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.     

Imaging the physical and morphological properties of a multi-zone young articular cartilage at microscopic resolution

PURPOSE: To characterize a number of physical and morphologic properties of young articular cartilage. These properties include the anisotropy of T(2) relaxation, optical retardation, orientation of the collagen fibrils, total thickness of the tissue, number of histologic sub-zones in the tissue, width of individual sub-zones, and correlation between the depths of the local T(2) maxima and the local retardation minima. MATERIALS AND METHODS: Microscopic magnetic resonance imaging (mciro MRI) and polarized light microscopy (PLM) were used to examine three side-by-side specimens from a humeral head of a three-month-old beagle that exhibited a unique topographic heterogeneity from three-zones centrally to multi-zone peripherally. RESULTS: The centrally located specimen showed that the collagen fibrils across the tissue depth have a pattern of the classic three histologic sub-zones (tangential, transitional, and radial). A much more complicated multi-zone structure was found in the specimen located peripherally, with a second transitional zone and a second tangential zone located at the deep part of the tissue. We also showed that the orientation of the collagen fibrils that form the cocoon-shaped territorial matrix surrounding the clusters of chondrocytes can be imaged by our PLM technique. CONCLUSION: The results from the young animal in this report, together with our observations from older animals, demonstrate that MRI and PLM can be used to study the epiphyseal expansion of cartilage in young animals during its growth and subsequent loss in older animals. An illustrative model for the structure of collagen fibrils in a humeral head is suggested as an extension to the classic three-zone model for young articular cartilage.     

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.     

MR-microscopic visualization of anisotropic internal cartilage structures using the magic angle technique

NMR microscopic studies of articular cartilage at 7.1 T are presented. Using a special experimental design, T₂-weighted spin-echo images of cartilage-bone plugs were taken under variable angles with respect to the static magnetic field B_o to visualize the angular-dependent representation of internal matrix structures mediated by the collagen network arrangement. To quantify the observed orientational effect in the MR images, exact measurements of the transverse relaxation time T₂ were taken using the CPMG sequence. The NMR experiments show the strong influence of the cartilage orientation with respect to the static magnetic field on the inhomogeneous appearance of the articular cartilage in the MR image. Additionally performed polarization light microscopic investigations demonstrate the direct relation between the oriented collagenous structures and the anisotropic regions observed in the MR images. A simple cartilage matrix model derived from the experimental findings is proposed, and consequences for the clinical assessment of the articular joint are discussed.     

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.     

T1ρ-relaxation in articular cartilage: Effects of enzymatic degradation

Spin-lattice relaxation in the rotating frame (T_1ρ) dispersion spectroscopy and imaging were used to study normal and enzymatically degraded bovine articular cartilage. Normal specimens demonstrate significant T_1ρ “dispersion” (～60 to ～130 ms) in the 100 Hz to 9 kHz frequency range. Proteoglycan-degraded specimens have 33% greater T_1ρ values than collagen-degraded or normal samples. T_1ρ-weighted images reveal structure not found in conventional T₁-or T₂-weighted images. Our results suggest that T_1ρ measurements are selectively sensitive to proteoglycan content. The potential of this method in distinguishing the early degenerative changes in cartilage associated with osteoarthritis is discussed.     

Orientational dependence of T2 relaxation in articular cartilage: A microscopic MRI (microMRI) study.

The experiments reported herein are the first MRI investigations of the orientational dependence of T(2) relaxation in articular cartilage at microscopic resolution over the 360 degrees angular space. For each of six canine cartilage specimens, 48 independent T(2)-weighted proton images were acquired for 12 different specimen orientations. Pixel-wise monoexponential fits of these proton images produced 12 T(2) relaxation images, each with an in-plane pixel resolution of 13.7 microm. Cartilage T(2) as a function of specimen orientation was shown to follow approximately the angular dependence of the nuclear dipole-dipole interaction, with local maxima at approximately 55 degrees, 125 degrees, 235 degrees, and 305 degrees. However, the relative amplitudes of the T(2) maxima deviated somewhat from those expected from the dipolar interaction. The amplitudes of these maxima also varied with tissue depth: the largest amplitudes were found in the radial zone, intermediate amplitudes were found in the superficial zone, and there was a continuous decrease in amplitude approaching the transitional zone from the superficial zone above and the radial zone below. We explain the discrepancy between the observed T(2) anisotropy and the angular dependence of the dipolar interaction by means of a simple model which considers the average of one isotropic and two anisotropic spin populations-the first being associated with "free" water, and the latter two arising from collagen-associated waters. We show that even for the "long" T(2) components, which arise in multiple-compartment studies of collagen-water systems, there appears to be two subpopulations. Each has the same peak value of T(2), but the angular dependence of one is shifted in phase by 90 degrees relative to the other by virtue of the fact that each is associated with groups of mutually perpendicular fibrils.     

Mapping the fiber orientation in articular cartilage at rest and under pressure studied by 2H double quantum filtered MRI.

The one-dimensional (2)H double quantum filtered (DQF) spectroscopic imaging technique was used to study the orientation of collagen fibers in articular cartilage. The method detects only water molecules in anisotropic environments, which in cartilage is caused by their interaction with the collagen fibers. A large quadrupolar splitting was observed in the calcified zone and a smaller splitting in the radial zone. In the transitional zone the splitting was not resolved and a small splitting was again detected in the superficial zone. From measurements performed at two orientations of the plug relative to the magnetic field it was deduced that in the calcified and radial zones the fibers are oriented perpendicular to the bone, bending at the transitional zone and flattening at the superficial zone. The effect of load applied to the cartilage-bone plug was monitored by the same technique. At low loads there is a small decrease in the quadrupolar splitting in the calcified zone, a marked decrease in the radial zone, and an increase of the splitting accompanied by a thickening of the superficial zone. Under high loads, while the thickening and the splitting of the superficial zone further increase, the splitting in the radial and calcified zones completely collapse. Pressure-induced changes in the thickness of the surface zone indicate flattening of the collagen fibers near the surface. The marked collapse of the splitting near the bone at high pressures may result from crimping of the collagen fibers.     

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.     

In vivo MRI of cartilage pathogenesis in surgical models of osteoarthritis

Objective To examine in vivo time-course changes in macromolecular composition of articular cartilage in two surgical models of osteoarthritis (goat: meniscal transection and cartilage incision; rabbit: medial meniscectomy).Design Collagen integrity and proteoglycan (PG) content were evaluated in both models by magnetization transfer (MT) and contrast-enhanced MRI, respectively. The MT rate k _m for the exchange process between the bulk water and water bound to collagen was determined as a marker of the collagen network. Local changes in cartilage fixed charge density, i.e., where PGs are depleted, were derived from T₁ relaxation maps as obtained after an infusion of Gd(DTPA)²⁻, a paramagnetic agent.Results In the goat model, the MT rate constant k _m was significantly higher at 2 weeks post surgery, a possible sign of cartilage swelling, then decreased below baseline values, most likely indicative of disruption in the collagen framework. Meanwhile, post-Gd(DTPA)²⁻ MRI acquisition indicated a significant and sustained loss of PGs. The rabbit model produced milder lesions. Although the difference was non-significant, k _m steadily decreased in response to the surgical insult while kinetics of Gd(DTPA)²⁻ uptake, after reaching a peak level at 6 weeks, were back to normal values after 12 weeks.Conclusion In the goat model, joint instability and cartilage damage was a permanent trigger for cartilage degeneration producing MRI changes. However, biomechanical stress due to partial medial meniscectomy in knees of mature rabbits produced only mild, focal lesions and PG depletion that was partially reversible. This proof-of-concept study identified MT and T₁ parameters as useful surrogate markers in animal models of osteoarthritis.     

T1ρ MRI of human musculoskeletal system

Magnetic resonance imaging (MRI) offers the direct visualization of the human musculoskeletal (MSK) system, especially all diarthrodial tissues including cartilage, bone, menisci, ligaments, tendon, hip, synovium, etc. Conventional MRI techniques based on T₁‐ and T₂‐weighted, proton density (PD) contrast are inconclusive in quantifying early biochemically degenerative changes in MSK system in general and articular cartilage in particular. In recent years, quantitative MR parameter mapping techniques have been used to quantify the biochemical changes in articular cartilage, with a special emphasis on evaluating joint injury, cartilage degeneration, and soft tissue repair. In this article we focus on cartilage biochemical composition, basic principles of T_1ρ MRI, implementation of T_1ρ pulse sequences, biochemical validation, and summarize the potential applications of the T_1ρ MRI technique in MSK diseases including osteoarthritis (OA), anterior cruciate ligament (ACL) injury, and knee joint repair. Finally, we also review the potential advantages, challenges, and future prospects of T_1ρ MRI for widespread clinical translation. J. Magn. Reson. Imaging 2015;41:586–600. © 2014 Wiley Periodicals, Inc.     

T1 assessment of hip joint cartilage following intra‐articular gadolinium injection: A pilot study

This pilot study defines the feasibility of cartilage assessment in symptomatic femoroacetabular impingement patients using intra‐articular delayed gadolinium‐enhanced MRI of cartilage (ia‐dGEMRIC). Nine patients were scanned preliminary to study the contrast infiltration process into hip joint cartilage. Twenty‐seven patients with symptomatic femoroacetabular impingement were subsequently scanned with intra‐articular delayed gadolinium‐enhanced MRI of cartilage. These T₁ findings were correlated to morphological findings. Zonal variations were studied. This pilot study demonstrates a significant difference between the pre‐ and postcontrast T₁ values (P < 0.001) remaining constant for 45 min. We noted higher mean T₁ values in morphologically normal‐appearing cartilage than in damaged cartilage, which was statistically significant for all zones except the anterior‐superior zone. Intraobserver (0.972) and interobserver correlation coefficients (0.933) were statistically significant. This study outlines the feasibility of intra‐articular delayed gadolinium‐enhanced MRI of cartilage for assessment of cartilage changes in patients with femoroacetabular impingement. It can also define the topographic extent and differing severities of cartilage damage. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Multicomponent T2* mapping of knee cartilage: Technical feasibility ex vivo

Disorganization of collagen fibers is a sign of early‐stage cartilage degeneration in osteoarthritic knees. Water molecules trapped within well‐organized collagen fibrils would be sensitive to collagen alterations. Multicomponent effective transverse relaxation (T₂*) mapping with ultrashort echo time acquisitions is here proposed to probe short T₂ relaxations in those trapped water molecules. Six human tibial plateau explants were scanned on a 3T MRI scanner using a home‐developed ultrashort echo time sequence with echo times optimized via Monte Carlo simulations. Time constants and component intensities of T₂* decays were calculated at individual pixels, using the nonnegative least squares algorithm. Four T₂*‐decay types were found: 99% of cartilage pixels having mono‐, bi‐, or nonexponential decay, and 1% showing triexponential decay. Short T₂* was mainly in 1‐6 ms, while long T₂* was ～22 ms. A map of decay types presented spatial distribution of these T₂* decays. These results showed the technical feasibility of multicomponent T₂* mapping on human knee cartilage explants. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

A B1‐insensitive high resolution 2D T1 mapping pulse sequence for dGEMRIC of the HIP at 3 Tesla

Early detection of cartilage degeneration in the hip may help prevent onset and progression of osteoarthritis in young patients with femoroacetabular impingement. Delayed gadolinium‐enhanced MRI of cartilage is sensitive to cartilage glycosaminoglycan loss and could serve as a diagnostic tool for early cartilage degeneration. We propose a new high resolution 2D T₁ mapping saturation–recovery pulse sequence with fast spin echo readout for delayed gadolinium‐enhanced magnetic resonance imaging of cartilage of the hip at 3 T. The proposed sequence was validated in a phantom and in 10 hips, using radial imaging planes, against a rigorous multipoint saturation–recovery pulse sequence with fast spin echo readout. T₁ measurements by the two pulse sequences were strongly correlated (R² > 0.95) and in excellent agreement (mean difference = ?8.7 ms; upper and lower 95% limits of agreement = 64.5 and ?81.9 ms, respectively). T₁ measurements were insensitive to B₁₊ variation as large as 20%, making the proposed T₁ mapping technique suitable for 3 T. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

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.     

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.     

Articular cartilage: correlation of histologic zones with signal intensity at MR imaging

Zones of high and low signal intensity on magnetic resonance (MR) images of articular cartilage were correlated with the four histologic zones normally found in such cartilage. Grossly normal articular cartilage from knees and ankles of a fresh cadaver were used in the study. The three zones identified on MR images included a low-intensity zone near the articular surface, a zone of higher signal intensity next to that, and a second zone of low intensity that was deep to the two others. The location of the superficial low-intensity zone corresponded to dense, tangentially oriented layers of collagen in the superficial histologic zone. Higher signal intensity deep to the superficial low-intensity zone correlated with cartilage in the transitional zone. The deep low-intensity zone correlated with a combination of deep radiate and calcified cartilage and cortical bone. Results of this study indicate that, with high resolution, MR imaging may demonstrate three zones of differing signal intensity in articular cartilage. The superficial low-intensity zone may be a useful marker of the surface of normal articular cartilage.     

Human articular cartilage: influence of aging and early symptomatic degeneration on the spatial variation of T2--preliminary findings at 3 T

PURPOSE: To determine if age and early symptomatic degeneration alter the spatial dependency of cartilage T2. MATERIALS AND METHODS: In 25 asymptomatic volunteers and six volunteers with symptoms of patellar chondromalacia, quantitative T2 maps of patellar cartilage were obtained with a multiecho, spin-echo magnetic resonance imaging sequence at 3.0 T. Spatial variation in T2 was evaluated as a function of participant age and symptoms. RESULTS: All asymptomatic volunteers demonstrated a continuous increase in T2 from the radial zone to the articular surface. In the population aged 46-60 years compared with younger volunteers, there was a statistically significant (P < .05) increase in T2 of the transitional zone. In symptomatic volunteers, the increase in T2 was larger in magnitude and focal in distribution. In five of the six symptomatic volunteers, the increase in T2 was greater than the 95% prediction interval determined from data in the corresponding age-matched asymptomatic population. CONCLUSION: Aging is associated with an asymptomatic increase in T2 of the transitional zone of articular cartilage. Preliminary results indicate this diffuse increase in T2 in senescent cartilage is different in appearance than the focally increased T2 observed in damaged articular cartilage.     

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.