The rotator cuff tendon (RCT) is the primary dynamic stabilizer of the glenohumeral joint and dysfunction can lead to abnormal joint kinematics, ultimately causing cartilage degeneration and cuff arthropathy. RCT pathology is common, present in up to 70% of cases that seek medical attention for shoulder pain. However, not all RCT pathology is equivalent and clinical decision making can be heavily influenced by knowledge of tissue status. Additionally, conventional MRI is limited due to the short T2 properties of tendon and the magic angle effect, which causes signal intensity changes in anisotropic structures dependent on orientation within the magnet. These changes often far exceed that produced by disease. This application proposes to perform a study that will implement quantitative MR biomarkers on RCT, which has not previously been performed. We have developed three new purpose-driven, ultrashort time-to-echo (UTE) sequences to combat the confounding factor of the magic angle effect while imaging the majority of the constituents of the RCT, which include water, collagen and proteoglycan/GAG. These sequences include multi-echo UTE-magnetization transfer, UTE bi- component, and adiabatic UTE-T1rho techniques. In our first aim, we compare the sensitivity of novel and conventional MR pulse sequences to the magic angle effect in RCT. Our hypothesis is that our novel UTE sequences will be resistant to the magic angle effects compared with conventional sequences. In our second aim, we propose to compare the relationship between novel UTE sequences and standard clinical quantitative sequences in an in vitro model of RCT degeneration with biochemical and histopathologic reference standards. Our hypothesis is that our novel UTE sequences will more strongly correlate with changes in RCT microstructural integrity. In our third aim, we apply the aforementioned techniques in whole shoulder specimens with normal and degenerated RCTs, implementing histopathologic and biomechanical reference standards. Our hypothesis is that novel UTE sequences will allow non-invasive tissue characterization (both structural and biomechanical). In our final aim, we will translate the novel MR pulse sequences to a cohort of patients with unilateral shoulder pain, utilizing measurements on the contralateral asymptomatic shoulder and clinical assessment tools as reference standards. Our hypothesis is that novel quantitative MR sequences can be successfully translated to the clinical setting where they can aid in the non-invasive characterization of RCT quality. Ultimately this information could be helpful to the orthopedic surgeon for pre-operative and post- operative tendon quality assessment.

Public Health Relevance

The magic angle effect is a major confounder in MR evaluation of rotator cuff tendon (RCT). This study proposes to use quantitative MR pulse sequences, implementing novel ultrashort time-to-echo (UTE) techniques which are magic angle resistant, to evaluate the microstructural integrity of human rotator cuff tendon. These sequences include multi-echo UTE-magnetization transfer, UTE bi-component, and adiabatic UTE-T1rho techniques. Sequences will be validated in both in vitro and ex vivo models of RCT degeneration and correlation will be made to biochemical, histopathologic, and biomechanical reference standards. In the final aim, sequences will be translated to cohorts of patients with and without shoulder pain.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Non-HHS Research Projects (I01)
Project #
5I01CX001388-02
Application #
9247702
Study Section
Cellular and Molecular Medicine (CAMM)
Project Start
2016-07-01
Project End
2021-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
VA San Diego Healthcare System
Department
Type
DUNS #
073358855
City
San Diego
State
CA
Country
United States
Zip Code
92161
Ma, Ya-Jun; Lu, Xing; Carl, Michael et al. (2018) Accurate T1 mapping of short T2 tissues using a three-dimensional ultrashort echo time cones actual flip angle imaging-variable repetition time (3D UTE-Cones AFI-VTR) method. Magn Reson Med 80:598-608
Ma, Ya-Jun; Tadros, Anthony; Du, Jiang et al. (2018) Quantitative two-dimensional ultrashort echo time magnetization transfer (2D UTE-MT) imaging of cortical bone. Magn Reson Med 79:1941-1949
Ma, Ya-Jun; Carl, Michael; Searleman, Adam et al. (2018) 3D adiabatic T1? prepared ultrashort echo time cones sequence for whole knee imaging. Magn Reson Med 80:1429-1439
Nguyen, S; Lu, X; Ma, Y et al. (2018) Musculoskeletal ultrasound for intra-articular bleed detection: a highly sensitive imaging modality compared with conventional magnetic resonance imaging. J Thromb Haemost 16:490-499
Zhu, Yanchun; Cheng, Xin; Ma, Yajun et al. (2018) Rotator cuff tendon assessment using magic-angle insensitive 3D ultrashort echo time cones magnetization transfer (UTE-Cones-MT) imaging and modeling with histological correlation. J Magn Reson Imaging 48:160-168
von Drygalski, Annette; Moore, Randy E; Nguyen, Sonha et al. (2018) Advanced Hemophilic Arthropathy: Sensitivity of Soft Tissue Discrimination With Musculoskeletal Ultrasound. J Ultrasound Med 37:1945-1956
Lu, Xing; Ma, Yajun; Chang, Eric Y et al. (2018) Simultaneous quantitative susceptibility mapping (QSM) and R2* for high iron concentration quantification with 3D ultrashort echo time sequences: An echo dependence study. Magn Reson Med 79:2315-2322
Park, C Kevin; Zlomislic, Vinko; Du, Jiang et al. (2018) Nonoperative Management of a Severe Proximal Rectus Femoris Musculotendinous Injury in a Recreational Athlete: A Case Report. PM R 10:1417-1421
Nguyen, Brian J; Burt, Ashley; Baldassarre, Randall L et al. (2018) The prognostic and diagnostic value of 18F-FDG PET/CT for assessment of symptomatic osteoarthritis. Nucl Med Commun 39:699-706
Ma, Ya-Jun; West, Justin; Nazaran, Amin et al. (2018) Feasibility of using an inversion-recovery ultrashort echo time (UTE) sequence for quantification of glenoid bone loss. Skeletal Radiol 47:973-980

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