Steady-state diffusion imaging for MR in-vivo evaluation of reparative cartilage after matrix-associated autologous chondrocyte transplantation at 3 tesla--preliminary results

OBJECTIVES: To demonstrate the feasibility of time-reversed fast imaging with steady-state precession (FISP) called PSIF for diffusion-weighted imaging of cartilage and cartilage transplants in a clinical study. MATERIAL AND METHODS: In a cross-sectional study 15 patients underwent MRI using a 3D partially balanced steady-state gradient echo pulse sequence with and without diffusion weighting at two different time points after matrix-associated autologous cartilage transplantation (MACT). Mean diffusion quotients (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) within the cartilage transplants were compared to diffusion quotients found in normal cartilage. RESULTS: The global diffusion quotient found in repair cartilage was significantly higher than diffusion values in normal cartilage (p<0.05). There was a decrease between the earlier and the later time point after surgery. CONCLUSIONS: In-vivo diffusion-weighted imaging based on the PSIF technique is possible. Our preliminary results show follow-up of cartilage transplant maturation in patients may provide additional information to morphological assessment.

Experimental model to evaluate in vivo and in vitro cartilage MR imaging by means of histological analyses

OBJECTIVES: Implementation of an experimental model to compare cartilage MR imaging by means of histological analyses. MATERIAL AND METHODS: MRI was obtained from 4 patients expecting total knee replacement at 1.5 and/or 3T prior surgery. The timeframe between pre-op MRI and knee replacement was within two days. Resected cartilage-bone samples were tagged with Ethi((R))-pins to reproduce the histological cutting course. Pre-operative scanning at 1.5T included following parameters for fast low angle shot (FLASH: TR/TE/FA=33ms/6ms/30 degrees , BW=110kHz, 120mmx120mm FOV, 256x256 matrix, 0.65mm slice-thickness) and double echo steady state (DESS: TR/TE/FA=23.7ms/6.9ms/40 degrees , BW=130kHz, 120x120mm FOV, 256x256 matrix, 0.65mm slice-thickness). At 3T, scan parameters were: FLASH (TR/TE/FA=12.2ms/5.1ms/10 degrees , BW=130kHz, 170x170mm FOV, 320x320, 0.5mm slice-thickness) and DESS (TR/TE/FA=15.6ms/4.5ms/25 degrees , BW=200kHz, 135mmx150mm FOV, 288x320matrix, 0.5mm slice-thickness). Imaging of the specimens was done the same day at 1.5T. MRI (Noyes) and histological (Mankin) score scales were correlated using the paired t-test. Sensitivity and specificity for the detection of different grades of cartilage degeneration were assessed. Inter-reader and intra-reader reliability was determined using Kappa analysis. RESULTS: Low correlation (sensitivity, specificity) was found for both sequences in normal to mild Mankin grades. Only moderate to severe changes were diagnosed with higher significance and specificity. The use of higher field-strengths was advantageous for both protocols with sensitivity values ranging from 13.6% to 93.3% (FLASH) and 20.5% to 96.2% (DESS). Kappa values ranged from 0.488 to 0.944. CONCLUSIONS: Correlating MR images with continuous histological slices was feasible by using three-dimensional imaging, multi-planar-reformat and marker pins. The capability of diagnosing early cartilage changes with high accuracy could not be proven for both FLASH and DESS.

Magnetization transfer contrast and T2 mapping in the evaluation of cartilage repair tissue with 3T MRI

PURPOSE: To use magnetization transfer (MT) imaging in the visualization of healthy articular cartilage and cartilage repair tissue after different cartilage repair procedures, and to assess global as well as zonal values and compare the results to T2-relaxation. MATERIALS AND METHODS: Thirty-four patients (17 after microfracture [MFX] and 17 after matrix-associated autologous cartilage transplantation [MACT]) were examined with 3T MRI. The MT ratio (MTR) was calculated from measurements with and without MT contrast. T2-values were evaluated using a multiecho, spin-echo approach. Global (full thickness of cartilage) and zonal (deep and superficial aspect) region-of-interest assessment of cartilage repair tissue and normal-appearing cartilage was performed. RESULTS: In patients after MFX and MACT, the global MTR of cartilage repair tissue was significantly lower compared to healthy cartilage. In contrast, using T2, cartilage repair tissue showed significantly lower T2 values only after MFX, whereas after MACT, global T2 values were comparable to healthy cartilage. For zonal evaluation, MTR and T2 showed a significant stratification within healthy cartilage, and T2 additionally within cartilage repair tissue after MACT. CONCLUSION: MT imaging is capable and sensitive in the detection of differences between healthy cartilage and areas of cartilage repair and might be an additional tool in biochemical cartilage imaging. For both MTR and T2 mapping, zonal assessment is desirable.

In vivo biochemical 7.0 Tesla magnetic resonance: preliminary results of dGEMRIC, zonal T2, and T2* mapping of articular cartilage

INTRODUCTION: Ultra-high-field whole-body systems (7.0 T) have a high potential for future human in vivo magnetic resonance imaging (MRI). In musculoskeletal MRI, biochemical imaging of articular cartilage may benefit, in particular. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping have shown potential at 3.0 T. Although dGEMRIC, allows the determination of the glycosaminoglycan content of articular cartilage, T2 mapping is a promising tool for the evaluation of water and collagen content. In addition, the evaluation of zonal variation, based on tissue anisotropy, provides an indicator of the nature of cartilage ie, hyaline or hyaline-like articular cartilage.Thus, the aim of our study was to show the feasibility of in vivo dGEMRIC, and T2 and T2* relaxation measurements, at 7.0 T MRI; and to evaluate the potential of T2 and T2* measurements in an initial patient study after matrix-associated autologous chondrocyte transplantation (MACT) in the knee. MATERIALS AND METHODS: MRI was performed on a whole-body 7.0 T MR scanner using a dedicated circular polarization knee coil. The protocol consisted of an inversion recovery sequence for dGEMRIC, a multiecho spin-echo sequence for standard T2 mapping, a gradient-echo sequence for T2* mapping and a morphologic PD SPACE sequence. Twelve healthy volunteers (mean age, 26.7 +/- 3.4 years) and 4 patients (mean age, 38.0 +/- 14.0 years) were enrolled 29.5 +/- 15.1 months after MACT. For dGEMRIC, 5 healthy volunteers (mean age, 32.4 +/- 11.2 years) were included. T1 maps were calculated using a nonlinear, 2-parameter, least squares fit analysis. Using a region-of-interest analysis, mean cartilage relaxation rate was determined as T1 (0) for precontrast measurements and T1 (Gd) for postcontrast gadopentate dimeglumine [Gd-DTPA(2-)] measurements. T2 and T2* maps were obtained using a pixelwise, monoexponential, non-negative least squares fit analysis; region-of-interest analysis was carried out for deep and superficial cartilage aspects. Statistical evaluation was performed by analyses of variance. RESULTS: Mean T1 (dGEMRIC) values for healthy volunteers showed slightly different results for femoral [T1 (0): 1259 +/- 277 ms; T1 (Gd): 683 +/- 141 ms] compared with tibial cartilage [T1 (0): 1093 +/- 281 ms; T1 (Gd): 769 +/- 150 ms]. Global mean T2 relaxation for healthy volunteers showed comparable results for femoral (T2: 56.3 +/- 15.2 ms; T2*: 19.7 +/- 6.4 ms) and patellar (T2: 54.6 +/- 13.0 ms; T2*: 19.6 +/- 5.2 ms) cartilage, but lower values for tibial cartilage (T2: 43.6 +/- 8.5 ms; T2*: 16.6 +/- 5.6 ms). All healthy cartilage sites showed a significant increase from deep to superficial cartilage (P < 0.001). Within healthy cartilage sites in MACT patients, adequate values could be found for T2 (56.6 +/- 13.2 ms) and T2* (18.6 +/- 5.3 ms), which also showed a significant stratification. Within cartilage repair tissue, global mean values showed no difference, with 55.9 +/- 4.9 ms for T2 and 16.2 +/- 6.3 ms for T2*. However, zonal assessment showed only a slight and not significant increase from deep to superficial cartilage (T2: P = 0.174; T2*: P = 0.150). CONCLUSION: In vivo T1 dGEMRIC assessment in healthy cartilage, and T2 and T2* mapping in healthy and reparative articular cartilage, seems to be possible at 7.0 T MRI. For T2 and T2*, zonal variation of articular cartilage could also be evaluated at 7.0 T. This zonal assessment of deep and superficial cartilage aspects shows promising results for the differentiation of healthy and affected articular cartilage. In future studies, optimized protocol selection, and sophisticated coil technology, together with increased signal at ultra-high-field MRI, may lead to advanced biochemical cartilage imaging.

Magnetic resonance imaging for diagnosis and assessment of cartilage defect repairs

Clinical magnetic resonance imaging (MRI) is the method of choice for the non-invasive evaluation of articular cartilage defects and the follow-up of cartilage repair procedures. The use of cartilage-sensitive sequences and a high spatial-resolution technique enables the evaluation of cartilage morphology even in the early stages of disease, as well as assessment of cartilage repair. Sequences that offer high contrast between articular cartilage and adjacent structures, such as the fat-suppressed, 3-dimensional, spoiled gradient-echo sequence and the fast spin-echo sequence, are accurate and reliable for evaluating intrachondral lesions and surface defects of articular cartilage. These sequences can also be performed together in reasonable examination times. In addition to morphology, new MRI techniques provide insight into the biochemical composition of articular cartilage and cartilage repair tissue. These techniques enable the diagnosis of early cartilage degeneration and help to monitor the effect and outcome of various surgical and non-surgical cartilage repair therapies.

High-resolution morphological and biochemical imaging of articular cartilage of the ankle joint at 3.0 T using a new dedicated phased array coil: in vivo reproducibility study

OBJECTIVE: The objective of this study was to evaluate the feasibility and reproducibility of high-resolution magnetic resonance imaging (MRI) and quantitative T2 mapping of the talocrural cartilage within a clinically applicable scan time using a new dedicated ankle coil and high-field MRI. MATERIALS AND METHODS: Ten healthy volunteers (mean age 32.4 years) underwent MRI of the ankle. As morphological sequences, proton density fat-suppressed turbo spin echo (PD-FS-TSE), as a reference, was compared with 3D true fast imaging with steady-state precession (TrueFISP). Furthermore, biochemical quantitative T2 imaging was prepared using a multi-echo spin-echo T2 approach. Data analysis was performed three times each by three different observers on sagittal slices, planned on the isotropic 3D-TrueFISP; as a morphological parameter, cartilage thickness was assessed and for T2 relaxation times, region-of-interest (ROI) evaluation was done. Reproducibility was determined as a coefficient of variation (CV) for each volunteer; averaged as root mean square (RMSA) given as a percentage; statistical evaluation was done using analysis of variance. RESULTS: Cartilage thickness of the talocrural joint showed significantly higher values for the 3D-TrueFISP (ranging from 1.07 to 1.14 mm) compared with the PD-FS-TSE (ranging from 0.74 to 0.99 mm); however, both morphological sequences showed comparable good results with RMSA of 7.1 to 8.5%. Regarding quantitative T2 mapping, measurements showed T2 relaxation times of about 54 ms with an excellent reproducibility (RMSA) ranging from 3.2 to 4.7%. CONCLUSION: In our study the assessment of cartilage thickness and T2 relaxation times could be performed with high reproducibility in a clinically realizable scan time, demonstrating new possibilities for further investigations into patient groups.

Cartilage T2 assessment at 3-T MR imaging: in vivo differentiation of normal hyaline cartilage from reparative tissue after two cartilage repair procedures--initial experience

PURPOSE: To prospectively compare cartilage T2 values after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) repair procedures. MATERIALS AND METHODS: The study had institutional review board approval by the ethics committee of the Medical University of Vienna; informed consent was obtained. Twenty patients who underwent MFX or MACT (10 in each group) were enrolled. For comparability, patients of each group were matched by mean age (MFX, 40.0 years +/- 15.4 [standard deviation]; MACT, 41.0 years +/- 8.9) and postoperative interval (MFX, 28.6 months +/- 5.2; MACT, 27.4 months +/- 13.1). Magnetic resonance (MR) imaging was performed with a 3-T MR imager, and T2 maps were calculated from a multiecho spin-echo measurement. Global, as well as zonal, quantitative T2 values were calculated within the cartilage repair area and within cartilage sites determined to be morphologically normal articular cartilage. Additionally, with consideration of the zonal organization, global regions of interest were subdivided into deep and superficial areas. Differences between cartilage sites and groups were calculated by using a three-way analysis of variance. RESULTS: Quantitative T2 assessment of normal native hyaline cartilage showed similar results for all patients and a significant trend of increasing T2 values from deep to superficial zones (P < .05). In cartilage repair areas after MFX, global mean T2 was significantly reduced (P < .05), whereas after MACT, mean T2 was not reduced (P > or = .05). For zonal variation, repair tissue after MFX showed no significant trend between different depths (P > or = .05), in contrast to repair tissue after MACT, in which a significant increase from deep to superficial zones (P < .05) could be observed. CONCLUSION: Quantitative T2 mapping seems to reflect differences in repair tissues formed after two surgical cartilage repair procedures. (c) RSNA, 2008.

T2 mapping in the knee after microfracture at 3.0 T: correlation of global T2 values and clinical outcome - preliminary results

OBJECTIVE: The aim of our study was to correlate global T2 values of microfracture repair tissue (RT) with clinical outcome in the knee joint. METHODS: We assessed 24 patients treated with microfracture in the knee joint. Magnetic resonance (MR) examinations were performed on a 3T MR unit, T2 relaxation times were obtained with a multi-echo spin-echo technique. T2 maps were obtained using a pixel wise, mono-exponential non-negative least squares fit analysis. Slices covering the cartilage RT were selected and region of interest analysis was done. An individual T2 index was calculated with global mean T2 of the RT and global mean T2 of normal, hyaline cartilage. The Lysholm score and the International Knee Documentation Committee (IKDC) knee evaluation forms were used for the assessment of clinical outcome. Bivariate correlation analysis and a paired, two tailed t test were used for statistics. RESULTS: Global T2 values of the RT [mean 49.8ms, standards deviation (SD) 7.5] differed significantly (P<0.001) from global T2 values of normal, hyaline cartilage (mean 58.5ms, SD 7.0). The T2 index ranged from 61.3 to 101.5. We found the T2 index to correlate with outcome of the Lysholm score (r(s)=0.641, P<0.001) and the IKDC subjective knee evaluation form (r(s)=0.549, P=0.005), whereas there was no correlation with the IKDC knee form (r(s)=-0.284, P=0.179). CONCLUSION: These findings indicate that T2 mapping is sensitive to assess RT function and provides additional information to morphologic MRI in the monitoring of microfracture.

Evaluation and comparison of cartilage repair tissue of the patella and medial femoral condyle by using morphological MRI and biochemical zonal T2 mapping

The objective of this study was to use advanced MR techniques to evaluate and compare cartilage repair tissue after matrix-associated autologous chondrocyte transplantation (MACT) in the patella and medial femoral condyle (MFC). Thirty-four patients treated with MACT underwent 3-T MRI of the knee. Patients were treated on either patella (n = 17) or MFC (n = 17) cartilage and were matched by age and postoperative interval. For morphological evaluation, the MR observation of cartilage repair tissue (MOCART) score was used, with a 3D-True-FISP sequence. For biochemical assessment, T2 mapping was prepared by using a multiecho spin-echo approach with particular attention to the cartilage zonal structure. Statistical evaluation was done by analyses of variance. The MOCART score showed no significant differences between the patella and MFC (p > or = 0.05). With regard to biochemical T2 relaxation, higher T2 values were found throughout the MFC (p < 0.05). The zonal increase in T2 values from deep to superficial was significant for control cartilage (p < 0.001) and cartilage repair tissue (p < 0.05), with an earlier onset in the repair tissue of the patella. The assessment of cartilage repair tissue of the patella and MFC afforded comparable morphological results, whereas biochemical T2 values showed differences, possibly due to dissimilar biomechanical loading conditions.

Comparison of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using inversion recovery and fast T1 mapping sequences

The delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique has shown promising results in pilot clinical studies of early osteoarthritis. Currently, its broader acceptance is limited by the long scan time and the need for postprocessing to calculate the T1 maps. A fast T1 mapping imaging technique based on two spoiled gradient echo images was implemented. In phantom studies, an appropriate flip angle combination optimized for center T1 of 756 to 955 ms yielded excellent agreement with T1 measured using the inversion recovery technique in the range of 200 to 900 ms, of interest in normal and diseased cartilage. In vivo validation was performed by serially imaging 26 hips using the inversion recovery and the Fast 2 angle T1 mapping techniques (center T1 756 ms). Excellent correlation with Pearson correlation coefficient R2 of 0.74 was seen and Bland-Altman plots demonstrated no systematic bias.

Upregulation of alpha-skeletal muscle actin and myosin heavy polypeptide gene products in degenerating rotator cuff muscles

Impaired function of shoulder muscles, resulting from rotator cuff tears, is associated with abnormal deposition of fat in muscle tissue, but corresponding cellular and molecular mechanisms, likely reflected by altered gene expression profiles, are largely unknown. Here, an analysis of muscle gene expression was carried out by semiquantitative RT-PCR in total RNA extracts of supraspinatus biopsies collected from 60 patients prior to shoulder surgery. A significant increase of alpha-skeletal muscle actin (p = 0.0115) and of myosin heavy polypeptide 1 (p = 0.0147) gene transcripts was observed in parallel with progressive fat deposition in the muscle, assessed on parasagittal T1-weighted turbo-spin-echo magnetic resonance images according to Goutallier. Upregulation of alpha-skeletal muscle actin and of myosin heavy polypeptide-1 has been reported to be associated with increased muscle tissue metabolism and oxidative stress. The findings of the present study, therefore, challenge the hypothesis that increased fat deposition in rotator cuff muscle after injury reflects muscle degeneration.

Prostate carcinoma: diffusion-weighted imaging as potential alternative to conventional MR and 11C-choline PET/CT for detection of bone metastases

In a technical development study approved by the institutional ethics committee, the feasibility of fast diffusion-weighted imaging as a replacement for conventional magnetic resonance (MR) imaging sequences (short inversion time inversion recovery [STIR] and T1-weighted spin echo [SE]) and positron emission tomography (PET)/computed tomography (CT) in the detection of skeletal metastases from prostate cancer was evaluated. MR imaging and carbon 11 ((11)C) choline PET/CT data from 11 consecutive prostate cancer patients with bone metastases were analyzed. Diffusion-weighted imaging appears to be equal, if not superior, to STIR and T1-weighted SE sequences and equally as effective as (11)C-choline PET/CT in detection of bone metastases in these patients. Diffusion-weighted imaging should be considered for further evaluation and comparisons with PET/CT for comprehensive whole-body staging and restaging in prostate and other cancers.

Cartilage damage in femoroacetabular impingement (FAI): preliminary results on comparison of standard diagnostic vs delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC)

OBJECTIVES: To study the three-dimensional (3D) T1 patterns in different types of femoroacetabular impingement (FAI) by utilizing delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and subsequent 3D T1 mapping. We used standard grading of OA by Tonnis grade on standard radiographs and morphological grading of cartilage in MRI for comparative analysis. METHODS: dGEMRIC was obtained from ten asymptomatic young-adult volunteers and 26 symptomatic FAI patients. MRI included the routine hip protocol and a dual-flip angle (FA) 3D gradient echo (GRE) sequence utilizing inline T1 measurement. Cartilage was morphologically classified from the radial images based on the extent of degeneration as: no degeneration, degeneration zone measuring <0.75 cm from the rim, >0.75 cm, or total loss. T1 findings were evaluated and correlated. RESULTS: All FAI types revealed remarkably lower T1 mean values in comparison to asymptomatic volunteers in all regions of interest. Distribution of the T1 dGEMRIC values was in accordance with the specific FAI damage pattern. In cam-types (n=6) there was a significant drop (P<0.05) of T1 in the anterior to superior location. In pincer-types (n=7), there was a generalized circumferential decrease noted. High inter-observer (intra-observer) reliability was noted for T1 assessment using intra-class correlation (ICC):intra-class coefficient=0.89 (0.95). CONCLUSIONS: We conclude that a pattern of zonal T1 variation does seem to exist that is unique for different sub-groups of FAI. The FA GRE approach to perform 3D T1 mapping has a promising role for further studies of standard MRI and dGEMRIC in the hip joint.

Multimodal approach in the use of clinical scoring, morphological MRI and biochemical T2-mapping and diffusion-weighted imaging in their ability to assess differences between cartilage repair tissue after microfracture therapy and matrix-associated autologous chondrocyte transplantation: a pilot study

OBJECTIVE: The aim of the present pilot study is to show initial results of a multimodal approach using clinical scoring, morphological magnetic resonance imaging (MRI) and biochemical T2-relaxation and diffusion-weighted imaging (DWI) in their ability to assess differences between cartilage repair tissue after microfracture therapy (MFX) and matrix-associated autologous chondrocyte transplantation (MACT). METHOD: Twenty patients were cross-sectionally evaluated at different post-operative intervals from 12 to 63 months after MFX and 12-59 months after MACT. The two groups were matched by age (MFX: 36.0+/-10.4 years; MACT: 35.1+/-7.7 years) and post-operative interval (MFX: 32.6+/-16.7 months; MACT: 31.7+/-18.3 months). After clinical evaluation using the Lysholm score, 3T-MRI was performed obtaining the MR observation of cartilage repair tissue (MOCART) score as well as T2-mapping and DWI for multi-parametric MRI. Quantitative T2-relaxation was achieved using a multi-echo spin-echo sequence; semi-quantitative diffusion-quotient (signal intensity without diffusion-weighting divided by signal intensity with diffusion weighting) was prepared by a partially balanced, steady-state gradient-echo pulse sequence. RESULTS: No differences in Lysholm (P=0.420) or MOCART (P=0.209) score were observed between MFX and MACT. T2-mapping showed lower T2 values after MFX compared to MACT (P=0.039). DWI distinguished between healthy cartilage and cartilage repair tissue in both procedures (MFX: P=0.001; MACT: P=0.007). Correlations were found between the Lysholm and the MOCART score (Pearson: 0.484; P=0.031), between the Lysholm score and DWI (Pearson:-0.557; P=0.011) and a trend between the Lysholm score and T2 (Person: 0.304; P=0.193). CONCLUSION: Using T2-mapping and DWI, additional information could be gained compared to clinical scoring or morphological MRI. In combination clinical, MR-morphological and MR-biochemical parameters can be seen as a promising multimodal tool in the follow-up of cartilage repair.

Quantitative T2 mapping during follow-up after matrix-associated autologous chondrocyte transplantation (MACT): full-thickness and zonal evaluation to visualize the maturation of cartilage repair tissue

The purpose of this article was to evaluate the potential of in vivo zonal T2-mapping as a noninvasive tool in the longitudinal visualization of cartilage repair tissue maturation after matrix-associated autologous chondrocyte transplantation (MACT). Fifteen patients were treated with MACT and evaluated cross-sectionally, with a baseline MRI at a follow-up of 19.7 +/- 12.1 months after cartilage transplantation surgery of the knee. In the same 15 patients, 12 months later (31.7 +/- 12.0 months after surgery), a longitudinal 1-year follow-up MRI was obtained. MRI was performed on a 3 Tesla MR scanner; morphological evaluation was performed using a double-echo steady-state sequence; T2 maps were calculated from a multiecho, spin-echo sequence. Quantitative mean (full-thickness) and zonal (deep and superficial) T2 values were calculated in the cartilage repair area and in control cartilage sites. A statistical analysis of variance was performed. Full-tickness T2 values showed no significant difference between sites of healthy cartilage and cartilage repair tissue (p < 0.05). Using zonal T2 evaluation, healthy cartilage showed a significant increase from the deep to superficial cartilage layers (p < 0.05). Cartilage repair tissue after MACT showed no significant zonal increase from deep to superficial cartilage areas during baseline MRI (p > 0.05); however, during the 1-year follow-up, a significant zonal stratification could be observed (p < 0.05). Morphological evaluation showed no significant difference between the baseline and the 1-year follow-up MRI. T2 mapping seems to be more sensitive in revealing changes in the repair tissue compared to morphological MRI. In vivo zonal T2 assessment may be sensitive enough to characterize the maturation of cartilage repair tissue.