T1ρ mapping of pediatric epiphyseal and articular cartilage in the knee

MR imaging is a uniquely powerful tool for investigating the structure and composition of the growing skeleton. MR imaging does not use ionizing radiation so it can safely be used to study the growth and development of structures such as epiphyseal and articular cartilage in children. Such studies may provide a greater understanding and early detection of perturbations in normal cartilaginous development that may leave permanent sequelae in the skeletally mature patient. Cartilage undergoes dramatic changes during the first 10 years of life but is more difficult to image than other tissues because it is present only in relatively thin layers, has relatively high density, and features a varied composition. Articular cartilage is composed of a semi-solid matrix of water (65–80%), collagen (15–20%), proteoglycan (~5%), and other proteins (~2%) (1). Proteoglycan (PG) content is of particular interest because of its role in epiphyseal and articular cartilage structure and development. A subset of PGs, glycosaminoglycans (GAGs), are highly negatively charged macromolecules that make up a large percentage of cartilage PG content and contain a high concentration of sulfate groups that strongly bind to water molecules (2). This binding affinity helps to support collagen’s triple-helical fiber structure which serves a variety of biomechanical functions in vivo, including shock absorption, flexibility, and smoothing of joint motions (3). Epiphyseal cartilage is found at the ends of long bones between the joint and the primary growth plate in children. The epiphysis is initially completely comprised of cartilage with a high concentration of GAG, but ossifies during development (4,5). By late adolescence, the epiphysis is typically completely ossified. During ossification GAG macromolecules degrade and the chondrocytes scattered in the epiphysis hypertrophy, reducing the amount of bound water. This transformation gives rise to higher signal on T2-weighted images (6). There has been much recent interest in developing new imaging methods to identify the disease state of tissues with large quantities of exchanging protons and to relate them to quantitative relaxation parameters. Proton exchange between water and labile groups in other molecules provides one such potential mechanism that introduces sensitivity for specific chemical components within a mixture. This may be particularly useful for substances such as GAG, which contain a large concentration of chemically exchanging hydroxyl groups. While methods that monitor magnetization transfer such as chemical exchange saturation transfer (CEST) provide direct measurement of exchange (7), other approaches, notably T2 and T1ρ sequences, are also affected by exchange on appropriate time scales and register as large dispersions in signal contrast (8). Measurements of relaxation time constants in the rotating frame (T1ρ and T2ρ) using spin-locking techniques have been shown to be sensitive to molecular motions and chemical exchange on the time scale of the locking field (γB1) (9,10). The advantage of the T1ρ technique lies in the ability to make dispersion measurements in an imaging context in a regime where other approaches, such as CEST or Carr-Purcell-Meiboom-Gill (CPMG) dispersion, may be technically difficult (11,12). For example, it is technically much easier to achieve high locking field strength (>1 kHz) than to use comparable CPMG pulse spacing, making spin locking more appropriate for use in an imaging context. Spin locking techniques typically involve the application of a long, low power B1 prepulse before an imaging sequence to impart T1ρ contrast. The first experiments measuring relaxation in the rotating frame are attributed to Redfield, and Lee and Goldburg (13,14). These types of measurements can, in principle, yield insights into the time scale of molecular motions, the sizes of different pools of protons, chemical and diffusive exchange processes, protein sizes and concentrations, and other attributes of interest (10,15–17). T1ρ contrast has previously been investigated in tissues such as cartilage, brain, breast, and muscle (18–21). However, there is little consensus on the relative contribution of chemical exchange and other changes in tissue composition and their interactions with water on quantitative measures of T1ρ. Articular cartilage has been studied in vivo with MRI using a variety of 2D and 3D methods, and articular cartilage degradation in adults has recently been assessed with T1ρ-weighted imaging (20,22–25). These studies report that early osteoarthritis (OA) changes are associated with the loss of PG and collagen, although early state molecular degradation is not typically seen on standard MRI using spin-echo and gradient recalled echo imaging sequences. T2 and T1ρ maps of articular cartilage have been made by several researchers while attempting to correlate proteoglycan degradation in OA to changes in T1ρ values (23,26). A competing technique, delayed Gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), is quantitatively sensitive to PG loss, but requires the use of an intravenous contrast agent (27). It would, therefore, be preferable, especially for children, to use an endogenous source of contrast such as the chemical exchange effects of labile protons on GAG. A variety of imaging studies have been performed to measure cartilage structural changes during the maturation process (4,28,29), but to date no applications of spin-lock techniques have been reported in children to quantify these effects in vivo. Thus, the purpose of this study is to determine the feasibility of T1ρ mapping of pediatric epiphyseal and articular cartilage.