Magnetic resonance imaging biomarkers such as T₂ and T_1rho have been widely used in the evaluation of osteoarthritis (OA). The principal confounding factor for T₂ and T1rho measures is the magic angle effect, which may result in a several fold increase in T₂ and T_1rho values. Magic angle independent MR biomarkers are highly desirable for more accurate assessment of OA. In this study we report the use of two-dimensional ultrashort echo time magnetization transfer (UTE-MT) imaging and modeling for magic angle independent assessment of the tissue properties.

A classic two-pool (i.e. water and macromolecular proton pools) MT model was introduced by Henkelman et al. for continuous wave MT (2). With this model, a long continuous MT RF pulse is needed to drive the two-pool system to the steady state. This may not be possible with typical MRI hardware systems and may also cause a very large SAR. To accomplish MT imaging on a conventional clinical scanners, Ramani et al. employed a continuous wave power equivalent (CWPE) method for pulsed wave saturation and applied this technique to image the brain in multiple sclerosis (3). By fitting Ramani’s model, a variety of parameters such as the T₂ values of both water (T_2w) and macromolecular protons (T_2m), macromolecular proton fractions (f), proton exchange rates from macromolecular to water (RM_0w) pools and recovery rate of longitudinal magnetization of water pool (R_w) can be obtained.

Human Achilles tendon samples dissected from cadaveric human ankle specimens (n=3, thickness=1.5cm) were harvested for this study. Data were acquired with a 2D UTE-MT sequence on a clinical 3T scanner (GE Healthcare Technologies, Milwaukee, WI). The UTE sequence employed a short rectangular pulse (duration=32µs) excitation followed by 2D radial ramp sampling with a minimal nominal TE of 8 µs. The MT preparation is consisted of a Fermi shaped RF pulse (duration = 8 ms) followed by a gradient crusher. The UTE-MT imaging protocol included: TR=100ms, TE=8 µs, FOV=4×4 cm², matrix=256×256, slice thickness=3mm, five MT powers (i.e. 300°, 600°, 900°, 1200° and 1500°) and five MT frequency offsets (i.e. 2, 5, 10, 20 and 50 kHz), respectively, with a total of 25 different MT datasets. The same protocol was applied to each tendon sample twice, one with the fiber parallel to the B0 field and the other with fibers oriented 55° relative to the B0 field. Two-pool UTE-MT modeling was performed on both datasets to investigate the angular dependence of each of the MT modeling parameters.

Figure 1a shows the sagittal views of the tendon images acquired with a clinical GRE sequence (TE/TR = 4/16.7 ms) with the two angular orientations. The two arrows besides the specimens indicated the orientation of the fibers in the specimens. The SNR of the data with angle = 55° was significantly higher than that of the data with angle =0° due to the magic angle effect. Figure 1b shows the corresponding axial UTE-MT images of the same tendon, with the imaging plane perpendicular to the fiber orientation.

Figure 2 shows the results of two-pool UTE-MT modeling. The images in the first and second rows are the results obtained with the two angular orientations. Both Gauss and Super-Lorentzian spectral absorption lineshapes for the macromolecular proton were investigated. The fitting residuals of Super-Lorentzian lineshape were slightly less than Gauss lineshape, with both results very similar to the previous work (4).

The physical parameters obtained from the two-pool MT modeling are shown in the Table 1. While T₂ increased by 95% with the Gaussian lineshape and 500% with the Super-Lorentzian lineshape due to the magic angle effect, changes were less than 9% for macromolecular proton fraction and 20% for RM0w, and no changes are observed in Rw. This suggests that UTE-MT modeling parameters such as f, R_M0w and R_w can be used as magic angle insensitive biomarkers of tissue properties.

UTE-MT modeling can provide a variety information about tissue properties, such as the macromolecular proton fraction and exchange rate between water and macromolecular protons which are much less sensitive to the magic angle effect compared with T₂ values of the water protons. These magic angle effect immune parameters may be useful markers for disease identification. UTE-MT modeling can be applied to both short and long T₂ tissues such as the Achilles tendon, ligaments, menisci, bone, calcified cartilage and superficial layers of cartilage, may provide a comprehensive magic angle independent “whole-organ” approach for evaluation of joint degeneration. This may have a major impact on early detection in OA, monitoring disease progression, and assessing response to therapy.