Spatial variation in T1 of healthy human articular cartilage of the knee joint

The longitudiual relaxation time T₁ of native cartilage is frequently assumed to be constant. To redress this, the spatial variation of T₁ in unenhanced healthy human knee cartilage in different compartments and cartilage layers was investigated. Knees of 25 volunteers were examined on a 1.5 T MRI system. A three-dimensional gradient-echo sequence with a variable flip angle, in combination with parallel imaging, was used for rapid T₁ mapping of the whole knee. Regions of interest (ROIs) were defined in five different cartilage segments (medial and lateral femoral cartilage, medial and lateral tibial cartilage and patellar cartilage). Pooled histograms and averaged profiles across the cartilage thickness were generated. The mean values were compared for global variance using the Kruskal–Wallis test and pairwise using the Mann–Whitney U-test. Mean T₁ decreased from 900–1100 ms in superficial cartilage to 400–500 ms in deep cartilage. The averaged T₁ value of the medial femoral cartilage was 702±68 ms, of the lateral femoral cartilage 630±75 ms, of the medial tibial cartilage 700±87 ms, of the lateral tibial cartilage 594±74 ms and of the patellar cartilage 666±78 ms. There were significant differences between the medial and lateral compartment (p<0.01). In each cartilage segment, T₁ decreased considerably from superficial to deep cartilage. Only small variations of T₁ between different cartilage segments were found but with a significant difference between the medial and lateral compartments.MRI relaxation parameters are used to evaluate cartilage degradation. T₂ has been investigated extensively and has been demonstrated to vary with water and collagen content and with collagen orientation in the different cartilage layers [1–8].The quantification of the longitudiual relaxation time T₁ of native cartilage has received less attention. In experimental studies, native T₁ has been demonstrated to correlate with mechanical properties [9] and to depend upon the macromolecular structure of cartilage [10]. However, it is frequently assumed to be constant across cartilage [11–13]. A few studies have investigated the mean values of a single compartment (10, 14–19] but have not investigated the depth-dependent variation. To our knowledge, no study has systematically compared T₁ of unenhanced human knee cartilage in different cartilage layers and in different cartilage compartments in healthy volunteers.

Table 1

T₁ of healthy human articular cartilage in the knee joint

Spatial variation in cartilage T2 of the knee.

Technical limitations imposed by resolution and B1 homogeneity have thus far limited quantitative in vivo T2 mapping of cartilage to the patella. The purpose of this study is to develop T2 mapping of the femoral/tibial joint and assess regional variability of cartilage T2 in the knee. Quantitative in vivo T2 mapping of the knee was performed on 15 asymptomatic adults (age, 22-44) using a 3T MR scanner. There is a consistent pattern of spatial variation in cartilage T2 with longer values near the articular surface. The greatest variation occurs in the patella, where T2 increases from 45.3 +/- 2.5 msec at a normalized distance of 0.33-67 +/- 5.5 msec at a distance of 1.0. These results demonstrate feasibility of performing in vivo T2 mapping of femoral tibial cartilage. Except for the superficial 15% where T2 values are lower, the spatial variation in T2 of femoral and tibial cartilage is similar to patellar cartilage.     

T2 quantitation of articular cartilage at 1.5 T

PURPOSE: To evaluate sources of error when using a multiecho sequence for quantitative T2 mapping of articular cartilage at 1.5 T. MATERIALS AND METHODS: Phantom measurements were used to assess the contribution of stimulated echoes to inaccuracy of T2 measurements in cartilage using a multiecho sequence. Five volunteer studies compared in vivo single-echo spin echo results to multiecho, single-slice and multiecho, multislice acquisitions for assessment of both the stimulated echo and magnetization transfer contrast (MTC) contributions to T2 measurement inaccuracy. RESULTS: Phantom experiments demonstrated that substantial inaccuracy (10%-13% longer T2 values) is introduced from stimulated echoes with a multiecho sequence with slice-selective refocusing pulses. The in vivo volunteer studies also demonstrated increases in measured T2 by up to 48% with a multiecho sequence. Use of the multiecho sequence in the multislice mode resulted in T2 values closer to the single-echo standards for the volunteer studies. However, this apparent increased accuracy should be regarded as circumstantial, as it only occurs because the error due to MTC has the opposite sign compared to the error due to the stimulated echo contribution. CONCLUSION: Use of a multiecho, multislice sequence for cartilage T2 measurements should be undertaken with the caution that substantial inaccuracy is introduced from stimulated echoes and MTC.     

磁共振成像研究膝股骨髁软骨T2值空间分布

目的 研究健康成人和早期骨性关节炎(osteoarthritis,OA)病人膝关节股骨内外髁软骨横向弛豫时间(T2值)空间分布.方法 采用Siemens 3.0T磁共振,正常组(20例;年龄25~38岁,平均28.7岁±4.5岁)25个膝关节和早期OA病人组(27例;年龄40~78岁,平均54.2岁±11岁)31个膝关节,应用T2图成像观察和测量2组股骨内外侧髁非负重区与负重区软骨T2值,并进行统计学分析.结果 正常组与早期OA组股骨髁负重区软骨平均T2值[(51.1±4.3) ms,(58.9±4.0) ms]明显高于各自非负重区[(47.2±3.8) ms,(53.5±4.1) ms],差异有统计学意义(F值分别为22.151和54.670,P值均<0.05);正常组股骨髁各区软骨浅层T2值明显高于深层,差异有统计学意义(F值分别为27.960、12.972、12.718、7.837,P值均<0.05);早期OA组股骨内外髁非负重区软骨浅层T2值明显高于深层(F值分别为6.062和10.436,P值均<0.05),负重区软骨浅层与深层比较差异无统计学意义(F值分别为1.208和1.472,P值均>0.05).结论 健康成人和早期OA病人膝关节股骨内外髁软骨T2值具有特定空间分布特点,对量化监测早期OA软骨病变具有参考价值.负重对软骨T2值空间分布有一定影响.     

T2 mapping of hip articular cartilage in healthy volunteers at 3T: a study of topographic variation

PURPOSE: To perform baseline T2 mapping of the hips of healthy volunteers, focusing on topographic variation, because no detailed study has involved hips. T2 mapping is a quantitative magnetic resonance imaging (MRI) technique that evaluates cartilage matrix components. MATERIALS AND METHODS: Hips of 12 healthy adults (six men and six women; mean age = 29.5 +/- 4.9 years) were studied with a 3.0-Tesla MRI system. T2 measurement in the oblique-coronal plane used a multi-spin-echo (MSE) sequence. Femoral cartilage was divided into 12 radial sections; acetabular cartilage was divided into six radial sections, and each section was divided into two layers representing the superficial and deep halves of the cartilage. T2 of these sections and layers were measured. RESULTS: Femoral cartilage T2 was the shortest (-20 degrees to 20 degrees and -10 degrees to 10 degrees, superficial and deep layers), with an increase near the magic angle (54.7 degrees ). Acetabular cartilage T2 in both layers was shorter in the periphery than the other parts, especially at 20 degrees to 30 degrees. There were no significant differences in T2 between right and left hips or between men and women. CONCLUSION: Topographic variation exists in hip cartilage T2 in young, healthy adults. These findings should be taken into account when T2 mapping is applied to patients with degenerative cartilage.     

Spatial assessment of articular cartilage proteoglycans with Gd-DTPA-enhanced T1 imaging.

In Gd-DTPA-enhanced T(1) imaging of articular cartilage, the MRI contrast agent with two negative charges is understood to accumulate in tissue inversely to the negative charge of cartilage glycosaminoglycans (GAGs) of proteoglycans (PGs), and this leads to a decrease in the T(1) relaxation time of tissue relative to the charge in tissue. By assuming a constant relaxivity for Gd-DTPA in cartilage, it has further been hypothesized that the contrast agent concentration in tissue could be estimated from consecutive T(1) measurements in the absence or presence of the contrast agent. The spatial sensitivity of the technique was examined at 9.4 T in normal and PG-depleted bovine patellar cartilage samples. As a reference, spatial PG concentration was assessed with digital densitometry from safranin O-stained cartilage sections. An excellent linear correlation between spatial optical density (OD) of stained GAGs and T(1) with Gd-DTPA was observed in the control and chondroitinase ABC-treated cartilage specimens, and the MR parameter accounted for approximately 80% of the variations in GAG concentration within samples. Further, the MR-resolved Gd-DTPA concentration proved to be an even better estimate for PGs, with an improved correlation. However, the linear relation between MR parameters and PG concentration did not apply in the deep tissue, where MR measurements overestimated the PG content. While the absolute [Gd-DTPA] determination may be prone to error due to uncertainty of relaxivity in cartilage, or to other contributing factors such as variations in tissue permeability, the experimental evidence highlights the sensitivity of this technique to reflect spatial changes in cartilage PG concentration in normal and degenerated tissue.     

T2 and T1rho MRI in articular cartilage systems.

T2 and T1rho have potential to nondestructively detect cartilage degeneration. However, reports in the literature regarding their diagnostic interpretation are conflicting. In this study, T2 and T1rho were measured at 8.5 T in several systems: 1) Molecular suspensions of collagen and GAG (pure concentration effects): T2 and T1rho demonstrated an exponential decrease with increasing [collagen] and [GAG], with [collagen] dominating. T2 varied from 90 to 35 ms and T1rho from 125 to 55 ms in the range of 15-20% [collagen], indicating that hydration may be a more important contributor to these parameters than previously appreciated. 2) Macromolecules in an unoriented matrix (young bovine cartilage): In collagen matrices (trypsinized cartilage) T2 and T1rho values were consistent with the expected [collagen], suggesting that the matrix per se does not dominate relaxation effects. Collagen/GAG matrices (native cartilage) had 13% lower T2 and 17% lower T1rho than collagen matrices, consistent with their higher macromolecular concentration. Complex matrix degradation (interleukin-1 treatment) showed lower T2 and unchanged T1rho relative to native tissue, consistent with competing effects of concentration and molecular-level changes. In addition, the heterogeneous GAG profile in these samples was not reflected in T2 or T1rho. 3) Macromolecules in an oriented matrix (mature human tissue): An oriented collagen matrix (GAG-depleted human cartilage) showed T2 and T(1rho) variation with depth consistent with 16-21% [collagen] and/or fibril orientation (magic angle effects) seen on polarized light microscopy, suggesting that both hydration and structure comprise important factors. In other human cartilage regions, T2 and T1rho abnormalities were observed unrelated to GAG or collagen orientation differences, demonstrating that hydration and/or molecular-level changes are important. Overall, these studies illustrate that T2 and T1rho are sensitive to biologically meaningful changes in cartilage. However, contrary to some previous reports, they are not specific to any one inherent tissue parameter.     

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.     

T2 of articular cartilage in the presence of Gd-DTPA2-.

T(2) information and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are both used to characterize articular cartilage. They are currently obtained in separate studies because Gd-DTPA(2-) (which is needed for dGEMRIC) affects the inherent T(2) information. In this study, T(2) was simulated and then measured at 8.45 T in 20 sections from two human osteochondral samples equilibrated with and without Gd-DTPA(2-). Both the simulations and data demonstrated that Gd-DTPA(2-) provides a non-negligible mechanism for relaxation, especially with higher (1 mM) equilibrating Gd-DTPA(2-) concentrations, and in areas of tissue with high T(2) (due to weak inherent T(2) mechanisms) and high tissue Gd-DTPA(2-) (due to a low glycosaminoglycan concentration). Nonetheless, T(2)-weighted images of cartilage equilibrated in 1 mM Gd-DTPA(2-) showed similar T(2) contrast with and without Gd-DTPA(2-), demonstrating that the impact on T(2) was not great enough to affect identification of T(2) lesions. However, T(2) maps of the same samples showed loss of conspicuity of T(2) abnormalities. We back-calculated inherent T(2)'s (T(2,bc)) using a T(2)-relaxivity value from a 20% protein phantom (r(2) = 9.27 +/- 0.09 mM(-1)s(-1)) and the Gd-DTPA(2-) concentration calculated from T(1,Gd). The back-calculation restored the inherent T(2) conspicuity, and a correlation between T(2) and T(2,bc) of r = 0.934 (P < 0.0001) was found for 80 regions of interest (ROIs) in the sections. Back-calculation of T(2) is therefore a viable technique for obtaining T(2) maps at high equilibrating Gd-DTPA(2-) concentrations. With T(2)-weighted images and/or low equilibrating Gd-DTPA(2-) concentrations, it may be feasible to obtain both T(2) and dGEMRIC information in the presence of Gd-DTPA(2-) without such corrections. These conditions can be designed into ex vivo studies of cartilage. They appear to be applicable for clinical T(2) studies, since pilot clinical data at 1.5 T from three volunteers demonstrated that calculated T(2) maps are comparable before and after "double dose" Gd-DTPA(2-) (as utilized in clinical dGEMRIC studies). Therefore, it may be possible to perform a comprehensive clinical examination of dGEMRIC, T(2), and cartilage volume in one scanning session without T(2) data correction.     

T2* measurement of the knee articular cartilage in osteoarthritis at 3T

Purpose:

To measure reproducibility, longitudinal and cross‐sectional differences in T2* maps at 3 Tesla (T) in the articular cartilage of the knee in subjects with osteoarthritis (OA) and healthy matched controls.

Materials and Methods:

MRI data and standing radiographs were acquired from 33 subjects with OA and 21 healthy controls matched for age and gender. Reproducibility was determined by two sessions in the same day, while longitudinal and cross‐sectional group differences used visits at baseline, 3 and 6 months. Each visit contained symptomological assessments and an MRI session consisting of high resolution three‐dimensional double‐echo‐steady‐state (DESS) and co‐registered T2* maps of the most diseased knee. A blinded reader delineated the articular cartilage on the DESS images and median T2* values were reported.

Results:

T2* values showed an intra‐visit reproducibility of 2.0% over the whole cartilage. No longitudinal effects were measured in either group over 6 months. T2* maps revealed a 5.8% longer T2* in the medial tibial cartilage and 7.6% and 6.5% shorter T2* in the patellar and lateral tibial cartilage, respectively, in OA subjects versus controls (P < 0.02).

Conclusion:

T2* mapping is a repeatable process that showed differences between the OA subject and control groups. J. Magn. Reson. Imaging 2012;35:1422–1429. © 2012 Wiley Periodicals Inc.     

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.     

Sodium MRI of human articular cartilage in vivo

Preliminary results from in vivo sodium MRI of human patellar articular cartilage are presented. Sodium images generated of an in vitro bovine patella clearly distinguish the region of proteoglycan depletion from the region of healthy cartilage. This provides the first evidence that sodium imaging may be used to detect changes due to osteoarthritis in vivo. The process of optimizing imaging time and signal-to-noise ratio, as well as potential implications in the detection of osteoar-thritic change, are discussed.     

Effect of multislice acquisition on T1 and T2 measurements of articular cartilage at 3T

PURPOSE: The aim of this study was to investigate the effect of magnetization transfer on multislice T1 and T2 measurements of articular cartilage. MATERIALS AND METHODS: A set of phantoms with different concentrations of collagen and contrast agent (Gd-DTPA2-) were used for the in vitro study. A total of 20 healthy knees were used for the in vivo study. T1 and T2 measurements were performed using fast-spin-echo inversion-recovery (FSE-IR) sequence and multi-spin-echo (MSE) sequence, respectively, in both in vitro and in vivo studies. We investigated the difference in T1 and T2 values between that measured by single-slice acquisition and that measured by multislice acquisition. RESULTS: Regarding T1 measurement, a large drop of T1 in all slices and also a large interslice variation in T1 were observed when multislice acquisition was used. Regarding T2 measurement, a substantial drop of T2 in all slices was observed; however, there was no apparent interslice variation when multislice acquisition was used. CONCLUSION: This study demonstrated that the adaptation of multislice acquisition technique for T1 measurement using FSE-IR methodology is difficult and its use for clinical evaluation is problematic. In contrast, multislice acquisition for T2 measurement using MSE was clinically applicable if inaccuracies caused by multislice acquisition were taken into account.     

T2 values of articular cartilage in clinically relevant subregions of the asymptomatic knee

Purpose

In order for T2 mapping to become more clinically applicable, reproducible subregions and standardized T2 parameters must be defined. This study sought to: (1) define clinically relevant subregions of knee cartilage using bone landmarks identifiable on both MR images and during arthroscopy and (2) determine healthy T2 values and T2 texture parameters within these subregions.

Methods

Twenty-five asymptomatic volunteers (age 18–35) were evaluated with a sagittal T2 mapping sequence. Manual segmentation was performed by three raters, and cartilage was divided into twenty-one subregions modified from the International Cartilage Repair Society Articular Cartilage Mapping System. Mean T2 values and texture parameters (entropy, variance, contrast, homogeneity) were recorded for each subregion, and inter-rater and intra-rater reliability was assessed.

Results

The central regions of the condyles had significantly higher T2 values than the posterior regions (P < 0.05) and higher variance than the posterior region on the medial side (P < 0.001). The central trochlea had significantly greater T2 values than the anterior and posterior condyles. The central lateral plateau had lower T2 values, lower variance, higher homogeneity, and lower contrast than nearly all subregions in the tibia. The central patellar regions had higher entropy than the superior and inferior regions (each P ≤ 0.001). Repeatability was good to excellent for all subregions.

Conclusion

Significant differences in mean T2 values and texture parameters were found between subregions in this carefully selected asymptomatic population, which suggest that there is normal variation of T2 values within the knee joint. The clinically relevant subregions were found to be robust as demonstrated by the overall high repeatability.     

Integrity of articular cartilage on T2 mapping associated with meniscal signal change

Objective

The purpose of this study was to investigate the relationship between T2 relaxation values (T2 RVs) within the superficial zone of articular cartilage and different types of meniscal degeneration/tear.

Materials and methods

A review of 310 consecutive knee MRIs which included an 8 echo T2 relaxation sequence, in patients referred for standard clinical indications, was performed independently and in blinded fashion by 2 observers. The posterior horns of the medial and lateral menisci were each evaluated and divided into 4 subgroups: Normal (control), Grade I/II meniscal signal, Grade III meniscal signal-simple tear (Grade III-S), and Grade III meniscal signal-complex tear (Grade III-C). After exclusion criteria were applied, the medial meniscal group consisted of 65 controls and 133 patients, while the lateral meniscal group consisted of 143 controls and 55 patients. T2 RVs were measured by an observer blinded to the clinical history and MRI grading. Measurements were obtained over the superficial zone of femoral and tibial articular cartilage adjacent to the center of the posterior horn of each meniscus to ensure consistency between measurements. Analysis of covariance adjusting for age and gender was used to compare T2 RVs between patients and controls.

Results

T2 RVs were significantly increased in patients with Grade III-C meniscal tears compared to controls over the medial tibial plateau (MTP; p = 0.0001) and lateral tibial plateau (LTP; p = 0.0008). T2 RVs were not increased in patients with Grade III-C meniscal tears over the medial femoral condyle (MFC; p = 0.11) or lateral femoral condyle (LFC; p = 0.99). Grade I/II meniscal signal was not associated with elevated T2 RVs over the MFC (p = 0.15), LFC (p = 0.69), MTP (p = 0.42), or LTP (p = 0.50). Grade III-S meniscal signal was not associated with elevated T2 RVs over the MFC (p = 0.54), LFC (p = 0.43), MTP (p = 0.30), or LTP (p = 0.38).

Conclusion

Grade III-C meniscal tears are associated with elevated T2 RVs in adjacent tibial articular cartilage. The results may have an impact on prognostication and treatment in order to delay or prevent the onset of osteoarthritis.     

Three-dimensional topographical variation of femoral cartilage T2 in healthy volunteer knees

Objective

Quantitative knee cartilage T2 assessment on limited two-dimensional midsagittal or midcoronal planes may be insufficient to assess variations in normal cartilage composition. The purpose of this work was to reveal characteristic 3D distribution of T2 values in femoral cartilage in healthy volunteer knees.

Materials and methods

Sixteen volunteers were enrolled in this study. One knee joint in each volunteer was imaged using a 3D fast image employing steady-state acquisition cycled phases (FIESTA-C) sequence for modeling distal femoral morphology, as well as a sagittal T2 mapping of cartilage. 3D distribution of cartilage T2 values was generated for the femoral condyles. At each medial and lateral condyle, four regions of interest (ROI) were manually defined based on the cartilage covered by the 3D surface model of the medial and lateral menisci.

Results

The 3D maps showed a relatively inhomogeneous distribution of cartilage T2 on the medial and lateral condyles. Cartilage T2 values in the internal half of the weight-bearing zone were significantly higher than those in all other zones on both lateral and medial condyles.

Conclusions

Analysis of 3D distribution of femoral cartilage T2 may be valuable in determining the site-specific normal range of cartilage T2 in the healthy knee joint.     

Proteoglycan-induced changes in T1rho-relaxation of articular cartilage at 4T.

Proteoglycan (PG) depletion-induced changes in T1rho (spin-lattice relaxation in rotating frame) relaxation and dispersion in articular cartilage were studied at 4T. Using a spin-lock cluster pre-encoded fast spin echo sequence, T1rho maps of healthy bovine specimens and specimens that were subjected to PG depletion were computed at varying spin-lock frequencies. Sequential PG depletion was induced by trypsinization of cartilage for varying amounts of time. Results demonstrated that over 50% depletion of PG from bovine articular cartilage resulted in average T1rho increases from 110-170 ms. Regression analysis of the data showed a strong correlation (R2 = 0.987) between changes in PG and T1rho. T1rho values were highest at the superficial zone and decreased gradually in the middle zone and again showed an increasing trend in the region near the subchondral bone. The potentials of this method in detecting early degenerative changes of cartilage are discussed. Also, T(1rho)-dispersion changes as a function of PG depletion are described.