Magnetic Resonance Imaging of Relative Glycosaminoglycan Distribution in Patients with Autologous Chondrocyte Transplants

Gillis, Amy; Bashir, Adil; McKeon, Brian; Scheller, Arnold D.; Gray, Martha L.; Burstein, Deborah

doi:10.1097/00004424-200112000-00010

Cited by 134 publications

(85 citation statements)

References 27 publications

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“…In addition, it has recently been reported that such a correlation also exists in autologous chondrocyte transplants in humans (27). Our data show that the FCD as determined in this manner correlates not only with biochemical composition but also with biomechanical properties.…”

Section: ϫsupporting

confidence: 78%

Matrix fixed‐charge density as determined by magnetic resonance microscopy of bioreactor‐derived hyaline cartilage correlates with biochemical and biomechanical properties

Chen¹,

Fishbein²,

Torzilli³

et al. 2003

Arthritis & Rheumatism

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Objective. To use noninvasive magnetic resonance imaging (MRI), biochemical analyses, and mechanical testing of engineered neocartilage grown in a hollowfiber bioreactor (HFBR) to establish tissue properties, and to test the hypothesis that MRI can be used to monitor biochemical and biomechanical properties of neocartilage.Methods. Chondrocytes from day 16 embryonic chick sterna were inoculated into an HFBR and maintained for up to 4 weeks with and without exposure to chondroitinase ABC. The fixed-charge density (FCD) of the cartilage was determined using the MRI gadolinium exclusion method. The sulfated glycosaminoglycan (S-GAG), hydroxyproline, and DNA contents were determined using biochemical procedures, while dynamic and equilibrium moduli were determined from mechanical indentation tests.Results. S-GAG content, tissue cross-sectional area, and equilibrium modulus of the neocartilage increased with development time. There was a gradient of S-GAG content across the length of control neocartilage at the 4-week time point, with higher values being found toward the inflow region. Exposure to chondroitinase ABC resulted in a decrease in tissue area, negative FCD, proteoglycan content, and equilibrium and dynamic moduli. The treated bioreactors displayed a lengthwise variation in S-GAG content, with higher values toward the outflow end. Linear correlations were established among FCD, proteoglycan content, and biomechanical properties.Conclusion. HFBR-derived neocartilage showed regional variation in S-GAG content under control conditions, and in the decrease of S-GAG in response to enzyme treatment. In addition, the results support the hypothesis that tissue parameters derived from MRI can be used to noninvasively monitor focal neocartilage formation and biochemical and biomechanical properties.

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Section: ϫsupporting

confidence: 78%

Matrix fixed‐charge density as determined by magnetic resonance microscopy of bioreactor‐derived hyaline cartilage correlates with biochemical and biomechanical properties

Chen¹,

Fishbein²,

Torzilli³

et al. 2003

Arthritis & Rheumatism

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“…The delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been shown to predict the PG content of cartilage (Bashir et al, 1999, whereas the T2 relaxation time reflects the integrity and arrangement of the collagen fibril network (Nieminen et al, 2000;Nieminen et al, 2001;Xia et al, 2001) as well as collagen and water content (Fragonas et al, 1998;Shapiro et al, 2001). Both techniques have been applied for in vivo analysis of human cartilage using clinical MR scanners (Gold et al, 2006), and e.g. cartilage maturation after repair operation has been successfully monitored (Gillis et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Both techniques have been applied for in vivo analysis of human cartilage using clinical MR scanners (Gold et al, 2006), and e.g. cartilage maturation after repair operation has been successfully monitored (Gillis et al, 2001). Acoustic properties of cartilage, i.e.…”

Section: Introductionmentioning

confidence: 99%

Comparison of novel clinically applicable methodology for sensitive diagnostics of cartilage degeneration

Kiviranta

Töyräs²,

Nieminen³

et al. 2007

eCM

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In order efficiently to target therapies intending to stop or reverse degenerative processes of articular cartilage, it would be crucial to diagnose osteoarthritis (OA) earlier and more sensitively than is possible with the existing clinical methods. Unfortunately, current clinical methods for OA diagnostics are insensitive for detecting the early degenerative changes, e.g., arising from collagen network damage or proteoglycan depletion. We have recently investigated several novel quantitative biophysical methods, including ultrasound indentation, quantitative ultrasound techniques and magnetic resonance imaging, for diagnosing the degenerative changes of articular cartilage, typical for OA. In this study, the combined results of these novel diagnostic methods were compared with histological (Mankin score, MS), compositional (proteoglycan, collagen and water content) and mechanical (dynamic and equilibrium moduli) reference measurements of the same bovine cartilage samples. Receiver operating characteristics (ROC) analysis was conducted to judge the diagnostic performance of each technique. Indentation and ultrasound techniques provided the most sensitive measures to differentiate samples of intact appearance (MS= 0) from early (13) degeneration. Furthermore, these techniques were good predictors of tissue composition and mechanical properties. The specificity and sensitivity analyses revealed that the mechano-acoustic methods, when further developed for in vivo use, may provide more sensitive probes for OA diagnostics than the prevailing qualitative X-ray and arthroscopic techniques. Noninvasive quantitative MRI measurements showed slightly lower diagnostic performance than mechano-acoustic techniques. The compared methods could possibly also be used for the quantitative monitoring of success of cartilage repair.

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“…12) (76,77). Increases in the dGEMRIC index have also been observed clinically in cartilage implants (78)(79)(80) and in the cartilage in several case studies of patients recovering from surgery and taking nutritional supplements (81).…”

Section: Should Mri Be Used To Determine Entry Criteria For Clinical mentioning

confidence: 73%

MRI for development of disease-modifying osteoarthritis drugs

Burstein

2006

NMR Biomed.

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MRI has advantages as an imaging modality for drug development through its potential to provide information regarding localized morphological parameters, in addition to metrics of the structural and molecular state of cartilage. These metrics have the potential to provide earlier indications of pathology and may progress more rapidly than radiographic measures. These combined scans of localized morphology and matrix parameters will most likely provide a fuller assessment of cartilage state and will improve the cost and practicality of an overall evaluation of cartilage status by MRI. In the first part of this review, the relevant parameters are presented in terms of the information content they might provide in the drug development process. In the second part, applications of the MRI parameters in preclinical and clinical drug development are presented.

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Magnetic Resonance Imaging of Relative Glycosaminoglycan Distribution in Patients with Autologous Chondrocyte Transplants

Cited by 134 publications

References 27 publications

Matrix fixed‐charge density as determined by magnetic resonance microscopy of bioreactor‐derived hyaline cartilage correlates with biochemical and biomechanical properties

Matrix fixed‐charge density as determined by magnetic resonance microscopy of bioreactor‐derived hyaline cartilage correlates with biochemical and biomechanical properties

Comparison of novel clinically applicable methodology for sensitive diagnostics of cartilage degeneration

MRI for development of disease-modifying osteoarthritis drugs

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