Frequency shifts of free water signals from compact bone: Simulations and measurements using a UTE-FID sequence.

PURPOSE: Free water in cortical bone is either contained in nearly cylindrical structures (mainly Haversian canals oriented parallel to the bone axis) or in more spherically shaped pores (lacunae). Those cavities have been reported to crucially influence bone quality and mechanical stability. Susceptibility differences between bone and water can lead to water frequency shifts dependent on the geometric characteristics. The purpose of this study is to calculate and measure the frequency distribution of the water signal in MRI in dependence of the microscopic bone geometry. METHODS: Finite element modeling and analytical approaches were performed to characterize the free water components of bone. The previously introduced UTE-FID technique providing spatially resolved FID-spectra was used to measure the frequency distribution pixel-wise for different orientations of the bone axis. RESULTS: The frequency difference between free water in spherical pores and in canals parallel to B0 amounts up to approximately 100 Hz at 3T. Simulated resonance frequencies showed good agreement with the findings in UTE-FID spectra. The intensity ratio of the two signal components (parallel canals and spherical pores) was found to vary between periosteal and endosteal regions. CONCLUSION: Spatially resolved UTE-FID examinations allow the determination of the frequency distribution of signals from free water in cortical bone. This frequency distribution indicates the composition of the signal contributions from nearly spherical cavities and cylindrical canals which allows for further characterization of bone structure and status.

Water phase transition and signal nulling in 3D dual-echo adiabatic inversion-recovery UTE (IR-UTE) imaging of myelin.

PURPOSE: The semisolid myelin sheath has very fast transverse relaxation and is invisible to conventional MRI sequences. UTE sequences can detect signal from myelin. The major challenge is the concurrent detection of various water components. METHODS: The inversion recovery (IR)-based UTE (IR-UTE) sequence employs an adiabatic inversion pulse to invert and suppress water magnetizations. TI plays a key role in water suppression, with negative water magnetizations (negative phase) before the null point and positive water magnetizations (positive phase) after the null point. A series of dual-echo IR-UTE images were acquired with different TIs to detect water phase transition. The effects of TR in phase transition and water suppression were also investigated using a relatively long TR of 500 ms and a short TR of 106 ms. The water phase transition in dual-echo IR-UTE imaging of myelin was investigated in five ex vivo and five in vivo human brains. RESULTS: An apparent phase transition was observed in the second echo at the water signal null point, where the myelin signal was selectively detected by the UTE data acquisition at the optimal TI. The water phase transition point varied significantly across the brain when the long TR of 500 ms was used, whereas the convergence of TIs was observed when the short TR of 106 ms was used. CONCLUSION: The results suggest that the IR-UTE sequence with a short TR allows uniform inversion and nulling of water magnetizations, thereby providing volumetric imaging of myelin.

Free-breathing 3D whole-heart joint T1/T2 mapping and water/fat imaging at 0.55 T.

PURPOSE: To develop and validate a highly efficient motion compensated free-breathing isotropic resolution 3D whole-heart joint T1/T2 mapping sequence with anatomical water/fat imaging at 0.55 T. METHODS: The proposed sequence takes advantage of shorter T1 at 0.55 T to acquire three interleaved water/fat volumes with inversion-recovery preparation, no preparation, and T2 preparation, respectively. Image navigators were used to facilitate nonrigid motion-compensated image reconstruction. T1 and T2 maps were jointly calculated by a dictionary matching method. Validations were performed with simulation, phantom, and in vivo experiments on 10 healthy volunteers and 1 patient. The performance of the proposed sequence was compared with conventional 2D mapping sequences including modified Look-Locker inversion recovery and T2-prepared balanced steady-SSFP sequence. RESULTS: The proposed sequence has a good T1 and T2 encoding sensitivity in simulation, and excellent agreement with spin-echo reference T1 and T2 values was observed in a standardized T1/T2 phantom (R2 = 0.99). In vivo experiments provided good-quality co-registered 3D whole-heart T1 and T2 maps with 2-mm isotropic resolution in a short scan time of about 7 min. For healthy volunteers, left-ventricle T1 mean and SD measured by the proposed sequence were both comparable with those of modified Look-Locker inversion recovery (640 ± 35 vs. 630 ± 25 ms [p = 0.44] and 49.9 ± 9.3 vs. 54.4 ± 20.5 ms [p = 0.42]), whereas left-ventricle T2 mean and SD measured by the proposed sequence were both slightly lower than those of T2-prepared balanced SSFP (53.8 ± 5.5 vs. 58.6 ± 3.3 ms [p < 0.01] and 5.2 ± 0.9 vs. 6.1 ± 0.8 ms [p = 0.03]). Myocardial T1 and T2 in the patient measured by the proposed sequence were in good agreement with conventional 2D sequences and late gadolinium enhancement. CONCLUSION: The proposed sequence simultaneously acquires 3D whole-heart T1 and T2 mapping with anatomical water/fat imaging at 0.55 T in a fast and efficient 7-min scan. Further investigation in patients with cardiovascular disease is now warranted.

Conversion map from quantitative parameter mapping to myelin water fraction: comparison with R1·R2* and myelin water fraction in white matter.

OBJECTIVE: To clarify the relationship between myelin water fraction (MWF) and R1⋅R2* and to develop a method to calculate MWF directly from parameters derived from QPM, i.e., MWF converted from QPM (MWFQPM). MATERIALS AND METHODS: Subjects were 12 healthy volunteers. On a 3 T MR scanner, dataset was acquired using spoiled gradient-echo sequence for QPM. MWF and R1⋅R2* maps were derived from the multi-gradient-echo (mGRE) dataset. Volume-of-interest (VOI) analysis using the JHU-white matter (WM) atlas was performed. All the data in the 48 WM regions measured VOI were plotted, and quadratic polynomial approximations of each region were derived from the relationship between R1·R2* and the two-pool model-MWF. The R1·R2* map was converted to MWFQPM map. MWF atlas template was generated using converted to MWF from R1·R2* per WM region. RESULTS: The mean MWF and R1·R2* values for the 48 WM regions were 11.96 ± 6.63%, and 19.94 ± 4.59 s-2, respectively. A non-linear relationship in 48 regions of the WM between MWF and R1·R2* values was observed by quadratic polynomial approximation (R2 ≥ 0.963, P < 0.0001). DISCUSSION: MWFQPM map improved image quality compared to the mGRE-MWF map. Myelin water atlas template derived from MWFQPM may be generated with combined multiple WM regions.

A field map updating algorithm to improve fat-water spiral imaging.

PURPOSE: An accurate field map is essential to separate fat and water signals in a dual-echo chemical shift encoded spiral MRI scan. A rapid low-resolution B0 map prescan is usually performed before each exam. Occasional inaccuracy in these field map estimates can lead to misclassification of the water and fat signals as well as blurring artifacts in the reconstruction. The present work proposes a self-consistent model to evaluate residual field offsets according to the image data to improve the reconstruction quality and facilitate the scan efficiency. THEORY AND METHODS: The proposed method compares the phase differences of the two-echo data after correcting for fat frequency offsets. A more accurate field map is approximated according to the phase discrepancies and improved image quality. Experiments were conducted with simulated off-resonance on a numerical phantom, five volunteer head scans, and four volunteer abdominal scans for validation. RESULTS: The initial reconstruction of the demonstrated examples exhibit blurring artifacts and misregistration of fat and water because of the inaccuracy of the field map. The proposed method updates the field map to amend the fat and water estimation and improve image quality. CONCLUSIONS: This work presents a model to improve the quality of fat-water imaging of the spiral MRI by estimating a better field map from the acquired data. It allows reducing the field map pre-scans before each spiral scan under normal circumstances to increase scan efficiency.

Reducing the ambiguity of field inhomogeneity and chemical shift effect for fat-water separation by field factor.

PURPOSE: To reduce the ambiguity between chemical shift and field inhomogeneity with flexible TE combinations by introducing a variable (field factor). THEORY AND METHODS: The ambiguity between chemical shift and field inhomogeneity can be eliminated directly from the multiple in-phase images acquired at different TEs; however, it is only applicable to few echo combinations. In this study, we accommodated such an implementation in flexible TE combinations by introducing a new variable (field factor). The effects of the chemical shift were removed from the field inhomogeneity in the candidate solutions, thus reducing the ambiguity problem. To validate this concept, multi-echo MRI data acquired from various anatomies with different imaging parameters were tested. The derived fat and water images were compared with those of the state-of-the-art fat-water separation algorithms. RESULTS: Robust fat-water separation was achieved with the accurate solution of field inhomogeneity, and no apparent fat-water swap was observed. In addition to the good performance, the proposed method is applicable to various fat-water separation applications, including different sequence types and flexible TE choices. CONCLUSION: We propose an algorithm to reduce the ambiguity of chemical shift and field inhomogeneity and achieved robust fat-water separation in various applications.

Assessing Tissue Hydration Dynamics Based on Water/Fat Separated MRI.

BACKGROUND: Optimal fluid status is an important issue in hemodialysis. Clinical evaluation of volume status and different diagnostic tools are used to determine hydration status in these patients. However, there is still no accurate method for this assessment. PURPOSE: To propose and evaluate relative lean water signal (LWSrel ) as a water-fat MRI-based tissue hydration measurement. STUDY TYPE: Prospective. POPULATION: A total of 16 healthy subjects (56 ± 6 years, 0 male) and 11 dialysis patients (60.3 ± 12.3 years, 9 male; dialysis time per week 15 ± 3.5 hours, dialysis duration 31.4 ± 27.9 months). FIELD STRENGTH/SEQUENCE: A 3 T; 3D spoiled gradient echo. ASSESSMENT: LWSrel , a measurement of the water concentration of tissue, was estimated from fat-referenced MR images. Segmentations of total adipose tissue as well as thigh and calf muscles were used to measure LWSrel and tissue volumes. LWSrel was compared between healthy subjects and dialysis patients, the latter before and after dialysis. Bioimpedance-based body composition monitor over hydration (BCM OH) was also measured. STATISTICAL TESTS: T-tests were used to compare differences between the healthy subjects and dialysis patients, as well as changes between before and after dialysis. Pearson correlation was calculated between MRI and non-MRI biomarkers. A P value <0.05 was considered statistically significant. RESULTS: The LWSrel in adipose tissue was significantly higher in the dialysis cohort compared with the healthy cohort (246.8% ± 60.0% vs. 100.0% ± 10.8%) and decreased significantly after dialysis (246.8 ± 60.0% vs. 233.8 ± 63.4%). Thigh and calf muscle volumes also significantly decreased by 3.78% ± 1.73% and 2.02% ± 2.50% after dialysis. There was a significant correlation between changes in adipose tissue LWSrel and ultrafiltration volume (r = 87), as well as with BCM OH (r = 0.66). DATA CONCLUSION: MRI-based LWSrel and tissue volume measurements are sensitive to tissue hydration changes occurring during dialysis. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Assessment of fluid removal using ultrasound, bioimpedance and anthropometry in pediatric dialysis: a pilot study.

BACKGROUND: Fluid overload is associated with morbidity and mortality in children receiving dialysis. Accurate clinical assessment is difficult, and using deuterium oxide (D2O) to measure total body water (TBW) is impractical. We investigated the use of ultrasound (US), bioimpedance spectroscopy (BIS), and anthropometry to assess fluid removal in children receiving maintenance hemodialysis (HD). METHODS: Participants completed US, BIS, and anthropometry immediately before and 1-2 h after HD for up to five sessions. US measured inferior vena cava (IVC) diameter, lung B-lines, muscle elastography, and dermal thickness. BIS measured the volume of extracellular (ECF) and intracellular (ICF) fluid. Anthropometry included mid-upper arm, calf and ankle circumferences, and triceps skinfold thickness. D2O was performed once pre-HD. We assessed the change in study measures pre- versus post-HD, and the correlation of change in study measures with percent change in body weight (%∆BW). We also assessed the agreement between TBW measured by BIS and D2O. RESULTS: Eight participants aged 3.4-18.5 years were enrolled. Comparison of pre- and post-HD measures showed significant decrease in IVC diameters, lung B-lines, dermal thickness, BIS %ECF, mid-upper arm circumference, ankle, and calf circumference. Repeated measures correlation showed significant relationships between %∆BW and changes in BIS ECF (rrm =0.51, 95% CI 0.04, 0.80) and calf circumference (rrm=0.80, 95% CI 0.51, 0.92). BIS TBW correlated with D2O TBW but overestimated TBW by 2.2 L (95% LOA, -4.75 to 0.42). CONCLUSION: BIS and calf circumference may be helpful to assess changes in fluid status in children receiving maintenance HD. IVC diameter, lung B-lines and dermal thickness are potential candidates for future studies.

Sheared two-dimensional radiofrequency excitation for off-resonance robustness and fat suppression in reduced field-of-view imaging.

PURPOSE: Two-dimensional (2D) echo-planar radiofrequency (RF) pulses are widely used for reduced field-of-view (FOV) imaging in applications such as diffusion-weighted imaging. However, long pulse durations render the 2D RF pulses sensitive to off-resonance effects, causing local signal losses in reduced-FOV images. This work aims to achieve off-resonance robustness for 2D RF pulses via a sheared trajectory design. THEORY AND METHODS: A sheared 2D RF pulse design is proposed to reduce pulse durations while covering identical excitation k-space extent as a standard 2D RF pulse. For a given shear angle, the number of sheared trajectory lines is minimized to obtain the shortest pulse duration, such that the excitation replicas are repositioned outside the slice stack to guarantee unlimited slice coverage. A target fat/water signal ratio of 5% is chosen to achieve robust fat suppression. RESULTS: Simulations, imaging experiments on a custom head and neck phantom, and in vivo imaging experiments in the spinal cord at 3 T demonstrate that the sheared 2D RF design provides significant improvement in image quality while preserving profile sharpnesses. In regions with high off-resonance effects, the sheared 2D RF pulse improves the signal by more than 50% when compared to the standard 2D RF pulse. CONCLUSION: The proposed sheared 2D RF design successfully reduces pulse durations, exhibiting significantly improved through-plane off-resonance robustness, while providing unlimited slice coverage and high fidelity fat suppression. This method will be especially beneficial in regions suffering from a variety of off-resonance effects, such as spinal cord and breast.

Estimating myelin-water content from anatomical and diffusion images using spatially undersampled myelin-water imaging through machine learning.

Myelin is vital for healthy neuronal development, and can therefore provide valuable information regarding neuronal maturation. Anatomical and diffusion weighted images (DWI) possess information related to the myelin content and the current study investigates whether quantitative myelin markers can be extracted from anatomical and DWI using neural networks. Thirteen volunteers (mean age 29y) are included, and for each subject, a residual neural network was trained using spatially undersampled reference myelin-water markers. The network is trained on a voxel-by-voxel basis, resulting in a large amount of training data for each volunteer. The inputs used are the anatomical contrasts (cT1w, cT2w), the standardized T1w/T2w ratio, estimates of the relaxation times (T1, T2) and their ratio (T1/T2), and common DWI metrics (FA, RD, MD, λ1, λ2, λ3). Furthermore, to estimate the added value of the DWI metrics, neural networks were trained using either the combined set (DWI, T1w and T2w) or only the anatomical (T1w and T2w) images. The reconstructed myelin-water maps are in good agreement with the reference myelin-water content in terms of the coefficient of variation (CoV) and the intraclass correlation coefficient (ICC). A 6-fold undersampling using both anatomical and DWI metrics resulted in ICC = 0.68 and CoV = 5.9%. Moreover, using twice the training data (3-fold undersampling) resulted in an ICC that is comparable to the reproducibility of the myelin-water imaging itself (CoV = 5.5% vs. CoV = 6.7% and ICC = 0.74 vs ICC = 0.80). To achieve this, beside the T1w, T2w images, DWI is required. This preliminary study shows the potential of machine learning approaches to extract specific myelin-content from anatomical and diffusion-weighted scans.

Spatiotemporal characterisation of ischaemic lesions in transient stroke animal models using diffusion free water elimination and mapping MRI with echo time dependence.

BACKGROUND AND PURPOSE: The excess fluid as a result of vasogenic oedema and the subsequent tissue cavitation obscure the microstructural characterisation of ischaemic tissue by conventional diffusion and relaxometry MRI. They lead to a pseudo-normalisation of the water diffusivity and transverse relaxation time maps in the subacute and chronic phases of stroke. Within the context of diffusion MRI, the free water elimination and mapping method (FWE) with echo time dependence has been proposed as a promising approach to measure the amount of free fluid in brain tissue robustly and to eliminate its biasing effect on other biomarkers. In this longitudinal study of transient middle cerebral artery occlusion (MCAo) in the rat brain, we investigated the use of FWE MRI with echo time dependence for the characterisation of the tissue microstructure and explored the potential of the free water fraction as a novel biomarker of ischaemic tissue condition. METHODS: Adult rats received a transient MCAo. Diffusion- and transverse relaxation-weighted MRI experiments were performed longitudinally, pre-occlusion and on days 1, 3, 4, 5, 6, 7 and 10 after MCAo on four rats. Histology was performed for non-stroke and 1, 3 and 10 days after MCAo on three different rats at each time point. RESULTS: The free water fraction was homogeneously increased in the ischaemic cortex one day after stroke. Between three and ten days after stroke, the core of the ischaemic tissue showed a progressive normalisation in the amount of free water, whereas the inner and outer border zones of the ischaemic cortex depicted a large, monotonous increase with time. The specific lesions in brain sections were verified by H&E and immunostaining. The tissue-specific diffusion and relaxometry MRI metrics in the ischaemic cortex were significantly different compared to their conventional counterpart. CONCLUSIONS: Our results demonstrate that the free water fraction in FWE MRI with echo time dependence is a valuable biomarker, sensitive to the progressive degeneration in ischaemic tissue. We showed that part of the heterogeneity previously observed in conventional parameter maps can be accounted for by a heterogeneous distribution of free water in the tissue. Our results suggest that the temporal evolution of the free fluid fraction map at the core and inner border zone can be associated with the pathological changes linked to the evolution of vasogenic oedema. Namely, the homogeneous increase in free water one day after stroke and its tendency to normalise in the core of the ischaemic cortex starting three days after stroke, followed by a progressive increase in free water at the inner border zone from three to ten days after stroke. Finally, the monotonous increase in free fluid in the outer border zone of the cortex reflects the formation of fluid-filled cysts.

Temperature dependence and histological correlation of inhomogeneous magnetization transfer and myelin water imaging in ex vivo brain.

PURPOSE: The promise of inhomogeneous magnetization transfer (ihMT) as a new myelin imaging method was studied in ex vivo human brain tissue and in relation to myelin water fraction (MWF). The temperature dependence of both methods was characterized, as well as their correspondence with a histological measure of myelin content. Unfiltered and filtered ihMT protocols were studied by adjusting the saturation scheme to preserve or attenuate signal from tissue with short dipolar relaxation time T1D. METHODS: ihMT ratio (ihMTR) and MWF maps were acquired at 7 T from formalin-fixed human brain samples at 22.5 °C, 30 °C and 37 °C. The impact of temperature on unfiltered ihMTR, filtered ihMTR and MWF was investigated and compared to myelin basic protein staining. RESULTS: Unfiltered ihMTR exhibited no temperature dependence, whereas filtered ihMTR increased with increasing temperature. MWF decreased at higher temperature, with an increasing prevalence of areas where the myelin water signal was unreliably determined, likely related to a reduction in T2 peak separability at higher temperatures ex vivo. MWF and ihMTR showed similar per-sample correlation with myelin staining at room temperature. At 37 °C, filtered ihMTR was more strongly correlated with myelin staining and had increased dynamic range compared to unfiltered ihMTR. CONCLUSIONS: Given the temperature dependence of filtered ihMT, increased dynamic range, and strong myelin specificity that persists at higher temperatures, we recommend carefully controlled temperatures close to 37 °C for filtered ihMT acquisitions. Unfiltered ihMT may also be useful, due to its independence from temperature, higher amplitude values, and sensitivity to short T1D components. Ex vivo myelin water imaging should be performed at room temperature, to avoid fitting issues found at higher temperatures.

Probing the myelin water compartment with a saturation-recovery, multi-echo gradient-recalled echo sequence.

PURPOSE: To investigate the effect of varying levels of T1 -weighting on the evolution of the complex signal from white matter in a multi-echo gradient-recalled echo (mGRE) saturation-recovery sequence. THEORY AND METHODS: Analysis of the complex signal evolution in an mGRE sequence allows the contributions from short- and long- T2∗ components to be separated, thus providing a measure of the relative strength of signals from the myelin water, and the external and intra-axonal compartments. Here we evaluated the effect of different levels of T1 -weighting on these signals, expecting that the previously reported, short T1 of the myelin water would lead to a relative enhancement of the myelin water signal in the presence of signal saturation. Complex, saturation-recovery mGRE data from the splenium of the corpus callosum from 5 healthy volunteers were preprocessed using a frequency difference mapping (FDM) approach and analyzed using the 3-pool model of complex signal evolution in white matter. RESULTS: An increase in the apparent T1 as a function of echo time was demonstrated, but this increase was an order of magnitude smaller than that expected from previously reported myelin water T1 -values. This suggests the presence of magnetization transfer and exchange effects which counteract the T1 -weighting. CONCLUSION: Variation of the B1+ amplitude in a saturation-recovery mGRE sequence can be used to modulate the relative strength of signals from the different compartments in white matter, but the modulation is less than predicted from previously reported T1 -values.

Robust water-fat separation based on deep learning model exploring multi-echo nature of mGRE.

PURPOSE: To design a new deep learning network for fast and accurate water-fat separation by exploring the correlations between multiple echoes in multi-echo gradient-recalled echo (mGRE) sequence and evaluate the generalization capabilities of the network for different echo times, field inhomogeneities, and imaging regions. METHODS: A new multi-echo bidirectional convolutional residual network (MEBCRN) was designed to separate water and fat images in a fast and accurate manner for the mGRE data. This new MEBCRN network contains 2 main modules, the first 1 is the feature extraction module, which learns the correlations between consecutive echoes, and the other one is the water-fat separation module that processes the feature information extracted from the feature extraction module. The multi-layer feature fusion (MLFF) mechanism and residual structure were adopted in the water-fat separation module to increase separation accuracy and robustness. Moreover, we trained the network using in vivo abdomen images and tested it on the abdomen, knee, and wrist images. RESULTS: The results showed that the proposed network could separate water and fat images accurately. The comparison of the proposed network and other deep learning methods shows the advantage in both quantitative metrics and robustness for different TEs, field inhomogeneities, and images acquired for various imaging regions. CONCLUSION: The proposed network could learn the correlations between consecutive echoes and separate water and fat images effectively. The deep learning method has certain generalization capabilities for TEs and field inhomogeneity. Although the network was trained only in vivo abdomen images, it could be applied for different imaging regions.

Quantitative bone marrow magnetic resonance imaging through apparent diffusion coefficient and fat fraction in multiple myeloma patients.

OBJECTIVE: Quantitative bone marrow (BM) MR sequences, as DWI and CSI, were used to evaluate BM water-fat composition. The aim of the study was to assess the potential usefulness of fat fraction (FF) and ADC, calculated by CSI or DWI, in diagnosing and classifying myeloma (MM) patients according to their different BM infiltration patterns. METHODS: The study group included 43 MM patients (19F; 24M; mean age 64 years), 15 asymptomatic, 15 symptomatic with diffuse BM infiltration and 13 symptomatic with focal lesions (FLs). The control group was made up of 15 healthy subjects (7F; 8M; mean age 64 years). MRI examinations consisted of sagittal T1w TSE on the spinal column, axial DWI (b 50-400-800 mm2/s) and coronal T2 Dixon, on the whole body. Mean ADC and FF were calculated placing 1 ROI on 6 vertebras and 2 ROIs on either the pelvis or FL. RESULTS: ANOVA with Bonferroni's correction showed a significant difference in ADC values among the different groups of MM patients (P < 0.05), while FF was only significantly different between patients with diffuse infiltration and patients with FL (P = 0.002). ADC allowed distinguishing MM patients from normal BM patients with diffuse BM infiltration (cutoff value: 0.491 × 10-3 mm2/s; sensitivity 73%, specificity 80%). FF helped better discriminate healthy controls from normal BM patients (cutoff = 0.33, sensitivity 73%, specificity 92%) and patients with diffuse BM infiltration from those with FL (cutoff = 0.16, sensitivity 82%, specificity 92%). CONCLUSION: ADC and FF are potentially useful parameter for the quantitative evaluation of BM infiltration in MM patients.

Multi-compartment relaxometry and diffusion informed myelin water imaging - Promises and challenges of new gradient echo myelin water imaging methods.

Myelin water fraction (MWF) mapping based on data fitting of a 3-pool exponential model of multi-echo gradient echo (mGRE) data using MRI shows great promises for in vivo myelin quantification. However, this multi-exponential fitting is ill-conditioned because of the similar relaxation times and frequency shifts of the various compartments. Additionally, the bound water residing in the myelin sheath of white matter is expected to have a faster longitudinal magnetisation recovery than that of the free water in the intra-axonal and extra-axonal space. When the Ernst angle is used to achieve maximum SNR and improve fitting, this will introduce a T1-weighting effect to the derived MWF. In this study, we first demonstrate that diffusion-weighted imaging can be used to infer the compartmental signal properties using an analytical fibre model to achieve a robust MWF estimation. Second, we show that by incorporating a variable flip angle scheme to the mGRE acquisition with a multi-compartment relaxometry model, not only the MWF is corrected from the T1 dependency but also the fitting procedure becomes less ill-conditioned and more SNR efficient. Finally, we demonstrate these two approaches can be combined to allow higher spatial resolution MWF maps than what has been reported to date with robust MWF estimation on a small cohort.

Myelin water imaging data analysis in less than one minute.

PURPOSE: Based on a deep learning neural network (NN) algorithm, a super fast and easy to implement data analysis method was proposed for myelin water imaging (MWI) to calculate the myelin water fraction (MWF). METHODS: A NN was constructed and trained on MWI data acquired by a 32-echo 3D gradient and spin echo (GRASE) sequence. Ground truth labels were created by regularized non-negative least squares (NNLS) with stimulated echo corrections. Voxel-wise GRASE data from 5 brains (4 healthy, 1 multiple sclerosis (MS)) were used for NN training. The trained NN was tested on 2 healthy brains, 1 MS brain with segmented lesions, 1 healthy spinal cord, and 1 healthy brain acquired from a different scanner. RESULTS: Production of whole brain MWF maps in approximately 33 â€‹s can be achieved by a trained NN without graphics card acceleration. For all testing regions, no visual differences between NN and NNLS MWF maps were observed, and no obvious regional biases were found. Quantitatively, all voxels exhibited excellent agreement between NN and NNLS (all R2>0.98, p â€‹< â€‹0.001, mean absolute error <0.01). CONCLUSION: The time for accurate MWF calculation can be dramatically reduced to less than 1 â€‹min by the proposed NN, addressing one of the barriers facing future clinical feasibility of MWI.

Quantitative age-dependent differences in human brainstem myelination assessed using high-resolution magnetic resonance mapping.

Previous in-vivo magnetic resonance imaging (MRI)-based studies of age-related differences in the human brainstem have focused on volumetric morphometry. These investigations have provided pivotal insights into regional brainstem atrophy but have not addressed microstructural age differences. However, growing evidence indicates the sensitivity of quantitative MRI to microstructural tissue changes in the brain. These studies have largely focused on the cerebrum, with very few MR investigations addressing age-dependent differences in the brainstem, in spite of its central role in the regulation of vital functions. Several studies indicate early brainstem alterations in a myriad of neurodegenerative diseases and dementias. The paucity of MR-focused investigations is likely due in part to the challenges imposed by the small structural scale of the brainstem itself as well as of substructures within, requiring accurate high spatial resolution imaging studies. In this work, we applied our recently developed approach to high-resolution myelin water fraction (MWF) mapping, a proxy for myelin content, to investigate myelin differences with normal aging within the brainstem. In this cross-sectional investigation, we studied a large cohort (n = 125) of cognitively unimpaired participants spanning a wide age range (21-94 years) and found a decrease in myelination with age in most brainstem regions studied, with several regions exhibiting a quadratic association between myelin and age. We believe that this study is the first investigation of MWF differences with normative aging in the adult brainstem. Further, our results provide reference MWF values.

Cerebral white matter diffusion properties and free-water with obstructive sleep apnea severity in older adults.

Characterizing the effects of obstructive sleep apnea (OSA) on the aging brain could be key in our understanding of neurodegeneration in this population. Our objective was to assess white matter properties in newly diagnosed and untreated adults with mild to severe OSA. Sixty-five adults aged 55 to 85 were recruited and divided into three groups: control (apnea-hypopnea index ≤5/hr; n = 18; 65.2 ± 7.2 years old), mild (>5 to ≤15 hr; n = 27; 64.2 ± 5.3 years old) and moderate to severe OSA (>15/hr; n = 20; 65.2 ± 5.5 years old). Diffusion tensor imaging metrics (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, and mean diffusivity) were compared between groups with Tract-Based Spatial Statistics within the white matter skeleton created by the technique. Groups were also compared for white matter hyperintensities volume and the free-water (FW) fraction. Compared with controls, mild OSA participants showed widespread areas of lower diffusivity (p < .05 corrected) and lower FW fraction (p < .05). Participants with moderate to severe OSA showed lower AD in the corpus callosum compared with controls (p < .05 corrected). No between-group differences were observed for FA or white matter hyperintensities. Lower white matter diffusivity metrics is especially marked in mild OSA, suggesting that even the milder form may lead to detrimental outcomes. In moderate to severe OSA, competing pathological responses might have led to partial normalization of diffusion metrics.

The Water-Fat Separation Method for Determining the Fat-free Component of Subcutaneous Adipose Tissue in Humans: A Brief Review.

Fat-free mass as well as lean soft tissue mass is a surrogate for skeletal muscle mass and is often used for the normalization of several physiological variables or for the diagnosing of low muscle mass in older adults. However, both fat-free mass and lean tissue mass include nonskeletal muscle components such as the fat-free component of adipose tissue fat cells. A technique known as water-fat MRI provides a noninvasive and radiation-free assessment of the fat-free component of adipose tissue in humans. However, if this method is impractical or unavailable, some authors suggest that a constant value for the fat-free component of adipose tissue can be used as an indirect estimate. The purpose of this review is to examine the fat fraction percentage of white (subcutaneous) adipose tissue in adolescents and young/middle-aged/older adults measured by water-fat MRI and provide discussion on how the fat-free adipose tissue values from the water-fat separation method compare with the constant value used in previous studies. Calculated mean values for the percentage of fat fraction in subcutaneous adipose tissue were 86.9% in the overall sample, 86.4% in adolescents (3 studies), and 87.1% in young, middle-aged and older adults (7 studies). This is similar to the 85% value proposed in the classical studies but in the majority of studies the 85% estimate was outside of the 95% confidence interval (CI) of the water-fat MRI estimate. There may be several factors to consider that may affect the fat fraction percentage (e.g. reliability of the MRI estimate, age, sex, obesity, etc.), however, at this time there is insufficient evidence to determine the effect of each of these variables. If the measurement is reliable, then this might suggest that the 85% constant may need to be altered to better reflect the water-fat MRI estimate.