Magnetic resonance (MR) imaging biomarkers such as T2, T2* and T1rho have been widely used, but are confounded by the magic angle effect. The purpose of this study is to investigate the use of the two-dimensional ultrashort echo time magnetization transfer (UTE-MT) sequence for potential magic angle independent MR biomarkers. Magnetization transfer was investigated in cadaveric Achilles tendon samples using the UTE-MT sequence at five MT powers and five frequency offsets ranging from 2–50 kHz. The protocol was applied at 5 sample orientations ranging from 0–90° relative to the B0 field. The results were analyzed with a two-pool quantitative MT model. Multiple TE data was also acquired and mono-exponential T2* was calculated for each orientation. Macromolecular proton fractions and exchange rates derived from UTE-MT modeling did not appreciably change between the various orientations whereas the T2* relaxation time demonstrated up to a 6-fold increase from 0° to 55°. The UTE-MT technique with two-pool modeling shows promise as a clinically compatible technique that is resistant to the magic angle effect. This method provides information on the macromolecular proton pool that cannot be directly obtained by other methods, including regular UTE techniques.

PURPOSE To investigate the effect of sample orientation on T1rho and T2 values of articular cartilage in histologically confirmed normal and abnormal regions using a whole-body 3T scanner, providing information on the angular dependence of T1rho and T2 in clinical imaging. MATERIALS AND METHODS Eight human cadaveric patellae were evaluated using a 2D CPMG sequence for T2 measurement as well as a 2D spin-locking prepared spiral sequence and a 3D magnetization-prepared angle-modulated partitioned-k-space spoiled gradient echo snapshots (3D MAPSS) sequence for T1rho measurement. Each sample was imaged at six angles from 0° to 100° relative to the B0 field. T2 and T1rho values were measured for three regions (medial, apex and lateral) with three layers (10% superficial, 60% middle, 30% deep). Multiple histopathologically confirmed normal and abnormal regions were also used to evaluate the angular dependence of T2 and T1rho relaxation in articular cartilage. RESULTS Our study demonstrated a strong magic angle effect for T1rho and T2 relaxation in articular cartilage, especially in the deeper layers of cartilage. On average over eight patellae, T2 values were increased by 231.8% (72.2% for superficial, 237.6% for middle, and 187.9% for deep layers) while T1rho values were increased by 92% (31.7% for superficial, 69% for middle, and 140% for deep layers) near the magic angle. Both normal and abnormal cartilage showed similar T1rho and T2 magic angle effect. CONCLUSIONS Changes in T1rho and T2 values due to the magic angle effect can be several times more than that caused by degeneration, and this may significantly complicate the clinical application of T1rho and T2 as an early surrogate marker for degeneration.

Clinical magnetic resonance imaging of multiple sclerosis (MS) has focused on indirect imaging of myelin in white matter by detecting signal from protons in the water associated with myelin. Here we show that protons in myelin can be directly imaged using ultrashort echo time (UTE) free induction decay (FID) and imaging sequences on a clinical 3T MR scanner. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to detect signal from myelin and simultaneously suppress signal from water protons. Validation studies were performed on myelin lipid and myelin basic protein (MBP) phantoms in the forms of lyophilized powders as well as suspensions in D2O and H2O. IR-UTE sequences were then used to image MS brain specimens, healthy volunteers, and patients. The T2* of myelin was measured using a UTE FID sequence, as well as UTE and IR- UTE sequences at different TEs. T2* values of ~110–330 μs were measured with UTE FID, as well as with UTE and IR-UTE sequences for myelin powders, myelin-D2O and myelin-H2O phantoms, consistent with selective imaging of myelin protons with IR-UTE sequences. Our studies showed myelin selective imaging of white matter in the brains in vitro and in vivo. Complete or partial signal loss was observed in specimens in areas of the brain with histopathologic evidence of myelin loss, and in the brain of patients with MS.

SUMMARY Objectives To determine T2* relaxation in articular cartilage using ultrashort echo time (UTE) imaging and bi-component analysis, with an emphasis on the deep radial and calcified cartilage. Methods Ten patellar samples were imaged using two-dimensional (2D) UTE and Car-Purcell-Meiboom-Gill (CPMG) sequences. UTE images were fitted with a bi-component model to calculate T2* and relative fractions. CPMG images were fitted with a single-component model to calculate T2. The high signal line above the subchondral bone was regarded as the deep radial and calcified cartilage. Depth and orientation dependence of T2*, fraction and T2 were analyzed with histopathology and polarized light microscopy (PLM), confirming normal regions of articular cartilage. An interleaved multi-echo UTE acquisition scheme was proposed for in vivo applications (n = 5). Results The short T2* values remained relatively constant across the cartilage depth while the long T2* values and long T2* fractions tended to increase from subchondral bone to the superficial cartilage. Long T2*s and T2s showed significant magic angle effect for all layers of cartilage from the medial to lateral facets, while the short T2* values and T2* fractions are insensitive to the magic angle effect. The deep radial and calcified cartilage showed a mean short T2* of 0.80 ± 0.05 ms and short T2* fraction of 39.93 ± 3.05% in vitro, and a mean short T2* of 0.93 ± 0.58 ms and short T2* fraction of 35.03 ± 4.09% in vivo. Conclusion UTE bi-component analysis can characterize the short and long T2* values and fractions across the cartilage depth, including the deep radial and calcified cartilage. The short T2* values and T2* fractions are magic angle insensitive.

Magnetization transfer (MT) imaging is one way to indirectly assess pools of protons with fast transverse relaxation. However, conventional MT imaging sequences are not applicable to short T2 tissues such as cortical bone. Ultrashort echo time (UTE) sequences with TEs as low as 8 μs can detect signals from different water components in cortical bone. In this study we aim to evaluate two-dimensional (2D) UTE-MT imaging of cortical bone and its application in assessing cortical bone porosity as measured by μCT and biomechanical properties. In total, 38 human cadaveric distal femur and proximal tibia bones were sectioned to produce 122 rectangular pieces of cortical bone for quantitative UTE-MT MR imaging, microcomputed tomography (μCT), and biomechanical testing. Off-resonance saturation ratios (OSR) with a series of MT pulse frequency offsets (Δf) were calculated and compared with porosity assessed with μCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation and linear regression. A moderate strong negative correlation was observed between OSR and μCT porosity (R2 = 0.46–0.51), while a moderate positive correlation was observed between OSR and yield stress (R2 = 0.25–0.30) and failure stress (R2 = 0.31–0.35), and a weak positive correlation (R2 = 0.09–0.12) between OSR and Young’s modulus at all off-resonance saturation frequencies. OSR determined with the UTE-MT sequence provides quantitative information on cortical bone and is sensitive to μCT porosity and biomechanical function.

Purpose We present three dimensional ultrashort echo time Cones (3D UTE Cones) techniques for quantification of total water T1s (T1TW), bound water T1s (T1BW) and pore water T1s (T1PW) in vitro and in vivo using a 3T scanner. Methods T1TW, T1BW and T1PW were measured with 3D Cones and adiabatic inversion recovery Cones (IR-Cones) sequences. 2D non-selective UTE techniques, including saturation recovery, variable TRs, and IR preparation approaches were compared with 3D-Cones techniques on bovine cortical bone samples (n=8). The 3D Cones sequences were used to measure T1TW, T1BW and T1PW in the tibial midshaft of healthy volunteers (n=8). Results Comparable T1s were achieved for cortical bone between 3D Cones and 2D UTE techniques as well as those published in the literature. The 3D Cones sequences showed a mean T1TW of 208±22 ms, a mean T1PW of 545±28 ms and a mean T1BW of 131±12 ms for bovine cortical bone, and a mean T1TW of 246±32 ms, a mean T1PW of 524±46 ms and a mean T1BW of 134±11 ms for the tibial midshaft of healthy volunteers. Conclusions The 3D Cones sequences can be used for fast volumetric assessment of bound and pore water T1s in vitro and in vivo.

Bone water exists in different states with the majority bound to the organic matrix and to mineral, and a smaller fraction in ‘free’ form in the pores of cortical bone. In this study we aimed to develop and evaluate ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques for assessment of T2*, T1 and concentration of collagen-bound and pore water in cortical bone using a 3T clinical whole-body scanner. UTE MRI together with an isotope study using tritiated and distilled water (THO-H2O) exchange as well as gravimetrical analysis were performed on ten sectioned bovine bone samples. In addition, 32 human cortical bone samples were prepared for comparison between pore water concentration measured with UTE MRI and cortical porosity derived from micro computed tomography (μCT). A short T2* of 0.27 ± 0.03 ms and T1 of 116±6 ms were observed for collagen-bound water in bovine bone. A longer T2* of 1.84 ± 0.52 ms and T1 of 527±28 ms were observed for pore water in bovine bone. UTE MRI measurements showed a pore water concentration of 4.7-5.3% by volume and collagen-bound water concentration of 15.7-17.9% in bovine bone. THO-H2O exchange studies showed a pore water concentration of 5.9 ± 0.6% and collagen-bound water concentration of 18.1 ± 2.1% in bovine bone. Gravimetrical analysis showed a pore water concentration of 6.3 ± 0.8% and collagen-bound water concentration of 19.2 ± 3.6% in bovine bone. A mineral water concentration of 9.5 ± 0.6% was derived in bovine bone with the THO-H2O exchange study. UTE measured pore water concentration is highly correlated (R2 = 0.72, P < 0.0001) with μCT porosity in the human cortical bone study. Both bovine and human bone studies suggest that UTE sequences could reliably measure collagen-bound and pore water concentration in cortical bone using a clinical scanner.

Water is present in cortical bone in different binding states. In this study we aimed to investigate the effects of inversion time (TI) on the signal from bound and pore water in cortical bone using an adiabatic inversion recovery prepared ultrashort echo time (IR-UTE) sequence on a clinical 3T scanner. In total ten bovine midshaft samples and four human tibial midshaft samples were harvested for this study. Each cortical sample was imaged with the UTE and IR-UTE sequences with a TR of 300 ms and a series of TIs ranging from 10 to 240 ms. Five healthy volunteers were also imaged with the same sequence. Single- and bi-component models were utilized to calculate the T2* and relative fractions of short and long T2* components. Bi-component behavior of the signal from cortical bone was seen with the IR-UTE sequence except with a TI of around 80 ms where the short T2* component alone were seen and a mono-exponential decay pattern was observed. In vivo imaging with the IR-UTE sequence provided high contrast-to-noise images with direct visualization of bound water and reduced signal from long T2 muscle and fat. Our preliminary results demonstrate that selective nulling of the pore water component can be achieved with the IR-UTE sequence with an appropriate TI, allowing selective imaging of the bound water component in cortical bone in vivo using clinical MR scanners.