Quantitative

Imaging

of Osteoarthritis

By Mark E. Adams and Carla J. Wallace Plain-film radiography currently remains the mainstay of imaging for diagnosis and follow-up in osteoarthritis (OA). However, recent studies have questioned some aspects of its use, particularly the correlation between radiographically evident joint-space narrowing and articular cartilage loss. The results with imaging modalities such as magnetic resonance imaging and ultrasound suggest that these methods will allow accurate noninvasive definition of the structure of atticular cartilage and other soft tissues of joints. Other modaliies, including microfocal radiography and high-resolution computed tomography, can produce detailed images of trabecular structure and bony alterations in osteoarthritis. Improvements in image analysis and data manipulation, including three-dimensional reconstruction and digitized storage and measurement of images, will likely enable improved quantitative assessment of the abnormalities demonstrated by these techniques. One can hope that such developments will facilitate not only improved detection and definition of OA, but also better evaluation of the effectiveness of pharmacological and physical therapy in practice and in clinical trials. Copyright 0 1991 by W.B. Saunders Company

history and epidemiology, or clinical trials in OA that have used imaging as an assessment technique. Physical measurements of distance and area are possible with all types of joint imaging; ac curacy is dependent on spatial and contrast resolution, image distortion and magnification. With the increasing use of computed imaging techniques-digitized plain film radiography, computed tomography (CT), ultrasound and magnetic resonance imaging (MRI)-these measurements are facilitated. Quantitative assessment of tissue properties such as electron density (with radiographs or CT), acoustic impedance (with ultrasound), and T, and T2 relaxation times (with MRI) has also become feasible. As yet, quantitative analysis of these tissue parameters has had little impact on our understanding of OA. At present it appears that none of these parameters could be used as a measure of tissue specificity, but their alteration in pathological states may facilitate quantitative assessment of disease.

INDEX WORDS: analysis.

The peripheral joint disturbance known as OA is extremely common, symptomatically affecting about 14% of the adult population. ’ OA develops slowly and its etiology and pathogenesis are poorly understood. Traditional thinking identifies the articular cartilage as the site of the earliest pathological changes, but decreased subchondral bony compliance with subsequent increased loading of cartilaginous surfaces, perhaps contributed to by subchondral microfractures, may, in fact, play a role in the pathogenesis of 0A.2 The late pathological changes of OA, many of which can be readily visualized with diagnostic imaging modalities, are well described in standard textbooks and are listed in Table 1. It is important to define OA, both to enable more specific imaging in clinical diagnosis and to increase the precision of assessments in research. A variety of definitions have been developed for clinical, pathological, biochemical, or radiographical studies. However, because these disciplines use different assessment techniques to

Osteoarthritis;

diagnosis;

imaging;

T

HIS article will review selected recent advances in quantitative assessment of imaging of structural changes in peripheral joints athicted with osteoarthritis (OA). It is beyond the scope of this article to review comprehensively all aspects of imaging in OA, studies of its natural

From the Departments of Medicine and Radiology, University of Calgary, and Foothills Hospital, Calgary, Alberta, Canada. Supported by Roussel Canada, Inc. Mark E. Adams, MD, FRCPC: Arthritis Society Chair in Research, Associate Professor of Medicine, University of Calgary; Carla J. Wallace, MD, FRCPC ChiefPhysician, MRI, Foothills Hospital; Assistant Professor of Radiology, University of Calgary. Address reprint requests to Mark E. Adams, MD, Department of Medicine, 3330 Hospital Dr NW, Calgary, AB T2N 4Nl. Canada. Copyright 0 1991 by W.B. Saunders Company 0049-0172/91/2006-2002$5.00/O

26

Definitions of Osteoarthritis and Their Relation to Joint Imaging

Seminars in ArVniris and Rheumatism, Vol20, No 6, SuppI

(June), 199 1: pp 26-39

27

QUANTITATIVE IMAGING OF OA

Table 1: Pathological Features of Osteoarthritis That May Appear on Imaging Cartilage degeneration

Fibrillation Fissuring Erosions Loss (joint-space narrowing)

Bone reaction

Increased vascularity Trabecular remodeling Subchondral sclerosis Eburnation Cyst formation Osteophyte formation Osteonecrosis

Synovial reaction

Synovial effusions Capsular fibrosis

Other features

Meniscal/ligament tears Pathological calcification

in early disease are nonspecific, and because there are no pathognomonic noninvasive diagnostic tests. The clinical definition proposed by the American College of Rheumatology (ACR) Criteria Committee6 emphasizes pain, osteophytosis, age, crepitus, and several other signs and symptoms. However, these criteria were not designed to aid in the diagnosis of individual cases in the clinical setting, but were intended to aid in the evaluation of studies of populations of patients with OA. Nevertheless, the inclusion of symptoms in a definition of OA designed for clinical use, rather than an exclusive reliance on radiographical or pathological findings, might enable earlier diagnosis in individual patients, at a time when the radiographs are still normal.

Angular deformities

Clinical Problems

measure different variables, it is possible that no one definition will satisfy all who are involved in studies of this disorder. Pathologically, OA often is defined by focal loss of cartilage, osteophyte formation, and subchondral sclerosis.3 If this definition, with its emphasis on macroscopic structural changes, were sufficient for all clinical purposes, plain radiographs would be ideally suited for the assessment of OA. However, these changes are late manifestations of the disease and reflect significant joint damage with remodeling or repair. In OA, focal cartilage fibrillation and ulceration precede the large scale cartilage loss that must be present before joint-space narrowing can be detected on radiographs.4 Furthermore, these features alone do not fully describe the pathological alterations in the joint: OA is often associated with disruption of the periarticular soft tissues, alterations that contribute to symptoms and disability, and probably accelerate the rate of progression of bony and cartilaginous pathology. That pain may arise from such soft tissue changes helps explain why the symptoms of OA and the radiographical findings are often discordant,5 and, in particular, why patients may exhibit symptoms before OA can be detected with radiography. Thus, the early stages of OA are hard to define clinically and study pathologically because the clinical features

There is little question that OA is a significant public health problem. At present, a cure for OA seems a remote possibility, so the current therapeutic goals are to relieve pain and preserve function. However, studies of experimental models of OA in animals have shown that some medical therapies, when instituted early in the disease process, may actually affect the rate of progression of OA. Some of these treatments appear to slow the rate of cartilage degeneration while others, particularly antiinflammatory doses of salicylates, accelerate the rate of damage to joints. 7-‘3In most of these studies, the evaluation of the rate of progression of joint damage has been based on histiopathological analysis, a method of assessment that is clearly inappropriate for therapeutic trials in humans. It is important to note that salicylates, the most consistently implicated of the deleterious drugs, are still commonly used in the treatment of OA, though perhaps fewer patients are now being prescribed antiinflammatory doses of salicylates for this condition since the publication of the above findings. It is reasonable to suspect that these drugs may affect the rate of progression of human OA. Biochemical studies of the cartilage, both of experimental animal models of OA and of human cartilage in culture, suggest hypotheses to explain the actions of these drugs on the progression of

28

articular damage.7~8~‘o~1 ’ The drugs that adversely affect the course of OA may do so by suppressing articular cartilage proteoglycan synthesis; those that seem to have a beneficial effect may inhibit breakdown of cartilage by proteases, or may suppress the production or action of mediators of cartilage destruction. These hypotheses for the mechanisms by which pharmacological therapy affects the rate of progression of osteoarthritis have given rise to the neologisms “chondroprotective” and “chondrodestructive” in referring to these therapies. However, the actions and mechanisms implied by these terms have yet to be proven in humans in vivo. Furthermore, despite the importance of articular cartilage in joint function, one must bear in mind that all the tissues of the joint, not just the articular cartilage, are involved in the osteoarthritic process, and these tissues may each be affected by these medications, perhaps in different ways. At present it is difficult to find incontrovertible evidence that pharmacological therapy affects the rate of progression of OA in humans, probably because of the lack of sensitive and accurate noninvasive follow-up assessment techniques. Retrospective reports suggest that OA of the hip progresses faster in patients treated with nonsteroidal antiinflammatory drugs (NSAIDS),“‘~ but the differences may have been due to patient selection, because patients with more severe OA usually receive more vigorous treatment and may have a higher prevalence of osteonecrosis. A prospective study using arthroscopic evaluations has shown that articular cartilage lesions may heal alter high tibial osteotomy,17 but the invasive nature of arthroscopy limits its usefulness as an assessment technique in controlled clinical trials of pharmacological treatments. One recent clinical study suggests that some of the deleterious effects that occur in experimental animal models of OA may also occur when NSAIDs currently are used to treat human OA.‘* The effects of a weak and a strong prostaglandin inhibitor (azapropazone and indomethacin) were compared in a prospective study of patients awaiting total hip arthroplasty, with pathological evaluation of the excised femoral head. Indomethacin appeared to be associated with accelerated cartilage loss. Although the patient selection criteria and lack of untreated controls have given rise to criticism of this study,

ADAMS

AND WALLACE

the findings emphasize the need to improve methods of defining and assessing the severity of OA. It is apparent that well-designed clinical studies in humans must be performed to address this issue definitively. Although it is feasible to obtain pathological material in some study designs, such as the two studies described above, for large scale studies it is critically important to develop improved noninvasive techniques for detecting OA earlier and evaluating its severity and progression quantitatively. Clearly, the development and validation of improved methods to quantify the imaging of OA would improve the chances of a successful outcome to such studies.

Limitations of Radiography in Correlation With Clinical Disease Plain film radiography has played a crucial role in the development of the current concepts of OA. The pathological features specified in the morphologic definition can be visualized radiographically; the clinical definition proposed by the ACR Clinical Criteria Committee requires the presence of osteophytes, which can be demonstrated on radiographs of the knee before they can be reliably detected on physical examination. However, radiographs are not sensitive to minor changes in OA, and therefore are not precise measures for short-term longitudinal studies. The natural history of OA and the correlation of its progression to radiographical findings is not well defined. Most cross-sectional surveys that have used radiographical assessments have detected an increasing prevalence of knee OA with age, though the magnitude of the increase depends upon the criteria used to define OA.‘9-23 The increasing prevalence of structural deterioration of knee articular cartilage with age is confirmed by autopsy studies.24*25 Osteophytosis, by itself, does not necessarily imply that the patient has progressive OA. Danielsson and Hernborg2’j found that only about 30% of patients with osteophytes on initial radiographs progressed to joint space narrowing at 14 to 18 year follow-up. Hernborg and Nilsson found that most patients with only osteophytes developed no other radiographically apparent structural changes in 10 years. However, in another study,28 7 1 patients with OA of the knee

QUANTITATIVE

29

IMAGING OF OA

Table 2: Advantages

and Disadvantages

of Different Imaging Modalities

Bone

Soft Tissue

Applicable

Detail

Detail

to Joints

Economy

Speed

+++

+/o

++++

++++

++++

++++

+

+++

+++

++

++

++

+++

it

++

Scintigraphy

t/0

0

Sonography

t

+++

+t t

tt +tt

t +

+++t

+

+

Plain radiograph Microfocal

radiograph

CT

MRI Abbreviations:

++ 0, least; ++++,

+tt+

most.

who were not treated by surgery were observed by Hernborg and Nilsson for 10 to 18 years. (In this study, OA was defined by subchondral sclerosis at the femoral-tibia1 joint combined with osteophytosis. Joint-space narrowing was not used because none of the initial radiographs were taken weight bearing.) Of 87 knees evaluated in their study, symptoms improved in 15, were unchanged in 23, and worsened in 49. Radiographical findings also progressed in the majority, but generally only in the knee joint compartment initially affected (usually the medial femoral-tibial joint). Thus, subchondral sclerosis and osteophytosis may prognosticate progressive OA. Although knee pain and radiographical findings correlate positively in population studies,‘9,23 individual patients with similar radiographical findings often exhibit a marked variation in the severity of their symptoms and disability. Gresham and Ratheyz9 compared symptoms and radiographical manifestations of OA. In a crosssectional study of 105 knees with at least minimal OA evident radiographically, 80 knees had crepitus and 77 knees had restriction of movement but only 47 knees were painful at the time of examination. Nevertheless, the frequency of each of these clinical findings was statistically significantly greater in this group of joints than in the radiographically unaffected knees. Massardo et a13’performed a prospective study of 3 1 patients, examined on two occasions 8 years apart, and found that symptoms and radiographs showed no correlation. The lack of correlation between the symptoms and radiographical signs of OA suggests that the processes causing structural abnormality are not identical to the ones giving rise to pain.

Preservation ofjoint function is a goal of treatment and is often evaluated in therapeutic trials. Joint function is complex and affected by many factors. Often a discordance between joint structure (as depicted on radiographs) and joint function exists; markedly deranged joints sometimes function surprisingly well, and, conversely, relatively mildly affected joints may function poorly. Summers et a13’ compared radiographical assessment and psychological variables as predictors of pain and functional impairment in OA. Disease severity, as estimated radiographically, accounted for little of the individual variability in clinical outcomes; psychological variables were stronger predictors of individual differences in functional impairment and pain. However, other factors being equal, one would expect that a structurally deranged joint would function less well than a structurally normal joint. IMAGING MODALITIES

A variety of imaging modalities have been used to assess OA. Those reviewed here are plain-film radiography, microfocal radiography, CT, scintigraphy, sonography, and MRI. No single technique is ideal for all purposes. Some of the advantages and disadvantages of each are listed in Table 2. Plain Roentgenograms As noted above, radiography is important in the diagnosis of OA as the features specified in the pathologic definition can be visualized, with joint-space narrowing generally thought to reflect cartilage 10~s.~However, there are limits to the information that can be provided by plain radiography. Plain radiographs of joints give ex-

30

cellent visualization of bony detail and excellent spatial resolution, but they generally provide poor definition of sot? tissues. Contrast, either with radiopaque material or with air (arthrography) helps delineate soft tissue structures, but this entails an invasive procedure. Three-dimensional information is not obtained, and the overlapping of structures can lead to difficulty in interpretation of the images. Furthermore, the features of OA that are visualized are strongly dependent on the views and the techniques used. As discussed above, it is debatable if osteophytosis alone is a satisfactory criterion for the radiographical diagnosis of osteoarthritis. Radiographs are not sensitive to minor changes, may not be accurate or precise measures of cartilage damage (assessed by loss of joint space-see below), and cannot portray most of the associated features in the soft tissues. Furthermore, they can not demonstrate a patient’s symptoms. Thus, it is possible that patients may have normal or nonspecific radiographs yet be affected by a symptomatic process that ultimately will evolve to radiographically evident OA. Pathological correlations. Kindynis et a13* compared routine and special projections, obtained prospectively in 50 consecutive patients with knee OA, and correlated findings with crosssections of pathological material. They found that the tunnel view was very useful in the evaluation of marginal and central osteophytes-sometimes the only osteophytes present-and in their differentiation from intraarticular loose bodies. Riddle et al33 compared the number of osteophytes and subchondral cysts seen using anteroposterior (AP) standing views versus enface views of tibia1 tables and their respective plateaus after resection from the knee joint. They found that the AP view was of limited value in demonstrating narrow osteophytes, those osteophytes located at extreme anterior or posterior positions on a plateau, or single cysts scattered across a plateau. Joint-space narrowing, as assessed radiographically, may not accurately reflect cartilage damage. Fife et al34 recently studied the correlation between cartilage damage seen at arthroscopy and joint-space narrowing seen by radiography in 16 1 patients. Articular cartilage appeared grossly normal at arthroscopy in 25 of the 76 patients with greater than 25% joint-space narrowing.

ADAMS

AND WALLACE

Nine of 22 patients with greater than 50% medial joint-space narrowing had normal medial compartment articular cartilage. Thirty-six of the 16 1 patients had “definite” joint-space narrowing radiographically, but had neither medial nor lateral compartment articular cartilage degeneration. Eight of these patients had patellofemoral degeneration, 18 had meniscal degeneration, and 8 had degeneration of both the patellofemoral compartment and the men&i. They thus concluded that joint-space narrowing is not a reliable indicator of articular cartilage loss. However, recent studies by Mattel et al35 found that small-focalspot radiography was superior to both MRI and ultrasound in reproducibility of measurements of articular cartilage thickness in the hip and knee. The debate continues. Grading scales and evaluations. Radiographical grading scales have been in use for many years in the study of OA and are essential to the performance of cross-sectional and longitudinal studies of the disease. The Kellgren-Lawrence scale, a global estimate of OA involvement, was developed in 1957 and has been considered a gold standard. However, there has been recent interest in validating and upgrading this scale and in developing methods of assessment of progression on serial radiography. To evaluate grading scales for the prevalence and progression of the individual radiographical features of hand OA, Kallman et al36assessed 11 hand joints individually for osteophytes, jointspace narrowing, subchondral cysts, subchondral sclerosis, lateral deformity, cortical collapse, and the Kellgren-Lawrence scale. Interreader agreement was good for each of the grading parameters except for cysts, and intrareader reliability was almost perfect. Altman et al37also developed methods of evaluating radiographical progression of OA of the hands, hips, and knees. The relative contribution of changes in individual joints or compartments, and of specific features such as joint-space narrowing or osteophytes, to disease progression was assessed. The reliability and concordance of scoring were evaluated for eight readers. The greatest sensitivity in detecting change was achieved using a posteroanterior (PA) radiograph of both hands assessed for narrowing, osteophytes, and erosions, and scoring 10 joints. For

QUANTITATIVE

IMAGING

31

OF OA

OA of the hip, the best results were obtained using a single AP radiograph assessed for joint-space narrowing and cyst formation. In the knee, assessment of an AP weight-bearing radiograph for joint-space narrowing, spurs, and subchondral sclerosis produced the greatest sensitivity. A radiographical scoring scale for evaluating posttraumatic OA after knee ligament injuries has also been developed.38 Image analysis. Dacre and Huskisson39 developed an automatic system for the measurement of joint space in the knee using computerized analysis of digitally stored images of PA knee radiographs. Automatic measurements were made using an edge-detection facility and two different edge-detection algorithms. Reproducibility, interobserver, and intraobserver relationships were good. However, reproducibility of patient positioning might present a problem in an automated system. Microfocal Radiography

Microfocal radiography produces magnified views with higher resolution of bony detail than plain radiographs and can give three-dimensional information if stereo views are taken. More accurate measurements may be obtainable from magnified films. Buckland-Wright et a140developed a high-definition microfocal x-ray unit allowing macroradiographical examination at 5X to 1OX magnification and with a high spatial resolution. This was used to assess quantitatively the rate of progression of hand 0A41 with 32 patients who had 5X macroradiographs taken of their wrists and hands at 6-month intervals over an 18-month period. Four different features were quantified: subchondral sclerosis, the number and size of osteophytes, juxtaarticular radiolucencies, and joint-space narrowing. Compared with normal subjects (who were also younger: x40 years v ~62 years), subchondral cortical thickness was greater in all patients at entry and showed a variable degree of change over the study period. Osteophytes and juxtaarticular radiolucencies were present in all patients at study entry; by the end of the study, osteophytes had increased in number and area, and juxtaarticular radiolucencies had increased in area but not in number. At entry, 44% of the patients had joint-space narrowing significantly greater than that in the normal sub-

jects; by 18 months, this proportion

increased to 65%. No correlation was found between subchondral sclerosis, osteophytes, juxtaarticular radiolucencies, and joint-space narrowing. These findings suggest that in OA of the hand, bony changes progress significantly before radiographic evidence of joint-space narrowing indicates cartilage thinning. Computed Tomography

CT creates thin-section planar images using multiple pinpoint x-ray beams (Fig 1). It has proven to be very useful, particularly in OA of the hip, in defining the three-dimensional relationships of bony structures, eg, femoral head migration in the coronal or transverse plane,42 and the correlation between patterns of hip OA and structural abnormalities such as femoral or acetabular anteversion, femoral neck-shaft angle, or acetabular inclination.43 For most joints, CT can only be obtained in the axial projection. Other planes can be reconstructed using computerized reformatting algorithms, but this technique requires multiple thin sections with a relatively high radiation dose, and the images have lower spatial resolution than direct CT images. CT can provide detailed qualitative assessment of the trabecular structure of bone, although intrinsically its spatial resolution is not as great as plain film radiography. Contrast resolution in soft tissue is greater with CT, however, and can be enhanced with the use of contrast materials including air. CT has also been very useful for quantifying bone density in osteoporosis. It has recently been used to assess trabecular and subchondral bone in experimental OA. Microscopic computed axial tomography was used by Layton et al4 to examine the trabecular architecture of subchondral bone of femoral heads in a guinea pig model of OA. They found that trabeculae were thicker and closer together, resulting in a highly significant increase in bone fraction (proportion of bone v marrow present in a given volume), suggesting that trabecular remodeling may be an early event in this model. This technique was also used to study the subchondral plate and trabecular bone in the canine experimental model of OA induced by transection of the anterior cruciate ligament.45 The subchondral plate was found to be slightly,

32

ADAMS

Fig 1:

AND WALLACE

Axial CT at mid-

patellar level. Note small spurs along the intercondylar notch and at the lateral patellofemoral joint.

but not statistically significant, thinner in the operated knee. The bone fraction in this knee was significantly decreased relative to the nonoperated side at 13 weeks, but not significantly different at 72 weeks. These changes were consistent with slight loss of bone due to decreased weight bearing in the operated limb. Nevertheless, subchondral sclerosis was seen on plain radiographs at 72 weeks. CT has also been used to study bone density in human OA in vivo. This is important because it has been suggested that increased bony trabecular density may predispose to OA, by decreasing bony compliance and thereby putting added stress on articular cartilage.46 Price et al used a quantitative CT method to assess density of trabecular and cortical bone in the radius in 40 women with generalized 0A.47 When age, weight, and height were considered, no significant differences were observed between patients and normal controls. But when only age was considered, trabecular bone density in the distal radius was 7% higher than predicted (P < .05). The authors believed that increased trabecular bone density was probably not an etiological factor in generalized OA, but rather that patients with osteoporosis may have a lower incidence of OA. Scintigraphy Conventional scintigraphy with bone-seeking agents such as technetium 99m methylene diphosphonate is usually abnormal in moderately advanced OA due to the remodeling changes in periarticular bone, and the pattern of bony change may be speciti~.~s However, some authors

have found that uptake is often normal in early or mild disease.48,49Perhaps refinements in scintigraphy, such as emission CT,” will improve its reliability. Its current usefulness in diagnosis and follow-up of OA is limited as it adds little or no information to clinical and radiographical assessment. Arthritis has been studied with several novel radionuclides and scanning techniques recently, including technetium 99m-labeled liposomes (which accumulate in inflamed synovium) and indium 111 chloride. These agents seem to be more promising for the study of rheumatoid arthritis (RA) than OA. In a study by O’Sullivan et al using technetium 99m-labeled liposomes,5’ clinically active erosive arthritis (rheumatoid or psoriatic) usually showed increased uptake. The majority of cases of OA studied showed no abnormal activity, but those with inflammatory changes showed some increased uptake, usually less intense than was seen in erosive conditions. Shmerling et aP2 performed iridium 111-chloride scans on 2 1 patients with RA and eight patients with severe OA. This agent has a high affinity for iron-binding proteins, behaving in a similar manner to gallium 67 (used to detect infection and some tumors); iron-binding proteins such as transferrin are found in increased concentration in inflamed synovium in RA. In the group with RA, significant correlations were observed between individual joint uptake on scan and peripheral joint pain, swelling, and abnormality on physical examination. In the group with OA, increased activity around joints correlated with the presence of pain, with 30% of painful joints

QUANTITATIVE

IMAGING

OF OA

showing increased uptake, compared with only 9% of asymptomatic joints. The authors believed this scanning technique might be valuable in assessing RA, but it remains to be seen whether or not it can be developed as a quantitative assessment of synovial involvement in OA. Other radionuclides may be useful in scanning cartilage. Yu et a153measured the biodistribution of [75Se]-bis-[/3-(N,N,N-trimethylamino)ethyl] selenide diiodide in adult guinea pigs. A higher concentration of radioactivity was observed in articular cartilage than in other tissues or organs, with minimal activity in blood, muscle, and bone. The compound was excreted rapidly in urine. Cartilage target-to-background ratios were high. Thus, this compound has potential as an agent for imaging articular cartilage and further studies in OA animals seem warranted. Sonography In 1984, Aisen and colleagues first showed that sonography could be used to evaluate the thickness of cartilage on the femoral condyles.54 Ultrasound examination is readily available, safe, inexpensive, and can give much information about the soft tissues and articular cartilage in accessible joints such as the shoulder and knee (Fig 2).55 However, portions of all joints are inaccessible to ultrasound as bone “blocks” the ultrasound beam, and good assessment of femoral condylar surfaces is only possible if the knee can be hyperflexed. Nevertheless this area merits further study. Mattel et al35 have presented preliminary results suggesting the possibility of defining not only artitular cartilage thickness, but also surface integrity. They believe that, in accessible areas of the knee, ultrasound is superior to MRI for measurement of articular cartilage thickness.35 Furthermore, signals from subchondral bone appear to be qualitatively different from normal in OA joints, having a “snowflake pattern”, and these signals may be analyzed and quantified. Magnetic Resonance Imaging MRI has aroused a great deal of interest because it combines the advantages of other imaging modalities without sharing many of their disadvantages. Like CT, it offers cross-sectional tomography. The degree of spatial resolution de-

33

pends on several factors, including magnetic field strength and signal-receiving coil design, but currently it is not as high as with radiography or CT. However, MRI shows definite superiority in contrast resolution, and thus has potential to detect previously undetectable lesions. Like ultrasound, MRI does not involve ionizing radiation, using only radiofrequency waves and a magnetic field, and is not associated with known biohazards other than those associated with ferromagnetic materials. It offers far more soft tissue information than radiography (Fig 3A). Signal intensity in MRI depends on several tissue characteristics, allowing great flexibility in manipulation of tissue contrast. Most current MRI depends upon the hydrogen nucleus. Besides offering data about hydrogen density, MRI also provides information about the chemical and physical environment in which the hydrogen protons reside through the T, and Tz relaxation times. These times are somewhat tissue-specific and determine the intensity of the radio signal that will be emitted from a given area. With appropriate techniques, images can be generated that emphasize one or the other of these parameters. Because relaxation times vary widely between tissues and change with disease states, MRI gives a remarkably high degree of soft tissue contrast resolution. At present, no single imaging sequence is best for all conditions and all tissues. Furthermore, there may be differences between various instruments based on the types of pulse sequences, reconstruction algorithms or other features specific to the manufacturer. MRI offers great promise as a noninvasive technique for visualization of early changes in the soft tissues in OA, for definition of the natural history, and for evaluation of effects of treatment on all joint structures including cartilage. Early studies have demonstrated the ability of MRI to visualize and differentiate ligaments, menisci, cortical bone, marrow, and muscle. Pathological changes can be seen in these structures that previously could not be defined non-invasively56-60 (Fig 3B). Articular cartilage is essential for normal joint function and it is desirable to visualize it clearly. Adams et aL6’ using a prospective double-blind clinical trial and concordance analysis, compared the evaluation of the depth of articular

ADAMS

Fig 2:

AND WALLACE

Ultrasound of the femoral artic-

ular cartilage (M, muscle; F, fatty tissue; A, articular cartilage; 6, subchondral bone). (A) Transverse image through the intercondylar notch (N). (B) Normal medial femoral condyle. (C) Medial femoral condyle with slight subchondral bony irregularity and a small marginal osteophyte.

QUANTITATIVE

IMAGING

35

OF OA

Fig 3:

MRI

ofthe

knee. These images were obtained

with a GE Signa 1.5 T Scanner, Software

Release

4.5. (A) Normal midsagittal T,-weighted image. Gradient echo sequence with a “spoiler” RF pulse (SPGR); TR = 40 ms, TE = 15 ms, Flip angle (0) = 1 O”, slice thickness between

= 3.0 mm. Note the differentiation

the articular cartilage,

the meniscus and

the synovial fluid. (B) Sagittal T2-weighted the same imaging parameters

gradient

as in a. Note the in-

creased signal in the posterior horn of the medial meniscus (M) and loss of the overlying articular cartilage (arrow). (C) Coronal T,-weighted

gradient echo im-

age. SPGR sequence; TR = 35 me, TE = 5 ms, 0 = 35”. slice thickness = 3.0 mm. Note the punchedout defect in the medial femoral condylar articular cartilage (arrow) and decreased signal in the adjacent bone due to subchondral sclerosis.

cartilage lesions noted at arthroscopy with that seen with MRI. The results demonstrated a moderate concordance between images obtained with the inversion-recovery pulse sequence and arthroscopy. It is noteworthy that these results

were obtained despite the low field strength (0.15 Tesla) of the MRI unit used. In an attempt to offset the intrinsically low spatial resolution of the low-field MRI device, they used a specially designed surface coil and multiple signal aver-

36

ages to obtain better images. Nevertheless, they believed that some small but deep (“punched out”) lesions of the cartilage likely were missed. With higher field strengths, it is possible to obtain multiple thinner images, as low as 1 mm or less in thickness, improving spatial resolution and decreasing partial volume averaging effects. Improvements in receiver coil design, pulse sequences, reconstruction algorithms, and hardware have decreased imaging time and further improved resolution. Robinson et a16* showed that an extremely high degree of structural detail could be observed in pig joints with field strengths of 4.7 T, several times greater than the maximum allowable in clinical imaging. The articular cartilage was easily visible and could be accurately measured. Even at 1.5 T, the highest field used clinically, several workers have demonstrated good cartilage visualization. It is necessary to define which imaging sequences are best for depicting articular cartilage. Lehner et al63 showed that the MR signal from articular cartilage is complex, and that one pulse sequence likely will not suffice for all purposes and all field strengths, in keeping with clinical observations.64 Several studies have used Tzweighted spin-echo sequences to visualize cartilage.65”7In general these results suggest that these pulse sequences may not visualize cartilage as well in some instruments as T,-weighted inversion recovery sequences. Some of the newer gradient imaging sequences, possible at higher field strengths, show great promise6’-” (Fig 3C). Several studies of the knee have compared MR images with cartilage pathology.66@,69 Mink and Deutsch’l demonstrated and classified the MR appearance of a variety of different pathological lesions in articular structures. Harms et a169 showed the potential of some of the newer pulse sequences and three-dimensional acquisition sequences to demonstrate pathology in a qualitative way. However, they gave little detail of their assessment criteria for cartilage lesions (presumably they used “lesion present or absent,” with no further grading). Tyrrel et al” performed an excellent preliminary study in which they analyzed knee MRI results and compared them retrospectively with the findings at arthroscopy. As acknowledged, awareness of the results of arthroscopy might have biased their results; however,

ADAMS

AND WALLACE

they emphasized that such retrospective studies must be performed first to improve image interpretation skills and to select ideal imaging protocols. Karvonen et al’* measured the thickness of articular cartilage on MR images of recently amputated knees, and compared this with sub sequent physical measurements of articular cartilage. They studied eight specimens, concentrating on selected areas of the femoral condyles and tibial plateaus to avoid partial volume averaging effects. They found that the MRI and gross anatomical measurements of cartilage thickness agreed well, with no statistically significant differences between them. In a comparative study, Li et al73 showed that MR correlated not only with radiographs, but also with clinical symptoms, at least in hip OA. The sensitivity and specificity of MRI of osteoarthritis is not defined at present and further studies are needed. It seems likely that improvements will continue to be demonstrated with newer apparatus and pulse sequences. Threedimensional image acquisition, and perhaps three-dimensional image reconstruction in nonorthogonal planes, may further improve the visualization of the pathological processes involved in OA. Two recent studies have used MRI to follow the progression of experimental osteoarthritis. In the first,74 MRI was used to assess the thickness of the hypertrophic cartilage that develops after anterior cruciate ligament transection in the dog knee.75,76Brandt et al” used MRI in longer-term follow-up studies of this experimental model of OA. They observed three animals for 45 months with conventional radiographs, gait analyses, and MRI. MRI showed that cartilage was thicker than normal up to 36 months after operation, in keeping with previous observations of cartilage hypertrophy in this model. However, by 45 months MRI showed striking loss of articular cartilage on the medial condyles of each dog. In two of the dogs, gross inspection showed complete loss of the articular cartilage from the weight-bearing surface.

Three-Dimensional Reconstruction and Image Analysis Three-dimensional reconstruction of CT images is proving to be useful in preoperative eval-

QUANTITATIVE

37

IMAGING OF OA

uation.‘* This technique, by measuring volumes rather than linear dimensions, might allow better assessment of the extent of osteophytosis in OA. If combined with MRI, the degree of cartilage loss in OA and the amount of synovial involvement might be evaluated more accurately. Paul et al79 used volume acquisition, three-dimensional reconstruction, and computerized identification of the tibia-femoral cartilage to assess the volume of cartilage in normal volunteers. The technique was reproducible, and might be useful in longitudinal studies. CONCLUSION

Improvements in quantitative imaging of OA is necessary to improve detection and definition

of osteoarthritis and to evaluate better the etfectiveness of pharmacological and physical therapy in practice and in clinical trials. Studies of MRI and ultrasound to date suggest that these methods will allow accurate noninvasive definition of the structure of articular cartilage and other soft tissues of joints. Microfocal radiography and highresolution CT can produce detailed images of trabecular structure and bony alterations in OA. Improvements in image analysis and data manipulation, including three-dimensional reconstruction and digitized storage and measurement of images, will likely enable improved quantitative assessment of the abnormalities demonstrated by these techniques.

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