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1.
Repeatability of in vivo measurement of multicomponent T2* relaxation in articular cartialges in human knee is important to clinical use. This study evaluated the repeatability of two‐component T2* relaxation on seven healthy human subjects. The left knee was scanned once a day in three consecutive days, on a clinical 3T MRI scanner with eight‐channel knee coil and ultrashort echo time pulse sequence at 11 echo times = 0.6–40 ms. The intrasubject and intersubject repeatability was evaluated via coefficient of variation (CV = standard deviation/mean) in four typical cartilage regions: patellar, anterior articular, femoral, and tibial regions. It was found that the intrasubject repeatability was good, with CV < 10% for the short‐ and long‐T2* relaxation time in the layered regions in the four cartilages (with one exception) and CV < 13% for the component intensity fraction (with two exceptions). The intersubject repeatability was also good, with CV ~8% (range 1–15%) for the short‐ and long‐T2* relaxation time and CV ~10% (range 2–20%) for the component intensity fraction. The long‐T2* component showed significantly better repeatability (CV ~8%) than the short‐T2* component (CV~12%) (P < 0.005). These CV values suggest that in vivo measurement of two‐component T2* relaxation in the knee cartilages is repeatable on clinical scanner at 3 T, with a signal‐to‐noise ratio of 90. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.  相似文献   

2.
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.  相似文献   

3.
The purpose of this pilot study was to longitudinally quantify the T2 laminar integrity of knee cartilage in a subset of subjects with osteoarthritis from the Osteoarthritis Initiative at baseline, 1‐year follow‐up, and 2‐year follow‐up. Cartilage from 13 subjects was divided into six compartments and subdivided into deep and superficial layers. At each time point, mean T2 values in superficial and deep layers were compared. Longitudinal analysis included full‐thickness mean T2, mean deep T2, mean superficial T2, mean T2 laminar difference, mean percentage T2 laminar difference, and two‐dimensional measures of cartilage thickness. More compartments showed significantly higher superficial T2 than deep T2 values at baseline and 1‐year follow‐up compared to 2‐year follow‐up. No significant longitudinal changes of full‐thickness mean T2 and superficial T2 values were observed. Significant longitudinal changes were observed in the deep T2 values, T2 laminar difference, and percentage T2 laminar difference. Cartilage thickness had no influence on T2 analysis. Results of this study suggest that laminar analysis may improve the sensitivity to detect longitudinal T2 changes and that disruption of the T2 laminar organization of knee cartilage may be present in knee osteoarthritis progressors. Further investigation is warranted to evaluate the potential of the presented methodology to better characterize evolution and pathophysiology of osteoarthritis. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.  相似文献   

4.
The effects of water loss on the T1 and T2* of bovine cortical bone were investigated using ultrashort echo time sequences with signals excited either by a short hard pulse or by two longer half pulses. Nine bovine femur samples were prepared and sequentially air‐ and oven‐dried. On average 3.42% of bone by weight was lost after air‐drying for 3 days, with another 5.98% of bone weight loss after oven‐drying at 100°C for 24 h. T1 and T2* were measured after every 1% decrease in weight, with 9–10% bone weight loss at the termination of the drying process. After both forms of drying, the overall T1 decreased 33% from 153 ± 18 ms to 102 ± 17 ms when measured using the hard pulse and from 186 ± 25 ms to 122 ± 23 ms when using the half pulses. T2* decreased by 45–50% from 368 ± 29 μs to 201 ± 19 μs using the hard pulse and from 379 ± 35 μs to 191 ± 17 μs using the half pulses. A steady decrease of 26–31% was observed in both T1 and T2* with the first 3–4% bone water loss after air‐drying. Oven‐drying at 100°C for 24 h resulted on an additional 4% T1 reduction but 25% T2* reduction. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.  相似文献   

5.
Cartilage magnetic resonance imaging T2 relaxation time is sensitive to hydration, collagen content, and tissue anisotropy, and a potential imaging‐based biomarker for knee osteoarthritis. This longitudinal pilot study presents an improved cartilage flattening technique that facilitates texture analysis using gray‐level co‐occurrence matrices parallel and perpendicular to the cartilage layers, and the application of this technique to the knee cartilage of 13 subjects of the osteoarthritis initiative at baseline, 1‐year follow‐up, and 2‐year follow‐up. Cartilage flattening showed minimum distortion (~ 0.5 ms) of mean T2 values between nonflattened and flattened T2 maps. Gray‐level co‐occurrence matrices texture analysis of flattened T2 maps detected a cartilage laminar organization at baseline, 1‐year follow‐up, and 2‐year follow‐up by yielding significant (P < 0.05) differences between texture parameters perpendicular and parallel to the cartilage layers. Tendencies showed higher contrast, dissimilarity, angular second moment, and energy perpendicular to the cartilage layers; and higher homogeneity, entropy, variance, and correlation parallel to them. Significant (P < 0.05) longitudinal texture changes were also detected reflecting subtle signs of a laminar disruption. Tendencies showed decreasing contrast, dissimilarity, and entropy; and increasing homogeneity, energy, and correlation. Results of this study warrant further investigation to complete the assessment of the usefulness of the presented methodology in the study of knee osteoarthritis. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.  相似文献   

6.
This study aimed to determine the feasibility, reproducibility, and reliability of the multiecho T*2 Magnetic resonance imaging technique at 3 T for myocardial and liver iron burden quantification and the relationship between T*2 values at 3 and 1.5 T. Thirty‐eight transfusion‐dependent patients and 20 healthy subjects were studied. Cardiac segmental and global T*2 values were calculated after developing a correction map to compensate the artifactual T*2 variations. The hepatic T*2 value was determined over a region of interest. The intraoperator and interoperator reproducibility for T*2 measurements at 3 T was good. A linear relationship was found between patients' R (1000/T*2) values at 3 and 1.5 T. Segmental correction factors were significantly higher at 3 T. A conversion formula returning T*2 values at 1.5 T from values at 3 T was proposed. A good diagnostic reliability for T*2 assessment at 3 T was demonstrated. Lower limits of normal for 3 T T*2 values were 23.3 ms, 21.1 ms, and 11.7 ms, for the global heart, mid‐ventricular septum, and liver, respectively. In conclusion, T*2 quantification of iron burden in the mid‐ventricular septum, global heart, and no heavy–moderate livers resulted to be feasible, reproducible, and reliable at 3 T. Segmental heart T*2 analysis at 3 T may be challenging due to significantly higher susceptibility artifacts. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.  相似文献   

7.
Fast quantitative MRI has become an important tool for biochemical characterization of tissue beyond conventional T1, T2, and T2*‐weighted imaging. As a result, steady‐state free precession (SSFP) techniques have attracted increased interest, and several methods have been developed for rapid quantification of relaxation times using steady‐state free precession. In this work, a new and fast approach for T2 mapping is introduced based on partial RF spoiling of nonbalanced steady‐state free precession. The new T2 mapping technique is evaluated and optimized from simulations, and in vivo results are presented for human brain at 1.5 T and for human articular cartilage at 3.0 T. The range of T2 for gray and white matter was from 60 msec (for the corpus callosum) to 100 msec (for cortical gray matter). For cartilage, spatial variation in T2 was observed between deep (34 msec) and superficial (48 msec) layers, as well as between tibial (33 msec), femoral, (54 msec) and patellar (43 msec) cartilage. Excellent correspondence between T2 values derived from partially spoiled SSFP scans and the ones found with a reference multicontrast spin‐echo technique is observed, corroborating the accuracy of the new method for proper T2 mapping. Finally, the feasibility of a fast high‐resolution quantitative partially spoiled SSFP T2 scan is demonstrated at 7.0 T for human patellar cartilage. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.  相似文献   

8.
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.  相似文献   

9.
Delayed gadolinium‐enhanced MRI of cartilage is a technique, which involves T1 mapping to identify changes in the structural integrity of cartilage associated with osteoarthritis. Currently, the gold standard is 2D inversion recovery turbo spin echo, which suffers from long acquisition times and limited coverage. Three‐dimensional variable flip angle (VFA) is an alternate technique, which has been shown to be accurate when an estimate of T1 is available a priori. This study validates the variable flip angle method for delayed gadolinium‐enhanced MRI of cartilage of the femoro‐tibial knee cartilage. When amplitude of (excitation) radiofrequency field inhomogeneities were minimized using nonselective pulses and amplitude of (excitation) radiofrequency field correction using an additional acquisition of a amplitude of (excitation) radiofrequency field map, the accuracy of T1 measurements were improved, and slice‐to‐slice variations over the 3D volume were minimized. In conclusion, fast 3D T1 mapping using the variable flip angle method with amplitude of (excitation) radiofrequency field correction appears to be an efficient and accurate method for delayed gadolinium‐enhanced MRI of cartilage of the knee. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.  相似文献   

10.

Purpose:

To investigate the transport of Gd‐DTPA2? in different layers of femoral knee cartilage in vivo.

Materials and Methods:

T1 measurements (1.5 Tesla) were performed in femoral knee cartilage of 23 healthy volunteers. The weight‐bearing central cartilage was analyzed before contrast and at eight time points after an intravenous injection of Gd‐DTPA2?: 12–60 min (4 volunteers) and 1–4 h (19 volunteers). Three regions of interest were segmented manually: deep, middle, and superficial.

Results:

Before contrast injection, a depth‐wise variation of T1 was observed with 50% higher values in the superficial region compared with the deep region. In the deep region, the uptake of Gd‐DTPA2? was not detected until 36 min and the concentration increased until 240 min, whereas in the superficial region, the uptake was seen already at 12 min and the concentration decreased after 180 min (P < 0.01). There was a difference between medial and lateral compartment regarding bulk, but not superficial Gd‐DTPA2? concentration. The bulk gadolinium concentration was negatively related to the cartilage thickness (r = ?0.68; P < 0.01).

Conclusion:

The depth‐wise and thickness dependent variations in Gd‐DTPA2 transport influence the interpretation of bulk dGEMRIC analysis in vivo. In thick cartilage, incomplete penetration of Gd‐DTPA2 will yield a falsely too long T1. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.
  相似文献   

11.
MRI imaging of hepatic iron overload can be achieved by estimating T2* values using multiple‐echo sequences. The purpose of this work is to develop and clinically evaluate a weighted least squares algorithm based on T2* Iterative Decomposition of water and fat with Echo Asymmetry and Least‐squares estimation (IDEAL) technique for volumetric estimation of hepatic T2* in the setting of iron overload. The weighted least squares T2* IDEAL technique improves T2* estimation by automatically decreasing the impact of later, noise‐dominated echoes. The technique was evaluated in 37 patients with iron overload. Each patient underwent (i) a standard 2D multiple‐echo gradient echo sequence for T2* assessment with nonlinear exponential fitting, and (ii) a 3D T2* IDEAL technique, with and without a weighted least squares fit. Regression and Bland–Altman analysis demonstrated strong correlation between conventional 2D and T2* IDEAL estimation. In cases of severe iron overload, T2* IDEAL without weighted least squares reconstruction resulted in a relative overestimation of T2* compared with weighted least squares. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.  相似文献   

12.
T and T2 relaxation time constants have been proposed to probe biochemical changes in osteoarthritic cartilage. This study aimed to evaluate the spatial correlation and distribution of T and T2 values in osteoarthritic cartilage. Ten patients with osteoarthritis (OA) and 10 controls were studied at 3T. The spatial correlation of T and T2 values was investigated using Z‐scores. The spatial variation of T and T2 values in patellar cartilage was studied in different cartilage layers. The distribution of these relaxation time constants was measured using texture analysis parameters based on gray‐level co‐occurrence matrices (GLCM). The mean Z‐scores for T and T2 values were significantly higher in OA patients vs. controls (P < 0.05). Regional correlation coefficients of T and T2 Z‐scores showed a large range in both controls and OA patients (0.2–0.7). OA patients had significantly greater GLCM contrast and entropy of T values than controls (P < 0.05). In summary, T and T2 values are not only increased but are also more heterogeneous in osteoarthritic cartilage. T and T2 values show different spatial distributions and may provide complementary information regarding cartilage degeneration in OA. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.  相似文献   

13.
Assessment of lung effective transverse relaxation time (T2*) may play an important role in the detection of structural and functional changes caused by lung diseases such as emphysema and chronic bronchitis. While T2* measurements have been conducted in both animals and humans at 1.5 T, studies on human lung at 3.0 T have not yet been reported. In this work, ultrashort echo time imaging technique was applied for the measurement and comparison of T2* values in normal human lungs at 1.5 T and 3.0 T. A 2D ultrashort echo time pulse sequence was implemented and evaluated in phantom experiments, in which an eraser served as a homogeneous short T2* sample. For the in vivo study, five normal human subjects were imaged at both field strengths and the results compared. The average T2* values measured during free‐breathing were 2.11(±0.27) ms at 1.5 T and 0.74(±0.1) ms at 3.0 T, respectively, resulting in a 3.0 T/1.5 T ratio of 2.9. Furthermore, comparison of the relaxation values at end‐expiration and end‐inspiration, accomplished through self‐gating, showed that during normal breathing, differences in T2* between the two phases may be negligible. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.  相似文献   

14.
Magnetic resonance T2* has been validated as a noninvasive means of assessing myocardial iron overload. However, the effect on myocardial T2* of factors such as shimming, variations in capillary geometry, and susceptibility in relation to the effects of iron has not been fully clarified. Since T2 is not affected by extrinsic magnetic field inhomogeneity and has different sensitivity to capillary geometry, investigation into the in vivo relationship between myocardial T2* and T2 measurements can shed light on this important issue. This study was performed in 136 thalassemia patients. The myocardial T2 and T2* thresholds for normality created identical no‐iron‐overload and iron‐overloaded patient groups. In the no‐iron group, there was no correlation between myocardial T2 and T2*. In the iron‐overloaded patients, there was a linear correlation (R2 = 0.89) between myocardial T2* and T2 measurements, which indicates that the iron deposition is the dominant factor in determining these two relaxation values in this scenario. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.  相似文献   

15.
The protocol for delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC) was adapted for the evaluation of transplanted osteochondral allograft cartilage. Eight patients with focal grade 4 cartilage defects of the femoral condyle were treated with single cylindrical osteochondral allografts. At 1 and 2 years, dGEMRIC image sequences were acquired and regions of interest (ROIs) were drawn in repair and native control cartilage. Mean T1 values of region of interest were used to calculate established dGEMRIC metrics. The correlation was measured between the ΔR1 and R1‐Post metrics for repair and native cartilage. T1 times were measured in deep and superficial zones of cartilage. A strong correlation was identified between full‐thickness, deep, and superficial ΔR1 and R1‐Post values for native cartilage and repair cartilage for all years (range: 0.893–1.0). The mean T1 times and ΔR1 rate between deep and superficial regions of articular cartilage were statistically different for all regions of the distal femora analyzed at 1 year and 2 years after osteochondral allograft transplantation (P < 0.05). The dGEMRIC pre‐Gadolinium scan is unnecessary when evaluating transplanted osteochondral allograft cartilage. The observation of stratified T1 and ΔR1 values indicates a need to re‐evaluate the methodology behind the placement of region of interest in dGEMRIC. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.  相似文献   

16.
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.  相似文献   

17.
Visualizing myelin in human brain may help the study of diseases such as multiple sclerosis. Previous studies based on T1 and T2 relaxation contrast have suggested the presence of a distinct water pool that may report directly on local myelin content. Recent work indicates that T2* contrast may offer particular advantages over T1 and T2 contrast, especially at high field. However, the complex mechanism underlying T2* relaxation may render interpretation difficult. To address this issue, T2* relaxation behavior in human brain was studied at 3 and 7 T. Multiple gradient echoes covering most of the decay curve were analyzed for deviations from mono‐exponential behavior. The data confirm the previous finding of a distinct rapidly relaxing signal component (T2* ~ 6 ms), tentatively attributed to myelin water. However, in extension to previous findings, this rapidly relaxing component displayed a substantial resonance frequency shift, reaching 36 Hz in the corpus callosum at 7 T. The component's fractional amplitude and frequency shift appeared to depend on both field strength and fiber orientation, consistent with a mechanism originating from magnetic susceptibility effects. The findings suggest that T2* contrast at high field may be uniquely sensitive to tissue myelin content and that proper interpretation will require modeling of susceptibility‐induced resonance frequency shifts. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.  相似文献   

18.

Purpose

To evaluate if the difference between pre‐ and post‐Gd‐DTPA2‐ relaxation rate (ΔR1) provides better differentiation of osteoarthritic patients (OA) from healthy subjects (HS) with dGEMRIC, as compared to post‐Gd‐DTPA2‐ spin‐lattice relaxation time (T1Gd).

Materials and Methods

Seventeen OA and 14 HS underwent pre‐ and 90 minutes postcontrast (Gd‐DTPA2‐) magnetic resonance imaging (MRI) of the knee, using inversion recovery fast spin‐echo and/or Lock–Locker sequences for T1 mapping. Effect sizes for T1pre, T1Gd, 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

T1Gd 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 T1pre. In addition, a high inverse correlation was observed between ΔR1 vs. T1Gd (R = 0.96).

Conclusion

Either T1Gd 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 T1Gd as the dGEMRIC index in the evaluation of native cartilage. J. Magn. Reson. Imaging 2009;29:494–497. © 2009 Wiley‐Liss, Inc.  相似文献   

19.
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‐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 images demonstrated laminae. At the same time, T values were greater than T2 at both orientations throughout the cartilage. T 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 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.  相似文献   

20.
Recent in vivo MRI studies at 7.0 T have demonstrated extensive heterogeneity of T2* relaxation in white matter of the human brain. In order to study the origin of this heterogeneity, we performed T2* measurements at 1.5, 3.0, and 7.0 T in normal volunteers. Formalin‐fixed brain tissue specimens were also studied using T2*‐weighted MRI, histologic staining, chemical analysis, and electron microscopy. We found that T2* relaxation rate (R2* = 1/T2*) in white matter in living human brain is linearly dependent on the main magnetic field strength, and the T2* heterogeneity in white matter observed at 7.0 T can also be detected, albeit more weakly, at 1.5 and 3.0 T. The T2* heterogeneity exists also in white matter of the formalin‐fixed brain tissue specimens, with prominent differences between the major fiber bundles such as the cingulum (CG) and the superior corona radiata. The white matter specimen with substantial difference in T2* has no significant difference in the total iron content, as determined by chemical analysis. On the other hand, evidence from histologic staining and electron microscopy demonstrates these tissue specimens have apparent difference in myelin content and microstructure. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.  相似文献   

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