Imaging of tissue degeneration in knee osteoarthritis using magnetic resonance and synchrotron radiation

Abstract: Osteoarthritis (OA) is a very common disease, especially in the knee. It is characterized by the breakdown of articular cartilage but involves all parts of the joint. OA is usually diagnosed at a late stage when the articular cartilage has begun to disappear. What happens before these macroscopic alterations is to alarge extent unknown. In this thesis the focus is on articular cartilage and meniscus and methods to study these tissues.Magnetic resonance imaging (MRI) is suitable for imaging of cartilage and meniscus, and quantitative imaging methods have the potential to probe the molecular composition and microstructure. Using such methods, we can gain new insight in the development of OA and the role of different structures of theknee.The results of this thesis show that MR relaxation times T2', T2 and T1 are longer in the posterior horn of medial menisci from patients with severe medial compartment knee OA, compared both to the contralateral meniscus and menisci from deceased donors without known knee OA (Paper I). Relaxationtimes also seem to reflect more subtle changes in the meniscus as they are associated with gold standard histopathological scoring of degeneration characteristics (Paper II).gagCEST is a promising MRI method that has the potential to directly reflect the glycosaminoglycan (GAG) depletion within early degeneration of articular cartilage. However, in a phantom study in this thesis, gagCEST demonstrated a low sensitivity to the type of GAG most abundant in mature human articular cartilage (Paper III).An intrinsic limitation to MRI is the low spatial resolution. Even though MRI-based techniques may have the ability to probe the microscopic composition, other methods are needed to directly visualize the microstructure of the tissue. Here we show that synchrotron radiation (SR)-based microcomputed tomography (μCT) with phase contrast enhancement can resolve the collagen fibre structure of meniscus tissue, including fibre crimping and structural changes related to degeneration (Paper IV). Imaging of tissue samples without fixation or embedding is of interest in studies of meniscus biomechanics.The methods evaluated in this thesis have the potential to detect and follow tissue degeneration in articular cartilage and meniscus and could become valuable tools in future studies to increase our knowledge of disease progression in OA.