Measurement of T1ρ dispersion with compressed sensing and magnetization prepared radial balanced steady-state free precession in spontaneous human osteoarthritis.

PURPOSE: To assess the potential for accelerating continuous-wave (CW) T1ρ dispersion measurement with compressed sensing approach via studying the effect that the data reduction has on the ability to detect differences between intact and degenerated articular cartilage with different spin-lock amplitudes and to assess quantitative bias due to acceleration. METHODS: Osteochondral plugs (n = 27, 4 mm diameter) from femur (n = 14) and tibia (n = 13) regions from human cadaver knee joints were obtained from commercial biobank (Science Care, USA) under Ethical permission 134/2015. MRI of specimens was performed at 9.4T with magnetization prepared radial balanced SSFP (bSSFP) readout sequence, and the CWT1ρ relaxation time maps were computed from the measured data. The relaxation time maps were evaluated in the cartilage zones for different acceleration factors. For reference, Osteoarthritis Research Society International (OARSI) grading and biomechanical measurements were performed and correlated with the MRI findings. RESULTS: Four-fold acceleration of CWT1ρ dispersion measurement by compressed sensing approach was feasible without meaningful loss in the sensitivity to osteoarthritic (OA) changes within the articular cartilage. Differences were significant between intact and OA groups in the superficial and transitional zones, and CWT1ρ correlated moderately with the reference measurements (0.3 < r < 0.7). CONCLUSION: CWT1ρ was able to differentiate between intact and OA cartilage even with four-fold acceleration. This indicates that acceleration of CWT1ρ dispersion measurement by compressed sensing approach is feasible with negligible loss in the sensitivity to osteoarthritic changes in articular cartilage.

T2* and quantitative susceptibility mapping in an equine model of post-traumatic osteoarthritis: assessment of mechanical and structural properties of articular cartilage.

OBJECTIVE: To investigate the potential of quantitative susceptibility mapping (QSM) and T2* relaxation time mapping to determine mechanical and structural properties of articular cartilage via univariate and multivariate analysis. METHODS: Samples were obtained from a cartilage repair study, in which surgically induced full-thickness chondral defects in the stifle joints of seven Shetland ponies caused post-traumatic osteoarthritis (14 samples). Control samples were collected from non-operated joints of three animals (6 samples). Magnetic resonance imaging (MRI) was performed at 9.4 T, using a 3-D multi-echo gradient echo sequence. Biomechanical testing, digital densitometry (DD) and polarized light microscopy (PLM) were utilized as reference methods. To compare MRI parameters with reference parameters (equilibrium and dynamic moduli, proteoglycan content, collagen fiber angle and -anisotropy), depth-wise profiles of MRI parameters were acquired at the biomechanical testing locations. Partial least squares regression (PLSR) and Spearman's rank correlation were utilized in data analysis. RESULTS: PLSR indicated a moderate-to-strong correlation (ρ = 0.49-0.66) and a moderate correlation (ρ = 0.41-0.55) between the reference values and T2* relaxation time and QSM profiles, respectively (excluding superficial-only results). PLSR correlations were noticeably higher than direct correlations between bulk MRI and reference parameters. 3-D parametric surface maps revealed spatial variations in the MRI parameters between experimental and control groups. CONCLUSION: Quantitative parameters from 3-D multi-echo gradient echo MRI can be utilized to predict the properties of articular cartilage. With PLSR, especially the T2* relaxation time profile appeared to correlate with the properties of cartilage. Furthermore, the results suggest that degeneration affects the QSM-contrast in the cartilage. However, this change in contrast is not easy to quantify.

Assessment of meniscus with adiabatic T1ρ and T2ρ relaxation time in asymptomatic subjects and patients with mild osteoarthritis: a feasibility study.

OBJECTIVE: To investigate the ability of magnetic resonance imaging (MRI) adiabatic relaxation times in the rotating frame (adiabatic T1ρ and T2ρ) to detect structural alterations in meniscus tissue of mild OA patients and asymptomatic volunteers. METHOD: MR images of 24 subjects (age range: 50-67 years, 12 male), including 12 patients with mild osteoarthritis (OA) (Kellgren-Lawrence (KL) = 1, 2) and 12 asymptomatic volunteers, were acquired using a 3 T clinical MRI system. Morphological assessment was performed using semiquantitative MRI OA Knee Score (MOAKS). Adiabatic T1ρ and T2ρ (AdT1ρ, AdT2ρ) relaxation time maps were calculated in regions of interest (ROIs) containing medial and lateral horns of menisci. The median relaxation time values of the ROIs were compared between subjects classified based on radiographic findings and MOAKS evaluations. RESULTS: MOAKS assessment of patients and volunteers indicated the presence of meniscal and cartilage lesions in both groups. For the combined cohort group, prolonged AdT1ρ was observed in the posterior horn of the medial meniscus (PHMED) in subjects with MOAKS meniscal tear (P < 0.05). AdT2ρ was statistically significantly longer in PHMED of subjects with MOAKS full-thickness cartilage loss (P < 0.05). After adjusting for multiple comparisons, differences in medians of observed AdT1ρ and AdT2ρ values between mild OA patients and asymptomatic volunteers did not reach statistical significance. CONCLUSION: AdT1ρ and AdT2ρ measurements have the potential to identify changes in structural composition of meniscus tissue associated with meniscal tear and cartilage loss in a cohort group of mild OA patients and asymptomatic volunteers.

Effect of collagen cross-linking on quantitative MRI parameters of articular cartilage.

OBJECTIVE: To investigate the sensitivity of quantitative magnetic resonance imaging (MRI) parameters to increase of collagen cross-linking in articular cartilage, a factor possibly contributing to the aging-related development of osteoarthritis (OA). The issue has not been widely studied although collagen cross-links may significantly affect the evaluation of cartilage imaging outcome. DESIGN: Osteochondral samples (n = 14) were prepared from seven bovine patellae. To induce cross-linking, seven samples were incubated in threose while the other seven served as non-treated controls. The specimens were scanned at 9.4 T for T1, T1Gd (dGEMRIC), T2, adiabatic and continuous wave (CW) T1ρ, adiabatic T2ρ and T1sat relaxation times. Specimens from adjacent tissue were identically treated and used for reference to determine biomechanical properties, collagen, proteoglycan and cross-link contents, fixed charge density (FCD), collagen fibril anisotropy and water concentration of cartilage. RESULTS: In the threose-treated sample group, cross-links (pentosidine, lysyl pyridinoline (LP)), FCD and equilibrium modulus were significantly (P < 0.05) higher as compared to the non-treated group. Threose treatment resulted in significantly greater T1Gd relaxation time constant (+26%, P < 0.05), although proteoglycan content was not altered. Adiabatic and CW-T1ρ were also significantly increased (+16%, +28%, P < 0.05) while pre-contrast T1 was significantly decreased (-10%, P < 0.05) in the threose group. T2, T2ρ and T1sat did not change significantly. CONCLUSION: Threose treatment induced collagen cross-linking and changes in the properties of articular cartilage, which were detected by T1, T1Gd and T1ρ relaxation time constants. Cross-linking should be considered especially when interpreting the outcome of contrast-enhanced MRI in aging populations.

Capturing fast relaxing spins with SWIFT adiabatic rotating frame spin-lattice relaxation (T1ρ) mapping.

Rotating frame spin-lattice relaxation, with the characteristic time constant T1ρ, provides a means to access motion-restricted (slow) spin dynamics in MRI. As a result of their restricted motion, these spins are sometimes characterized by a short transverse relaxation time constant T2 and thus can be difficult to detect directly with conventional image acquisition techniques. Here, we introduce an approach for three-dimensional adiabatic T1ρ mapping based on a magnetization-prepared sweep imaging with Fourier transformation (MP-SWIFT) sequence, which captures signal from almost all water spin populations, including the extremely fast relaxing pool. A semi-analytical procedure for T1ρ mapping is described. Experiments on phantoms and musculoskeletal tissue specimens (tendon, articular and epiphyseal cartilages) were performed at 9.4 T for both the MP-SWIFT and fast spin echo (FSE) read outs. In the phantom with liquids having fast molecular tumbling and a single-valued T1ρ time constant, the measured T1ρ values obtained with MP-SWIFT and FSE were similar. Conversely, in normal musculoskeletal tissues, T1ρ values measured with MP-SWIFT were much shorter than the values obtained with FSE. Studies of biological tissue specimens demonstrated that T1ρ-weighted SWIFT provides higher contrast between normal and diseased tissues relative to conventional acquisitions. Adiabatic T1ρ mapping with SWIFT readout captures contributions from the otherwise undetected fast relaxing spins, allowing more informative T1ρ measurements of normal and diseased states.

Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis.

OBJECTIVE: Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage. DESIGN: Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically. RESULTS: Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge. CONCLUSIONS: Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC.

Adiabatic rotating frame relaxation of MRI reveals early cartilage degeneration in a rabbit model of anterior cruciate ligament transection.

OBJECTIVE: To investigate the sensitivity of seven quantitative magnetic resonance imaging (MRI) parameters (adiabatic T1ρ, adiabatic T2ρ, continuous wave (CW) T1ρ, relaxation along a fictitious field (RAFF), T2 measured with adiabatic double echo (DE) and Carr-Purcell-Meiboom-Gill (CPMG) sequence, and T1 during off-resonance saturation [magnetization transfer (MT)]) to detect early osteoarthritic changes in a rabbit model of anterior cruciate ligament transection (ACLT). METHODS: ACLT was unilaterally induced in the knees of New Zealand White rabbits (n = 8) while contralateral joints served as controls. Femoral condyles of the joints were harvested 4 weeks post-ACLT. MRI was performed at 9.4 T. For reference, quantitative histology, Mankin grading and biomechanical measurements were conducted. RESULTS: Reference methods demonstrated early, superficial cartilage degeneration in the ACLT group, including significant loss of proteoglycans in both medial and lateral compartments, increased collagen fibril anisotropy in the lateral condyle and decreased biomechanical properties at both medial and lateral compartments. CW-T1ρ was prolonged in the lateral compartment of ACLT joints while adiabatic T1ρ and T2ρ detected degenerative changes in tissue in both lateral and medial condyles (P < 0.05). DE-T2 was significantly (P < 0.05) elevated only in the lateral compartment while CPMG-T2, MT or RAFF did not show a statistically significant difference between the groups. CONCLUSIONS: Adiabatic T1ρ and T2ρ relaxation times detected most sensitively early degenerative changes in cartilage 4 weeks post-ACLT in a rabbit model.

Diffusion of Gd-DTPA²â» into articular cartilage.

OBJECTIVES: The delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) technique is a method proposed for non-invasive measurement of cartilage glycosaminoglycan (GAG) content. In this method, gadopentetate (Gd-DTPA²â») is assumed to distribute in cartilage in inverse relation to the GAG distribution, thus allowing quantification of the GAG content. For accurate GAG quantification, the kinetics of Gd-DTPA²â» in articular cartilage is of critical importance. However, the diffusion of Gd-DTPA²â» has not been systematically studied over long time periods using MRI-feasible gadopentetate concentrations. Thus, the present study aims to investigate the diffusion of gadopentetate into cartilage in vitro in intact and enzymatically degraded cartilage. METHODS: The diffusion of gadopentetate into bovine articular cartilage was investigated at 9.4 T over 18-h time period using repeated T(1) measurements in two models, (1) comparing intact and trypsin-treated tissue and (2) assessing the effect of penetration direction. The diffusion process was further assessed by determining the gadopentetate flux and diffusivity. The results were compared with histological and biochemical reference methods. RESULTS AND CONCLUSIONS: The results revealed that passive diffusion of Gd-DTPA²â» was significantly slower than previously assumed, leading to overestimation of the GAG content at equilibrating times of few hours. Moreover, Gd-DTPA²â» distribution was found to depend not only on GAG content, but also on collagen content and diffusion direction. Interestingly, the dGEMRIC technique was found to be most sensitive to cartilage degradation in the early stages of diffusion process, suggesting that full equilibrium between gadopentetate and cartilage may not be required in order to detect cartilage degeneration.

Mechanical characterization of articular cartilage by combining magnetic resonance imaging and finite-element analysis: a potential functional imaging technique.

Magnetic resonance imaging (MRI) provides a method for non-invasive characterization of cartilage composition and structure. We aimed to see whether T(1) and T(2) relaxation times are related to proteoglycan (PG) and collagen-specific mechanical properties of articular cartilage. Specifically, we analyzed whether variations in the depthwise collagen orientation, as assessed by the laminae obtained from T(2) profiles, affect the mechanical characteristics of cartilage. After MRI and unconfined compression tests of human and bovine patellar cartilage samples, fibril-reinforced poroviscoelastic finite-element models (FEM), with depthwise collagen orientations implemented from quantitative T(2) maps (3 laminae for human, 3-7 laminae for bovine), were constructed to analyze the non-fibrillar matrix modulus (PG specific), fibril modulus (collagen specific) and permeability of the samples. In bovine cartilage, the non-fibrillar matrix modulus (R = -0.64, p < 0.05) as well as the initial permeability (R = 0.70, p < 0.05) correlated with T(1). In bovine cartilage, T(2) correlated positively with the initial fibril modulus (R = 0.62, p = 0.05). In human cartilage, the initial fibril modulus correlated negatively (R = -0.61, p < 0.05) with T(2). Based on the simulations, cartilage with a complex collagen architecture (5 or 7 laminae), leading to high bulk T(2) due to magic angle effects, provided higher compressive stiffness than tissue with a simple collagen architecture (3 laminae). Our results suggest that T(1) reflects PG-specific mechanical properties of cartilage. High T(2) is characteristic to soft cartilage with a classical collagen architecture. Contradictorily, high bulk T(2) can also be found in stiff cartilage with a multilaminar collagen fibril network. By emerging MRI and FEM, the present study establishes a step toward functional imaging of articular cartilage.

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

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.

T2 relaxation time and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of human patellar cartilage at 1.5 T and 9.4 T: Relationships with tissue mechanical properties.

Quantitative magnetic resonance imaging (MRI) techniques have been developed for noninvasive assessment of the structure of articular cartilage. T2 relaxation time is sensitive to the integrity and orientation of the collagen network, while T1 relaxation time in presence of Gd-DTPA2- (dGEMRIC) reflects the proteoglycan content of cartilage. In the present study, human patellar cartilage samples were investigated in vitro to determine the ability of MRI parameters to reveal topographical variations and to predict mechanical properties of cartilage at two different field strengths. T2 and dGEMRIC measurements at 1.5 T and 9.4 T were correlated with the static and dynamic compressive moduli at six anatomical locations of the patellar surface. Statistically significant linear correlations were observed between MRI and mechanical parameters at both field strengths, especially between T2 and Young's modulus. No significant difference was found between the T2 measurements at different field strengths in predicting mechanical properties of the tissue. Topographical variation of T2 values at both field strengths was similar to that of Young's moduli. The current results demonstrate the feasibility of quantitative MRI, particularly T2 mapping, to reflect the mechanical properties of human patellar cartilage at both field strengths.

Proteoglycan and collagen sensitive MRI evaluation of normal and degenerated articular cartilage.

Quantitative magnetic resonance imaging (MRI) techniques have earlier been developed to characterize the structure and composition of articular cartilage. Particularly, Gd-DTPA(2-)-enhanced T1 imaging is sensitive to cartilage proteoglycan content, while T2 relaxation time mapping is indicative of the integrity and arrangement of the collagen network. However, the ability of these techniques to detect early osteoarthrotic changes in cartilage has not been demonstrated. In this study, normal and spontaneously degenerated bovine patellar cartilage samples (n=32) were investigated in vitro using the aforementioned techniques. For reference, mechanical, histological and biochemical properties of the adjacent tissue were determined, and a grading system, the cartilage quality index (CQI), was used to score the structural and functional integrity of each sample. As cartilage degeneration progressed, a statistically significant increase in the superficial T2 (r=0.494, p<0.05) and a decrease in superficial and bulk T1 in the presence of Gd-DTPA(2-) (r=-0.681 and -0.688 (p<0.05), respectively) were observed. Gd-DTPA(2-)-enhanced T1 imaging served as the best predictor of tissue integrity and accounted for about 50% of the variation in CQI. The present results reveal that changes in the quantitative MRI parameters studied are indicative of structural and compositional alterations as well as the mechanical impairment of spontaneously degenerated articular cartilage.

Estimation of mechanical properties of articular cartilage with MRI - dGEMRIC, T2 and T1 imaging in different species with variable stages of maturation.

BACKGROUND: Magnetic resonance imaging (MRI) is one of the most potential methods for non-invasive diagnosis of cartilage disorders. Several methods have been established for clinical use; T(1) relaxation time imaging with negatively charged contrast agent (delayed gadolinium enhanced MRI of cartilage, dGEMRIC) has been shown to be sensitive to proteoglycan (PG) content while T(2) relaxation time has been demonstrated to express properties of the collagen fibril network. The use of native T(1) relaxation time has received less attention. OBJECTIVE: In the present study, magnetic resonance (MR) parameters of different types of patellar cartilage were studied with respect to the mechanical properties of the tissue. The general usefulness of the parameters to predict mechanical properties was investigated using cartilage from different species and stages of maturation. METHODS: dGEMRIC, T(2) and native T(1) relaxation times of healthy mature human, juvenile porcine and juvenile bovine articular cartilage samples were measured at 9.4T at 25 degrees C. Mechanical properties (Young's modulus and dynamic modulus) of the samples were measured in unconfined compression using a material testing device. The relationships between MRI and mechanical parameters and potential differences between different types of tissues were tested statistically. RESULTS: Significant, but varying relationships were established between T(1) or T(2) relaxation time and mechanical properties, depending on tissue type. The values of mechanical parameters were in line with the results previously reported in the literature. Unexpectedly, dGEMRIC showed no statistically significant association with the mechanical properties. Variation in the assumption of native T(1) value did not induce significant differences in the calculated contrast agent concentration, and consequently did not affect prediction of mechanical properties. CONCLUSION: For patellae, a complex variation in the relationships between T(2) and mechanical properties in different groups was revealed. The results support the conclusion that juvenile animal tissue, exhibiting a highly complex collagenous architecture, may not always serve as a realistic model for mature human tissue with a typical three-zone network organization, and other than bulk metrics are required for the analysis of cartilage T(2). As the multilayered collagen network can strongly control the mechanical characteristics of juvenile tissue, it may mask the mechanical role of PGs and explain why dGEMRIC could not predict mechanical parameters in patellar cartilage.

T(2) relaxation time mapping reveals age- and species-related diversity of collagen network architecture in articular cartilage.

OBJECTIVE: The magnetic resonance imaging (MRI) parameter T(2) relaxation time has been shown to be sensitive to the collagen network architecture of articular cartilage. The aim of the study was to investigate the agreement of T(2) relaxation time mapping and polarized light microscopy (PLM) for the determination of histological properties (i.e., zone and fibril organization) of articular cartilage. METHODS: T(2) relaxation time was determined at 9.4 T field strength in healthy adult human, juvenile bovine and juvenile porcine patellar cartilage, and related to collagen anisotropy and fibril angle as measured by quantitative PLM. RESULTS: Both T(2) and PLM revealed a mutually consistent but varying number of collagen-associated laminae (3, 3-5 or 3-7 laminae in human, porcine and bovine cartilage, respectively). Up to 44% of the depth-wise variation in T(2) was accounted for by the changing anisotropy of collagen fibrils, confirming that T(2) contrast of articular cartilage is strongly affected by the collagen fibril anisotropy. A good correspondence was observed between the thickness of T(2)-laminae and collagenous zones as determined from PLM anisotropy measurements (r=0.91, r=0.95 and r=0.91 for human, bovine and porcine specimens, respectively). CONCLUSIONS: According to the present results, T(2) mapping is capable of detecting histological differences in cartilage collagen architecture among species, likely to be strongly related to the differences in maturation of the tissue. This diversity in the MRI appearance of healthy articular cartilage should also be recognized when using juvenile animal tissue as a model for mature human cartilage in experimental studies.

Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 characteristics of human knee articular cartilage: topographical variation and relationships to mechanical properties.

The macromolecular structure and mechanical properties of articular cartilage are interrelated and known to vary topographically in the human knee joint. To investigate the potential of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T1, and T2 mapping to elucidate these differences, full-thickness cartilage disks were prepared from six anatomical locations in nonarthritic human knee joints (N = 13). Young's modulus and the dynamic modulus at 1 Hz were determined with the use of unconfined compression tests, followed by quantitative MRI measurements at 9.4 Tesla. Mechanical tests revealed reproducible, statistically significant differences in moduli between the patella and the medial/lateral femoral condyles. Typically, femoral cartilage showed higher Young's (>1.0 MPa) and dynamic (>8 MPa) moduli than tibial or patellar cartilage (Young's modulus < 0.9 MPa, dynamic modulus < 8 MPa). dGEMRIC moderately reproduced the topographical variation in moduli. Additionally, T1, T2, and dGEMRIC revealed topographical differences that were not registered mechanically. The different MRI and mechanical parameters showed poor to excellent linear correlations, up to r = 0.87, at individual test sites. After all specimens were pooled, dGEMRIC was the best predictor of compressive stiffness (r = 0.57, N = 77). The results suggest that quantitative MRI can indirectly provide information on the mechanical properties of human knee articular cartilage, as well as the site-dependent variations of these properties. Investigators should consider the topographical variation in MRI parameters when conducting quantitative MRI of cartilage in vivo.