Key Facts
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Ultrasound is now a well-established imaging modality helping early diagnosis and follow-up of rheumatologic disorders.
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Dynamic ultrasound imaging and assessment of vascularity are among the most useful contributions of ultrasound.
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Color and power Doppler examination demonstrate subtle intra/periarticular synovial vascularity, which correlate well with the underlying inflammatory activity.
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High frequency transducers (7.5–20 MHz) deliver high resolution imaging of superficial structures, a resolution greater than that of magnetic resonance imaging or computed tomography.
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Joint aspiration/injection can be performed more accurately under direct ultrasound guidance.
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Anisotropy should not be mistaken for tendinosis. Anisotropy occurs when the sound beam is oblique to the tendon fibers producing an artifactual hypoechoic appearance.
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Diagnostic accuracy of musculoskeletal ultrasound relies heavily on the experience of the sonographer and technology.
HISTORY OF MUSCULOSKELETAL ULTRASOUND IN RHEUMATOLOGY
Since the publication of the first B-scan image of joint in 1972 by Daniel G. McDonald and George R. Leopold for differentiation of Baker’s cyst from thrombophlebitis, extensive technical advancements have taken place in the field of diagnostic ultrasound, leading to much improved visualization of soft tissues and more consistent demonstration of abnormalities. Tremendous progress has been made since the first demonstration of synovitis in rheumatoid arthritis (RA) in 1978, which was later followed by the first application of power Doppler demonstrating hyperemia in musculoskeletal disease in 1994. Thousands of publications have followed the first report of quantitative ultrasound by K.T. Dussik in 1958, and musculoskeletal (MSK) sonography is now considered by many as an indispensable integral part in the management of inflammatory arthritis.
IMAGING PRINCIPLES
Ultrasound is now a well-established imaging modality that assists in early diagnosis and follow-up of rheumatologic disorders in many leading centers throughout the world. Its popularity results from the distinct advantages it offers when compared with other modalities ( Box 7-1 ). More centers can afford ultrasound machines than magnetic resonance imaging (MRI) machines. Unlike computed tomography (CT), no ionizing radiation is involved, yet ultrasound can deliver multiplanar capability in real time. Often a radiologist lacks clinical history. Ultrasound provides the opportunity to interact with the patient during the examination. This helps in targeted examination generating a focused report. Comparison with the asymptomatic contralateral side is helpful to confirm and assess the extent of subtle findings. Dynamic ultrasound imaging and assessment of vascularity are among the most useful contributions of ultrasound.
ADVANTAGES
No ionizing radiation
Real time evaluation
Blood flow assessment
Multiplanar
DISADVANTAGES
Operator dependent
Cannot identify bone marrow edema
Not all areas are accessible to study
When available, MRI remains the gold standard for early diagnosis of rheumatologic disorders. However, many places do not have ready access to MRI, and even when available, it can be expensive. Widespread use of MRI for diagnosis and follow-up may not be practical in many institutions. Ultrasound has an undoubted complementary role in this situation. In the correct hands, it can act as a primary modality in the absence of MRI, both for diagnosis and follow-up. Interaction with the patient is a significant advantage—radiologists are all too aware that the diagnostic accuracy is greatly enhanced by the availability of correct history.
There are, however, many variables in ultrasound imaging. Diagnostic accuracy of MSK ultrasound relies heavily on the experience of the sonographer (the ultrasound technologist) and on the technology itself. Among various modalities, ultrasound is shown to have the largest interobserver and intraobserver variation in reproducibility.
Ultrasound examinations generally are operator dependent.
A long learning curve is a significant limiting factor, as it takes the operator a long time to train and to perform at acceptable standards; more importantly, partial training may reduce the diagnostic yield and accuracy and reflects badly on the outcome of ultrasound studies.
Ultrasound has some technical limitations. The most serious technical disadvantage for rheumatologic studies is the inability to identify marrow edema, which is considered by some as pre-erosive change.
Bone marrow edema may be a pre-erosive change; bone marrow edema cannot be demonstrated on ultrasound but can be documented on MRI examination.
Treatment initiated at this stage could produce long remission without development of erosions.
Terminology and Scanning Planes
An understanding of normal anatomy in gray scale is crucial to diagnosing abnormalities.
In ultrasound imaging, the position and intensities of returning echoes are shown as a two-dimensional image.
Normal echogenicity of various soft tissues should be well understood ( Table 7-1 ). Structures examined under ultrasound can be hyperechoic, isoechoic, hypoechoic, or anechoic or show mixed echogenicity relative to surrounding tissue. A cystic fluid collection is anechoic with posterior through-transmission of sound waves. Compressibility of the lesion suggests fluid content. Similarly, septated cystic collections could represent abscess, hematoma, or seroma. Correlation with history is vital for correct diagnosis.
Tendons and ligaments are generally hyperechoic and show characteristic fibrillar echotexture ( Figure 7-1 ). A tendon affected by tendinosis is hypoechoic. Tendinosis is the preferred term to tendinitis as often there is no histologic evidence of inflammation. Synovial proliferation (synovitis) can be easily demonstrated very early by ultrasound as hypoechoic, isoechoic, or hyperechoic relative to surrounding tissues. However, synovitis is a nonspecific finding and can be seen in all types of inflammatory arthritis including infection. Depending on the location (i.e., site of interest being accessible by probe), early erosions and periosteal reaction can also be easily visualized in most occasions prior to their demonstration on radiographs. An abnormality is traditionally scanned in its longitudinal and transverse planes. Dynamic examination also provides an opportunity to scan in various planes to better define the extent of the pathology and its relation to surrounding anatomy.
Recent Advances in Technology
The role of ultrasound is developing as technology evolves. High-frequency transducers (7.5 to 20 Mhz) deliver high-resolution imaging of superficial structures, a resolution greater than that of MRI or CT. Current ultrasound equipment is already capable of resolving power of less than 0.1 mm, which is not possible by CT or MRI. This high resolution is unfortunately at the expense of tissue penetration. Hence the depth of resolution is extremely limited with high-frequency transducers. Musculoskeletal structures being analyzed are mostly superficially located and thus extremely amenable to scanning with high-resolution probes.
High-resolution scanning uses high-frequency transducers to evaluate superficial structures such as tendons.
Color and power Doppler examinations demonstrate subtle intraarticular/periarticular synovial vascularity, which correlates well with the underlying inflammatory activity.
Color Doppler is a technique in which colors superimposed on an image of a blood vessel indicate the speed and direction of blood flow in the vessel. Power Doppler is many times more sensitive in detecting blood flow than color Doppler.
Power Doppler has the ability to differentiate inflammatory arthritis from other types of synovial proliferation. However, ultrasound in general cannot differentiate between aseptic and septic joint effusions. Power Doppler has been shown to be equivalent to contrast-enhanced MRI in the assessment of inflammatory activity.
Intravenous microbubble contrast agents significantly increase the sensitivity of detecting tissue vascularity by power Doppler examination. Their use may help quantify inflammatory activity by estimating the signal intensity changes following contrast administration. Their role in rheumatology is evolving. They also have a potential but so far undefined role in drug delivery and release at the target tissue.
Three-dimensional (3D) imaging (sometimes termed four dimensional [4D] because of real-time dynamic component) is a result of ongoing new technical advances. Its role is evolving in the general management of the rheumatology patient. Further research is needed to establish its usefulness in clinical practice. In the future there is a potential for 3D imaging of the target tissue to be performed in seconds by somebody with limited training. 3D reconstructions in the desired plane could then be recreated on the workstation similar to other cross-sectional studies. Likely indications for 3D technology include early detection of erosions or enthesitis and better definition of partial tendon tears.
Extended field of view technology associated with development of small and more maneuverable probes further promotes the utility of ultrasound in rheumatology practice. This technology is helpful in defining the extent of an abnormality (e.g., tendon tear, tendinosis), which is greater than the probe size, thereby providing a global perspective.
MUSCULOSKELETAL APPLICATIONS
General Indications of Ultrasound in Rheumatology
Early Diagnosis of Arthritis
Traditionally radiographs have been obtained to look for osseous changes such as erosions, but these are late features of the disease process. Ultrasound is an excellent modality to target symptomatic sites for assessment of early soft tissue changes (hyperemia, synovitis), which invariably precede osseous changes. This helps in early diagnosis and facilitates early treatment. Institution of disease modifying therapy aims to reverse these soft tissue changes, control irreversible tissue damage, and leads to better long-term remission of the disease.
Assessment and Quantification of Inflammatory Activity of Rheumatoid Arthritis
Histologically, activity of synovial proliferation directly correlates with hyperemia detected by Doppler ultrasound. It has been shown that highly perfused active pannus leads to erosive change in the adjacent bone. Advancements in Doppler technology make it a realistic possibility to assess microvascular blood flow in synovial proliferation and enthesis inflammation. In the future, there is a potential for further increase in the sensitivity of Doppler imaging to detect tissue vascularity with the use of ultrasound microbubble contrast agents.
Assessment of Response to Treatment
Early and intensive disease-modifying therapy has been advocated to delay and sometimes prevent long-term damage of RA, which includes erosions and fibrosis. The drugs used are strong and can be potentially toxic. To limit its side effects, the drug dose should be balanced with the effectiveness in response. Ultrasound is a very useful tool in monitoring drug effectiveness in response to treatment. Studies have shown that activity of disease is directly proportional to the perfusion. Intensity of Doppler signals decreases dramatically with anti-tumor necrosis factor (TNF)-alpha, corticosteroid, and soluble TNF-alpha receptor–etanercept treatment and hence is very useful in monitoring response. Similarly, contrast-enhanced ultrasound has also shown increased sensitivity in demonstrating synovial vascularity and hence has a strong potential for monitoring therapy.
Invasive Procedure Guidance: Diagnostic and Therapeutic
Ultrasound is very sensitive in detecting fluid collections in joints, tendons, and bursae. It is often better and more consistent than clinical examination in diagnosing subtle joint effusions and therefore is the investigation of choice, potentially significantly affecting patient management.
Joint aspiration can be performed under direct ultrasound guidance (generally for the deeper joints or more difficult fluid collections). Using ultrasound only for the purpose of surface marking of the skin can also be followed by aspiration as an alternative. A skin mark is generally placed at the intersection of the two planes (longitudinal and transverse) where the fluid is best visualized; the depth of fluid is maximal and easily accessible while avoiding the neurovascular structures in the needle path. Ultrasound-guided joint aspiration is often two to three times more successful than conventional joint aspiration by a clinician. Intraarticular needle placement is twice as likely to be successful with than without ultrasound guidance. Studies have shown that more than 30% of intended intraarticular injections miss the target when attempted without imaging guidance. Despite a dry aspiration attempt following correct needle placement, joint lavage and aspiration can be helpful in small joints for obtaining synovial cells, often essential for the diagnosis of crystal arthropathy.
Where possible, therapeutic soft tissue injections should be performed under image guidance, and ultrasound is generally the preferred modality. It has been shown that the desired results are more likely to be obtained by ultrasound guidance, avoiding inadvertent injection of steroids into tendons and fascia, which can result in degeneration and rupture. Ultrasound is also very helpful in guiding soft tissue/synovial biopsies and draining abscesses.
Assessment of Long-Term Complications (e.g., Tendon Tears, Tendinosis) and Role in Follow-Up
Ultrasound is a useful modality, is readily available, and is helpful in assessing treatment response of synovitis, resolution of hematoma, abscess formation, and joint effusion. Tendon tears can be reliably assessed and separation of torn tendon ends clearly measured following dynamic examination. Ultrasound follow-up is typically more feasible than MRI and can be equally accurate.
Rheumatoid Arthritis
Ultrasound can be routinely used for early diagnosis, monitoring therapy, and guiding intervention in RA. Early rheumatologic changes such as hyperemia and synovial proliferation are nonosseous in nature and well demonstrated by ultrasound and color Doppler imaging.
Early changes of synovial proliferation and hyperemia may be demonstrated on ultrasound before bone changes are visible on radiographs.
Early and aggressive treatment of the disease by potent disease-modifying therapy helps delay the progression of the disease and prevent irreversible changes such as erosions and fibrosis.
Joints most commonly involved in early RA and assessed by ultrasound are those of the wrists, hands, and feet. For diagnostic purposes all symptomatic joints can be assessed. Image findings include hyperemia, synovial proliferation, effusion, erosions, tenosynovitis, tendinosis, and tendon tears. All these findings are important for diagnosis but are not specific for RA. Clinical history and pattern of joint involvement are most important in providing definitive diagnosis. RA patients often present with bilaterally symmetric polyarthritis, predominantly involving small joints of the hands.
Hyperemia
Hyperemia is the earliest finding of RA that can be imaged. It signifies ongoing acute inflammation or acute exacerbation of a chronic disease process. Color Doppler ultrasound can detect subtle flow and quantify the vascularity ( Figure 7-2 ). There is high correlation between color Doppler ultrasound and contrast-enhanced MRI for detection of hyperemia and synovitis. As previously discussed, this is most useful in assessing the activity of the disease and monitoring response to treatment.
Synovitis
Ultrasound is sensitive in detecting early synovitis, with a limiting factor being accessibility of the joint. Assessment of synovial volume is important, as it directly relates to disease activity. Assessing synovial volume is time consuming and has mostly been performed by MRI. However, with the advent of volumetric imaging in ultrasound, this assessment may become an easier task. Pannus is described as focal mass-like proliferation of synovium of inflammatory origin, ranging from hypoechoic to hyperechoic relative to the surrounding soft tissues ( Figure 7-3 ). Sometimes a conglomeration of focal synovial masses is seen in the late phase of RA, grouped together as extensive pannus formation. Pannus can demonstrate increased vascularity or can be avascular.
Joint Effusion
When joint effusion is seen as a solitary finding, infection should be excluded, as the appearance of fluid is not specific whether due to infection, inflammation, or crystal deposition disease.
All joint effusion appears similar on ultrasound, with the exception of acute hemorrhage.
Hemorrhage into the joints will also have similar appearance, although acutely it will appear hyperechoic. Ultrasound is very sensitive in detecting joint effusions and is capable of visualizing 2 1 to mL of joint fluid ( Figure 7-4 ). In active inflammatory arthritis, effusion often coexists with synovitis.
Erosions
Erosions are often associated with synovitis and are generally irreversible. Erosive change is suspected when juxtaarticular cortical irregularity is seen adjacent to synovitis ( Figure 7-5 ). About 47% of patients may develop radiographic evidence of erosions within 1 year of diagnosis. This study was published before the advent of early aggressive combination therapy with disease-modifying antirheumatic drugs (DMARDs), which seems to have significantly influenced the outcome of the disease. In 1999, McQueen et al. reported detecting more carpal erosions by MRI (45%) than by radiography (15%), 4 months after onset of symptoms. Ultrasound can detect and monitor erosions and is more sensitive than radiography and comparable to MRI in assessing finger joint and metatarsophalangeal (MTP) joint erosions. In fact, ultrasound is seven times more likely to demonstrate erosions compared with radiography. It is also possible to assess the vascularity adjacent to an erosion, hence demonstrating synovial inflammatory activity.
However, ultrasound has significant limitations. It cannot assess marrow edema, considered by many to be a preerosive change. Also it is limited by probe accessibility, being excellent in assessing joints such as the second and fifth metacarpophalangeal (MCP) joint and the first and fifth MTP joints but more limited in assessing others such as the carpal joints of the wrist.
The joints of the wrist have limited accessibility to ultrasound examination. MRI would be a more appropriate choice of advanced imaging techniques to identify synovitis or early erosion.
Tenosynovitis, Tendinosis, and Tendon Tear
Ultrasound can be considered a reference standard for assessment of superficial tendons. Tenosynovitis can be a coexistent early finding in RA, especially around the wrist ( Figure 7-6 ). Comparison with an asymptomatic side may help in assessing subtle tenosynovitis; however, because RA is a systemic disease with symmetric involvement and the other asymptomatic side may demonstrate subclinical involvement, comparison may be problematic. Tendinosis and tendon tear are findings generally not seen in acute phase RA. Tendinosis generally results in a hypoechoic tendon with focal increase in volume, sometimes demonstrating increased vascularity ( Figure 7-7 ). Tendon tear is a late complication.
Absence of extensive proliferative bone changes such as enthesitis or periosteal reaction assists in differentiating RA from seronegative arthropathies (e.g., psoriasis, Reiter’s syndrome, ankylosing spondylitis). Some of the specific points of individual joint involvement in RA are described in the following section.
Wrist
The tendon sheath of the extensor carpi ulnaris is typically the early site of tenosynovitis in the wrist ( Figure 7-8 ). Early erosive changes seen in the ulnar styloid are partially related to its close proximity to the extensor carpi ulnaris. Tenosynovitis of flexor tendons at the wrist as they pass beneath the flexor retinaculum can result in decrease in the volume of the carpal tunnel, causing carpal tunnel syndrome. Carpal tunnel syndrome can be satisfactorily assessed by ultrasound and later confirmed by invasive nerve conduction studies when needed ( Figure 7-9 ).
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