Longitudinal evaluation of cartilage composition of matrix-associated autologous chondrocyte transplants with 3-T delayed gadolinium-enhanced MRI of cartilage

OBJECTIVE: The purposes of this study were to use delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) to evaluate the zonal distribution of glycosaminoglycans (GAGs) in normal cartilage and repair tissue and to use 3-T MRI to monitor the GAG content in matrix-associated autologous chondrocyte transplants. SUBJECTS AND METHODS: Fifteen patients who underwent matrix-associated autologous chondrocyte transplantation in the knee joint underwent MRI at baseline and 3-T follow-up MRI 1 year later. Total and zonal changes in longitudinal relaxivity (deltaR1) and relative deltaR1 were calculated for repair tissue and normal hyaline cartilage and compared by use of analysis of variance. RESULTS: There was a significant difference between the mean deltaR1 of repair tissue and that of reference cartilage at baseline and follow-up (p < 0.001). There was a significant increase in deltaR1 value and a decrease in GAG content from the deep layer to the superficial layer in the reference cartilage and almost no variation and significantly higher values for the repair tissue at both examinations. At 1-year follow-up imaging, there was a 22.7% decrease in deltaR1 value in the deep zone of the transplant. CONCLUSION: T1 mapping with dGEMRIC at 3 T shows the zonal structure of normal hyaline cartilage, highly reduced zonal variations in repair tissue, and a tendency toward an increase in global and zonal GAG content 1 year after transplantation.

Differentiating normal hyaline cartilage from post-surgical repair tissue using fast gradient echo imaging in delayed gadolinium-enhanced MRI (dGEMRIC) at 3 Tesla

The purpose was to evaluate the relative glycosaminoglycan (GAG) content of repair tissue in patients after microfracturing (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint with a dGEMRIC technique based on a newly developed short 3D-GRE sequence with two flip angle excitation pulses. Twenty patients treated with MFX or MACT (ten in each group) were enrolled. For comparability, patients from each group were matched by age (MFX: 37.1 +/- 16.3 years; MACT: 37.4 +/- 8.2 years) and postoperative interval (MFX: 33.0 +/- 17.3 months; MACT: 32.0 +/- 17.2 months). The Delta relaxation rate (DeltaR1) for repair tissue and normal hyaline cartilage and the relative DeltaR1 were calculated, and mean values were compared between both groups using an analysis of variance. The mean DeltaR1 for MFX was 1.07 +/- 0.34 versus 0.32 +/- 0.20 at the intact control site, and for MACT, 1.90 +/- 0.49 compared to 0.87 +/- 0.44, which resulted in a relative DeltaR1 of 3.39 for MFX and 2.18 for MACT. The difference between the cartilage repair groups was statistically significant. The new dGEMRIC technique based on dual flip angle excitation pulses showed higher GAG content in patients after MACT compared to MFX at the same postoperative interval and allowed reducing the data acquisition time to 4 min.

Comparison of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using inversion recovery and fast T1 mapping sequences

The delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique has shown promising results in pilot clinical studies of early osteoarthritis. Currently, its broader acceptance is limited by the long scan time and the need for postprocessing to calculate the T1 maps. A fast T1 mapping imaging technique based on two spoiled gradient echo images was implemented. In phantom studies, an appropriate flip angle combination optimized for center T1 of 756 to 955 ms yielded excellent agreement with T1 measured using the inversion recovery technique in the range of 200 to 900 ms, of interest in normal and diseased cartilage. In vivo validation was performed by serially imaging 26 hips using the inversion recovery and the Fast 2 angle T1 mapping techniques (center T1 756 ms). Excellent correlation with Pearson correlation coefficient R2 of 0.74 was seen and Bland-Altman plots demonstrated no systematic bias.

CD69 upregulation on T cells as an in vitro marker for delayed-type drug hypersensitivity

BACKGROUND: T cells play a key role in delayed-type drug hypersensitivity reactions. Their reactivity can be assessed by their proliferation in response to the drug in the lymphocyte transformation test (LTT). However, the LTT imposes limitations in terms of practicability, and an alternative method that is easier to implement than the LTT would be desirable. METHODS: Four months to 12 years after acute drug hypersensitivity reactions, CD69 upregulation on T cells of 15 patients and five healthy controls was analyzed by flow cytometry. RESULTS: All 15 LTT-positive patients showed a significant increase of CD69 expression on T cells after 48 h of drug-stimulation exclusively with the drugs incriminated in drug-hypersensitivities. A stimulation index of 2 as cut-off value allowed discrimination between nonreactive and reactive T cells in LTT and CD69 upregulation. T cells (0.5-3%) showed CD69 up-regulation. The reactive cell population consisted of a minority of truly drug reactive T cells secreting cytokines and a higher number of bystander T cells activated by IL-2 and possibly other cytokines. CONCLUSIONS: CD69 upregulation was observed after 2 days in all patients with a positive LTT after 6 days, thus appearing to be a promising tool to identify drug-reactive T cells in the peripheral blood of patients with drug-hypersensitivity reactions.

Prevention of delayed cerebral vasospasm by continuous intrathecal infusion of glyceroltrinitrate and nimodipine in the rabbit model in vivo

OBJECTIVE: Intrathecal bolus administration of nitric oxide donors and calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Intrathecal continuous administration of these substances for CVS prevention has not been extensively evaluated. This study compared the efficacy of continuous intrathecal infusions of the NO donor glyceroltrinitrate and nimodipine in preventing delayed CVS associated with SAH in an animal model in vivo. METHODS: New Zealand White rabbits were randomly assigned to six groups: no SAH/NaCl, no SAH/NO, no SAH/nimodipine, SAH/NaCl, SAH/NO, or SAH/nimodipine. Glyceroltrinitrate (GTN) at 0.5 microg/microl (0.5 microl/h) or nimodipine at 0.2 microg/microl (10 microl/h) or NaCl was continuously infused into the cisterna magna via an Alzet osmotic pump from day 0 to day 5 after injection of 1.0 ml autologous blood. The magnitude of spasm in the basilar artery was determined by comparison of pre- and posttreatment angiography and was calculated as proportional change in intraluminal diameter based on automatic measurements. RESULTS: A total of 55 experiments and 110 angiograms were performed. SAH was associated with vasoconstriction of the basilar artery (SAH/NaCl group 19.85+/-2.94%). Continuous intrathecal injection of GTN and nimodipine prevented SAH-induced CVS. There was significant prevention of CVS in animals treated with GTN (SAH/NO group 5.93+/-5.2%, n=11) and nimodipine (SAH/nimodipine group: 0.55+/-2.66%, n=9). There was no significant difference between the treatment groups and controls in prevention of CVS. CONCLUSIONS: This study demonstrates that prophylactic continuous intrathecal administration of either GTN or nimodipine equally prevents SAH-associated CVS in an animal model.

Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study

OBJECTIVES: To investigate delayed HIV diagnosis and late initiation of antiretroviral therapy (ART) in the Swiss HIV Cohort Study. METHODS: Two sub-populations were included: 1915 patients with HIV diagnosis from 1998 to 2007 and within 3 months of cohort registration (group A), and 1730 treatment-naïve patients with CD4>or=200 cells/microL before their second cohort visit (group B). In group A, predictors for low initial CD4 cell counts were examined with a median regression. In group B, we studied predictors for CD4<200 cells/microL without ART despite cohort follow-up. RESULTS: Median initial CD4 cell count in group A was 331 cells/microL; 31% and 10% were <200 and <50 cells/microL, respectively. Risk factors for low CD4 count were age and non-White race. Homosexual transmission, intravenous drug use and living alone were protective. In group B, 30% initiated ART with CD4>or=200 cells/microL; 18% and 2% dropped to CD4 <200 and <50 cells/microL without ART, respectively. Sub-Saharan origin was associated with lower probability of CD4 <200 cells/microL without ART during follow-up. Median CD4 count at ART initiation was 207 and 253 cells/microL in groups A and B, respectively. CONCLUSIONS: CD4<200 cells/microL and, particularly, CD4<50 cells/microL before starting ART are predominantly caused by late presentation. Earlier HIV diagnosis is paramount.

Cartilage damage in femoroacetabular impingement (FAI): preliminary results on comparison of standard diagnostic vs delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC)

OBJECTIVES: To study the three-dimensional (3D) T1 patterns in different types of femoroacetabular impingement (FAI) by utilizing delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and subsequent 3D T1 mapping. We used standard grading of OA by Tonnis grade on standard radiographs and morphological grading of cartilage in MRI for comparative analysis. METHODS: dGEMRIC was obtained from ten asymptomatic young-adult volunteers and 26 symptomatic FAI patients. MRI included the routine hip protocol and a dual-flip angle (FA) 3D gradient echo (GRE) sequence utilizing inline T1 measurement. Cartilage was morphologically classified from the radial images based on the extent of degeneration as: no degeneration, degeneration zone measuring <0.75 cm from the rim, >0.75 cm, or total loss. T1 findings were evaluated and correlated. RESULTS: All FAI types revealed remarkably lower T1 mean values in comparison to asymptomatic volunteers in all regions of interest. Distribution of the T1 dGEMRIC values was in accordance with the specific FAI damage pattern. In cam-types (n=6) there was a significant drop (P<0.05) of T1 in the anterior to superior location. In pincer-types (n=7), there was a generalized circumferential decrease noted. High inter-observer (intra-observer) reliability was noted for T1 assessment using intra-class correlation (ICC):intra-class coefficient=0.89 (0.95). CONCLUSIONS: We conclude that a pattern of zonal T1 variation does seem to exist that is unique for different sub-groups of FAI. The FA GRE approach to perform 3D T1 mapping has a promising role for further studies of standard MRI and dGEMRIC in the hip joint.

Delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) of hip joint cartilage in femoroacetabular impingement (FAI): Are pre- and postcontrast imaging both necessary?

The purpose of this study was to assess if delayed gadolinium MRI of cartilage using postcontrast T(1) (T(1Gd)) is sufficient for evaluating cartilage damage in femoroacetabular impingement without using noncontrast values (T(10)). T(1Gd) and DeltaR(1) (1/T(1Gd) - 1/T(10)) that include noncontrast T(1) measurements were studied in two grades of osteoarthritis and in a control group of asymptomatic young-adult volunteers. Differences between T(1Gd) and DeltaR(1) values for femoroacetabular impingement patients and volunteers were compared. There was a very high correlation between T(1Gd) and DeltaR(1) in all study groups. In the study cohort with Tonnis grade 0, correlation (r) was -0.95 and -0.89 with Tonnis grade 1 and -0.88 in asymptomatic volunteers, being statistically significant (P < 0.001) for all groups. For both T(1Gd) and DeltaR(1), a statistically significant difference was noted between patients and control group. Significant difference was also noted for both T(1Gd) and DeltaR(1) between the patients with Tonnis grade 0 osteoarthritis and those with grade 1 changes. Our results prove a linear correlation between T(1Gd) and DeltaR(1), suggesting that T(1Gd) assessment is sufficient for the clinical utility of delayed gadolinium MRI of cartilage in this setting and additional time-consuming T(10) evaluation may not be needed.

Delayed gadolinium enhanced MRI of cartilage (dGEMRIC): Molekulare MRT-Bildgebung des Hüftgelenkknorpels [Delayed gadolinium enhanced MRI of cartilage (dGEMRIC): molecular MRI of hip joint cartilage]

Factors such as instability and impingement lead to early cartilage damage and osteoarthritis of the hip joint. The surgical outcome of joint-preserving surgery about the hip joint depends on the preoperative quality of joint cartilage.For in vivo evaluation of cartilage quality, different biochemically sensitive magnetic resonance imaging (MRI) procedures have been tested, some of which have the potential of inducing a paradigm shift in the evaluation and treatment of cartilage damage and early osteoarthritis.Instead of reacting to late sequelae in a palliative way, physicians could assess cartilage damage early on, and the treatment intensity could be adequate and based on the disease stage. Furthermore, the efficiency of different therapeutic interventions could be evaluated and monitored.This article reviews the recent application of delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and discusses its use for assessing cartilage quality in the hip joint. dGEMRIC is more sensitive to early cartilage changes in osteoarthritis than are radiographic measures and might be a helpful tool for assessing cartilage quality.

Assessment of osteoarthritis in hips with femoroacetabular impingement using delayed gadolinium enhanced MRI of cartilage

PURPOSE: To determine the feasibility of assessing early osteoarthritis (OA) in hips with femoroacetabular impingement (FAI) using delayed Gadolinium enhanced MRI of Cartilage (dGEMRIC). MATERIALS AND METHODS: Thirty-seven hips in 30 patients who had a dGEMRIC scan and radiographic evidence of FAI were identified. Clinical symptoms were assessed. Radiographic measurements were performed to determine acetabular and femoral morphology. The severity of radiographic OA was determined using Tönnis grade and minimum joint space width (JSW). On MRI, the alpha angle was measured on the sagittal oblique slices. Correlations between dGEMRIC index, patient symptoms, morphologic measurements, radiographic OA, and age were determined. RESULTS: Significant correlations were observed between dGEMRIC index, pain (P < 0.05), and alpha angle (P < 0.05). The correlation of dGEMRIC with alpha angle suggests that hips with more femoral deformity show signs of early OA. CONCLUSION: The results of osteoplasty for FAI depend on the amount of pre-existing OA in the joint. dGEMRIC may be a useful technique for diagnosis and staging of early osteoarthritis in hips with impingement.