Morphological and compositional monitoring of a new cell-free cartilage repair hydrogel technology – GelrinC by MR using semi-quantitative MOCART scoring and quantitative T2 index and new zonal T2 index calculation

SummaryObjectiveTo evaluate cartilage repair tissue (RT) using MOCART scoring for morphological and T2 mapping for biochemical assessment following implantation of GelrinC, a biosynthetic, biodegradable hydrogel implant.DesignMR imaging (1.5/3T) was performed on 21 patients at six sites. Standard protocols were used for MOCART evaluation at 1 week (baseline) 1, 3, 6, 12, 18 and 24 months. Multi-echo SE was used for T2 mapping. Global (T2 in RT divided by T2 in normal cartilage) and zonal T2 index (deep T2 divided by superficial T2) of RT were calculated.ResultsAverage MOCART score was 71.8 (95% CI 62.2 to 81.3) at six, 75.2 (95% CI 62.8 to 87.5) at twelve, 71.8 (95% CI 55.4 to 88.2) at eighteen and 84.4 (95% CI 77.7 to 91.0) at twenty-four months. The global T2 index ranged between 0.8 and 1.2 (normal healthy cartilage) in 1/11 (9%) patients at baseline, 8/12 (67%) at 12 months, 11/13 (85%) at 18 months and 13/16 (81%) at 24 months. The zonal T2 index for RT was <20% difference to the zonal T2 index for normal cartilage in: 6/12 patients (50%) at 12 months, 7/13 (53.8%) at 18 months and 10/16 (63.5%) at 24 months. The standard deviation for T2 showed a significant decrease over the study.ConclusionsThe increase of MOCART scores over follow-up indicates improving cartilage repair tissue. Global and zonal T2 repair values at 24 months reached normal cartilage in 81% and 63.5% of the patients respectively, reflecting collagen organization similar to hyaline cartilage

Six-month follow-up of the patients with the low-grade femoral cartilage lesions using T2 mapping at 3 and 7 Tesla

Transverse relaxation time (T2) maps were assessed as a potential marker for the long-term follow-up of the patients with cartilage lesions ICRS Grade I-II in four time points (baseline, 8 days, 3 and 6 months). T2 mapping was based on a 3D triple echo steady state imaging sequence delivering high quality high-resolved T2 maps at ultra-high field MRI. The results showed opposite trends of T2 values at 3T (a decrease) and 7T (an increase) over time. The statistically significant difference was found in case of deep zone of the cartilage lesion at 3T. T2 mapping could be used in the future as a good alternative to cartilage biopsies in clinical trials on new therapies aimed at cartilage regeneration

Compositional assessment of low-grade cartilage lesions using T2 mapping at 3 and 7 Tesla MRI: a one year follow-up study

T2 maps were assessed as a potential marker for the long-term follow-up of the patients with cartilage lesions ICRS Grade I-II in five time points (baseline, 8 days, 3, 6 and 12 months). For the T2 mapping, a 3D triple echo steady state sequence which is capable of delivering high quality high-resolved T2 maps at ultra-high field MRI was used. We observed a significant decrease in T2 values at 3T over time in superficial zone of the cartilage defect. There was no statistically significant change at 7T. T2 mapping could be used in the future as a good alternative to cartilage biopsies in clinical trials on new therapies aimed at cartilage regeneration

Raman spectroscopic probe provides optical biomarkers of cartilage composition predictive of tissue function

ObjectiveThe diagnosis of early osteoarthritis when therapeutic interventions may be most effective at reversing cartilage degeneration presents a clinical challenge. We describe a Raman arthroscopic probe and spectral analysis that measures biomarkers reflective of the content of predominant cartilage extracellular matrix (ECM) constituents—glycosaminoglycans (GAG), collagen, water—essential to cartilage function. We compare the capability of Raman-probe-derived biomarkers to predict functional properties of cartilage to quantitative MRI and histopathology assessments. DesignOsteochondral blocks were sectioned from 6 bovine femoral condyles with no macroscopic injury (n=62 blocks) and 6 condyles with a focal chondral lesion (n=32 blocks), but no macroscopic degeneration of surrounding cartilage (n=34 blocks). Blocks from 10 human knees were further analyzed (age 27–75; n=235 blocks). Using a custom arthroscopic Raman spectroscopy probe, spectra of chondral layers were measured and subjected to multivariate linear decomposition to extract ECM biomarker scores, reflecting the contribution of each ECM constituent to the spectra. Blocks were further analyzed for elastic modulus, T2/T2* MRI relaxation times, and OARSI scores. ResultsFor bovine tissues, Raman biomarkers revealed depleted GAG and cartilage softening peripheral to the lesion despite no macroscopic degeneration. Raman biomarkers accounted for 78% of GAG content variation and 71% of modulus variation. For human tissues, Raman biomarkers accounted for 71% of modulus variation. Raman biomarkers accounted for a greater variation of modulus (71%−72%) than OARSI (12–54%), T2* (15%−27%), or T2 (25%−30%). ConclusionsThese data support the application of Raman-probe-derived biomarkers for molecular assessment of key ECM constituents that define cartilage properties in health and disease.</p

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

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