Osteoarthritis (OA) is a degenerative whole joint disease. Simultaneous PET-MR imaging provides a unique opportunity to study bone-cartilage interactions in joint degeneration, and provides a key to the pathophysiology of OA.
Osteoarthritis (OA) is a multifactorial disease that causes joint degeneration, affects 27 million U.S. adults [1, 2], with symptoms such as stiffness, limited joint function and pain which lead to severe disability and impact the overall quality of life. OA primarily affects weight-bearing joints such as the knee and hip joints, and joint pain is one of the most important outcome measures in OA. Pain is often measured using questionnaires and patient reported outcomes (PROMs), such as the Knee Outcomes in Osteoarthritis Scores (KOOS) [3], Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [4]for the knee joint and Hip Outcomes in Osteoarthritis Scores (HOOS)[5]for the hip joint.
In addition to knee OA, degenerative disorders of the hip are also highly prevalent; one in four people have a lifetime risk of developing symptomatichip osteoarthritis by the age of 85 [6]and individuals with this disease experience substantial pain and disability [7]. Well known as a risk factor for hip OA, femoroacetabular impingement (FAI) is a morphological abnormality of the hip joint, which causes abnormal joint loading patterns and may cause acetabular cartilage delamination [8]. Increased shear forces within the hip joint, particularly due to the cam-type impingement, may cause enlargement of the cartilage flap and lead to complete detachment from the adjacent cartilage thereby producing loose bodies and full-cartilage thickness defects [9]. Late stage, symptomatic knee or hip OA is treated by total or partial joint replacement, and while this surgically invasive remedy offers relief, joint replacements often fail after 10-15 years, with shorter life spans in obese individuals [10]. Cartilage loss, meniscus changes, subchondral bone changes, ligament, bone marrow changes and changes in other joint tissues are all implicated in OA. The alarming burden of OA that affects subjects at different age and activity levels calls for the development of quantitative biomarkers for joint degenerative disease to fill the void that exists for early diagnosis, monitoring and assessing the extent of whole joint degeneration.
Bone cartilage crosstalk is considered as one of the key factors in understanding OA pathogenesis[11]. A hypothetical model for OA pathogenesis has been proposed by Burr et. al. [12], whereby repetitive joint loading causes an initial increase in bone remodeling, that is associated with increased vascular invasion of the deep layers of cartilage, which allows access to the cartilage by chondrolytic enzymes unopposed by inhibitors of the degradative proteinases, that cause a breakdown of the extra-cellular matrix, loss of proteoglycan and collagen, and thus a loss of cartilage compressive stiffness, and an overload of the joint. Subchondral bone changes are present prior and during development of OA and increased bone blood flow and bone remodeling as demonstrated by 18F Sodium Fluoride (NaF) positron emission tomography (PET)-computed tomography (CT) [13]may be associated with patellofemoral pain and later stage morphological changes in cartilage.
This course provides an overview of recent PET-MR methods for studying bone-cartilage interactions in OA.
Simultaneous PET-MRI was also recently used to study cartilage and bone interactions in the knee [14][15-18]. Recent efforts to study the distribution of [18F]-Sodium Fluoride (NaF) uptake and blood flow in the femur and acetabulum in hip osteoarthritis (OA) patients and study associations between bone remodeling and cartilage composition in the presence of morphological abnormalities using PET/MR have also been presented.
In hip OA subjects, [18F]-NaF PET/MR dynamic scans of the hip were acquired while acquiring three-dimensional (1) fast spin-echo CUBE for morphology grading (2) T1ρ/T2 Magnetization-Prepared Angle-Modulated Partitioned k-Space Spoiled Gradient Echo Snapshots (MAPSS) for cartilage, bone segmentation, bone shape modeling, T1ρ/T2 quantification. Patlak kinetic parameters and SUV values were calculated for each patient, using a fully automated post-processing pipeline. Shape modeling was performed to extract the variations in bone shapes in the patients.
Savic et. al. [18]performed a pilot study analyzing sixteen OA subjects and showed increased uptake of NaF in the knee in OA subjects. Similar results were obtained by Kogan at el, by analyzing 22 subjects with knee pain or injury. Both studies showed increase in SUV in proximity of morphological abnormalities as bone marrow edema. Significant relationships between dynamic quantitative PET measurements as slope Kiand semi-quantitative SUVavgand SUVmax (R2 = 0.7) in all bone compartments, thus supporting the use of both metrics to characterize bone remodeling and blood flow were also showed in [18]. This study also explored correlations between voxel based relaxation time T1ρ and T2 in the cartilage with sodium fluoride uptake metrics (slope Kiand SUV), showing correlations not only not only in adjacent regions but also in compartments that are not adjoining. Correlations between SUV and cartilage compositional data were also recently shown in ACL subjects [16].
Direct associations between quantitative MR and PET evidence of bone remodeling were established in the acetabulum and femur in hip OA. Associations of shaft thickness with SUV in the femur (P=0.07) and Kpatin the acetabulum (P=0.02), cam deformity with acetabular score (P=0.09), osteophytic growth on the femur head with Kpat (P=0.01). Pain had increased correlations with SUV in the acetabulum and femur (when shaft thickness was accounted for.
1. Neogi, T., The epidemiology and impact of pain in osteoarthritis.Osteoarthritis Cartilage, 2013. 21(9): p. 1145-53.
2. Lawrence, R.C., et al., Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.Arthritis Rheum, 2008. 58(1): p. 26-35.
3. Roos, E.M., et al., Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure.J Orthop Sports Phys Ther, 1998. 28(2): p. 88-96.
4. Ackerman, I., Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).Aust J Physiother, 2009. 55(3): p. 213.
5. Rannou, F., et al., Should aggregate scores of the Medical Outcomes Study 36-item Short Form Health Survey be used to assess quality of life in knee and hip osteoarthritis? A national survey in primary care.Osteoarthritis Cartilage, 2007. 15(9): p. 1013-8.
6. Murphy, L.B., et al., One in four people may develop symptomatic hip osteoarthritis in his or her lifetime.Osteoarthritis and Cartilage, 2010. 18(11): p. 1372-1379.
7. Salaffi, F., et al., Health-related quality of life in older adults with symptomatic hip and knee osteoarthritis: a comparison with matched healthy controls.Aging Clin Exp Res, 2005. 17(4): p. 255-63.
8. Anderson, L.A., et al., Acetabular cartilage delamination in femoroacetabular impingement. Risk factors and magnetic resonance imaging diagnosis.J Bone Joint Surg Am, 2009. 91(2): p. 305-13.
9. Beaule, P.E. and E.J. Zaragoza, Surgical images: musculoskeletal acetabular cartilage delamination demonstrated by magnetic resonance arthrography: inverted "Oreo" cookie sign.Can J Surg, 2003. 46(6): p. 463-4.
10. Bulstrode, C.J.K. and C. Swales, The musculoskeletal system at a glance. 2007: Wiley-Blackwell.
11. Findlay, D.M. and J.S. Kuliwaba, Bone-cartilage crosstalk: a conversation for understanding osteoarthritis.Bone Res, 2016.4: p. 16028.
12. Burr, D.B. and M.A. Gallant, Bone remodelling in osteoarthritis.Nat Rev Rheumatol, 2012. 8(11): p. 665-73.
13. Draper, C.E., et al., Comparison of MRI and (1)(8)F-NaF PET/CT in patients with patellofemoral pain.J Magn Reson Imaging, 2012. 36(4): p. 928-32.
14. Kogan, F., et al., PET/MRI of metabolic activity in osteoarthritis: A feasibility study.J Magn Reson Imaging, 2017. 45(6): p. 1736-1745.
15. Kogan, F., et al., Applications of PET-MRI in musculoskeletal disease.J Magn Reson Imaging, 2018. 48(1): p. 27-47.
16. Kogan, F., et al., Quantitative imaging of bone-cartilage interactions in ACL-injured patients with PET-MRI.Osteoarthritis Cartilage, 2018. 26(6): p. 790-796.
17. Kogan, F., A.P. Fan, and G.E. Gold, Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease.Quant Imaging Med Surg, 2016. 6(6): p. 756-771.
18. Savic, D., et al., Imaging Bone-Cartilage Interactions in Osteoarthritis Using [(18)F]-NaF PET-MRI.Mol Imaging, 2016. 15: p. 1-12.