Relaxation anisotropy in cartilage by NMR microscopy (μMRI) at 14-μm resolution

To study the structural anisotropy and the magic-angle effect in articular cartilage, T₁, and T₂ images were constructed at a series of orientations of cartilage specimens in the magnetic field by using NMR microscopy (μMRI). An isotropic T₁, and a strong anisotropic T₂ were observed across the cartilage tissue thickness. Three distinct regions in the microscopic MR images corresponded approximately to the superficial, transitional, and radial histological zones in the cartilage. The percentage decrease of T₂ follows the pattern of the curve of (3cos²θ ? 1)² at the radial zone, where the collagen fibrils are perpendicular to the articular surface. In contrast, little orientational dependence of T₂ was observed at the transitional zone, where the collagen fibrils are more randomly oriented. The result suggests that the interactions between water molecules and proteoglycans have a directional nature, which is somehow influenced by collagen fibril orientation. Hence, T₂ anisotropy could serve as a sensitive and noninvasive marker for molecular-level orientations in articular cartilage.     

Further studies on the anisotropic distribution of collagen in articular cartilage by μMRI

To further study the anisotropic distribution of the collagen matrix in articular cartilage, microscopic magnetic resonance imaging experiments were carried out on articular cartilages from the central load‐bearing area of three canine humeral heads at 13 μm resolution across the depth of tissue. Quantitative T₂ images were acquired when the tissue blocks were rotated, relative to B₀, along two orthogonal directions, both perpendicular to the normal axis of the articular surface. The T₂ relaxation rate (R₂) was modeled, by three fibril structural configurations (solid cone, funnel, and fan), to represent the anisotropy of the collagen fibrils in cartilage from the articular surface to the cartilage/bone interface. A set of complex and depth‐dependent characteristics of collagen distribution was found in articular cartilage. In particular, there were two anisotropic components in the superficial zone and an asymmetrical component in the radial zone of cartilage. A complex model of the three‐dimensional fibril architecture in articular cartilage is proposed, which has a leaf‐like or layer‐like structure in the radial zone, arises in a radial manner from the subchondral bone, spreads and arches passing the isotropic transitional zone, and exhibits two distinct anisotropic components (vertical and transverse) in the surface portion of the tissue. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Reduction of residual dipolar interaction in cartilage by spin‐lock technique

The influence of radiofrequency (RF) spin‐lock pulse on the laminar appearance of articular cartilage in MR images was investigated. Spin‐lock MRI experiments were performed on bovine cartilage plugs on a 4.7 Tesla small‐bore MRI scanner, and on human knee cartilage in vivo on a 1.5 Tesla clinical scanner. When the normal to the surface of cartilage was parallel to B₀, a typical laminar appearence was exhibited in T₂‐weighted images of cartilage plugs, but was absent in T_1ρ‐weighted images of the same plugs. At the “magic angle” orientation (when the normal to the surface of cartilage was 54.7° with respect to B₀), neither the T₂ nor the T_1ρ images demonstrated laminae. At the same time, T_1ρ values were greater than T₂ at both orientations throughout the cartilage. T_1ρ dispersion (i.e., the dependence of the relaxation rate on the spin‐lock frequency ω₁) was observed, which reached a steady‐state value of close to 2 kHz in both parallel and magic‐angle orientations. These results suggest that residual dipolar interaction from motionally‐restricted water and relaxation processes, such as chemical exchange, contribute to T_1ρ dispersion in cartilage. Further, one can reduce the laminar appearance in human articular cartilage by applying spin‐lock RF pulses, which may lead to a more accurate diagnosis of degenerative changes in cartilage. Magn Reson Med 52:1103–1109, 2004. © 2004 Wiley‐Liss, Inc.     

Angle‐sensitive MRI for quantitative analysis of fiber‐network deformations in compressed cartilage

Purpose

To demonstrate the feasibility of a novel experimental method to quantitatively analyze fiber‐network deformation in compressed cartilage by angle‐sensitive magnetic resonance imaging (MRI) of cartilage.

Methods

Three knee cartilage samples of an adult sheep were imaged in a high‐resolution MRI scanner at 7 T. Main fiber orientation and its “offset” from the direction perpendicular to the bone‐cartilage boundary were derived from MR images taken at different orientations with respect to B₀. Bending of the collagen fibers was determined from weight‐bearing MRI with the load (up to 1.0 MPa) applied over the whole sample surface. A “fascicle” model of the cartilage ultrastructure was assumed to analyze characteristic intensity variations in T₂‐weighted images under load.

Results

T₂‐weighted MR images showed a strong variation of the signal intensities with sample orientation. In the T₂‐weighted weight‐bearing series, regions of high signal intensity underwent shifts from the lateral to the central parts in all three cartilage samples. The bending of the collagen fibers was determined to be 27.2°, 35.4°, and 40.0° per MPa, respectively.

Conclusion

Assuming a “fascicle” model, the presented MRI method provides quantitative measures of structural adjustments in compressed cartilage. Our preliminary analysis suggests that cartilage fiber deformation includes both bending and crimping.     

A method for generating magnetic resonance microimaging T2 maps with low sensitivity to diffusion

Generating T₂ maps in magnetic resonance microimaging is often complicated by the self-diffusion of water molecules. A modification of the standard spin-echo pulse sequence is proposed which minimizes this effect. Experiments with doped water confirmed that the T₂ values obtained with the modified sequence were equal within the experimental error to the value obtained by the spectroscopic Carr-Purcell-Meiboom-Gill method. The applicability of the technique is demonstrated by generating T₂ maps of porcine articular cartilage. Key words: MR microimaging; relaxation; diffusion; cartilage.     

Influence of knee positions on T2, T*2, and dGEMRIC mapping in porcine knee cartilage

We examined the influence of flexed knee positions on cartilage MR assessments. Sagittal T₂, T*₂, and delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) maps of the femoral cartilage were obtained in eight 6‐month‐old porcine femorotibial joints in the extended knee position (position A: flexion 0° and femoral shaft in parallel with the amplitude of static field), flexed knee position (position B: flexion 40° and femoral shaft oriented at 40° to the amplitude of static field), and oblique‐placed knee‐extended position (position C: flexion 0° and femoral shaft oriented at 40° to the amplitude of static field). Comparison of the MR parameters between positions A and C showed isolated influence of the magic‐angle effect, and comparison between positions A and B showed effects of knee flexion. Proteoglycan and hydroxyproline content in cartilage specimen at each region of interest had no significant correlation with T₂, T*₂, and dGEMRIC values. At the central zone, located on a weight‐bearing area and parallel to the amplitude of static field, T₂/T*₂/dGEMRIC values increased by 6.8/11/0.8% at position C and by 24/44/31% at position B compared with position A. There was a significant increase in T₂ and T*₂ values at position B compared with those at position A. The substantial changes in T₂, T*₂, and dGEMRIC were shown in response to knee flexion, presumably due to the compounding influence of the magic‐angle effect and change in the intra‐articular biomechanical condition. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Magnetic resonance imaging reflects cartilage proteoglycan degradation in the rabbit knee

Cartilage degeneration in osteoarthritis is initiated by a loss of proteoglycan. Intra-articular injection of papain causes a reversible loss of proteoglycan in rabbit knees. Rabbits were scanned with magnetic resonance imaging (MRI), using a 1.5T Signa superconducting magnet with 3 inch surface coil. Spin echo sequences were performed in the coronal and sagittal planes at 0, 24, 48, and 72 h after intra-articular injection of papain to obtain T₁, proton density, and T₂-weighted images. Cartilage proteoglycan content was measured biochemically and histochemically. Reduced articular cartilage thickness in the MR images of papain-treated knees corresponded to changes in cartilage proteoglycan content.     

Kinematic biomechanical assessment of human articular cartilage transplants in the knee using 3-T MRI: an in vivo reproducibility study

The aims of this study were to examine the clinical feasibility and reproducibility of kinematic MR imaging with respect to changes in T ₂ in the femoral condyle articular cartilage. We used a flexible knee coil, which allows acquisition of data in different positions from 40° flexion to full extension during MR examinations. The reproducibility of T ₂ measurements was evaluated for inter-rater and inter-individual variability and determined as a coefficient of variation (CV) for each volunteer and rater. Three different volunteers were measured twice and regions of interest (ROIs) were selected by three raters at different time points. To prove the clinical feasibility of this method, 20 subjects (10 patients and 10 age- and sex-matched volunteers) were enrolled in the study. Inter-rater variability ranged from 2 to 9 and from 2 to 10% in the deep and superficial zones, respectively. Mean inter-individual variability was 7% for both zones. Different T ₂ values were observed in the superficial cartilage zone of patients compared with volunteers. Since repair tissue showed a different behavior in the contact zone compared with healthy cartilage, a possible marker for improved evaluation of repair tissue quality after matrix-associated autologous chondrocyte transplantation (MACT) may be available and may allow biomechanical assessment of cartilage transplants.     

An MRI method for measuring T2 in the presence of static and RF magnetic field Inhomogeneities

A magnetic resonance imaging method for measuring the T₂ relaxation time constant is proposed. It is based on the assumption that, under very general conditions, the MR signal near a spin echo has a special symmetry arising from the refocusing nature of the 180° RF pulse. A gradient echo sampling of the spin echo (GESSE) sequence is implemented to evaluate T₂ by collecting multiple gradient echoes before and after the spin echo. This approach is a modification of the GESFIDE sequence proposed by Ma and Wehrli. However, our approach compares images that are not separated by any RF pulses and, as a result, is insensitive to slice profile imperfections. In addition, the calculated T₂ value does not rely on any special assumptions about the MRI signal behavior in the presence of an inhomogeneous static magnetic field and, hence, is insensitive to the presence of static magnetic field inhomogeneities.     

MR microscopy of articular cartilage at 1.5 T: orientation and site dependence of laminar structures

OBJECTIVE: To evaluate MR microscopic images of normal-appearing porcine hyaline cartilage ( n=15) in vitro obtained with an MR microscope using an independent console system (MRMICS) at 1.5 T. DESIGN AND RESULTS: The MRMICS is a portable imaging system consisting of a radiofrequency system, gradient power supplies and a personal computer. The images from the MRMICS showed a laminar structure of porcine cartilage similar to the structure demonstrated with other MR imaging techniques. The laminar structures of the articular cartilage, were, however heterogeneous in respect of signal intensity and thickness, which varied according to the site resected. The MR laminar appearance was most comparable to the staining with Masson's trichrome for collagen. CONCLUSION: MRMICS is a useful add-on system for obtaining microscopic MR images of articular cartilage in vitro.     

Basic physics of nuclear magnetic resonance

This review of basic physics of nuclear magnetic resonance (NMR) discusses precession of magnetic nuclei in a static external field, introduces the concept of the rotating frame, and describes excitation of nuclei by an RF field. Treats subject of T₁ and T₂ relaxation from the dual viewpoints of (1) phenomena of relaxation times for both the longitudinal and transverse magnetization and (2) relaxation resulting from local field fluctuations. It describes practical ways in which T₁ and T₂ are measured (i.e., inversion recovery and spin-echo) and gives the value of the nuclear magnetization in thermodynamic equilibrium with a static external field. It discusses the reduction of NMR signal resulting from saturation. These concepts are related to clinical use with a set of four spin-echo images of a human head.     

Short TE MR Microscopy: Accurate measurement and zonal differentiation of normal hyaline cartilage

The purpose of this study was to use MR imaging to accurately measure the thickness of hyaline cartilage and determine the MR contrast parameters for differentiation of cartilage zones in normal human cartilage samples. Cartilage samples were examined using three dimensional spin-echo MR microscopy at 9.4 T with a voxel size of 31 × 31 × 300 μm. Effects of T₂ signal loss, susceptibility, and partial volume on measured thickness of cartilage were investigated. Thickness measurements were obtained on corresponding histological sections for comparison. Optimal contrast parameters for delineation of cartilage zones were evaluated using magnetization transfer, inversion recovery, T₁, and T₂ contrast. T₂ relaxation losses were identified as the primary source of discrepancy between the measured thickness of cortical bone and hyaline cartilage. Good contrast for zonal differentiation was obtained using T₁ weighting. We conclude that images obtained using short TE MR microscopy can be used to accurately measure cartilage and bone thickness in human specimens, and can demonstrate zones within normal cartilage.     

Orientation-dependent changes in MR signal intensity of articular cartilage: a manifestation of the “magic angle” effect

Objective: To study magnetic resonance (MR) imaging pattern of normal hyaline articular cartilage in the knee joint with regard to the contribution of the “magic angle” effect to the MR signal. Design. Thirty-two healthy volunteers were imaged in a standard supine position in a 1.5-T unit using spin echo and gradient echo sequences. Nine volunteers were reimaged with the knee flexed. The signal behavior of the hyaline cartilage of the femoral condyles was evaluated qualitatively and quantitatively. The extended and flexed positions of the nine volunteers were compared. Results. A superficial and a deep hyperintense layer and a hypointense middle cartilage layer were observed. Segments of increased signal intensity were visible along the condyles; a magic angle effect on signal intensity was evident in the hypointense middle layer with both gradient echo and spin echo images. Conclusion. The MR signal behavior of hyaline cartilage is influenced by the alignment of the collagen fibers within the cartilage in relation to the magnetic field. Failure to recognize this effect may lead to inaccurate diagnosis.     

Diffusion and relaxation mapping of cartilage-bone plugs and excised disks using microscopic magnetic resonance imaging

Spatially resolved maps of proton self-diffusion coefficients (D) and relaxation times (T₁ and T₂) were obtained on cartilage-bone plug samples and on excised disks of canine cartilage at a transverse resolution of 30 μm, using microscopic magnetic resonance imaging (micro-MRI). Results are compared for excised disks of cartilage and intact cartilage-bone plugs. Correlations between the absolute water concentration, the self-diffusion coefficient and the T₁ relaxation are reported. The diffusion coefficient is not a linear function of water concentration. The thickness of the disks is 600 μm, compared with the ca. 900 μm observed for the cartilage-bone plugs, presumably due to the absence of the interfacial or tidemark layer of interdigitated cartilage and bone in the former samples. Our results suggest that excised disks of cartilage are excellent models for the articular surface and the first 500 or so microns of tissue. The molecular parameters of spin-spin and spin-lattice relaxation times, as well as the water self-diffusion coefficient, are virtually identical in the two types of samples. However, the cartilage-bone plugs have the additional feature of permitting the study of the tidemark region, a region that likely plays a major role in the transmission of mechanical force.     

Anisotropy of NMR properties of tissues

Orientational anisotropy of T₂ and T₁ relaxation times, diffusion, and magnetization transfer has been investigated for six different tissues: tendon, cartilage, kidney, muscle, white matter, and optic nerve. Relaxation anisotropy was observed for tendon and cartilage, and diffusional anisotropy was measured in kidney, muscle, white matter, and optic nerve. All other NMR measurements of these tissues showed no orientational dependence. This pattern of NMR anisotropies can be interpreted from the underlying geometrical structures of the tissues.     

Comparison of MRI T2 Relaxation Changes of Knee Articular Cartilage before and after Running between Young and Old Amateur Athletes

ObjectiveTo compare changes in T2 relaxation on magnetic resonance (MR) images of knee articular cartilage in younger and older amateur athletes before and after running.ResultsChanges in global cartilage T2 values after running did not differ significantly between the age groups. In terms of the depth variation, relatively higher T2 values in the older group than in the younger group were observed mainly in the superficial layers of the femoral and tibial cartilage (p < 0.05).ConclusionAge-related cartilage changes may occur mainly in the superficial layer of cartilage where collagen matrix degeneration is primarily initiated. However, no trend is observed regarding a global T2 changes between the younger and older age groups in response to exercise.     

In Vivo sodium multiple quantum spectroscopy of human articular cartilage

The authors report, for the first time, sodium properties of human articular cartilage in vivo using sodium multiple-quantum-filtered methods with a surface coil. A flip angle-independent, phase-cycled pulse sequence was used to obtain triple-quantum-filtered spectra as a function of preparation time. Biexponential relaxation rates were calculated by fitting the triple-quantum-filtered spectral amplitudes to a theoretical expression. Theoretical analysis of the flip angle dependence of even rank two-quantum coherence (T₂²), odd rank two-quantum coherence (T₂³), and triple-quantum coherence are presented and verified against experimental results on a cartilage specimen. Sodium multiple-quantum-filtered spectral lineshapes obtained in vivo correlate well with those observed on in vivo specimens. Relaxation rates obtained from asymptomatic volunteers were found to be: T_2rise= 1.0 ± 0.12 ms, T_2decay= 12.0 ± 0.75 ms (mean ± SD). The diagnostic potential of this method in detecting early changes in articular cartilage is described.     

Three-Dimensional NMR microscopy of rat spleen and liver

Three-dimensional microscopic NMR images of spleen and liver specimens from rats injected wlth dextran magnetite particles and from controls were obtained at 4.7 T, using a specially designed probe in conjunction with a 3D filtered back projection reconstruction algorithm. All of the images were reconstructed as 64³ arrays with (25 μm)³ isotropic voxels. With the aid of the MR contrast agent, the red pulp and marginal zone of the spleen and the portal triad of the liver could be distinguished from the surrounding tissue in T₂-weighted images. For mature rat spleen, natural contrast in T₂-weighted images was found to distinguish the same features. Histolog-ical examinations of the tissues with and without contrast agent were also performed using an optical microscope. Microscoplc NMR images, despite their lower resolution, clearly revealed many features seen in the optical images.     

23Na and 2H magnetic resonance studies of osteoarthritic and osteoporotic articular cartilage

In this study, the short component of the ²³Na T₂ (T_2f) and the ²³Na and ²H quadrupolar interactions (ν_Q) were measured in bone‐cartilage samples of osteoarthritic (OA) and osteoporotic (OP) patients. ²³Na ν_Q was found to increase in osteoarthritic articular cartilage relative to controls. Similar results were found in bovine cartilage following proteoglycan (PG) depletion, a condition that prevails in osteoarthritis. ²³Na ν_Q and 1/T_2f for articular cartilage obtained from osteoporotic patients were significantly larger than for control and osteoarthritic cartilage. Decalcification of both human and bovine articular cartilage resulted in an increase of ²³Na ν_Q and 1/T_2f, showing the same trend as the osteoporotic samples. Differences in the ratio of the intensity of the large ²H splitting to that of the small one in the calcified zone were also observed. In osteoporosis, this ratio was twice as large as that obtained for both control and osteoarthritic samples. The ²H and ²³Na results can be interpreted as due to sodium ions and water molecules filling the void created by the calcium depletion and to calcium ions being located in close association with the collagen fibers. To the best of our knowledge, this is the first study reporting differences of NMR parameters in cartilage of osteoporotic patients. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

T1ρ MRI quantification of arthroscopically confirmed cartilage degeneration

Nine asymptomatic subjects and six patients underwent T₁ρ MRI to determine whether Outerbridge grade 1 or 2 cartilage degeneration observed during arthroscopy could be detected noninvasively. MRI was performed 2‐3 months postarthroscopy, using sagittal T₁‐weighted and axial and coronal T₁ρ MRI, from which spatial T₁ρ relaxation maps were calculated from segmented T₁‐weighted images. Median T₁ρ relaxation times of patients with arthroscopically documented cartilage degeneration and asymptomatic subjects were significantly different (P < 0.001), and median T₁ρ exceeded asymptomatic articular cartilage median T₁ρ by 2.5 to 9.2 ms. In eight observations of mild cartilage degeneration at arthroscopy (Outerbridge grades 1 and 2), mean compartment T₁ρ was elevated in five, but in all observations, large foci of increased T₁ρ were observed. It was determined that T₁ρ could detect some, but not all, Outerbridge grade 1 and 2 cartilage degeneration but that a larger patient population is needed to determine the sensitivity to these changes. Magn Reson Med 63:1376–1382, 2010. © 2010 Wiley‐Liss, Inc.