Proteoglycan (PG) depletion-induced changes in T 1 (spin-lattice relaxation in rotating frame) relaxation and dispersion in articular cartilage were studied at 4T. Using a spin-lock cluster pre-encoded fast spin echo sequence, T 1 maps of healthy bovine specimens and specimens that were subjected to PG depletion were computed at varying spin-lock frequencies.

In this article, both sodium magnetic resonance (MR) and T 1r relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T 1r , a brief description of (i) principles of measuring T 1r relaxation, (ii) pulse sequences for computing T 1r relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T 1r in biological tissues and (v) effects of exchange and dipolar interaction on T 1r dispersion are discussed. Correlation of T 1r relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokineinduced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T 1r data from osteoarthritic specimens, animal models, healthy human subjects and as well from osteoarthritic patients are provided. The current status of T 1r relaxation mapping of cartilage and future directions is also discussed. Copyright # 2006 John Wiley & Sons, Ltd. KEYWORDS: cartilage; arthritis; spin-lock; T1rho; sodium; MRI OSTEOARTHRITIS Osteoarthritis (OA) affects more than half of the population above the age of 65 (1,2) and has a significant negative impact on the quality of life of elderly individuals (3). The economic costs in the USA from OA have been estimated to be more than 1% of the gross domestic product (4). OA is now increasingly viewed as a metabolically active joint disorder of diverse etiologies. The biochemistry of the disease is characterized by the following changes in cartilage: reduced proteoglycan (PG) concentration, possible changes in the size of collagen fibril and aggregation of PG, increased water content and increased rate of synthesis and degradation of matrix macromolecules. The earliest changes in the cartilage due to OA result in a partial breakdown in the proteoglyc...

Results from this study suggest that T1rho may provide a tool for the diagnosis of early degenerative changes in the disc. T1rho-weighted MRI is a noninvasive technique that may provide higher dynamic range than T2 and does not require a high static field or exogenous contrast agents.

One of the initiating steps of osteoarthritis is the loss of proteoglycan (PG) molecules from the cartilage matrix. One method for assessing cartilage integrity, therefore, is to measure the PG content or fixed charge density (FCD) of cartilage. This report shows the feasibility of calculating FCD by 23 Na MRI and introduces MRI protocols for human studies, in vivo.23 Na MRI was used to measure the sodium concentration inside bovine patellar cartilage. The sodium concentration was then converted to FCD (mM) by considering ideal Donnan equilibrium. These FCD measurements were compared to FCD measurements obtained through standard dimethylmethylene blue PG assays. There was a high correlation (slope ‫؍‬ 0.89, r 2 ‫؍‬ 0.81) between the FCD measurements obtained by 23 Na MRI and those obtained by the PG assays. These methods were then employed in quantifying the FCD of articular cartilage of human volunteers in vivo. Two imaging protocols were compared: one using a birdcage coil, the other using a transmit/receive surface coil. Both methodologies gave similar results, with the average sodium concentration of normal human patellar cartilage ranging from ϳ ϳ240 to 260 mM. This corresponds to

No abstract

The origin of spin locking image artifacts in the presence of B 0 and B 1 magnetic field imperfections is shown theoretically using the Bloch equations and experimentally at low (ω 1 ≪ Δω 0 ), intermediate (ω 1 ~ Δω 0 ) and high (ω 1 ≫ Δω 0 ) spin locking field strengths. At low spin locking fields, the magnetization is shown to oscillate about an effective field in the rotating frame causing signature banding artifacts in the image. At high spin lock fields, the effect of the resonance offset Δω 0 is quenched, but imperfections in the flip angle cause oscillations about the ω 1 field. A new pulse sequence is presented that consists of an integrated spin echo and spin lock experiment followed by magnetization storage along the -z-axis. It is shown that this sequence almost entirely eliminates banding artifacts from both types of field inhomogeneities at all spin locking field strengths. The sequence was used to obtain artifact free images of agarose in inhomogeneous B 0 and B 1 fields, offresonance spins in fat and in vivo human brain images at 3T. The new pulse sequence can be used to probe very low frequency (0-400 Hz) dynamic and static interactions in tissues without contaminating B 0 and B 1 field artifacts.

The feasibility of using sodium magnetic resonance (MR) imaging to detect proteoglycan loss in early-stage osteoarthritis is evaluated. Fixed charge density (FCD) maps were calculated from sodium MR imaging data collected in nine healthy volunteers and three individuals with symptoms of early-stage osteoarthritis by using a 4.0-T clinical MR imaging unit. Data from the healthy individuals revealed a mean FCD of -182 mmol/L +/- 9. Data from the symptomatic subjects revealed focal regions of decreased FCD, with mean values ranging from -108 to -144 mmol/L, indicating proteoglycan loss from the cartilage matrix. The data suggest that sodium MR imaging has potential for use as a quantitative diagnostic tool to measure changes in proteoglycan content in early-stage osteoarthritis.

The influence of radiofrequency (RF) spin-lock pulse on the laminar appearance of articular cartilage in MR images was investigated. Spin-lock MRI experiments were performed on bovine cartilage plugs on a 4.7 Tesla small-bore MRI scanner, and on human knee cartilage in vivo on a 1.5 Tesla clinical scanner. When the normal to the surface of cartilage was parallel to B 0 , a typical laminar appearence was exhibited in T 2 -weighted images of cartilage plugs, but was absent in T 1 -weighted images of the same plugs. At the "magic angle" orientation (when the normal to the surface of cartilage was 54.7°w ith respect to B 0 ), neither the T 2 nor the T 1 images demonstrated laminae. At the same time, T 1 values were greater than T 2 at both orientations throughout the cartilage. T 1 dispersion (i.e., the dependence of the relaxation rate on the spin-lock frequency 1 ) was observed, which reached a steady-state value of close to 2 kHz in both parallel and magic-angle orientations. These results suggest that residual dipolar interaction from motionally-restricted water and relaxation processes, Articular cartilage is a soft connective tissue that covers the ends of bones and acts as a shock-absorbing tissue (1). It is responsible for load distribution, and provides a lowfriction surface. It is composed of water (65-80%), proteoglycans (PG; 5%), collagen (15-20%), and noncollagenous proteins (2-5). The PGs are highly charged macromolecules with a central protein core to which glycosaminoglycans (GAG) are attached (6,7). The GAGs have a high concentration of negatively charged sulfate groups, which attract positive ions and water molecules to maintain electroneutrality. The strong water-binding affinity of PGs produces an osmotic pressure that must be balanced by restraining forces in the collagen fibril network. The collagen in cartilage is primarily type II, and is present in the form of triple helical fibrils. These fibrils form a highly organized anisotropic fibrous meshwork that lends the cartilage its extremely high tensile strength and resistance to shear forces. These special properties are essentially influenced by the size, spatial arrangement, and linkage of the collagen fibers. Among all tissues, collagen fibers appear to be very specific, naturally weakly hydrated, and highly structured.Cartilage is subdivided into three structural zones on the basis of the collagen fiber orientation, which changes depthwise. The fibrils are densely packed and oriented parallel to the articular surface in the superficial zone, randomly in the transitional zone, and perpendicular to the articular surface in the radial zone, which makes up the major part of the aricular cartilage. A schematic of the orientation of collagen fibers in cartilage is shown in Fig. 1 (8,9). The deepest region of the articular cartilage is the calcified region, which separates the articular cartilage from the subchondral bone. The tide-mark region represents a histologically demonstrable region separating the radial and calcified cartilage zones. Th...