MRI visualization of proteoglycan depletion in articular cartilage via intravenous administration of Gd-DTPA

Trattnig, Siegfried; Mlynárik, Vladı́mir; Breitenseher, Martin; Huber, Monika; Zembsch, Alexander; Rand, Thomas; Imhof, Herwig

doi:10.1016/s0730-725x(98)00215-x

Cited by 138 publications

(84 citation statements)

References 18 publications

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“…The GAG distribution would then be inversely related to the Gd-DTPA 2-concentration, or directly related to the T 1 values after penetration of the contrast agent into the cartilage, T 1 (Gd) [9]. Studies in vitro have validated that proteoglycan estimates based on dGEMRIC measurements to be in very good agreement with biochemical assays or histology [10][11][12][13][14][15][16], and in vivo data that are consistent with the premise has been reported in animal models [17][18][19][20] and clinically [11,21].…”

Section: Introductionsupporting

confidence: 65%

Preliminary Evaluation of Potential Disease Modification by Hylan G-F 20 (Synvisc®) Using dGEMRIC

Prasad¹,

Schnitzer²,

Krishnan³

2012

J Mol Imag Dynamic

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The objective of the present study was to utilize delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC), as a reflection of cartilage matrix integrity, to evaluate the effects of a specific hyaluronan, hylan G-F 20 (SYNVISC ® ; Genzyme Biosurgery, Cambridge, MA) in OA patients over the course of 6 months, and to utilize these data to determine effect size and power calculations for future studies. An open-label, single-blind exploratory study of patients having knee OA (Trail registration: NCT00949494) was performed in thirty subjects (20 active, intra-articular injections (3, week apart) with hylan G-F 20; 10 control). dGEMRIC data was obtained at baseline, 3 and 6 months. No changes were measurable with hylan administration under the clinical and imaging conditions utilized in the current study. The lack of response in the current study may be because the subjects had a relatively advanced stage of disease with respect to cartilage integrity.

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Section: Introductionsupporting

confidence: 65%

Preliminary Evaluation of Potential Disease Modification by Hylan G-F 20 (Synvisc®) Using dGEMRIC

Prasad¹,

Schnitzer²,

Krishnan³

2012

J Mol Imag Dynamic

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“…However, measurement of DR 1 is still required to calculate GAG content directly [41,42]. Nonetheless, T 1,Gd has been correlated with proteoglycan content [27,79,99]. T 1,Gd also varies depending on the region of cartilage [31,49] and is higher in load-bearing cartilage compared with non-contact regions [100].…”

Section: T 1 Mapping and Delayed Gadolinium-enhanced Magnetic Resonanmentioning

confidence: 99%

Probing articular cartilage damage and disease by quantitative magnetic resonance imaging

Chan

Neu

2013

J. R. Soc. Interface.

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Osteoarthritis (OA) is a debilitating disease that reflects a complex interplay of biochemical, biomechanical, metabolic and genetic factors, which are often triggered by injury, and mediated by inflammation, catabolic cytokines and enzymes. An unmet clinical need is the lack of reliable methods that are able to probe the pathogenesis of early OA when disease-rectifying therapies may be most effective. Non-invasive quantitative magnetic resonance imaging (qMRI) techniques have shown potential for characterizing the structural, biochemical and mechanical changes that occur with cartilage degeneration. In this paper, we review the background in articular cartilage and OA as it pertains to conventional MRI and qMRI techniques. We then discuss how conventional MRI and qMRI techniques are used in clinical and research environments to evaluate biochemical and mechanical changes associated with degeneration. Some qMRI techniques allow for the use of relaxometry values as indirect biomarkers for cartilage components. Direct characterization of mechanical behaviour of cartilage is possible via other specialized qMRI techniques. The combination of these qMRI techniques has the potential to fully characterize the biochemical and biomechanical states that represent the initial changes associated with cartilage degeneration. Additionally, knowledge of in vivo cartilage biochemistry and mechanical behaviour in healthy subjects and across a spectrum of osteoarthritic patients could lead to improvements in the detection, management and treatment of OA.

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“…It has been shown that delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) reflects the GAG concentration in tissue (12)(13)(14)(15)(16)(17), and is sensitive to physiologic and pathologic conditions in vivo (18 -22). With this technique, the anionic paramagnetic contrast agent Gd-DTPA 2Ϫ (Magnevist; Berlex, Wayne, NJ) distributes in inverse relation to the negatively charged GAGs, resulting in an approximately linear relation between cartilage GAG content and T 1 relaxation time in the presence of the contrast agent (12,13,16).…”

Section: ؊1mentioning

confidence: 99%

T₂ of articular cartilage in the presence of Gd‐DTPA²⁻

Nieminen

Menezes

et al. 2004

Magnetic Resonance in Med

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T 2 information and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are both used to characterize articular cartilage. They are currently obtained in separate studies because Gd-DTPA 2؊ (which is needed for dGEMRIC) affects the inherent T 2 information. In this study, T 2 was simulated and then measured at 8.45 T in 20 sections from two human osteochondral samples equilibrated with and without Gd-DTPA 2؊. Both the simulations and data demonstrated that Gd-DTPA 2؊ provides a non-negligible mechanism for relaxation, especially with higher (1 mM) equilibrating Gd-DTPA 2؊ concentrations, and in areas of tissue with high T 2 (due to weak inherent T 2 mechanisms) and high tissue Gd-DTPA 2؊ (due to a low glycosaminoglycan concentration). Nonetheless, T 2 -weighted images of cartilage equilibrated in 1 mM Gd-DTPA 2؊ showed similar T 2 contrast with and without Gd-DTPA 2؊, demonstrating that the impact on T 2 was not great enough to affect identification of T 2 lesions. However, T 2 maps of the same samples showed loss of conspicuity of T 2 abnormalities. We back-calculated inherent T 2 's (T 2,bc ) using a T 2 -relaxivity value from a 20% protein phantom (r 2 ‫؍‬ 9.27 ؎ 0.09 mM ؊1 s ؊1) and the Gd-DTPA 2؊ concentration calculated from T 1,Gd . The back-calculation restored the inherent T 2 conspicuity, and a correlation between T 2 and T 2,bc of r ‫؍‬ 0.934 (P < 0.0001) was found for 80 regions of interest (ROIs) in the sections. Backcalculation of T 2 is therefore a viable technique for obtaining T 2 maps at high equilibrating Gd-DTPA 2؊ concentrations. With T 2 -weighted images and/or low equilibrating Gd-DTPA 2؊ concentrations, it may be feasible to obtain both T 2 and dGEMRIC information in the presence of Gd-DTPA 2؊ without such corrections. These conditions can be designed into ex vivo studies of cartilage. They appear to be applicable for clinical T 2 studies, since pilot clinical data at 1.5 T from three volunteers demonstrated that calculated T 2 maps are comparable before and after "double dose" Gd-DTPA 2؊ (as utilized in clinical dGEMRIC studies). Therefore, it may be possible to perform a comprehensive clinical examination of dGEMRIC, T 2 , and cartilage volume in one scanning session without T 2 data correction.

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MRI visualization of proteoglycan depletion in articular cartilage via intravenous administration of Gd-DTPA

Cited by 138 publications

References 18 publications

Preliminary Evaluation of Potential Disease Modification by Hylan G-F 20 (Synvisc®) Using dGEMRIC

Preliminary Evaluation of Potential Disease Modification by Hylan G-F 20 (Synvisc®) Using dGEMRIC

Probing articular cartilage damage and disease by quantitative magnetic resonance imaging

T₂ of articular cartilage in the presence of Gd‐DTPA²⁻

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MRI visualization of proteoglycan depletion in articular cartilage via intravenous administration of Gd-DTPA

Cited by 138 publications

References 18 publications

Preliminary Evaluation of Potential Disease Modification by Hylan G-F 20 (Synvisc®) Using dGEMRIC

Preliminary Evaluation of Potential Disease Modification by Hylan G-F 20 (Synvisc®) Using dGEMRIC

Probing articular cartilage damage and disease by quantitative magnetic resonance imaging

T2 of articular cartilage in the presence of Gd‐DTPA2−

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T₂ of articular cartilage in the presence of Gd‐DTPA²⁻