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.     

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.     

Multicomponent T2 relaxation analysis in cartilage

MR techniques are sensitive to the early stages of osteoarthritis, characterized by disruption of collagen and loss of proteoglycan (PG), but are of limited specificity. Here, water compartments in normal and trypsin‐degraded bovine nasal cartilage were identified using a nonnegative least squares multiexponential analysis of T₂ relaxation. Three components were detected: T_2,1 = 2.3 ms, T_2,2 = 25.2 ms, and T_2,3 = 96.3 ms, with fractions w₁ = 6.2%, w₂ = 14.5%, and w₃ = 79.3%, respectively. Trypsinization resulted in increased (P < 0.01) values of T_2,2 = 64.2 ms and T_2,3 = 149.4 ms, supporting their assignment to water compartments that are bound and loosely associated with PG, respectively. The T₂ of the rapidly relaxing component was not altered by digestion, supporting assignment to relatively immobile collagen‐bound water. Relaxation data were simulated for a range of TE, number of echoes, and SNR to guide selection of acquisition parameters and assess the accuracy and precision of experimental results. Based on this, the expected experimental accuracy of measured T₂s and associated weights was within 2% and 4% respectively, with precision within 1% and 3%. These results demonstrate the potential of multiexponential T₂ analysis to increase the specificity of MR characterization of cartilage. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

T2 measurement in articular cartilage: Impact of the fitting method on accuracy and precision at low SNR

T₂ relaxation time is a promising MRI parameter for the detection of cartilage degeneration in osteoarthritis. However, the accuracy and precision of the measured T₂ may be substantially impaired by the low signal‐to‐noise ratio of images available from clinical examinations. The purpose of this work was to assess the accuracy and precision of the traditional fit methods (linear least‐squares regression and nonlinear fit to an exponential) and two new noise‐corrected fit methods: fit to a noise‐corrected exponential and fit of the noise‐corrected squared signal intensity to an exponential. Accuracy and precision have been analyzed in simulations, in phantom measurements, and in seven repetitive acquisitions of the patellar cartilage in six healthy volunteers. Traditional fit methods lead to a poor accuracy for low T₂, with overestimations of the exact T₂ up to 500%. The noise‐corrected fit methods demonstrate a very good accuracy for all T₂ values and signal‐to‐noise ratio. Even more, the fit to a noise‐corrected exponential results in precisions comparable to the best achievable precisions (Cramér‐Rao lower bound). For in vivo images, the traditional fit methods considerably overestimate T₂ near the bone‐cartilage interface. Therefore, using an adequate fit method may substantially improve the sensitivity of T₂ to detect pathology in cartilage and change in T₂ follow‐up examinations. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

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.     

Quantification of T(2) relaxation changes in articular cartilage with in situ mechanical loading of the knee

PURPOSE: To devise a method for producing in vivo MRI images of the knee under physiologically significant loading, and to compare and evaluate the changes in cartilage characteristics before and during in situ compression of the knee. MATERIAL AND METHODS: A total of 26 asymptomatic subjects were imaged on a 1.5 Tesla Philips Intera scanner using a commercially available knee coil. Routine anatomical images were followed by T(2) map acquisition. These scans were repeated following in situ compression of the knee using a MR compatible loading jig. RESULTS: Following loading to body weight, several regions of femoral cartilage show early alteration of T(2) relaxation time, most significantly in the medial and lateral peripheral zones. There were no significant changes in the tibial cartilage. CONCLUSIONS: The results establish the feasibility of measuring changes on MRI with in situ axial loading.     

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.     

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.     

Global and regional reproducibility of T2 relaxation time measurements in human patellar cartilage.

Seven T2 maps (multiecho (ME) sequence: 3000 ms, eight echoes with 13.2 ms of echo spacing, 20 sections) and T1-weighted (T1-w) fast low-angle shot (FLASH-water excitation (WE)) data sets from four imaging sessions (right patellae of 10 healthy volunteers) were obtained. A segmentation of cartilage (WE sequence) was overlaid on the ME data and T2 values were calculated for total cartilage, three layers, three facets (global), and 240 ROIs (regional). Reproducibility (precision error) was calculated as the root mean square average (RMSA) of the individual coefficients of variation (COVs, %) and standard deviations (SDs, ms) for intra- and intersession reproducibility. The precision error was 3-7% and 6-29% for global and regional T2, respectively. There was no difference between intra- and intersession reproducibility, but there was worse reproducibility in the superficial layers compared to the deeper layers. Peripheral ROI reproducibility (mean=13%) was worse than in the central portions (mean=11%), but omission of the periphery did not positively affect the globally calculated T2 reproducibility. The precision errors were small compared to reported changes in diseased cartilage, suggesting good discriminatory power of the technique. Our data provide a first estimate of global and regional reproducibility errors of T2 in healthy cartilage, and may serve as a basis for sample size calculations and aid study designs for longitudinal and cross-sectional trials in osteoarthritis (OA).     

Combined T1-T2 mapping of human femoro-tibial cartilage with turbo-mixed imaging at 1.5T

PURPOSE: To evaluate the influence of Gd-DTPA on cartilage T2 mapping using turbo-mixed (tMIX) imaging, and to show the possible usefulness of the tMIX technique for simultaneously acquiring T1 and T2 information in cartilage. MATERIALS AND METHODS: Twenty volunteers underwent MRI of the knee using the tMIX sequence before and after gadolinium administration. T1 and T2 maps were calculated. The mean T1 was determined on the pre- and postcontrast T1 maps. T2 relaxation values before and after gadolinium administration were statistically analyzed. RESULTS: The obtained relaxation values are in correspondence with previously published data. The mean T1 before gadolinium administration was 449 msec +/- 34.2 msec (SD), and after gadolinium administration it was 357 msec +/- 55.8 msec (SD). The postcontrast T1 relaxation range was 221.5-572.8 msec. The mean T2 of the precontrast T2 maps was 34.2 msec +/- 3.1 msec (SD), and the mean T2 of the postcontrast T2 maps was 32.5 msec +/- 3.1 msec (SD). These are statistically significant different values. A correction for the postcontrast T2 values, using a back-calculation algorithm, yielded a 98% correlation with the precontrast T2 values. CONCLUSION: The absolute difference of pre- and postcontrast T2 is very small and is ruled out using the back-calculation algorithm. Combined T1-T2 tMIX cartilage mapping is a valuable alternative for separate T1 and T2 cartilage mapping.     

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.     

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.     

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.     

Modifications of orientational dependence of microscopic magnetic resonance imaging T(2) anisotropy in compressed articular cartilage

PURPOSE: To investigate the compression-induced changes in the orientational characteristics in T(2) anisotropy of articular cartilage using microscopic magnetic resonance imaging (microMRI). MATERIALS AND METHODS: Six beagle specimens were subjected to various levels of strain (0% to 27%) and were imaged at a minimum of two orientations (0 degrees and 55 degrees ). Two specimens at 14% and 27% strain were imaged at every 5 degrees increment over the first quadrant of the angular space. Quantitative two-dimensional T(2) images and three-dimensional T(2) anisotropy maps of cartilage were constructed at a 19.8-microm in-depth resolution. RESULTS: The load-induced laminar appearance of cartilage at the magic angle became more distinct as the strain level increased. T(2) anisotropy maps of cartilage at 14% and 27% strain exhibited load-induced modifications in the collagen fibril ultrastructure, with a new peak toward the cartilage-bone interface and alterations to orientational dependence of T(2) anisotropy. CONCLUSION: Distinct alternations in the orientational dependence of microMRI T(2) anisotropy reflect the organizational modification of the collagen matrix due to external loading. This approach could become useful in detecting changes in cartilage's macromolecular structure due to injury or diseases.     

Value of precontrast T1 for dGEMRIC of native articular cartilage

Purpose

To evaluate if the difference between pre‐ and post‐Gd‐DTPA^2‐ relaxation rate (ΔR₁) provides better differentiation of osteoarthritic patients (OA) from healthy subjects (HS) with dGEMRIC, as compared to post‐Gd‐DTPA^2‐ spin‐lattice relaxation time (T_1Gd).

Materials and Methods

Seventeen OA and 14 HS underwent pre‐ and 90 minutes postcontrast (Gd‐DTPA^2‐) magnetic resonance imaging (MRI) of the knee, using inversion recovery fast spin‐echo and/or Lock–Locker sequences for T₁ mapping. Effect sizes for T_1pre, T_1Gd, and ΔR₁ were calculated, and receiver operating characteristic (ROC) curve and regression analysis were also performed to assess the effectiveness of each parameter in the separation of OA and HS.

Results

T_1Gd and ΔR₁ were almost identical in terms of areas under ROC curves (0.903 and 0.914, respectively), and effect sizes (1.34 and 1.31, respectively). These were significantly higher than T_1pre. In addition, a high inverse correlation was observed between ΔR₁ vs. T_1Gd (R = 0.96).

Conclusion

Either T_1Gd or ΔR₁ could be used as an index in the evaluation of native cartilage. However, considering the practical logistical cost involved in terms of time and effort to acquire precontrast T₁ measurements, our data further support the continued use of T_1Gd as the dGEMRIC index in the evaluation of native cartilage. J. Magn. Reson. Imaging 2009;29:494–497. © 2009 Wiley‐Liss, Inc.