Purpose

To develop a 3D adiabatic T_1ρ prepared ultrashort echo time cones (3D AdiabT_1ρ UTE-Cones) sequence for whole knee imaging on a clinical 3T scanner.

Methods

A train of adiabatic full passage pulses were used for spin locking, followed by time-efficient multispoke UTE acquisition to detect signals from both short and long T₂ tissues in the whole knee joint. A modified signal model was proposed for multispoke UTE data fitting. The feasibility of this 3D AdiabT_1ρ UTE-Cones technique was demonstrated through numerical simulation, phantom, and ex vivo knee sample studies. The 3D AdiabT_1ρ UTE-Cones technique was then applied to 6 in vivo knee joints of healthy volunteers to measure T_1ρ values of quadriceps tendon, patellar tendon, anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), meniscus, patellar cartilage, and muscle.

Results

Numerical simulation, phantom and ex vivo knee sample studies demonstrated the feasibility of whole knee imaging using the proposed multispoke 3D AdiabT_1ρ UTE-Cones sequence. The healthy volunteer knee study demonstrated an averaged T_1ρ of 13.9 ± 0.7 ms for the quadriceps tendon, 9.7 ± 0.8 ms for the patellar tendon, 34.9 ± 2.8 ms for the ACL, 21.6 ± 1.4 ms for the PCL, 22.5 ± 1.9 ms for the meniscus, 44.5 ± 2.4 ms for the patellar cartilage, and 43.2 ± 1.1 ms for the muscle.

Conclusion

The 3D AdiabT_1ρ UTE-Cones sequence allows volumetric T_1ρ assessment of both short and long T₂ tissues in the knee joint on a clinical 3T scanner.

Purpose

To evaluate the echo dependence of 3D ultrashort echo time (TE) quantitative susceptibility mapping (3D UTE-QSM) and effective transverse relaxation rate ( R2*) measurement in the setting of high concentrations of iron oxide nanoparticles.

Methods

A phantom study with iron concentrations ranging from 2 to 22 mM was performed using a 3D UTE Cones sequence. Simultaneous QSM processing with morphology-enabled dipole inversion (MEDI) and R2* single exponential fitting was conducted offline with the acquired 3D UTE data. The dependence of UTE-QSM and R2* on echo spacing (ΔTE) and first TE (TE₁ ) was investigated.

Results

A linear relationship was observed between UTE-QSM measurement and iron concentration up to 22 mM only, with the minimal TE₁ of 0.032 ms and ΔTE of less than 0.1 ms. A linear relationship was observed between R2* and iron concentration up to 22 mM only when TE₁ was less than 0.132 ms and ΔTE was less than 1.2 ms. UTE-QSM with MEDI processing showed strong dependence on ΔTE and TE₁ , especially at high iron concentrations.

Conclusion

UTE-QSM is more sensitive than R2* measurement to TE selection. Both an ultrashort TE₁ and a small ΔTE are needed to achieve accurate QSM for high iron concentrations. Magn Reson Med 79:2315-2322, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

PURPOSE:UTE sequences with a minimal nominal TE of 8 µs have shown promise for direct imaging of myelin protons (T2 , < 1 ms). However, there is still debate about the efficiency of 2D slice-selective UTE sequences in exciting myelin protons because the half excitation pulses used in these sequences have a relatively long duration (e.g., 0.3-0.6 ms). Here, we compared UTE and inversion-recovery (IR) UTE sequences used with either hard or half excitation pulses (durations 32 µs or 472 µs, respectively) for imaging myelin in native and deuterated ovine brain at 3T. METHODS:Freshly frozen ovine brains were dissected into ∼2 mm-thick pure white matter and ∼3 to 8 mm-thick cerebral hemisphere specimens, which were imaged before and/or after different immersion time in deuterium oxide. RESULTS:Bicomponent T2* analysis of UTE signals obtained with hard excitation pulses detected an ultrashort T2 component (STC) fraction (fS ) of 0% to 10% in native specimens, and up to ∼86% in heavily deuterated specimens. fS values were significantly affected by the TIs used in IR-UTE sequences with either hard or half excitation pulses in native specimens but not in heavily deuterated specimens. The STC T2* was in the range of 150 to 400 µs in all UTE and IR-UTE measurements obtained with either hard or half excitation pulses. CONCLUSION:Our results further support myelin protons as the major source of the ultrashort T2* signals seen on IR-UTE images and demonstrate the potential of IR-UTE sequences with half excitation pulses for directly imaging myelin using clinical scanners. Magn Reson Med 80:538-547, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Purpose

To measure T₁ relaxations for the major tissues in whole knee joints on a clinical 3T scanner.

Methods

The 3D UTE-Cones actual flip angle imaging (AFI) method was used to map the transmission radiofrequency field (B₁ ) in both short and long T₂ tissues, which was then used to correct the 3D UTE-Cones variable flip angle (VFA) fitting to generate accurate T₁ maps. Numerical simulation was carried out to investigate the accuracy of T₁ measurement for a range of T₂ values, excitation pulse durations, and B₁ errors. Then, the 3D UTE-Cones AFI-VFA method was applied to healthy volunteers (N = 16) to quantify the T₁ of knee tissues including cartilage, meniscus, quadriceps tendon, patellar tendon, anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), marrow, and muscles at 3T.

Results

Numerical simulation showed that the 3D UTE-Cones AFI-VFA technique can provide accurate T₁ measurements (error <1%) when the tissue T₂ is longer than 1 ms and a 150 μs excitation RF pulse is used and therefore is suitable for most knee joint tissues. The proposed 3D UTE-Cones AFI-VFA method showed an average T₁ of 1098 ± 67 ms for cartilage, 833 ± 47 ms for meniscus, 800 ± 66 ms for quadriceps tendon, 656 ± 43 ms for patellar tendon, 873 ± 38 ms for ACL, 832 ± 49 ms for PCL, 379 ± 18 ms for marrow, and 1393 ± 46 ms for muscles.

Conclusion

The 3D UTE-Cones AFI-VFA method allows volumetric T₁ measurement of the major tissues in whole knee joints on a clinical 3T scanner.

Purpose

To investigate the effect of stretching sampling window on quantitative 3D ultrashort TE (UTE) imaging of cortical bone at 3 T.

Methods

Ten bovine cortical bone and 17 human tibial midshaft samples were imaged with a 3T clinical MRI scanner using an 8-channel knee coil. Quantitative 3D UTE imaging biomarkers, including T₁ , T2∗ , magnetization transfer ratio and magnetization transfer modeling, were performed using radial or spiral Cones sampling trajectories with various durations. Errors in UTE-MRI biomarkers as a function of sampling time were evaluated using radial sampling as a reference standard.

Results

For both bovine and human cortical bone samples, no significant differences were observed for all UTE biomarkers (single-component T2∗ , bicomponent T2∗ and relative fractions, T₁ , magnetization transfer ratio, and magnetization transfer modeling of macromolecular fraction) for spiral sampling windows of 992 µs to 1600 µs compared with a radial sampling window of 688 µs.

Conclusion

The total scan time can be reduced by 76% with quantification errors less than 5%. Quantitative UTE-MRI techniques can be greatly accelerated using longer sampling windows without significant quantification errors.

PURPOSE: To test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model. METHODS: Non-aqueous myelin protons have ultrashort T2s and are invisible with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T2 water signal so that the remaining signal is from the ultrashort T2 myelin component. In this study, eight 8-week-old C57BL/6 mice were fed cuprizone (n = 4) or control chow (n = 4) for 5 weeks and then imaged by 3D IR-UTE MRI. The differences in IR-UTE signal were compared in the major white matter tracts in the brain and correlated with the Luxol Fast Blue histochemical marker of myelin. RESULTS: IR-UTE signal decreased in cuprizone-treated mice in white matter known to be sensitive to demyelination in this model, such as the corpus callosum, but not in white matter known to be resistant to demyelination, such as the internal capsule. These findings correlated with histochemical staining of myelin content. CONCLUSIONS: 3D IR-UTE MRI was sensitive to cuprizone-induced demyelination in the mouse brain, and is a promising noninvasive method for measuring brain myelin content.

Cortical bone assessment using magnetic resonance imaging (MRI) has recently received great attention in an effort to avoid the potential harm associated with ionizing radiation-based techniques. Ultrashort echo time MRI (UTE-MRI) techniques can acquire signal from major hydrogen proton pools in cortical bone, including bound and pore water, as well as from the collagen matrix. This study aimed to develop and evaluate the feasibility of a technique for mapping bound water, pore water, and collagen proton densities in human cortical bone ex vivo and in vivo using three-dimensional UTE Cones (3D-UTE-Cones) MRI. Eight human tibial cortical bone specimens (63 ± 19 years old) were scanned using 3D-UTE-Cones sequences on a clinical 3 T MRI scanner and a micro-computed tomography (μCT) scanner. Total, bound, and pore water proton densities (TWPD, BWPD, and PWPD, respectively) were measured using UTE and inversion recovery UTE (IR-UTE) imaging techniques. Macromolecular proton density (MMPD), a collagen representation, was measured using TWPD and macromolecular fraction (MMF) obtained from two-pool UTE magnetization transfer (UTE-MT) modeling. The correlations between proton densities and μCT-based measures were investigated. The 3D-UTE-Cones techniques were further applied on ten young healthy (34 ± 3 years old) and five old (78 ± 6 years old) female volunteers to evaluate the techniques' feasibility for translational clinical applications. In the ex vivo study, PWPD showed the highest correlations with bone porosity and bone mineral density (BMD) (R = 0.79 and - 0.70, p < 0.01). MMPD demonstrated moderate to strong correlations with bone porosity and BMD (R = -0.67 and 0.65, p < 0.01). MMPD showed strong correlation with age in specimens from female donors (R = -0.91, p = 0.03, n = 5). The presented comprehensive 3D-UTE-Cones imaging protocol allows quantitative mapping of protons in major pools of cortical bone ex vivo and in vivo. PWPD and MMPD can serve as potential novel biomarkers to assess bone matrix and microstructure, as well as bone age- or injury-related variations.

Ultrashort echo time magnetic resonance imaging (UTE-MRI) techniques have been increasingly used to assess cortical bone microstructure. High resolution micro computed tomography (μCT) is routinely employed for validating the MRI-based assessments. However, water protons in cortical bone may reside in micropores smaller than the detectable size ranges by μCT. The goal of this study was to evaluate the upper limit of UTE-MRI and compare its efficacy to μCT at determining bone porosity ex vivo. This study investigated the correlations between UTE-MRI based quantifications and histomorphometric measures of bone porosity that cover all pores larger than 1 μm. Anterior tibial midshaft specimens from eleven donors (51 ± 16 years old, 6 males, 5 females) were scanned on a clinical 3 T-MRI using UTE magnetization transfer (UTE-MT, three power levels and five frequency offsets) and UTE-T2* sequences. Two-pool MT modeling and bi-component exponential T2* fitting were performed on the MRI datasets. Specimens were then scanned by μCT at 9 μm voxel size. Histomorphometry was performed on hematoxylin and eosin (H&E) stained slides imaged at submicron resolution. Macromolecular fraction from MT modeling, bi-component T2* fractions, and short component T2* showed strong correlations (R > 0.7, p < 0.01) with histomorphometric total and large-pores (>40 μm) porosities as well as with μCT-based porosity. UTE-MRI could also assess small pores variations with moderate correlations (R > 0.5, p < 0.01). The UTE-MRI techniques can detect variations of bone porosity comprised of pores below the range detectable by μCT. Such fine pore variations can contribute differently to the development of bone diseases or to the bone remodeling process, however, this needs to be investigated. In scanned specimens, major porosity changes were from large pores, therefore the μCT employment was likely adequate to validate UTE-MRI biomarkers.

Intracortical bone porosity is a key microstructural parameter that determines bone mechanical properties. While clinical MRI visualizes the cortical bone with a signal void, ultrashort echo time (UTE) MRI can acquire high signal from cortical bone, thus enabling quantitative assessments. Magnetization transfer (MT) imaging combined with UTE-MRI can indirectly assess protons in the bone collagenous matrix, which are inversely related to porosity. This study aimed to examine UTE-MT MRI techniques to evaluate intracortical bone porosity. Eighteen human cortical bone specimens from the tibial and fibular midshafts were scanned using UTE-MT sequences on a clinical 3 T MRI scanner and on a high-resolution micro-computed tomography (μCT) scanner. A series of MT pulse saturation powers (500°, 1000°, 1500°) and frequency offsets (2, 5, 10, 20, 50 kHz) were used to measure the macromolecular fraction (MMF) and macromolecular T₂ (T_2MM ) using a two-pool MT model. The measurements were made on 136 different regions of interest (ROIs). ROIs were selected at three cortical bone layers (from endosteum to periosteum) and four anatomical sites (anterior, mid-medial, mid-lateral, and posterior) to provide a wide range of porosity. MMF showed moderate to strong correlations with intracortical bone porosity (R = -0.67 to -0.73, p < 0.01) and bone mineral density (BMD) (R = +0.46 to +0.70, p < 0.01). Comparing the average MMF between cortical bone layers revealed a significant increase from the endosteum towards the periosteum. Such a pattern was in agreement with porosity reduction and BMD increase towards the periosteum. These results suggest that the two-pool UTE-MT technique can potentially serve as a novel and accurate tool to assess intracortical bone porosity.

Purpose

Direct myelin imaging can improve the characterization of myelin-related diseases such as multiple sclerosis. In this study, we explore a novel method to directly image myelin using inversion recovery-prepared hybrid encoding (IR-HE) UTE MRI.

Methods

The IR-HE sequence uses an adiabatic inversion pulse to suppress the long T₂ white matter signal, followed by 3D dual-echo HE utilizing both single point imaging and radial frequency encoding, for which the subtraction image between 2 echoes reveals the myelin signal with high contrast. To reduce scan time, it is common to obtain multiple spokes per IR. Here, we invented a novel method to improve the HE, adapted for the multi-spoke IR imaging-termed interleaved HE-for which single point imaging encoding is interleaved between radial frequency encodings near nulling point to allow more efficient IR-signal suppression. To evaluate the proposed approach, a computer simulation, myelin phantom experiment, an ex vivo experiment with a cadaveric multiple sclerosis brain, and an in vivo experiment with 8 healthy volunteers and 13 multiple sclerosis patients were performed.

Results

The computer simulation showed that IR-interleaved HE allows for improved contrast of myelin signal with reduced imaging artifacts. The myelin phantom experiment showed IR-interleaved HE allows direct imaging of myelin lipid with excellent suppression of water signal. In the ex vivo and in vivo experiments, the proposed method demonstrated highly specific imaging of myelin in white matter of the brain.

Conclusion

IR-interleaved HE allows for time-efficient, high-contrast direct myelin imaging and can detect demyelinated lesions in multiple sclerosis patients.