Glycosaminogycans (GAGs) are involved in numerous vital functions in the human body. Mapping the GAG concentration in vivo is desirable for the diagnosis and monitoring of a number of diseases such as osteoarthritis, which affects millions of individuals. GAG loss in cartilage is typically an initiating event in osteoarthritis. Another widespread pathology related to GAG is intervertebral disk degeneration. Currently existing techniques for GAG monitoring, such as delayed gadolinium-enhanced MRI contrast (dGEMRIC), T1, and 23 Na MRI, have some practical limitations. We show that by exploiting the exchangeable protons of GAG one may directly measure the localized GAG concentration in vivo with high sensitivity and therefore obtain a powerful diagnostic MRI method.cartilage ͉ MRI ͉ osteoarthritis ͉ NOE ͉ proteoglycan

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, we present an up-to-date overview of the potential biomedical applications of sodium MRI in vivo. Sodium MRI is a subject of increasing interest in translational imaging research as it can give some direct and quantitative biochemical information on the tissue viability, cell integrity and function, and therefore not only help the diagnosis but also the prognosis of diseases and treatment outcomes. It has already been applied in vivo in most of human tissues, such as brain for stroke or tumor detection and therapeutic response, in breast cancer, in articular cartilage, in muscle and in kidney, and it was shown in some studies that it could provide very useful new information not available through standard proton MRI. However, this technique is still very challenging due to the low detectable sodium signal in biological tissue with MRI and hardware/software limitations of the clinical scanners. The article is divided in three parts: (1) the role of sodium in biological tissues, (2) a short review on sodium magnetic resonance, and (3) a review of some studies on sodium MRI on different organs/diseases to date.

Sodium NMR spectroscopy and MRI have become popular in recent years through the increased availability of high-field MRI scanners, advanced scanner hardware and improved methodology. Sodium MRI is being evaluated for stroke and tumor detection, for breast cancer studies, and for the assessment of osteoarthritis and muscle and kidney functions, to name just a few. In this article, we aim to present an up-to-date review of the theoretical background, the methodology, the challenges and limitations, and current and potential new applications of sodium MRI.

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Osteoarthritis (OA), a leading cause of disability, affects 27 million people in the United States and its prevalence is rising along with the rise in obesity. So far, biomechanical or behavioral interventions as well as attempts to develop disease-modifying OA drugs have been unsuccessful. This may be partly due to antiquated imaging outcome measures such as radiography, which are still endorsed by regulatory agencies such as the United States Food and Drug Administration (FDA) for use in clinical trials. Morphological magnetic resonance imaging (MRI) allows unparalleled multi-feature assessment of the OA joint. Furthermore, advanced MRI techniques also enable evaluation of the biochemical or ultrastructural composition of articular cartilage relevant to OA research. These compositional MRI techniques have the potential to supplement clinical MRI sequences in identifying cartilage degeneration at an earlier stage than is possible today using morphologic sequences only. The purpose of this narrative review is to describe compositional MRI techniques for cartilage evaluation, which include T2 mapping, T2* Mapping, T1 rho, dGEMRIC, gagCEST, sodium imaging and diffusion weighted imaging (DWI). We also reviewed relevant clinical studies that have utilized these techniques for the study of OA. The different techniques are complementary. Some focus on isotropy or the collagen network (e.g., T2 mapping) and others are more specific in regard to tissue composition, e.g., gagCEST or dGEMRIC that convey information on the GAG concentration. The application and feasibility of these techniques is also discussed, as they will play an important role in implementation in larger clinical trials and eventually clinical practice.

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.