Glutamate (Glu) exhibits a pH and concentration dependent chemical exchange saturation transfer effect (CEST) between its -amine group and bulk water, here termed GluCEST. GluCEST asymmetry is observed at ~3 parts per million downfield from bulk water. Following middle cerebral artery occlusion in the rat brain, an approximately 100% elevation of GluCEST in the ipsilateral side compared to the contralateral side was observed, and is predominantly due to pH changes. In a rat brain tumor model with blood brain barrier disruption, intravenous Glu injection resulted in a clear elevation of GluCEST and a comparable increase in the proton magnetic resonance spectroscopy signal of Glu. GluCEST maps from healthy human brain at 7T were also obtained. These results demonstrate the feasibility and potential of GluCEST for mapping relative changes in Glu concentration as well as pH in vivo. Potential contributions from other brain metabolites to the GluCEST effect are also discussed.

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.

Purpose:To quantify the spin-lattice relaxation time in the rotating frame (T 1 ) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T 1 with OA disease progression and compare it with the transverse relaxation time (T 2 ). Materials and Methods:Human cartilage specimens were obtained from consenting patients (N ϭ 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T 2 -and T 1 -weighted images were obtained on a 4.0 Tesla whole-body GE Signa scanner (GEMS, Milwaukee, WI, USA). A 7-cm diameter transmit/receive quadrature birdcage coil tuned to 170 MHz was employed.Results: All of the surgical knee replacement OA cartilage specimens showed elevated relaxation times (T 2 and T 1 ) compared to healthy cartilage tissue. In various grades of OA specimens, the T 1 relaxation times varied from 62 Ϯ 5 msec to 100 Ϯ 8 msec (mean Ϯ SEM) depending on the degree of cartilage degeneration. However, T 2 relaxation times varied only from 32 Ϯ 2 msec to 45 Ϯ 4 msec (mean Ϯ SEM) on the same cartilage specimens. The increase in T 2 and T 1 in various clinical grades of OA specimens were ϳ5-50% and 30 -120%, respectively, compared to healthy specimens. The degenerative status of the cartilage specimens was also confirmed by histological evaluation. Conclusion:Preliminary results from a limited number of knee specimens (N ϭ 8) suggest that T 1 relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T 1 has a higher dynamic range (Ͼ100%) for detecting early pathology compared to T 2 . This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T 2 . Because of these advantages, T 1 relaxation mapping may be useful for evaluating early OA therapy.

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...