Prospective Cohort Study

Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in older adults (1) Often OA is referred to as degenerative joint disease “(DJD)” This is a misnomer because OA is not simply a process of wear and tear but rather abnormal remodeling of joint tissues driven by a host of inflammatory mediators within the affected joint The most common risk factors for OA include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors, including malalignment and abnormal joint shape (2, 3) Despite the multifactorial nature of OA, the pathological changes seen in osteoarthritic joints have common features that affect the entire joint structure resulting in pain, deformity and loss of function

The pathologic changes seen in OA joints (Figures 1 and ​and2)2) include degradation of the articular cartilage, thickening of the subchondral bone, osteophyte formation, variable degrees of synovial inflammation, degeneration of ligaments and, in the knee, the menisci, and hypertrophy of the joint capsule There can also be changes in periarticular muscles, nerves, bursa, and local fat pads that may contribute to OA or the symptoms of OA The findings of pathological changes in all of the joint tissues are the impetus for considering OA as a disease of the joint as an organ resulting in “joint failure” In this review, we will summarize the key features of OA in the various joint tissues affected and provide an overview of the basic mechanisms currently thought to contribute to the pathological changes seen in these tissues






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Figure 1


Sagittal inversion recovery (A–C) and coronal fast spin echo (D–F) images illustrating the magnetic resonance imaging findings of osteoarthritis (A) reactive synovitis (thick white arrow), (B) subchondral cyst formation (white arrow), (C) bone marrow edema (thin white arrows), (D) partial thickness cartilage wear (thick black arrow), (E–F) full thickness cartilage wear (thin black arrows), subchondral sclerosis (arrowhead) and marginal osteophyte formation (double arrow) Image courtesy of Drs Hollis Potter and Catherine Hayter, Hospital for Special Surgery, New York, NY

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.34453

Osteoarthritis: A Disease of the Joint as an Organ

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60243-2.pdf

Osteoarthritis: an update with relevance for clinical practice

The role of synovitis in osteoarthritis pathogenesis

Chemical exchange saturation transfer (CEST) imaging is a relatively new magnetic resonance imaging contrast approach in which exogenous or endogenous compounds containing either exchangeable protons or exchangeable molecules are selectively saturated and after transfer of this saturation, detected indirectly through the water signal with enhanced sensitivity. The focus of this review is on basic magnetic resonance principles underlying CEST and similarities to and differences with conventional magnetization transfer contrast. In CEST magnetic resonance imaging, transfer of magnetization is studied in mobile compounds instead of semisolids. Similar to magnetization transfer contrast, CEST has contributions of both chemical exchange and dipolar cross-relaxation, but the latter can often be neglected if exchange is fast. Contrary to magnetization transfer contrast, CEST imaging requires sufficiently slow exchange on the magnetic resonance time scale to allow selective irradiation of the protons of interest. As a consequence, magnetic labeling is not limited to radio-frequency saturation but can be expanded with slower frequency-selective approaches such as inversion, gradient dephasing and frequency labeling. The basic theory, design criteria, and experimental issues for exchange transfer imaging are discussed. A new classification for CEST agents based on exchange type is proposed. The potential of this young field is discussed, especially with respect to in vivo application and translation to humans.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mrm.22761

Chemical exchange saturation transfer (CEST): what is in a name and what isn't?

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), T1ρ, and 23Na 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

https://www.pnas.org/content/pnas/105/7/2266.full.pdf

Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST)

Proteoglycan (PG) depletion-induced changes in T1rho (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, T1rho maps of healthy bovine specimens and specimens that were subjected to PG depletion were computed at varying spin-lock frequencies. Sequential PG depletion was induced by trypsinization of cartilage for varying amounts of time. Results demonstrated that over 50% depletion of PG from bovine articular cartilage resulted in average T1rho increases from 110-170 ms. Regression analysis of the data showed a strong correlation (R2 = 0.987) between changes in PG and T1rho. T1rho values were highest at the superficial zone and decreased gradually in the middle zone and again showed an increasing trend in the region near the subchondral bone. The potentials of this method in detecting early degenerative changes of cartilage are discussed. Also, T(1rho)-dispersion changes as a function of PG depletion are described.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mrm.1208

Proteoglycan-induced changes in T1ρ-relaxation of articular cartilage at 4T

Purpose
To quantify the spin-lattice relaxation time in the rotating frame (T1ρ) in various clinical grades of human osteoarthritis (OA) cartilage specimens obtained from total knee replacement surgery, and to correlate the T1ρ with OA disease progression and compare it with the transverse relaxation time (T2).

Materials and Methods
Human cartilage specimens were obtained from consenting patients (N = 8) who underwent total replacement of the knee joint at the Pennsylvania Hospital, Philadelphia, PA, USA. T2- and T1ρ-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 (T2 and T1ρ) compared to healthy cartilage tissue. In various grades of OA specimens, the T1ρ relaxation times varied from 62 ± 5 msec to 100 ± 8 msec (mean ± SEM) depending on the degree of cartilage degeneration. However, T2 relaxation times varied only from 32 ± 2 msec to 45 ± 4 msec (mean ± SEM) on the same cartilage specimens. The increase in T2 and T1ρ in various clinical grades of OA specimens were ∼5–50% 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 = 8) suggest that T1ρ relaxation mapping is a sensitive noninvasive marker for quantitatively predicting and monitoring the status of macromolecules in early OA. Furthermore, T1ρ has a higher dynamic range (>100%) for detecting early pathology compared to T2. This higher dynamic range can be exploited to measure even small macromolecular changes with greater accuracy compared to T2. Because of these advantages, T1ρ relaxation mapping may be useful for evaluating early OA therapy. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/jmri.20536

T1rho relaxation mapping in human osteoarthritis (OA) cartilage: comparison of T1rho with T2.

Proteoglycan Depletion–Induced Changes in Transverse Relaxation Maps of Cartilage

In this article we present an up-to-date overview of the potential biomedical applications of sodium magnetic resonance imaging (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 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.

/pdf/biomedical-applications-of-sodium-mri-in-vivo-17icfih0qc.pdf

Ravinder R. Regatte

Papers

Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer (gagCEST)

Proteoglycan-induced changes in T1ρ-relaxation of articular cartilage at 4T

T1rho relaxation mapping in human osteoarthritis (OA) cartilage: comparison of T1rho with T2.

Proteoglycan Depletion–Induced Changes in Transverse Relaxation Maps of Cartilage

Biomedical Applications of Sodium MRI In Vivo