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. Another challenge is that the tissue microstructure is wildly different within the gray and white matter of the brain. In this review, we use results from multidimensional diffusion encoding techniques to discuss these challenges and their tentative solutions. Multidimensional encoding increases the information content of the data by varying not only the b-value and the encoding direction but also additional experimental parameters such as the shape of the b-tensor and the echo time. Three main insights have emerged from such encoding. First, multidimensional data contradict common model assumptions on diffusion and T2 relaxation, and illustrates how the use of these assumptions cause erroneous interpretations in both healthy brain and pathology. Second, many model assumptions can be dispensed with if data are acquired with multidimensional encoding. The necessary data can be easily acquired in vivo using protocols optimized to minimize Cramér-Rao lower bounds. Third, microscopic diffusion anisotropy reflects the presence of axons but not dendrites. This insight stands in contrast to current 'neurite models' of brain tissue, which assume that axons in white matter and dendrites in gray matter feature highly similar diffusion. Nevertheless, as an axon-based contrast, microscopic anisotropy can differentiate gray and white matter when myelin alterations confound conventional MRI contrasts.

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 9.4 T. Six datasets (baseline plus five datasets after injection) were acquired for each animal in a study group and a control group (13 and 10 female adult Wistar rats, respectively). For each dataset, ASL images at ten different inversion times were acquired. The CTT model was adapted to the use of a measured arterial input function, implying the use of a realistic labelling profile. Repeated measures ANOVA was used (alpha error = 0.05). RESULTS: After injection, significant differences between the study group and control group were observed for relative CBF in white matter (up to 20 percentage points) and putamen (up to 18-20 percentage points) and for relative CTT in putamen (up to 35-40 percentage points). CONCLUSIONS: Haemodynamic changes caused by injection of damaged RBCs were observed by ASL-based CBF and CTT measurements. Damaged RBCs can be used as a tool for test and validation of perfusion imaging modalities. CTT model fitting was challenging to stabilise at experimental signal-to-noise ratio levels, and the number of free parameters was minimised.

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. MATERIAL AND METHODS: AIFs with reasonable appearance, selected on the basis of conventional criteria related to timing, shape, and peak concentration, were registered from both ΔR2* and QSM images and mutually compared by visual inspection. Both ΔR2*- and QSM-based AIFs were used for perfusion calculations based on tissue concentration data from ΔR2*as well as QSM images. RESULTS: AIFs based on ΔR2* and QSM data showed very similar shapes and the estimated cerebral blood flow values and mean transit times were similar. Analysis of corresponding ΔR2* versus QSM-based concentration estimates yielded a transverse relaxivity estimate of 89 s-1 mM-1, for voxels identified as useful AIF candidate in ΔR2* images according to the conventional criteria. DISCUSSION: Interestingly, arterial concentration time curves based on ΔR2* versus QSM data, for a standard DSC-MRI experiment, were generally very similar in shape, and the relaxivity obtained in voxels representing blood was similar to tissue relaxivity obtained in previous studies.

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. To estimate the model parameters, in vivo human data were collected with multiple echo times (TE), inversion times (TI) and b-values, which allowed a direct relaxation estimate alongside estimation of perfusion, diffusion and fractional volume parameters. Compared to conventional two-compartment models (with and without relaxation compensation), the three-compartment model showed less effects of CSF contamination. The proposed model yielded significantly different volume fractions of blood and tissue compared to the non-relaxation-compensated model, as well as to the conventional two-compartment model, suggesting that previously reported parameter ranges, using models that do not account for relaxation, should be reconsidered.

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. For example, diffusional variance decomposition (DIVIDE) takes advantage of tensor-valued encoding to probe microscopic diffusion anisotropy independent of orientation coherence. The drawback is that tensor-valued encoding generally requires gradient waveforms that are more demanding on hardware; it has therefore been used primarily in MRI systems with relatively high performance. The purpose of this work was to explore tensor-valued diffusion encoding on clinical MRI systems with varying performance to test its technical feasibility within the context of DIVIDE. We performed whole-brain imaging with linear and spherical b-tensor encoding at field strengths between 1.5 and 7 T, and at maximal gradient amplitudes between 45 and 80 mT/m. Asymmetric gradient waveforms were optimized numerically to yield b-values up to 2 ms/µm2. Technical feasibility was assessed in terms of the repeatability, SNR, and quality of DIVIDE parameter maps. Variable system performance resulted in echo times between 83 to 115 ms and total acquisition times of 6 to 9 minutes when using 80 signal samples and resolution 2×2×4 mm3. As expected, the repeatability, signal-to-noise ratio and parameter map quality depended on hardware performance. We conclude that tensor-valued encoding is feasible for a wide range of MRI systems-even at 1.5 T with maximal gradient waveform amplitudes of 33 mT/m-and baseline experimental design and quality parameters for all included configurations. This demonstrates that tissue features, beyond those accessible by conventional diffusion encoding, can be explored on a wide range of MRI systems.

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). Material and Methods 2D-PC measurements in the aqueduct were performed in nine healthy individuals at 7T. Measurement accuracy was determined using a phantom. Aqueduct area, mean velocity, maximum velocity, minimum velocity, net flow, and mean flow were determined using in-plane resolutions 0.8 × 0.8, 0.5 × 0.5, 0.3 × 0.3, and 0.2 × 0.2 mm2. Feasibility criteria were defined based on scan time and spatial and temporal resolution. Results Phantom validation of 2D-PC MR showed good accuracy. In vivo, stroke volume was -8.2 ± 4.4, -4.7 ± 2.8, -6.0 ± 3.8, and -3.7 ± 2.1 µL for 0.8 × 0.8, 0.5 × 0.5, 0.3 × 0.3, and 0.2 × 0.2 mm2, respectively. The scan with 0.3 × 0.3 mm2 resolution fulfilled the feasibility criteria for a wide range of heart rates and aqueduct diameters. Conclusion 7T MR enables non-invasive quantification of CSF flow and velocity in the cerebral aqueduct with high spatial resolution.

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. If not accounted for, this will subsequently result in apparent CBV and CBF estimates that are higher than those reported previously at lower field strengths. The aims of this study were therefore to assess the feasibility of 7 T DSC-MRI and to investigate the apparent field-strength dependence of CBV and CBF estimates. In total, 8 healthy volunteers were examined using DSC-MRI at 7 T. A reduced CA dose of 0.05 mmol/kg was administered to decrease susceptibility artifacts. CBV, CBF, and MTT maps were calculated using standard DSC-MRI tracer-kinetic theory. Subject-specific arterial partial volume correction factors were obtained using a tail-scaling approach. Compared with literature values obtained using the tail-scaling approach at 1.5 T and 3 T, the CBV and CBF values of the present study were found to be further overestimated. This observation is potentially related to an inferred field-strength dependence of transverse relaxivities, although issues related to the CA dose must also be considered.

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. By selecting a CSF reference region of interest (ROI), the values of all QSM images were shifted to show no CA-induced change in CSF. CA concentration and cerebral blood volume (CBV) were estimated using shifted QSM data. CSF reference ROI optimization was evaluated by investigation of CBV repeatability. The CBV age dependence was analysed and tissue T2* relaxivity was estimated. RESULTS: The best repeatability of CBV, using an optimal CSF reference ROI, showed test-versus-retest correlations of r = 0.81 and r = 0.91 for white and grey matter, respectively. A slight CBV decrease with age was observed, and the estimated in vivo T2* relaxivity was 85 mM-1s-1. CONCLUSION: Provided that a carefully selected CSF reference ROI is used to shift QSM image values, susceptibility information can be used to estimate concentration of contrast agent and to calculate CBV.

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. The AXR variance was investigated by test-retest acquisitions in six brain regions in 18 healthy volunteers. Preoperative FEXI data and postoperative microphotos were obtained in six meningiomas and five astrocytomas. RESULTS: Protocol optimization reduced the coefficient of variation of AXR by approximately 40%. Test-retest AXR values were heterogeneous across normal brain regions, from 0.3 ± 0.2 s-1 in the corpus callosum to 1.8 ± 0.3 s-1 in the frontal white matter. According to analysis of statistical power, in all brain regions except one, group differences of 0.3-0.5 s-1 in the AXR can be inferred using 5 to 10 subjects per group. An AXR difference of this magnitude was observed between meningiomas (0.6 ± 0.1 s-1 ) and astrocytomas (1.0 ± 0.3 s-1 ). CONCLUSIONS: With the optimized protocol, FEXI has the ability to infer relevant differences in the AXR between two populations for small group sizes. Magn Reson Med 77:1104-1114, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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 (CMRO2 ) were quantified in a test-retest study. Cerebral blood flow (CBF) data, required for CMRO2 estimation, were obtained using dynamic susceptibility contrast MRI (DSC-MRI). OEF and CMRO2 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. The EPI phase data were included to elucidate whether an extra HR-GRE scan is needed to obtain information about OEF and CMRO2 , or if this information can be extracted from the DSC-MRI experiment only. METHODS: Twenty healthy volunteers were scanned using 3 T MRI on two occasions. Oxygen saturation levels were obtained from phase data measured in the great cerebral vein of Galen, based on HR-GRE as well as EPI phase maps. In combination with DSC-MRI CBF, this allowed for calculation of OEF and CMRO2 . RESULTS: High-resolution-gradient echo- and EPI-based phase images resulted in similar OEF spread and repeatability, with coefficients of variation/intraclass correlation coefficients of 0·26/0·95 and 0·23/0·81, respectively. Absolute OEF values (HR-GRE: 0·40 ± 0·11, EPI: 0·35 ± 0·08) were consistent with literature data. CMRO2 showed similar repeatability, somewhat increased spread and reasonable absolute values (HR-GRE: 3·23 ± 1·26 ml O2 /100 g min-1 , EPI: 2·79 ± 0·89 ml O2 /100 g min-1 ). DISCUSSION: In general, the results obtained by HR-GRE and EPI showed comparable characteristics. The EPI methodology could potentially be improved using a slightly modified DSC-MRI protocol (e.g. with regard to spatial resolution and slice gap).

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. METHODS: A linear mixed perfusion model for DSC-MRI was derived and evaluated by way of simulations. Twenty healthy volunteers were scanned twice, including DSC-MRI, arterial spin labeling (ASL), and partial volume measurements. Two different algorithms for PVC were employed and assessed. RESULTS: Simulations showed that the derived model had a tendency to overestimate perfusion values in voxels with high fractions of cerebrospinal fluid. PVC reduced the tissue volume dependence of DSC-MRI perfusion values from 44.4% to 4.2% in gray matter and from 55.3% to 14.2% in white matter. One PVC method significantly improved the voxel-wise repeatability, but PVC did not improve the spatial agreement between DSC-MRI and ASL perfusion maps. CONCLUSION: Significant PVEs were found for DSC-MRI perfusion estimates, and PVC successfully reduced those effects. The findings suggest that PVC might be an important consideration for DSC-MRI applications. Magn Reson Med 77:2203-2214, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

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. We performed dMRI using a novel encoding scheme for diffusional variance decomposition (DIVIDE) in 7 meningiomas and 8 gliomas prior to surgery. The diffusional variance was quantified from dMRI in terms of the total mean kurtosis (MKT), and DIVIDE was used to decompose MKT into components caused by microscopic anisotropy (MKA) and isotropic heterogeneity (MKI). Diffusion anisotropy was evaluated in terms of the fractional anisotropy (FA) and microscopic fractional anisotropy (µFA). Quantitative microscopy was performed on the excised tumor tissue, where structural anisotropy and cell density were quantified by structure tensor analysis and cell nuclei segmentation, respectively. In order to validate the DIVIDE parameters they were correlated to the corresponding parameters derived from microscopy. We found an excellent agreement between the DIVIDE parameters and corresponding microscopy parameters; MKA correlated with cell eccentricity (r=0.95, p<10-7) and MKI with the cell density variance (r=0.83, p<10-3). The diffusion anisotropy correlated with structure tensor anisotropy on the voxel-scale (FA, r=0.80, p<10-3) and microscopic scale (µFA, r=0.93, p<10-6). A multiple regression analysis showed that the conventional MKT parameter reflects both variable cell eccentricity and cell density, and therefore lacks specificity in terms of microstructure characteristics. However, specificity was obtained by decomposing the two contributions; MKA was associated only to cell eccentricity, and MKI only to cell density variance. The variance in meningiomas was caused primarily by microscopic anisotropy (mean±s.d.) MKA=1.11±0.33 vs MKI=0.44±0.20 (p<10-3), whereas in the gliomas, it was mostly caused by isotropic heterogeneity MKI=0.57±0.30 vs MKA=0.26±0.11 (p<0.05). In conclusion, DIVIDE allows non-invasive mapping of parameters that reflect variable cell eccentricity and density. These results constitute convincing evidence that a link exists between specific aspects of tissue heterogeneity and parameters from dMRI. Decomposing effects of microscopic anisotropy and isotropic heterogeneity facilitates an improved interpretation of tumor heterogeneity as well as diffusion anisotropy on both the microscopic and macroscopic scale.

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. Resulting cerebral blood flow (CBF) data for grey matter (GM) were compared with pseudo-continuous arterial spin labelling (ASL). During the main bolus CA passage, the apparent spatial shift (pixel shift) of the superior sagittal sinus (seen in single-shot echo-planar imaging (EPI)) was converted to CA concentration and compared with conventional ΔR2*-based data and with a predicted phase-based VOF from the pre-bolus experiment. RESULTS: The phase-based pre-bolus VOF resulted in a reasonable inter-individual GM CBF variability (coefficient of variation 28 %). Comparison with ASL CBF values implied a tissue R2*-relaxivity of 32 mM-1 s-1. Pixel-shift data at low concentrations (data not available at peak concentrations) were in reasonable agreement with the predicted phase-based VOF. CONCLUSION: Susceptibility-induced phase shifts and pixel shifts are potentially useful for large-vein CA quantification. Previous predictions of a higher R2*-relaxivity in tissue than in blood were supported.

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. Simulations were used to compare the performance of the proposed analysis method with conventional IVIM analysis. With flow compensation, strong rephasing was observed for the in vivo data, approximately cancelling the IVIM effect. The joint analysis yielded physiologically reasonable perfusion fraction maps. Estimated perfusion fractions were 2.43 ± 0.81% in gray matter, 1.81 ± 0.90% in deep gray matter, and 1.64 ± 0.72% in white matter (mean ± SD, n = 8). Simulations showed improved accuracy and precision when using joint analysis of flow-compensated and non-flow-compensated data, compared with conventional IVIM analysis. Double diffusion encoding with flow compensation was feasible for in vivo imaging of the perfusion fraction in the brain. The strong rephasing implied that blood flowing through the cerebral microvascular system was closer to the ballistic limit than the diffusive limit.

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. Brownian motion of labelled spins in a potential was described by a one-dimensional general Langevin equation as the starting point, and as a Fokker-Planck differential equation for the averaged distribution of labelled spins at the end point, which takes into account the effects of flow and dispersion of labelled water by the pseudorandom nature of the microvasculature and the transcapillary permeability. Multi-inversion time (multi-TI) ASL data were acquired in 14 healthy subjects on two occasions in a test-retest design, using a pulsed ASL sequence and three-dimensional gradient and spin echo (3D-GRASE) readout. Based on an error analysis to predict the size of a region of interest (ROI) required to obtain reasonably precise parameter estimates, data were analysed in two relatively large ROIs, i.e. the occipital lobe (OC) and the insular cortex (IC). The average values of CTT in OC were 260 ± 60 ms in the first experiment and 270 ± 60 ms in the second experiment. The corresponding IC values were 460 ± 130 ms and 420 ± 139 ms, respectively. Information related to the water transfer time may be important for diagnostics and follow-up of cerebral conditions or diseases characterised by a disrupted blood-brain barrier or disturbed capillary blood flow.

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. This is a major limitation to the use of FA as a biomarker for "tissue integrity", especially in regions of complex microarchitecture. In this work, we seek to circumvent this limitation by disentangling the effects of microscopic diffusion anisotropy from the orientation dispersion. The microscopic fractional anisotropy (µFA) and the order parameter (OP) were calculated from the contrast between signal prepared with directional and isotropic diffusion encoding, where the latter was achieved by magic angle spinning of the q-vector (qMAS). These parameters were quantified in healthy volunteers and in two patients; one patient with meningioma and one with glioblastoma. Finally, we used simulations to elucidate the relation between FA and µFA in various micro-architectures. Generally, µFA was high in the white matter and low in the gray matter. In the white matter, the largest differences between µFA and FA were found in crossing white matter and in interfaces between large white matter tracts, where µFA was high while FA was low. Both tumor types exhibited a low FA, in contrast to the µFA which was high in the meningioma and low in the glioblastoma, indicating that the meningioma contained disordered anisotropic structures, while the glioblastoma did not. This interpretation was confirmed by histological examination. We conclude that FA from DTI reflects both the amount of diffusion anisotropy and orientation dispersion. We suggest that the µFA and OP may complement FA by independently quantifying the microscopic anisotropy and the level of orientation coherence.

Submaximal adenosine-induced coronary hyperaemia with 12 h caffeine abstinence: implications for clinical adenosine perfusion imaging tests.

BACKGROUND: Adenosine is widely used as a vasodilator agent in myocardial perfusion imaging. Caffeine inhibits the effect, but the time of caffeine abstinence needed is under discussion and varies from 12 to 24 h. Therefore, our aim was to examine whether the time of caffeine abstinence affects the hyperaemic response using quantification of coronary sinus flow (CS F) with cardiac magnetic resonance (CMR) during adenosine infusion. METHODS: Healthy individuals (n = 16, eight females, age 41 ± 3 years) underwent two CMR examinations with 12 and 24 h of caffeine abstinence. CS F was quantified with phase-contrast velocity mapping (PC-)CMR during adenosine infusion (140 µg kg(-1)  min(-1) ) and rest and the CS F reserve between adenosine and rest was calculated. Myocardial perfusion (MP) was calculated as CS F × heart rate/left ventricular mass. Cardiac output (CO) was quantified using PC-CMR of the ascending aorta. RESULTS: The CS F reserve was lower after 12 h abstinence compared to 24 h (4·31 ± 0·57 versus 5·32 ± 0·76, P = 0·03). In six of 16 subjects (38%), CS F reserve was >30% higher with longer caffeine abstinence. MP during adenosine was lower after 12 h compared to 24 h caffeine abstinence (3·59 ± 0·37 versus 4·23 ± 0·28 ml min(-1) g(-1) ; P = 0·046). The increase in CO during adenosine between the two occasions did not differ (55 ± 7% and 55 ± 6%, P = 0·11). Interobserver variability for CS F/heartbeat was -0·05 ± 1·00 ml. CONCLUSIONS: Hyperaemia during adenosine is lower in some patients with 12 h of caffeine abstinence compared to 24 h. Longer caffeine abstinence, that is 24 h, is of value before pharmacological stress testing as the individual response is not known and the individual variation is large.

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. Flow was compared to 2D through-plane phase contrast (PC) upstream from the restriction. RESULTS: Results obtained with 3D through-plane PC as well as 4D PC at shortest TE using a spiral readout showed excellent agreements with the maximum velocity values obtained with CFD (<1 % for both methods), while larger deviations were seen using Cartesian readouts (-2.3 and 13 %, respectively). Peak pressure drop calculations from 3D through-plane PC and 4D PC spiral sequences were respectively 14 and 13 % overestimated compared to CFD. CONCLUSION: Identification of the maximum velocity location, as well as the accurate velocity quantification can be obtained in stenotic regions using short-TE spiral volumetric PC imaging.

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. The intraclass correlation coefficient was 0.52 for the tail-scaling approach and 0.86 for the prebolus administration concept. CONCLUSION: Both correction methods resulted in considerably reduced arterial PVEs, leading to quantitative estimates of perfusion approaching those typically obtained by other perfusion modalities. The CBF estimates obtained using the prebolus administration concept showed superior repeatability. Potential sources of uncertainty in the tail-scaling approach include the use of venous concentration curves influenced by PVEs or by geometric distortions (ie, vessel pixel shifts) in the steady-state period.

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. MATERIALS AND METHODS: Four volunteers were scanned twice at 1.5 T, 3 T as well as 7 T. By correcting for field-strength-dependent effects of relaxation, estimates of corrected CBV (cCBV) were obtained in deep gray matter (DGM), frontal gray matter (FGM) and frontal white matter (FWM), using Bayesian analysis. In addition, simulations were performed to facilitate the interpretation of experimental data. RESULTS: In DGM, FGM and FWM we obtained cCBV estimates of 2.2 ml/100 ml, 2.7 ml/100 ml, 1.4 ml/100 ml at 1.5 T; 3.7 ml/100 ml, 5.0 ml/100 ml, 3.2 ml/100 ml at 3 T and 15.5 ml/100 ml, 20.3 ml/100 ml, 7.0 ml/100 ml at 7 T. CONCLUSION: Quantitative cCBV values obtained at 1.5 T and 3 T corresponded better to physiological reference values, while 7 T showed the largest deviation from expected values. Simulations of synthetic tissue voxels indicated that the discrepancy at 7 T can partly be explained by SNR issues. Results were generally more repeatable at 7 T (intraclass correlation coefficient, ICC=0.84) than at 1.5 T (ICC=0.68) and 3 T (ICC=0.46).