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.

A simple CO2 equilibration method for measuring blood oxygen isotope compositions.

RATIONALE: Blood water oxygen isotope compositions can provide valuable insights into physiological processes and ecological patterns. While blood samples are commonly drawn for medical or scientific purposes, blood fractions are infrequently measured for oxygen isotopic compositions (δ18 O) because such measurements are time consuming and expensive. METHODS: We sampled blood from sheep, goats, and iguanas raised in field and animal laboratories into serum, EDTA, heparin, and uncoated plastic vials commonly used in medical and scientific research, then separated red blood cell (RBC) and plasma or serum blood fractions. These were injected into helium-flushed Exetainer tubes where they naturally outgassed endogenous CO2 (goat blood), or into He- and CO2 -flushed tubes (iguana blood). The CO2 gas was sampled on a GasBench II system, and δ18 O was measured by an isotope ratio mass spectrometer (IRMS). RESULTS: Repeated δ18 O measurements were stable over multiple days. The addition of desiccated blood solids to water standards had little impact on their δ18 O measurements, suggesting that organic molecular constituents within blood serum and plasma do not interfere with blood water δ18 O values. We observed slight but statistically significant δ18 O offsets between plasma, serum and RBC fractions. Mass-dependent body water turnover times for iguanas were derived from the data. CONCLUSIONS: We demonstrate that a simple blood-CO2 equilibration method using the GasBench can quickly, reliably and accurately characterize water δ18 O in the plasma, RBC, and whole blood fractions of mammalian and reptilian blood samples (precision ≤ 0.1‰). This method will expand the application of blood stable isotope analysis in physiological and medical research.

Metabolic acceleration and the evolution of human brain size and life history.

Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

Total Body and Extracellular Water Measures Are Unrelated to Cramp Sensitivity in Euhydrated Cramp-Prone Individuals.

ABSTRACT: Earp, JE, Stearns, RL, Agostinucci, J, Lepley, AS, and Ward-Ritacco, CL. Total body and extracellular water measures are unrelated to cramp sensitivity in euhydrated cramp-prone individuals. J Strength Cond Res 36(9): 2653-2656, 2022-Spectral bioelectrical impedance analysis (BIA) is a valid and noninvasive tool for measuring total body water (TBW), intracellular water (ICW), and extracellular water (ECW). As altered hydration and electrolyte imbalance have been proposed as one of 2 etiologies for exercise-associated muscle cramps (EAMC), the purpose of this study was to determine if distribution of body water is related to cramp sensitivity in similarly hydrated cramp-prone individuals. To this end, 11 euhydrated subjects who regularly experience EAMC had their relative TBW, ICW, and ECW assessed using 8-pole spectral BIA. Subjects' cramp sensitivity was then assessed by electrically stimulating the tibial nerve at increasing frequencies until a muscle cramp occurred, allowing for the determination of the threshold frequency (TF) at which the cramp occurred. It was observed that TF was not significantly related to TBW ( r = 0.087, p = 0.368), ICW ( r = 0.105, p = 0.338), ECW ( r = 0.087, p = 0.368), or ECW:TBW ( r = 0.147, p = 0.280). As cramp etiology is poorly understood, these results add to a growing body of literature questioning the role of hydration and electrolyte imbalance in EAMC. Although fluid distribution may be unrelated to TF in those who commonly experience EAMC, additional research is needed to compare those who commonly experience cramps (athletes as well as individuals with specific neuropathies or pharmacologically induced cramps) with those who do not experience cramps and to determine if acute shifts in body water compartmentalization are related to changes in cramp sensitivity.

Tunable diode laser-based two-line thermometry: a noncontact thermometer for active body temperature measurement.

A precise and fast optical thermometer based on a tunable diode laser absorption spectroscopy is developed for breath diagnostics with relevance to noncontact body temperature measurement. As water vapor (H2O) is the major component in human breath, two optimal absorption lines of H2O at 1392 nm and 1371 nm are selected for sensitive body temperature measurement by systematically investigating the near-infrared spectral database. The optical thermometer is developed using two distributed feedback diode lasers with the time-division multiplexing technique to achieve real-time measurement. The sensor performance such as accuracy, repeatability, and time response is tested in a custom-designed gas cell with its temperature controlled in the range of 20°C-50°C. By measuring the test air with different water concentrations, the sensor consistently shows a quadratic response to temperature with an R-squared value of 0.9998. Under the readout rate of 1 s, the sensor achieves a measurement precision of 0.16°C, suggesting its potential applications to fast, accurate, and noncontact body temperature measurements.

Modelling of chemical species of Al, Mn, Zn, and Pb in river body waters of industrial areas of West Rhodope Mountain, Bulgaria.

The assessment of the ecological status of natural surface water, in terms of dominant trace metals, within an area subject to various sources of pollution including a non-ferrous metal ore mining, such as the West Rhodope Mountain, Bulgaria, is significant. The present study estimates the ecological status of river body waters at industrial areas of the West Rhodope Mountain, Bulgaria, simultaneously evaluating the possibility of state forecasting, together with assessing the potential risks, through the study of scenarios focusing on (i) possible variations of physicochemical parameters such as pH, concentration levels of trace metals, sulphates, and dissolved organic carbon (DOC) of surface water and (ii) consideration of potential spontaneous precipitation reactions in the studied waters. The ecological status of river body waters was assessed through a combination of experimental field, laboratory, and computational techniques. Al, Mn, Zn, and Pb were found to be the dominant pollutants with a variety of chemical species and distribution. The most significant difference characterizing the chemical species distribution in light of total spontaneous crystallization in the systems was found for Pb, followed by Zn and Mn, with the differences being more significant at lower trace metal levels. The calculated species were discussed on the basis of HSAB (hard and soft acids and bases) principle.

Comparing saliva and urine samples for measuring breast milk intake with the 2H oxide dose-to-mother technique among children 2-4 months old.

Saliva and urine are the two main body fluids sampled when breast milk intake is measured with the 2H oxide dose-to-mother technique. However, these two body fluids may generate different estimates of breast milk intake due to differences in isotope enrichment. Therefore, we aimed to assess how the estimated amount of breast milk intake differs when based on saliva and urine samples and to explore whether the total energy expenditure of the mothers is related to breast milk output. We used a convenience sample of thirteen pairs of mothers and babies aged 2-4 months, who were exclusively breastfed and apparently healthy. To assess breast milk intake, we administered doubly labelled water to the mothers and collected saliva samples from them, while simultaneously collecting both saliva and urine from their babies over a 14-d period. Isotope ratio MS was used to analyse the samples for 2H and 18O enrichments. Mean breast milk intake based on saliva samples was significantly higher than that based on urine samples (854·5 v. 812·8 g/d, P = 0·029). This can be attributed to slightly higher isotope enrichments in saliva and to a poorer model fit for urine samples as indicated by a higher square root of the mean square error (14·6 v. 10·4 mg/kg, P = 0·001). Maternal energy expenditure was not correlated with breast milk output. Our study suggests that saliva sampling generates slightly higher estimates of breast milk intake and is more precise as compared with urine and that maternal energy expenditure does not influence breast milk output.

Motion-corrected 3D whole-heart water-fat high-resolution late gadolinium enhancement cardiovascular magnetic resonance imaging.

BACKGROUND: Conventional 2D inversion recovery (IR) and phase sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) have been widely incorporated into routine CMR for the assessment of myocardial viability. However, reliable suppression of fat signal, and increased isotropic spatial resolution and volumetric coverage within a clinically feasible scan time remain a challenge. In order to address these challenges, this work proposes a highly efficient respiratory motion-corrected 3D whole-heart water/fat LGE imaging framework. METHODS: An accelerated IR-prepared 3D dual-echo acquisition and motion-corrected reconstruction framework for whole-heart water/fat LGE imaging was developed. The acquisition sequence includes 2D image navigators (iNAV), which are used to track the respiratory motion of the heart and enable 100% scan efficiency. Non-rigid motion information estimated from the 2D iNAVs and from the data itself is integrated into a high-dimensional patch-based undersampled reconstruction technique (HD-PROST), to produce high-resolution water/fat 3D LGE images. A cohort of 20 patients with known or suspected cardiovascular disease was scanned with the proposed 3D water/fat LGE approach. 3D water LGE images were compared to conventional breath-held 2D LGE images (2-chamber, 4-chamber and stack of short-axis views) in terms of image quality (1: full diagnostic to 4: non-diagnostic) and presence of LGE findings. RESULTS: Image quality was considered diagnostic in 18/20 datasets for both 2D and 3D LGE magnitude images, with comparable image quality scores (2D: 2.05 ± 0.72, 3D: 1.88 ± 0.90, p-value = 0.62) and overall agreement in LGE findings. Acquisition time for isotropic high-resolution (1.3mm3) water/fat LGE images was 8.0 ± 1.4 min (3-fold acceleration, 60-88 slices covering the whole heart), while 2D LGE images were acquired in 5.6 ± 2.2 min (12-18 slices, including pauses between breath-holds) albeit with a lower spatial resolution (1.40-1.75 mm in-plane × 8 mm slice thickness). CONCLUSION: A novel framework for motion-corrected whole-heart 3D water/fat LGE imaging has been introduced. The method was validated in patients with known or suspected cardiovascular disease, showing good agreement with conventional breath-held 2D LGE imaging, but offering higher spatial resolution, improved volumetric coverage and good image quality from a free-breathing acquisition with 100% scan efficiency and predictable scan time.

Electric-field penetration depth and dielectric spectroscopy observations of human skin.

BACKGROUND: The dynamic behavior of water molecules remains an important subject for understanding human skin. The change in the dynamics of water molecules from those in bulk water can be effectively observed by dielectric spectroscopy. To study water in the human skin in vivo, non-invasive and non-destructive measurements are essential. Since many unknowns remain from previous research, in this report we employ a two-layer dielectric model to evaluate the penetration depth of the electric field and use the results in measurements on human skin. MATERIALS AND METHODS: We used open-ended coaxial probes with different diameters to perform time-domain reflectometry (TDR) measurements for an acetone-Teflon double-layer model and for human skin from various parts of the body. RESULTS: The electric-field penetration depth obtained from model measurements increases with the increasing outer diameter of open-ended coaxial electrodes. For skin measurements, the relaxation strength corresponding to the water content shows a clear dependence on the epidermal thickness of the measured body parts. CONCLUSION: We determined the depth distribution of the water content of skin from results of dielectric measurements obtained using electrodes with various electric-field penetration depths. We found exponential decays with the thickness of the epidermis of each body part for several examinees. This study suggests an effective method for detailed evaluations of human skin.

Implications of the variation in biological 18 O natural abundance in body water to inform use of Bayesian methods for modelling total energy expenditure when using doubly labelled water.

RATIONALE: Variation in 18 O natural abundance can lead to errors in the calculation of total energy expenditure (TEE) when using the doubly labelled water (DLW) method. The use of Bayesian statistics allows a distribution to be assigned to 18 O natural abundance, thus allowing a best-fit value to be used in the calculation. The aim of this study was to calculate within-subject variation in 18 O natural abundance and apply this to our original working model for TEE calculation. METHODS: Urine samples from a cohort of 99 women, dosed with 50 g of 20% 2 H2 O, undertaking a 14-day breast milk intake protocol, were analysed for 18 O. The within-subject variance was calculated and applied to a Bayesian model for the calculation of TEE in a separate cohort of 36 women. This cohort of 36 women had taken part in a DLW study and had been dosed with 80 mg/kg body weight 2 H2 O and 150 mg/kg body weight H2 18 O. RESULTS: The average change in the δ18 O value from the 99 women was 1.14‰ (0.77) [0.99, 1.29], with the average within-subject 18 O natural abundance variance being 0.13‰2 (0.25) [0.08, 0.18]. There were no significant differences in TEE (9745 (1414), 9804 (1460) and 9789 (1455) kJ/day, non-Bayesian, Bluck Bayesian and modified Bayesian models, respectively) between methods. CONCLUSIONS: Our findings demonstrate that using a reduced natural variation in 18 O as calculated from a population does not impact significantly on the calculation of TEE in our model. It may therefore be more conservative to allow a larger variance to account for individual extremes.

Water-soluble quercetin modulates the choleresis and bile lipid ratio in rats.

Water-soluble analogue of quercetin, corvitin is used in patients with myocardial infarction as blocker of 5-lipoxygenase. However, its effects on secretion, lipid content and physico-chemical properties of bile have not been understood yet. We investigated the effect of corvitin, applied in different doses, on the level of bile flow, the content of bile free and esterified cholesterol, phospholipids, triacylglycerols, and free fatty acids. In order to determine stability of the bile colloidal system, we examined the relationship between different lipid components. The rats were injected intraportally with a bolus of corvitin. At doses of 2.5, 5, and 10 mg/kg, the latter increased bile flow and concentration of total cholates, as well as free fatty acids. Corvitin (5 mg/kg) elevated phospholipids and cholesterol content, but at a dose of 10 mg/kg it increased the concentration of bile cholesterol esters and triacylglycerols. Corvitin applied at doses of 2.5 and 10 mg/kg increased total cholates/cholesterol ratio, but at a dose of 10 mg/kg, the drug reduced cholesterol / esterified cholesterol ratio. The results suggest that corvitin exerts choleretic effect and improves stability of bile colloidal system.

[Human Body Water Composition Measurement:Methods and Clinical Application].

Being the largest single component of the human body,water is essential for life. Disease can lead to salt and water imbalance, and it is particularly important to measure the content and distribution of water in body. The current body water measurement methods are still not mature,and it's even hard to measure extracellular and intracellular water. Isotope dilution method(ID),bioelectrical impedance analysis(BIA),skinfold thickness measurement,and resonant cavity perturbation(RCP)are the commonly used methods for measuring human body water composition. This paper analyzes the advantages and disadvantages of these methods and concludes that all these four methods can be used to measure total body water;more specifically,ID and BIA can measure extracellular water and intracellular water,whereas BIA is more suitable for clinical applications such as monitoring of fluid balance,guiding of fluid management,assessment of lymphedema and nutritional risk,and management of obesity. Body water measurement will play more important roles in diagnosis,prevention,treatment,and prognosis of diseases.

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.

A model describing diffusion in prostate cancer.

PURPOSE: Quantitative diffusion MRI has frequently been studied as a means of grading prostate cancer. Interpretation of results is complicated by the nature of prostate tissue, which consists of four distinct compartments: vascular, ductal lumen, epithelium, and stroma. Current diffusion measurements are an ill-defined weighted average of these compartments. In this study, prostate diffusion is analyzed in terms of a model that takes explicit account of tissue compartmentalization, exchange effects, and the non-Gaussian behavior of tissue diffusion. METHOD: The model assumes that exchange between the cellular (ie, stromal plus epithelial) and the vascular and ductal compartments is slow. Ductal and cellular diffusion characteristics are estimated by Monte Carlo simulation and a two-compartment exchange model, respectively. Vascular pseudodiffusion is represented by an additional signal at b = 0. Most model parameters are obtained either from published data or by comparing model predictions with the published results from 41 studies. Model prediction error is estimated using 10-fold cross-validation. RESULTS: Agreement between model predictions and published results is good. The model satisfactorily explains the variability of ADC estimates found in the literature. CONCLUSION: A reliable model that predicts the diffusion behavior of benign and cancerous prostate tissue of different Gleason scores has been developed. Magn Reson Med 78:316-326, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Field inhomogeneity correction for gradient echo myelin water fraction imaging.

PURPOSE: Recently, the multi-echo gradient echo (MGRE) sequence has been proposed for multicomponent T2* (MC T2*) based myelin water fraction (MWF) mapping. This approach has appeal because it can provide fast whole-brain coverage, has low specific absorption rate, and short echo spacing. However, the MGRE signal requires correction for accurate MWF mapping, because of its sensitivity to magnetic field inhomogeneities (ΔB0 ). We propose a ΔB0 correction method for 2D MGRE data obtained for MWF mapping. THEORY AND METHODS: Latter-echo MGRE data were fit to estimate B0 gradients in the slice-select direction ( Gz). The decay signal was corrected for the effects of Gz, and MC T2* analysis was performed using nonnegative least-squares fitting. The method was evaluated using simulations and its performance demonstrated in healthy volunteers. RESULTS: Simulations showed that MWFs are significantly biased in the presence of Gz and that our correction method leads to accurate MWF estimates. In vivo MWF maps obtained from corrected data showed recovery of MWF estimates in areas of high ΔB0, and overall good agreement with literature values obtained with the reference MC T2-based method. CONCLUSION: A new algorithm was presented for ΔB0 correction of 2D MGRE echo data acquired for MWF imaging. Simulations and in vivo data showed an improvement in MWF estimates. Magn Reson Med 78:49-57, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Robust water fat separated dual-echo MRI by phase-sensitive reconstruction.

PURPOSE: The purpose of this work was to develop and evaluate a robust water-fat separation method for T1-weighted symmetric two-point Dixon data. THEORY AND METHODS: A method for water-fat separation by phase unwrapping of the opposite-phase images by phase-sensitive reconstruction (PSR) is introduced. PSR consists of three steps; (1), identification of clusters of tissue voxels; (2), unwrapping of the phase in each cluster by solving Poisson's equation; and (3), finding the correct sign of each unwrapped opposite-phase cluster, so that the water-fat images are assigned the correct identities. Robustness was evaluated by counting the number of water-fat swap artifacts in a total of 733 image volumes. The method was also compared to commercial software. RESULTS: In the water-fat separated image volumes, the PSR method failed to unwrap the phase of one cluster and misclassified 10. One swap was observed in areas affected by motion and was constricted to the affected area. Twenty swaps were observed surrounding susceptibility artifacts, none of which spread outside the artifact affected regions. The PSR method had fewer swaps when compared to commercial software. CONCLUSION: The PSR method can robustly produce water-fat separated whole-body images based on symmetric two-echo spoiled gradient echo images, under both ideal conditions and in the presence of common artifacts. Magn Reson Med 78:1208-1216, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Measurement of bound and pore water T1 relaxation times in cortical bone using three-dimensional ultrashort echo time cones sequences.

PURPOSE: We present three-dimensional ultrashort echo time Cones (3D UTE Cones) techniques for quantification of total water T1 ( T1TW), bound water T1 ( T1BW), and pore water T1 ( T1PW) in vitro and in vivo using a 3 Tesla (T) scanner. METHODS: T1TW, T1BW, and T1PW were measured with three-dimensional (3D) Cones and adiabatic inversion recovery Cone (IR-Cone) sequences. Two-dimensional (2D) nonselective ultrashort echo time (UTE) techniques, including saturation recovery, variable repetition times (TRs), and inversion recovery (IR) preparation approaches were compared with 3D-Cones techniques on bovine cortical bone samples (n = 8). The 3D Cones sequences were used to measure T1TW, T1BW, and T1PW in the tibial midshaft of healthy volunteers (n = 8). RESULTS: Comparable T1 images were achieved for cortical bone between 3D Cones and 2D UTE techniques as well as those published in the literature. The 3D Cones sequences showed a mean T1TW of 208 ± 22 ms, a mean T1PW of 545 ± 28 ms, and a mean T1BW of 131 ± 12 ms for bovine cortical bone; and a mean T1TW of 246 ± 32 ms, a mean T1PW of 524 ± 46 ms, and a mean T1BW of 134 ± 11 ms for the tibial midshaft of healthy volunteers. CONCLUSIONS: The 3D Cones sequences can be used for fast volumetric assessment of bound and pore water T1 images in vitro and in vivo. Magn Reson Med 77:2136-2145, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Heterogeneous anisotropic magnetic susceptibility of the myelin-water layers causes local magnetic field perturbations in axons.

One goal of MRI is to determine the myelin water fraction in neural tissue. One approach is to measure the reduction in T2 * arising from microscopic perturbations in the magnetic field caused by heterogeneities in the magnetic susceptibility of myelin. In this paper, analytic expressions for the induced magnetic field distribution are derived within and around an axon, assuming that the myelin susceptibility is anisotropic. Previous models considered the susceptibility to be piecewise continuous, whereas this model considers a sinusoidally varying susceptibility. Many conclusions are common in both models. When the magnetic field is applied perpendicular to the axon, the magnetic field in the intraaxonal space is uniformly perturbed, the magnetic field in the myelin sheath oscillates between the lipid and water layers, and the magnetic field in the extracellular space just outside the myelin sheath is heterogeneous. These field heterogeneities cause the spins to dephase, shortening T2 *. When the magnetic field is applied along the axon, the field is homogeneous within water-filled regions, including between lipid layers. Therefore the spins do not dephase and the magnetic susceptibility has no effect on T2 *. Generally, the response of an axon is given as the superposition of these two contributions. The sinusoidal model uses a different set of approximations compared with the piecewise model, so their common predictions indicate that the models are not too sensitive to the details of the myelin-water distribution. Other predictions, such as the sensitivity to water diffusion between myelin and water layers, may highlight differences between the two approaches. Copyright © 2016 John Wiley & Sons, Ltd.

Fundamentals of diffusion MRI physics.

Diffusion MRI is commonly considered the "engine" for probing the cellular structure of living biological tissues. The difficulty of this task is threefold. First, in structurally heterogeneous media, diffusion is related to structure in quite a complicated way. The challenge of finding diffusion metrics for a given structure is equivalent to other problems in physics that have been known for over a century. Second, in most cases the MRI signal is related to diffusion in an indirect way dependent on the measurement technique used. Third, finding the cellular structure given the MRI signal is an ill-posed inverse problem. This paper reviews well-established knowledge that forms the basis for responding to the first two challenges. The inverse problem is briefly discussed and the reader is warned about a number of pitfalls on the way.

Mechanisms of T2 * anisotropy and gradient echo myelin water imaging.

In MRI, structurally aligned molecular or micro-organization (e.g. axonal fibers) can be a source of substantial signal variations that depend on the structural orientation and the applied magnetic field. This signal anisotropy gives us a unique opportunity to explore information that exists at a resolution several orders of magnitude smaller than that of typical MRI. In this review, one of the signal anisotropies, T2 * anisotropy in white matter, and a related imaging method, gradient echo myelin water imaging (GRE-MWI), are explored. The T2 * anisotropy has been attributed to isotropic and anisotropic magnetic susceptibility of myelin and compartmentalized microstructure of white matter fibers (i.e. axonal, myelin, and extracellular space). The susceptibility and microstructure create magnetic frequency shifts that change with the relative orientation of the fiber and the main magnetic field, generating the T2 * anisotropy. The resulting multi-component magnitude decay and nonlinear phase evolution have been utilized for GRE-MWI, assisting in resolving the signal fraction of the multiple compartments in white matter. The GRE-MWI method has been further improved by signal compensation techniques including physiological noise compensation schemes. The T2 * anisotropy and GRE-MWI provide microstructural information on a voxel (e.g. fiber orientation and tissue composition), and may serve as sensitive biomarkers for microstructural changes in the brain. Copyright © 2016 John Wiley & Sons, Ltd.