Toward the use of MRI measurements of bound and pore water in fracture risk assessment.

The current clinical assessment of fracture risk lacks information about the inherent quality of a person's bone tissue. Working toward an imaging-based approach to quantify both a bone tissue quality marker (tissue hydration as water bound to the matrix) and a bone microstructure marker (porosity as water in pores), we hypothesized that the concentrations of bound water (Cbw) are lower and concentrations of pore water (Cpw) are higher in patients with osteoporosis (OP) than in age- and sex-matched adults without the disease. Using recent developments in ultrashort echo time (UTE) magnetic resonance imaging (MRI), maps of Cbw and Cpw were acquired from the uninjured distal third radius (Study 1) of 20 patients who experienced a fragility fracture of the distal radius (Fx) and 20 healthy controls (Non-Fx) and from the tibia mid-diaphysis (Study 2) of 30 women with clinical OP (low T-scores) and 15 women without OP (normal T-scores). In Study 1, Cbw was significantly lower (p = 0.0018) and Cpw was higher (p = 0.0022) in the Fx than in the Non-Fx group. In forward stepwise, logistic regression models using Bayesian Information Criterion for selecting the best set of predictors (from imaging parameters, age, BMI, and DXA scanner type), the area-under-the-receiver operator characteristics-curve (AUC with 95 % confidence intervals) was 0.73 (0.56, 0.86) for hip aBMD (best predictors without MRI) and 0.86 (0.70, 0.95) for the combination of Cbw and Cpw (best predictors overall). In Study 2, Cbw was significantly lower (p = 0.0005) in women with OP (23.8 ± 4.3 1H mol/L) than in women without OP (29.9 ± 6.4 1H mol/L); Cpw was significantly higher by estimate of 2.9 1H mol/L (p = 0.0298) with clinical OP, but only when accounting for the type of UTE-MRI scan with 3D providing higher values than 2D (p < 0.0001). Lastly, Cbw, but not Cpw, was sensitive to bone forming osteoporosis medications over 12-months. UTE-MRI-derived measurements of bound and pore water concentrations are potential, aBMD-independent predictors of fracture risk.

Liver T1 Relaxation Quantification Using a 3-Dimensional Interleaved Look-Locker Acquisition With T2 Preparation Pulse Sequence (3D-QALAS): Comparison With Conventional 2-Dimensional MOLLI.

BACKGROUND: Changes in liver magnetic resonance imaging T1 relaxation times are associated with histologic inflammation and fibrosis. OBJECTIVE: To compare liver T1 measurements obtained using a novel single-breath-hold 3-dimensional (3D) whole-liver T1 estimation method (3D-QALAS) to standard-of-care 2-dimensional (2D) modified Look-Locker (2D-MOLLI) measurements. METHODS: With institutional review board approval, research magnetic resonance imaging examinations were performed in 19 participants at 1.5 T. T1 relaxometry of the liver was performed using a novel 3D whole-liver T1 estimation method (3D-QALAS) as well as a 2D modified Look-Locker (2D-MOLLI) method. The 3D method covered the entire liver in a single breath hold, whereas 2D imaging was performed at 4 anatomic levels in 4 consecutive breath holds. T1 measurements from parametric maps were obtained by a single operator, and region-of-interest area-weighted mean T1 values were calculated. Pearson correlation ( r ) was used to assess correlation between T1 estimation methods, and the paired t test and Bland-Altman analysis were used to compare agreement in T1 measurements. RESULTS: In 18 participants (1 participant was excluded from analysis because of respiratory motion artifacts on 3D-QALAS images), 2D-MOLLI and 3D-QALAS mean T1 measurements were strongly correlated ( r = 0.95, [95% CI: 0.87-0.98]; P < 0.0001). 2D-MOLLI T1 values were significantly longer than 3D-QALAS values (647.2 ± 87.3 milliseconds vs. 554.7 ± 75.8 milliseconds; P < 0.0001) with mean bias = 92.5 milliseconds (95% limits of agreement, 36.8, 148.2 milliseconds). CONCLUSION: Whole-liver T1 measurements obtained using a novel single-breath-hold 3D T1 estimation method correlate with a standard-of-care multiple consecutive-breath-hold 2D single-slice method but demonstrate systematic bias that should be considered or corrected when used in a clinical or research setting.

Distortion-free, high-isotropic-resolution diffusion MRI with gSlider BUDA-EPI and multicoil dynamic B0 shimming.

PURPOSE: We combine SNR-efficient acquisition and model-based reconstruction strategies with newly available hardware instrumentation to achieve distortion-free in vivo diffusion MRI of the brain at submillimeter-isotropic resolution with high fidelity and sensitivity on a clinical 3T scanner. METHODS: We propose blip-up/down acquisition (BUDA) for multishot EPI using interleaved blip-up/blip-down phase encoding and incorporate B0 forward-modeling into structured low-rank reconstruction to enable distortion-free and navigator-free diffusion MRI. We further combine BUDA-EPI with an SNR-efficient simultaneous multislab acquisition (generalized slice-dithered enhanced resolution ["gSlider"]), to achieve high-isotropic-resolution diffusion MRI. To validate gSlider BUDA-EPI, whole-brain diffusion data at 860-µm and 780-µm data sets were acquired. Finally, to improve the conditioning and minimize noise penalty in BUDA reconstruction at very high resolutions where B0 inhomogeneity can have a detrimental effect, the level of B0 inhomogeneity was reduced by incorporating slab-by-slab dynamic shimming with a 32-channel AC/DC coil into the acquisition. Whole-brain 600-µm diffusion data were then acquired with this combined approach of gSlider BUDA-EPI with dynamic shimming. RESULTS: The results of 860-µm and 780-µm datasets show high geometry fidelity with gSlider BUDA-EPI. With dynamic shimming, the BUDA reconstruction's noise penalty was further alleviated. This enables whole-brain 600-µm isotropic resolution diffusion imaging with high image quality. CONCLUSIONS: The gSlider BUDA-EPI method enables high-quality, distortion-free diffusion imaging across the whole brain at submillimeter resolution, where the use of multicoil dynamic B0 shimming further improves reconstruction performance, which can be particularly useful at very high resolutions.

A multi-inversion multi-echo spin and gradient echo echo planar imaging sequence with low image distortion for rapid quantitative parameter mapping and synthetic image contrasts.

PURPOSE: Brain imaging exams typically take 10-20 min and involve multiple sequential acquisitions. A low-distortion whole-brain echo planar imaging (EPI)-based approach was developed to efficiently encode multiple contrasts in one acquisition, allowing for calculation of quantitative parameter maps and synthetic contrast-weighted images. METHODS: Inversion prepared spin- and gradient-echo EPI was developed with slice-order shuffling across measurements for efficient acquisition with T1 , T2 , and T2∗ weighting. A dictionary-matching approach was used to fit the images to quantitative parameter maps, which in turn were used to create synthetic weighted images with typical clinical contrasts. Dynamic slice-optimized multi-coil shimming with a B0 shim array was used to reduce B0 inhomogeneity and, therefore, image distortion by >50%. Multi-shot EPI was also implemented to minimize distortion and blurring while enabling high in-plane resolution. A low-rank reconstruction approach was used to mitigate errors from shot-to-shot phase variation. RESULTS: The slice-optimized shimming approach was combined with in-plane parallel-imaging acceleration of 4× to enable single-shot EPI with more than eight-fold distortion reduction. The proposed sequence efficiently obtained 40 contrasts across the whole-brain in just over 1 min at 1.2 × 1.2 × 3 mm resolution. The multi-shot variant of the sequence achieved higher in-plane resolution of 1 × 1 × 4 mm with good image quality in 4 min. Derived quantitative maps showed comparable values to conventional mapping methods. CONCLUSION: The approach allows fast whole-brain imaging with quantitative parameter maps and synthetic weighted contrasts. The slice-optimized multi-coil shimming and multi-shot reconstruction approaches result in minimal EPI distortion, giving the sequence the potential to be used in rapid screening applications.

Diffusion-PEPTIDE: Distortion- and blurring-free diffusion imaging with self-navigated motion-correction and relaxometry capabilities.

PURPOSE: To implement the time-resolved relaxometry PEPTIDE technique into a diffusion acquisition to provide self-navigated, distortion- and blurring-free diffusion imaging that is robust to motion, while simultaneously providing T2 and T2∗ mapping. THEORY AND METHODS: The PEPTIDE readout was implemented into a spin-echo diffusion acquisition, enabling reconstruction of a time-series of T2 - and T2∗ -weighted images, free from conventional echo planar imaging (EPI) distortion and blurring, for each diffusion-encoding. Robustness of PEPTIDE to motion and shot-to-shot phase variation was examined through a deliberate motion-corrupted diffusion experiment. Two diffusion-relaxometry in vivo brain protocols were also examined: (1)1 × 1 × 3 mm3 across 32 diffusion directions in 20 min, (2)1.5 × 1.5 × 3.0 mm3 across 6 diffusion-weighted images in 3.4 min. T2 , T2∗ , and diffusion parameter maps were calculated from these data. As initial exploration of the rich diffusion-relaxometry data content for use in multi-compartment modeling, PEPTIDE data were acquired of a gadolinium-doped asparagus phantom. These datasets contained two compartments with different relaxation parameters and different diffusion orientation properties, and T2 relaxation variations across these diffusion directions were explored. RESULTS: Diffusion-PEPTIDE showed the capability to provide high quality diffusion images and T2 and T2∗ maps from both protocols. The reconstructions were distortion-free, avoided potential resolution losses exceeding 100% in equivalent EPI acquisitions, and showed tolerance to nearly 30° of rotational motion. Expected variation in T2 values as a function of diffusion direction was observed in the two-compartment asparagus phantom (P < .01), demonstrating potential to explore diffusion-PEPTIDE data for multi-compartment modeling. CONCLUSIONS: Diffusion-PEPTIDE provides highly robust diffusion and relaxometry data and offers potential for future applications in diffusion-relaxometry multi-compartment modeling.

Blood Oxygen Level-Dependent MRI of the Myocardium with Multiecho Gradient-Echo Spin-Echo Imaging.

Background Myocardial oxygenation imaging could help determine the presence of microvascular dysfunction associated with increased cardiovascular risk. However, it is challenging to depict the potentially small oxygenation alterations with current noninvasive cardiac MRI blood oxygen level-dependent (BOLD) techniques. Purpose To demonstrate the cardiac application of a gradient-echo spin-echo (GESE) echo-planar imaging sequence for dynamic and quantitative heartbeat-to-heartbeat BOLD MRI and evaluate the sequence in populations both healthy and with hypertension in combination with a breath hold-induced CO2 intervention. Materials and Methods GESE echo-planar imaging sequence was performed in 18 healthy participants and in eight prospectively recruited participants with hypertension on a 3.0-T MRI system. T2 and T2* maps were calculated per heartbeat with a four-parameter fitting technique. Septal regions of interests were used to determine T2 and T2* values per heartbeat and examined over the course of a breath hold to determine BOLD changes. T2 and T2* changes of healthy participants and participants with hypertension were compared by using a nonparametric Mann-Whitney test. Results GESE echo-planar imaging approach gave spatially stable T2 and T2* maps per heartbeat for healthy participants and participants with hypertension, with mean T2 values of 43 msec ± 5 (standard deviation) and 46 msec ± 9, respectively, and mean T2* values of 28 msec ± 5 and 22 msec ± 5, respectively. The healthy participants exhibited increasing T2 and T2* values over the course of a breath hold with a mean positive slope of 0.2 msec per heartbeat ± 0.1 for T2 and 0.2 msec per heartbeat ± 0.1 for T2*, whereas for participants with hypertension these dynamic T2 and T2* values had a mean negative slope of -0.2 msec per heartbeat ± 0.2 for T2 and -0.1 msec per heartbeat ± 0.2 for T2*. The difference in these mean slopes between healthy participants and participants with hypertension was significant for both T2 (P < .001) and T2* (P < .001). Conclusion Gradient-echo spin-echo echo-planar imaging sequence provided quantitative T2 and T2* maps per heartbeat and enabled dynamic heartbeat-to-heartbeat blood oxygen level-dependent (BOLD)-response imaging by analyzing changes in T2 and T2* over the time of a breath-hold intervention. This approach could identify differences in the BOLD response between healthy participants and participants with hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Friedrich in this issue.

High-fidelity, high-isotropic-resolution diffusion imaging through gSlider acquisition with B1+ and T1 corrections and integrated ΔB0 /Rx shim array.

PURPOSE: B1+ and T1 corrections and dynamic multicoil shimming approaches were proposed to improve the fidelity of high-isotropic-resolution generalized slice-dithered enhanced resolution (gSlider) diffusion imaging. METHODS: An extended reconstruction incorporating B1+ inhomogeneity and T1 recovery information was developed to mitigate slab-boundary artifacts in short-repetition time (TR) gSlider acquisitions. Slab-by-slab dynamic B0 shimming using a multicoil integrated ΔB0 /Rx shim array and high in-plane acceleration (Rinplane = 4) achieved with virtual-coil GRAPPA were also incorporated into a 1-mm isotropic resolution gSlider acquisition/reconstruction framework to achieve a significant reduction in geometric distortion compared to single-shot echo planar imaging (EPI). RESULTS: The slab-boundary artifacts were alleviated by the proposed B1+ and T1 corrections compared to the standard gSlider reconstruction pipeline for short-TR acquisitions. Dynamic shimming provided >50% reduction in geometric distortion compared to conventional global second-order shimming. One-millimeter isotropic resolution diffusion data show that the typically problematic temporal and frontal lobes of the brain can be imaged with high geometric fidelity using dynamic shimming. CONCLUSIONS: The proposed B1+ and T1 corrections and local-field control substantially improved the fidelity of high-isotropic-resolution diffusion imaging, with reduced slab-boundary artifacts and geometric distortion compared to conventional gSlider acquisition and reconstruction. This enabled high-fidelity whole-brain 1-mm isotropic diffusion imaging with 64 diffusion directions in 20 min using a 3T clinical scanner.

Accelerated spin-echo functional MRI using multisection excitation by simultaneous spin-echo interleaving (MESSI) with complex-encoded generalized slice dithered enhanced resolution (cgSlider) simultaneous multislice echo-planar imaging.

PURPOSE: Spin-echo functional MRI (SE-fMRI) has the potential to improve spatial specificity when compared with gradient-echo fMRI. However, high spatiotemporal resolution SE-fMRI with large slice-coverage is challenging as SE-fMRI requires a long echo time to generate blood oxygenation level-dependent (BOLD) contrast, leading to long repetition times. The aim of this work is to develop an acquisition method that enhances the slice-coverage of SE-fMRI at high spatiotemporal resolution. THEORY AND METHODS: An acquisition scheme was developed entitled multisection excitation by simultaneous spin-echo interleaving (MESSI) with complex-encoded generalized slice dithered enhanced resolution (cgSlider). MESSI uses the dead-time during the long echo time by interleaving the excitation and readout of 2 slices to enable 2× slice-acceleration, while cgSlider uses the stable temporal background phase in SE-fMRI to encode/decode 2 adjacent slices simultaneously with a "phase-constrained" reconstruction method. The proposed cgSlider-MESSI was also combined with simultaneous multislice (SMS) to achieve further slice-acceleration. This combined approach was used to achieve 1.5-mm isotropic whole-brain SE-fMRI with a temporal resolution of 1.5 s and was evaluated using sensory stimulation and breath-hold tasks at 3T. RESULTS: Compared with conventional SE-SMS, cgSlider-MESSI-SMS provides 4-fold increase in slice-coverage for the same repetition time, with comparable temporal signal-to-noise ratio. Corresponding fMRI activation from cgSlider-MESSI-SMS for both fMRI tasks were consistent with those from conventional SE-SMS. Overall, cgSlider-MESSI-SMS achieved a 32× encoding-acceleration by combining Rinplane × MB × cgSlider × MESSI = 4 × 2 × 2 × 2. CONCLUSION: High-quality, high-resolution whole-brain SE-fMRI was acquired at a short repetition time using cgSlider-MESSI-SMS. This method should be beneficial for high spatiotemporal resolution SE-fMRI studies requiring whole-brain coverage.

Highly accelerated multishot echo planar imaging through synergistic machine learning and joint reconstruction.

PURPOSE: To introduce a combined machine learning (ML)- and physics-based image reconstruction framework that enables navigator-free, highly accelerated multishot echo planar imaging (msEPI) and demonstrate its application in high-resolution structural and diffusion imaging. METHODS: Single-shot EPI is an efficient encoding technique, but does not lend itself well to high-resolution imaging because of severe distortion artifacts and blurring. Although msEPI can mitigate these artifacts, high-quality msEPI has been elusive because of phase mismatch arising from shot-to-shot variations which preclude the combination of the multiple-shot data into a single image. We utilize deep learning to obtain an interim image with minimal artifacts, which permits estimation of image phase variations attributed to shot-to-shot changes. These variations are then included in a joint virtual coil sensitivity encoding (JVC-SENSE) reconstruction to utilize data from all shots and improve upon the ML solution. RESULTS: Our combined ML + physics approach enabled Rinplane × multiband (MB) = 8- × 2-fold acceleration using 2 EPI shots for multiecho imaging, so that whole-brain T2 and T2 * parameter maps could be derived from an 8.3-second acquisition at 1 × 1 × 3-mm3 resolution. This has also allowed high-resolution diffusion imaging with high geometrical fidelity using 5 shots at Rinplane × MB = 9- × 2-fold acceleration. To make these possible, we extended the state-of-the-art MUSSELS reconstruction technique to simultaneous multislice encoding and used it as an input to our ML network. CONCLUSION: Combination of ML and JVC-SENSE enabled navigator-free msEPI at higher accelerations than previously possible while using fewer shots, with reduced vulnerability to poor generalizability and poor acceptance of end-to-end ML approaches.

Accelerated whole-brain perfusion imaging using a simultaneous multislice spin-echo and gradient-echo sequence with joint virtual coil reconstruction.

PURPOSE: Dynamic susceptibility contrast imaging requires high temporal sampling, which poses limits on achievable spatial coverage and resolution. Additionally, more encoding-intensive multi-echo acquisitions for quantitative imaging are desired to mitigate contrast leakage effects, which further limits spatial encoding. We present an accelerated sequence that provides whole-brain coverage at an improved spatio-temporal resolution, to allow for dynamic quantitative R2 and R2 * mapping during contrast-enhanced imaging. METHODS: A multi-echo spin and gradient-echo sequence was implemented with simultaneous multislice acquisition. Complementary k-space sampling between repetitions and joint virtual coil reconstruction were used along with a dynamic phase-matching technique to achieve high-quality reconstruction at 9-fold acceleration, which enabled 2 × 2 × 5 mm whole-brain imaging at TR of 1.5 to 1.7 seconds. The multi-echo images from this sequence were fit to achieve quantitative R2 and R2 * maps for each repetition, and subsequently used to find perfusion measures including cerebral blood flow and cerebral blood volume. RESULTS: Images reconstructed using joint virtual coil show improved image quality and g-factor compared with conventional reconstruction methods, resulting in improved quantitative maps with a 9-fold acceleration factor and whole-brain coverage during the dynamic perfusion acquisition. CONCLUSION: The method presented shows the advantage of using a joint virtual coil-GRAPPA reconstruction to allow for high acceleration factors while maintaining reliable image quality for quantitative perfusion mapping, with the potential to improve tumor diagnostics and monitoring.

Phase-matched virtual coil reconstruction for highly accelerated diffusion echo-planar imaging.

PURPOSE: To propose a virtual coil (VC) acquisition/reconstruction framework to improve highly accelerated single-shot EPI (SS-EPI) and generalized slice dithered enhanced resolution (gSlider) acquisition in high-resolution diffusion imaging (DI). METHODS: For robust VC-GRAPPA reconstruction, a background phase correction scheme was developed to match the image phase of the reference data with the corrupted phase of the accelerated diffusion-weighted data, where the corrupted phase of the diffusion data varies from shot to shot. A Gy prewinding-blip was also added to the EPI acquisition, to create a shifted-ky sampling strategy that allows for better exploitation of VC concept in the reconstruction. To evaluate the performance of the proposed methods, 1.5 mm isotropic whole-brain SS-EPI and 860 µm isotropic whole-brain gSlider-EPI diffusion data were acquired at an acceleration of 8-9 fold. Conventional and VC-GRAPPA reconstructions were performed and compared, and corresponding g-factors were calculated. RESULTS: The proposed VC reconstruction substantially improves the image quality of both SS-EPI and gSlider-EPI, with reduced g-factor noise and reconstruction artifacts when compared to the conventional method. This has enabled high-quality low-noise diffusion imaging to be performed at 8-9 fold acceleration. CONCLUSIONS: The proposed VC acquisition/reconstruction framework improves the reconstruction of DI at high accelerations. The ability to now employ such high accelerations will allow DI with EPI at reduced distortion and faster scan time, which should be beneficial for many clinical and neuroscience applications.

Motion-robust sub-millimeter isotropic diffusion imaging through motion corrected generalized slice dithered enhanced resolution (MC-gSlider) acquisition.

PURPOSE: To develop an efficient MR technique for ultra-high resolution diffusion MRI (dMRI) in the presence of motion. METHODS: gSlider is an SNR-efficient high-resolution dMRI acquisition technique. However, subject motion is inevitable during a prolonged scan for high spatial resolution, leading to potential image artifacts and blurring. In this study, an integrated technique termed Motion Corrected gSlider (MC-gSlider) is proposed to obtain high-quality, high-resolution dMRI in the presence of large in-plane and through-plane motion. A motion-aware reconstruction with spatially adaptive regularization is developed to optimize the conditioning of the image reconstruction under difficult through-plane motion cases. In addition, an approach for intra-volume motion estimation and correction is proposed to achieve motion correction at high temporal resolution. RESULTS: Theoretical SNR and resolution analysis validated the efficiency of MC-gSlider with regularization, and aided in selection of reconstruction parameters. Simulations and in vivo experiments further demonstrated the ability of MC-gSlider to mitigate motion artifacts and recover detailed brain structures for dMRI at 860 µm isotropic resolution in the presence of motion with various ranges. CONCLUSION: MC-gSlider provides motion-robust, high-resolution dMRI with a temporal motion correction sensitivity of 2 s, allowing for the recovery of fine detailed brain structures in the presence of large subject movements.

Improving parallel imaging by jointly reconstructing multi-contrast data.

PURPOSE: To develop parallel imaging techniques that simultaneously exploit coil sensitivity encoding, image phase prior information, similarities across multiple images, and complementary k-space sampling for highly accelerated data acquisition. METHODS: We introduce joint virtual coil (JVC)-generalized autocalibrating partially parallel acquisitions (GRAPPA) to jointly reconstruct data acquired with different contrast preparations, and show its application in 2D, 3D, and simultaneous multi-slice (SMS) acquisitions. We extend the joint parallel imaging concept to exploit limited support and smooth phase constraints through Joint (J-) LORAKS formulation. J-LORAKS allows joint parallel imaging from limited autocalibration signal region, as well as permitting partial Fourier sampling and calibrationless reconstruction. RESULTS: We demonstrate highly accelerated 2D balanced steady-state free precession with phase cycling, SMS multi-echo spin echo, 3D multi-echo magnetization-prepared rapid gradient echo, and multi-echo gradient recalled echo acquisitions in vivo. Compared to conventional GRAPPA, proposed joint acquisition/reconstruction techniques provide more than 2-fold reduction in reconstruction error. CONCLUSION: JVC-GRAPPA takes advantage of additional spatial encoding from phase information and image similarity, and employs different sampling patterns across acquisitions. J-LORAKS achieves a more parsimonious low-rank representation of local k-space by considering multiple images as additional coils. Both approaches provide dramatic improvement in artifact and noise mitigation over conventional single-contrast parallel imaging reconstruction. Magn Reson Med 80:619-632, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

3D MR fingerprinting with accelerated stack-of-spirals and hybrid sliding-window and GRAPPA reconstruction.

PURPOSE: Whole-brain high-resolution quantitative imaging is extremely encoding intensive, and its rapid and robust acquisition remains a challenge. Here we present a 3D MR fingerprinting (MRF) acquisition with a hybrid sliding-window (SW) and GRAPPA reconstruction strategy to obtain high-resolution T1, T2 and proton density (PD) maps with whole brain coverage in a clinically feasible timeframe. METHODS: 3D MRF data were acquired using a highly under-sampled stack-of-spirals trajectory with a steady-state precession (FISP) sequence. For data reconstruction, kx-ky under-sampling was mitigated using SW combination along the temporal axis. Non-uniform fast Fourier transform (NUFFT) was then applied to create Cartesian k-space data that are fully-sampled in the in-plane direction, and Cartesian GRAPPA was performed to resolve kz under-sampling to create an alias-free SW dataset. T1, T2 and PD maps were then obtained using dictionary matching. RESULTS: Phantom study demonstrated that the proposed 3D-MRF acquisition/reconstruction method is able to produce quantitative maps that are consistent with conventional quantification techniques. Retrospectively under-sampled in vivo acquisition revealed that SW + GRAPPA substantially improves quantification accuracy over the current state-of-the-art accelerated 3D MRF. Prospectively under-sampled in vivo study showed that whole brain T1, T2 and PD maps with 1 mm3 resolution could be obtained in 7.5 min. CONCLUSIONS: 3D MRF stack-of-spirals acquisition with hybrid SW + GRAPPA reconstruction may provide a feasible approach for rapid, high-resolution quantitative whole-brain imaging.

30-Second bound and pore water concentration mapping of cortical bone using 2D UTE with optimized half-pulses.

PURPOSE: MRI of cortical bone has the potential to offer new information about fracture risk. Current methods are typically performed with 3D acquisitions, which suffer from long scan times and are generally limited to extremities. This work proposes using 2D UTE with half pulses for quantitatively mapping bound and pore water in cortical bone. METHODS: Half-pulse 2D UTE methods were implemented on a 3T Philips Achieva scanner using an optimized slice-select gradient waveform, with preparation pulses to selectively image bound or pore water. The 2D methods were quantitatively compared with previously implemented 3D methods in the tibia in five volunteers. RESULTS: The mean difference between bound and pore water concentration acquired from 3D and 2D sequences was 0.6 and 0.9 mol 1 H/Lbone (3 and 12%, respectively). While 2D pore water methods tended to slightly overestimate concentrations relative to 3D methods, differences were less than scan-rescan uncertainty and expected differences between healthy and fracture-prone bones. CONCLUSION: Quantitative bound and pore water concentration mapping in cortical bone can be accelerated by 2 orders of magnitude using 2D protocols with optimized half-pulse excitation. Magn Reson Med 77:945-950, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Advances in imaging approaches to fracture risk evaluation.

Fragility fractures are a growing problem worldwide, and current methods for diagnosing osteoporosis do not always identify individuals who require treatment to prevent a fracture and may misidentify those not a risk. Traditionally, fracture risk is assessed using dual-energy X-ray absorptiometry, which provides measurements of areal bone mineral density at sites prone to fracture. Recent advances in imaging show promise in adding new information that could improve the prediction of fracture risk in the clinic. As reviewed herein, advances in quantitative computed tomography (QCT) predict hip and vertebral body strength; high-resolution HR-peripheral QCT (HR-pQCT) and micromagnetic resonance imaging assess the microarchitecture of trabecular bone; quantitative ultrasound measures the modulus or tissue stiffness of cortical bone; and quantitative ultrashort echo-time MRI methods quantify the concentrations of bound water and pore water in cortical bone, which reflect a variety of mechanical properties of bone. Each of these technologies provides unique characteristics of bone and may improve fracture risk diagnoses and reduce prevalence of fractures by helping to guide treatment decisions.

Differences in sensitivity to microstructure between cyclic- and impact-based microindentation of human cortical bone.

Unlike the known relationships between traditional mechanical properties and microstructural features of bone, the factors that influence the mechanical resistance of bone to cyclic reference point microindention (cRPI) and impact microindention (IMI) have yet to be identified. To determine whether cRPI and IMI properties depend on microstructure, we indented the tibia mid-shaft, the distal radius, and the proximal humerus from 10 elderly donors using the BioDent and OsteoProbe (neighboring sites). As the only output measure of IMI, bone material strength index (BMSi) was significantly different across all three anatomical sites being highest for the tibia mid-shaft and lowest for the proximal humerus. Total indentation distance (inverse of BMSi) was higher for the proximal humerus than for the tibia mid-shaft but was not different between other anatomical comparisons. As a possible explanation for the differences in BMSi, pore water, as determined by 1 H nuclear magnetic resonance, was lowest for the tibia and highest for the humerus. Moreover, the local intra-cortical porosity, as determined by micro-computed tomography, was negatively correlated with BMSi for both arm bones. BMSi was also positively correlated with peak bending stress of cortical bone extracted from the tibia mid-shaft. Microstructural correlations with cRPI properties were not significant for any of the bones. The one exception was that average energy dissipated during cRPI was negatively correlated with local tissue mineral density in the tibia mid-shaft. With higher indentation force and larger tip diameter than cRPI, only IMI appears to be sensitive to the underlying porosity of cortical bone. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1442-1452, 2017.

MRI-derived bound and pore water concentrations as predictors of fracture resistance.

Accurately predicting fracture risk in the clinic is challenging because the determinants are multi-factorial. A common approach to fracture risk assessment is to combine X-ray-based imaging methods such as dual-energy X-ray absorptiometry (DXA) with an online Fracture Risk Assessment Tool (FRAX) that includes additional risk factors such as age, family history, and prior fracture incidents. This approach still does not adequately diagnose many individuals at risk, especially those with certain diseases like type 2 diabetes. As such, this study investigated bound water and pore water concentrations (Cbw and Cpw) from ultra-short echo time (UTE) magnetic resonance imaging (MRI) as new predictors of fracture risk. Ex vivo cadaveric arms were imaged with UTE MRI as well as with DXA and high-resolution micro-computed tomography (µCT), and imaging measures were compared to both whole-bone structural and material properties as determined by three-point bending tests of the distal-third radius. While DXA-derived areal bone mineral density (aBMD) and µCT-derived volumetric BMD correlated well with structural strength, they moderately correlated with the estimate material strength with gender being a significant covariate for aBMD. MRI-derived measures of Cbw and Cpw had a similar predictive ability of material strength as aBMD but did so independently of gender. In addition, Cbw was the only imaging parameter to significantly correlate with toughness, the energy dissipated during fracture. Notably, the strength of the correlations with the material properties of bone tended to be higher when a larger endosteal region was used to determine Cbw and Cpw. These results indicate that MRI measures of Cbw and Cpw have the ability to probe bone material properties independent of bone structure or subject gender. In particular, toughness is a property of fracture resistance that is not explained by X-ray based methods. Thus, these MRI-derived measures of Cbw and Cpw in cortical bone have the potential to be useful in clinical populations for evaluating fracture risk, especially involving diseases that affect material properties of the bone beyond its strength.

In Vivo Quantitative MR Imaging of Bound and Pore Water in Cortical Bone.

PURPOSE: To translate and evaluate an in vivo magnetic resonance (MR) imaging protocol for quantitative mapping of collagen-bound and pore water concentrations in cortical bone that involves relaxation-selective ultrashort echo time (UTE) methods. MATERIALS AND METHODS: All HIPAA-compliant studies were performed with institutional review board approval and written informed consent. UTE imaging sequences were implemented on a clinical 3.0-T MR imaging unit and were used for in vivo imaging of bound and pore water in cortical bone. Images of the lower leg and wrist were acquired in five volunteers each (lower leg: two men and three women aged 24, 24, 49, 30, and 26 years; wrist: two men and three women aged 31, 23, 25, 24, and 26 years) to generate bound and pore water concentration maps of the tibia and radius. Each volunteer was imaged three times, and the standard error of the measurements at the region-of-interest (ROI) level was computed as the standard deviation across studies, pooled across volunteers and ROIs. RESULTS: Quantitative bound and pore water maps in the tibia and radius, acquired in 8-14 minutes, had per-voxel signal-to-noise ratios of 18 (bound water) and 14 (pore water) and inter-study standard errors of approximately 2 mol (1)H per liter of bone at the ROI level. CONCLUSION: The results of this study demonstrate the feasibility of quantitatively mapping bound and pore water in vivo in human cortical bone with practical human MR imaging constraints.