Correlation of T_1ρ with fixed charge density in cartilage

Abstract

Purpose:To establish the specificity of T 1 with respect to fixed charge density (FCD) as a measure of proteoglycan (PG) content in cartilage during the onset of osteoarthritis (OA). Materials and Methods:T 1 -weighted and sodium MRI were performed on cartilage samples of enzymatically degraded bovine explants and natural osteoarthritic human samples representing controlled and physiological models of OA, respectively. Spatial maps of T 1 and FCD (measured using the previously validated method of sodium MRI) were calculated from image data. Data were extracted from the maps and subjected to linear regression to compare changes in T 1 with changes in FCD in each model. Tissue samples were subjected to histological staining for a reduction in PG content.Results: Plots of normalized T 1 rate vs. FCD were found to be strongly correlated (R 2 Ͼ 0.75 and 0.85) in both models with nearly the same slope of Ϸ1/2 (P Ͼ 0.51). Loss of PG in bovine and human tissue was confirmed by histology. Conclusion:The strong correlation of the FCD and T 1 data in both the controlled and physiological models demonstrates that changes in T 1 are due predominantly to changes in PG content. This work is a first step in establishing T 1 as a method of quantifying PG changes in early-stage OA. THE PATHOLOGY OF THE disease osteoarthritis (OA) results in significant changes to the biochemical composition of cartilage. Loss of proteoglycan content (PG) from the extracellular matrix (ECM) is characteristic of the early development of OA (1-3). Although changes in collagen content and structure have been discerned, during the beginning stages of the disease the collagenous component of the ECM is often preserved (3-5). A noninvasive technique to detect biochemical changes that precede morphological degeneration in tissue will have a substantial impact on early diagnosis and the evaluation of therapeutic efficacy of treatment.The sodium MRI method has previously been established as an accurate measure of fixed charge density (FCD), as validated by spectrophotometric assay (6). The direct relationship between FCD and PG allows FCD data obtained via sodium MRI to be used as a spatially resolved measure of PG. Since the FCD measurement is affected only by charged species, sodium MRI provides a highly specific measure of PG and can be used as a gold standard for validating other methods of PG quantification.A promising alternative to sodium MRI to detect PG changes in vivo is T 1 -weighted MRI (7). T 1 , the spinlattice relaxation in the rotating frame, is sensitive to low frequency interactions between water molecules and their local macromolecular environment, such as the PG constituent of the ECM in cartilage. T 1 -weighting can be incorporated into an MR imaging sequence by "T 1 -preparing" the magnetization using a long duration spin-lock pulse. The amplitude of the spin-lock pulse is commonly referenced in terms of its nutation frequency (␥B 1 ), which is on the order of a few kilohertz. T 1 is sensitive to molecular interaction processes having...

Sodium and T1ρ MRI for molecular and diagnostic imaging of articular cartilage

“…This is completely in conflict with several results from IL-1b studies on a larger group of samples and on an in vivo animal model where a significant increases in T 1r ( Figure 25) were observed (54,177). (3) At the higher field (8.5 T), T 1r should be lower than that at 1.5 T, but the T 1r numbers measured in human cartilage in this study are almost 50% higher than those observed at 1.5 T. This result was not explained.…”

“…In direct contradiction to the above study, in human OA specimens (n ¼ 7) with different Mankin grades (0-3), a strong correlation between T 1r rate and FCD measured from sodium MRI was observed (Figure 28), indicating that T 1r relaxation rate may be useful in studying the OA process in humans (177). Nevertheless, a study on a large group of human osteoarthritic specimens is needed to obtain statistically significant results.…”

“…T 1r studies in solution-state NMR have been reviewed extensively (166)(167)(168). There has been a considerable amount of work on biological tissues using T 1r -spectroscopy and imaging dealing with tumors, muscle, myocardium, blood flow and cartilage (26,165,(169)(170)(171)(172)(173)(174)(175)(176)(177)(178)(179).…”

“…This is because depletion of collagen from cartilage is not feasible without affecting PG content. To overcome this limitation, an indirect approach was used (177) in which spatial maps of proton T 1r and sodium maps of FCD were computed on bovine specimens subjected to trypsininduced PG degradation and human OA specimens with different Mankin grade (232). The loss of PG was confirmed by histology in these specimens.…”

T1ρ relaxation mapping in human osteoarthritis (OA) cartilage: Comparison of T1ρ with T2

“…In contrast to previous studies (19,20), in the current study we aimed to measure T 1 relaxation in human cartilage specimens obtained from surgical replacement of knee joints. Recent in vitro and in vivo studies on cartilage have demonstrated that the T 1 is sensitive to changes in the PG content of cartilage (7,8,21). In a study of bovine cartilage it was shown that the T 1 relaxation rate changes linearly with changes in the PG content of cartilage (6).…”