T1ρ Magnetic Resonance Imaging Research Articles

T1ρ, T2 mapping, and EPIC-µCT Imaging in a Canine Model of Knee Osteochondral Injury.

The dog is the most commonly used large animal model for the study of osteoarthritis. Optimizing methods for assessing cartilage health would prove useful in reducing the number of dogs needed for a valid study of osteoarthritis and cartilage repair. Twelve beagles had critical-sized osteochondral defects created in the medial femoral condyle of both knees. Eight dogs had T1ρ and T2 magnetic resonance imaging (MRI) performed approximately 6 months after defect creation. Following MRI evaluations, all 12 dogs were humanely euthanatized and cartilage samples were obtained from the medial and lateral femoral condyles, medial and lateral tibial plateaus, trochlear groove, and patella for proteoglycan and collagen quantification. Equilibrium partitioning of an ionic contrast (EPIC)-µCT was then performed followed by the histologic assessment of the knees. Correlations between T1ρ, T2, EPIC-µCT and proteoglycan, collagen, and histology scores were assessed using a multivariate analysis accounting for correlations from samples within the same knee and in the same dog. Pearson's correlation coefficients were calculated to assess the strength of significant relationships. Correlations between µCT values and biochemical or histologic assessment were weak to moderately strong (0.09-0.41; p < 0.0001-0.66). There was a weak correlation between the T2 values and cartilage proteoglycan (-0.32; p = 0.04). The correlation between T1ρ values and cartilage proteoglycan were moderately strong (-0.38; p < 0.05) while the strongest correlation was between the T1ρ values and histological assessment of cartilage with a correlation coefficient of 0.58 (p < 0.0001). These data suggest that T1ρ shows promise for possible utility in the translational study of cartilage health and warrants further development in this species. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:368-377, 2020.

Gait Mechanics and T1ρ MRI of Tibiofemoral Cartilage 6 Months after ACL Reconstruction.

Aberrant walking biomechanics after anterior cruciate ligament reconstruction (ACLR) are hypothesized to be associated with deleterious changes in knee cartilage. T1ρ magnetic resonance imaging (MRI) is sensitive to decreased proteoglycan density of cartilage. Our purpose was to determine associations between T1ρ MRI interlimb ratios (ILR) and walking biomechanics 6 months after ACLR. Walking biomechanics (peak vertical ground reaction force (vGRF), vGRF loading rate, knee extension moment, knee abduction moment) were extracted from the first 50% of stance phase in 29 individuals with unilateral ACLR. T1ρ MRI ILR (ACLR limb/uninjured limb) was calculated for regions of interest in both medial and lateral femoral (LFC) and medial and lateral tibial condyles. Separate, stepwise linear regressions were used to determine associations between biomechanical outcomes and T1ρ MRI ILR after accounting for walking speed and meniscal/chondral injury (P ≤ 0.05). Lesser peak vGRF in the ACLR limb was associated with greater T1ρ MRI ILR for the LFC (posterior ΔR = 0.14, P = 0.05; central ΔR = 0.15, P = 0.05) and medial femoral condyle (central ΔR = 0.24, P = 0.01). Lesser peak vGRF loading rate in the ACLR limb (ΔR = 0.21, P = 0.02) and the uninjured limb (ΔR = 0.27, P = 0.01) was associated with greater T1ρ MRI ILR for the anterior LFC. Lesser knee abduction moment for the injured limb was associated with greater T1ρ MRI ILR for the anterior LFC (ΔR = 0.16, P = 0.04) as well as the posterior medial tibial condyle (ΔR = 0.13, P = 0.04). Associations between outcomes related to lesser mechanical loading during walking and greater T1ρ MRI ILR were found 6 months after ACLR. Although preliminary, our results suggest that underloading of the ACLR limb at 6 months after ACLR may be associated with lesser proteoglycan density in the ACLR limb compared with the uninjured limb.

Thermoreversible hyaluronan-hydrogel and autologous nucleus pulposus cell delivery regenerates human intervertebral discs in an ex vivo, physiological organ culture model.

Numerous studies show promise for cell-based tissue engineering strategies aiming to repair painful intervertebral disc (IVD) degeneration. However, clinical translation to human IVD repair is slow. In the present study, the regenerative potential of an autologous nucleus pulposus (NP)-cell-seeded thermoresponsive hyaluronic acid hydrogel in human lumbar IVDs was assessed under physiological conditions. First, agarose-encased in vitro constructs were developed, showing greater than 90 % NP cell viability and high proteoglycan deposition within HA-pNIPAM hydrogels following 3 weeks of dynamic loading. Second, a bovine-induced IVD degeneration model was used to optimise and validate T1ρ magnetic resonance imaging (MRI) for detection of changes in proteoglycan content in isolated intact IVDs. Finally, isolated intact human lumbar IVDs were pre-scanned using the established MRI sequence. Then, IVDs were injected with HA-pNIPAM hydrogel alone or autologous NP-cell-seeded. Next, the treated IVDs were cultured under cyclic dynamic loading for 5 weeks. Post-treatment T1ρ values were significantly higher as compared to pre-treatment scans within the same IVD and region of interest. Histological evaluation of treated human IVDs showed that the implanted hydrogel alone accumulated proteoglycans, while those that contained NP cells also displayed neo-matrix-surrounded cells within the gel. The study indicated a clinical potential for repairing early degenerative human IVDs using autologous cells/hydrogel suspensions. This unique IVD culture set-up, combined with the long-term physiological culture of intact human IVDs, allowed for a more clinically relevant evaluation of human tissue repair and regeneration, which otherwise could not be replicated using the available in vitro and in vivo models.

Matrix changes in articular cartilage in the knee of patients with rheumatoid arthritis after biological therapy: 1-year follow-up evaluation by T2 and T1ρ MRI quantification

To estimate the morphological changes in the articular cartilage of the knees of patients with rheumatoid arthritis treated with biological disease-modifying anti-rheumatic drugs (bDMARDs). Cartilage-specific magnetic resonance imaging (MRI) results, including T2 and T1ρ mapping of the femorotibial joint of 17 patients, were obtained before and 1 year after starting treatment with bDMARDs. Regions of interest were selected on the sagittal images of the cartilage of the medial and lateral femoral condyles (MFC, LFC) and the tibial plateau (MTP, LTP). Cartilage thickness, T2, and T1ρ were measured, and the correlations of their changes were evaluated. The mean changes in cartilage thickness tended to decrease in all four condyles, and the rate was significant in the MFC. T2 and T1ρ tended to increase, and T2 in the MFC significantly increased. Changes in cartilage thickness after 1 year showed a moderate correlation with the baseline T2 in the MFC as well as changes in T2 in the MTP. Decreasing cartilage thickness and matrix changes appeared in the MFC after 1 year of treatment with bDMARDs. Microstructural damage of the cartilage at baseline is a predictor for further cartilage damage in the knee joint, even if treatment with bDMARDs is effective.

Associations Between Slower Walking Speed and T1ρ Magnetic Resonance Imaging of Femoral Cartilage Following Anterior Cruciate Ligament Reconstruction.

To determine whether walking speed, collected at 6 and 12 months following anterior cruciate ligament reconstruction (ACLR), is associated with inter-extremity differences in proteoglycan density, measured via T1ρ magnetic resonance imaging, in tibiofemoral articular cartilage 12 months following ACLR. Twenty-one individuals with a unilateral patellar-tendon autograft ACLR (10 women and 11 men, mean ± SD age 23.9 ± 2.7 years, mean ± SD body mass index 23.9 ± 2.7 kg/m2 ) were recruited for participation in this study. Walking speed was collected using 3-dimensional motion capture at 6 and 12 months following ACLR. The articular cartilage of the medial femoral condyle (MFC) and lateral femoral condyle and medial and lateral tibial condyles was manually segmented and subsectioned into 3 regions of interest (anterior, central, and posterior) based on the location of the meniscus in the sagittal plane. Inter-extremity mean T1ρ relaxation time ratios (T1ρ ACLR extremity / T1ρ contralateral extremity) were calculated and used for analysis. Pearson product-moment correlations were used to determine associations between walking speed and inter-extremity differences in T1ρ relaxation time ratios. Slower walking speed 6 months post-ACLR was significantly associated with higher T1ρ relaxation time ratios in the MFC of the ACLR extremity 12 months following ACLR (posterior MFC, r = -0.51, P = 0.02; central MFC, r = -0.47, P = 0.04). Similarly, slower walking speed at 12 months post-ACLR was significantly associated with higher T1ρ relaxation time ratios in the posterior MFC ACLR extremity (r = -0.47, P = 0.04) 12 months following ACLR. Slower walking speed at 6 and 12 months following ACLR may be associated with early proteoglycan density changes in medial femoral compartment cartilage health in the first 12 months following ACLR.

Lesser Mechanical Loading During Walking Gait Associates with Worse Proteoglycan Density 6 months Following Anterior Cruciate Ligament Reconstruction

Optimal mechanical loading is necessary to decrease the risk of posttraumatic osteoarthritis (PTOA) following anterior cruciate ligament reconstruction (ACLR) and lesser mechanical loading early following ACLR may increase the risk for PTOA onset. T1ρ magnetic resonance imaging (MRI) has been used to measure cartilage composition at early time points following ACLR. PURPOSE: To determine the association between proteoglycan density of femoral cartilage derived from T1ρ MRI relaxation times and peak vertical ground reaction force (vGRF) and instantaneous vGRF loading rate (vGRF-LR) during walking gait 6 months following ACLR. METHODS: Twenty-nine individuals (52% female, BMI = 24±3 kg/m2) with a unilateral patellar-tendon autograft ACLR participated in this study. Five trials of walking gait at self-selected speed were performed 6 months following ACLR. Peak vGRF and instantaneous vGRF-LR were extracted from the first 50% of the stance phase in both limbs. T1ρ relaxation times were calculated for articular cartilage in the medial and lateral condyles (MFC & LFC) by fitting a monoexponential model. The weight bearing MFC and LFC cartilage was manually segmented into posterior, central, and anterior regions of interest (ROI) based on the location of the meniscus in the sagittal plane. Affine and deformable registration techniques were used to register the ACLR limb to the uninjured limb. Inter-limb mean T1ρ relaxation time ratios (RTR = ACLR limb / uninjured limb) were calculated for each ROI. Separate, stepwise linear regressions were used to determine the unique associations between vGRF outcomes and T1ρ RTR in each ROI after accounting for walking speed and meniscal injury (ΔR2; P≤ 0.05). RESULTS: In the ACLR limb, lesser vGRF during gait was associated with lesser proteoglycan density in the posterior (ΔR2=0.22, P=0.02) and central LFC (ΔR2=0.22, P=0.02), as well as the posterior (ΔR2=0.12, P=0.05) and central MFC (ΔR2=0.21, P=0.01). vGRF-LR in the ACLR limb and all vGRF outcomes in the contralateral limb did not significantly associate with T1ρ RTR for any ROI. CONCLUSIONS: Individuals with lesser vGRF in the ACLR limb presented with T1ρ MRI findings consistent with deteriorating cartilage health. Understanding how loading affects joint health is critical to developing interventions to delay PTOA onset.

Evaluation of Lumbar Intervertebral Disc Degeneration Using T1ρ and T2 Magnetic Resonance Imaging in a Rabbit Disc Injury Model.

Study DesignAn in vivo histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted.PurposeTo clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated.Overview of LiteratureThe early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content.MethodsUsing New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining.ResultsDisc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs (p<0.05). There was a significant difference between grade 1 and grade 2 IVDs only in terms of T1ρ values (p<0.05).ConclusionsT1ρ and T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration.

Synovial Fluid Profile at the Time of Anterior Cruciate Ligament Reconstruction and Its Association With Cartilage Matrix Composition 3 Years After Surgery

Background: Anterior cruciate ligament tears can lead to posttraumatic osteoarthritis. In addition to biomechanical factors, changes in biochemical profiles within the knee joint after injury and anterior cruciate ligament reconstruction (ACLR) may play a role in accelerating joint degeneration. Hypothesis/Purpose: It was hypothesized that cartilage matrix composition after ACLR is associated with the degree of inflammatory response after initial injury. This study evaluated the association between the inflammatory response after injury—as indicated by cytokine, metalloproteinase, and cartilage degradation marker concentrations in synovial fluid—and articular cartilage degeneration, measured by T1ρ and T2 quantitative magnetic resonance imaging up to 3 years after ACLR. Study Design: Cohort study; Level of evidence, 2. Methods: Twenty-six subjects from a longitudinal cohort study who underwent ACLR at a mean 8.5 weeks after injury (range, 4-19 weeks) had synovial fluid aspirated at the time of surgery. Immunoassays quantified biomarkers in synovial fluid. T1ρ and T2 values of articular cartilage were calculated with magnetic resonance scans acquired prior to surgery and at 6 months and 1, 2, and 3 years after surgery. Pearson correlation coefficients were calculated among the various biomarkers. K-means clustering was used to group subjects with similar biomarker profiles. Generalized estimating equations were used to find the overall differences in T1ρ and T2 values throughout these first 3 years after surgery between the clusters while controlling for other factors. Results: Significant and strong correlations were observed between several cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α) and 2 matrix metalloproteinases (MMP-1 and MMP-3) (P < .05). Moderate correlations were found among combinations of C-terminal crosslinked telopeptide type II collagen, N-terminal telopeptide, cartilage oligomeric matrix protein, and sulfated glycosaminoglycan (P < .05). Two clusters were generated, 1 of which was characterized by lower concentrations of cytokines (IL-6, IL-8, IL-10, tumor necrosis factor α) and MMP-1 and MMP-3 and higher sulfated glycosaminoglycan. This cluster was associated with significantly higher T1ρ and T2 values in the medial tibial and patellar cartilage over the first 3 years after ACLR. Conclusion: At the time of ACLR surgery, profiles of synovial fluid inflammatory cytokines, degradative enzymes, and cartilage breakdown products show promise as predictors of abnormal cartilage tissue integrity (increased T1ρ and T2 values) throughout the first 3 years after surgery. Clinical Relevance: The results suggest an intricate relationship between inflammation and cartilage turnover, which can in turn be influenced by timing after injury and patient factors.

Influence of Age, BMI, Gender and Lumbar Level on T1ρ Magnetic Resonance Imaging of Lumbar Discs in Healthy Asymptomatic Adults.

To assess the T1ρ range of lumbar intervertebral discs in healthy asymptomatic individuals at 1.5 T and to investigate the influence of age, body mass index (BMI), gender, and lumbar level on T1ρ relaxation. In a prospective study, a total of 81 volunteers aged 20 - 80 years were included in this study and divided into three age groups (A: 20 - 39y; B: 40 - 59y; C: 60 - 80y). All of the volunteers underwent magnetic resonance imaging (MRI) at 1.5 T with acquisition of sagittal T1ρ images. The calculated T1ρ relaxation times were correlated with age, BMI, gender, and lumbar level relative to the total disc, the annulus fibrosus, and the nucleus pulposus. Age had a significant influence on T1ρ relaxation times at all lumbar levels, with increasing age being associated with reduced relaxation times. There was also a significant difference between age groups A vs. C and B vs. C (P = 0.0008 and P = 0.0149, respectively). No significant differences in T1ρ relaxation time were observed between men and women (P > 0.05). BMI showed a significant negative correlation with T1ρ relaxation times (P < 0.0001). Analysis of the lumbar level revealed a significant decrease in relaxation times from L1/2 to L5 / S1 (P = 0.0013). Increasing age correlated significantly with advanced lumbar disc degeneration in asymptomatic individuals, particularly in those aged 60 or older. Increasing BMI correlated significantly with increasing degeneration. The lower discs showed more degeneration than the upper ones. · Increasing age significantly reduces the T1ρ relaxation time in the intervertebral discs (P < 0.05). · Gender does not significantly influence T1ρ relaxation times (P > 0.05). · BMI shows a significant negative correlation with T1ρ relaxation times (P < 0.01). · Significantly shorter relaxation times in lower lumbar spine vs. upper lumbar spine (P < 0.01). · Gübitz R, Lange T, Gosheger G et al. Influence of Age, BMI, Gender and Lumbar Level on T1ρ Magnetic Resonance Imaging of Lumbar Discs in Healthy Asymptomatic Adults. Fortschr Röntgenstr 2018; 190: 144 - 151.

Surgical Correction of Cam Deformity in Association with Femoroacetabular Impingement and Its Impact on the Degenerative Process within the Hip Joint.

Cam morphology in association with femoroacetabular impingement (FAI) is a recognized cause of hip pain and cartilage damage and proposed as a leading cause of arthritis. The purpose of this study was to analyze the functional and biomechanical effects of the surgical correction of the cam deformity on the degenerative process associated with FAI. Ten male patients with a mean age of 34.3 years (range, 23.1 to 46.5 years) and a mean body mass index (and standard deviation) of 26.66 ± 4.79 kg/m underwent corrective surgery for cam deformity in association with FAI. Each patient underwent a computed tomography (CT) scan to assess acetabular bone mineral density (BMD), high-resolution T1ρ magnetic resonance imaging (MRI) of the hips to assess proteoglycan content, and squatting motion analysis as well as completed self-administered functional questionnaires (Hip disability and Osteoarthritis Outcome Score [HOOS]) both preoperatively and 2 years postoperatively. At a mean follow-up of 24.5 months, improvements in functional scores and squat performance were seen. Regarding the zone of impingement in the anterosuperior quadrant of the acetabular rim, the mean change in BMD at the time of follow-up was -31.8 mg/cc (95% confidence interval [CI], -11 to -53 mg/cc) (p = 0.008), representing a 5% decrease in BMD. The anterosuperior quadrant also demonstrated a significant decrease in T1ρ values, reflecting a stabilization of the cartilage degeneration. Significant correlations were noted between changes in clinical functional scores and changes in T1ρ values (r = -0.86; p = 0.003) as well as between the BMD and maximum vertical force (r = 0.878; p = 0.021). Surgical correction of a cam deformity in patients with symptomatic FAI not only improved clinical function but was also associated with decreases in T1ρ values and BMD. These findings are the first, to our knowledge, to show that alteration of the hip biomechanics through surgical intervention improves the overall health of the hip joint. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Multimodal quantitative magnetic resonance imaging for lumbar intervertebral disc degeneration.

The present study investigated the application of the T1ρ and T2 relaxation mapping magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the evaluation of intervertebral disc degeneration (IDD). A total of 93 asymptomatic subjects were imaged with T1ρ and T2 mapping, as well as DWI. Pfirrmann grading was performed and correlation analysis was conducted for T1ρ, T2 and DWI results with the grading results and age. Pfirrmann grading indicated 69 cases of grade I, 240 cases of grade II, 101 cases of grade III, 43 cases of grade IV and 12 cases of grade V. MRI showed that the T1ρ values of the nucleus pulposi at L4/5 and L5/S1 were significantly reduced (P<0.05) and no significant differences were observed in the T2 values compared with the values of the nucleus pulposus at L1/2, L2/3 and L3/4. The apparent diffusion coefficient (ADC) values of L1/2 were significantly decreased from L2/3 and L3/4 (P<0.05). Correlation analysis revealed that the T1ρ, T, and ADC values were positively correlated with each other. Moreover, the T1ρvalues were significantly decreased with the increase of Pfirrmann grades (P<0.05), with the exception of grades IV and V. However, T2 and ADC values were not significantly different between grades I and II or IV and V. In addition, the T1ρ, T2 and ADC values were significantly decreased with the increase of age in patients with IDD (P<0.05). T1ρ and T2 mapping and DWI are promising techniques for the in vivo diagnosis of IDD, which may be useful in determining the appropriate prevention and treatment options for the disease.

T1ρ/T2 mapping and histopathology of degenerative cartilage in advanced knee osteoarthritis.

AIMTo investigate whether normal thickness cartilage in osteoarthritic knees demonstrate depletion of proteoglycan or collagen content compared to healthy knees.METHODSMagnetic resonance (MR) images were acquired from 5 subjects scheduled for total knee arthroplasty (TKA) (mean age 70 years) and 20 young healthy control subjects without knee pain (mean age 28.9 years). MR images of T1ρ mapping, T2 mapping, and fat suppressed proton-density weighted sequences were obtained. Following TKA each condyle was divided into 4 parts (distal medial, posterior medial, distal lateral, posterior lateral) for cartilage analysis. Twenty specimens (bone and cartilage blocks) were examined. For each joint, the degree and extent of cartilage destruction was determined using the Osteoarthritis Research Society International cartilage histopathology assessment system. In magnetic resonance imaging (MRI) analysis, 2 readers performed cartilage segmentation for T1ρ/T2 values and cartilage thickness measurement.RESULTSEleven areas in MRI including normal or near normal cartilage thickness were selected. The corresponding histopathological sections demonstrated mild to moderate osteoarthritis (OA). There was no significant difference in cartilage thickness in MRI between control and advanced OA samples [medial distal condyle, P = 0.461; medial posterior condyle (MPC), P = 0.352; lateral distal condyle, P = 0.654; lateral posterior condyle, P = 0.550], suggesting arthritic specimens were morphologically similar to normal or early staged degenerative cartilage. Cartilage T2 and T1ρ values from the MPC were significantly higher among the patients with advanced OA (P = 0.043). For remaining condylar samples there was no statistical difference in T2 and T1ρ values between cases and controls but there was a trend towards higher values in advanced OA patients.CONCLUSIONThough cartilage is morphologically normal or near normal, degenerative changes exist in advanced OA patients. These changes can be detected with T2 and T1ρ MRI techniques.

RNA Sequencing Reveals a Role of TonEBP Transcription Factor in Regulation of Pro-inflammatory Genes in Response to Hyperosmolarity in Healthy Nucleus Pulposus Cells: A HOMEOSTATIC RESPONSE?

Transcription factor tonicity-responsive enhancer-binding protein (TonEBP/NFAT5) is critical for osmo-adaptation and extracellular matrix homeostasis of nucleus pulposus (NP) cells in their hypertonic tissue niche. Recent studies implicate TonEBP signaling in inflammatory disease and rheumatoid arthritis pathogenesis. However, broader functions of TonEBP in the disc remain unknown. RNA sequencing was performed on NP cells with TonEBP knockdown under hypertonic conditions. 1140 TonEBP-dependent genes were identified and categorized using Ingenuity Pathway Analysis. Bioinformatic analysis showed enrichment of matrix homeostasis and cytokine/chemokine signaling pathways. C-C motif chemokine ligand 2 (CCL2), interleukin 6 (IL6), tumor necrosis factor (TNF), and nitric oxide synthase 2 (NOS2) were studied further. Knockdown experiments showed that TonEBP was necessary to maintain expression levels of these genes. Gain- and loss-of-function experiments and site-directed mutagenesis demonstrated that TonEBP binding to a specific site in the CCL2 promoter is required for hypertonic inducibility. Despite inhibition by dominant-negative TonEBP, IL6 and NOS2 promoters were not hypertonicity-inducible. Whole-disc response to hypertonicity was studied in an ex vivo organ culture model, using wild-type and haploinsufficient TonEBP mice. Pro-inflammatory targets were induced by hypertonicity in discs from wild-type but not TonEBP-haploinsufficient mice. Mechanistically, NF-κB activity increased with hypertonicity and was necessary for hypertonic induction of target genes IL6, TNF, and NOS2 but not CCL2 Although TonEBP maintains transcription of genes traditionally considered pro-inflammatory, it is important to note that some of these genes also serve anabolic and pro-survival roles. Therefore, in NP cells, this phenomenon may reflect a physiological adaptation to diurnal osmotic loading of the intervertebral disc.

T1ρ Magnetic Resonance Imaging to Assess Cartilage Damage After Primary Shoulder Dislocation

Background: Patients who suffer anterior shoulder dislocations are at higher risk of developing glenohumeral arthropathy, but little is known about the initial cartilage damage after a primary shoulder dislocation. T1ρ is a magnetic resonance imaging (MRI) technique that allows quantification of cartilage proteoglycan content and can detect physiologic changes in articular cartilage. Purpose: This study aimed to establish baseline T1ρ MRI values for glenoid and humeral head cartilage, determine whether T1ρ MRI can detect glenohumeral cartilage damage after traumatic primary shoulder dislocation, and assess for patterns in cartilage damage in anterior shoulder dislocation. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Nine male patients (mean age, 32.0 years; range, 20-59 years) who sustained first-time anterior shoulder dislocations underwent 3T T1ρ MRI. Five healthy controls (mean age, 27.4 years; range, 24-30 years) without prior dislocation or glenohumeral arthritis also underwent 3T T1ρ MRI. The T1ρ relaxation constant was determined for the entire glenoid and humeral head for patients with a dislocation and for healthy controls. The glenoid and humeral head were divided into 9 zones, and T1ρ values were determined for each zone in dislocated and control shoulders to identify patterns in cartilage damage in dislocated shoulders. Results: Average overall T1ρ values for humeral head cartilage in dislocated shoulders were significantly greater than in controls (41.7 ± 3.9 ms vs 38.4 ± 0.6 ms, respectively; P = .03). However, average overall T1ρ values for glenoid cartilage were not significantly different in dislocated shoulders compared with controls (44.0 ± 3.3 ms vs 44.6 ± 2.4 ms, respectively; P = .40), suggesting worse damage to humeral head cartilage. T1ρ values in the posterior-middle humeral head were higher in patients with a dislocation compared with controls (41.5 ± 3.8 ms vs 38.2 ± 2.2 ms, respectively; P = .021) and trended toward significance in the posterior-superior and middle-superior zones (35.2 ± 4.9 ms vs 31.3 ± 1.0 ms and 33.7 ± 5.0 ms vs 30.5 ± 1.3 ms, respectively; P = .056). These 3 humeral head zones are where Hill-Sachs lesions predominate. T1ρ values in the anterior-inferior glenoid zone trended toward significance in patients with a dislocation compared with controls (47.4 ± 5.0 ms vs 43.5 ± 3.5 ms, respectively; P = .073). Conclusion: Humeral head cartilage sustained greater damage than glenoid cartilage in primary dislocation. T1ρ values were higher in glenohumeral zones associated with Bankart and Hill-Sachs lesions. Widespread initial cartilage damage may predispose patients to glenohumeral arthropathy.

Measurement of Myocardial T1ρ with a Motion Corrected, Parametric Mapping Sequence in Humans.

PurposeTo develop a robust T1ρ magnetic resonance imaging (MRI) sequence for assessment of myocardial disease in humans.Materials and MethodsWe developed a breath-held T1ρ mapping method using a single-shot, T1ρ-prepared balanced steady-state free-precession (bSSFP) sequence. The magnetization trajectory was simulated to identify sources of T1ρ error. To limit motion artifacts, an optical flow-based image registration method was used to align T1ρ images. The reproducibility and accuracy of these methods was assessed in phantoms and 10 healthy subjects. Results are shown in 1 patient with pre-ventricular contractions (PVCs), 1 patient with chronic myocardial infarction (MI) and 2 patients with hypertrophic cardiomyopathy (HCM).ResultsIn phantoms, the mean bias was 1.0 ± 2.7 msec (100 msec phantom) and 0.9 ± 0.9 msec (60 msec phantom) at 60 bpm and 2.2 ± 3.2 msec (100 msec) and 1.4 ± 0.9 msec (60 msec) at 80 bpm. The coefficient of variation (COV) was 2.2 (100 msec) and 1.3 (60 msec) at 60 bpm and 2.6 (100 msec) and 1.4 (60 msec) at 80 bpm. Motion correction improved the alignment of T1ρ images in subjects, as determined by the increase in Dice Score Coefficient (DSC) from 0.76 to 0.88. T1ρ reproducibility was high (COV < 0.05, intra-class correlation coefficient (ICC) = 0.85–0.97). Mean myocardial T1ρ value in healthy subjects was 63.5 ± 4.6 msec. There was good correspondence between late-gadolinium enhanced (LGE) MRI and increased T1ρ relaxation times in patients.ConclusionSingle-shot, motion corrected, spin echo, spin lock MRI permits 2D T1ρ mapping in a breath-hold with good accuracy and precision.

Inter- and intra-rater reliability of patellofemoral kinematic and contact area quantification by fast spin echo MRI and correlation with cartilage health by quantitative T1ρ MRI

BackgroundPatellar maltracking is a leading cause of patellofemoral pain syndrome (PFPS). The aim of this study was to determine the inter- and intra-rater reliability of a semi-automated program for magnetic resonance imaging (MRI) based patellofemoral kinematics. MethodsSixteen subjects (10 with PFPS [mean age 32.3; SD 5.2; eight females] and six controls without PFPS 19 [mean age 28.6; SD 2.8; three females]) participated in the study. One set of T2-weighted, fat-saturated fast spin-echo (FSE) MRIs were acquired from each subject in full extension and 30° of knee flexion. MRI including axial T1ρ relaxation time mapping sequences was also performed on each knee. Following image acquisitions, regions of interest for kinematic MRI, and patellar and trochlear cartilage were segmented and quantified with in-house designed spline- based MATLAB semi-automated software. ResultsIntraclass Correlations Coefficients (ICC) of calculated kinematic parameters were good to excellent, ICC > 0.8 in patellar flexion, rotation, tilt, and translation (anterior -posterior, medial -lateral, and superior -inferior), and contact area translation. Only patellar tilt in the flexed position and motion from extended to flexed state was significantly different between PFPS and control patients (p=0.002 and p=0.006, respectively). No significant correlations were identified between patellofemoral kinematics and contact area with T1ρ relaxation times. ConclusionsA semi-automated, spline-based kinematic MRI technique for patellofemoral kinematic and contact area quantification is highly reproducible with the potential to help better understand the role of patellofemoral maltracking in PFPS and other knee disorders. Level of EvidenceLevel IV

Comparison of multiple quantitative MRI parameters for characterization of the goat cartilage in an ongoing osteoarthritis: dGEMRIC, T1ρ and sodium

Rationale and ObjectivesOsteoarthritis (OA) is a degenerative joint disease leading to cartilage deterioration by loss of matrix, fibrillation, formation of fissures, and ultimately complete loss of the cartilage surface. Here, three magnetic resonance imaging (MRI) techniques, dGEMRIC (delayed Gadolinium enhanced MRI of cartilage; dG1=T1,post; dG2=1/T1,post-1/T1,pre), T1ρ,and sodium MRI, are compared in a preclinical in vivo study to evaluate the differences in their potential for cartilage characterization and to establish an examination protocol for a following clinical study. Materials and MethodsOA was induced in 12 caprine knees (6 control, 6 therapy). Adipose derived stem cells were injected afterwards as a treatment. The animals were examined healthy, 3 and 16 weeks postoperatively with all three MRI methods.Using statistical analysis, the OA development and the degree of correlation between the different MRI methods were determined. ResultsA strong correlation was observed between the dGEMRIC indices dG1 and dG2 (r=–0.87) which differ only in considering or not considering the T1 baseline. Moderate correlations were found between T1ρ and dG1 (r=0.55), T1ρ and dG2 (r=0.47) and at last, sodium and dG1 (r=0.45).The correlations found in this study match to the biomarkers which the methods are sensitive to. ConclusionEven though the goat cartilage is significantly thinner than the human cartilage and even more in a degenerated cartilage, all three methods were able to characterize the cartilage over the whole period of time during an ongoing OA.Due to measurement and post processing optimizations, as well as the correlations detected in this work, the overall measurement time in future goat studies can be minimized. Moreover, an examination protocol for characterizing the cartilage in a clinical study was established.

T1ρ magnetic resonance imaging quantification of early articular cartilage degeneration in a rabbit model.

BackgroundOsteoarthritis (OA) is a serious problem in the recent aging society, and early diagnosis and intervention of articular cartilage degeneration are very important for the onset of OA. Therefore, development of newer MRI techniques is necessary and expected for detection of early articular cartilage degeneration.Methods24 rabbits were randomly divided into four equal experimental groups (Group A, B, C, D) to establish articular cartilage models in different grades of early degeneration by injecting papain into the left knee joint cavity. Another 8 rabbits were considered as blank control (Group E), and then randomized into four subgroups (EA, EB, EC, ED). T1ρ and T2-weighted images of the bilateral knee joints were obtained for rabbits by using 3.0 T MRI. Group A, B, C, and D were imaged respectively at 1, 2, 3, and 4 weeks post-operation, and EA, EB, EC, ED underwent the same period imaging. Rabbits were sacrificed after scanning and the femoral condyle cartilage (FCC) was histological examined. T1ρ values of the femoral condyle cartilage were measured and statistically analyzed, and contrasted with the histologic results.ResultsT1ρ values of the left side in experimental groups were significantly higher than the right side (P < 0.05), and which increased gradually with the passage of post-operation time (P < 0.05). Histological examination demonstrated the proteoglycan content of the left side decreased, and indicated the occurrence of early degeneration.ConclusionsT1ρ MRI can sensitively and quantitatively reflect the change in proteoglycans prior to the morphologic alterations of articular cartilage, and T1ρ value is gradually increased with a decrease in proteoglycan content, therefore that T1ρ could potentially act as a reliable tool to identify early cartilage degeneration.

An Update on the Pathogenesis of Osteochondrosis.

Osteochondrosis is defined as a focal disturbance in endochondral ossification. The cartilage superficial to an osteochondrosis lesion can fracture, giving rise to fragments in joints known as osteochondrosis dissecans (OCD). In pigs and horses, it has been confirmed that the disturbance in ossification is the result of failure of the blood supply to epiphyseal growth cartilage and associated ischemic chondronecrosis. The earliest lesion following vascular failure is an area of ischemic chondronecrosis at an intermediate depth of the growth cartilage (osteochondrosis latens) that is detectable ex vivo, indirectly using contrast-enhanced micro- and conventional computed tomography (CT) or directly using adiabatic T1ρ magnetic resonance imaging. More chronic lesions of ischemic chondronecrosis within the ossification front (osteochondrosis manifesta) are detectable by the same techniques and have also been followed longitudinally in pigs using plain CT. The results confirm that lesions sometimes undergo spontaneous resolution, and in combination, CT and histology observations indicate that this occurs by filling of radiolucent defects with bone from separate centers of endochondral ossification that form superficial to lesions and by phagocytosis and intramembranous ossification of granulation tissue that forms deep to lesions. Research is currently aimed at discovering the cause of the vascular failure in osteochondrosis, and studies of spontaneous lesions suggest that failure is associated with the process of incorporating blood vessels into the advancing ossification front during growth. Experimental studies also show that bacteremia can lead to vascular occlusion. Future challenges are to differentiate between causes of vascular failure and to discover the nature of the heritable predisposition for osteochondrosis.

Is the contralateral hip at risk in patients with unilateral symptomatic cam femoroacetabular impingement? A quantitative T1ρ MRI study

To assess the profile of weight-bearing cartilage of hips with a cam deformity using T1ρ magnetic resonance imaging (MRI) and evaluate for a side-to-side difference in the T1ρ profile of patients with bilateral cam morphology but only unilateral hip pain. 19 patients with bilateral cam morphology undergoing osteochondroplasty for unilateral hip pain were prospectively recruited. Anterior and anterosuperior alpha angles were measured using computer tomography. All patients underwent bilateral 1.5T T1ρ MRI. The cartilage bilayer of the hip joint was evaluated and the mean T1ρ relaxation time calculated for each quadrant of the weight-bearing surface. Mean T1ρ relaxation times were not significantly different when each quadrant was compared to the rest of the weight-bearing surface of the symptomatic (P = 0.068) and asymptomatic hips (P = 0.102). There was also no significant side-to-side difference between the same quadrants of symptomatic and asymptomatic hips. No correlation was detected between alpha angle and the mean T1ρ relaxation time in each quadrant. There was no significant difference in mean alpha angles between the symptomatic and asymptomatic sides at the anterior (54.2 vs 56.0°; P = 0.382) and anterosuperior positions (65.1 vs 65.2°; P = 0.971). We conclude that previously observed regional variation in T1ρ values of normal hips is altered in hips with cam morphology. No difference in T1ρ values between symptomatic and asymptomatic cam hips was demonstrated. Therefore, regardless of the presence of hip pain, a cam deformity may predispose to hip joint cartilage degradation and increase the risk of hip osteoarthritis.