Imaging techniques for evaluation of the painful joint

INTRODUCTION — Joint pain may be due to a broad array of conditions. Imaging studies of the joint, in combination with clinical and laboratory evaluation, are often helpful in establishing a specific diagnosis. The choice of imaging procedure is based upon the clinical situation, the differential diagnostic considerations, and the availability of specific imaging modalities. Guidelines for the use of musculoskeletal imaging for specific clinical situations are included among the American College of Radiology appropriateness criteria [1].

Sufficient history should be provided to assist the radiologist in study interpretation. Thus, the quality and location of pain, as well as any history of trauma, pertinent medical history, and laboratory data, are invaluable information when interpreting an imaging study [2].

An overview of the use of the diagnostic imaging modalities and techniques to evaluate joint pain is presented here. Detailed discussions of these techniques in specific diseases are presented separately (see appropriate topic reviews), as is the use of musculoskeletal ultrasound. (See "Musculoskeletal ultrasonography: Nomenclature, technical considerations, and basic principles of use" and "Musculoskeletal ultrasonography: Clinical applications" and "Musculoskeletal ultrasonography: Guided injection and aspiration of joints and related structures".)

RADIOGRAPHY — Radiography remains the initial imaging choice in many, if not most, bone and joint disorders. Radiography utilizes a radiograph tube with a two-dimensional image detector, a sheet of film, or digital detector. In most radiology departments, radiographic images are digital and thus are interpreted on a computer display.

Radiographs have the greatest resolution of all available imaging modalities. Densities that can be distinguished on radiographs are calcium, soft tissue, fat, and air. Radiography is especially useful for detecting and/or evaluating:

●Fractures

●Periosteal reaction

●Soft tissue calcification or ossification

●Localized lesions of bone

●Orthopedic hardware

●Bone dysplasias and other skeletal deformities

Two systems are available to produce digital projection radiographs, computed radiography and digital radiography. Computed radiography (CR) was introduced commercially in the early 1980s. In a CR system, a photostimulable storage phosphor screen or image plate acts as the detector that interacts with the x-rays, thus capturing a latent image; a laser light is used to stimulate the phosphor to luminesce, thus extracting the latent image from the screen and converting it into a digital image [3]. In CR, traditional film cassettes are replaced by storage phosphor cassettes, and chemical film processing is replaced by CR readers [3]. The images can be printed onto film or can be transmitted to a picture archiving and communication system (PACS) workstation.

Digital radiography (DR), introduced in the 1990s, refers to devices in which the digitization of the radiograph signal takes place within the detector itself via a photodiode and thin-film transistor (TFT) array [4]. This approach provides an immediate full-fidelity image on a display monitor. Detection devices can use either a direct or an indirect conversion mechanism.

Both CR and DR systems provide greater latitude than film screen systems and decrease the number of images that need to be repeated. The advantages of direct radiography include increased productivity and equivalent or better image quality at a potentially lower radiation dose to the patient [5,6]. Images are rapidly available for checking image quality and for interpretation, and systems can be networked for easy distribution of images.

The expense of installing CR or DR equipment is a disadvantage of digital radiography. DR systems coupled with a PACS allow images to be captured, stored, reviewed, interpreted, and distributed within minutes. DR systems are most often installed in high-volume areas, while CR systems can provide digital imaging to lower-volume areas at decreased expense and can provide a mechanism for capturing difficult examinations such as bedside "portables."

Regardless of which display method is used, a minimum of two radiographic projections at right angles are usually obtained to fully appreciate the area of interest, since abnormalities can potentially be obscured by superimposition. Standardized imaging protocols that may vary depending on clinical indication are used for most joints. Radiographic examination is relatively inexpensive, rapid, and nearly universally available.

Fluoroscopy — As a "real-time" radiographic imaging modality, fluoroscopy can be used to observe the motion of joints, to guide proper needle insertion into deep-seated joints, such as the hip or sacroiliac joint, and for intraoperative purposes [7]. It may also accurately detect focal cortical disease, fractures, and ligamentous instability, as the patient can be optimally positioned or a specific joint can be mechanically stressed under real-time imaging.

Arthrography — Generally, radiographic examinations show soft tissues (e.g. muscles, cartilage, joint fluid, menisci) to be the same density and therefore indistinguishable from one another. Arthrography refers to imaging following the injection of contrast material into a joint, and is often performed using fluoroscopic guidance. The injected contrast outlines intraarticular structures and differentiates them from adjacent soft tissues. It also distends the joint for better separation and visualization of structures [8,9].

Using sterile technique and local anesthesia, the joint space is entered with a needle. Synovial fluid may be aspirated for diagnostic purposes. Next, a contrast agent, such as iodinated contrast, is typically injected. Additionally, medication (eg, anesthetic and/or glucocorticoid) can be injected into the joint for therapeutic purposes as part of an arthrographic procedure.

Arthrography facilitates identification of intra-articular ("loose") bodies, certain ligament or tendon injuries, synovial or cartilage abnormalities, sinus tracts, and loosening of joint prostheses [10]. During the fluoroscopic portion of the examination, "real-time" tracking of contrast as it passes into and fills the joint can highlight abnormalities such as synovitis or abnormal contrast leakage. Arthrography can also be followed by computed tomography (CT; CT arthrography) or magnetic resonance imaging (MRI; MR arthrography, using a dilute gadolinium solution) for imaging. (See 'MR arthrography' below.)

Complications of arthrography are few, with the most common being synovial irritation (chemical synovitis) induced by the iodinated contrast agent, urticaria, and vasovagal reaction. Infection is rare [11,12].

Tomography — Conventional tomography uses reciprocal motion of the radiograph source and film about a fulcrum. This technique been replaced by CT.

Tomosynthesis — Tomosynthesis produces three-dimensional images by using several low-dose radiographs obtained at different angles. This technique, which has been used more commonly for breast imaging, has been applied to musculoskeletal problems including evaluation of fractures, hip prostheses, and rheumatoid arthritis (RA) [13,14]. A comparison of radiography, tomosynthesis, and MRI for the detection of erosion in a group of 20 consecutive patients with established RA found significantly more erosions with tomosynthesis and MRI than with radiography. Tomosynthesis was comparable to MRI with a sensitivity and specificity of 94.8 percent and 97.8 percent, respectively [13].

The radiation dose of tomosynthesis is lower than that of CT, and only slightly higher than that of radiography. A study comparing tomosynthesis with CT for the detection of erosions in the feet of RA patients reported a sensitivity and specificity for tomosynthesis of 80 and 75 percent, respectively [15]. Another study which evaluated tomosynthesis for the detection of hand and wrist erosions in RA patients found a sensitivity and specificity of 77.6 and 89.9 percent, respectively [16]. However, significantly more erosions were found with CT when compared with tomosynthesis, and significantly more erosions were found with tomosynthesis when compared with radiography.

COMPUTED TOMOGRAPHY — CT has become an important diagnostic aid in the evaluation of the musculoskeletal system. As examples, CT is extremely useful in detecting radiographically occult fractures of the acetabulum, cervical spine, wrist, and foot [17]. It is helpful in evaluating cortical destruction by metastatic lesions that may predispose to pathologic fracture. Ossific or calcific densities within a joint can be seen. Additionally, gas in soft tissues associated with necrotizing fasciitis can be detected, and newer techniques allow orthopedic hardware to be evaluated.

In CT utilizing a rotating radiograph source in the axial plane, attenuation values are processed by a computer to produce a cross-sectional image. Post-acquisition data processing allows for far greater latitude concerning image display compared with radiography. Equipment with a single linear array of detectors or with a two-dimensional array of multiple detectors (multidetector CT [MDCT]) may be used.

Helical CT involves continuous patient translation through the gantry at a constant rate during radiograph source rotation and data acquisition [18]. A volume set of data is, therefore, obtained in a relatively short period of time, often in a single breath hold. Helical CT results in decreased artifacts due to motion and respiratory misregistration. It also provides the capability for applications such as CT angiography [19].

MDCT allows thin sections to be obtained in shorter scan times. MDCT scanners using wide two‐dimensional
array detectors
allow large anatomical volumes to be imaged and reconstructed into thin overlapping sections in just a few seconds, facilitating oblique, multiplanar, and three-dimensional reconstructions.

Air-filled spaces, fatty tissue, muscle, and cortical and cancellous bone may all be evaluated with a single CT acquisition. Images may be displayed to best demonstrate soft tissues or bones. In contrast to radiography, complicated bony structures and complex pathological processes are displayed with clarity and without being obscured by superimposed structures.

Manipulation of the imaging data allows high-quality multiplanar reformations and three-dimensional displays to be created at a workstation or in a picture archiving and communication system (PACS). This is particularly useful in evaluating skeletal trauma, guiding surgical planning, and identifying relationships between structures and between fracture fragments [20].

Although the absolute resolution of CT is less than that of radiography, CT is superior in resolving subtle cortical disease. Small cortical or subchondral fractures and osteochondral intra-articular bodies are better seen on CT than on radiographs. CT has also been used to detect and calculate the volume of erosions in rheumatoid arthritis (RA) [21,22], and may be more accurate than MRI or ultrasound for the detection of bone erosions [23].

CT imaging also has benefits for certain indications compared with MRI. As an example, soft tissue calcifications and bony abnormalities are better characterized with CT, although MRI is superior for soft tissue contrast. Osteoid osteomas are usually better demonstrated on CT [24] (see "Nonmalignant bone lesions in children and adolescents", section on 'Osteoid osteoma'). The CT exam requires less time and tends to be less alarming to claustrophobic patients. Also, the presence of metallic implants or pacemakers and the use of life-support equipment do not preclude the use of CT, whereas some of these devices are contraindications to MRI. (See 'Contraindications to MRI' below.)

Technical advances and advanced image reconstruction methods have reduced the artifacts produced by metallic implants, so bone and soft tissue near hardware can be examined more easily [25,26]. In one series, retrospective evaluation of multidetector CT (MDCT) scanning for determining the presence of orthopedic hardware complications was performed in 109 patients (114 studies) [27]. Clinical or operative follow-up in 80 percent of cases provided the reference standard. The sensitivity and specificity of this imaging technique for detecting orthopedic hardware complications in patients with follow-up were 74 and 95 percent, respectively. CT was considerably better than radiography for the detection of these complications.

CT is frequently utilized for the purposes of guiding bone and soft tissue biopsy and aspiration procedures [28].

Dual-energy CT (DECT), in which an area is scanned simultaneously with two tubes at different energies (eg, 80 and 140 kVp), can be used to differentiate materials with similar CT numbers (related to the linear attenuation coefficient) such as iodine and bone [29]. Multiple techniques have been developed for acquiring dual-energy data. DECT can detect tophi and distinguish them from pseudogout and other soft tissue masses [30,31]. Pooled DECT sensitivity and specificity of 11 studies with a mean duration of gout of seven years were 0.87 (0.79 to 0.93) and 0.84 (0.75 to 0.90), respectively [32]. A prospective assessment of 40 patients with gout (mean duration 13 years, 88 percent of whom were on uric acid-lowering therapy) showed a sensitivity of 78 and 84 percent (depending on inclusion criteria) and a specificity of 93 percent [33]. The software algorithm used can significantly affect the positivity for urate [34]. The volume of tophi and subclinical tophi can be assessed using this method [35]. In one study, 15 percent of patients with asymptomatic hyperuricemia had subclinical monosodium urate crystal deposits on foot and ankle DECT scans [36]. However, the clinical significance of these subclinical deposits needs to be determined in a larger population. DECT has shown utility in gout evaluation of the musculoskeletal system identifying extraarticular or deep deposits not amenable to aspiration or other imaging [37]. Another study has shown high sensitivity of DECT for acute calcium pyrophosphate (CPP) crystal arthritis using synovial fluid crystal analysis as a reference standard, and further studies are in progress in this arena [38]. (See "Clinical manifestations and diagnosis of gout", section on 'Role of imaging in diagnosis'.)

Considerations for use — It is important to carefully review the indications for each CT examination and minimize the radiation dose as much as possible [39,40], particularly in children [41,42].

CT arthrography may be a substitute for patients who cannot have an MRI examination. CT arthrography of the knee, for example, may be used in patients with suspected internal derangement who cannot have MRI [43].

MAGNETIC RESONANCE IMAGING — MRI depicts internal structures based upon their chemical composition [44].

The principle of MRI is that, when a patient is placed in the bore of a super conducting electromagnet, free hydrogen nuclei within the tissues will align their inherent magnetic dipoles with that of the magnetic field. This creates a new atomic low-energy state. Rapid pulses of radio-frequency electromagnetic radiation are then imparted to the tissues, which deflect the spinning nuclei off their axes, creating a higher-energy state. As the nuclei return to their baseline state, they emit electromagnetic energy that varies in intensity based upon chemical composition. The energy released by the nuclei relaxing to their baseline energy level can be localized in space and can be quantified, and a cross-sectional image of the area can be produced. Anatomy-specific receiving coils that detect the released electromagnetic radiation are placed directly over the body part (joint) during scanning. A more detailed discussion of MRI is presented separately. (See "Principles of magnetic resonance imaging".)

Clinical MRI systems are available in several field strengths, usually ranging from 0.5 to 3 Tesla. Some advantages of higher field strength are increased signal to noise (providing higher spatial resolution), shorter image acquisition times, and improved imaging after intravenous contrast [45]. Whole body open-magnet systems provide greater ease in patient positioning, can be used for larger patients, and decrease claustrophobia. However, these magnets are often low- or mid-field with limited signal to noise [45].

Extremity magnets are often low-field magnets that are primarily designed for imaging of peripheral joints. Claustrophobia is avoided since only the part to be examined is placed within the magnet's bore. The use of low-field extremity magnets for imaging rheumatoid arthritis (RA) has been a topic of ongoing discussion, especially since these magnets are small enough to be located in an office or clinic [46].

Extremity MRI is more sensitive than radiography for the detection of joint erosions. This was illustrated in a study of 44 patients that revealed four times more erosions with extremity MRI than with radiography [47,48]. The authors of the study proposed that MRI of both hands could be used as a screening tool and that examining one hand could be used to monitor erosions over time.

Uses of MRI — A major advantage of MRI is its ability to evaluate noncalcified body tissues. For example, menisci, articular cartilage, cruciate ligaments, tendons, and joint fluid that would be indistinguishable on a radiograph are readily distinguished on MRI. Thus, MRI is particularly useful for the evaluation of soft tissue changes such as internal derangement, articular cartilage integrity, and synovitis. An infinite number of reconstruction planes allow for the sagittal, coronal, and axial displays of these complex structures. Normal tendons are completely black (low signal) on traditional MRI sequences. Tendons in early stages of degeneration demonstrate abnormal (increased) signal intensity and contour alterations, and complete disruptions are often readily identified.

MRI is also very sensitive in detecting subtle changes in the water content of tissues due to inflammation, neoplasm, trauma, or ischemia (see "Principles of magnetic resonance imaging"). Changes within the intramedullary canal of bone alter the normal marrow signal and are depicted with great clarity by MRI. Thus, conditions such as avascular necrosis, transient regional osteoporosis, early infections, subtle trauma, ischemia, and infiltrative processes are best visualized using MRI.

Contraindications to MRI — Each patient must be evaluated for both indications and contraindications to MRI. Several sources are available for reference regarding MRI safety [49] and contraindications to MRI including the American College of Radiology (ACR) website, www.mrisafety.com, and device or implant manufacturer information. The imaging provider can help evaluate for safety issues.

Examples of contraindications to MRI include the presence of [50]:

●Orbital metallic foreign bodies

●Most cardiac pacemakers – Some MRI conditional device implantable cardiac pacemakers may be scanned on a 1.5 T magnet with the pacemaker turned off during the time of the study, and the patient under the care of a cardiologist with monitoring, only after the case is deemed medically necessary by the radiologist and clinician and the appropriate risk-benefit analysis has been performed [51]

●Implanted defibrillators

●Most cochlear implants

●Some aneurysm clips

MR-guided biopsy — Given the superior soft tissue contrast resolution inherent to MRI, it is not surprising that MR-guided biopsy has evolved as a tool to obtain tissue diagnosis for both bone and soft tissue lesions. With the use of special instrumentation, it has been found that MRI guidance is feasible for biopsies, spine procedures, cyst aspirations, therapeutic injections, and tumor ablation [52]. As MRI becomes increasingly available, it is likely that it will also become increasingly used for these purposes. By combining fluoroscopy with MRI to form hybrid systems, the advantages of each system can be utilized in a synergistic way [52].

MR arthrography — The administration of a dilute solution of gadolinium into a joint, followed by MRI, produces an MR arthrogram that allows the intraarticular structures (such as cartilage surfaces) to be better-defined and increases the ability to detect adjacent ligamentous or tendinous disruptions. MR arthrography is often used in evaluating the shoulder and the hip for labral tears. The gadolinium contrast agents that are available for use have generally not been explicitly approved for intra-articular injection by regulatory agencies in the US and Europe; thus, such use is "off-label" [53,54].

Indirect MR arthrography — After intravenous administration, gadolinium contrast material will diffuse into joints, even normal ones [55]. This diffusion can be utilized to provide an "indirect" or "intravenous" arthrogram, which can be helpful in delineating articular cartilage and other intraarticular structures. An increased rate of diffusion of contrast will occur in patients with active inflammatory arthritis. (See 'MRI uses in rheumatic disorders' below.)

Concerns expressed below regarding toxicity when used in patients with moderate to severe renal compromise also apply to intravenous MR arthrography. (See 'Potential gadolinium toxicity in renal failure' below.)

Intravenous contrast for MRI — Intravenously administered contrast agents, such as gadolinium, highlight vascular structures and may make some pathologic processes more conspicuous. MRI contrast agents reflect tissue vascularity and perfusion. In general, malignant soft tissue tumors show greater and more rapid contrast enhancement than benign lesions, although differentiation of benign from malignant lesions is limited [56]. Avascular, necrotic, and cystic areas will not show enhancement. Therefore, when there is a question of whether a lesion is solid or cystic, intravenous contrast can be helpful; this distinction can also be made with ultrasound. Intravenous contrast is also used in evaluating bone tumors.

Potential gadolinium toxicity in renal failure — Patients with moderately or severely impaired renal function (eg, estimated glomerular filtration rate of less than 30 mL/min) may need to avoid gadolinium-containing MRI contrast agents due to an enhanced risk of developing nephrogenic systemic fibrosis depending on the type of gadolinium agent/class used. The latest version of the ACR Manual on Contrast Media is a helpful resource for determining nephrogenic systemic fibrosis risk relative to the type of gadolinium agent used [57]. (See "Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy in advanced kidney disease", section on 'Prevention'.)

MRI uses in rheumatic disorders — The following areas are illustrative of some of the ways MRI can be used in the evaluation of rheumatic disease:

●Osteoarthritis – MRI is generally not used for the diagnosis of OA, as clinical evaluation together with radiography appear to be the most effective methods for diagnosis, as indicated by a systematic review and meta-analysis of relevant studies [58]. The eventual role of MRI in the management of OA requires further clarification, and additional epidemiologic studies are needed [59]. MRI does demonstrate all of the structures that may be involved in OA, including the subchondral bone, articular cartilage, menisci, ligaments, and synovium. MRI is most often used as a research tool in OA, and several scoring systems have been developed for these purposes [60-62].

MRI may be used to quantify articular cartilage and to display it as a three-dimensional surface-rendered image [63]. In one study, cartilage volumes were evaluated in 107 OA patients at baseline, 12 months, and 24 months; determination of cartilage volume loss allowed identification of patients who were slow, intermediate, or fast progressors [64]. Clinical factors (such as a high body mass index) and morphological factors (such as severe meniscal extrusion) were predictors of rapid progression.

●Cartilage repair – Orthopaedic techniques are being developed and refined to replace damaged articular cartilage. These procedures are especially used in the knee [65]. Techniques include microfracture, autografts and allografts, and autologous chondrocyte implantation (ACI), procedures described in some detail in the above reference [66-69]. While arthroscopy provides the gold standard for assessment of the repair, MRI can provide information about the fill of the defect, its integration, the signal intensity of the repair tissue, and the status of the subchondral bone in addition to assessing the remainder of the joint [65]. One study used delayed gadolinium-enhanced MRI (dGEMRIC) at 3Tesla to evaluate two groups of 10 patients each who had undergone ACI and microfracture, respectively [69]. At a mean time after surgery of 17 months, there was a statistically significant increase in the relative glycosaminoglycan (GAG) content within the ACI group as compared with the microfracture group [69]. (See "Overview of surgical therapy of knee and hip osteoarthritis".)

●Rheumatoid arthritis – There is a lack of clarity regarding the indications for routine high-field MRI for the diagnosis and management of patients with RA [45,70]. A European Alliance of Associations for Rheumatology (EULAR; formerly known as European League Against Rheumatism) task force studied the role of MRI in RA in the clinical setting and their recommendations have been published [71]. Synovial hypertrophy, erosive disease, small subchondral cysts, and subchondral bone marrow edema not observed on radiographs can be visualized on MRI [72]. In one study of 31 patients with early RA who had swelling of the metacarpophalangeal joints, MRI detected bone marrow edema in 21 patients compared with 3 of 31 healthy control subjects. Synovial enhancement patterns can indicate active versus inactive RA. Bone marrow edema, synovitis, and erosion appear to be related, and, interestingly, bone marrow edema (osteitis) appears to be more predictive of erosion than is synovitis [73]. (See "Clinical manifestations of rheumatoid arthritis", section on 'MRI'.)

●Sacroiliitis/spondyloarthritis – MRI of the sacroiliac (SI) joints is helpful for evaluating patients with clinically suspected sacroiliitis/spondyloarthritis with negative SI joint radiographs [74]. MRI can indicate the activity of disease with bone marrow edema/osteitis, synovitis, enthesitis, and capsulitis, suggesting active inflammation. Bone marrow edema/osteitis, in particular, has been thought to be essential for the diagnosis of active sacroiliitis [75]. Because bone marrow edema can be assessed without contrast administration, and because bone marrow edema always accompanies post contrast signs of inflammation (osteitis) [76], a noncontrast MRI with appropriate sequences (eg, short tau inversion recovery [STIR] and T1-weighted images) is usually sufficient to make a diagnosis of sacroiliitis and to quantify active inflammation [77]. However, some experts note that contrast may ensure maximum diagnostic confidence in patients with early sacroiliitis [77]. Erosion, sclerosis, fatty replacement of bone marrow, and fusion can also be evaluated. CT may be useful for diagnosis if radiographs are normal and MRI cannot be performed [74]. CT is best for identifying cortical erosive destruction and sclerosis and ankyloses that are more in keeping with previous inflammation [78]. Intravenous contrast is usually also not necessary for established sacroiliitis or for following disease [77]. MR evaluation of the early inflammatory changes of the vertebral body corner (Romanus lesions) within the spine is also useful in diagnosis of spondyloarthropathy, appearing as edema within the subchondral bone before true erosions occur [79]. (See "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'MRI of sacroiliac joints'.)

●Gout – Radiography is the usual method for imaging the effects of gout, whereas dual-energy CT (DECT) scan has shown promise for detecting subclinical gout and evidence of gout not apparent on other imaging modalities (see 'Computed tomography' above). MRI findings in gout have been described but are not specific. Tophi appear as masses that demonstrate intermediate or low signal intensity on T1-weighted images and heterogeneous (or variable) signal intensity on T2-weighted or fluid-sensitive sequences [80,81]. Tophi can enhance heterogeneously after administration of intravenous contrast. Bone erosions adjacent to tophi produce cortical destruction but only mild to moderate bone marrow edema [80,82]. Marked amounts of bone marrow edema are suggestive of osteomyelitis in the correct clinical setting [82].

Other findings seen in gout are effusion and intratendinous tophi. In one study, MRI was 63 percent sensitive and 98 percent specific for the diagnosis of chronic gouty arthritis [83]. MRI may have advantages over ultrasound in that deeper structures can be assessed with MRI [80]. As noted above, patients with gout and osteomyelitis may be differentiated from those without osteomyelitis [82]. (See "Clinical manifestations and diagnosis of gout", section on 'Imaging'.)

●Metallic arthroplasties – Technical advances have improved the quality of MRI around these prostheses so that osteolysis or fracture, the joint capsule synovitis, muscles, nerves, vessels, and tendons may be assessed [84,85]. In patients suspected of having complications associated with metal-on-metal prostheses, MRI is the imaging examination of choice [86,87]. (See "Complications of total hip arthroplasty", section on 'Sequelae from metal-on-metal wear debris'.)

Evaluation of 46 total knee prostheses (41 patients) using an MRI technique tailored to reduce metal susceptibility artifact resulted in surgical or other therapeutic procedures in 20 patients and influenced treatment in all patients [88].

NUCLEAR MEDICINE — Nuclear medicine uses the tracer principle. Scintigraphic images are produced following the administration of a radiopharmaceutical. The radiopharmaceutical distributes in the body based upon its chemical and biological properties. Radiation, mostly gamma photons, emitted from the agent is converted into planar or tomographic images. The unique aspect of scintigraphy is that radiotracer localization reflects molecular, metabolic, physiologic, and/or pathologic conditions of the body [89].

A number of nuclear imaging examinations have been used for evaluation of joint pain, including bone scan, labeled leukocyte scintigraphy (white blood cell [WBC] scan), gallium scan (using gallium-67 citrate), and positron emission tomography (PET), which is performed with 2-(fluorine-18) fluoro-2-deoxy-D-glucose (FDG) or fluorine-18 sodium fluoride (NaF). The type of scan depends upon the clinical indication. Of these examinations, the gallium scan will not be discussed as it is indicated primarily for evaluation of spondylodiscitis.

Bone scan — Bone scan is the most common nuclear imaging examination used to evaluate joint conditions. Bone scan may play a complementary role when other imaging studies are negative or inconclusive, but a strong clinical suspicion of bony abnormality remains. Technetium-99m (Tc-99m)-labeled diphosphonate, in the form of either methylene diphosphonate (MDP) or hydroxymethylene diphosphonate (HDP), is the most widely used bone scan tracer. Diphosphonate is adsorbed onto the surface of hydroxyapatite crystals. Increased bone uptake of this tracer mostly reflects increased bone turnover or remodeling in response to underlying processes (eg, infection, neoplasms, trauma, arthritis, etc). In the acute phase of infection or inflammation, increased tracer uptake is also due, in part, to increased blood flow, while the contribution of blood flow to bone uptake in chronic conditions is substantially less. Thus, greater acuity and severity of an inflammatory process generally results in findings of more increased blood flow and blood pool activity on the three-phase bone scan. However, the intensity on the delayed phase of the scan does not necessarily reflect the degree of inflammatory activity.

Bone scan is a highly sensitive technique for the detection of a large number of bone, joint, and periarticular disorders, including fracture, infection, tumor, arthritis, and metabolic bone disease [90]; thus, a negative study effectively excludes most bone and joint abnormalities. A finding of "increased tracer uptake" on a bone scan is nonspecific, although recognition of characteristic patterns of uptake and/or locations of involvement typical of different disease processes may provide more specific diagnostic information. Bone scan can also be useful for documenting the presence of arthritis and for assessing the extent and distribution of disease. Other studies, such as FDG-PET or labeled WBC scans, may be more suitable for assessing serial changes in inflammatory activity.

Bone scan findings and issues of importance in particular articular diseases include the following:

●Osteoarthritis – Bone scan may show abnormal areas of uptake before radiography shows evidence of osteoarthritis (OA). While conventional bone scan is generally not performed for assessment of OA, some evidence suggests that single photon emission CT (SPECT or SPECT/CT) may play a role in the assessment of patients with OA:

•SPECT or SPECT/CT findings are well-correlated with clinical findings, such as pain scores and physical examination in patients with knee OA.

•SPECT or SPECT/CT is reported to be a sensitive tool for identifying early OA [91,92].

•There is also a significant correlation between the intensity of uptake on SPECT-CT in the medial and lateral knee compartments and the varus or valgus alignment of the knee. In one study, SPECT-CT reflected the specific loading pattern of the knee with regard to its alignment and the severity of OA [93]. Thus, SPECT-CT could be used in the follow-up assessment of patients after realignment treatments or osteotomies, or it could be used with the use of deloader devices or insoles.

•SPECT/CT improves the specificity; a considerable number of lesions initially thought to represent OA on conventional bone scan and SPECT were reclassified as fractures, or a number of lesions initially thought to represent osteomyelitis were reclassified as OA, fracture, or soft-tissue inflammation [94].

●Rheumatoid arthritis – Bone scans generally are not used in the routine clinical management of rheumatoid arthritis (RA). However, a negative scan essentially excludes active RA in patients with persistent polyarthralgia because of the high sensitivity of bone scan for inflammatory joint disease [95]. Some observations in patients with RA include the following:

•The distribution of tracer uptake may help distinguish seronegative arthritis from RA (eg, by demonstrating increased uptake in the distal interphalangeal joints in psoriatic arthritis versus in the metacarpophalangeal joints in RA).

•Some studies but not others have suggested that erosions are most likely to develop in joints showing high tracer uptake, particularly when high activity persists [96,97]. One study suggested that bone scan could differentiate between early nonerosive RA and systemic lupus erythematosus (SLE) [98]. However, the uptake is nonspecific and not distinguishable from OA; thus, symptoms and location of specific joint involvement provide important clinical context.

•Although the blood pool phase provides some information on the degree of inflammation, bone scan is generally not useful for assessing the level of activity of the arthritis, in part because it does not differentiate actively inflamed joints from chronically damaged ones [99,100].

•In pediatric patients, it may be difficult to assess juvenile RA, particularly in the peripheral small joints, due to normally increased uptake in the adjacent growth plates.

●Sacroiliitis – Bone scan has not become a widely used method for the evaluation of sacroiliitis because of its suboptimal specificity, although comparing the tracer uptake in the sacroiliac joints with a reference region, typically the sacrum, on a planar bone scan has been used to evaluate sacroiliitis. MRI has been found to be more accurate than quantitative planar bone scan in the detection of early sacroiliitis [101,102]. SPECT bone imaging together with MRI may provide complementary information. In one study, use of MRI and bone SPECT together provided objective and complementary evidence of sacroiliitis in patients with clinical features of inflammatory spinal disease in the absence of conventional radiographic changes [103].

●Osteonecrosis (avascular necrosis) – Bone scans are not the diagnostic procedure of choice for diagnosing osteonecrosis. Bone scan of the hip typically shows decreased tracer uptake in the affected femoral head during the early stage of osteonecrosis, followed by variable degrees of increased uptake during the reparative stage. Osteonecrosis of the knee is typically associated with increased uptake regardless of the stage. In older female patients with acute knee pain who are suspected of having spontaneous osteonecrosis of the knee, intense tracer uptake in the medial femoral condyle is highly suggestive of the diagnosis. Osteonecrosis may also involve the lateral femoral condyle or the medial tibial plateau. (See "Clinical manifestations and diagnosis of osteonecrosis (avascular necrosis of bone)", section on 'Limited role of radionuclide bone scanning'.)

●Painful joint replacement – A normal bone scan may be useful in the evaluation of patients with a painful joint replacement, as it is consistent with an absence of infection or other processes that may cause increased tracer activity around the hip or knee prosthesis; such findings on bone scan reflect increased bone mineral turnover and may result from any of a number of conditions in addition to infection. Additionally, there are numerous patterns of periprosthetic uptake associated with asymptomatic prostheses. However, the overall accuracy of conventional bone imaging in the evaluation of prosthesis complication (either infection or loosening) is about 50 to 70 percent, primarily due to poor specificity, and it is best used as a screening test. If the utility of conventional bone scan is to be maximized, it may be necessary to perform serial imaging, including baseline studies [104].

SPECT/CT is increasingly used for assessment of painful joint prosthesis replacement [105]. The technique is reported to be a promising tool for evaluation of post-knee arthroplasty pain, as the technique offers the combined analysis of tracer uptake distribution and intensity as well as the ability to measure prosthetic component position [106]. It may also identify the cause of pain in patients with unexplained pain after a metal on metal (MOM) total hip arthroplasty [107]. (See "Complications of total hip arthroplasty", section on 'Sequelae from metal-on-metal wear debris'.)

Labeled leukocyte scintigraphy — Labeled leukocyte scintigraphy (WBC scan) may be performed to evaluate for infectious processes such as osteomyelitis or an infected joint replacement. To perform a WBC scan, the patient's own white blood cells are labeled with either indium-111 or Tc-99m and are reinjected. (See "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis", section on 'Nuclear modalities'.)

Increased WBC uptake around a painful joint replacement is a nonspecific finding. In patients with joint replacements, there is often reconversion of yellow marrow to red marrow. As labeled WBCs accumulate both in sites of infection and in red bone marrow, increased WBC uptake around joint replacements is, thus, not specific for infection. Distinguishing these two processes can be done by performing complementary WBC scanning and bone marrow imaging with Tc-99m-sulfur colloid. While both WBCs and sulfur colloid accumulate in red marrow, WBCs accumulate in infection, but sulfur colloid does not [108,109]. Therefore, increased activity on the labeled leukocyte images without corresponding activity on the sulfur colloid images is due to infection.

WBC scanning is not useful clinically in the management of RA, but it has been employed in research settings. In RA, labeled WBCs may accumulate in active inflammatory arthritis. In a study of 21 patients with RA, there was a significant correlation between the local manifestation of the active disease (swollen joint count) and the labeled leukocyte accumulation [110]. Another study suggested that semiquantitative values obtained with labeled WBC scan could distinguish active RA from inactive RA or osteoarthritis [111]. Labeled WBC accumulation has also been reported to be a sensitive index for monitoring RA activity in response to pharmacologic interventions, unlike quantitative bone scintigraphy [112].

PET scan — The most common clinical application of PET/CT is in oncology (eg, for staging known malignancies, monitoring the effect of treatment, and evaluation of tumor recurrence), followed by cardiology (eg, evaluation of ischemia, viability) and neurology (eg, differential diagnosis of dementia, Parkinson syndrome) [113]. While PET is not routinely used in the clinical evaluation of arthritis, it has been employed in the research setting.

PET is a diagnostic examination that involves the acquisition of physiologic images based upon the detection of two coincident gamma photons (positrons) traveling in opposite directions. These photons are generated from the annihilation of a positron with a native electron. Positron-emitting radionuclides are tagged to metabolically active pharmaceuticals and administered intravenously to the patient [114].

PET performed with FDG provides qualitative and quantitative metabolic information [113]. FDG is a radiopharmaceutical analogue of glucose that is taken up by metabolically active cells such as tumor cells [113].

PET and CT are separately performed, typically one immediately followed by the other on a hybrid PET/CT system. Generally, three sets of images, ie, PET images, CT images, and co-registered PET/CT images, are displayed on a viewing station. Metabolic activity of the area of interest is assessed both by visual inspection of the images and by measuring a semiquantitative value of FDG uptake, called standardized uptake value (SUV) [113].

A few examples of PET scan findings in specific diseases are as follows:

●FDG-PET in rheumatoid arthritis – Since the FDG-PET studies showing increased FDG uptake in active RA were reported first in 1995 [115], many researchers have examined the utility of FDG-PET in patients with RA [115-122]. However, FDG-PET/CT is not routinely used in patients with RA in the United States.

Whole-body evaluation with FDG-PET/CT can detect the extent of disease activity, even at subclinical levels [117]. The sensitivity of FDG-PET for detecting inflamed joints in patients with RA is reported to be high (up to 90 percent) [116]. While healthy joints do not show abnormally increased FDG uptake, the presence of increased FDG uptake alone does not necessarily differentiate RA from other joint diseases such as OA or other inflammatory joint diseases [118,119]. However, biodistribution patterns of involved joints can be used to help distinguish among joint diseases [119].

Several studies have also shown a correlation between FDG uptake and other parameters of inflammation such as pannus formation on MRI [115], painful/swollen joints [116], and acute phase reactants [116]. In addition, early changes in FDG uptake in RA may predict clinical outcomes, as several reports have found that the changes in SUV in the inflamed joint correlate well with the clinical response assessed at various time points following treatment [115,120-122].

●FDG-PET in prosthetic joint infection – FDG-PET is highly sensitive for the inflamed prosthetic joint. However, studies have demonstrated varied results of FDG-PET in diagnosing prosthetic joint infection, and its role has not yet been fully established [123,124]. (See "Prosthetic joint infection: Epidemiology, microbiology, clinical manifestations, and diagnosis", section on 'Radiographic imaging'.)

●FDG-PET in spondylodiscitis – MRI is the gold standard for the diagnosis of discitis; however, FDG-PET is a useful adjunct to MRI and can be used when MRI is inconclusive or cannot be performed. Several investigations have shown that FDG-PET is highly sensitive and specific in the diagnosis of nontuberculous spondylodiscitis. One series of 38 patients with suspected spondylodiscitis with inconclusive results on conventional imaging reported sensitivity, specificity, and accuracy of FDG-PET/CT of 81.8, 100, and 89.5 percent, respectively [125]. Positive and negative predictive values were 100 and 80 percent, respectively [125,126]. Sensitivity, specificity, and accuracy of MRI performed on the same patients were 75, 71.4, and 74.1 percent, respectively [125]. FDG-PET also has utility in assessment of treatment response, as changes on MRI do not correlate with clinical response [126]. A prospective study including 30 patients with spinal infection found that the change in SUV max between the initial and the follow-up FDG-PET was the best predictor of residual infection [126,127].

●FDG and fluoride PET in ankylosing spondylitis – Limited data suggest that ankylosing spondylitis (AS) activity is better reflected by bone activity on sodium fluoride PET/CT than inflammation on FDG-PET [128,129]. Additional studies are necessary to better define the role of each tracer in patients with AS.

ULTRASOUND — Ultrasonography (US), sometimes referred to as ultrasound imaging or sonography, is an imaging modality that utilizes reflected pulses of high-frequency (ultrasonic) sound waves. Musculoskeletal US can be used to assess soft tissues, cartilage, bone surfaces (cortical integrity), and fluid-containing structures and is becoming more widely available for diagnostic and therapeutic use in outpatient settings. US can be used clinically for assessing and monitoring inflammatory arthritis, for imaging tendons and bursae, and for guiding the aspiration and/or injection of joints or soft tissues.

Among the possible advantages of US are the avoidance of radiation exposure and of the inconvenience associated with use of fluoroscopy for procedures involving otherwise difficult-to-enter joints and other spaces. Limitations of US include poor soft tissue penetration of sound waves and their complete reflection by bone, resulting in limited acoustic windows for imaging joint pathology, as well as the substantial operator-dependence of US examination.

The clinical applications of musculoskeletal US, the technical aspects of musculoskeletal US, and the use of US imaging for joint, tendon, and bursal injections and for aspiration of fluid are addressed in detail separately. (See "Musculoskeletal ultrasonography: Clinical applications" and "Musculoskeletal ultrasonography: Nomenclature, technical considerations, and basic principles of use" and "Musculoskeletal ultrasonography: Guided injection and aspiration of joints and related structures".)

SUMMARY AND RECOMMENDATIONS

●Radiographs are the imaging study of choice for routine evaluation of fractures, inflammatory and degenerative arthritides, metabolic bone disease, and developmental deformities. (See 'Radiography' above.)

●CT may be useful in detecting cortical bony lesions and is widely used in fracture detection, especially in complex areas such as the cervical spine. Dual-energy CT (DECT) has shown utility in gout evaluation of the musculoskeletal system, identifying extraarticular or deep deposits not amenable to aspiration or other imaging. DECT has also shown utility in acute calcium pyrophosphate (CPP) crystal arthritis evaluation. (See 'Computed tomography' above.)

●Internal derangement of a joint and soft tissue injuries are best evaluated with MRI. MRI can evaluate all of the tissues involved in osteoarthritis (OA) and can detect synovitis, erosion, and bone marrow edema (osteitis) in patients with rheumatoid arthritis. (See 'Magnetic resonance imaging' above.)

●Nuclear medicine studies may play a complementary role when other imaging studies are negative or inconclusive but when there remains a strong clinical suspicion of bony abnormality. Positron emission tomography (PET) is an important modality for evaluating the metabolic activity of tumors and shows promise in the evaluation of arthritides as well, but its role in routine clinical practice has not been established. (See 'Nuclear medicine' above and 'Bone scan' above and 'PET scan' above.)

●Musculoskeletal ultrasound (US) can be used to assess soft tissues, cartilage, bone surfaces, and fluid-containing structures. US can be used clinically for assessing and monitoring inflammatory arthritis, for imaging tendons and bursae, and for guiding the aspiration and/or injection of joints or soft tissues. (See 'Ultrasound' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Barbara N Weissman, MD, and Chun K Kim, MD, who contributed to an earlier version of this topic review.