Purpose

To demonstrate the feasibility of a new method for measuring T₁ of short T₂ species based on an adiabatic inversion recovery-prepared three-dimensional ultrashort echo time Cones (3D IR-UTE-Cones) sequence.

Methods

T₁ values for short T₂ species were quantified using 3D IR-UTE-Cones data acquired with different repetition times (TRs) and inversion times (TIs). An inversion efficiency factor Q was introduced into the fitting model to accurately calculate T₁ values for short T₂ species. Experiments were performed on twelve MnCl₂ aqueous solution phantoms with a wide range of T₁ values and T₂* values on a 3 T clinical MR system to verify the efficacy of the proposed method. For comparison, a variable flip angle UTE (VFA-UTE) sequence, a variable TR UTE (VTR-UTE) sequence, and a conventional 2D IR fast spin echo (IR-FSE) sequence were also used to quantify T₁ values of those phantoms. T₁ values were compared between all performed sequences.

Results

The proposed 3D IR-UTE-Cones method provided higher contrast images of short T₂ phantoms and measured much shorter T₁ values than the VFA-UTE, VTR-UTE and 2D IR-FSE methods. T₁ values as short as 2.95 ms could be measured by the 3D IR-UTE-Cones sequence. The 3D IR-UTE-Cones methods with different TRs were applied to different ranges of T₁ measurement, and the scan time was significantly decreased by using 5 TIs along the recovery curves to perform fitting with comparable accuracy.

Conclusion

The 3D IR-UTE-Cones sequence could accurately measure short T₁ values while providing high contrast images of short T₂ species.

While conventional MRI sequences cannot visualize tissues from the osteochondral junction (OCJ) due to these tissues' short transverse T₂ /T₂ * relaxations, ultrashort echo time (UTE) sequences can overcome this limitation. A 2D UTE sequence with a dual adiabatic inversion recovery preparation (DIR-UTE) for selective imaging of short T₂ tissues with high contrast has previously been developed, but high sensitivity to eddy currents and aliased out-of-slice excitation make it difficult to image the thin layer of the OCJ in vivo. Here, we combine the DIR scheme with a 3D UTE cones sequence for volumetric imaging of OCJ tissues in vivo, aiming to generate higher OCJ contrast compared with a recently developed single IR-prepared UTE sequence with a fat saturation module (IR-FS-UTE). All sequences were implemented on a 3-T clinical scanner. The DIR-UTE cones sequence combined a 3D UTE cones sequence with two narrow-band adiabatic IR preparation pulses centered on water and fat spectrum frequencies, respectively. The 3D DIR-UTE cones sequence was first applied to a phantom, then to the knees of four healthy volunteers and four patients diagnosed with osteoarthritis and compared with the IR-FS-UTE sequence. In both phantom and volunteer studies, the proposed DIR-UTE cones sequence showed much higher contrast for OCJ imaging than the IR-FS-UTE sequence did. The 3D DIR-UTE cones sequence showed a significantly higher contrast-to-noise ratio between the OCJ and subchondral bone fat (mean, standard deviation [SD]: 25.7 ± 2.3) and between the OCJ and superficial layers of cartilage (mean, SD: 22.2 ± 3.5) compared with the IR-FS-UTE sequence (mean, SD: 10.8 ± 2.5 and 16.3 ± 2.6, respectively). The 3D DIR-UTE cones sequence is feasible for imaging of the OCJ region of the knee in vivo and produces both high resolution and high contrast.

Long T₂ water contamination is a major challenge with direct in vivo UTE imaging of ultrashort T₂ components in the brain since water contributes most of the signal detected from white and gray matter. The Short TR Adiabatic Inversion Recovery prepared Ultrashort TE (STAIR-UTE) sequence can significantly suppress water signals and simultaneously image ultrashort T₂ components. However, the TR used may not be sufficiently short to allow the STAIR preparation to completely suppress all the water signals in the brain due to specific absorption rate (SAR) limitations on clinical MR scanners. In this study, we describe a STAIR prepared dual-echo UTE sequence with complex Echo Subtraction (STAIR-dUTE-ES) which improves water suppression for selective ultrashort T₂ imaging compared with that achieved with the STAIR-UTE sequence. Numerical simulations showed that the STAIR-dUTE-ES technique can effectively suppress water signals and allow accurate quantification of ultrashort T₂ protons. Volunteer and Multiple Sclerosis (MS) patient studies demonstrated the feasibility of the STAIR-dUTE-ES technique for selective imaging and quantification of ultrashort T₂ components in vivo. A significantly lower mean UltraShort T₂ Proton Fraction (USPF) was found in lesions in MS patients (5.7 ± 0.7%) compared with that in normal white matter of healthy volunteers (8.9 ± 0.6%). The STAIR-dUTE-ES sequence provides robust water suppression for volumetric imaging and quantitation of ultrashort T₂ component. The reduced USPF in MS lesions shows the clinical potential of the sequence for diagnosis and monitoring treatment in MS.

Background

In this study, we investigated the feasibility of quantitative ultrashort echo time (qUTE) magnetic resonance (MR) imaging techniques in the detection and quantification of iron oxide nanoparticle (IONP)-labeled stem cells.

Methods

A stem cell phantom containing multiple layers of unlabeled or labeled stem cells with different densities was prepared. The phantom was imaged with quantitative UTE (qUTE) MR techniques [i.e., UTE-T₁ mapping, UTE-T₂* mapping, and UTE-based quantitative susceptibility mapping (UTE-QSM)] as well as with a clinical T₂ mapping sequence on a 3T clinical MR system. For T₁ mapping, a variable flip angle (VFA) method based on actual flip angle imaging (AFI) technique was utilized. For T₂* mapping and UTE-QSM, multiple images with variable, interleaved echo times including UTE images and gradient recalled echo (GRE) images were used. For UTE-QSM, the phase information from the multi-echo images was utilized and processed using a QSM framework based on the morphology-enabled dipole inversion (MEDI) algorithm. The qUTE techniques were also evaluated in an ex vivo experiment with a mouse injected with IONP-labeled stem cells.

Results

In the phantom experiment, the parameters estimated with qUTE techniques showed high linearity with respect to the density of IONP-labeled stem cells (R²>0.99), while the clinical T₂ parameter showed impaired linearity (R²=0.87). In the ex vivo mouse experiment, UTE-T₂* mapping and UTE-QSM showed feasibility in the detection of injected stem cells with high contrast, whereas UTE-T₁ and UTE-T₂* showed limited detection. Overall, UTE-QSM demonstrated the best contrast of all, with other methods being subjected more to a confounding factor due to different magnetic susceptibilities of various types of neighboring tissues, which creates inhomogeneous contrast that behaves similar to IONP.

Conclusions

In this study, we evaluated the feasibility of a series of qUTE imaging techniques as well as conventional T₂ mapping for the detection of IONP-labeled stem cells in vitro and ex vivo. UTE-QSM performed superior amongst other qUTE techniques as well as conventional T₂ mapping in detecting stem cells with high contrast.

Ultra-short echo time (UTE) MRI with post-processing is a promising technique in bone imaging that produces a similar contrast to computed tomography (CT). Here, we propose a 3D slab-selective ultrashort echo time (UTE) sequence together with image post-processing to image bone structures in the lumbar spine. We also explore the intermodality agreement between the UTE and CT images. The lumbar spines of two healthy volunteers were imaged with 3D UTE using five different resolutions to determine the best imaging protocol. Then, four patients with low back pain were imaged with both the 3D UTE sequence and CT to investigate agreement between the imaging methods. Two other patients with low back pain were then imaged with the 3D UTE sequence and clinical conventional T1-weighted and T2-weighted fast spin-echo (FSE) MRI sequences for qualitative comparison. The 3D UTE sequence together with post-processing showed high contrast images of bone and high intermodality agreement with CT images. In conclusion, post-processed slab-selective UTE imaging is a feasible approach for highlighting bone structures in the lumbar spine and demonstrates significant anatomical correlation with CT images.

OBJECTIVES: To evaluate articular cartilage degeneration using quantitative three-dimensional ultrashort-echo-time cones adiabatic-T1ρ (3D UTE-Cones-AdiabT1ρ) imaging. METHODS: Sixty-six human subjects were recruited for this study. Kellgren-Lawrence (KL) grade and Whole-Organ Magnetic-Resonance-Imaging Score (WORMS) were evaluated by two musculoskeletal radiologists. The human subjects were categorized into three groups, namely normal controls (KL0), doubtful-minimal osteoarthritis (OA) (KL1-2), and moderate-severe OA (KL3-4). WORMS were regrouped to encompass the extent of lesions and the depth of lesions. The UTE-Cones-AdiabT1ρ values were obtained using 3D UTE-Cones data acquisitions preceded by seven paired adiabatic full passage pulses that corresponded to seven spin-locking times (TSLs) of 0, 12, 24, 36, 48, 72, and 96 ms. The performance of the UTE-Cones-AdiabT1ρ technique in evaluating the degeneration of knee cartilage was assessed via the ANOVA comparisons with subregional analysis and Spearmans correlation coefficient as well as the receiver-operating-characteristic (ROC) curve. RESULTS: UTE-Cones-AdiabT1ρ showed significant positive correlations with KL grade (r = 0.15, p < 0.05) and WORMS (r = 0.57, p < 0.05). Higher UTE-Cones-AdiabT1ρ values were observed in both larger and deeper lesions in the cartilage. The differences in UTE-Cones-AdiabT1ρ values among different extent and depth groups of cartilage lesions were all statistically significant (p < 0.05). Subregional analyses showed that the correlations between UTE-Cones-AdiabT1ρ and WORMS varied with the location of cartilage. The AUC value of UTE-Cones-AdiabT1ρ for mild cartilage degeneration (WORMS=1) was 0.8. The diagnostic threshold value of UTE-Cones-AdiabT1ρ for mild cartilage degeneration was 39.4 ms with 80.8% sensitivity. CONCLUSIONS: The 3D UTE-Cones-AdiabT1ρ sequence can be useful in quantitative evaluation of articular cartilage degeneration. KEY POINTS: • The 3D UTE-Cones-AdiabT1ρ sequence can distinguish mild cartilage degeneration from normal cartilage with a diagnostic threshold value of 39.4 ms for mild cartilage degeneration with 80.8% sensitivity. • Higher UTE-Cones-AdiabT1ρ values were observed in both larger and deeper lesions in the articular cartilage. • UTE-Cones-AdiabT1ρ is a promising biomarker for quantitative evaluation of early cartilage degeneration.

Background

T_1ρ has been extensively reported as a sensitive biomarker of biochemical changes in the nucleus pulposus (NP) and annulus fibrosis of intervertebral discs (IVDs). However, no T_1ρ study of cartilaginous endplates (CEPs) has yet been reported because the relatively long echo times (TEs) of conventional clinical T_1ρ sequences cannot effectively capture the fast-decaying magnetic resonance signals of CEPs, which have very short T₂/T₂*s. This can be overcome by using ultrashort echo time (UTE) T_1ρ acquisitions.

Methods

Seventeen subjects underwent UTE with adiabatic T_1ρ preparation (UTE-Adiab-T_1ρ) and T₂-weighted fast spin echo imaging of their lumbar spines. Each IVD was manually segmented into seven regions (i.e., outer anterior annulus fibrosis, inner anterior annulus fibrosis, outer posterior annulus fibrosis, inner posterior annulus fibrosis, superior CEP, inferior CEP, and NP). T_1ρ values of these sub-regions were correlated with IVD modified Pfirrmann grades and subjects' ages. In addition, T_1ρ values were compared in subjects with and without low back pain (LBP).

Results

Correlations of T_1ρ values of the outer posterior annulus fibrosis, superior CEP, inferior CEP, and NP with modified Pfirrmann grades were significant (P<0.05) with R values of 0.51, 0.36, 0.38, and -0.94, respectively. Correlations of T_1ρ values of the outer anterior annulus fibrosis, outer posterior annulus fibrosis, and NP with ages were significant with R equal to 0.52, 0.71, and -0.76, respectively. T_1ρ differences of the outer posterior annulus fibrosis, inferior CEP, and NP between the subjects with and without LBP were significant (P=0.005, 0.020, and 0.000, respectively).

Conclusions

The UTE-Adiab-T_1ρ sequence can quantify T_1ρ of whole IVDs including CEPs. This is an advance, and of value for comprehensive assessment of IVD degeneration.

Conventional magnetic resonance imaging (MRI) is not capable of detecting signal from the deep cartilage due to its short transverse relaxation time (T2). Moreover, several quantitative MRI techniques are significantly influenced by the magic angle effect. The combinations of ultrashort echo time (UTE) MRI with magnetization transfer (UTE-MT) and Adiabatic T_1ρ (UTE-AdiabT_1ρ) imaging allow magic angle-insensitive assessments of all regions of articular cartilage. The purpose of this study was to investigate the correlations between quantitative three-dimensional UTE MRI biomarkers and mechanical properties of human tibiofemoral cartilage specimens. In total, 40 human tibiofemoral cartilage specimens were harvested from three male and four female donors (64 ± 18 years old). Cartilage samples were scanned using a series of quantitative 3D UTE Cones T₂* (UTE-T₂*), T₁ (UTE-T₁), UTE-AdiabT_1ρ, and UTE-MT sequences in a standard knee coil on a clinical 3T scanner. UTE-MT data were acquired with a series of MT powers and frequency offsets to calculate magnetization transfer ratio (MTR), as well as macromolecular fraction (MMF) and macromolecular T₂ (T₂mm) through modeling. Cartilage stiffness and Hayes elastic modulus were measured using indentation tests. Correlations of 3D UTE Cones MRI measurements in the superficial layer, deep layer, and global regions of interest (ROIs) with mechanical properties were investigated. Cartilage mechanical properties demonstrated highest correlations with UTE measures of the superficial layer of cartilage. AdiabT_1ρ, MTR, and MMF in superficial layer ROIs showed significant correlations with Hayes elastic modulus (p < 0.05, R = -0.54, 0.49, and 0.66, respectively). These UTE measures in global ROIs showed significant, though slightly lower, correlations with Hayes elastic modulus (p < 0.05, R = -0.37, 0.52, and 0.60, respectively). Correlations between other UTE MRI measurements (T₂*, T₁, and T₂mm) and mechanical properties were non-significant. The 3D UTE-AdiabT_1ρ and UTE-MT sequences were highlighted as promising surrogates for non-invasive assessment of cartilage mechanical properties. MMF from UTE-MT modeling showed the highest correlations with cartilage mechanics.

Ultrashort echo time (UTE) sequences can image tissues with transverse T ₂ /T ₂ * relaxations too short to be efficiently observed on routine clinical MRI sequences, such as the vertebral body cartilaginous endplate (CEP). Here, we describe a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence to highlight the CEP of vertebral bodies in comparison to the intervertebral disc (IVD) and bone marrow fat (BF) at 3 T. The IR-FS-UTE sequence used a 3D UTE sequence combined with an adiabatic IR preparation pulse centered in the middle of the water and fat peaks, while a fat saturation module was used to suppress the signal from fat. A slab-selective half pulse was used for signal excitation, and a 3D center-out cones trajectory was used for more efficient data sampling. The 3D IR-FS-UTE sequence was applied to an ex vivo human spine sample, as well as the spines of six healthy volunteers and of three patients with back pain. Bright continuous lines representing signal from CEP were found in healthy IVDs. The measured contrast-to-noise ratio was 18.5 ± 4.9 between the CEP and BF, and 20.3 ± 4.15 between the CEP and IVD for the six volunteers. Abnormal IVDs showed CEP discontinuity or irregularity in the sample and patient studies. In conclusion, the proposed 3D IR-FS-UTE sequence is feasible for imaging the vertebral body's CEP in vivo with high contrast.

Tendons and bones comprise a special interacting unit where mechanical, biochemical, and metabolic interplays are continuously in effect. Bone loss in osteoporosis (OPo) and its earlier stage disease, osteopenia (OPe), may be coupled with a reduction in tendon quality. Noninvasive means for quantitatively evaluating tendon quality during disease progression may be critically important for the improvement of characterization and treatment optimization in patients with bone mineral density disorders. Though clinical magnetic resonance imaging (MRI) sequences are not typically capable of directly visualizing tendons, ultrashort echo time MRI (UTE-MRI) is able to acquire a high signal from tendons. Magnetization transfer (MT) modeling combined with UTE-MRI (i.e., UTE-MT-modeling) can indirectly assess macromolecular proton content in tendons. This study aimed to determine whether UTE-MT-modeling could detect differences in tendon quality across a spectrum of bone health. The lower legs of 14 OPe (72 ± 6 years) and 31 OPo (73 ± 6 years) female patients, as well as 30 female participants with normal bone (Normal-Bone, 36 ± 19 years), are imaged using UTE sequences on a 3T MRI scanner. Institutional review board approval is obtained for the study, and all recruited subjects provided written informed consent. A T1 measurement and UTE-MT-modeling are performed on the anterior tibialis tendon (ATT), posterior tibialis tendon (PTT), and the proximal Achilles tendon (PAT) of all subjects. The macromolecular fraction (MMF) is estimated as the main measure from UTE-MT-modeling. The mean MMF in all the investigated tendons was significantly lower in OPo patients compared with the Normal-Bone cohort (mean difference of 24.2%, p < 0.01), with the largest Normal-Bone vs. OPo difference observed in the ATT (mean difference of 32.1%, p < 0.01). Average MMF values of all the studied tendons are significantly lower in the OPo cohort compared with the OPe cohort (mean difference 16.8%, p = 0.02). Only the PPT shows significantly higher T1 values in OPo patients compared with the Normal-Bone cohort (mean difference 17.6%, p < 0.01). Considering the differences between OPo and OPe groups with similar age ranges, tendon deterioration associated with declining bone health was found to be larger than a priori detected differences caused purely by aging, highlighting UTE-MT MRI techniques as useful methods in assessing tendon quality over the course of progressive bone weakening.