In vivo biochemical assessment of cartilage with gagCEST MRI: Correlation with cartilage properties.

To assess articular cartilage in vivo, a noninvasive measurement is proposed to evaluate damage of the cartilage. It is hypothesized that glycosaminoglycan chemical exchange saturation transfer (gagCEST) can be applied as a noninvasive imaging technique as it would relate to electromechanical indentation and GAG content as measured with biochemical assays. This pilot study applies gagCEST MRI in total knee arthroplasty (TKA) patients to assess substantially damaged articular cartilage. The outcome was verified against electromechanical indentation and biochemical assays to assess the potential of gagCEST MRI. Five TKA patients were scanned on a 7.0 T MRI with a gagCEST sequence. Articular resurfacing cuts after TKA were obtained for electromechanical and biochemical analyses. The gagCEST MRI measurements on the medial condyle showed a moderate correlation with the GAG content, although sensitivity on the lateral condyle was lacking. Additionally, a strong negative correlation of gagCEST MRI with the electromechanical measurements was observed in the regression analysis. Correlation of gagCEST MRI with electromechanical measurements was shown, but the correlation of gagCEST MRI with GAG content was not convincing. In conclusion, gagCEST could be a useful tool to assess the GAG content in articular cartilage noninvasively, although the mismatch in heterogeneity requires further investigation.

Can sodium MRI be used as a method for mapping of cartilage stiffness?

OBJECTIVE: Sodium concentration is responsible for (at least part of) the stiffness of articular cartilage due to the osmotic pressure it generates. Therefore, we hypothesized that we could use sodium MRI to approximate the stiffness of cartilage to assess early cartilage degeneration. METHODS: Four human tibial plateaus were retrieved from patients undergoing total knee replacement (TKR), and their cartilage stiffness mapped with indentation testing, after which samples were scanned in a 7 T MRI to determine sodium concentration. The relation of biomechanical parameters to MRI sodium and glycosaminoglycan (GAG) concentration was explored by a linear mixed model. RESULTS: Weak correlations of GAG concentration with apparent peak modulus (p = 0.0057) and apparent equilibrium modulus (p = 0.0181) were observed and lack of correlation of GAG concentration versus MRI sodium concentration was observed. MRI sodium concentration was not correlated with apparent peak modulus, though a moderate correlation of MRI sodium concentration with permeability was shown (p = 0.0014). DISCUSSION AND CONCLUSION: Although there was correlation between GAG concentration and cartilage stiffness, this was not similar with sodium concentration as measured by MRI. Thus, if the correlation between MRI sodium imaging and GAG concentration could be resolved, this strategy for assessing cartilage functional quality still holds promise.

T2* mapping in an equine articular groove model: Visualizing changes in collagen orientation.

T2* mapping is promising for the evaluation of articular cartilage collagen. In this work, a groove model in a large animal is used as a model for posttraumatic arthritis. We hypothesized that T2* mapping could be employed to differentiate between healthy and (subtly) damaged cartilage. Eight carpal joints were obtained from four adult Shetland ponies that had been included in the groove study. In this model, grooves were surgically created on the proximal articular surface of the intermediate carpal bone (radiocarpal joint) and the radial facet of the third carpal bone (middle carpal joint) by either coarse disruption or sharp incision. After 9 months, T2* mapping of the entire carpal joint was carried out on a 7.0-T whole-body magnetic resonance imaging (MRI) scanner by means of a gradient echo multi-echo sequence. Afterwards, assessment of collagen orientation was carried out based on Picrosirius Red-stained histological sections, visualized by polarized light microscopy (PLM). The average T2* relaxation time in grooved samples was lower than in contralateral control sites. Opposite to the grooved areas, the "kissing sites" had a higher average T2* relaxation time than the grooved sites. PLM showed mild changes in orientation of the collagen fibers, particularly around blunt grooves. This work shows that T2* relaxation times are different in healthy cartilage vs (early) damaged cartilage, as induced by the equine groove model. Additionally, the average T2* relaxation times are different in kissing lesions vs the grooved sites.

Detection of early cartilage damage: feasibility and potential of gagCEST imaging at 7T.

OBJECTIVES: The purpose was to implement a fast 3D glycosaminoglycan Chemical Exchange Saturation Transfer (gagCEST) sequence at 7 T, test stability and reproducibility in cartilage in the knee in healthy volunteers, and evaluate clinical applicability in cartilage repair patients. METHODS: Experiments were carried out on a 7-T scanner using a volume transmit coil and a 32-channel receiver wrap-around knee coil. The 3D gagCEST measurement had an acquisition time of 7 min. Signal stability and reproducibility of the GAG effect were assessed in eight healthy volunteers. Clinical applicability of the method was demonstrated in five patients before cartilage repair surgery. RESULTS: Coefficient of variation of the gagCEST signal was 1.9%. The reproducibility of the GAG effect measurements was good in the medial condyle (ICC = 0.87) and excellent in the lateral condyle (ICC = 0.97). GAG effect measurements in healthy cartilage ranged from 2.6%-12.4% compared with 1.3%-5.1% in damaged cartilage. Difference in GAG measurement between healthy cartilage and damaged cartilage was significant (p < 0.05). CONCLUSIONS: A fast 3D gagCEST sequence was applied at 7 T for use in cartilage in the knee, acquired within a clinically feasible scan time of 7 min. We demonstrated that the method has high stability, reproducibility and clinical applicability. KEY POINTS: • gagCEST measurements are stable and reproducible • A non-invasive GAG measurement with gagCEST can be acquired in 7 min • gagCEST is able to discriminate between healthy and damaged cartilage.

Resource utilization in lung cancer diagnostic procedures: Current use and budget consequences.

OBJECTIVES: The main objective of this study is to determine the current use of lung cancer diagnostic procedures in two large hospitals in the Netherlands, to explore deviations in guideline adherence between the hospitals, and to estimate the budget impact of the diagnostic work-up as well as the over- and underutilization. MATERIALS & METHODS: A state transition model for the diagnostic pathway for lung cancer patients was developed using existing clinical practice guidelines (CPG) combined with a systematic literature. In addition to the CPGs depicting current practice, diagnostic utilization was gathered in two large hospitals representing an academic tertiary care hospital and a large regional teaching hospital for patients, who were selected from the Netherlands cancer registry. RESULTS: The total population consisted of 376 patients with lung cancer. Not in all cases the guideline was followed, for instance in the usage of MR brain with stage III lung cancer patients (n = 70). The state-transition model predicts an average budget impact for the diagnostic pathway per patient estimated of € 2496 in the academic tertiary care hospital and € 2191 in the large regional teaching hospital. CONCLUSION: The adherence to the CPG's differed between hospitals, which questions the adherence to CPG's in general. Adherence to CPG's could lead to less costs in the diagnostic pathway for lung cancer patients.