7. Abstract Magnetic resonance imaging (MRI) is widely used for the diagnosis of advanced osteoarthritis (OA), but is less sensitive for the diagnosis of early OA. There are three major barriers to progress in evaluation of early OA. First, OA is a ?whole organ disease? involving all the principal knee joint tissues. However, many tissues or tissue components such as the deep layers of cartilage, menisci, ligaments, tendons and bone have short T2s and show little or no signal with conventional clinical sequences. Second, distinct proton groups, namely water protons and macromolecular protons are present in most joint tissues. Macromolecular protons in many the knee joint tissues, especially the short T2 tissues have not been investigated with clinical sequences. Third, extensive research over the past two decades has focused on two particular biomarkers for OA: T2 and T1?, with T2 sensitive to collagen degradation, and T1? sensitive to proteoglycan (PG) depletion. The main confounding factor is the magic angle effect, which may result in a several fold increase in T2 and T1? when the tissue fibers are oriented ~54? to the B0 field. This often far exceeds the change produced by disease. We have developed 3D ultrashort echo time (UTE) sequences with TEs as short as 8 s that are 100-1000 times shorter than the TEs of clinical sequences. These allow us to directly image ?MR invisible? joint tissues. Recently adiabatic spin-lock imaging has been proposed to measure T1?. Magnetization transfer (MT) imaging has been introduced to assess macromolecular protons. Most importantly, the adiabatic T1? and MT biomarkers are magic angle insensitive. In this proposal, we will further develop a 3D adiabatic-UTE-T1? sequence for magic angle insensitive T1? measurement, and a UTE-MT sequence for magic angle insensitive biomarkers of MT ratio (MTR) and MT modeling of macromolecular fractions and exchange rates. We will further evaluate the 3D adiabatic-UTE-T1? and UTE-MT techniques for evaluation of macromolecules and water components in both short and long T2 tissues in normal knee joint specimens (Aim 1). We expect that the UTE-adiabatic-T1? biomarker will be sensitive to PG depletion, while the UTE MTR and MT modeling parameters will be sensitive to PG and collagen changes in the knee joint tissues. Then we will compare the novel 3D UTE and clinical sequences for quantitative evaluation of cadaveric human knee specimens with normal (n=20), mild (n=20) and moderate (n=20) OA (Aim 2). We expect that the UTE-adiabatic-T1? and UTE-MT sequences will be more sensitive to degeneration in the principal knee joint tissues than conventional clinical sequences. Finally, we will apply 3D UTE-adiabatic-T1? and UTE-MT techniques to evaluate knee joint degeneration in healthy volunteers (n=20) and patients (n=20) 6 months, 1 year, and 2 years after anterior cruciate ligament (ACL) reconstruction. We will correlate the MR measures with clinical scores (Aim 3). We expect the UTE measures will be more sensitive than clinical MRI measures to changes in the knee of patients after ACL reconstruction. The study is likely to have a major impact on making early OA diagnosis and monitoring disease progression.

Public Health Relevance

The goal of this project is to develop novel ultrashort echo time (UTE) magnetic resonance imaging (MRI) sequences for morphological imaging and quantitative evaluation of the principal tissues of the knee joint and apply these to the study of knee joint degeneration in vitro and in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR062581-08
Application #
10122909
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Zheng, Xincheng
Project Start
2013-09-01
Project End
2023-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
8
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Ma, Ya-Jun; Chang, Eric Y; Carl, Michael et al. (2018) Quantitative magnetization transfer ultrashort echo time imaging using a time-efficient 3D multispoke Cones sequence. Magn Reson Med 79:692-700
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
Ma, Ya-Jun; Zhao, Wei; Wan, Lidi et al. (2018) Whole knee joint T1 values measured in vivo at 3T by combined 3D ultrashort echo time cones actual flip angle and variable flip angle methods. Magn Reson Med :
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
Chen, Bimin; Zhao, Yinghua; Cheng, Xin et al. (2018) Three-dimensional ultrashort echo time cones (3D UTE-Cones) magnetic resonance imaging of entheses and tendons. Magn Reson Imaging 49:4-9

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