Quantum dipole interactions and transient hydrogen bond orientation order in cells, cellular membranes and myelin sheath: Implications for MRI signal relaxation, anisotropy, and T1 magnetic field dependence.

PURPOSE: Despite significant impact on the study of human brain, MRI lacks a theory of signal formation that integrates quantum interactions involving proton dipoles (a primary MRI signal source) with brain intricate cellular environment. The purpose of the present study is developing such a theory. METHODS: We introduce the Transient Hydrogen Bond (THB) model, where THB-mediated quantum dipole interactions between water and protons of hydrophilic heads of amphipathic biomolecules forming cells, cellular membranes and myelin sheath serve as a major source of MR signal relaxation. RESULTS: The THB theory predicts the existence of a hydrogen-bond-driven structural order of dipole-dipole connections within THBs as a primary factor for the anisotropy observed in MRI signal relaxation. We have also demonstrated that the conventional Lorentzian spectral density function decreases too fast at high frequencies to adequately capture the field dependence of brain MRI signal relaxation. To bridge this gap, we introduced a stretched spectral density function that surpasses the limitations of Lorentzian dispersion. In human brain, our findings reveal that at any time point only about 4% to 7% of water protons are engaged in quantum encounters within THBs. These ultra-short (2 to 3 ns), but frequent quantum spin exchanges lead to gradual recovery of magnetization toward thermodynamic equilibrium, that is, relaxation of MRI signal. CONCLUSION: By incorporating quantum proton interactions involved in brain imaging, the THB approach introduces new insights on the complex relationship between brain tissue cellular structure and MRI measurements, thus offering a promising new tool for better understanding of brain microstructure in health and disease.

Microscopic theory of spin-spin and spin-lattice relaxation of bound protons in cellular and myelin membranes-A lateral diffusion model (LDM).

PURPOSE: Deciphering salient features of biological tissue cellular microstructure in health and diseases is an ultimate goal of MRI. While most MRI approaches are based on studying MR properties of tissue "free" water indirectly affected by tissue microstructure, other approaches, such as magnetization transfer (MT), directly target signals from tissue-forming macromolecules. However, despite three-decades of successful applications, relationships between MT measurements and tissue microstructure remain elusive, hampering interpretation of experimental results. The goal of this paper is to develop microscopic theory connecting the structure of cellular and myelin membranes to their MR properties. THEORY AND METHODS: Herein we introduce a lateral diffusion model (LDM) that explains the T2 (spin-spin) and T1 (spin-lattice) MRI relaxation properties of the macromolecular-bound protons by their dipole-dipole interaction modulated by the lateral diffusion of long lipid molecules forming cellular and myelin membranes. RESULTS: LDM predicts anisotropic T1 and T2 relaxation of membrane-bound protons. Moreover, their T2 relaxation cannot be described in terms of a standard R2  = 1/T2 relaxation rate parameter, but rather by a relaxation rate function R2 (t) that depends on time t after RF excitation, having, in the main approximation, a logarithmic behavior: R2 (t) ∼ lnt. This anisotropic non-linear relaxation leads to an absorption lineshape that is different from Super-Lorentzian traditionally used in interpreting MT experiments. CONCLUSION: LDM-derived analytical equations connect the membrane-bound protons T1 and T2 relaxation with dynamic distances between protons in neighboring membrane-forming lipid molecules and their lateral diffusion. This sheds new light on relationships between MT parameters and microstructure of cellular and myelin membranes.

Evaluating brain damage in multiple sclerosis with simultaneous multi-angular-relaxometry of tissue.

OBJECTIVE: Multiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination. METHODS: Twenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric was determined in normal-appearing cortical gray matter (NAGM), normal-appearing subcortical white matter (NAWM), and demyelinating lesions. MPF metric was evaluated for correlations with physical and cognitive test scores. Comparisons were made between HC and MS and between MS subtypes. Furthermore, correlations were determined between MPF and neuropathology in the biopsied person. RESULTS: SMART-derived MPF in NAGM and NAWM were lower in MS than HC (p < 0.001). MPF in NAGM, NAWM and lesions differentiated RRMS from PMS (p < 0.01, p < 0.001, p < 0.001, respectively), whereas lesion volumes did not. MPF in NAGM, NAWM and lesions correlated with the Expanded Disability Status Scale (p < 0.01, p < 0.001, p < 0.001, respectively) and nine-hole peg test (p < 0.001, p < 0.001, p < 0.01, respectively). MPF was lower in the histopathologically confirmed inflammatory demyelinating lesion than the contralateral NAWM and increased in the biopsied lesion over time, mirroring improved clinical performance. INTERPRETATION: SMART-derived MPF metric holds potential as a quantitative imaging biomarker of demyelination and remyelination.

In vivo evaluation of heme and non-heme iron content and neuronal density in human basal ganglia.

Non-heme iron is an important element supporting the structure and functioning of biological tissues. Imbalance in non-heme iron can lead to different neurological disorders. Several MRI approaches have been developed for iron quantification relying either on the relaxation properties of MRI signal or measuring tissue magnetic susceptibility. Specific quantification of the non-heme iron can, however, be constrained by the presence of the heme iron in the deoxygenated blood and contribution of cellular composition. The goal of this paper is to introduce theoretical background and experimental MRI method allowing disentangling contributions of heme and non-heme irons simultaneously with evaluation of tissue neuronal density in the iron-rich basal ganglia. Our approach is based on the quantitative Gradient Recalled Echo (qGRE) MRI technique that allows separation of the total R2* metric characterizing decay of GRE signal into tissue-specific (R2t*) and the baseline blood oxygen level-dependent (BOLD) contributions. A combination with the QSM data (also available from the qGRE signal phase) allowed further separation of the tissue-specific R2t* metric in a cell-specific and non-heme-iron-specific contributions. It is shown that the non-heme iron contribution to R2t* relaxation can be described with the previously developed Gaussian Phase Approximation (GPA) approach. qGRE data were obtained from 22 healthy control participants (ages 26-63 years). Results suggest that the ferritin complexes are aggregated in clusters with an average radius about 100nm comprising approximately 2600 individual ferritin units. It is also demonstrated that the concentrations of heme and non-heme iron tend to increase with age. The strongest age effect was seen in the pallidum region, where the highest age-related non-heme iron accumulation was observed.

Lorentzian effects in magnetic susceptibility mapping of anisotropic biological tissues.

The ultimate goal of MRI is to provide information on biological tissue microstructure and function. Quantitative Susceptibility Mapping (QSM) is one of the newer approaches for studying tissue microstructure by means of measuring phase of Gradient Recalled Echo (GRE) MRI signal. The fundamental question in the heart of this approach is: what is the relationship between the net phase/frequency of the GRE signal from an imaging voxel and the underlying tissue microstructure at the cellular and sub-cellular levels? In the presence of external magnetic field, biological media (e.g. cells, cellular components, blood) become magnetized leading to the MR signal frequency shift that is affected not only by bulk magnetic susceptibility but by the local cellular environment as well. The latter effect is often termed the Lorentzian contribution to the frequency shift. Evaluating the Lorentzian contribution - one of the most intriguing and challenging problems in this field - is the main focus of this review. While the traditional approach to this problem is based on introduction of an imaginary Lorentzian cavity, a more rigorous treatment was proposed recently based on a statistical approach and a direct solution of the Maxwell equations. This approach, termed the Generalized Lorentzian Tensor Approach (GLTA), is especially fruitful for describing anisotropic biological media. The GLTA adequately accounts for two types of anisotropy: anisotropy of magnetic susceptibility and tissue structural anisotropy (e.g., cylindrical axonal bundles in white matter). In the framework of the GLTA the frequency shift due to the local environment is described in terms of the Lorentzian tensor L̂ which can have a substantially different structure than the susceptibility tensor χ̂. While the components of χ̂ are compartmental susceptibilities "weighted" by their volume fractions, the components of L̂ are additionally weighted by specific numerical factors depending on cellular geometrical symmetry. In addition to describing the GLTA that is a phenomenological approach largely based on considering the system symmetry, we also briefly discuss a microscopic approaches to the problem that are based on modeling of the MR signal in different regimes (i.e. static dephasing vs. motion narrowing) and in different cellular environments (e.g., accounting for WM microstructure).

Phase-sensitive B1 mapping: Effects of relaxation and RF spoiling.

PURPOSE: To develop a phase-based B1 mapping technique accounting for the effects of imperfect RF spoiling and magnetization relaxation. THEORY AND METHODS: The technique is based on a multi-gradient-echo sequence with 2 successive orthogonal radiofrequency (RF) excitation pulses followed by the train of gradient echoes measurements. We have derived a theoretical expression relating the MR signal phase produced by the 2 successive RF pulses to the B1 field and B0 -related frequency shift. The expression takes into account effects of imperfections of RF spoiling and T1 and T2* relaxations. RESULTS: Our computer simulations and experiments revealed that imperfections of RF spoiling cause significant errors in B1 mapping if not accounted for. By accounting for these effects along with effects of magnetization relaxation and frequency shift, we demonstrated the high accuracy of our approach. The technique has been tested on spherical phantoms and a healthy volunteer. CONCLUSION: In this paper, we have proposed, implemented, and demonstrated the accuracy of a new phase-based technique for fast and robust B1 mapping based on the measured MR signal phase, frequency, and relaxation. Because imperfect RF spoiling effects are accounted for, this technique can be applied with short TRs and therefore substantially reduces the scan time. Magn Reson Med 80:101-111, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Simultaneous multi-angular relaxometry of tissue with MRI (SMART MRI): Theoretical background and proof of concept.

PURPOSE: Accurate measurement of tissue-specific relaxation parameters is an ultimate goal of quantitative MRI. The objective of this study is to introduce a new technique, simultaneous multiangular relaxometry of tissue with MRI (SMART MRI), which provides naturally coregistered quantitative spin density, longitudinal and transverse relaxation rate constant maps along with parameters characterizing magnetization transfer (MT) effects. THEORY AND METHODS: SMART MRI is based on a gradient-recalled echo MRI sequence with multiple flip angles and multiple gradient echoes and a derived theoretical expression for the MR signal generated in this experimental conditions. The theory, based on Bloch-McConnell equations, takes into consideration cross-relaxation between two water pools: "free" and "bound" to macromolecules. It describes the role of cross-relaxation effects in formation of longitudinal and transverse relaxation of "free" water signal, thus providing background for measurements of these effects without using MT pulses. Bayesian analysis is used to optimize SMART MRI sequence parameters. RESULTS: Data obtained on three participants demonstrate feasibility of the proposed approach. CONCLUSION: SMART MRI provides quantitative measurements of longitudinal and transverse relaxation rate constants of "free" water signal affected by cross-relaxation effects. It also provides information on some essential MT parameters without requiring off-resonance MT pulses. Magn Reson Med 77:1296-1306, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Effects of biological tissue structural anisotropy and anisotropy of magnetic susceptibility on the gradient echo MRI signal phase: theoretical background.

Quantitative susceptibility mapping is a potentially powerful technique for mapping tissue magnetic susceptibility from gradient recalled echo (GRE) MRI signal phase. In this review, we present up-to-date theoretical developments in analyzing the relationships between GRE signal phase and the underlying tissue microstructure and magnetic susceptibility at the cellular level. Two important phenomena contributing to the GRE signal phase are at the focus of this review - tissue structural anisotropy (e.g. cylindrical axonal bundles in white matter) and magnetic susceptibility anisotropy. One of the most intriguing and challenging problems in this field is calculating the so-called Lorentzian contribution to the phase shift induced by the local environment - magnetized tissue structures that have dimensions smaller than the imaging voxel (e.g. cells, cellular components, blood capillaries). In this review, we briefly discuss a "standard" approach to this problem, based on introduction of an imaginary Lorentzian cavity, as well as a more recent method - the generalized Lorentzian tensor approach (GLTA) - that is based on a statistical approach and a direct solution of the magnetostatic Maxwell equations. The latter adequately accounts for both types of anisotropy: the anisotropy of magnetic susceptibility and the structural tissue anisotropy. In the GLTA the frequency shift due to the local environment is characterized by the Lorentzian tensor L^, which has a substantially different structure than the susceptibility tensor χ^. While the components of χ^ are compartmental susceptibilities "weighted" by their volume fractions, the components of L^ are weighted by specific numerical factors depending on tissue geometrical microsymmetry. In multi-compartment structures, the components of the Lorentzian tensor also depend on the compartmental relaxation properties, hence the MR pulse sequence settings. Copyright © 2016 John Wiley & Sons, Ltd.

Diffusion lung imaging with hyperpolarized gas MRI.

Lung imaging using conventional 1 H MRI presents great challenges because of the low density of lung tissue, lung motion and very fast lung tissue transverse relaxation (typical T2 * is about 1-2 ms). MRI with hyperpolarized gases (3 He and 129 Xe) provides a valuable alternative because of the very strong signal originating from inhaled gas residing in the lung airspaces and relatively slow gas T2 * relaxation (typical T2 * is about 20-30 ms). However, in vivo human experiments should be performed very rapidly - usually during a single breath-hold. In this review, we describe the recent developments in diffusion lung MRI with hyperpolarized gases. We show that a combination of the results of modeling of gas diffusion in lung airspaces and diffusion measurements with variable diffusion-sensitizing gradients allows the extraction of quantitative information on the lung microstructure at the alveolar level. From an MRI scan of less than 15 s, this approach, called in vivo lung morphometry, allows the provision of quantitative values and spatial distributions of the same physiological parameters as measured by means of 'standard' invasive stereology (mean linear intercept, surface-to-volume ratio, density of alveoli, etc.). In addition, the approach makes it possible to evaluate some advanced Weibel parameters characterizing lung microstructure: average radii of alveolar sacs and ducts, as well as the depth of their alveolar sleeves. Such measurements, providing in vivo information on the integrity of pulmonary acinar airways and their changes in different diseases, are of great importance and interest to a broad range of physiologists and clinicians. We also discuss a new type of experiment based on the in vivo lung morphometry technique combined with quantitative computed tomography measurements, as well as with gradient echo MRI measurements of hyperpolarized gas transverse relaxation in the lung airspaces. Such experiments provide additional information on the blood vessel volume fraction, specific gas volume and length of the acinar airways, and allow the evaluation of lung parenchymal and non-parenchymal tissue. Copyright © 2015 John Wiley & Sons, Ltd.

Experimental evidence of age-related adaptive changes in human acinar airways.

The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized (3)He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized (3)He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger.

Generalized Lorentzian Tensor Approach (GLTA) as a biophysical background for quantitative susceptibility mapping.

PURPOSE: Quantitative susceptibility mapping (QSM) is a potentially powerful technique for mapping tissue magnetic susceptibility from gradient recalled echo (GRE) MRI. Herein we aim to derive the relationships between GRE signal phase and the underlying tissue microstructure and magnetic susceptibility at the cellular level. METHODS: We use Maxwell's equations and a statistical approach to derive the expression for the magnetic-susceptibility-induced MR signal frequency shift of the GRE signal in single- and multicompartment systems, in which inhomogeneous magnetic field is induced by the cellular constituents (proteins, lipids, iron, etc.) distributed in intra- and extracellular spaces. RESULTS: We introduce the Generalized Lorentzian Tensor Approach (GLTA) that accounts for both types of anisotropy: the anisotropy of magnetic susceptibility and the structural tissue anisotropy. In the GLTA the frequency shift due to the local environment is characterized by the Lorentzian tensor L⁁ which has a substantially different structure than the susceptibility tensor χ⁁. While components of χ⁁ are simply compartmental susceptibilities "weighted" by their relative volumes, the components of L⁁ are weighted by specific numerical factors depending on tissue micro-symmetry and parameters related to the MR pulse sequence. We also provide equations bridging phenomenological and microscopic considerations. CONCLUSION: The GLTA provides a consistent background for deciphering phase data.

Probing lung microstructure with hyperpolarized 3He gradient echo MRI.

In this paper we demonstrate that gradient echo MRI with hyperpolarized (3)He gas can be used for simultaneously extracting in vivo information about lung ventilation properties, alveolar geometrical parameters, and blood vessel network structure. This new approach is based on multi-gradient-echo experimental measurements of hyperpolarized (3)He gas MRI signal from human lungs and a proposed theoretical model of this signal. Based on computer simulations of (3)He atoms diffusing in the acinar airway tree in the presence of an inhomogeneous magnetic field induced by the susceptibility differences between lung tissue (alveolar septa, blood vessels) and lung airspaces, we derive analytical expressions relating the time-dependent MR signal to the geometrical parameters of acinar airways and the blood vessel network. Data obtained on eight healthy volunteers are in good agreement with literature values. This information is complementary to the information obtained by means of the in vivo lung morphometry technique with hyperpolarized 3He diffusion MRI previously developed by our group, and opens new opportunities to study lung microstructure in health and disease.

On the role of neuronal magnetic susceptibility and structure symmetry on gradient echo MR signal formation.

PURPOSE: Phase images obtained by gradient-recalled echo (GRE) MRI provide new contrast in the brain that is distinct from that obtained with conventional T1-weighted and T2-weighted images. The results are especially intriguing in white matter where both signal amplitude and phase display anisotropic properties. However, the biophysical origins of these phenomena are not well understood. The goal of this article is to provide a comprehensive theory of GRE signal formation based on a realistic model of neuronal structure. METHODS: We use Maxwell equations to find the distribution of magnetic field induced by myelin sheath and axon. We account for both anisotropy of neuronal tissue "magnetic micro-architecture" and anisotropy of myelin sheath magnetic susceptibility. RESULTS: Model describes GRE signal comprising of three compartments-axonal, myelin, and extracellular. Both axonal and myelin water signals have frequency shifts that are affected by the magnetic susceptibility anisotropy of long molecules forming lipid bilayer membranes. These parts of frequency shifts reach extrema for axon oriented perpendicular to the magnetic field and are zeros in a parallel case. Myelin water signal is substantially non-monoexponential. CONCLUSIONS: Both, anisotropy of neuronal tissue "magnetic micro-architecture" and anisotropy of myelin sheath magnetic susceptibility, are important for describing GRE signal phase and magnitude.

Commentary on "The influence of lung airways branching structure and diffusion time on measurements and models of short-range 3He gas MR diffusion".

In a recently published paper by Parra-Robles and Wild, the authors challenge the in vivo lung morphometry technique (based on hyperpolarized gas diffusion MRI) developed by our Washington University research group. In this Commentary we demonstrate that the main conclusion of Parra-Robles and Wild, that our MRI-based lung morphometry technique "produces inaccurate estimates of the airway dimensions", does not have any scientific basis and is not in agreement with the considerable body of peer-reviewed scientific reports as well as with Parra-Robles and Wild's own data. On the contrary, our technique has a strong theoretical background, is validated, and provides accurate 3D tomographic information on lung microstructural parameters previously available only from invasive biopsy specimens. This technique has already produced a number of results related to lung morphology and function that were not previously available. In our Commentary we also discuss a number of other incorrect statements in and shortcomings of Parra-Robles and Wild's paper.

Probing lung microstructure with hyperpolarized noble gas diffusion MRI: theoretical models and experimental results.

The introduction of hyperpolarized gases ((3)He and (129)Xe) has opened the door to applications for which gaseous agents are uniquely suited-lung MRI. One of the pulmonary applications, diffusion MRI, relies on measuring Brownian motion of inhaled hyperpolarized gas atoms diffusing in lung airspaces. In this article we provide an overview of the theoretical ideas behind hyperpolarized gas diffusion MRI and the results obtained over the decade-long research. We describe a simple technique based on measuring gas apparent diffusion coefficient (ADC) and an advanced technique, in vivo lung morphometry, that quantifies lung microstructure both in terms of Weibel parameters (acinar airways radii and alveolar depth) and standard metrics (mean linear intercept, surface-to-volume ratio, and alveolar density) that are widely used by lung researchers but were previously available only from invasive lung biopsy. This technique has the ability to provide unique three-dimensional tomographic information on lung microstructure from a less than 15 s MRI scan with results that are in good agreement with direct histological measurements. These safe and sensitive diffusion measurements improve our understanding of lung structure and functioning in health and disease, providing a platform for monitoring the efficacy of therapeutic interventions in clinical trials.

Blood oxygenation level-dependent (BOLD)-based techniques for the quantification of brain hemodynamic and metabolic properties - theoretical models and experimental approaches.

The quantitative evaluation of brain hemodynamics and metabolism, particularly the relationship between brain function and oxygen utilization, is important for the understanding of normal human brain operation, as well as the pathophysiology of neurological disorders. It can also be of great importance for the evaluation of hypoxia within tumors of the brain and other organs. A fundamental discovery by Ogawa and coworkers of the blood oxygenation level-dependent (BOLD) contrast opened up the possibility to use this effect to study brain hemodynamic and metabolic properties by means of MRI measurements. Such measurements require the development of theoretical models connecting the MRI signal to brain structure and function, and the design of experimental techniques allowing MR measurements to be made of the salient features of theoretical models. In this review, we discuss several such theoretical models and experimental methods for the quantification of brain hemodynamic and metabolic properties. The review's main focus is on methods for the evaluation of the oxygen extraction fraction (OEF) based on the measurement of the blood oxygenation level. A combination of the measurement of OEF and the cerebral blood flow (CBF) allows an evaluation to be made of the cerebral metabolic rate of oxygen consumption (CMRO2 ). We first consider in detail the magnetic properties of blood - magnetic susceptibility, MR relaxation and theoretical models of the intravascular contribution to the MR signal under different experimental conditions. We then describe a 'through-space' effect - the influence of inhomogeneous magnetic fields, created in the extravascular space by intravascular deoxygenated blood, on the formation of the MR signal. Further, we describe several experimental techniques taking advantage of these theoretical models. Some of these techniques - MR susceptometry and T2 -based quantification of OEF - utilize the intravascular MR signal. Another technique - quantitative BOLD - evaluates OEF by making use of through-space effects. In this review, we target both scientists just entering the MR field and more experienced MR researchers interested in the application of advanced BOLD-based techniques to the study of the brain in health and disease.

Optimization strategies for evaluation of brain hemodynamic parameters with qBOLD technique.

Quantitative blood oxygenation level dependent technique provides an MRI-based method to measure tissue hemodynamic parameters such as oxygen extraction fraction and deoxyhemoglobin-containing (veins and prevenous part of capillaries) cerebral blood volume fraction. It is based on a theory of MR signal dephasing in the presence of blood vessel network and experimental method-gradient echo sampling of spin echo previously proposed and validated on phantoms and animals. In vivo human studies also demonstrated feasibility of this approach but also recognized that obtaining reliable results requires high signal-to-noise ratio in the data. In this paper, we analyze in detail the uncertainties of the quantitative blood oxygenation level dependent parameter estimates in the framework of the Bayesian probability theory, namely, we examine how the estimated parameters oxygen extraction fraction and deoxygenated cerebral blood volume fraction depend on their "true values," signal-to-noise ratio, and data sampling strategies. On the basis of this analysis, we develop strategies for optimization of the quantitative blood oxygenation level dependent technique for deoxygenated cerebral blood volume and oxygen extraction fraction evaluation. In particular, it is demonstrated that the use of gradient echo sampling of spin echo sequence allows substantial decrease of measurement errors as the data are acquired on both sides of spin echo. We test our theory on phantom mimicking the structure of blood vessel network. A 3D gradient echo sampling of spin echo pulse sequence is used for the acquisition of the MRI signal that was subsequently analyzed by Bayesian Application Software. The experimental results demonstrated a good agreement with theoretical predictions.

Voxel spread function method for correction of magnetic field inhomogeneity effects in quantitative gradient-echo-based MRI.

PURPOSE: Macroscopic magnetic field inhomogeneities adversely affect different aspects of MRI images. In quantitative MRI when the goal is to quantify biological tissue parameters, they bias and often corrupt such measurements. The goal of this article is to develop a method for correction of macroscopic field inhomogeneities that can be applied to a variety of quantitative gradient-echo-based MRI techniques. METHODS: We have reanalyzed a basic theory of gradient echo MRI signal formation in the presence of background field inhomogeneities and derived equations that allow for correction of magnetic field inhomogeneity effects based on the phase and magnitude of gradient echo data. We verified our theory by mapping effective transverse relaxation rate in computer simulated, phantom, and in vivo human data collected with multi-gradient echo sequences. RESULTS: The proposed technique takes into account voxel spread function effects and allowed obtaining virtually free from artifacts effective transverse relaxation rate maps for all simulated, phantom and in vivo data except of the edge areas with very steep field gradients. CONCLUSION: The voxel spread function method, allowing quantification of tissue specific effective transverse relaxation rate-related tissue properties, has a potential to breed new MRI biomarkers serving as surrogates for tissue biological properties similar to longitudinal and transverse relaxation rate constants widely used in clinical and research MRI.