Lidi Wan^{1,2}, Yajun Ma^{1}, Saeed Jerban^{1}, Micheal Carl^{3}, Eric Y Chang^{1,4}, Guangyu Tang^{2}, and Jiang Du^{1}

We have developed a series of 3D UTE-Cones MRI techniques for quantitative assessment of all major tissues in the knee joint. Continuing improvements in scan time will facilitate their clinical use, but it remains unclear how acceleration affects quantification. This study focused on the effects of stretching sampling windows on quantitative UTE biomarkers in cadaveric human knee joint tissues. We found that extending sampling windows results in vastly reduce scan time without adverse effects on quantitative accuracy of T1, AdiabaticT1ρ, macromolecular fraction and MTR of articular cartilage, menisci, tendons and ligaments in the knee joint.

**Sample preparation:** High resolution whole knee imaging was performed on 9 whole knee joint specimens from 8 donors (65 ± 26 years old, 7 males and 1 female).

**UTE sequences:** All imaging was performed on a 3T clinical MRI scanner (MR750, GE Healthcare Technologies, Milwaukee, WI, USA) using a knee coil. All 3D UTE-Cones sequences used a short rectangular excitation pulse followed by 3D spiral sampling with various data acquisition window lengths (Figure 1a, 1b). Three quantitative imaging protocols were performed: T1 was mapped using a 3D UTE-Cones AFI-VFA method with B1 correction (FAs = 5, 10, 20, 30 ˚, TR = 20 ms), AdiabaticT1ρ was mapped using the 3D UTE-Cones-Adiabatic T1ρ sequence which employs adiabatic full passage pulse train prepared UTE-Cones acquisitions (spin lock time=0, 12, 24, 36, 48, 72, 96 ms, TR=500, FA=10˚), MTR and MT modeling were performed with a 3D UTE-Cones-MT sequence (MT saturation power = 500°, 1000°, and 1500°, frequency offset = 2, 5, 10, 20, and 50 kHz, TR=100 ms, FA = 7˚). A two-pool MT modeling was performed for calculation of macromolecular proton fraction. Cones trajectories were used for all quantitative UTE measurements. Each measurement was repeated with three sampling windows: Cones_1.0 with no stretching and 1116 µs sampling window (reference), Cones_1.5 with a stretching factor of 1.5 and 1668 µs sampling window, and Cones_2.0 with a stretching factor of 2.0 and 2232 µs sampling window . Other imaging parameters included: FOV = 15×15×8 cm, acquisition matrix = 256×256, 40 slices, and bandwidth = 166 kHz.

**Data analysis:** The effect of sampling window on each biomarker was investigated for cartilage, menisci, ligaments and tendons using manually drawn regions-of-interest (ROIs). Error percentage [(Results longer cones –Results Cones 1.0)/ Results Cones 1.0] for each biomarker was calculated for Cones_1.5 and Cones_2.0 using results from Cones_1.0 as a reference standard.

Figure 2 shows no distinct morphological differences between Cones_1.0 to Cones_2.0 for long T2 tissue components such as the superficial layer of cartilage. However, short T2 blurring was observed in tissues with short T2 components such as the deep layer of cartilage and ligaments (e.g. PCL).

Figure 3 shows that the signal intensities of T1, AdiabaticT1ρ and MT images decreased for all evaluated tissues by increasing the stretching factor, indicating signal loss for all knee joint tissues by extending the sampling window.

Figure 4 summarizes 3D UTE-Cones biomarker measurements and errors for cartilage, menisci, tendons and ligaments with all three sampling windows. As for T1, AdiabaticT1ρ, macromolecular fraction and MTR, non-significantly increased errors were observed with a longer sampling window. The error percentages were within 5% for all evaluated tissues except the ligaments with error larger than 5% when sampling window was 2232 µs. (p>0.05).

1. Brandt KD, Radin EL, Dieppe PA, van de Putte L. Yet more evidence that osteoarthritis is not a cartilage disease. Annals of the rheumatic diseases 2006;65(10):1261-1264.

2. Hunter DJ, Zhang YQ, Niu JB, Tu X, Amin S, Clancy M, Guermazi A, Grigorian M, Gale D, Felson DT. The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis. Arthritis and rheumatism 2006;54(3):795-801.

3. Tan AL, Toumi H, Benjamin M, Grainger AJ, Tanner SF, Emery P, McGonagle D. Combined high-resolution magnetic resonance imaging and histological examination to explore the role of ligaments and tendons in the phenotypic expression of early hand osteoarthritis. Annals of the rheumatic diseases 2006;65(10):1267-1272.

4. Ma YJ, Carl M, Searleman A, Lu X, Chang EY, Du J. 3D adiabatic T1rho prepared ultrashort echo time cones sequence for whole knee imaging. Magnetic resonance in medicine 2018;80(4):1429-1439. 5. Ma YJ, Carl M, Shao H, Tadros AS, Chang EY, Du J. Three-dimensional ultrashort echo time cones T1rho (3D UTE-cones-T1rho ) imaging. 2017;30(6).

6. Ma YJ, Chang EY, Carl M, Du J. Quantitative magnetization transfer ultrashort echo time imaging using a time-efficient 3D multispoke Cones sequence. Magnetic resonance in medicine 2018;79(2):692-700.

7. Ma YJ, Chang EY, Carl M, Du J. Quantitative magnetization transfer ultrashort echo time imaging using a time-efficient 3D multispoke Cones sequence. Magnetic resonance in medicine 2017.

8. Ma YJ, Lu X, Carl M, Zhu Y, Szeverenyi NM, Bydder GM, Chang EY, Du J. 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. Magnetic resonance in medicine 2018;80(2):598-608.

Figure 1. UTE
pulse sequence diagrams: 3D UTE-Cones
with a short rectangular hard pulse excitation is followed by 3D spiral
sampling with a very short TE of 32 µs.

Figure 2. Two representative
slices of 3D UTE-Cones AFI-VFA T1 (a-c), 3D UTE-Cones-AdiabaticT1ρ (d-f)
and 3D UTE-Cones-MT (i-k) magnitude images
of the same whole knee specimen with different sampling windows: cones1.0
(a, d, i), cones1.5 (b, e, j), cones2.0 (c, f, k).

Figure 3. Signal intensity variation of T1 (TR=20, FA=30°, TE=32 µs), T1ρ (spin
lock time=0 ms, TR=500, FA=10˚), and MT
(FA=500°, offset=2000 Hz, TE= 32 µs) images with different sampling
windows (Cones 1.0: 1116 µs; Cones 1.5: 1668µs; Cones 2.0: 2232 µs) of representative ROIs for cartilage, menisci, tendons and
ligaments, as shown in 3a. The corresponding signal
intensity variation curves of T1, T1ρ, and MT images were shown in b, c and d respectively, with dots
representing the mean value and error bar representing the standard deviation
of signal intensity of nine knee joint specimens.

Figure 4. Mean and
standard deviation of MR properties in the
major tissues of knee joint, including cartilage, menisci, tendons and
ligaments. Errors
compare the results of Cones 1.5 and Cones 2.0 with Cones 1.0, which is the
reference standard.
MMF: macromolecular fraction, MTR: magnetization transfer ratio