Abstract and Introduction
Ultrasound has become popular among rheumatologists as the first-choice imaging investigation for the evaluation and monitoring of osteoarthritis (OA). Because of recent improvement in technology, ultrasound has the ability to demonstrate and assess the minimal structural abnormalities, which involve the pathophysiology and progression of OA, such as articular cartilage, synovial tissue, bony cortex, and other soft tissue. Nowadays, ultrasonography is a promising technique for assessing soft tissue abnormalities such as joint effusion, synovial hypertrophy, Baker cyst, and other structural changes including the decrease in cartilage thickness, meniscus bulging, and formation of osteophyte. Ultrasonography not only possesses diagnostic potential in knee OA but also reveals long-term predictability for disease progress as imaging biomarker. Ultrasonography has also been proven as a useful tool in guiding therapeutic interventions and monitoring treatment effectiveness. This review addresses the utility, reliability, and potential utilization of ultrasonography as an imaging technique in knee OA.
Osteoarthritis (OA) is the most common cause of rheumatic disorder and a frequent health problem in the community where symptomatic knee OA has been prevalent in 6% to 10% of the adult population. Traditionally, OA has been defined as degenerative changes in bone, cartilage, and the soft tissues of the joints. Recently, OA is regarded as a failure of the joint as an organ, much like renal or cardiac failure.[1,2] Nondestructive synovial proliferation, joint effusions, popliteal cysts, tendonitis, and bursitis are frequent findings in OA. Therefore, an imaging modality is requisite in order to assess the various structures within and around the joint, to measure a variety of the pathological aspects of OA.
As a criterion standard, radiological imaging has been used to diagnose and classify the severity of knee OA such as the Kellgren and Lawrence system. However, radiographs have several limitations, such as the inability to evaluate soft tissue structures and the related inflammation. In addition, radiographic features of OA do not agree with the symptoms of OA.
In recent years, the imaging techniques such as ultrasonography (US) have been used for better understanding and assessing the pathology of different musculoskeletal diseases. Ultrasonography affords the abilities of scanning multiple planes at the same joint, providing a "one-stop" answer to many rheumatic problems, which is not answerable only by clinical examination. Ultrasonography has no hazard of ionizing radiation and can provide the multiplanar nature of the modality. It can also visualize soft tissue structures such as the meniscal extrusion and cartilage, which involve the pathophysiology and progression of OA.[8,9] This relatively inexpensive technology with the added advantages of portability and real-time dynamic examination can lead to a diagnostics service in the community. Modern US systems can use beam steering and compound imaging technologies to allow wider fields of view. High-resolution probes with frequencies of up to 20 MHz are being applied in routine joint assessment. To address the utility, reliability, and potential uses of US as an imaging technique in knee OA, we searched the articles in MEDLINE (34), EMBASE (65), EBM Reviews (29), AMED (3), Scopus (63), Web of Science (76), and the Cochrane Central Registers for Controlled Trials from their conception up to September 2015. These databases were looked up individually for all possible terms and combination of terms to accommodate differences in their search engines. Hand searches were also performed in addition to additional searches through Google Scholar and Reference Manager Search engines. The keywords used in combination (OR) are knee osteoarthritis, knee osteoarthrosis, osteoarthritis, ultrasonography, and ultrasound. The combination (AND) is used between knee osteoarthritis/knee osteoarthritis and ultrasonography/ultrasound. All key terms are limited to title/abstract. Then the duplicate terms are removed, and among the maximum 105 full texts, articles concerning therapeutic ultrasound or animal studies are excluded for narrative review.
Cartilage thickness ranges from 0.1 mm on the articular surface of the head of the proximal phalanx to 2.6 mm on the lateral femoral condyle of the knee joint. In 1984, ultrasound was used to determine the thickness of the articular cartilage, as well as to detect changes in its surface and internal characteristics such as the ratings of clarity and sharpness. Loss of clarity of the cartilaginous layer and loss of the normal sharpness of the synovial space–cartilage interface are the earlier features of cartilage damage.
The weight-bearing surfaces of the femoral cartilage can be assessed by transverse suprapatellar scan with the knee in maximal flexion (Fig. 1) or with an infrapatellar transverse scan with the leg fully extended. Cartilage is characterized in early OA by loss of the sharp contour and the various echogenicities of the cartilage matrix on the ultrasound images. An asymmetric narrowing of the cartilaginous band follows in the later disease process. It was reported that multiple sonographers demonstrated good reproducibility and high levels of agreement between US and histology in assessing the normal to moderately damaged cartilage. In addition, measurement of cartilage thickness is rapid (several seconds), painless, and noninvasive.
It has been demonstrated that the ultrasonographic grading (in vitro) of femoral cartilage correlated well with the histologic grading (OARSI Osteoarthritis Cartilage Histopathology Assessment System) of anterior and middle areas of femoral articular cartilage (ρ = 0.78, 0.89, both P < 0.001). According to this ultrasonographic grading, grade 1 showed a homogenously anechoic cartilage band with sharp anterior and posterior margins; grade 2 showed blurring or obliteration of the margin of the cartilage band; grade 3 included blurring, obliteration of the margin, and narrowing of the cartilage band; grade 4 was coded if the cartilage band could not be visualized.
Recently, it was reported that the semiquantitative ultrasonographic grading system may well reflect the clinical symptoms and functions in knee OA on evaluation against the visual analog scale, Western Ontario and McMaster Universities Arthritis Index, and Lequesne index.[17,18] The US grading system for femoral cartilage has been proposed after validating against the arthroscopic Noyes grading for cartilage degeneration, and this outcome score includes assessment of local reduction of thickness, loss of the normal sharpness of cartilage interfaces, and increased echogenicity. The cartilage was evaluated as grade 0 if they showed a monotonous anechoic band with sharp hyperechoic anterior and posterior interfaces. Grade 1 changes include loss of the normal sharpness of cartilage interfaces and/or increased echogenicity of the cartilage. Grade 2A changes were as follows: in addition to the previously mentioned changes, clear local thinning (<50%) of the cartilage. Grade 2B changes showed local thinning of the cartilage of more than 50% but less than 100%. Grade 3 changes included 100% local loss of the cartilage tissue (Fig. 2). The sum of cartilage grades in all 3 sites of the femoral cartilage at the medial and lateral femoral condyles, as well as at the intercondylar notch area (sulcus) had the highest correlation between US and arthroscopy (rs = 0.655, P < 0.001). However, it still needs further validation studies, which might include, for example, quantitative magnetic resonance imaging or histology as references. Noninvasive knee US is a promising technique for screening and evaluating degenerative changes of articular cartilage.
Typical examples of different cartilage degenerative US grades (0, 1, 2A, 2B, 3) in the knee joint.20 Reprinted with permission from Elsevier.
The early bone changes in the OA joint are characterized by hyperechoic signal at the site of the attachment of the joint capsule to the bony cartilaginous margin, which will eventually form as osteophytes on the conventional radiography. In advanced disease, the bony profile of the osteophytes is evident. Moderate to substantial validity was reported in comparing ultrasonographic osteophytes to those seen on radiographs.
A novel atlas for scoring osteophytes in the tibiofemoral joint was used to prove that the US was more sensitive in detecting osteophytes than plain radiographs at the medial compartment of the tibiofemoral joint (Fig. 3). Furthermore, osteophyte size detected with US, compared with only their presence, is a better predictor of the articular cartilage degeneration as there is a significant correlation between osteophyte size (summed US grade) and the arthroscopic grade of degenerative changes of the articular cartilage at the medial compartment. The grading of osteophyte size was as follows: grade 0 included no osteophytes, that is, a smooth cortical surface; grade 1 demonstrated small and distinct cortical protrusion(s) of the bony surface; grade 2 showed larger protrusion(s) of the bony surface; grade 3 included very large protrusion(s) of the bony surface. However, it should be noted that this result is based on a small trial of 26 patients.
The US atlas for knee osteophyte detection.23 Reprinted with permission from Taylor & Francis.
Recently, US score is developed in knee OA and includes relevant domains measuring (1) morphological changes in the medial compartment and lateral compartment such as osteophyte and meniscus extrusion, (2) inflammatory markers in medial compartment and lateral compartment such as synovial hypertrophy and Doppler activity, and (3) effusion. Bony changes demonstrated a strong correlation between the morphological changes in the medial and lateral compartments and the corresponding Kellgren-Lawrence score. Total ultrasound score displayed substantial reliability and reproducibility, with interclass correlations coefficients ranging from 0.75 to 0.97. Construct validity was confirmed with statistically significant correlation coefficients (0.47–0.81, P < 0.01). However, relevance for longitudinal studies remains to be demonstrated, for example, during treatment.
Soft Tissue Changes
It has been increasingly recognized that synovitis plays a more important role in the pathogenesis of OA than previously thought. A small to moderate amount of synovitis and effusion is commonly detected in patients with knee OA (Fig. 4). Depending on the study, between 47% and 100% of patients were noted to have synovitis and/or effusion of the symptomatic knee.[25,26] A large European League Against Rheumatism study of 600 people with knee OA demonstrated synovial hypertrophy or effusion in 46%. Synovial hypertrophy was defined as synovial thickening of ≥4 mm and effusion recorded as present or absent based on the depth of fluid of more than 4 mm or less than 4 mm in the suprapatellar recess. Ultrasonography is more sensitive than clinical examination in detecting synovitis and correlates well with magnetic resonance imaging and arthroscopic findings. Synovitis or joint effusion detected by US also shows a relationship with pain in knee OA.[28–30]
The serial arthroscopies performed on knees with symptomatic but preradiographic OA revealed a clear association between the presence of synovitis and the future development of medial cartilage loss (an odds ratio for progression of the arthroscopic chondropathy score of 3.11 [1.07–5.69]), suggesting that, at its earliest stages, before visible cartilage degeneration has occurred, ultrasonographic synovitis has a potential role in predicting the structural progression of knee OA.
Power Doppler can be utilized to assess synovial flow, which denotes increased synovial vascularization (Fig. 5). Increased Doppler signal correlates with increased vascularity seen on histologic examination of synovial tissue of knee OA. In a study that used a novel technique of digital synovial vascularization quantification with contrast enhancement for detecting synovitis in patients with knee OA, US of the superior recess revealed an effusion or synovial thickening in 58% in B-mode, 63% in power Doppler sonography, and 95% with contrast medium enhancement.
Increased bidirectional Power Doppler signals in the suprapatellar fat pad and quadriceps tendon around the suprapatellar recess. Sagittal plane (in black and white).
On the other hand, there were reports that no association between US features and the degree of knee pain was detected after 1-year follow-up, and further studies are still warranted to answer which part of pain in knee OA is explained by soft tissue pathology and whether US is the imaging method of choice to measure this pathology.
In a systemic review in 2009, a paucity of reliability data was highlighted with regard to interreader and intrareader reliability in image acquisition and the scoring of stored images.
Monitoring and Intervention
In clinical trials in knee OA, outcome measures usually include structural assessment, functional status, and the level of pain. Serological markers are unavailable for monitoring disease progression in OA, and imaging markers using US abnormalities will be valuable in this scenario. Studies are still lacking to identify and precisely determine a population in which OA progresses more rapidly.
Recently, US prediction in the long-term progress of knee OA is reported. After 1-year follow-up, meniscal protrusion (Fig. 6) and Baker cyst (Fig. 7) might be useful for long-term prediction of clinical or radiological outcome, although effusion, synovial hypertrophy, and infrapatellar bursitis seem to be more temporary phenomena. A longitudinal association between Baker cyst at baseline and radiological and clinical progression was found after 2-year follow-up.
Longitudinal ultrasonographic images of the medial joint line (in black and white). A, Position of probe footprint. B, Ultrasonographic image of a normal knee shows distal femur (f), proximal tibia (t), triangular outline of the medial meniscus (m, dashed arrows), and the linear echoes produced by the medial collateral ligament (mcl, solid arrows). C, Ultrasonographic image shows medial meniscal extrusion (m, dashed arrows). D, Ultrasonographic image in knee OA demonstrates medial meniscal extrusion (m) with resulting displacement of the medial collateral ligament (arrows) and obvious osteophytes (*) proximal and distal to the joint line.11 Reprinted with permission from Elsevier.
In another study, increased meniscal bulging and presence of Baker cyst/joint effusion were correlated with worse pain or poorer function.
A 3-year multicenter European League Against Rheumatism prospective study determined the predictors for joint replacement in more than 500 subjects with knee OA. The multivariate analysis demonstrated that the presence of a joint effusion (≥4 vs. <4 mm) at baseline was a significant independent predictor of joint replacement at 3 years (hazard ratio, 2.63 [95% confidence interval, 1.70–4.06]).
Ultrasonography has proved to be an effective and safe imaging method for guiding intra-articular injections because of the advantage of visualizing the proper needle positioning inside the joint cavity. In a study of 62 patients with symptomatic knee OA to investigate the predictive value of US characteristics by defining responders as patients with numeric rating pain scale of 4 or less at 4 weeks after glucocorticoid injection, no US characteristic of inflammation has the ability to reliably predict those who respond to intra-articular glucocorticoids, requiring further study in a large-scale trial. Given the disagreement between radiographic morphological changes and symptoms in OA, further studies should establish the usefulness and value of US-detected changes in terms of effectiveness of therapeutic interventions.
J Clin Rheumatol. 2016;22(6):324-329. © 2016 Lippincott Williams & Wilkins