Imaging Osteoarthritis
James (J.D.) Johnston, PhD, PEng
Assistant Professor
Department of Mechanical Engineering
University of Saskatchewan
Saskatoon, SK
Osteoarthritis (OA) is a painful, debilitating disease characterized by degenerated cartilage and altered subchondral bone. The exact etiology of OA is unknown. Currently, most of our understanding of cartilage and subchondral bone changes with OA are from animal models, which may not be applicable to humans, and cadaveric studies, where longitudinal assessments are not possible and changes cannot be related to clinical symptoms. Medical imaging offers unique potential for examining and tracking OA pathogenesis in vivo.
This article is focused on three medical imaging technologies currently used to study OA: conventional X-ray; magnetic resonance imaging (MRI); and computed tomography (CT). For each imaging technology, this article will identify OA-relevant metrics, associated strengths/limitations, and potential in the assessment of OA pathogenesis and progression.
Figure 1: (a) Positioning of the patient for x-ray, which involves usage of a fixed 10o caudal x-ray beam. (b) Example of good alignment whereby the anterior and posterior margins at the center of the plateau (arrow) are aligned. (c) Example of poor alignment where there is wide separation of the anterior and posterior margins. Reproduced with permission from Hunter et al20 and Le Graverand et al21.
Conventional X-ray can detect bony characteristics of OA, including osteophytes, sclerosis and subchondral cysts. It can also be used to measure, indirectly, cartilage thickness via joint space width (JSW): the measured distance between two articulating bones, and joint space narrowing (JSN): a report change in JSW. X-ray is typically used in conjunction with semi-quantitative scoring methods to classify OA severity. The commonly used Kellgren-Lawrence scoring system1 grades OA severity through qualitative, subjective assessments of JSN, osteophyte presence, and subchondral sclerosis. Strengths of X-ray include low cost, simplicity of use, and wide availability. However, the tool represents a 3-dimensional (3D) structure as a 2D projection image and JSW and JSN results are therefore sensitive to patient positioning (Figure 1), patients are exposed to ionizing radiation, and the tool cannot be used to directly image cartilage or other soft tissues potentially involved in OA pathogenesis (e.g., meniscal tear).
Figure 2: Anterior (inferior and lateral) view of 3D representation of tibial knee cartilage and meniscus from MRI data. Medial and lateral tibial cartilage displayed by varying greyscale intensities for illustrating cartilage thickness. Meniscus displayed between tibial cartilage and distal femur. Reproduced with permission from Eckstein et al22.
MRI offers multi-planar 3D images, nonionizing radiation, and the ability to simultaneously image various joint structures affected by OA, including cartilage, menisci, ligaments, synovium, and fluid collections (e.g., bone marrow lesions or BMLs). In addition, MRI can be used for indirect assessment of trabecular bone by imaging high intensity fluid surrounding trabecular bone. Semi-quantitative scoring methods such as WORMS2, BLOKS3, and recent MOAKS4 are often used to score OA severity. Beyond qualitative scoring, MRI combined with image processing methods can be used to quantify cartilage morphology. The quantitative MRI (qMRI) technique involves segmenting (outlining) cartilage regions to obtain a 3D object which, via custom algorithms, can be used to obtain local cartilage thickness, volume, and surface area (Figure 2)5. qMRI is primarily intended for tracking OA progression, but has recently been used for indirect measurement of cartilage stiffness via assessments of cartilage thickness under unloaded and loaded conditions6. MRI can also be used to image cartilage composition through usage of contrast agents or via measures of T2 or T1rho. MRI-based compositional measures have shown strong associations with cartilage stiffness7. Recent MRI studies show that acute loading8 and moderate/strenuous physical activity9 have negative effects on cartilage composition. Limitations of MRI include limited access, long imaging times (~20 minutes or longer for a series of scans), and possible image distortion and geometrical inaccuracy with suboptimal coils. MRI is also unable to account for the mineralization and porosity of subchondral cortical bone and trabecular bone near the subchondral surface which have minimal fluid presence.
Figure 3: (a) Representative image of proximal tibial subchondral bone mineral density from an individual with lateral OA. Density is measured in relation to depth from the subchondral bone surface. Varying greyscale intensities illustrate subchondral density. White circle indicates a local region of high density. (b) Representative image of density distributions in the proximal femur. Varying greyscale intensities illustrate subchondral density. Reproduced with permission from Johnston et al23 and Wright et al15.
CT, like X-ray, can detect bony characteristics of OA (osteophytes, sclerosis, subchondral cysts). CT in combination with a calibration phantom (known as quantitative CT or QCT) can also be used to quantify bone mineral density (BMD) (i.e., amount of bone per unit volume). QCT is particularly useful for studying OA as various studies have shown direct relationships between bone density and the presence or severity of knee OA10-12. In recent years QCT combined with custom image processing has been increasingly used for OA research. In particular, depth-specific imaging techniques which measure BMD in relation to depth from the subchondral bone surface have been used at the proximal tibia13,14, proximal femur15, acetabulum16,17 and distal tibia18 (Figure 3). Ex vivo comparisons between OA and normal proximal tibiae have shown promising results with higher regional density (17-36%) in OA knees14. The benefits of CT include wide availability, rapid scan times (seconds for hundreds of axial QCT images), simplicity of use, and 3D images with high bone contrast and small voxel sizes (0.5-0.625 mm). Concerns regarding ionizing radiation dosage with CT are minimal due to the low presence of radiosensitive tissues at the knee joint, with effective dosages for a complete knee scan comparable to 1.5x dosage from a transatlantic flight from Europe to North America13,19. CT though, like X-ray, is unable to directly image soft joint tissues such as cartilage and the tool is less ideal for studying hip OA due to the presence of radiosensitive tissues.
There is presently no cure for OA, and the exact etiology is unknown. Acquired information offered by medical imaging technologies, especially from early stages of OA, could shed light on how OA disease initiates and develops. This information could lead to early OA detection and assist with monitoring treatments (e.g., drug therapy, bracings) aimed at preventing or delaying OA onset and progression.
References