Tracking Rheumatic Disease Through Imaging




This review recounts the historical, current, and future involvement of radiology and imaging in the diagnosis, management, and follow-up of patients with various rheumatic conditions. Radiographs are the mainstay of imaging patients with rheumatic conditions, although magnetic resonance imaging and ultrasonography are routinely used for early diagnosis of disease. Computed tomography remains useful in evaluating the extent of involvement of inflammatory spondyloarthropathies that classically involve the axial skeleton and sacroiliac joints. Molecular imaging has begun to play an innovative role in evaluating patients with arthritis, aiming to identify disease earlier and provide greater specificity.


Key points








  • The use of imaging has rapidly evolved over the past 50 years, paralleling its increasing role in the diagnosis, monitoring, and follow-up of patients with rheumatic conditions.



  • At present, radiographs are the mainstay of imaging, although magnetic resonance imaging and ultrasonography are routinely used for early diagnosis of disease, specifically for the identification of subclinical synovitis and erosions in rheumatoid arthritis.



  • Computed tomography remains useful in evaluating the extent of involvement of inflammatory spondyloarthropathies that classically involve the axial skeleton and sacroiliac joints.



  • Molecular imaging will likely play a key role in the future imaging of rheumatic conditions (specifically rheumatoid arthritis), with very specific and targeted tracers being used to identify early subclinical disease activity.






Introduction


Imaging has played an integral role in the diagnosis of rheumatologic conditions since the development of the radiograph. Over the years, the role of imaging has changed from a purely diagnostic technique, often only obtained after symptoms have been present for some time, to that of an earlier diagnostic tool, with the intent to identify disease sooner, thus leading to earlier initiation of treatment with the ultimate goal of halting structural bone damage. In addition, providing an objective outcomes measure of various therapies, including specific targeted biological agents, has advanced the role of imaging to that of a key component in the diagnostic workup and clinical follow-up of patients with rheumatic diseases. More recently, molecular imaging has begun to play an innovative role in evaluating patients with arthritis, aiming to identify disease earlier and provide greater specificity. This review recounts the historical, current, and future involvement of radiology and imaging in the diagnosis, management, and follow-up of patients with various rheumatic conditions.




Introduction


Imaging has played an integral role in the diagnosis of rheumatologic conditions since the development of the radiograph. Over the years, the role of imaging has changed from a purely diagnostic technique, often only obtained after symptoms have been present for some time, to that of an earlier diagnostic tool, with the intent to identify disease sooner, thus leading to earlier initiation of treatment with the ultimate goal of halting structural bone damage. In addition, providing an objective outcomes measure of various therapies, including specific targeted biological agents, has advanced the role of imaging to that of a key component in the diagnostic workup and clinical follow-up of patients with rheumatic diseases. More recently, molecular imaging has begun to play an innovative role in evaluating patients with arthritis, aiming to identify disease earlier and provide greater specificity. This review recounts the historical, current, and future involvement of radiology and imaging in the diagnosis, management, and follow-up of patients with various rheumatic conditions.




Radiographs and nuclear scintigraphy


Conventional radiographs played the earliest role in the diagnosis of rheumatic conditions. Identification of erosions, joint-space narrowing, and distribution of disease were, and continue to be, invaluable to the rheumatologist in making a definitive diagnosis and, therefore, in instituting accurate and appropriate treatment ( Fig. 1 ). Gradually the radiographic patterns of various arthritides were defined: the radiographic pattern of polyarthritis in reactive arthritis (formerly known as Reiter syndrome), for example, was elucidated in 1971. In addition, specialized radiographic views have been developed throughout the years, increasing the diagnostic capabilities of radiographs and resulting in improved visualization of small joints, including those previously often obscured by other overlying osseous structures on routine frontal and lateral views (eg, the pisotriquetral joint view).




Fig. 1


Posteroanterior view of the left hand of a 65-year-old woman, demonstrating classic changes of rheumatoid arthritis with osteopenia, preferential proximal joint involvement in the carpus and carpometacarpal joints and erosions.


Nuclear scintigraphy has also been used in the diagnosis of rheumatic conditions, primarily in the 1960s and 1970s ( Fig. 2 ). The intravenous administration of strontium-85 ( 85 Sr) was one of the earliest radionuclide imaging methods used to identify bone marrow alterations in the setting of arthritis by localizing changes of osteoarthritis to either the medial or lateral compartments of the knee. Furthermore, radioactive technetium ( 99m Tc) was used to identify areas of active joint inflammation in a rheumatoid knee in comparison with a normal control.




Fig. 2


Static images of the hands from a 3-phase bone scan in a 46-year-old woman with rheumatoid arthritis, demonstrating uptake throughout the carpus consistent with rheumatoid involvement.


Nuclear scintigraphy has always been limited by its relatively low specificity; however, even early on, attempts were made to use radioactive tracers to better define bone marrow changes, specifically with respect to characterizing arthritis. In 1970 Muheim and Bohne published their experience with using 85 Sr in 51 patients (52 knees) with supposed spontaneous osteonecrosis of the knee. Based on their conclusions, they suggested that nuclear scintimetry could potentially differentiate primary osteoarthritis from arthritis secondary to osteonecrosis.


Radioactive tracers were used to further identify and characterize arthritis and their secondary complications throughout the early 1970s. Applications were expanded to include evaluation of the periarticular soft tissues, such as the identification of dissecting popliteal cysts, and soft-tissue changes in rheumatoid arthritis, such as tendinitis and bursitis.


Nuclear scintigraphy was further used in the early 1970s to evaluate the axial skeleton, an area often visualized with some difficulty on conventional radiographs, such as the sacroiliac joints in ankylosing spondylitis. Strontium-87m ( 87m Sr) demonstrated increased uptake in the sacroiliac joints in patients with active disease as demonstrated by both clinical presentation and laboratory values (erythrocyte sedimentation rate >40 mm/h). Lentle and colleagues not only identified the scintigraphic imaging findings throughout both the axial and appendicular skeletons in patients with ankylosing spondylitis, but also further emphasized the increased sensitivity of bone scintigraphy compared with conventional radiographs in diagnosing sacroiliac joint disease.




Computed tomography


As nuclear scintigraphy positioned itself to be an extremely sensitive diagnostic tool in the armamentarium of imaging for the diagnosis of rheumatic conditions in the 1970s, the relatively poor specificity necessitated a better imaging method to evaluate the regional anatomy in greater detail. The advent of computed tomography (CT) in the early 1980s allowed for a more detailed anatomic evaluation of articular surfaces, specifically those traditionally more difficult to evaluate with plain radiography, such as the sacroiliac joints and skull base.


Fam and colleagues used CT to study 28 consecutive patients with low back pain and clinical findings suggestive of ankylosing spondylitis, and compared CT findings with routine radiographs of the sacroiliac joints. Each sacroiliac joint was evaluated using the standardized and previously validated New York criteria: grade 0 = normal; grade 1 = suspicious for erosions or sclerosis; grade 2 = mildly abnormal with definite erosions or sclerosis but without alteration in joint width; grade 3 = moderately abnormal with erosions, iliac and sacral sclerosis, joint space narrowing or widening, and/or partial ankylosis; and grade 4 = severe abnormality with complete ankylosis. In 5 sacroiliac joints, CT demonstrated changes of sacroiliitis that had not been identified on conventional radiographs. The investigators concluded that even mild sacroiliac joint abnormalities, such as those encountered with a relatively early disease presentation, were more clearly seen on CT than on routine radiographs.


The tomographic multiplanar capabilities of CT, with the ability to perform sagittal and coronal reformatted images, lent itself to become a core element in imaging of patients with inflammatory disease, specifically within the axial skeleton (eg, spondyloarthropathies such as ankylosing spondylitis). The identification of erosions and malalignment at the C1-C2 articulation in patients with rheumatoid arthritis was now available through CT, with its ability to exquisitely identify the osseous structures in an area often clouded in routine lateral and flexion/extension radiographs, and with the added benefit of axial cross-sectional imaging allowing for the diagnosis of potential associated stenosis of the central canal ( Fig. 3 ).




Fig. 3


Coronal reformatted CT scan of a 58-year-old woman, demonstrating erosive changes at the C1-C2 articulation eroding both the medial and lateral margins of the dens ( arrows ).


Although CT has the relative limitation of ionizing radiation, it remains a key modality in the evaluation of patients with inflammatory conditions, especially the spondyloarthropathies whereby there is primarily involvement of the axial skeleton. Of significance, recent technological advances, such as iterative reconstruction techniques and imaging with fewer kilovolts, have resulted in diagnostic images with overall lower radiation dose to the patient, an important consideration in the pediatric and young adult population.




Ultrasonography


Ultrasonography began to be used to image clinical patients with suspected rheumatic disease in the late 1970s. Cooperberg and colleagues assessed rheumatoid patients with knee synovitis with ultrasonography and compared findings with the clinical presentation and conventional arthrography; this was the first description of the gray-scale appearance of synovial thickening and joint effusion in the knee. In 1988, ultrasonography was further expanded to evaluate tenosynovitis and synovitis in the hand in patients with rheumatoid arthritis, as well as to identify erosions.


The 1990s then saw an exponential increase in the use of ultrasonography in the evaluation of rheumatic disease, primarily because of the availability and portability of ultrasound equipment, as well as the attractive feature of having no ionizing radiation. Improvements in transducer technology and software applications such as extended field of view and power Doppler resulted in increased diagnostic accuracy and validation of ultrasonography in the evaluation of inflammatory changes in rheumatic disease, and its adoption as a technology that aided the physician and the patient in therapeutic decision-making and assessing the response to treatment.


In addition to the joint changes identifiable with ultrasonography such as synovitis and erosions, the sonographic appearance of normal and abnormal articular cartilage has been described. Grassi and colleagues evaluated the distal femoral articular cartilage in normal subjects and those with osteoarthritis. Based on their examinations, the investigators defined the sonographic appearance of normal hyaline articular cartilage to be a homogeneous hypoechoic or anechoic band of tissue (given the high water content of normal cartilage) outlining the subchondral bone with a sharp superficial interface. Abnormal, degenerated osteoarthritic cartilage, on the other hand, was identified by increased echogenicity of the articular cartilage (due to decreased water content), loss of the normal sharpness of the synovial-cartilage interface, loss of clarity of the cartilaginous layer, narrowing of the cartilage, and increased echogenicity of the posterior bone-cartilage interface. Advanced applications such as this, capable of detailed evaluation of articular cartilage, have increased the diagnostic abilities of ultrasonography beyond that of simply identifying synovitis and erosions, and have positioned ultrasonography as a key modality in the imaging workup of patients with suspected rheumatic disorders.


The use of ultrasonography has rapidly expanded beyond the identification and distribution of synovitis and erosions, primarily because of the development and application of power Doppler. Power Doppler imaging is an extremely sensitive detector of blood flow, being approximately 3 to 5 times more sensitive than conventional color Doppler. It has the additional technical advantages of being angle independent and not affected by aliasing, thus allowing for technically easier scanning. Power Doppler has been validated in identifying areas of inflammation in both hip and knee synovitis, in combination with histopathology ( Fig. 4 ). Of importance, power Doppler is very sensitive to states of slow blood flow, resulting in its ability to diagnose inflammation in small peripheral joints such as those involved in rheumatoid arthritis. The tumor-like synovial proliferation in rheumatoid arthritis, in concert with the resultant increase in angiogenesis, is directly responsible for the increased blood flow seen with power Doppler.




Fig. 4


Gray-scale ( A ) and power Doppler ( B ) images of the carpus demonstrate diffuse synovial thickening with visualization of marked active inflammatory changes when power Doppler is applied.


In addition to its utility in diagnosis, power Doppler ultrasonography is now used as a primary outcomes measure, monitoring response to therapy after injections or systemic treatment with disease-modifying antirheumatic drugs (DMARDs) (xenobiotic and biological agents). Fiocco and colleagues have shown that both gray-scale and power Doppler are reliable measures of disease activity in both rheumatoid and psoriatic knees. Furthermore, both power and spectral Doppler changes have been documented after treatment with systemic administration of tumor necrosis factor α blockers. It has been shown that some patients who have been characterized by being in remission using the Disease Activity Score for 28 joints, the Clinical Disease Activity Index, or the Simplified Disease Activity Index actually have ultrasonographically defined active inflammation. Thus there has been a recent call for the use of ultrasonography as a key component in defining “true” disease remission that has heretofore been based solely on clinical and laboratory test grounds.

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Oct 1, 2017 | Posted by in RHEUMATOLOGY | Comments Off on Tracking Rheumatic Disease Through Imaging
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