrusion of the medial meniscal body, responsible for radiographic joint space narrowing (arrowheads and white line). No cartilage loss is observed during the follow-up interval.



Fig 2


Radiographic diagnosis of osteoarthritis. Follow-up of a patient with anterior cruciate ligament disruption. A. At baseline, only a small equivocal osteophyte is depicted at the medial joint margin (arrowhead). B. At the follow-up examination 3 years later, definite osteophytes at the medial joint margin are observed at the tibia (arrow) and femur (arrowhead).


Semiquantitative assessments


The severity of radiographic OA can be assessed using semi-quantitative scoring systems. The Kellgren and Lawrence (KL) grading system is a widely accepted scheme used for defining radiographic OA based on the presence of a definite osteophyte (=grade 2) ( Fig. 2 ). However, KL grading has its limitations; in particular, KL 3 summarizes a scale of JSN severity from “definite” to almost “bone-to-bone” that cannot be accounted for. A modification of KL grading has been suggested to improve the sensitivity to change in longitudinal knee OA studies , with a recommendation that OA be defined by a combination of JSN and the presence of definite osteophytes in a knee that did not have this combination on the prior radiographic assessment. For OA progression, a focus on JSN alone using either a semi-quantitative or a quantitative approach was recommended.


The Osteoarthritis Research Society International (OARSI) atlas uses a different approach and grades tibiofemoral JSN and osteophytes separately for each compartment (medial tibiofemoral, lateral tibiofemoral, and patellofemoral) of the knee. This compartmental scoring appears to be more sensitive to longitudinal radiographic changes than KL grading . A recent study using data from the Osteoarthritis Initiative (OAI) demonstrated that the centralized radiographic reading is important from the viewpoint of observer reliability, as even expert readers seem to apply different thresholds for JSN grading .


Quantitative assessments


Quantitative JSW measurements can be accomplished either manually or by a software application. JSW is the distance between the projected femoral and tibial margins on the radiographic image. Quantification of JSW using image-processing software does require a digital image either, with digitized plain films or images acquired using fully digital modalities, such as computed radiography and digital radiography. Minimum JSW is the standard metric, but some groups have investigated the use of location-specific JSW . Various degrees of responsiveness have been observed depending on the degree of OA severity, length of the follow-up period, and the knee positioning protocol .


Measurements of JSW obtained from knee radiographs have been found to be reliable, especially when the study lasted longer than 2 years and when the radiographs were obtained with the knee in a standardized flexed position . Studies of hip OA have generated conflicting results when correlating JSW and symptoms. However, it has been shown that JSW can predict hip joint replacement .




Radiography


Radiography is the simplest, least-expensive, and most widely deployed imaging modality. It enables detection of OA-associated bony features, such as osteophytes, subchondral sclerosis, and cysts . Radiography can also determine joint space width (JSW), a surrogate of cartilage thickness and meniscal integrity, but precise measurement of each of these articular structures is not possible by conventional X-ray-based methods . Despite this limitation, slowing of radiographically detected joint space narrowing (JSN) is the only structural end point currently approved by the U.S. Food and Drug Administration (FDA) to demonstrate efficacy of disease-modifying OA drugs in phase-III clinical trials. Osteoarthritis is radiographically defined by the presence of marginal osteophytes . Progression of JSN is the most commonly used criterion for the assessment of structural OA progression, and the total loss of JSW (“bone-on-bone” appearance) is one of the indicators for joint replacement .


Recent research efforts revealed that cartilage loss is not the only contributor to joint space loss, but that changes in the meniscus, such as meniscal extrusion or subluxation, are also responsible for JSN ( Fig. 1 ) . The lack of sensitivity and specificity of radiography for the detection of OA-associated articular tissue damage and its poor sensitivity to change at follow-up imaging are important limitations of this modality. Variations in semi-flexed knee positioning, which occur during image acquisition despite standardization, can also be problematic. Such variations can affect the quantitative measurement of various radiographic parameters of OA including JSW . Despite these limitations, radiography remains the gold standard for establishing an imaging-based diagnosis of OA and assessment of structural modification in clinical trials of knee OA ( Fig. 2 ).




Fig. 1


Comparison of magnetic resonance imaging (MRI) and radiography for visualization of knee osteoarthritis. A. Baseline posterior–anterior radiograph shows normal medial tibiofemoral joint space width (arrows). B. At 3-year follow-up, definite joint space narrowing is observed. C. Baseline MRI of same knee shows multiple tissues relevant to osteoarthritis not depicted by the radiograph: Cartilage is visualized in a direct fashion as a structure of intermediate signal intensity in this proton-density weighted coronal MRI image (white arrows). The anterior (white arrowhead) and posterior (black arrowhead) cruciate ligaments are clearly depicted as hypointense structures. In addition, the menisci are visualized as hypointense triangular structures in the medial and lateral joint spaces (black arrows). Note that the medial meniscus is aligned with the medial joint margin (white line). D. At the 3-year follow-up, the MRI shows incident meniscal extrusion of the medial meniscal body, responsible for radiographic joint space narrowing (arrowheads and white line). No cartilage loss is observed during the follow-up interval.



Fig 2


Radiographic diagnosis of osteoarthritis. Follow-up of a patient with anterior cruciate ligament disruption. A. At baseline, only a small equivocal osteophyte is depicted at the medial joint margin (arrowhead). B. At the follow-up examination 3 years later, definite osteophytes at the medial joint margin are observed at the tibia (arrow) and femur (arrowhead).


Semiquantitative assessments


The severity of radiographic OA can be assessed using semi-quantitative scoring systems. The Kellgren and Lawrence (KL) grading system is a widely accepted scheme used for defining radiographic OA based on the presence of a definite osteophyte (=grade 2) ( Fig. 2 ). However, KL grading has its limitations; in particular, KL 3 summarizes a scale of JSN severity from “definite” to almost “bone-to-bone” that cannot be accounted for. A modification of KL grading has been suggested to improve the sensitivity to change in longitudinal knee OA studies , with a recommendation that OA be defined by a combination of JSN and the presence of definite osteophytes in a knee that did not have this combination on the prior radiographic assessment. For OA progression, a focus on JSN alone using either a semi-quantitative or a quantitative approach was recommended.


The Osteoarthritis Research Society International (OARSI) atlas uses a different approach and grades tibiofemoral JSN and osteophytes separately for each compartment (medial tibiofemoral, lateral tibiofemoral, and patellofemoral) of the knee. This compartmental scoring appears to be more sensitive to longitudinal radiographic changes than KL grading . A recent study using data from the Osteoarthritis Initiative (OAI) demonstrated that the centralized radiographic reading is important from the viewpoint of observer reliability, as even expert readers seem to apply different thresholds for JSN grading .


Quantitative assessments


Quantitative JSW measurements can be accomplished either manually or by a software application. JSW is the distance between the projected femoral and tibial margins on the radiographic image. Quantification of JSW using image-processing software does require a digital image either, with digitized plain films or images acquired using fully digital modalities, such as computed radiography and digital radiography. Minimum JSW is the standard metric, but some groups have investigated the use of location-specific JSW . Various degrees of responsiveness have been observed depending on the degree of OA severity, length of the follow-up period, and the knee positioning protocol .


Measurements of JSW obtained from knee radiographs have been found to be reliable, especially when the study lasted longer than 2 years and when the radiographs were obtained with the knee in a standardized flexed position . Studies of hip OA have generated conflicting results when correlating JSW and symptoms. However, it has been shown that JSW can predict hip joint replacement .




MRI


Because of high cost per examination, MRI is not routinely used in clinical initial assessment or during disease follow-up of OA patients. However, MRI has become a key imaging tool for OA research thanks to its ability to visualize pathologies that are not detected on radiographs, that is, articular cartilage, menisci, ligaments, synovium, capsular structures, fluid collections, and bone marrow lesions (BMLs) . MRI enables the following: the joint can be evaluated as a whole organ; multiple tissue changes can be monitored simultaneously over several time points; pathologic changes of pre-radiographic OA can be detected at a much earlier stage of the disease; physiologic changes within joint tissues (e.g., cartilage and menisci) can be assessed before morphologic changes become apparent.


An important point to note is that one needs to select appropriate MRI pulse sequences for the purpose of each study. For example, focal cartilage defects and BMLs are best assessed using fluid-sensitive fast spin echo sequences (e.g., T2-weighted, proton density-weighted or intermediate-weighted) with fat suppression ( Figs. 3 and 4 ) . Meniscal tears are better visualized on standard turbo spin echo sequences compared to three-dimensional (3D) gradient echo sequences ( Fig. 5 ). MR images may sometimes be affected by artifacts that mimic pathological findings. For example, so-called susceptibility artifacts can be misinterpreted as cartilage loss or meniscal tear if the observer is unaware of this phenomenon . Gradient recalled echo sequences are known to be particularly prone to this type of artifact ( Fig. 6 ) . To ascertain optimal assessment of MRI-derived data, trained expert musculoskeletal radiologists should be consulted when designing imaging-based OA studies and interpreting data generated in those studies.




Fig. 3


Longitudinal evaluation of focal cartilage lesion using MRI. Example shows development of small focal cartilage defect over a 2-year time period visualized by intermediate-weighted MRI, which is ideally suited to depict early focal cartilage surface changes. A. At baseline, very discrete surface indentation of cartilaginous surface is observed (arrowhead). B. At the 2-year follow-up, a definite fissure-like full thickness defect has developed, which undermines the chondral coverage representing partial delamination. The chondral fragment is at high risk of detachment.



Fig. 4


Role of sequence selection in MRI assessment of different osteoarthritis features. A. Coronal fast low angle shot (FLASH) image shows an area of intrachondral low signal within the weight-bearing portion of the lateral femur (arrowhead). B. Corresponding coronal intermediate-weighted fat-saturated image shows that this signal change corresponds to a focal full-thickness defect that was not visualized on the FLASH image. Conventional spine echo sequences are superior in depicting focal cartilage lesions.



Fig. 5


Comparison of intermediate-weighted (IW) fat-suppressed image and dual echo at steady state (DESS) image for the detection of a meniscal tear. A. A horizontal oblique tear is shown at the posterior horn of the medial meniscus visualized as a hyperintense line reaching both the inferior and superior surfaces of the mensicus (arrows). B. The corresponding DESS image shows only intrameniscal hyperintensity (arrowhead), a nonspecific finding on unknown relevance.



Fig. 6


Artifacts on MRI. A. Coronal dual echo steady state (DESS) image shows a hypointense linear finding in the medial tibiofemoral joint space. So-called vacuum phenomenon is responsible for this artifact, which must not be mistaken as a solid structure. Assessment of the articular surface is impaired and signal loss with the cartilaginous contour must no be mistaken as a surface lesion (white arrow). B. Coronal IW image also shows artifact (arrow), but clearly depicts some remaining cartilage in the medial tibiofemoral joint.


An MRI-based definition of OA has recently been proposed . Tibiofemoral OA on MRI is defined as either (a) the presence of both, definite osteophyte formation and full-thickness cartilage loss, or (b) the presence of one of the features in (a) and one of the following: subchondral BML or cyst not associated with meniscal or ligamentous attachments; meniscal subluxation, maceration or degenerative (horizontal) tear; partial-thickness cartilage loss; and bone attrition. In addition, with MRI, OA can be classified into hypertrophic and atrophic phenotypes, according to the size of the osteophytes .


Importantly, the use of MRI has led to significant findings about the association of pain with BMLs and synovitis , with implications for future OA clinical trials. Systematic reviews have demonstrated that MRI biomarkers of OA have concurrent and predictive validity, with good responsiveness and reliability . The OARSI–FDA Working Group now recommends MRI as a suitable imaging tool for cartilage morphology in clinical trials .


Semiquantitative MRI assessment of knee OA


A detailed review article focusing on semiquantitative MRI assessment of OA has been published recently , and we will give an essential summary of this approach in this article. In addition to the three well-established scoring systems – the Whole Organ Magnetic Resonance Imaging Score (WORMS) , the Knee Osteoarthritis Scoring System (KOSS) , and the Boston Leeds Osteoarthritis Knee Score (BLOKS) – a new scoring system called the MR Imaging Osteoarthritis Knee Score (MOAKS) has been added to the literature. Of the three systems, WORMS and BLOKS have been widely disseminated and used, though only a limited number of studies have directly compared the two systems. Two recent studies identified the relative strengths and weaknesses of the two systems in regard to certain features assumed to be most relevant to the natural history of the disease, including cartilage, meniscus, and BMLs . WORMS and BLOKS have their weaknesses and it may be difficult for investigators to choose which is more suitable for the particular aims of the study they are planning. Additionally, both these systems have undergone unpublished modifications that make it difficult for general readers to determine the differences between the original description and how they have been applied in later research. The use of within-grade changes for longitudinal assessment of cartilage damage and BMLs is a good example , which has also been applied to radiographic OA assessment in order to increase sensitivity to change . Within-grade scoring describes progression or improvement of a lesion that does not meet the criteria of a full-grade change, but it does represent a definite visual change. It has become common practice to incorporate these within-grade changes whenever longitudinal cartilage assessment is contemplated, and a recent study demonstrated that within-grade changes in semiquantitative MRI assessment of cartilage and BMLs are valid and their use may increase the sensitivity of semiquantitative readings in detecting longitudinal changes in these structures .


By integrating expert readers’ experience with all of the available scoring tools and the published data comparing different scoring systems, MOAKS was developed as a refined scoring tool for cross-sectional and longitudinal semiquantitative MR assessment of knee OA. It includes semiquantitative scoring of the following pathological features: BMLs; subchondral cysts; articular cartilage; osteophytes; Hoffa-synovitis and synovitis-effusion; meniscus; tendons and ligaments; and periarticular features such as cysts and bursitides. Using MOAKS, Bloecker and colleagues showed that knees with medial JSN were associated with greater meniscal extrusion and damage compared to knees without medial JSN . Since MOAKS is a new scoring system, it needs more data to demonstrate its validity and reliability when applied to OA studies.


Synovitis is an important feature of OA and shows a demonstrated association with pain . The mechanically induced joint injury is thought to lead to variable inflammatory responses . Although synovitis can be evaluated with non-contrast-enhanced MRI by using the presence of signal changes in Hoffa fat pad or joint effusion as an indirect marker of synovitis, only contrast-enhanced MRI can reveal the true extent of synovial inflammation ( Fig. 7 ) . Scoring systems of synovitis based on contrast-enhanced MRI have been published , and these could potentially be used in clinical trials of new OA drugs that target synovitis.




Fig. 7


Visualization of synovitis using non-enhanced and contrast-enhanced MRI. A. Axial proton-density weighted fat-saturated image shows marked hyperintensity within the joint cavity suggesting severe joint effusion (asterisk). In addition, there is a large subchondral cyst in the lateral facet of the patella (arrowhead) and diffuse bone marrow edema in the lateral patella and trochlea (arrows). B. Axial T1-weighted fat-saturated image after contrast administration clearly visualizes severe synovial thickening depicted as contrast enhancement (asterisks). The arrow points to true amount of effusion, which is only discrete and visualized as linear hypointensity within the joint cavity.


Semiquantitative MRI assessment of hand OA


Radiography is still the imaging modality of choice clinically for OA of the hand, but the use of more sensitive imaging techniques such as ultrasound and MRI is becoming more common, especially in OA research ( Fig. 8 ). However, the literature concerning MRI of pathological features of hand OA is still sparse, and studies have been performed without applying standardized methods . In 2011, Haugen and colleagues proposed a semiquantitative MRI scoring system for hand OA features using an extremity 1.0 T MR system, called the Oslo Hand OA MRI Score (OHOA-MRI) : it incorporates osteophyte presence and JSN (0–3 scale) and malalignment (absence/presence) similar to the OARSI atlas . Scoring of key pathological features such as synovitis, flexor tenosynovitis, erosions, osteophytes, JSN, and BMLs showed good to very good intra- and inter-reader reliability. Using this scoring system, Haugen and colleagues showed that MRI could detect approximately twice as many joints with erosions and osteophytes as conventional radiography ( p < 0.001), but identification of JSN, cysts, and malalignment was similar . The same group of investigators showed in another study that MRI-assessed moderate/severe synovitis, BMLs, erosions, attrition, and osteophytes were associated with joint tenderness independently of each other . These studies demonstrated that some of the semiquantitatively assessed MRI features of hand OA may be potential targets for therapeutic interventions.




Fig. 8


Finger osteoarthritis. Distal interphalangeal joint shows characteristic radiographic signs of osteoarthritis including marginal osteophyte formation (arrows) and asymmetric joint space narrowing (arrowhead). Soft tissue changes such as synovitis are only poorly visualized by X-ray and are depicted as increased soft tissue opacity reflecting soft tissue swelling.


Semiquantitative MRI assessment of hip OA


The hip joint has a spherical structure and its very thin covering of articular hyaline cartilage makes MRI assessment of the hip much more difficult than the knee ( Fig. 9 ). Roemer and colleagues developed a whole-organ semiquantitative multi-feature scoring method called the Hip Osteoarthritis MRI Scoring System (HOAMS) for use in observational studies and clinical trials of hip joints . In HOAMS, 14 articular features are assessed: cartilage morphology, subchondral BMLs, subchondral cysts, osteophytes, acetabular labrum, synovitis (only scored when contrast-enhanced sequences were available), joint effusion, loose bodies, attrition, dysplasia, trochanteric bursitis/insertional tendonitis of the greater trochanter, labral hypertrophy, paralabral cysts and herniation pits at the supero-lateral femoral neck ( Fig. 10 ). HOAMS demonstrated satisfactory reliability and good agreement concerning intra- and inter-observer assessment, but further validation, assessment of responsiveness, and iterative refinement of the scoring system are still needed to maximize its utility in clinical trials and epidemiological studies.




Fig. 9


Multimodality imaging of severe hip osteoarthritis with pathologic correlation. A. Anterior–posterior radiograph shows marked joint space narrowing and an aceteabular oseophyte. In addition, there are distinct subchondral cystic lesions in the femoral head (arrows) and acetabulum (arrowheads). B. Coronal proton-denisty-weighted MRI depicts these subchondral cysts as hyperintense, fluid-equivalent lesions in the acetabulum (large arrows) and femoral head (small arrows). Note in addition, there is marked diffuse bone marrow edema viaualized as areas of hyperintensity in the femoral head (asterisks). C. Corresponding hematoxylin-eosin stain of histologic cut of femoral head confirms large subchondral cysts of the femoral head (arrows). Eosinophilic changes of the femoral head in the subchondral bone represent a mixture of edema, subchondral sclerosis, and fibrosis (asterisks).



Fig. 10


Hip osteoarthritis: Sagittal intermediate-weighted fat-suppressed image shows diffuse full-thickness cartilage loss at the central superior weight bearing part of the joint. Note that due to the physiologic very thin cartilage, a clear delineation of acetabular and femoral cartilage is not possible. In addition, there are subchondral BMLs in the femoral head (arrows) and acetabulum (arrowheads).


MRI assessment of spine OA


MRI enables imaging evaluation of the morphologic changes of the lumbar spine, including alterations of the disc and vertebral endplate, facet joint lesions, spinal canal narrowing, and nerve root compromise ( Fig. 11 ). Pfirrmann et al. proposed a five-level classification system specifically for lumbar intervertebral disc degeneration based on sagittal images from routine T2-weighted MRI with grade I representing normal findings and grade V corresponding to the most severe degenerative changes. More recently, Griffith et al. conducted a reliability study for an eight-level modified Pfirrmann grading system that includes a description of the alterations expected for each grade and a panel of 24 reference images, demonstrating this method to be reliable and useful for discerning severity of disc degeneration in elderly subjects.




Fig. 11


Osteoarthritis of the lumbar spine. Sagittal T2-weighted MRI shows marked degenerative changes including narrowing of the intervertebral spaces (arrowheads), marked disk bulging (arrows), and osseous endplate changes representing lipomatous marrow conversion (Modic II changes). Multisegmental spinal canal stenosis is observed as a result of disk alterations. In comparison to CT, MRI superiorly depicts soft tissue changes and bone marrow alterations.


Friedrich et al. graded facet joint OA on a 0–3 scale following MRI evaluation of disc degeneration and herniation, scoliosis and anterolisthesis using criteria adapted from a CT-based scoring system . The overall findings of this study suggested that degenerative changes of the facet joints are mainly attributable to degenerative disc disease and that instability at a discovertebral joint is associated with stress and overload of the facet joints.


A recent epidemiologic study from Japan reported a very high prevalence of MRI-detected disc degeneration (grades 4 and 5 in the Pfirrmann Classification) of >70% in people under 50 years and more than 90% in people older than 50 . Age and obesity were associated with the presence of disk degeneration at all levels, and low back pain was associated with the presence of degenerative disc disease in the lumbar region.


MRI assessment of shoulder OA


To the authors’ knowledge, only one study has reported semiquantitative grading of acromioclavicular joint OA: de Abreu et al. developed a scoring system in which, acromioclavicular joint OA severity on scale of 1–3 was defined according to the presence – and the size for selected features – of hyperintensity on T2-weighted images indicative of subchondral cysts, bone sclerosis, osteophytes, soft-tissue proliferation, and mass effect on the rotator cuff. Using this grading scheme, the researchers demonstrated that features of acromioclavicular joint OA are more frequently detected with MRI than with conventional radiography and concluded that better evaluation of acromioclavicular joint OA and the effect of this disease on the underlying rotator cuff is possible with MRI ( Fig. 12 ) .




Fig. 12


MRI of shoulder osteoarthritis. A. Coronal non-fat-suppressed T1-weighted image of glenohumeral osteoarthritis. Bony pathology is well visualized on T1-weighted non-fat-suppressed MRI. A large inferior osteophyte is present at the humeral head (small arrow). A small calcified loose body is seen adjacent to osteophyte (white arrowhead). Subchondral sclerosis is depicted as linear hypointensity directly adjacent to humeral cortex (large arrows). B. Coronal T1-weighted fat-saturated image after intravenous contrast administration shows marked synovitis in the axillary recess and an additional osteophytes at the inferior glenoid that was not depicted on the T1 weighted non-fat-suppressed image (arrow). In addition, there is a complete tear of the supraspinatus tendon medial to the tendon attachment at the greater tubercle (arrowhead). Note areas of diffuse bone marrow edema in the humeral head (asterisks).


Quantitative analysis of articular cartilage and other tissues


Quantitative measurement of cartilage morphology requires high-resolution 3D imaging sequences that delineate the bone–cartilage interface and cartilage surface with adequate contrast. Such measurements have been validated in spoiled gradient echo images and more recently in double echo steady-state images , and the sensitivity to change has been reported for both image contrasts . Cartilage quantification requires segmentation of the hyaline cartilage tissue ( Figs. 13 and 14 ) and exploits the 3D nature of MRI data sets to evaluate tissue dimensions (such as thickness, area volume, and others) as continuous variables. A nomenclature for MRI-based cartilage measures was proposed by Eckstein and colleagues : for example, VC, cartilage volume; AC, area of cartilage surface; tAB, total area of subchondral bone; dAB, denuded area of subchondral bone; ThCtAB.Me, mean cartilage thickness over the tAB; and others. Because the above measures are partly correlated among each other, Buck et al. identified a core subset of measures that provide independent information cross-sectionally and longitudinally: these were ThCtAB.Me, tAB, and dAB . Among these, dAB was shown to be associated with concurrent and incident knee pain . Change in ThCtAB.Me was also shown to be related to an important clinical outcome, that is, the likelihood of having knee replacement in the future , in particular when cartilage loss occurred in the central medial femorotibial compartment .




Fig. 13


High-resolution knee MRI obtained with spoiled gradient-echo (SPGR) sequences with water excitation, in the same person: (A) sagittal image; (B) axial image; (C) coronal image; (D) same coronal image with the medial tibial cartilage marked (i.e., segmented) blue, medial femoral cartilage marked yellow, lateral tibial cartilage marked green, and lateral femoral cartilage marked red.



Fig. 14


(A, B) 3D reconstruction and visualization of knee cartilage plates from a sagittal MR imaging data set. A. View on to the medial side, B. view on to the lateral side: medial tibial cartilage marked blue, medial femoral cartilage marked yellow, lateral tibial cartilage marked green, lateral femoral cartilage marked red, femoral trochlear cartilage marked turquoise, and patellar cartilage marked magenta.


Analysis in total knee cartilage plates and compartments has been extended methodologically to reporting changes in defined subregions . The spatial pattern of subregional cartilage change has been reported in various cohorts , including OAI participants with 1-, 2-, and 4-year follow-up . These approaches have led to the observation that (regional) cartilage thickening, predominantly in the external medial femoral condyle, likely may be an early event in OA pathophysiology . Based on subregional cartilage analysis, an (extended) ordered values approach was proposed for analyzing the magnitude of subregional changes in cartilage thickness independent of their anatomic location . This approach was found more efficient in discriminating longitudinal rates of change between healthy knees and those with different radiographic OA grades , and superior in detecting risk factors of OA progression .


Among different predictors of structural progression , malalignment and baseline medial or lateral radiographic JSN of the affected compartment were particularly effective in identifying participants with a high risk of subsequent cartilage loss. This relationship is likely because of an association between high dynamic load and cartilage loss . Systemic and subchondral bone density and subchondral trabecular structure were also found to have an association with cartilage change , the latter also with the risk of knee replacement . Distinct from these structural predictors, presence of frequent pain at baseline was independently associated with structural progression . Further, the amount of physical activity, measured by a pedometer, was deleteriously related to knee structural change, but only in those with preexisting structural abnormalities and with low baseline cartilage thickness . Further, weight gain was associated with greater cartilage loss, while weight loss was associated with less cartilage volume loss in subjects with meniscal tears; however, no such relationship was found in the (larger) subcohort without meniscal lesions .


The relationship between cartilage loss and endocrine factors has also been explored: In a cross-sectional study, Wei et al. observed that parity, but not the use of hormone replacement therapy or oral contraceptives, was independently associated with lower tibial cartilage volume. Stannus et al. recently reported that serum leptin levels, high body mass index (BMI), and high trunk and high total body fat were negatively associated with knee cartilage thickness. The latter associations disappeared after adjustment for leptin, indicating that this “adipokine” may mediate the association between obesity and cartilage thickness. Baseline leptin levels were also associated with longitudinal cartilage thinning, and the authors suggested that leptin leads to catabolic cartilage degradation when present in excess, whereas it may involve anabolic chondrocyte activity and beneficial effects on cartilage under physiological conditions .


Quantitative measurements of cartilage volume and thickness change have been used as outcomes in intervention studies, for instance, evaluating the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) , celecoxib , physical exercise , licofelone , chondroitin sulfate , and sprifermin (fibroblast growth factor 18) on articular cartilage. In these studies, drug effects were observed laterally, but they mostly did not reach statistical significance in the medial compartment. Nevertheless, quantitative methods were reported to be superior to semiquantitative ones in assessing cartilage change and in detecting structure modification by drug treatment . A 2-month surgical joint distraction was found to be very effective in regenerating cartilage in participants with late-stage knee OA, increasing cartilage thickness and decreasing denuded areas . A sustained benefit on cartilage structure after this intervention was observed also after a 2-year follow-up .


Quantitative MRI analysis of the meniscus


Wirth and colleagues presented a technique for 3D quantitative analysis of meniscal shape, position, and signal intensity , which was shown to display adequate inter-observer and intra-observer precision . Quantitative measures of extrusion were found to display moderate correlations with semiquantitative (MOAKS) extrusion scores . However, both the quantitative and semiquantitative extrusion measures only partly explained coverage of tibial cartilage by the meniscus, and a negative association between meniscus width and tibial coverage was observed, which was as strong as that of extrusion . Semiautomatic segmentation approaches to the meniscus also have been explored .


When examining healthy reference subjects from the OAI, Bloecker et al. found the meniscus surface area to strongly correspond with tibial plateau area in the same compartment and tibial coverage by the meniscus to be similar between men and women (50% in the medial and 58% in the lateral compartment) . In knees with medial radiographic JSN, medial tibial coverage was, however, only 36% in JSN1 and as little as 31% in JSN2/3 knees, compared with 45% in contralateral no-JSN knees . The medial JSN knees showed greater meniscus extrusion and damage (MOAKS), but no significant difference in meniscus volume; no differences in lateral meniscus measures were observed between knees with and without medial JSN . In the same cohort, side differences in medial radiographic JSW were found to be associated with the percentage of medial tibial plateau coverage by the meniscus ( r 2 ≈ 25%), whereas lower correlation coefficients were observed for other meniscus measures, such as size and extrusion . The between-knee differences of radiographic JSW most strongly correlated with side differences in cartilage thickness of the central medial, weight-bearing femur ( r 2 ≈ 50%), whereas other femorotibial subregions displayed lower coefficients . The exclusion of the knees with nonoptimal alignment (i.e., rim distance) between the tibial plateau and the X-ray beam improved the correlation with femoral cartilage thickness with radiographic JSW to ≈65%, whereas the relationship with meniscus measures was not affected . These findings suggest that radiographic JSW provides a better representation of (central) femoral cartilage thickness when optimal radiographic positioning is achieved .


Comparing quantitative meniscus position, size, and shape measures between OA and healthy reference knees, the peripheral margin appeared more bulged, with lesser tibial coverage and greater extrusion in OA knees . While no difference in medial meniscus size was observed, the lateral meniscus body displayed a slightly larger volume (as well as more bulging and extrusion) than healthy knees . The authors also described an association between meniscal extrusion and presence/absence of knee pain between contralateral knees with discordant pain and concordant radiographic knee OA status . These results suggest that meniscus extrusion is associated with pain, independently of radiographic status, potentially through mechanical irritation of the joint capsule.


Other than menisci, investigators have used quantitative MRI to assess BMLs , synovitis , and joint effusion . However, it should be kept in mind that using segmentation approaches for ill-defined lesions such as BMLs is more challenging than segmentation of clearly delineated structures, such as cartilage, menisci, and effusion.


Compositional MRI


Compositional MRI allows visualization of the biochemical properties of different joint tissues. It is therefore very sensitive to early, pre-morphologic changes that cannot be seen on conventional MRI. The vast majority of studies applying compositional MRI has focused on cartilage, although the technique can also be used to assess other tissues, such as the meniscus or ligaments. Compositional imaging of cartilage matrix changes can be performed using advanced MRI techniques, such as delayed Gadolinium Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC), T1 rho, and T2 mapping ( Fig. 15 ) .


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Nov 10, 2017 | Posted by in RHEUMATOLOGY | Comments Off on The role of imaging in osteoarthritis

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