Evaluation of cartilage repair tissue in the knee and ankle joint using sodium magnetic resonance imaging at 7 Tesla

Die Gelenksknorpel von Erwachsenen weisen kein oder ein nur sehr limitiertes intrinsisches Vermögen zur Selbstreparatur auf. Da unbehandelte Knorpeldefekte sich oft zur Gelenksarthrose entwickeln, sollten symptomatische Defekte behandelt werden. Unterschiedliche Knorpelreparaturverfahren wurden mit dem Ziel entwickelt, die Gelenksfunktion wiederherzustellen und eine weitere Degeneration des Knorpels zu verhindern indem Reparaturgewebe mit der gleichen Struktur, Zusammensetzung, und biomechanischen Eigenschaften wie der native Knorpel verwendet wird. Verschiedene Knorpelreparaturverfahren wie etwa Knochenmarksstimulationstechniken (BMS) einschliesslich Mikrofrakturierung (MFX) oder zell-basierte Techniken wie beispielsweise die Matrix-assozierte Autologe Chondrozyten Transplantation (MACT) wurden entwickelt. Da Biopsien des Knorpelersatzgewebes invasiv sind und nicht beliebig wiederholt werden können ist eine nicht-invasive Methode notwendig, die es erlaubt die Qualität des Knorpels und des Reparaturgewebes im zeitlichen Verlauf zu verfolgen. Negativ geladene Glykosaminoglykane (GAG) sind sehr wichtig für die Knorpelfunktion, da sie positive Ionen wie etwa Natrium anziehen. Die hohe Konzentration von Ionen im Knorpel ist für den hohen osmotischen Druck verantwortlich, der dem Knorpel seine hohe Belastbarkeit gegen Kompression verschafft. Da GAG durch Natrium-Ionen kompensiert werden, wurde die Natrium-Magnetresonanzbildgebung (MRI) als eine sensitive Methode für die in vivo Evaluierung der GAG Konzentration in nativem Knorpel, jedoch nicht in Reparaturgewebe, validiert. Das Hauptziel dieser Doktorarbeit ist deshalb die Natrium 7 Tesla MRI für die Evaluierung von Knorpelreparaturgewebequalität in Patienten nach unterschiedlichen Knorpelreparationstechniken im Knie und im Sprunggelenk zu optimieren und zu validieren. In unseren Studien wurde Natrium MRI weltweit erstmals für die klinische Evaluierung von Knorpelreparaturgewebe verwendet. Die starke Korrelation zwischen Natriumbildgebung und dGEMRIC (eine andere GAG-sensitive Technik) in Patienten nach MACT des femoralen Knorpels beweisen die Sensitivität der Natriumbildgebung für Änderungen des GAG Gehaltes in nativem Knorpel und Reparaturgewebe in vivo. Ein Vergleich zwischen BMS und MACT Patienten zeigte signifikant niedrigere Natriumwerte in Reparaturgewebe als in nativem femoralem Knorpel. Obwohl das morphologische Erscheinungsbild von Reparaturgewebe in BMS und MACT Patienten ähnlich war, deuten unsere Natrium MRI Resultate auf einen höheren GAG Gehalt hin, und daher auf Reparaturgewebe von höherer Qualität in Patienten nach MACT im Gegensatz zu Patienten nach BMS Behandlung. Eine ausreichend hohe Sensitivität der Natrium MRI für Änderungen im GAG Gehalt in dünnen Gelenksknorpeln wie dem Sprunggelenk wurde durch eine starke Korrelation gezeigt, die zwischen den Natriumresultaten und dem histochemisch evaluierten GAG Gehalt in Kadavergelenkspräparaten beobachtet wurde. Im Gegensatz zu unserer Ergebnissen beim femoralen Knorpel des Kniegelenkes, scheint MFX und MACT beim Knorpel Reparaturgewebe des Talus am Sprunggelenk einen ähnlichen GAG Gehalt und ähnlichen morphologischen Erscheinungsbild zu produzieren, allerdings von niedrigerer Qualität als bei nativem Knorpel. Natrium MRI liefert Informationen über die GAG Konzentration, welche entscheidend für die ordentliche Funktion des Reparaturgewebes ist und welches deshalb vorteilhaft für die nicht-invasive Evaluierung der Effizienz von Knorpelreparaturoperationen und der Beurteilung von neuen Knorpelreparaturverfahren ist.Articular cartilage of adults shows no or very limited intrinsic capacity for self-repair. Since untreated chondral defects often progress to osteoarthritis, symptomatic defects should be treated. Different cartilage repair procedures have been developed with the goal to restore joint function and prevent further cartilage degeneration by providing repair tissue of the same structure, composition, and biomechanical properties as native cartilage. Various cartilage repair procedures have been developed; including bone marrow stimulation (BMS) techniques such as microfracture (MFX), cell-based techniques such as matrix-associated autologous chondrocyte transplantation (MACT), and others. Since biopsies of cartilage repair tissue are invasive and cannot be repeated, a noninvasive method is needed that could follow-up the quality of cartilage and repair tissue. Negatively charged glycosaminoglycans (GAG) are very important for cartilage function as they attract positive ions such as sodium. The high concentration of ions in cartilage is responsible for osmotic pressure providing cartilage its resilience to compression. Since GAGs are counterbalanced by sodium ions, sodium magnetic resonance imaging (MRI) was validated as a sensitive method for the in vivo evaluation of GAG concentration in native cartilage but not for repair tissue. Thus, the main goal of this thesis was to optimize and validate sodium 7 Tesla MRI for the evaluation of cartilage repair tissue quality in patients after different cartilage repair surgeries in the knee and ankle joint. In our studies, sodium MRI was used for the first time for the clinical evaluation of cartilage repair tissue. A strong correlation found between sodium imaging and dGEMRIC (another GAG-sensitive technique) in patients after MACT on femoral cartilage proved sensitivity of sodium MRI to GAG changes in native cartilage and repair tissue in vivo. Comparison between BMS and MACT patients showed significantly lower sodium values in repair tissue than in native femoral cartilage. Although morphological appearance of repair tissue was similar in BMS and MACT patients, our sodium MRI results suggest higher GAG content, and thus repair tissue of higher quality, in patients after MACT than in patients after BMS treatment. Sufficiently high sensitivity of sodium imaging to changes in the GAG content in thin ankle cartilage was demonstrated by a strong correlation observed between the sodium results and the histochemically evaluated GAG content in cadaver ankle samples. In contrast to our findings from femoral cartilage of knee joint, MFX and MACT in talar cartilage of ankle joint seems to produce repair tissue with a similar GAG content and similar morphological appearance, however, of lower quality than native cartilage. Sodium MRI provides information on the GAG concentration that is crucial for proper function of repair tissue and might be therefore beneficial in non-invasive evaluation of efficacy of cartilage repair surgery and in assessment of new cartilage repair procedures.submitted by Stefan ZbynAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZusammenfassung in deutscher SpracheMedizinische Universität Wien, Dissertation, 2015OeBB(VLID)171440

A comparison of multi-echo spin-echo and triple-echo steady-state T2 mapping for in vivo evaluation of articular cartilage

To assess the clinical relevance of T-2 relaxation times, measured by 3D triple-echo steady-state (3D-TESS), in knee articular cartilage compared to conventional multi-echo spin-echo T-2-mapping. Thirteen volunteers and ten patients with focal cartilage lesions were included in this prospective study. All subjects underwent 3-Tesla MRI consisting of a multi-echo multi-slice spin-echo sequence (CPMG) as a reference method for T-2 mapping, and 3D TESS with the same geometry settings, but variable acquisition times: standard (TESSs 4:35min) and quick (TESSq 2:05min). T-2 values were compared in six different regions in the femoral and tibial cartilage using a Wilcoxon signed ranks test and the Pearson correlation coefficient (r). The local ethics committee approved this study, and all participants gave written informed consent. The mean quantitative T-2 values measured by CPMG (mean: 46 +/- 9ms) in volunteers were significantly higher compared to those measured with TESS (mean: 31 +/- 5ms) in all regions. Both methods performed similarly in patients, but CPMG provided a slightly higher difference between lesions and native cartilage (CPMG: 90ms -> 61ms [31%],p=0.0125;TESS 32ms -> 24ms [24%],p=0.0839). 3D-TESS provides results similar to those of a conventional multi-echo spin-echo sequence with many benefits, such as shortening of total acquisition time and insensitivity to B-1 and B-0 changes. aEuro cent 3D-TESS T (2) mapping provides clinically comparable results to CPMG in shorter scan-time. aEuro cent Clinical and investigational studies may benefit from high temporal resolution of 3D-TESS. aEuro cent 3D-TESS T (2) values are able to differentiate between healthy and damaged cartilage.P 25246-B24(VLID)308411

Biochemical (T2, T2* and magnetisation transfer ratio) MRI of knee cartilage : feasibility at ultra-high field (7T) compared with high field (3T) strength

This study compares the performance and the reproducibility of quantitative T2, T2* and the magnetisation transfer ratio (MTR) of articular cartilage at 7T and 3T

Quantitative sodium MR imaging at 7 T: initial results and comparison with diffusion-weighted imaging in patients with breast tumors

To investigate the clinical feasibility of a quantitative sodium 23 (Na) magnetic resonance (MR) imaging protocol developed for breast tumor assessment and to compare it with 7-T diffusion-weighted imaging (DWI). Materials and Methods: Written informed consent in this institutional review board-approved study was obtained from eight healthy volunteers and 17 patients with 20 breast tumors (five benign, 15 malignant). To achieve the best image quality and reproducibility, the Na sequence was optimized and tested on phantoms and healthy volunteers. For in vivo quantification of absolute tissue sodium concentration (TSC), an external phantom was used. Static magnetic field, or B, and combined transmit and receive radiofrequency field, or B, maps were acquired, and image quality, measurement reproducibility, and accuracy testing were performed. Bilateral Na and DWI sequences were performed before contrast material-enhanced MR imaging in patients with breast tumors. TSC and apparent diffusion coefficient (ADC) were calculated and correlated for healthy glandular tissue and benign and malignant lesions. Results: The Na MR imaging protocol is feasible, with 1.5-mm inplane resolution and 16-minute imaging time. Good image quality was achieved, with high reproducibility (mean TSC values 6 standard deviation for the test, 36 mmol per kilogram of wet weight ± 2 [range, 34-37 mmol/kg ± for the retest, 37 mmol/kg ±1 [range, 35-39 mmol/kg]; P = .610) and accuracy (r = 0.998,

Sodium MR imaging of the lumbar intervertebral disk at 7 T: correlation with T2 mapping and modified Pfirrmann score at 3 T - preliminary results

PURPOSE: To compare sodium imaging of lumbar intervertebral disks in asymptomatic volunteers at 7-T magnetic resonance (MR) imaging with quantitative T2 mapping and morphologic scoring at 3 T. MATERIALS AND METHODS: Following ethical board approval and informed consent, the L2-3 to L5-S1 disks were examined in 10 asymptomatic volunteers (nine men, one woman; mean age, 30 years; range, 23-43 years). At 7 T, normalized sodium signal-to-noise ratios were calculated, by using region-of-interest analysis. At 3 T, T2 mapping was performed with a multiecho spin-echo sequence (repetition time msec/echo times msec, 1500/24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156). T2 values were calculated over the nucleus, with a pixelwise, monoexponential nonnegative least-squares-fit analysis. Morphologic grading according to a modified Pfirrmann score was assessed independently by three experienced musculoskeletal radiologists, and Pearson correlation analysis of the covariates was performed. RESULTS: The mean normalized sodium signal intensity was 275.5±115.4 (standard deviation). The T2 mapping showed a mean value of 89.8 msec±19.34. The median modified Pfirrmann score was 2b (90% had score≤3c). The Pearson correlation coefficient showed a cubic function between sodium imaging and the modified Pfirrmann score, a moderate inverse correlation between T2 mapping and the modified Pfirrmann score (r=-0.62), and no correlation between sodium imaging and T2 mapping (r=0.06). CONCLUSION: The results suggest that MR imaging of the intervertebral disk, using sodium imaging and T2 mapping, can help characterize different component changes and that both of these methods are to some degree related to the Pfirrmann score