Mikko J. Nissi

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). Youngs 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 Youngs (>1.0 MPa) and dynamic (>8 MPa) moduli than tibial or patellar cartilage (Youngs 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. Magn Reson Med 52:41–46, 2004.

Mechanical characterization of articular cartilage by combining magnetic resonance imaging and finite-element analysis—a potential functional imaging technique

Magnetic resonance imaging (MRI) provides a method for non-invasive characterization of cartilage composition and structure. We aimed to see whether T(1) and T(2) relaxation times are related to proteoglycan (PG) and collagen-specific mechanical properties of articular cartilage. Specifically, we analyzed whether variations in the depthwise collagen orientation, as assessed by the laminae obtained from T(2) profiles, affect the mechanical characteristics of cartilage. After MRI and unconfined compression tests of human and bovine patellar cartilage samples, fibril-reinforced poroviscoelastic finite-element models (FEM), with depthwise collagen orientations implemented from quantitative T(2) maps (3 laminae for human, 3-7 laminae for bovine), were constructed to analyze the non-fibrillar matrix modulus (PG specific), fibril modulus (collagen specific) and permeability of the samples. In bovine cartilage, the non-fibrillar matrix modulus (R = -0.64, p < 0.05) as well as the initial permeability (R = 0.70, p < 0.05) correlated with T(1). In bovine cartilage, T(2) correlated positively with the initial fibril modulus (R = 0.62, p = 0.05). In human cartilage, the initial fibril modulus correlated negatively (R = -0.61, p < 0.05) with T(2). Based on the simulations, cartilage with a complex collagen architecture (5 or 7 laminae), leading to high bulk T(2) due to magic angle effects, provided higher compressive stiffness than tissue with a simple collagen architecture (3 laminae). Our results suggest that T(1) reflects PG-specific mechanical properties of cartilage. High T(2) is characteristic to soft cartilage with a classical collagen architecture. Contradictorily, high bulk T(2) can also be found in stiff cartilage with a multilaminar collagen fibril network. By emerging MRI and FEM, the present study establishes a step toward functional imaging of articular cartilage.

Diffusion of Gd-DTPA2− into articular cartilage

OBJECTIVES The delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) technique is a method proposed for non-invasive measurement of cartilage glycosaminoglycan (GAG) content. In this method, gadopentetate (Gd-DTPA²⁻) is assumed to distribute in cartilage in inverse relation to the GAG distribution, thus allowing quantification of the GAG content. For accurate GAG quantification, the kinetics of Gd-DTPA²⁻ in articular cartilage is of critical importance. However, the diffusion of Gd-DTPA²⁻ has not been systematically studied over long time periods using MRI-feasible gadopentetate concentrations. Thus, the present study aims to investigate the diffusion of gadopentetate into cartilage in vitro in intact and enzymatically degraded cartilage. METHODS The diffusion of gadopentetate into bovine articular cartilage was investigated at 9.4 T over 18-h time period using repeated T(1) measurements in two models, (1) comparing intact and trypsin-treated tissue and (2) assessing the effect of penetration direction. The diffusion process was further assessed by determining the gadopentetate flux and diffusivity. The results were compared with histological and biochemical reference methods. RESULTS AND CONCLUSIONS The results revealed that passive diffusion of Gd-DTPA²⁻ was significantly slower than previously assumed, leading to overestimation of the GAG content at equilibrating times of few hours. Moreover, Gd-DTPA²⁻ distribution was found to depend not only on GAG content, but also on collagen content and diffusion direction. Interestingly, the dGEMRIC technique was found to be most sensitive to cartilage degradation in the early stages of diffusion process, suggesting that full equilibrium between gadopentetate and cartilage may not be required in order to detect cartilage degeneration.

Assessment of interstitial water content of articular cartilage with T1 relaxation

The interstitial water content typically increases in the early degeneration of articular cartilage. Previously, T(2) relaxation has been related to water content, yet it is known to be strongly affected by the collagen orientation. Articular cartilage plugs from the bovine patella, femur and tibia (N=20) were mapped for T(1) and T(2) at 9.4 T to test the ability of T(1) relaxation to reflect cartilage water content. As a reference, water and proteoglycan (PG) contents were determined. Significant (P<.01) linear associations were demonstrated between the relaxation rates and tissue water content (R(1): r=-.81, R(2): r=-.60) and PG content (R(1): r=.75). After adjustment for the tissue water content, partial correlation analysis did not show significant associations between the relaxation rates and tissue PG content. After the effect of PGs was removed, significant (P<.05) linear correlation between the relaxation rates and tissue water content (R(1): r=-.48, R(2): r=-.50) was observed. Thus, the spin-lattice relaxation rate is proposed to provide a biomarker for water content in articular cartilage.

Multiparametric MRI assessment of human articular cartilage degeneration: Correlation with quantitative histology and mechanical properties

To evaluate the sensitivity of quantitative MRI techniques (T1, T1,Gd, T2, continous wave (CW) T1ρ dispersion, adiabatic T1ρ, adiabatic T2ρ, RAFF and inversion‐prepared magnetization transfer (MT)) for assessment of human articular cartilage with varying degrees of natural degeneration.

Evaluation of chondral repair using quantitative MRI.

Various quantitative magnetic resonance imaging (qMRI) biomarkers, including but not limited to parametric MRI mapping, semiquantitative evaluation, and morphological assessment, have been successfully applied to assess cartilage repair in both animal and human studies. Through the interaction between interstitial water and constituent macromolecules the compositional and structural properties of cartilage can be evaluated. In this review a comprehensive view of a variety of quantitative techniques, particularly those involving parametric mapping, and their relationship to the properties of cartilage repair is presented. Some techniques, such as T2 relaxation time mapping and delayed gadolinium‐enhanced MRI of cartilage (dGEMRIC), are well established, while the full potential of more recently introduced techniques remain to be demonstrated. A combination of several MRI techniques is necessary for a comprehensive characterization of chondral repair. J. Magn. Reson. Imaging 2012; 36:1287–1299.

Acetabular Cartilage Assessment in Patients with Femoroacetabular Impingement by Using T2* Mapping with Arthroscopic Verification

PURPOSE To evaluate the ability of T2* mapping to help differentiate damaged from normal acetabular cartilage in patients with femoroacetabular impingement (FAI). MATERIALS AND METHODS The institutional review board approved this retrospective study, and the requirement to obtain informed consent was waived. The study complied with HIPAA guidelines. The authors reviewed T2* relaxation time maps of 28 hips from 26 consecutive patients (mean patient age, 28.2 years; range, 12-53 years; eight male patients (nine hips) with a mean age of 26.7 years [range, 16-53 years]; 18 female patients (19 hips) with a mean age of 28.9 years [range, 12-46 years]). Conventional diagnostic 3.0-T magnetic resonance (MR) arthrography was augmented by including a multiecho gradient-recalled echo sequence for T2* mapping. After imaging, acetabular and femoral data were separated and acetabular regions of interest were identified. Arthroscopic cartilage assessment with use of a modified Beck scale for acetabular cartilage damage was performed by an orthopedic surgeon who was blinded to the results of T2* mapping. A patient-specific acetabular projection with a T2* overlay was developed to anatomically correlate imaging data with those from surgery (the standard of reference). Results were analyzed by using receiver operating characteristic (ROC) curves. RESULTS The patient-specific acetabular projection enabled co-localization between the MR imaging and arthroscopic findings. T2* relaxation times for normal cartilage (Beck score 1, 35.3 msec ± 7.0) were significantly higher than those for cartilage with early changes (Beck score 2, 20.7 msec ± 6.0) and cartilage with more advanced degeneration (Beck scores 3-6, ≤19.8 msec ± 5.6) (P < .001). At ROC curve analysis, a T2* value of 28 msec was identified as the threshold for damaged cartilage, with a 91% true-positive and 13% false-positive rate for differentiating Beck score 1 cartilage (normal) from all other cartilages. CONCLUSION The patient-specific acetabular projection with a T2* mapping overlay enabled good anatomic localization of cartilage damage defined with a T2* threshold of 28 msec and less.

MRI rotating frame relaxation measurements for articular cartilage assessment

In the present work we introduced two MRI rotating frame relaxation methods, namely adiabatic T1ρ and Relaxation Along a Fictitious Field (RAFF), along with an inversion-prepared Magnetization Transfer (MT) protocol for assessment of articular cartilage. Given the inherent sensitivity of rotating frame relaxation methods to slow molecular motions that are relevant in cartilage, we hypothesized that adiabatic T1ρ and RAFF would have higher sensitivity to articular cartilage degradation as compared to laboratory frame T2 and MT. To test this hypothesis, a proteoglycan depletion model was used. Relaxation time measurements were performed at 0 and 48h in 10 bovine patellar specimens, 5 of which were treated with trypsin and 5 untreated controls were stored under identical conditions in isotonic saline for 48h. Relaxation times measured at 48h were longer than those measured at 0h in both groups. The changes in T2 and MT relaxation times after 48h were approximately 3 times larger in the trypsin treated specimens as compared to the untreated group, whereas increases of adiabatic T1ρ and RAFF were 4 to 5 fold larger. Overall, these findings demonstrate a higher sensitivity of adiabatic T1ρ and RAFF to the trypsin-induced changes in bovine patellar cartilage as compared to the commonly used T2 and MT. Since adiabatic T1ρ and RAFF are advantageous for human applications as compared to standard continuous-wave T1ρ methods, adiabatic T1ρ and RAFF are promising tools for assessing cartilage degradation in clinical settings.

The effect of fMRI task combinations on determining the hemispheric dominance of language functions.

IntroductionThe purpose of this study is to establish the most suitable combination of functional magnetic resonance imaging (fMRI) language tasks for clinical use in determining language dominance and to define the variability in laterality index (LI) and activation power between different combinations of language tasks.MethodsActivation patterns of different fMRI analyses of five language tasks (word generation, responsive naming, letter task, sentence comprehension, and word pair) were defined for 20 healthy volunteers (16 right-handed). LIs and sums of T values were calculated for each task separately and for four combinations of tasks in predefined regions of interest. Variability in terms of activation power and lateralization was defined in each analysis. In addition, the visual assessment of lateralization of language functions based on the individual fMRI activation maps was conducted by an experienced neuroradiologist.ResultsA combination analysis of word generation, responsive naming, and sentence comprehension was the most suitable in terms of activation power, robustness to detect essential language areas, and scanning time. In general, combination analyses of the tasks provided higher overall activation levels than single tasks and reduced the number of outlier voxels disturbing the calculation of LI.ConclusionsA combination of auditory and visually presented tasks that activate different aspects of language functions with sufficient activation power may be a useful task battery for determining language dominance in patients.

Surgical induction, histological evaluation, and MRI identification of cartilage necrosis in the distal femur in goats to model early lesions of osteochondrosis

OBJECTIVE Identify and interrupt the vascular supply to portions of the distal femoral articular-epiphyseal cartilage complex (AECC) in goat kids to induce cartilage necrosis, characteristic of early lesions of osteochondrosis (OC); then utilize magnetic resonance imaging (MRI) to identify necrotic areas of cartilage. DESIGN Distal femora were perfused and cleared in goat kids of various ages to visualize the vascular supply to the distal femoral AECC. Vessels located on the axial aspect of the medial femoral condyle (MFC) and on the abaxial side of the lateral trochlear ridge were transected in eight 4- to 5-day-old goats to induce cartilage necrosis. Goats were euthanized 1, 2, 3, 4, 5, 6, 9, and 10 weeks post operatively and operated stifles were harvested. Adiabatic T1ρ relaxation time maps of the harvested distal femora were generated using a 9.4 T MR scanner, after which samples were evaluated histologically. RESULTS Interruption of the vascular supply to the MFC caused lesions of cartilage necrosis in 6/8 goat kids that were demonstrated histologically. Adiabatic T1ρ relaxation time mapping identified these areas of cartilage necrosis in 5/6 cases. No significant findings were detected after transection of perichondrial vessels supplying the lateral trochlear ridge. CONCLUSIONS Cartilage necrosis, characteristic of early OC, can be induced by interrupting the vascular supply to the distal femoral AECC in goat kids. The ability of high field MRI to identify these areas of cartilage necrosis in the AECC using the adiabatic T1ρ sequence suggests that this technique may be useful in the future for the early diagnosis of OC.