Persistent Biomechanical Alterations After ACL Reconstruction Are Associated With Early Cartilage Matrix Changes Detected by Quantitative MR.

BackgroundThe effectiveness of anterior cruciate ligament (ACL) reconstruction in preventing early osteoarthritis is debated. Restoring the original biomechanics may potentially prevent degeneration, but apparent pathomechanisms have yet to be described. Newer quantitative magnetic resonance (qMR) imaging techniques, specifically T1ρ and T2, offer novel, noninvasive methods of visualizing and quantifying early cartilage degeneration.PurposeTo determine the tibiofemoral biomechanical alterations before and after ACL reconstruction using magnetic resonance imaging (MRI) and to evaluate the association between biomechanics and cartilage degeneration using T1ρ and T2.Study designCohort study; Level of evidence, 2.MethodsKnee MRIs of 51 individuals (mean age, 29.5 ± 8.4 years) with unilateral ACL injuries were obtained prior to surgery; 19 control subjects (mean age, 30.7 ± 5.3 years) were also scanned. Follow-up MRIs were obtained at 6 months and 1 year. Tibial position (TP), internal tibial rotation (ITR), and T1ρ and T2 were calculated using an in-house Matlab program. Student t tests, repeated measures, and regression models were used to compare differences between injured and uninjured sides, observe longitudinal changes, and evaluate correlations between TP, ITR, and T1ρ and T2.ResultsTP was significantly more anterior on the injured side at all time points (P < .001). ITR was significantly increased on the injured side prior to surgery (P = .033). At 1 year, a more anterior TP was associated with elevated T1ρ (P = .002) and T2 (P = .026) in the posterolateral tibia and with decreased T2 in the central lateral femur (P = .048); ITR was associated with increased T1ρ in the posteromedial femur (P = .009). ITR at 6 months was associated with increased T1ρ at 1 year in the posteromedial tibia (P = .029).ConclusionPersistent biomechanical alterations after ACL reconstruction are related to significant changes in cartilage T1ρ and T2 at 1 year postreconstruction. Longitudinal correlations between ITR and T1ρ suggest that these alterations may be indicative of future cartilage injury, leading to degeneration and osteoarthritis.Clinical relevanceNewer surgical techniques should be developed to eliminate the persistent anterior tibial translation commonly seen after ACL reconstruction. qMR will be a useful tool to evaluate the ability of these newer techniques to prevent cartilage changes

T1ρ-based fibril-reinforced poroviscoelastic constitutive relation of human articular cartilage using inverse finite element technology

BackgroundMapping of T1ρ relaxation time is a quantitative magnetic resonance (MR) method and is frequently used for analyzing microstructural and compositional changes in cartilage tissues. However, there is still a lack of study investigating the link between T1ρ relaxation time and a feasible constitutive relation of cartilage which can be used to model complicated mechanical behaviors of cartilage accurately and properly.MethodsThree-dimensional finite element (FE) models of ten in vitro human tibial cartilage samples were reconstructed such that each element was assigned by material-level parameters, which were determined by a corresponding T1ρ value from MR maps. A T1ρ-based fibril-reinforced poroviscoelastic (FRPE) constitutive relation for human cartilage was developed through an inverse FE optimization technique between the experimental and simulated indentations.ResultsA two-parameter exponential relationship was obtained between the T1ρ and the volume fraction of the hydrated solid matrix in the T1ρ-based FRPE constitutive relation. Compared with the common FRPE constitutive relation (i.e., without T1ρ), the T1ρ-based FRPE constitutive relation indicated similar indentation depth results but revealed some different local changes of the stress distribution in cartilages.ConclusionsOur results suggested that the T1ρ-based FRPE constitutive relation may improve the detection of changes in the heterogeneous, anisotropic, and nonlinear mechanical properties of human cartilage tissues associated with joint pathologies such as osteoarthritis (OA). Incorporating T1ρ relaxation time will provide a more precise assessment of human cartilage based on the individual in vivo MR quantification

Exact solvability of potentials with spatially dependent effective masses

We discuss the relationship between exact solvability of the Schroedinger equation, due to a spatially dependent mass, and the ordering ambiguity. Some examples show that, even in this case, one can find exact solutions. Furthermore, it is demonstrated that operators with linear dependence on the momentum are nonambiguous.Comment: 12 page

Hierarchical Wave Functions Revisited

We study the hierarchical wave functions on a sphere and on a torus. We simplify some wave functions on a sphere or a torus using the analytic properties of wave functions. The open question, the construction of the wave function for quasielectron excitations on a torus, is also solved in this paper.Comment: 28 pages, Late

A novel epigenetic AML1-ETO/THAP10/miR-383 mini-circuitry contributes to t(8;21) leukaemogenesis

DNA methylation patterns are frequently deregulated in t(8;21) acute myeloid leukaemia (AML), but little is known of the mechanisms by which specific gene sets become aberrantly methylated. Here, we found that the promoter DNA methylation signature of t(8;21)(+) AML blasts differs from that of t(8;21)(-) AMLs. This study demonstrated that a novel hypermethylated zinc finger-containing protein, THAP10, is a target gene and can be epigenetically suppressed by AML1-ETO at the transcriptional level in t(8;21) AML. Our findings also show that THAP10 is a bona fide target of miR-383 that can be epigenetically activated by the AML1-ETO recruiting co-activator p300. In this study, we demonstrated that epigenetic suppression of THAP10 is the mechanistic link between AML1-ETO fusion proteins and tyrosine kinase cascades. In addition, we showed that THAP10 is a nuclear protein that inhibits myeloid proliferation and promotes differentiation both in vitro and in vivo Altogether, our results revealed an unexpected and important epigenetic mini-circuit of AML1-ETO/THAP10/miR-383 in t(8;21) AML, in which epigenetic suppression of THAP10 predicts a poor clinical outcome and represents a novel therapeutic target