David Stelzeneder

Cartilage Quality Assessment by Using Glycosaminoglycan Chemical Exchange Saturation Transfer and 23Na MR Imaging at 7 T

PURPOSE To compare a glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging method, which enables sampling of the water signal as a function of the presaturation offset (z-spectrum) at 13 points in clinically feasible imaging times, with sodium 23 ((23)Na) magnetic resonance (MR) imaging in patients after cartilage repair surgery (matrix-associated autologous chondrocyte transplantation and microfracture therapy). MATERIALS AND METHODS One female patient (67.3 years), and 11 male patients (median age, 28.8 years; interquartile range [IQR], 24.6-32.3 years) were examined with a 7-T whole-body system, with approval of the local ethics committee after written informed consent was obtained. A modified three-dimensional gradient-echo sequence and a 28-channel knee coil were used for gagCEST imaging. (23)Na imaging was performed with a circularly polarized knee coil by using a modified gradient-echo sequence. Statistical analysis of differences and Spearman correlation were applied. RESULTS The median of asymmetries in gagCEST z-spectra summed over all offsets from 0 to 1.3 ppm was 7.99% (IQR, 6.33%-8.79%) in native cartilage and 5.13% (IQR, 2.64%-6.34%) in repair tissue. A strong correlation (r = 0.701; 95% confidence interval: 0.21, 0.91) was found between ratios of signal intensity from native cartilage to signal intensity from repair tissue obtained with gagCEST or (23)Na imaging. The median of dimensionless ratios between native cartilage and repair tissue was 1.28 (IQR, 1.20-1.58) for gagCEST and 1.26 (IQR, 1.21-1.48) for (23)Na MR imaging. CONCLUSION The high correlation between the introduced gagCEST method and (23)Na imaging implies that gagCEST is a potentially useful biomarker for glycosaminoglycans.

Treatment of Full-Thickness Chondral Defects With Hyalograft C in the Knee A Prospective Clinical Case Series With 2 to 7 Years’ Follow-up

Background Tissue engineering has become available for cartilage repair in clinical practice. Hypothesis The treatment of full-thickness chondral defects in the knee with a hyaluronan-based scaffold seeded with autolo-gous chondrocytes provides stable improvement of clinical outcome up to 7 years. Study Design Case series; Level of evidence, 4. Methods Fifty-three patients with deep osteochondral defects in the knee were treated with Hyalograft C. The mean age at implantation was 32 6 12 years, the mean defect size was 4.4 6 1.9 cm2, and the mean body mass index was 24.5 6 3.8 kg/m2. Implantations were performed with miniarthrotomy or arthroscopy. The primary indications for implantation with Hyalograft C included young patients with a stable joint, normal knee alignment, and isolated chondral defects with otherwise healthy adjacent cartilage. The secondary indications were patients who did not meet the primary indication criteria or were salvage procedures. Forty-two patients with primary indications and 11 patients with secondary indications were evaluated. Outcome was evaluated with the International Cartilage Repair Society and International Knee Documentation Committee scales, the Lysholm score, the modified Cincinnati score, and with Kaplan-Meier survival analysis. Statistical analysis consisted of bivariate correlation analysis and unpaired, 2-tailed t tests. Results A highly significant increase (P<001) in all knee scores was found in patients treated for the primary indications. Nine of 11 secondary indication cases underwent total knee arthroplasty due to persisting pain between 2 and 5 years after implantation. Graft failure occurred in 3 of 42 patients with primary indication between 6 months and 5 years after implantation. Kaplan-Meier survival demonstrated significantly different chances for survival between primary and secondary outcome and between simple, complex, and salvage cases, respectively (P <.001). Conclusion Hyalograft C autograft provides clinical improvement in healthy young patients with single cartilage defects. Less complicated surgery and lower morbidity are considered advantages of the technique. The results of treatment with Hyalograft C as a salvage procedure or in patients with osteoarthritis are poor.

23Na MR Imaging at 7 T after Knee Matrix―associated Autologous Chondrocyte Transplantation: Preliminary Results

PURPOSE To evaluate the feasibility of sodium 7-T magnetic resonance (MR) imaging in repaired tissue and native cartilage of patients after matrix-associated autologous chondrocyte transplantation (MACT) and compare results with delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) at 3 T. MATERIALS AND METHODS Ethical approval was provided by the local ethics committee; written informed consent was obtained from all patients. Six women and six men (mean age, 32.8 year ± 8.2 [standard deviation] and 32.3 years ± 12.7, respectively) were included. Mean time between MACT and MR was 56 months ± 28. A variable three-dimensional (3D) gradient-echo (GRE) dual-flip-angle technique was used for T1 mapping before and after contrast agent administration at 3 T. All patients were also examined at 7 T (mean delay, 70.5 days ± 80.1). A sodium 23-only transmit-receive knee coil was used with the 3D GRE sequence. A statistical analysis of variance and Pearson correlation were applied. RESULTS Mean signal-to-noise ratio (SNR) was 24 in native cartilage and was 16 in transplants (P < .001). Mean sodium signal intensities normalized with the reference sample were 174 ± 53 and 267 ± 42 for repaired tissue in the cartilage transplant and healthy cartilage, respectively (P < .001). Mean postcontrast T1 values were 510 msec ± 195 and 756 msec ± 188 for repaired tissue and healthy cartilage, respectively (P = .005). Mean score of MR observation of cartilage repair tissue was 75 ± 14. Association between postcontrast T1 and normalized sodium signal values showed a high Pearson correlation coefficient (R) of 0.706 (P = .001). A high correlation of R = 0.836 (P = .001) was found between ratios of normalized sodium values and ratios of T1 postcontrast values. CONCLUSION With the modified 3D GRE sequence at 7 T, a sufficiently high SNR in sodium images was achieved, allowing for differentiation of repaired tissue from native cartilage after MACT. A strong correlation was found between sodium imaging and dGEMRIC in patients after MACT.

Quantitative T2 mapping of the patella at 3.0T is sensitive to early cartilage degeneration, but also to loading of the knee.

Objective The aim of the study was to explore the sensitivity and robustness of T2 mapping in the detection and quantification of early degenerative cartilage changes at the patella. Materials and methods Forty-two patients (22 women, 20 men) with a mean age of 30.3 years and a symptomatic cartilage defect of ICRS grade ≤2 were examined using a 3 T MRI with an 8-channel knee coil. The cartilage lesion was graded based on high-resolution PD TSE and 3D isotropic TrueFISP images. T2 maps were calculated from a standard MESE-sequence, performed at the beginning and at the end of the scan (40 min in-between). Depending on the defect size, a region-of-interest (ROI) analysis was performed on 1–3 consecutive slices. Mean T2 values for the deep, superficial, and global layer as well as the zonal variation were compared among defect grades (ANOVA, post hoc Duncan-test) and over time (Students t-test). Results T2-measurements directly correlated with the extent of cartilage defect (ICRS grade) at all layers and at both time-points. However, correlations were closer for the second measurement at the end of the scan. In this unloaded state, differences in T2-values became more pronounced and were significant even between cartilage of normal appearance adjacent to the defect and healthy cartilage of control patients (both ICRS grade 0). In contrast, there were no such differences among grades in the zonal variation at any time. Conclusion T2 mapping might be a sensitive method for the detection of early cartilage degeneration at the patella in the unloaded joint.

Assessment of articular cartilage repair tissue after matrix-associated autologous chondrocyte transplantation or the microfracture technique in the ankle joint using diffusion-weighted imaging at 3 Tesla

OBJECTIVE The objective was to compare patients after matrix-associated autologous chondrocyte transplantation (MACT) and microfracture therapy (MFX) of the talus using diffusion-weighted imaging (DWI), with morphological and clinical scoring. MATERIALS AND METHODS Twenty patients treated with MACT or MFX (10 per group) were examined using 3 T magnetic resonance imaging (MRI) at 48 ± 21.5 and 59.6 ± 23 months after surgery, respectively. For comparability, patients from each group were matched by age, body mass index, and follow-up. American Orthopaedic Foot and Ankle Society (AOFAS) score served as clinical assessment tool pre- and postoperatively. DWI was obtained using a partially balanced, steady-state gradient echo pulse sequence, as well as the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, based on a 2D proton density-weighted turbo spin-echo sequence and a 3D isotropic true fast imaging with steady-state precession sequence. Semi-quantitative diffusion quotients were calculated after region of interest analysis of repair tissue (RT) and healthy control cartilage, and compared among both groups. RESULTS The mean AOFAS score improved significantly (P = 0.001) for both groups (MACT: 48.8 ± 20.4-83.6 ± 9.7; MFX: 44.3 ± 16.5-77.6 ± 13.2). No differences in the AOFAS (P = 0.327) and MOCART (P = 0.720) score were observed between MACT and MFX postoperatively. DWI distinguished between healthy cartilage and cartilage RT in the MFX group (P = 0.016), but not after MACT treatment (P = 0.105). Significant correlations were found between MOCART score and DWI index after MFX (Pearson: -0.648; P = 0.043), and between the diffusivity and longer follow-up interval in MACT group (Pearson: -0.647, P = 0.043). CONCLUSION Whereas conventional scores reveal a similar outcome after MACT or MFX treatment in the ankle joint, DWI was able to distinguish between different RT qualities, as reported histologically for these diverse surgical procedures.

Quantitative T2 evaluation at 3.0 T compared to morphological grading of the lumbar intervertebral disc: A standardized evaluation approach in patients with low back pain

BACKGROUND The purpose of our investigation was to compare quantitative T2 relaxation time measurement evaluation of lumbar intervertebral discs with morphological grading in young to middle-aged patients with low back pain, using a standardized region-of-interest evaluation approach. PATIENTS AND METHODS Three hundred thirty lumbar discs from 66 patients (mean age, 39 years) with low back pain were examined on a 3.0T MR unit. Sagittal T1-FSE, sagittal, coronal, and axial T2-weighted FSE for morphological MRI, as well as a multi-echo spin-echo sequence for T2 mapping, were performed. Morphologically, all discs were classified according to Pfirrmann et al. Equally sized rectangular regions of interest (ROIs) for the annulus fibrosus were selected anteriorly and posteriorly in the outermost 20% of the disc. The space between was defined as the nucleus pulposus. To assess the reproducibility of this evaluation, inter- and intraobserver statistics were performed. RESULTS The Pfirrmann scoring of 330 discs showed the following results: grade I: six discs (1.8%); grade II: 189 (57.3%); grade III: 96 (29.1%); grade IV: 38 (11.5%); and grade V: one (0.3%). The mean T2 values (in milliseconds) for the anterior and the posterior annulus, and the nucleus pulposus for the respective Pfirrmann groups were: I: 57/30/239; II: 44/67/129; III: 42/51/82; and IV: 42/44/56. The nucleus pulposus T2 values showed a stepwise decrease from Pfirrmann grade I to IV. The posterior annulus showed the highest T2 values in Pfirrmann group II, while the anterior annulus showed relatively constant T2 values in all Pfirrmann groups. The inter- and intraobserver analysis yielded intraclass correlation coefficients (ICC) for average measures in a range from 0.82 (anterior annulus) to 0.99 (nucleus). CONCLUSIONS Our standardized method of region-specific quantitative T2 relaxation time evaluation seems to be able to characterize different degrees of disc degeneration quantitatively. The reproducibility of our ROI measurements is sufficient to encourage the use of this method in future investigations, particularly for longitudinal studies.

Patterns of joint damage seen on MRI in early hip osteoarthritis due to structural hip deformities

OBJECTIVE The aim of this study was to evaluate differences in damage patterns assessed using magnetic resonance imaging (MRI) between hips with femoroacetabular impingement (FAI) and developmental dysplasia of the hip (DDH) as well as to correlate MRI findings with delayed Gadolinium enhanced MRI of cartilage (dGEMRIC) and with patient pain. DESIGN This retrospective study included 40 patients (mean age 28.6 ± 11.2 years) who underwent dGEMRIC and morphological MRI of the hip. Twenty-one hips with FAI and 19 with DDH were investigated. A self-developed morphological grading (MRI score) and dGEMRIC evaluation were done on seven radial reformats obtained from an isotropic 3D True-fast imaging with steady state precession (FISP) sequence and an isotropic T1-mapping sequence. The observed damage patterns were summed up into sub-scores and a total MRI score. RESULTS Labrum damage, paralabral cysts, and acetabular rim bone cysts were more common in DDH patients than in FAI patients. No significant differences were seen in the occurrence of cartilage damage, bone cysts, or osteophytes. In DDH (but not in FAI), the dGEMRIC index demonstrated a tendency for lower values in areas next to cartilage defects. There was no association between labrum damage and dGEMRIC index. A moderate correlation was seen between Western Ontario and McMaster Universities (WOMAC) pain score and cartilage damage, paralabral cysts, and the total MRI score. CONCLUSIONS This study confirms a higher prevalence of labrum damage but not cartilage damage in patients with DDH in comparison to patients with FAI. In addition, our data suggests an association of cartilage damage and paralabral cysts with patient reported pain.

Evaluation of native hyaline cartilage and repair tissue after two cartilage repair surgery techniques with 23Na MR imaging at 7 T: initial experience

OBJECTIVE To compare the sodium normalized mean signal intensity (NMSI) values between patients after bone marrow stimulation (BMS) and matrix-associated autologous chondrocyte transplantation (MACT) cartilage repair procedures. METHODS Nine BMS and nine MACT patients were included. Each BMS patient was matched with one MACT patient according to age [BMS 36.7 ± 10.7 (mean ± standard deviation) years; MACT 36.9 ± 10.0 years], postoperative interval (BMS 33.5 ± 25.3 months; MACT 33.2 ± 25.7 months), and defect location. All magnetic resonance imaging (MRI) measurements were performed on a 7 T system. Proton images served for morphological evaluation of repair tissue using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. Sodium NMSI values in the repair area and morphologically normal cartilage were calculated. Clinical outcome was assessed right after MRI. Analysis of covariance, t-tests, and Pearson correlation coefficients were evaluated. RESULTS Sodium NMSI was significantly lower in BMS (P = 0.004) and MACT (P = 0.006) repair tissue, compared to reference cartilage. Sodium NMSI was not different between the reference cartilage in MACT and BMS patients (P = 0.664), however it was significantly higher in MACT than in BMS repair tissue (P = 0.028). Better clinical outcome was observed in BMS than in MACT patients. There was no difference between MOCART scores for MACT and BMS patients (P = 0.915). We did not observe any significant correlation between MOCART score and sodium repair tissue NMSI (r = -0.001; P = 0.996). CONCLUSIONS Our results suggest higher glycosaminoglycan (GAG) content, and therefore, repair tissue of better quality in MACT than in BMS patients. Sodium imaging might be beneficial in non-invasive evaluation of cartilage repair surgery efficacy.

Cartilage repair of the ankle: first results of T2 mapping at 7.0 T after microfracture and matrix associated autologous cartilage transplantation

BACKGROUND Both microfracture (MFX) and matrix associated autologous cartilage transplantation (MACT) are currently used to treat cartilage defects of the talus. T2 mapping of the ankle at 7 T has the potential to assess the collagen fibril network organization of the native hyaline cartilage and of the repair tissue (RT). This study provides first results regarding the properties of cartilage RT after MFX (mean follow-up: 113.8 months) and MACT (65.4 months). METHODS A multi-echo spin-echo sequence was used at 7 T to assess T2 maps in 10 volunteer cases, and in 10 cases after MFX and MACT each. Proton weighted morphological images and clinical data were used to ensure comparable baseline criteria. RESULTS A significant zonal variation of T2 was found in the volunteers. T2 of the superficial and the deep layer was 39.3 ± 5.9 ms and 21.1 ± 3.1 ms (zonal T2 index calculated by superficial T2/deep T2: 1.87 ± 0.2, P < 0.001). In MFX, T2 of the reference cartilage was 37.4 ± 5.0 ms and 25.3 ± 3.5 ms (1.51 ± 0.3, P < 0.001). In the RT, T2 was 43.4 ± 10.5 ms and 36.3 ± 7.7 ms (1.20 ± 0.2, P = 0.009). In MACT, T2 of the reference cartilage was 39.0 ± 9.1 ms and 27.1 ± 6.6 ms (1.45 ± 0.2, P < 0.001). In the RT, T2 was 44.6 ± 10.4 ms and 38.6 ± 7.3 ms (1.15 ± 0.1, P = 0.003). The zonal RT T2 variation differed significantly from the reference cartilage in both techniques (MFX: P = 0.004, MACT: P = 0.001). CONCLUSION T2 mapping at 7 T allows for the quantitative assessment of the collagen network organization of the talus. MACT and MFX yielded RT with comparable T2 properties.

Delayed gadolinium-enhanced MRI of cartilage in the ankle at 3 T: Feasibility and preliminary results after matrix-associated autologous chondrocyte implantation

To demonstrate the feasibility of delayed gadolinium‐enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in the ankle at 3 T and to obtain preliminary data on matrix associated autologous chondrocyte (MACI) repair tissue.