Štefan Zbýň

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.

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.

Clinical applications at ultrahigh field (7 T). Where does it make the difference

Presently, three major MR vendors provide commercial 7‐T units for clinical research under ethical permission, with the number of operating 7‐T systems having increased to over 50. This rapid increase indicates the growing interest in ultrahigh‐field MRI because of improved clinical results with regard to morphological as well as functional and metabolic capabilities. As the signal‐to‐noise ratio scales linearly with the field strength (B0) of the scanner, the most obvious application at 7 T is to obtain higher spatial resolution in the brain, musculoskeletal system and breast. Of specific clinical interest for neuro‐applications is the cerebral cortex at 7 T, for the detection of changes in cortical structure as a sign of early dementia, as well as for the visualization of cortical microinfarcts and cortical plaques in multiple sclerosis. In the imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology can be visualized with excellent resolution. The dynamic and static blood oxygenation level‐dependent contrast increases linearly with the field strength, which significantly improves the pre‐surgical evaluation of eloquent areas before tumor removal. Using susceptibility‐weighted imaging, the plaque–vessel relationship and iron accumulation in multiple sclerosis can be visualized for the first time. Multi‐nuclear clinical applications, such as sodium imaging for the evaluation of repair tissue quality after cartilage transplantation and 31P spectroscopy for the differentiation between non‐alcoholic benign liver disease and potentially progressive steatohepatitis, are only possible at ultrahigh fields. Although neuro‐ and musculoskeletal imaging have already demonstrated the clinical superiority of ultrahigh fields, whole‐body clinical applications at 7 T are still limited, mainly because of the lack of suitable coils. The purpose of this article was therefore to review the clinical studies that have been performed thus far at 7 T, compared with 3 T, as well as those studies performed at 7 T that cannot be routinely performed at 3 T. Copyright

Evaluation of cartilage repair and osteoarthritis with sodium MRI

The growing need for early diagnosis and higher specificity than that which can be achieved with morphological MRI is a driving force in the application of methods capable of probing the biochemical composition of cartilage tissue, such as sodium imaging. Unlike morphological imaging, sodium MRI is sensitive to even small changes in cartilage glycosaminoglycan content, which plays a key role in cartilage homeostasis. Recent advances in high‐ and ultrahigh‐field MR systems, gradient technology, phase‐array radiofrequency coils, parallel imaging approaches, MRI acquisition strategies and post‐processing developments have resulted in many clinical in vivo sodium MRI studies of cartilage, even at 3 T. Sodium MRI has great promise as a non‐invasive tool for cartilage evaluation. However, further hardware and software improvements are necessary to complete the translation of sodium MRI into a clinically feasible method for 3‐T systems. This review is divided into three parts: (i) cartilage composition, pathology and treatment; (ii) sodium MRI; and (iii) clinical sodium MRI studies of cartilage with a focus on the evaluation of cartilage repair tissue and osteoarthritis. Copyright

Sodium MR Imaging of Achilles Tendinopathy at 7 T: Preliminary Results

PURPOSE To investigate the feasibility of sodium magnetic resonance (MR) imaging in the diagnosis of Achilles tendinopathy. MATERIALS AND METHODS Institutional review board approval and written informed consent were obtained. Twenty healthy volunteers and eight patients with Achilles tendinopathy were examined by using a 7-T whole-body MR imager with a 15-channel sodium knee coil. The sodium signal-to-noise ratio (SNR) from each region, as well as from the whole Achilles tendon, was compared between patients and healthy control subjects. The changes in SNR were assessed with a two-tailed unpaired t test in three regions of the Achilles tendon: the insertion area, the middle portion, and the muscle-tendon junction. P values less than .05 were considered to indicate a statistically significant difference. To validate a relationship between the sodium SNR and the glycosaminoglycan content in tendon, five cadaver ankles were examined with MR imaging and immunohistologically. The Pearson correlation coefficient between sodium SNR and glycosaminoglycan content was calculated. RESULTS Significant differences (P < .05) in the mean sodium SNR of healthy control subjects (mean SNR, 4.9 ± 2.1 [standard deviation]) and patients with chronic Achilles tendinopathy (mean SNR, 9.3 ± 2.3) were observed. Similar results were found at the insertion (mean SNR in control subjects, 6.7 ± 2.3; mean SNR in patients, 12.3 ± 4.5; P < .05) and the midportion (mean SNR in control subjects, 5.1 ± 1.9; mean SNR in patients, 9.4 ± 3.0; P < .05) of the Achilles tendon. At the muscle-tendon junction, the sodium SNR difference between control subjects and patients was small but still bellow the significance level (P = .0137). The increase in sodium SNR was observed in all regions independently of the location of morphologic findings. The Pearson correlation coefficient between sodium SNR and glycosaminoglycan content was 0.71. CONCLUSION Sodium MR imaging may allow detection of the proteoglycan content increase in Achilles tendinopathy and thus identify the biochemical changes in the early stages of tendinopathy.

Chronic peripheral hyperinsulinemia in type 1 diabetic patients after successful combined pancreas kidney transplantation does not affect ectopic lipid accumulation in skeletal muscle and liver.

OBJECTIVE So far it is unclear whether chronic peripheral hyperinsulinemia per se might contribute to ectopic lipid accumulation and consequently insulin resistance. We investigated the effects of systemic instead of portal insulin release in type 1 diabetic patients after successful pancreas-kidney transplantation (PKT) with systemic venous drainage on the intracellular lipid content in liver and soleus muscle, endogenous glucose production (EGP), and insulin sensitivity. RESEARCH DESIGN AND METHODS In nine PKT patients and nine matching nondiabetic control subjects, intrahepatocellular lipids (IHCLs) and intramyocellular lipids (IMCLs) were measured using 1H nuclear magnetic resonance spectroscopy. Fasting EGP was measured using d-[6,6-2H2]glucose tracer dilution. A 3-h 75-g oral glucose tolerance test (OGTT) allowed us to assess kinetics of glucose, free fatty acids, insulin, and C-peptide concentrations in plasma and to calculate the clamp-like index (CLIX) for insulin sensitivity and the hepatic insulin resistance (HIR) index. RESULTS The PKT patients displayed approximately twofold increased fasting insulin (20 ± 6 vs. 9 ± 3 μU/ml; P < 0.0002) compared with that in nondiabetic control subjects and ∼10% increased fasting glucose (P < 0.02) concentrations, but during the OGTT areas under the concentration curves of C-peptide and insulin were similar. IHCL (PKT, 2.9 ± 2.5%; nondiabetic control subjects, 4.4 ± 6.6%), IMCL (PKT, 1.0 ± 0.4%; nondiabetic control subjects, 1.0 ± 0.5%), CLIX (PKT, 8 ± 2; nondiabetic control subjects, 7 ± 3), HIR (PKT, 25.6 ± 13.2; nondiabetic control subjects, 35.6 ± 20 [mg · min−1 · kg−1] × [μU/ml]), and EGP (PKT, 1.6 ± 0.2; nondiabetic control subjects, 1.7 ± 0.2 mg · min−1 · kg−1) were comparable between PKT patients and nondiabetic control subjects. IHCL was negatively correlated with CLIX in all participants (r = −0.55; P < 0.04). CONCLUSIONS Despite fasting peripheral hyperinsulinemia because of systemic venous drainage, type 1 diabetic patients after PKT show similar IHCL, IMCL, insulin sensitivity, and fasting EGP in comparison with nondiabetic control subjects. These results suggest that systemic hyperinsulinemia per se does not cause ectopic lipid accumulation in liver and skeletal muscle.

Quantitative MRI analysis of menisci using biexponential T2* fitting with a variable echo time sequence

The goal of this study was to differentiate between normal, degenerative meniscus, and meniscal tears using monoexponentially and biexponentially calculated T2*. Meniscal disease, characterized by an altered collagen fiber matrix, might be detectable in vivo using quantitative T2* mapping.

Sodium magnetic resonance imaging of ankle joint in cadaver specimens, volunteers, and patients after different cartilage repair techniques at 7 T: initial results.

ObjectivesThe goal of cartilage repair techniques such as microfracture (MFX) or matrix-associated autologous chondrocyte transplantation (MACT) is to produce repair tissue (RT) with sufficient glycosaminoglycan (GAG) content. Sodium magnetic resonance imaging (MRI) offers a direct and noninvasive evaluation of the GAG content in native cartilage and RT. In the femoral cartilage, this method was able to distinguish between RTs produced by MFX and MACT having different GAG contents. However, it needs to be clarified whether sodium MRI can be useful for evaluating RT in thin ankle cartilage. Thus, the aims of this 7-T study were (1) to validate our sodium MRI protocol in cadaver ankle samples, (2) to evaluate the sodium corrected signal intensities (cSI) in cartilage of volunteers, (3) and to compare sodium values in RT between patients after MFX and MACT treatment. Materials and MethodsFive human cadaver ankle samples as well as ankles of 9 asymptomatic volunteers, 6 MFX patients and 6 MACT patients were measured in this 7-T study. Sodium values from the ankle samples were compared with histochemically evaluated GAG content. In the volunteers, sodium cSI values were calculated in the cartilages of ankle and subtalar joint. In the patients, sodium cSI in RT and reference cartilage were measured, morphological appearance of RT was evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system, and clinical outcome before and after surgery was assessed using the American Orthopaedic Foot and Ankle Society score and Modified Cincinnati Knee Scale. All regions of interest were defined on morphological images and subsequently transferred to the corresponding sodium images. Analysis of variance, t tests, and Pearson correlation coefficients were evaluated. ResultsIn the patients, significantly lower sodium cSI values were found in RT than in reference cartilage for the MFX (P = 0.007) and MACT patients (P = 0.008). Sodium cSI and MOCART scores in RT did not differ between the MFX and MACT patients (P = 0.185). No significant difference in sodium cSI was found between reference cartilage of the volunteers and the patients (P = 0.355). The patients showed significantly higher American Orthopaedic Foot and Ankle Society and Modified Cincinnati scores after treatment than they did before treatment. In the volunteers, sodium cSI was significantly higher in the tibial cartilage than in the talar cartilage of ankle joint (P = 0.002) and in the talar cartilage than in the calcaneal cartilage of subtalar joint (P < 0.001). Data from the cadaver ankle samples showed a strong linear relationship between the sodium values and the histochemically determined GAG content (r = 0.800; P < 0.001; R2 = 0.639). ConclusionsThis study demonstrates the feasibility of in vivo quantification of sodium cSI, which can be used for GAG content evaluation in thin cartilages of ankle and subtalar joints at 7 T. A strong correlation observed between the histochemically evaluated GAG content and the sodium values proved the sufficient sensitivity of sodium MRI to changes in the GAG content of cartilages in the ankle. Both MFX and MACT produced RT with lower sodium cSI and, thus, of lower quality compared with reference cartilage in the patients or in the volunteers. Our results suggest that MFX and MACT produce RT with similar GAG content and similar morphological appearance in patients with similar surgery outcome. Sodium MRI at 7 T allows a quantitative evaluation of RT quality in the ankle and may thus be useful in the noninvasive assessment of new cartilage repair procedures.

Sodium MR Imaging of Articular Cartilage Pathologies.

Many studies have proved that noninvasive sodium MR imaging can directly determine the cartilage GAG content, which plays a central role in cartilage homeostasis. New technical developments in the recent decade have helped to transfer this method from in vitro to pre-clinical in vivo studies. Sodium imaging has already been applied for the evaluation of cartilage and repair tissue in patients after various cartilage repair surgery techniques and in patients with osteoarthritis. These studies showed that this technique could be helpful not only for assessment of the cartilage status, but also predictive for osteoarthritis. However, due to the low detectable sodium MR signal in cartilage, sodium imaging is still challenging, and further hardware and software improvements are necessary for translating sodium MR imaging into clinical practice, preferably to 3T MR systems.

Regression error estimation significantly improves the region-of-interest statistics of noisy MR images

PURPOSE The region-of-interest (ROI) selection and evaluation is one of the key factors in the successful evaluation of radiological images. However, the presence of noise in images may lead to incorrect diagnosis. The aim of this study was to test the hypothesis that the weighting by error estimation in ROI assessment might significantly improve the validity of the results. METHODS As a model, the data maps of the transverse relaxation time constants (T2) from patients who underwent a matrix-associated chondrocyte transplantation procedure on the femoral condyle were analyzed. Artificial noise with a Rician density probability distribution was added to each TE image. ROIs were processed either as a regular arithmetic mean or as a weighted mean, in which weighted coefficients were calculated with regard to fitting error estimates [coefficient of determination (R2); root mean squared error (RMSE), mean absolute error (MSE), mean squared error (MAE), and chi-squared error (χ2)]. RESULTS The global T2 values in repair tissue (mean±standarddeviation, 62±7ms; range 51-70 ms) and in healthy cartilage (mean±SD, 49±6ms; range 40-60 ms) were significantly different (p<0.001). With a 45% or greater decrease from the original SNR value (corresponding to a noise level of 35% of random value), the statistical significance was lost (P>0.05); however, the use of the coefficient of determination (R2) as a correction factor was able to maintain the p-value of <0.05 up to a 56% decrease from the original SNR value. CONCLUSIONS The results of this study can prospectively be applied in a wide range of radiological imaging techniques in cases when error estimation is possible. Our analysis on MR images with artificially added noise showed that utilization of the correlation of determination (R2) as a weighting parameter in ROI evaluation may significantly improve the differentiation between native and transplanted cartilage tissue in noisy images. This could be an added benefit in the non-invasive monitoring of the post-operative status of patients with cartilage transplants if the MR images are not ideal (e.g., lower field strength or lower SNR).