We propose to develop a novel UTE-T1rho magnetic resonance imaging (MRI) sequence at 7 Tesla that will provide multiexponential measures of T1rho and T2 in the superficial, deep, and calcified layers of cartilage. T1rho relaxation values have been correlated with proteoglycan concentration in cartilage, while T2 relaxation has been shown to relate to the collagen fiber structure. The use of 7 Tesla imaging will allow for higher signal to noise ratio and possibly higher resolution, potentially improving the accuracy of T1rho measurement. Additionally, T1rho sensitivity will increase at 7 Tesla, potentially allowing for detection of smaller changes.
Aim 1 will focus on development of the combined UTE-T1rho sequence at 3 Tesla and 7 Tesla. Initial work will focus on conversion of individual UTE and T1rho sequences from 3 Tesla to 7 Tesla. The sequences will then be combined at 3 Tesla to learn lessons on a less challenging application. Lastly, the lessons learned at 3 Tesla will be used to combine the sequences at 7 Tesla.
In Aim 2, the sequences developed in Aim 1 will be validated in experiments with phantoms, bovine cartilage, and human cartilage. Initial experiments will be performed in phantoms with varying concentrations of agarose to validate the T1rho and UTE measures of the sequences. Experiments in excised cartilage samples from 6-18 month bovine knees will be imaged with the combined sequence and the multiexponential T1rho/T2 values will be examined. Enzyme treatments will be performed to help separate the contributions from collagen and proteoglycans. Lastly, human cartilage samples from patients undergoing total knee replacement will be imaged with the combined sequence to determine multiexponential T1rho/T2 values in human tissue.
In Aim 3, a feasibility study of twenty volunteers will be conducted to test and optimize the combined sequences in vivo and provide preliminary data for future studies. The volunteers will be split evenly between four groups. Group 1 will consist of healthy controls between the age of 20-35, Group 2 will consist of volunteers (age 35-60) with a Kellgren-Lawrence (KL) score of 0, Group 3 will consist of volunteers with KL=1-2 (mild OA), and Group 4 will consist of volunteers with KL=3-4 (severe OA). Volunteers in Group 1 will be imaged with the combined sequence at 3 Tesla and 7 Tesla, while the other groups will be imaged only at 7 Tesla. Multiexponential T1rho/T2 values will be examined for all volunteers. Relevance Currently, T1rho imaging at 3 Tesla is used as a marker for proteoglycan loss in cartilage during the early stages of OA. This work will improve the sensitivity of these measurements and allow for T1rho measurements in areas of cartilage with short T2, such as the deep and calcified layers. Additionally, the sequences developed will allow for multiexponential fitting of the T1rho and T2 values, potentially providing new markers for cartilage degeneration. All of these improvements will also potentially allow for improved detection of biochemical changes to cartilage due to the onset of OA.

Public Health Relevance

This work will improve the sensitivity of T1rho measurements of knee cartilage and allow for these measurements in areas of cartilage with short T2, such as the deep and calcified layers. Additionally, the sequences developed will allow for multiexponential fitting of the T1rho and T2 values, potentially providing new markers for cartilage degeneration. All of these improvements will also potentially allow for improved detection of biochemical changes to cartilage due to the onset of OA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR062964-02
Application #
8546680
Study Section
Special Emphasis Panel (ZRG1-F10B-S (20))
Program Officer
Lester, Gayle E
Project Start
2012-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$53,942
Indirect Cost
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143