7. Abstract Entheses are regions where tendons, ligaments and joint capsules are connected to bone. They are transition zones between flexible and rigid tissues, and stress concentrates at the junction between these two types of tissue as a result of their widely different mechanical properties. Entheses are very commonly involved in many diseases including the overuse syndromes, the early stages of osteoarthritis (OA) and psoriatic arthropathy (PsA). Despite its importance, assessment of enthesitis is difficult. Clinical exam based on tenderness on direct palpation may not be sensitive nor specific. Ultrasound can show enthesial abnormalities, but is operator dependent. Conventional MR imaging has not been helpful in demonstrating the key tissues present in normal entheses which have short T2*s and show little or no signal. As a result normal entheses have not been identifiable with clinical MR imaging. Furthermore, clinical MR imaging biomarkers like T2 (a biomarker of collagen) and T1? (a biomarker of proteoglycan or PG) show strong magic angle effects, which may result in a several fold increase in T2 and T1? when the tissue fibers are oriented ~55? to the B0 field. We have developed 3D ultrashort echo time (UTE) sequences with TEs of 8 s that are 100~1000 times shorter than the TEs of clinical sequences, allowing us to image entheses. Recent studies show that adiabatic spin-locking and magnetization transfer (MT) imaging are magic angle insensitive. The combination of UTE and adiabatic T1? may allow magic angle insensitive assessment of PG changes in entheses. The combination of UTE and MT may provide magic angle insensitive evaluation of water and collagen proton fractions and exchange rates in entheses. Both UTE-adiabatic-T1? and UTE-MT require T1 compensation. UTE with actual flip angle imaging (AFI) allows accurate T1 mapping of short T2 tissues. Our central hypothesis is that the ability to directly image and quantify the entheses with UTE sequences will provide a new option for correlating structure with mechanical function, and an important method for recognizing change in disease. Our objective is to use UTE for systematic and comprehensive characterization of tendons and entheses in PsA patients.
In Aim 1 we will develop UTE sequences for assessment of PG, collagen and water components in tendons and entheses in normal ankles (n=10).
In Aim 2 we will compare UTE and clinical sequences for quantitative evaluation of ankle specimens with no abnormality (n=20), and well established PsA (n=20). We will correlate MRI measures with histopathology, PLM, biochemistry and biomechanics.
In Aim 3 we will apply UTE sequences to the Achilles tendon enthesis in normal controls (n=30), PsA patients with no clinically evident enthesitis (n=30) and with active enthesitis (n=30). The PsA patients will be treated with tumor necrosis factor (TNF) inhibitors, and will be scanned again at two, six and 12 months to access longitudinal changes. We will correlate the MR measures with physical examination and patient reported outcomes (PROs). We expect that UTE MRI measures will be highly correlated with PROs, enthesial inflammation and subclinical enthesitis.
Our objective is to use newly developed 3D UTE Cones sequences, including 3D Cones T2*, Cones-AFI T1, Cones-adiabatic-T1? and Cones-MT for a systematic and comprehensive characterization of tendons and entheses in patients with psoriatic arthropathy (PsA). We will evaluate Cones sequences for morphological and quantitative evaluation of tendons and entheses in ankle specimens with no abnormality and with well established PsA, using histology, polarized light microscopy (PLM), biochemical essay and biomechanical testing as reference standards, followed by cross sectional and longitudinal studies of healthy volunteers and PsA patients without and with active enthesitis treated with tumor necrosis factor (TNF) inhibitors. We will correlate the UTE MRI measures with clinical outcomes including physical examination and patient reported outcomes (PROs), and we expect that 3D UTE Cones sequences will be better correlated with PROs, enthesial inflammation and subclinical enthesitis, and more sensitive to longitudinal changes in the tendons and entheses subject to TNF treatment than conventional clinical sequences.
