Added value of high-resolution ultrasound and MRI in the evaluation of rheumatologic diseases

Rheumatologic diseases are a heterogeneous group of disorders affecting the joints, muscles, bones, tendons, ligaments, and cartilage. Some of the most commonly known rheumatologic conditions include osteoarthritis, rheumatoid arthritis, gout, juvenile idiopathic arthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), polymyalgia rheumatica, Sjögren’s syndrome, psoriatic arthritis, systemic sclerosis, vasculitis, and fibromyalgia. These diseases are typically chronic and can cause pain, inflammation, stiffness, and impaired function. This can lead to morbidity and work disability with significant socio-economic impact. A report by the CDC states that during 2016–2018, about 58.5 million (23.7%) US adults had arthritis and about 43.9% of them had arthritis-attributable activity limitations⁽¹⁾. An estimated 78 million (26%) US adults are projected to have arthritis by the year 2040⁽²⁾.

Clinical examinations can have limitations in terms of subjectivity and lack of sensitivity in the detection of early signs of rheumatologic diseases. Hence, imaging plays a crucial role in the diagnosis, treatment response, and management of rheumatologic disorders.

Radiographs are typically the initial imaging modality for evaluating joint and osseous damage. They reveal joint space narrowing, joint subluxation, bone erosions, osteophytes, and osteopenia. However, these changes occur late in the disease process, hence the need for other imaging modalities to help with early diagnosis.

High-resolution US (HRUS) and magnetic resonance imaging (MRI) are useful in detecting early symptoms of inflammation, erosions, synovitis, and other disease-specific alterations, allowing treatment to be initiated earlier, and thus improving patient outcomes, and establishing remission. They allow an objective and quantitative evaluation of disease activity, such as synovial thickness and vascularity, as well as quantifying joint damage. HRUS has the advantage of being a portable, widely accessible, low-cost real-time imaging modality with dynamic capabilities and high spatial resolution. Lack of radiation, ability to image multiple sites at once and compare bilateral joints, intervention guidance, and point-of-care application allowing quick correlation between clinical and imaging findings are just a few of the advantages that have made US so popular in rheumatology practice. Recent US advancements, such as high-resolution images, power Doppler, elastography, contrast-enhanced US, and microvascular imaging, broaden the scope of its applications. High-resolution US presents hurdles in terms of deeper penetration, difficulties with identifying intraosseous lesions, operator dependency, and reproducibility.

MRI, with its superior soft tissue contrast, provides a detailed examination of the internal structure of bones and joints including the identification of bone marrow edema. However, its use is limited by restricted availability, longer scanning time, higher cost, and in some cases patient claustrophobia.

RA is a chronic autoimmune disorder of unknown etiology, but several genetic and environmental factors have been implicated in causation. The disease is characterized by synovial inflammation leading to the proliferation of synovium, also known as pannus, which if left untreated can eventually cause joint destruction and disability. With the advances in US and MRI, early diagnosis is possible, and therapy with newer, more effective disease-modifying anti-rheumatic drugs can be initiated to achieve remission before irreversible damage occurs. RA involves the proximal joints of the hand (wrist, metacarpophalangeal (MCP), and proximal interphalangeal joints (PIP)) and feet (midfoot, metatarsophalangeal (MTP), and proximal interphalangeal joints (PIP)). The involvement is usually bilateral and symmetric.

Conventional radiographs are usually the first-line imaging modality for RA. Features seen on radiographs include periarticular osteopenia, symmetrical joint space narrowing, marginal erosions, and soft tissue swelling (Fig. 1). In the early stages, the radiographs appear normal and thus, in the revised 2010 ACR/ EULAR diagnostic criteria, radiographic erosions are not included, as they represent a late stage in the disease course. US and MRI are more sensitive than radiographs and clinical examination in the early detection of disease⁽³⁾, as pre-erosive synovitis can be seen in both modalities.

Fig. 1.

Synovitis

Synovial hypertrophy (SH) in US is defined as abnormal hypoechoic (relative to subdermal fat, but sometimes isoechoic or hyperechoic) intraarticular tissue that is non-displaceable and poorly compressible⁽⁴⁾ (Fig. 2). These features help in differentiating synovial hypertrophy from joint effusion (Fig. 3).

Fig. 2.

Fig. 3.

Synovitis is diagnosed when synovial hypertrophy exhibits signal on color flow Doppler interrogation (Fig. 4). PD is considered more sensitive than CD in identifying and quantifying increased vascularity and can be used to monitor disease activity and treatment response⁽⁵⁾. Szkudlarek et al.⁽⁶⁾ developed a semiquantitative grading of the PD evaluation of synovitis: grade 0 – no flow; grade 1 – single-vessel signals; grade 2 – less than half of the area of the synovium-filled with vessels; grade 3 – more than half of the area of the synovium filled with vessels (Fig. 5).

Fig. 4.

Fig. 5.

A EULAR-OMERACT combined scoring system for grading synovitis in rheumatoid arthritis was proposed in 2017⁽⁷⁾ (Tab. 2).

Tab. 2.

EULAR-OMERACT combined scoring system for grading synovitis in rheumatoid arthritis

Grade 0	Normal joint	No GS-detected SH and no PD signal (within the synovium)
Grade 1	Minimal Synovitis	Grade 1 SH and ≤ Grade 1 PD signal
Grade 2	Moderate Synovitis	Grade 2 SH and ≤ Grade 2 PD signal or Grade 1 SH and Grade 2 PD signal
Grade 3	Severe Synovitis	Grade 3 SH and ≤ Grade 3 PD signal or Grade 1 or 2 SH and Grade 3 PD signal

GS – grayscale; SH – synovial hypertrophy; PD – power Doppler

Researchers assessed the inter- and intraobserver reliability and concluded that the EULAR-OMERACT score demonstrated moderate-good reliability in MCP joints using a standardized scan and was equally applicable to non-MCP joints⁽⁸⁾.

On MRI, SH appears as thickened synovium, and it is hyperintense on T2-weighted images, which makes it difficult to differentiate it from effusion. Consequently, contrast administration can be useful to distinguish enhancing synovium from non-enhancing effusion (Fig. 6). Synovial enhancement should be examined within 10 minutes from contrast administration, after which the contrast agent diffuses into the synovial fluid⁽⁹⁾. MRI can be used to quantify synovial volume, which has been shown to correlate with disease activity⁽¹⁰⁾.

Fig. 6.

Dynamic contrast-enhanced (DCE) MRI can assess the rate of contrast uptake by the inflamed synovium and help monitor disease activity and treatment response.

Some studies have found that US is less sensitive than MRI in the early detection of synovitis and tenosynovitis, but highly specific⁽¹¹⁾.

In a systematic review and meta-analysis, Takase-Minegishi et al.⁽¹²⁾ compared the accuracy of US-detected synovitis versus MRI in the wrist, MCP, PIP, and knee joints, and found good agreement of US and MRI for detecting synovitis in the MCP and PIP joints, lower agreement for the wrist, and low agreement for the knee joint^(12,13). They concluded that US seemed to be a valid and reproducible technique for detecting synovitis in the wrist and finger joints. PD US showed better overall diagnostic accuracy than grayscale US.

Erosions

Chronic synovitis leads to periarticular bone resorption which forms bone erosions. The presence of bone erosions at the time of RA diagnosis is a poor long-term prognostic indicator. On US, erosions appear as an intraarticular discontinuity in the cortical bone surface identified on two orthogonal planes (Fig. 7). A study by Wakefield et al.⁽¹⁴⁾ demonstrated that US was more sensitive in the detection of erosions than radiography, especially in early disease. In a study by Zayat et al.⁽¹⁵⁾ to determine the specificity of US-detected bone erosions, the authors found that the presence of erosions is not specific for RA but larger erosions in the 2^nd and 5^th MCP, 5^th MTP joints, and distal ulna were highly specific for and predictive of RA. Erosions of any size in the 5^th MTP joint were both specific and sensitive for RA (specificity 85.4% and sensitivity 68.6%). Active inflammation associated with erosions can be detected with PD.

Fig. 7.

Potential pitfalls include normal cortical depressions, or pseudoerosions, commonly seen in the carpals and metacarpals (Fig. 8).

Fig. 8.

A recent semi-quantitative scoring system was developed for scoring erosions on US by the OMERACT task force⁽¹⁶⁾ (Tab. 3).

Tab. 3.

Scoring of bone erosions on US by the OMERACT task force

Grade 0	Intact cortical bone
Grade 1	Single small erosion (diameter: ≤2 mm)
Grade 2	Single large erosion (diameter: >2 mm) or 2 small erosions or 1 large and 1 small erosion
Grade 3	2 large erosions or ≥3 erosions, regardless of size

On MRI, bone erosions are sharply marginated bone defects that are seen in at least two planes, with a cortical break visualized in at least one plane with low signal intensity on T1-weighted images^(9,17) (Fig. 9). Histologically, they represent localized replacement of bone marrow fat by inflammatory cells adjacent to a cortical bone barrier⁽¹⁸⁾. The fluid or inflammatory tissue within the erosion appears hyperintense on T2-weighted images and may show enhancement on post-contrast T1-weighted images (Fig. 9).

Fig. 9.

Aleo et al.⁽⁵⁾ found that low-field MRI is probably more sensitive than US in the detection of erosions.

Bone marrow edema

Bone marrow edema appears as an ill-defined hyperintense area in the bone on T2FS or STIR (Fig. 10) sequences, and hypointense on T1W images showing post-contrast enhancement. The detection of bone marrow edema is unique to MRI. These lesions likely represent precursor lesions to subsequent bone erosion⁽¹⁹⁾ and a risk factor for progression to structural joint damage. US is limited in its evaluation of internal bone structure.

Fig. 10.

Tenosynovitis

On US, tenosynovitis is defined as hypoechoic or anechoic thickened tissue, either with or without fluid within the tendon sheath, which is seen in two perpendicular planes and which may exhibit a Doppler signal⁽⁴⁾ (Fig. 11). Tenosynovitis of the extensor carpi ulnaris (Fig. 12) is the most common, and represents an independent risk factor of erosive joint damage^(10,20). A study by Ohrndorf et al.⁽¹¹⁾ found the specificity to detect tenosynovitis in grayscale and PD to be higher than the sensitivity.

Fig. 11.

Fig. 12.

On MRI, tenosynovitis appears as peritendinous fluid with thickening and enhancement of the tendon sheath (Fig. 13).

Fig. 13.

Bao et al.⁽²¹⁾ concluded that US could be as sensitive and specific as contrast-enhanced MRI for the diagnosis of subclinical synovitis and tenosynovitis.

Synovitis leads to cartilage damage. Hyaline cartilage abnormalities can be detected by US, including cartilage thinning, blurring of margins, loss of clarity of the cartilaginous layer which may lose its normal homogeneously hypoechoic appearance, and irregularities of subchondral bone (Fig. 14).

Fig. 14.

Other manifestations of RA include rheumatoid nodules, tendinitis, carpal tunnel syndrome, and bursitis, which can be confidently diagnosed clinically and detected by both US and MRI. Enthesitis and sacroiliitis are uncommon manifestations in RA, and are best detected by MRI.

Spondyloarthropathies (SpA) are a heterogeneous group of inflammatory disorders including ankylosing spondylitis (AS), psoriatic arthritis, reactive arthritis, enteropathic arthritis, and undifferentiated spondyloarthritis. Enthesitis is a cardinal feature of SpA. Other features include synovitis, tenosynovitis, paratenonitis, and soft tissue edema. The main use of US in SpA is for the detection of enthesitis. Common sites for enthesitis are the insertion of the extensor tendons of fingers, Achilles tendon, plantar fascia, and quadriceps tendon.

On HRUS, enthesitis appears as heterogeneous hypoechogenicity of the enthesis, loss of normal fibrillar echotexture of the tendon insertion, intratendinous hypoechoic areas, punctate calcific foci, blurring of tendon margins, thickening of the insertion site of tendon, irregularities, and erosions of subentheseal bone, and perientheseal swelling (Fig. 15). Perientheseal diffusion of inflammatory fluid noted on imaging has been reported to be a characteristic finding of SpA and cause perientheseal swelling⁽²²⁾. Multiple and irregular enthesophytes and calcific deposits are more specific for SpA-related enthesitis⁽²²⁾. PDUS can show an increased signal in active inflammation of the enthesis and can be used to assess treatment response (Fig. 16).

Fig. 15.

Fig. 16.

Dactylitis, a feature of psoriatic arthritis, is associated with flexor tenosynovitis, diffuse extensor paratenonitis, soft tissue thickening, or edema (Fig. 17). Palmar plate inflammation, digital enthesitis, and collateral ligament enthesitis are other features that may be present in psoriatic arthritis⁽²³⁾.

Fig. 17.

MRI studies of patients with dactylitis have shown increased signals at the palmar plate.

The role of MRI in SpA is to diagnose active inflammatory lesions, monitor disease activity, and diagnose complications, such as cartilage damage, tendon tears, and osteonecrosis. MRI is primarily used for the imaging of sacroiliac joints in axial SpA to detect sacroiliitis (Fig. 18).

Fig. 18.

On MRI, an abnormal enthesis is hyperintense on fluid-sensitive sequences and hypointense on T1-weighted images. The bony part of an enthesis may show significant bone marrow edema (Fig. 19). On post-contrast images, both fibrous and bony parts of the enthesis show enhancement. When synovium is present in an adjacent bursa or joint, it can also appear inflamed. Enthesophytes can also be detected at the bursal site⁽⁹⁾. The presence of bone marrow edema indicates inflammatory enthesitis. MRI is very sensitive in detecting active inflammatory enthesitis, even though in a systematic review, Aleo et al. found that US was more sensitive to detect early changes of enthesopathy than MRI⁽⁵⁾.

Fig. 19.

Osteoarthritis is the most widespread form of arthritis. The most commonly affected joints are the weight-bearing type, or the ones used repetitively – the hip, knee, foot, and hand. Radiography is the primary imaging modality to evaluate OA. Radiographic features include marginal osteophytes, asymmetrical joint space narrowing, subchondral sclerosis, and subchondral cysts (Fig. 20). Joint space narrowing is an indirect surrogate marker to assess articular cartilage loss on radiographs. Increasingly, HRUS and MRI are being utilized for the evaluation of soft tissues in the OA joint.

Fig. 20.

HRUS can detect alterations in cartilage, marginal osteophytes, effusion, synovitis, and bursal distention.

On US, normal cartilage appears as a homogeneous hypoechoic to anechoic structure of uniform thickness. In OA, the cartilage may appear heterogeneous, with uneven thickness and fuzzy contours. Osteophytes appear as echogenic elevated bony projections near the articular margin (Fig. 21). Several studies have demonstrated the presence of grayscale synovitis in hand OA⁽²⁴⁾.

Fig. 21.

In the knee joint, HRUS is more sensitive than radiography to depict tibiofemoral osteophytes⁽²⁵⁾. Part of normal knee menisci can be seen on US, appearing as triangular echogenic structures lying within the confines of the bony margins. HRUS is able to identify meniscal injury in some instances which can be associated with other structural tissue damage in the knee and can increase the risk of progression to OA (Fig. 22)⁽²⁶⁾.

Fig. 22.

US has limitations in visualizing joint tissues due to the limited acoustic window which may be further limited by the presence of large osteophytes. Also, it cannot assess the bone changes like subchondral cysts, sclerosis, and bone marrow alterations which are all common features of OA.

US is comparative to MRI in the assessment of osteophytes, bone erosions, and synovitis, in erosive and hand nodal OA⁽²⁴⁾.

MRI has the advantage of visualizing bone, intraarticular tissues, cartilage, ligaments, menisci, and internal bone structure (Fig. 23).

Fig. 23.

Recent developments in MRI, including high-resolution threedimensional sequences, allow the quantification of articular cartilage. Quantitative measurements of cartilage volume and thickness change are used in studies to evaluate different treatment outcomes.

Techniques that analyze cartilage composition like T2-mapping, which assesses collagen and water content (Fig. 24), and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), which assesses glycosaminoglycan content, have been developed. These are being investigated for the early diagnosis of OA, monitoring treatment response, and possible intervention at an early reversible stage⁽²⁵⁾.

Fig. 24.

Gout is an inflammatory arthritis associated with hyperuricemia. It is characterized by the deposition of monosodium urate crystals in the articular and extraarticular tissues, synovitis, and bone erosions.

HRUS can accurately assess crystal deposition in various tissues, including the synovial membrane, cartilage, tendons, bursae, and soft tissues. In the early stages, US reveals characteristic features such as effusion and echogenic synovitis⁽²⁴⁾. Hyperechoic spots representing crystals can be observed in the joint and periarticular tissues (Fig. 25, Fig. 26). PD US can detect increased color signals in the inflamed synovial tissue (Fig. 25, Fig. 26). Gouty tophi appear as heterogeneous structures with a peripheral hypoechoic rim. Monosodium urate crystals deposit on the superficial surface of the hyaline cartilage, generating an echogenic line over subjacent hypoechoic cartilage and parallel echogenic bone cortex, giving the appearance of a double contour known as the “double contour” sign⁽²⁷⁾ (Fig. 27).

Fig. 25.

Fig. 26.

Fig. 27.

Studies have shown that US correlates well with MRI in the detection of tophi⁽²⁸⁾. Erosions are more easily detected on US than on radiography⁽²⁹⁾. Gouty erosions can be intraarticular or extraarticular. There is evidence that reduction is US features of gout parallels the reduction in serum urate levels⁽²⁴⁾.

MRI is helpful in the assessment of the extent of joint, tendon, and bursal involvement, and in diagnosing complications, including tendon tears. On MRI, tophi are low signal on T1-weighted MRI and mostly intermediate signal on T2-weighted MRI, and can show enhancement on post-contrast images. Low signal foci on T2-weighted images most likely represent calcifications (Fig. 28).

Fig. 28.

In pseudogout, calcium pyrophosphate crystals deposit (CPPD) as echogenic foci of different sizes or as a linear band within the substance of the hyaline cartilage. These findings have a moderate sensitivity but an excellent specificity to differentiate between gout and pseudogout.

In CPPD disease, echogenic spots may be seen at the fibrocartilage sites, such as the menisci, and triangular fibrocartilage. In the tendons, crystals can appear as linear hyperechoic areas and in the synovial cavity as hyperechoic dots of variable sizes (Fig. 29).

Fig. 29.

Calcifications in the Achilles tendon are highly specific for CPPD disease and US has shown a high agreement with radiography in the detection of entheseal calcifications and enthesophytosis in this disease⁽²²⁾.

DCE-MRI allows measurement of tissue perfusion and has clinical applications in the assessment for synovial changes to help guide diagnosis, monitor disease activity, and evaluate treatment efficacy. For example, reduction in synovial perfusion has been shown to be a more sensitive indicator of treatment response than synovial volume⁽³⁰⁾.

Contrast-enhanced US (CEUS) utilizes microbubble-based contrast agents to intensify the Doppler signal in small vessels and help identify synovitis⁽³¹⁾. It can thus aid in determining disease activity. The use of CEUS is also being investigated in inflammatory back pain and sacroiliitis. Microvascular imaging is another technique that enhances low-flow signals and can be used in the detection of active synovitis⁽³¹⁾. US elastography measures the stiffness of tissues qualitatively (strain elastography) and quantitatively (shear wave elastography)⁽³²⁾. In inflammation and even in osteoarthritis, there are pathological alterations in muscles and tendons. For example, tendons become softer with reduced elasticity. Further research is needed to evaluate the diagnostic capabilities and potential clinical application of these techniques in various musculoskeletal conditions.

Dual-energy CT (DECT) employs simultaneous scanning using two energy sources of different X-ray energy levels (80 kV and 140 kV). Evaluation of the different attenuations of the scanned object allows analysis of the chemical composition of materials, which can be color-coded for visualization and then measured. By analyzing the differences in X-ray absorption between uric acid crystals and surrounding tissues, DECT can detect the presence and distribution of urate crystals in gout (Fig. 30). It can assess the volume of crystals and help in differentiating gout from other crystal deposition diseases.

Fig. 30.

HRUS and MRI are valuable imaging modalities in rheumatology for assessing musculoskeletal structures and detecting inflammatory and structural changes, with good diagnostic performance. HRUS is low-cost, easily accessible, portable, and provides real-time imaging with high resolution. It enables detailed evaluation of superficial joints, tendons, cartilage, and entheses, providing information on synovial hypertrophy, tenosynovitis, vascularity, effusion, and bone erosions for early detection and monitoring of disease activity in various rheumatic conditions. PD US improves US sensitivity for diagnosing active inflammation.

MRI provides superior soft tissue contrast and allows comprehensive assessment of intraarticular structures, bone, and detection of bone marrow edema. It assesses disease activity, structural lesions, and complications. Advanced MRI techniques aid in early diagnosis, treatment monitoring, and intervention for various rheumatic diseases.

Both modalities offer complementary information and can be used in combination to provide a comprehensive assessment of disease activity, treatment response, and prognostic evaluation, increasing diagnostic accuracy and improving patient outcomes. Ongoing advancements in imaging technology will further refine these modalities, enhancing their clinical utility.