Probing brain tissue microstructure with MRI: principles, challenges, and the role of multidimensional diffusion-relaxation encoding.

Diffusion MRI uses the random displacement of water molecules to sensitize the signal to brain microstructure and to properties such as the density and shape of cells. Microstructure modeling techniques aim to estimate these properties from acquired data by separating the signal between virtual tissue 'compartments' such as the intra-neurite and the extra-cellular space. A key challenge is that the diffusion MRI signal is relatively featureless compared with the complexity of brain tissue.

Effects of red blood cells with reduced deformability on cerebral blood flow and vascular water transport: measurements in rats using time-resolved pulsed arterial spin labelling at 9.4 T.

Background: Our aim was to introduce damaged red blood cells (RBCs) as a tool for haemodynamic provocation in rats, hypothesised to cause decreased cerebral blood flow (CBF) and prolonged water capillary transfer time (CTT), and to investigate whether expected changes in CBF could be observed and if haemodynamic alterations were reflected by the CTT metric.

Methods: Damaged RBCs exhibiting a mildly reduced deformability were injected to cause aggregation of RBCs. Arterial spin labelling (ASL) magnetic resonance imaging experiments were performed at 9.

Dynamic contrast-enhanced QSM for perfusion imaging: a systematic comparison of ΔR2*- and QSM-based contrast agent concentration time curves in blood and tissue.

Objective: In dynamic susceptibility contrast MRI (DSC-MRI), an arterial input function (AIF) is required to quantify perfusion. However, estimation of the concentration of contrast agent (CA) from magnitude MRI signal data is challenging. A reasonable alternative would be to quantify CA concentration using quantitative susceptibility mapping (QSM), as the CA alters the magnetic susceptibility in proportion to its concentration.

Estimation of diffusion, perfusion and fractional volumes using a multi-compartment relaxation-compensated intravoxel incoherent motion (IVIM) signal model.

Compartmental diffusion MRI models that account for intravoxel incoherent motion (IVIM) of blood perfusion allow for estimation of the fractional volume of the microvascular compartment. Conventional IVIM models are known to be biased by not accounting for partial volume effects caused by free water and cerebrospinal fluid (CSF), or for tissue-dependent relaxation effects. In this work, a three-compartment model (tissue, free water and blood) that includes relaxation terms is introduced.

Tensor-valued diffusion encoding for diffusional variance decomposition (DIVIDE): Technical feasibility in clinical MRI systems.

Microstructure imaging techniques based on tensor-valued diffusion encoding have gained popularity within the MRI research community. Unlike conventional diffusion encoding-applied along a single direction in each shot-tensor-valued encoding employs diffusion encoding along multiple directions within a single preparation of the signal. The benefit is that such encoding may probe tissue features that are not accessible by conventional encoding.

Investigation of cerebrospinal fluid flow in the cerebral aqueduct using high-resolution phase contrast measurements at 7T MRI.

Background The cerebral aqueduct is a central conduit for cerebrospinal fluid (CSF), and non-invasive quantification of CSF flow in the aqueduct may be an important tool for diagnosis and follow-up of treatment. Magnetic resonance (MR) methods at clinical field strengths are limited by low spatial resolution. Purpose To investigate the feasibility of high-resolution through-plane MR flow measurements (2D-PC) in the cerebral aqueduct at high field strength (7T).

Dynamic Susceptibility Contrast MRI at 7 T: Tail-Scaling Analysis and Inferences About Field Strength Dependence.

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) following bolus injection of gadolinium contrast agent (CA) is widely used for the estimation of brain perfusion parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) for both clinical and research purposes. Although it is predicted that DSC-MRI will have superior performance at high magnetic field strengths, to the best of our knowledge, there are no reports of 7 T DSC-MRI in the literature. It is plausible that the transfer of DSC-MRI to 7 T may be accompanied by increased [Formula: see text] relaxivity in tissue and a larger difference in [Formula: see text]-versus-concentration relationships between tissue and large vessels.

Assessment of MRI contrast agent concentration by quantitative susceptibility mapping (QSM): application to estimation of cerebral blood volume during steady state.

Objective: One major issue in dynamic susceptibility contrast MRI (DSC-MRI) is to accurately determine contrast agent (CA) concentration, since T2* relaxivity in vivo is generally unknown and varies between blood and tissue. In this study, quantitative susceptibility mapping (QSM) was used for quantification of CA concentration.

Materials And Methods: A DSC-MRI protocol, including phase data acquisition, was applied to 20 healthy volunteers in a test-retest study.

The link between diffusion MRI and tumor heterogeneity: Mapping cell eccentricity and density by diffusional variance decomposition (DIVIDE).

The structural heterogeneity of tumor tissue can be probed by diffusion MRI (dMRI) in terms of the variance of apparent diffusivities within a voxel. However, the link between the diffusional variance and the tissue heterogeneity is not well-established. To investigate this link we test the hypothesis that diffusional variance, caused by microscopic anisotropy and isotropic heterogeneity, is associated with variable cell eccentricity and cell density in brain tumors.

A linear mixed perfusion model for tissue partial volume correction of perfusion estimates in dynamic susceptibility contrast MRI: Impact on absolute quantification, repeatability, and agreement with pseudo-continuous arterial spin labeling.

Purpose: The partial volume effect (PVE) is an important source of bias in brain perfusion measurements. The impact of tissue PVEs in perfusion measurements with dynamic susceptibility contrast MRI (DSC-MRI) has not yet been well established. The purpose of this study was to suggest a partial volume correction (PVC) approach for DSC-MRI and to study how PVC affects DSC-MRI perfusion results.

Dynamic susceptibility contrast perfusion MRI using phase-based venous output functions: comparison with pseudo-continuous arterial spin labelling and assessment of contrast agent concentration in large veins.

Objectives: Contrast agent (CA) relaxivities are generally not well established in vivo, and the relationship between frequency/phase shift and magnetic susceptibility might be a useful alternative for CA quantification.

Materials And Methods: Twenty volunteers (25-84 years old) were investigated using test-retest pre-bolus dynamic susceptibility-contrast (DSC) magnetic resonance imaging (MRI). The pre-bolus phase-based venous output function (VOF) time integral was used for arterial input function (AIF) rescaling.

Optimal experimental design for filter exchange imaging: Apparent exchange rate measurements in the healthy brain and in intracranial tumors.

Purpose: Filter exchange imaging (FEXI) is sensitive to the rate of diffusional water exchange, which depends, eg, on the cell membrane permeability. The aim was to optimize and analyze the ability of FEXI to infer differences in the apparent exchange rate (AXR) in the brain between two populations.

Methods: A FEXI protocol was optimized for minimal measurement variance in the AXR.

Quantification of microcirculatory parameters by joint analysis of flow-compensated and non-flow-compensated intravoxel incoherent motion (IVIM) data.

The aim of this study was to improve the accuracy and precision of perfusion fraction and blood velocity dispersion estimates in intravoxel incoherent motion (IVIM) imaging, using joint analysis of flow-compensated and non-flow-compensated motion-encoded MRI data. A double diffusion encoding sequence capable of switching between flow-compensated and non-flow-compensated encoding modes was implemented. In vivo brain data were collected in eight healthy volunteers and processed using the joint analysis.

Characterization of ClpS2, an essential adaptor protein for the cyanobacterium Synechococcus elongatus.

The adaptor protein ClpS associates to the Clp protease and promotes degradation of N-end rule substrates in eubacteria and in algal/plant chloroplasts. Cyanobacteria are unusual in having two distinct ClpS paralogs. Although ClpSl is typical of bacterial ClpS, ClpS2 differs in crucial ways.

Dual stoichiometry and subunit organization in the ClpP1/P2 protease from the cyanobacterium Synechococcus elongatus.

The Clp protease is conserved among eubacteria and most eukaryotes, and uses ATP to drive protein substrate unfolding and translocation into a chamber of sequestered proteolytic active sites. To investigate the proteolytic core of the ClpXP1/P2 protease from the cyanobacterium Synechococcus elongatus we have used a non-denaturing mass spectrometry approach. We show that the proteolytic core is a double ring tetradecamer consisting of an equal number of ClpP1 and ClpP2 subunits with masses of 21.

Quantification of normal cerebral oxygen extraction and oxygen metabolism by phase-based MRI susceptometry: evaluation of repeatability using two different imaging protocols.

Introduction: Global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO ) were quantified in a test-retest study. Cerebral blood flow (CBF) data, required for CMRO estimation, were obtained using dynamic susceptibility contrast MRI (DSC-MRI). OEF and CMRO were quantified using two separate data sets, that is, conventional high-resolution (HR) gradient echo (GRE) phase maps as well as echo planar imaging (EPI) phase maps taken from the baseline (precontrast) part of the DSC-MRI time series.

Measurement of vascular water transport in human subjects using time-resolved pulsed arterial spin labelling.

Most approaches to arterial spin labelling (ASL) data analysis aim to provide a quantitative measure of the cerebral blood flow (CBF). This study, however, focuses on the measurement of the transfer time of blood water through the capillaries to the parenchyma (referred to as the capillary transfer time, CTT) as an alternative parameter to characterise the haemodynamics of the system. The method employed is based on a non-compartmental model, and no measurements need to be added to a common time-resolved ASL experiment.

Quantification of microscopic diffusion anisotropy disentangles effects of orientation dispersion from microstructure: applications in healthy volunteers and in brain tumors.

The anisotropy of water diffusion in brain tissue is affected by both disease and development. This change can be detected using diffusion MRI and is often quantified by the fractional anisotropy (FA) derived from diffusion tensor imaging (DTI). Although FA is sensitive to anisotropic cell structures, such as axons, it is also sensitive to their orientation dispersion.

Intravoxel incoherent motion (IVIM) imaging at different magnetic field strengths: what is feasible?

Background: Due to limited SNR the cerebral applications of the intravoxel incoherent motion (IVIM) concept have been sparse. MRI hardware developments have resulted in improved SNR and this may justify a reassessment of IVIM imaging for non-invasive quantification of the cerebral blood volume (CBV) as a first step toward determining the optimal field strength.

Purpose: To investigate intravoxel incoherent motion imaging for its potential to assess cerebral blood volume (CBV) at three different MRI field strengths.

Partial volume correction of brain perfusion estimates using the inherent signal data of time-resolved arterial spin labeling.

Quantitative perfusion MRI based on arterial spin labeling (ASL) is hampered by partial volume effects (PVEs), arising due to voxel signal cross-contamination between different compartments. To address this issue, several partial volume correction (PVC) methods have been presented. Most previous methods rely on segmentation of a high-resolution T1 -weighted morphological image volume that is coregistered to the low-resolution ASL data, making the result sensitive to errors in the segmentation and coregistration.

Volumetric velocity measurements in restricted geometries using spiral sampling: a phantom study.

Object: The aim of this study was to evaluate the accuracy of maximum velocity measurements using volumetric phase-contrast imaging with spiral readouts in a stenotic flow phantom.

Materials And Methods: In a phantom model, maximum velocity, flow, pressure gradient, and streamline visualizations were evaluated using volumetric phase-contrast magnetic resonance imaging (MRI) with velocity encoding in one (extending on current clinical practice) and three directions (for characterization of the flow field) using spiral readouts. Results of maximum velocity and pressure drop were compared to computational fluid dynamics (CFD) simulations, as well as corresponding low-echo-time (TE) Cartesian data.

Reduction of arterial partial volume effects for improved absolute quantification of DSC-MRI perfusion estimates: comparison between tail scaling and prebolus administration.

Purpose: To evaluate and mutually compare the tail-scaling approach and the prebolus administration concept for reduction of arterial partial volume effects (PVEs), because reproducible absolute quantification of cerebral blood flow (CBF) by dynamic susceptibility contrast magnetic resonance imaging (MRI) is often hampered by PVEs in the arterial input function (AIF) registration.

Materials And Methods: Twenty healthy volunteers were scanned in a test-retest study with 7-20 days between investigations to examine the quantitative values and the repeatability of CBF estimates obtained from the tail-scaling and the prebolus administration approaches.

Results: Average grey matter CBF was 80 ± 18 mL/100 g/min (mean ± SD) using tail-scaling and 56 ± 18 mL/100 g/min using prebolus administration.

Automatic brain segmentation using fractional signal modeling of a multiple flip angle, spoiled gradient-recalled echo acquisition.

Object: The aim of this study was to demonstrate a new automatic brain segmentation method in magnetic resonance imaging (MRI).

Materials And Methods: The signal of a spoiled gradient-recalled echo (SPGR) sequence acquired with multiple flip angles was used to map T1, and a subsequent fit of a multi-compartment model yielded parametric maps of partial volume estimates of the different compartments. The performance of the proposed method was assessed through simulations as well as in-vivo experiments in five healthy volunteers.

Absolute quantification of perfusion by dynamic susceptibility contrast MRI using Bookend and VASO steady-state CBV calibration: a comparison with pseudo-continuous ASL.

Objective: Dynamic susceptibility contrast MRI (DSC-MRI) tends to return elevated estimates of cerebral blood flow (CBF) and cerebral blood volume (CBV). In this study, subject-specific calibration factors (CFs), based on steady-state CBV measurements, were applied to rescale the absolute level of DSC-MRI CBF.

Materials And Methods: Twenty healthy volunteers were scanned in a test-retest approach.