Quantitative gradient recalled echo (qGRE) MRI enables in vivo measurement of pre-atrophic neurodegeneration in a mouse model of Alzheimer's disease.

Robust methods are needed for preclinical evaluation of novel Alzheimer Disease (AD) therapies to accelerate drug discovery. Quantitative Gradient Recalled Echo (qGRE) MRI has shown promise to provide insight into neurodegeneration in AD prior to atrophy development in humans, highlighting areas of low neuronal density. In this study a novel qGRE method (20 echoes, TE=2-40ms) is shown to non-invasively measure the longitudinal neuronal loss in the hippocampus of a mouse model of AD tauopathy Tg4510.

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

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.

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.

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.

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.

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

Purpose: To develop a phase-based B 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 B field and B -related frequency shift.

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.

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.

Diffusion lung imaging with hyperpolarized gas MRI.

Lung imaging using conventional H MRI presents great challenges because of the low density of lung tissue, lung motion and very fast lung tissue transverse relaxation (typical T * is about 1-2 ms). MRI with hyperpolarized gases ( He and Xe) provides a valuable alternative because of the very strong signal originating from inhaled gas residing in the lung airspaces and relatively slow gas T * relaxation (typical T * is about 20-30 ms). However, in vivo human experiments should be performed very rapidly - usually during a single breath-hold.

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.

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.

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.

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.

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.

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.

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.

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.

Biophysical mechanisms of MRI signal frequency contrast in multiple sclerosis.

Phase images obtained with gradient echo MRI provide image contrast distinct from T1- and T2-weighted images. It is commonly assumed that the local contribution to MRI signal phase directly relates to local bulk tissue magnetic susceptibility. Here, we use Maxwell's equations and Monte Carlo simulations to provide theoretical background to the hypothesis that the local contribution to MRI signal phase does not depend on tissue bulk magnetic susceptibility but tissue magnetic architecture--distribution of magnetic susceptibility inclusions (lipids, proteins, iron, etc.

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.

Quantitative phenomenological model of the BOLD contrast mechanism.

Different theoretical models of the BOLD contrast mechanism are used for many applications including BOLD quantification (qBOLD) and vessel size imaging, both in health and disease. Each model simplifies the system under consideration, making approximations about the structure of the blood vessel network and diffusion of water molecules through inhomogeneities in the magnetic field created by deoxyhemoglobin-containing blood vessels. In this study, Monte-Carlo methods are used to simulate the BOLD MR signal generated by diffusing water molecules in the presence of long, cylindrical blood vessels.

In vivo detection of acinar microstructural changes in early emphysema with (3)He lung morphometry.

Purpose: To quantitatively characterize early emphysematous changes in the lung microstructure of current and former smokers with noninvasive helium 3 ((3)He) lung morphometry and to compare these results with the clinical standards, pulmonary function testing (PFT) and low-dose computed tomography (CT).

Materials And Methods: This study was approved by the local institutional review board, and all subjects provided informed consent. Thirty current and former smokers, each with a minimum 30-pack-year smoking history and mild or no abnormalities at PFT, underwent (3)He lung morphometry.

Imaging lung microstructure in mice with hyperpolarized 3He diffusion MRI.

Quantitative measurement of lung microstructure is of great significance in assessment of pulmonary disease, particularly in the earliest stages. The technique for MRI-based 3He lung morphometry was previously developed and validated for human lungs, and was recently extended to ex vivo mouse lungs. The technique yields accurate, quantitative information about the microstructure and geometry of acinar airways.