Osteoarthritis is a prevalent and disabling disease affecting an increasingly large swathe of the world population. While clinical osteoarthritis is a late-stage condition for which disease-modifying opportunities are limited, osteoarthritis typically develops over decades, offering a long window of time to potentially alter its course. The etiology of osteoarthritis is multifactorial, showing strong associations with highly modifiable risk factors of mechanical overload, obesity and joint injury. As such, characterization of pre-osteoarthritic disease states will be critical to support a paradigm shift from palliation of late disease towards prevention, through early diagnosis and early treatment of joint injury and degeneration to reduce osteoarthritis risk.
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Characterized by degenerative changes in the bones, cartilage, menisci, ligaments, and synovial tissue, osteoarthritis OA has evolved to be considered a disease of the whole joint. Using imaging, OA has traditionally been diagnosed with radiographs that demonstrate joint space width JSW and osteophytes.
Recently, additional modalities such as magnetic resonance imaging MRI , ultrasound US , and optical coherence tomography OCT , have enhanced OA diagnosis and management through improvements in soft tissue depiction. Early identification of OA is crucial to improving clinical decision-making and advancing the understanding of disease progression and treatment options.
This article will review the various modalities available for OA imaging and assessment, focusing on their utility as tissue-specific diagnostic tools for OA of the knee. Despite the development of newer imaging techniques, the radiograph remains the most accessible tool in the evaluation of the OA joint. The knee joint is typically evaluated using the extended-knee radiograph, which is a bilateral anteroposterior image acquired while the patient is weight-bearing, with both knees in full extension.
More recently, flexed-knee radiographs with varying degrees of flexion and x-ray beam angles have been employed to improve intra-articular visualization. Radiographs are used to evaluate osteophyte formation and joint space narrowing JSN ; grading schemes such as the Kellgren-Lawrence grading scheme [ 1 ] and the Osteoarthritis Research Society International classification score establish guidelines for the diagnosis of OA progression [ 2 ].
MRI manipulates image contrast to highlight different tissue types. Common contrast methods include 2D or multi-slice T 1 -weighted, proton density PD , and T 2 -weighted imaging [ 3 ].
Recent improvements in hardware, software, gradients, and radiofrequency RF coils have led to the use of fast or turbo-spin echo imaging, fat saturation and water excitation [ 3 ] to improve tissue contrast. Several semiquantitative, morphologic MRI scoring systems have been developed for evaluation of the knee joint in OA.
Modified forms of the Outerbridge scale are routinely used for assessment of cartilage lesions, specifically with regard to defect depth. Whole-organ assessment, however, has proven increasingly useful, as it allows thorough evaluation of articular features. Furthermore, whole organ assessment has shown reliability, specificity, and sensitivity and an ability to identify lesion progression [ 4 — 7 ].
Optical coherence tomography OCT captures cross-sectional echographs of infrared light and acquires near-real time images of articular cartilage [ 8 ]. This method requires placement of the endoscope immediately on the cartilage, so is done at the time of arthroscopy.
OCT is incorporated into arthroscopes and generates cross-sectional images of articular cartilage at resolutions comparable to low-power histology [ 9 — 11 ].
Consequently, OCT can provide quantitative information about the disease state of articular cartilage [ 12 ]. OCT has been shown to be sensitive to collagen structural changes resulting from acute trauma and degeneration [ 9 , 13 , 14 ] and OA-associated changes in cartilage birefringence [ 13 ].
Current US technology offers many advantages, including multiplanar image acquisition, the ability to image dynamic structures in real-time, lack of ionizing radiation [ 15 ], and utility in interventional procedures [ 16 , 17 ]. Furthermore, US is cost-effective and can be used without contrast enhancement CE to visualize various tissues involved in OA [ 18 ].
Bony changes in OA have traditionally been assessed using radiographs. In the early stages of disease onset, developments such as osteophytes, subchondral sclerosis, or subchondral cysts are well visualized with this modality. As OA progresses, radiography is used to assess JSW, which provides an indirect measure of the integrity of both hyaline and fibrocartilage.
OA severity is often classified by subsequent JSN and the simultaneous appearance of subchondral bone abnormalities such as cysts or sclerosis [ 1 , 19 , 20 ]. Since the s, the standard view for radiographic assessment of the tibiofemoral joint has been the extended-knee radiograph, which is a bilateral anteroposterior image acquired while the patient is weight-bearing, with both knees in full extension [ 21 ] Figure 1. More recently, alternative imaging protocols have proposed imaging of the flexed knee to address the shortcomings of the extended-knee radiograph, which is suboptimal for longitudinal joint assessment [ 22 ].
These protocols utilize different degrees of knee flexion, x-ray beam angles, and positioning strategies, but all create a contact point between the tibia and posterior aspect of the femoral condyle for improved visualization of the joint space [ 23 — 26 ]. A Antero-posterior weight bearing radiographs of a patient with joint space narrowing and osteophyte formation consistent with bilateral medial osteoarthritis of the knee. Joint pace narrowing is greater in the right knee arrow compare with the left knee.
B A magnified view of the right knee joint. The arrow denotes medial JSN. Osteophyte formation can be seen on the femur and tibia. JSW and subsequent JSN were originally assessed using manual techniques that required minimal additional equipment or processing software [ 27 , 28 ]. However, these methods were time consuming and subjective and have since been largely abandoned in favor of automated assessment, which provides quick and precise measurements of JSW.
In addition to improving reproducibility of semi-quantitative scoring or manual measurements, automated assessment has also sparked additional characterizations of joint space, including minimum JSW, mean JSW, joint space area, and location-specific JSW [ 29 ]. Several studies have shown minimum JSW to be most reproducible and most sensitive to OA-related changes [ 30 , 31 ]. Currently, the Kellgren-Lawrence KL grading scheme is the most-widely used and accepted standard for diagnosis of radiographic OA [ 1 , 32 ].
Radiographic OA receives a KL grade of 2, denoting the presence of definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph [ 1 ] Figure 1. Further disease progression is graded as KL 3, characterized by multiple osteophytes, definite JSN, sclerosis, possible bony deformity and KL grade 4, which is defined by large osteophytes, marked JSN, severe sclerosis and definitely bony deformity [ 1 ].
The KL grading scheme has been criticized for characterizing the progression of OA as a linear process and combining osteophyte and JSN measurements [ 29 ]. More recently, the Osteoarthritis Research Society International atlas has developed OA classification scores that evaluate tibiofemoral JSN and osteophytes separately in each compartment [ 2 , 33 ]. While radiography is useful for evaluation of JSW, a study by Amin et al.
Consequently, MRI is regarded as an important modality for bone imaging because it can provide contrast that improves the assessment of subchondral bone integrity and lesions. Changes in subchondral bone composition are important to note in the progression of OA and well-visualized using MRI.
In particular, bone marrow edema-like lesions BMLs , subchondral cyst-like lesions, and subchondral bone attrition are notable features indicating disease progression. BMLs are degenerative lesions consisting of edema, bone marrow necrosis, fibrosis, and trabecular abnormalities [ 35 , 36 ]. They are often detected in conjunction with neighboring cartilage damage [ 37 , 38 ] and several recent studies have demonstrated a correlation between BMLs and progressive cartilage damage [ 39 — 41 ] Figure 2.
They are best visualized on MRI using PD-weighted, intermediate-weighted, T2-weighted, or short tau inversion recovery and appear as hypointense regions on T1-weight SE images [ 36 , 42 — 44 ].
Bone marrow edema and bone marrow lesions depicted on the medial femur on a T2-weighted fat suppressed MRI A and medial tibial plateau on an intermediate-weighted fat suppressed MRI B. The exact origin of subchondral cyst-like lesions remains to be elucidated, but it is currently thought that they result either from synovial fluid intrusion as a consequence of elevated intra-articular pressure [ 45 , 46 ] or from traumatic bone necrosis following impact of articular surfaces [ 47 , 48 ].
Subchondral cyst-like lesions appear as areas of well-defined fluid-like signal intensity on non-enhanced imaging sequences. Subchondral bone attrition is frequently observed in patients with advanced OA but has also been viewed in patients with mild OA who do not exhibit JSN on standard radiographs [ 51 ]. It may be caused by altered mechanical loading resulting in subchondral remodeling and is associated with concomitant BMLs [ 52 ]. On MRI, subchondral bone attrition appears as depression or flattening of the subchondral surface.
Changes in subchondral bone are seen on MRI long before changes are seen on radiographs. Multiple imaging modalities are used to study articular cartilage, as its degeneration is often regarded as the structural hallmark of OA progression.
Conventional radiography provides an indirect measure of articular cartilage through evaluation of JSW but is unable to detect early chondral damage. Arthrography combined with either x-ray or computed tomography CT is used to assess cartilage surface contour [ 53 ], but does not provide soft tissue information. Many recent studies including the Osteoarthritis Initiative OAI utilize MRI for cartilage examination, as it provides exquisite contrast and enables both morphologic and physiologic imaging techniques.
Morphological assessment of cartilage provides information about tissue size and structural integrity. Many techniques enable imaging of fissuring and focal or diffuse cartilage loss. Three-dimension spoiled gradient recalled echo imaging with fat suppression 3D-SPGR is the current standard for morphological imaging of cartilage [ 54 , 55 ]. SPGR acquires nearly isotropic voxels, producing excellent resolution images with high cartilage signal and low signal from adjacent joint fluid.
DEFT returns magnetization to the z-axis with a degree pulse that results in enhanced signal in tissues with long T1 relaxation times. In cartilage imaging, DEFT heightens synovial fluid signal and preserves cartilage signal, resulting in bright synovial fluid at a short TR, high cartilage SNR, and improved imaging of full cartilage thickness [ 56 ].
Similarly, three dimensional dual-echo steady-state DESS imaging results in high signal intensity in both cartilage and synovial fluid, which enables morphological assessment of cartilage. This is the sequence of choice for the Osteoarthritis Initiative [ 59 ].
Diffusion-weighted imaging in patellar cartilage in vivo using a DESS technique. Figure 3A uses low diffusion-weighting. Figure 3B uses high diffusion-weighting. Both imaging techniques afford high resolution, high signal-to-noise ratios, and the ability to calculate apparent diffusion coefficients.
Cartilage solid arrow and joint fluid dashed arrow are well seen on both images. Images courtesy of Ernesto Staroswiecki. Another group of methods hallmarked by excellent synovial fluid-cartilage contrast is steady-state free precession SSFP MRI techniques. In all of these techniques, fluid is depicted with increased signal, while cartilage signal intensity is preserved, resulting in excellent contrast and diagnostic utility.
Several derivatives of SSFP exist. The advantages of VIPR are substantial; banding artifacts are reduced, high SNR is obtained, high contrast between tissues is achieved, and short acquisition times are possible [ 61 ]. More recently, MR technology has evolved to provide quantitative information about the physiological content of articular cartilage. These developments have been useful in identifying early damage and breakdown.
In OA, proteoglycan and collagen content are reduced [ 65 ]. This disrupts the collagen network and results in increased water content and matrix degradation. Newer methods of MRI exploit these macromolecule changes to provide a quantitative understanding of the breakdown process.
In cartilage, changes in transverse relaxation times T 2 are dependent upon the quantity of water and the integrity of the proteoglycan-collagen matrix.
By measuring the spatial distribution of T 2 relaxation times throughout articular cartilage, areas of increased or decreased water content which generally correlate with cartilage damage can be identified. Generally, a multi-echo spin-echo is used to shorten scan time and signal levels are fitted to one or more decaying exponentials, depending upon whether more than one T 2 distribution is anticipated in the tissue [ 66 ].
T 2 mapping software is currently commercially available, allowing for simple implementation on most imaging systems Figure 4. T2 mapping of articular cartilage in the medial femur of a patient with osteoarthritis at two time points.
Mapping software allows visualization of the spatial distribution; notice the increased T2 relaxation times in Figure 4B. The T2 relaxation time is overlaid on the images using a color map, with the scale in milliseconds. T1rho mapping is sensitive to the macromolecule content of tissue and therefore very effective in visualizing early changes in OA [ 67 , 68 ]. When proteoglycan depletion occurs in the earliest phases of OA, the physio-chemical interactions in the macromolecule environment are disrupted and T1rho allows measurement of the interaction between motion-restricted water molecules and their extracellular environment [ 69 ].
Elevated T1rho relaxation times have been measured in osteoarthritic knee cartilage when compared with normal cartilage [ 70 — 72 ] Figure 5. T1rho mapping is a physiologic MRI method that has been shown to be sensitive to proteoglycan PG changes in articular cartilage. In osteoarthritis, decreases in PG content correspond with increases in T1rho relaxation times. Early degeneration of articular cartilage is seen by the increased relaxation time in B.
Images courtesy of Li X et al.
Early diagnosis to enable early treatment of pre-osteoarthritis
Diagnosis of Osteoarthritis: Imaging