Hematocrit Measurement with R2* and Quantitative Susceptibility Mapping in Postmortem Brain.

BACKGROUND AND PURPOSE: Noninvasive venous oxygenation quantification with MR imaging will improve the neurophysiologic investigation and the understanding of the pathophysiology in neurologic diseases. Available MR imaging methods are limited by sensitivity to flow and often require assumptions of the hematocrit level. In situ postmortem imaging enables evaluation of methods in a fully deoxygenated environment without flow artifacts, allowing direct calculation of hematocrit. This study compares 2 venous oxygenation quantification methods in in situ postmortem subjects. MATERIALS AND METHODS: Transverse relaxation (R2*) mapping and quantitative susceptibility mapping were performed on a whole-body 4.7T MR imaging system. Intravenous measurements in major draining intracranial veins were compared between the 2 methods in 3 postmortem subjects. The quantitative susceptibility mapping technique was also applied in 10 healthy control subjects and compared with reference venous oxygenation values. RESULTS: In 2 early postmortem subjects, R2* mapping and quantitative susceptibility mapping measurements within intracranial veins had a significant and strong correlation (R2 = 0.805, P = .004 and R2 = 0.836, P = .02). Higher R2* and susceptibility values were consistently demonstrated within gravitationally dependent venous segments during the early postmortem period. Hematocrit ranged from 0.102 to 0.580 in postmortem subjects, with R2* and susceptibility as large as 291 seconds-1 and 1.75 ppm, respectively. CONCLUSIONS: Measurements of R2* and quantitative susceptibility mapping within large intracranial draining veins have a high correlation in early postmortem subjects. This study supports the use of quantitative susceptibility mapping for evaluation of in vivo venous oxygenation and postmortem hematocrit concentrations.

Cognitive Implications of Deep Gray Matter Iron in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Deep gray matter iron accumulation is increasingly recognized in association with multiple sclerosis and can be measured in vivo with MR imaging. The cognitive implications of this pathology are not well-understood, especially vis-à-vis deep gray matter atrophy. Our aim was to investigate the relationships between cognition and deep gray matter iron in MS by using 2 MR imaging-based iron-susceptibility measures. MATERIALS AND METHODS: Forty patients with multiple sclerosis (relapsing-remitting, n = 16; progressive, n = 24) and 27 healthy controls were imaged at 4.7T by using the transverse relaxation rate and quantitative susceptibility mapping. The transverse relaxation rate and quantitative susceptibility mapping values and volumes (atrophy) of the caudate, putamen, globus pallidus, and thalamus were determined by multiatlas segmentation. Cognition was assessed with the Brief Repeatable Battery of Neuropsychological Tests. Relationships between cognition and deep gray matter iron were examined by hierarchic regressions. RESULTS: Compared with controls, patients showed reduced memory (P < .001) and processing speed (P = .02) and smaller putamen (P < .001), globus pallidus (P = .002), and thalamic volumes (P < .001). Quantitative susceptibility mapping values were increased in patients compared with controls in the putamen (P = .003) and globus pallidus (P = .003). In patients only, thalamus (P < .001) and putamen (P = .04) volumes were related to cognitive performance. After we controlled for volume effects, quantitative susceptibility mapping values in the globus pallidus (P = .03; trend for transverse relaxation rate, P = .10) were still related to cognition. CONCLUSIONS: Quantitative susceptibility mapping was more sensitive compared with the transverse relaxation rate in detecting deep gray matter iron accumulation in the current multiple sclerosis cohort. Atrophy and iron accumulation in deep gray matter both have negative but separable relationships to cognition in multiple sclerosis.

Structural and functional quantitative susceptibility mapping from standard fMRI studies.

Standard functional MRI (fMRI), which includes resting-state or paradigm-driven designs, is widely used in studies of brain function, aging, and disease. These fMRI studies typically use two-dimensional gradient echo-planar imaging, which inherently contains phase data that enables quantitative susceptibility mapping (QSM). This work focuses on the dual value of QSM within fMRI studies, by providing both a localized analysis of functional changes in activated tissue, and iron-sensitive structural maps in deep grey matter (DGM). Using a visual paradigm fMRI study on healthy volunteers at clinical (1.5 T) and high field strength (4.7 T), we perform functional analysis of magnitude and QSM time series, and at the same time harness structural QSM of iron-rich DGM, including globus pallidus, putamen, caudate head, substantia nigra, and red nucleus. The effects of fMRI spatial resolution and time series variation on structural DGM QSM are investigated. Our results indicate that structural DGM QSM is feasible within existing fMRI studies, provided that the voxel dimensions are equal to or less than 3 mm, with higher resolutions preferred. The mean DGM QSM values were about 40 to 220 ppb, while the interquartile ranges of the DGM QSM time series varied from about 3 to 9 ppb, depending on structure and resolution. In contrast, the peak voxel functional QSM (fQSM) changes in activated visual cortex ranged from about -10 to -30 ppb, and functional clusters were consistently smaller on QSM than magnitude fMRI. Mean-level DGM QSM of the time series was successfully extracted in all cases, while fQSM results were more prone to residual background fields and showed less functional change compared with standard magnitude fMRI. Under the conditions prescribed, standard fMRI studies may be used for robust mean-level DGM QSM, enabling study of DGM iron accumulation, in addition to functional analysis. Copyright © 2016 John Wiley & Sons, Ltd.

The effect of concomitant gradient fields on diffusion tensor imaging.

Concomitant gradient fields are transverse magnetic field components that are necessarily present to satisfy Maxwell's equations when magnetic field gradients are utilized in magnetic resonance imaging. They can have deleterious effects that are more prominent at lower static fields and/or higher gradient strengths. In diffusion tensor imaging schemes that employ large gradients that are not symmetric about a refocusing radiofrequency pulse (unlike Stejskal-Tanner, which is symmetric), concomitant fields may cause phase accrual that could corrupt the diffusion measurement. Theory predicting the error from this dephasing is described and experimentally validated for both Reese twice-refocused and split gradient single spin-echo diffusion gradient schemes. Bias in apparent diffusion coefficient values was experimentally found to worsen with distance from isocenter and with increasing duration of gradient asymmetry in both a phantom and in the brain. The amount of error from concomitant gradient fields depends on many variables, including the diffusion gradient pattern, pulse sequence timing, maximum effective gradient amplitude, static magnetic field strength, voxel size, slice distance from isocenter, and partial Fourier fraction. A prospective correction scheme that can reduce concomitant gradient errors is proposed and verified for diffusion imaging.

In vivo quantification of hippocampal subfields using 4.7 T fast spin echo imaging.

Several neuropsychiatric disorders involving hippocampal structural changes have been studied extensively using volumetric magnetic resonance imaging (MRI). These studies have mostly measured total hippocampal volume while the present study aimed to delineate and measure hippocampal subfields within the whole hippocampus and subdivisions along its longitudinal axis. Images were acquired at 4.7 T in 11 healthy subjects (5 males and 6 females, aged 23-56 years), using a fast spin echo (FSE) sequence with 0.52 x 0.68 x 1.0 mm(3) native resolution, collecting 90 contiguous coronal slices. Subiculum, cornu ammonis (CA1-3), and dentate gyrus were traced manually within the hippocampal head, body, and tail. We reported volumes for the subfields and demonstrated differences in the distribution within the hippocampus and its parts. The biggest part of the dentate gyrus was located in the hippocampal body, following the hippocampal head and tail. In contrast, the hippocampal head had the largest part of CA1-3, following the hippocampal body and tail. The hippocampal tail had the smallest portion of the subiculum compared to hippocampal head and tail. Subfield volumes were consistent between hemispheres and showed distributions within the longitudinal subdivisions that were consistent with histological data. Direct measurements of subfield distribution along the longitudinal axis of the hippocampus may be more sensitive to detecting disease effects than total volume measures and the differential distribution of subfield volumes may aid in the interpretation of measurements obtained at lower field strength and spatial resolution.

Quantitative evaluation of nonrepetitive phase-encoding orders for first-pass, 3D contrast-enhanced MR angiography.

In this work, a detailed quantitative comparison was made of many alternative phase-encoding strategies for first-pass 3D MR angiography where each phase encode is only sampled once during the transient passage of contrast agent. A series of standard sequential and centric phase-encoding orders including elliptical centric were tested, as well as a new order called elliptical sequential. The characteristics of the different phase-encoding orders were tested using a computer simulation followed by experimental verification using a variable flip angle scheme. The characteristics to be considered included: arterial intensity, arterial-to-venous contrast, degree of artifact, and the blurring of the point-spread function. By making use of a wide range of start times and a rapidly varying contrast curve, the quantitative results clearly indicate the widely varying merits of each phase-encoding order. In general, when an optimal start time is used techniques that sample the low k-space views most compactly will produce the best results; however, the same methods are more problematic when the bolus arrival time deviates substantially from that expected.

On the cause of increased aliasing in the slice-select direction in 3D contrast-enhanced magnetic resonance angiography.

The combination of short repetition times and large flip angles typically used in 3D contrast-enhanced magnetic resonance angiography (3D CE MRA) can significantly alter the expected shape of the slab profile for unenhanced tissues, which can cause increased aliasing in the slice select direction. In this work, this increased slice select aliasing is demonstrated and explained from both theoretical and experimental points of view. The effect is due to the Ernst angle of unenhanced background tissue occurring on the falling edges of the flip angle profile that has been set for the significantly reduced T(1) of contrast-enhanced blood. The deleterious aliasing effects are magnified substantially when the chosen volume is placed close to surface coil reception with the slice select direction perpendicular to the coil axis. Magn Reson Med 44:336-338, 2000.

Carotid arteries: maximizing arterial to venous contrast in fluoroscopically triggered contrast-enhanced MR angiography with elliptic centric view ordering.

PURPOSE: To obtain high-spatial-resolution, venous-suppressed, contrast material-enhanced, three-dimensional (3D) magnetic resonance (MR) angiograms of the carotid arteries and aortic arch by using an elliptic centric view ordering with MR fluoroscopic triggering. MATERIALS AND METHODS: Forty consecutive patients with cerebrovascular disease in the differential diagnosis were evaluated with fluoroscopically triggered 3D MR angiography (gadoteridol dose range, 0.1-0.3 mmol per kilogram of body weight; mean acquisition time, 40 second +/- 8 [SD]). The contrast-enhanced 3D MR angiograms were evaluated for overall quality, vascular signal intensity, venous suppression, and motion artifact. Twenty patients also underwent two-dimensional (2D) time-of-flight (TOF) MR angiography. The overall quality of the 2D TOF MR angiograms and comparative quality between the 2D TOF and contrast-enhanced 3D MR angiograms were determined. RESULTS: The contrast-enhanced 3D MR angiograms were of excellent or more than adequate quality for diagnosis in 36 of the 40 studies (90%). In 35 of the 38 contrast-enhanced 3D studies in which the contrast material bolus was detected fluoroscopically, the internal jugular vein signal intensity was either not detectable or barely visible. In 18 of the 20 patients who also underwent 2D TOF MR angiography, the quality of the contrast-enhanced 3D MR angiograms was graded as markedly superior or superior. CONCLUSION: Contrast-enhanced, elliptic centric 3D MR angiography with real-time MR fluoroscopic triggering offers high-spatial-resolution images of the carotid arteries and aortic arch with reliable venous suppression.

Arterial phase carotid and vertebral artery imaging in 3D contrast-enhanced MR angiography by combining fluoroscopic triggering with an elliptical centric acquisition order.

Arterial-phase three-dimensional (3D) contrast-enhanced MR angiograms of the carotid and vertebral arteries from their origins through the carotid bifurcations were obtained in 20 patients using acquisition times over 30 sec by using an MR fluoroscopy-triggered pulse sequence with elliptical centric view order. The typical pixel size was 0.8 mm (x) x 1.6 mm (y) x 1.5 mm (z), and 32-48 coronal slices were acquired. The fluoroscopic monitoring of bolus arrival was effective in 18 of the 20 cases; two failures were attributed directly to a poor choice of RF coil. To exploit peak arterial-to-venous contrast, the central 3D views were acquired first in the most compact time period possible for the given TR. For the 18 successfully triggered cases, arterial-phase 3D images were obtained with excellent venous suppression as demonstrated by an average internal jugular vein to common carotid signal enhancement ratio of only 0.05 +/- 0.04.

Performance of an elliptical centric view order for signal enhancement and motion artifact suppression in breath-hold three-dimensional gradient echo imaging.

An elliptical centric phase-encoding (PE) order is applied to steady-state 3DFT imaging as performed during a single breath-hold or following contrast agent administration. In a set of simulation, phantom, and in vivo experiments, this truly centric PE order is shown to be both more resistant to breathing artifact and more capable of suppressing undesirable venous signals that can arise following peak arterial enhancement than a number of other centric PE techniques that are presently in use. Unlike other PE orders, the elliptical centric ordering changes with the relative dimensions of the two PE fields of view and is optimal based on increasing k-space radius. It thus creates a temporally diminishing importance to the PE order. The specific advantages of such an acquisition are demonstrated.

Fluoroscopically triggered contrast-enhanced three-dimensional MR angiography with elliptical centric view order: application to the renal arteries.

PURPOSE: To determine the reliability of obtaining arterial-phase, contrast-material-enhanced three-dimensional (3D) magnetic resonance (MR) angiograms of the renal arteries by using a technique that combines two-dimensional real-time MR fluoroscopy and a 3D MR angiographic acquisition with elliptical centric view order. MATERIALS AND METHODS: Twenty-five consecutive patients suspected of having renal artery disease were evaluated with the fluoroscopically triggered technique by using a mean dose of 0.18 mmol/kg gadoteridol. Left renal vein suppression, inferior vena cava suppression, motion artifact, and image quality for depiction of the renal arteries were each evaluated on a five-point scale (1 = best). The findings were compared with those of another 25 consecutive patients who underwent conventional gadolinium-enhanced 3D MR angiography. RESULTS: The fluoroscopically triggered technique produced 4.6 times less left renal vein enhancement than did the conventional method (P < .01). With the fluoroscopically triggered technique, visualization of the renal arteries was adequate for diagnosis in 24 patients (96%) and the overall result (score of 1-3 for all criteria) was of good quality in 22 patients (88%). CONCLUSION: With this fluoroscopically triggered MR angiographic technique, high-quality, arterial phase, relatively motion immune angiograms can be routinely obtained.

Three-dimensional magnetization-prepared time-of-flight MR angiography of the carotid and vertebral arteries.

Three-dimensional magnetization-prepared (MP) MR angiography (MRA) was applied to the carotid and vertebral arteries by using ECG triggering, a slab selective RF inversion pulse, centric phase encoding and acquisition during diastole. Both theoretically and experimentally, the MP MRA sequence was shown to perform well in cases where there was substantial blood replenishment during the inversion time TI (>330 ms). In comparison with standard, ungated, steady-state 3D time-of-flight MRA in 13 consecutive volunteers, the MP MRA images demonstrated better background suppression with less artifact and generally had more uniform vessel depiction. The MP MRA sequence was generally superior for portraying vessels exhibiting high pulsatility such as the carotid siphon. However, in distal vessels with slow flow and incomplete blood replenishment, the MP MRA technique was inferior due to increased loss of vessel signal. The reasons for this increased signal loss are identified and improvements to the MP MRA sequence are suggested.

Metabolite-specific NMR spectroscopy in vivo.

An outline is presented of metabolite-specific in vivo NMR spectroscopy (particularly in brain). It reviews from a physical spectroscopist's perspective, the need for and the methods of observation of, individual metabolite resonances.

Observing N-acetyl aspartate via both its N-acetyl and its strongly coupled aspartate groups in in vivo proton magnetic resonance spectroscopy.

The approximately 2.6 ppm aspartate multiplet of N-acetyl aspartate (NAA) is considered a potential source of additional information on N-acetyl aspartate in vivo. Because the aspartate multiplet is the AB part of a strongly coupled ABX system it gives rise, as is shown in the analysis presented, to a significant field-strength dependence in the echo-time-dependent modulations of the response to typical spatial-localization sequences. The echo-time dependence of this response is developed analytically, not only for the STEAM and the PRESS localization sequences, but also for a spin-echo sequence. It is then verified experimentally at 2.35 T. The field-strength dependence of the response is demonstrated by evaluating the changes in the echo-time-dependent responses to each of the three sequences at field strengths of 1.5, 2.35, and 4.0 T. By means of these results, the preferred sequence (PRESS) can be optimized for the NAA aspartate multiplet at each field strength, as is illustrated with the human brain spectra obtained in vivo at 1.5 T. These in vivo spectra compare the optimal, long TE timing (163 ms) with a suboptimal TE (70 ms), for the observation of the approximately 2.6 ppm aspartate resonances of NAA.

3D MR angiography of pulmonary arteries using real-time navigator gating and magnetization preparation.

An ECG-triggered magnetization-prepared segmented 3D fast gradient echo sequence was developed to perform pulmonary arterial MR angiography. A selective inversion recovery pulse was used in the magnetization preparation to suppress venous vasculature. A real-time gating technique based on navigator echoes was implemented to reduce respiration effects. Pencil-beam navigator echoes were acquired immediately before and after the readout train and processed in real-time to dynamically measure the diaphragm position, which was used to control data acquisition with an accept-or-reject-reacquire logic. In a study of 10 volunteers, a gated 3D acquisition with 28 slices required on average approximately 4 min of acquisition time, and six to seven segmental arteries related to the interlobar trunk of the pulmonary artery were depicted. The use of SIR pulse reduced venous signal by 99%. The gated acquisitions were superior to the ungated acquisitions (n = 10, P < 0.005). The real-time navigator gating technique is effective for reduction of respiration effects and thereby makes high resolution 3D MRA of the pulmonary arteries feasible.

Improved centric phase encoding orders for three-dimensional magnetization-prepared MR angiography.

New centric phase encoding orders are introduced for transient state three-dimensional MR imaging. Unlike previous centric orders, these variants are not fixed with respect to differences in the relative y and z fields of view, but are tailored to account for the, differential degrees of gradient dephasing in the Ky and Kz phase encoding directions and thus maintain the highest weighting for the most central k-space values. The new centric orders are compared with previous methods in both simulation and experimental magnetization-prepared MR angiography of the carotid and renal arteries. In comparison with other tested centric orders, the new methods provided better retention of true vessel shape caused by isotropic blurring across the phase encoding plane. In addition, the new methods provided increased contrast, with the degree of improvement over previous methods depending on vessel orientation, size, and degree of inflow.

Multiple breathhold 3D time-of-flight MR angiography of the renal arteries.

A technique is described for angiographic imaging of the renal arteries with acquisition performed over several periods of suspended respiration. The 3D Fourier transform (FT) gradient-echo angiographic sequence uses magnetization preparation and appropriately chosen delay times for background nulling and time-of-flight enhancement of the vasculature. The sequence was applied to 10 volunteers, each of whom was imaged in three ways: (i) over a series of breathholds in which feedback was provided to enable reproducible breathholding; (ii) over a series of breathholds with no feedback; and (iii) over continuous respiration. Results were evaluated by measuring the transverse extent of the well-delineated renal vasculature and by noting the distal extent of the vasculature branching (main, segmental, and interlobar branches). The transverse extent of renal vasculature visible with breathhold feedback, breathholding, and free breathing was 6.1 +/- 0.9 cm, 5.0 +/- 1.8 cm, and 4.0 +/- 1.4 cm, respectively (mean +/- SD). Breathhold feedback enabled visualization of segmental renal arteries bilaterally in all 10 volunteers.

Yield enhancement of a double-quantum filter sequence designed for the edited detection of GABA.

To overcome limitations in the signal to noise ratio (S/N) of previously proposed multiple-quantum filters (MQFs), designed for editing the GABA A2 multiplet from the creatine (Cr) singlet in proton spectroscopy of brain, a new double-quantum filter is proposed which significantly enhances S/N (thereby making it comparable with the spin-echo difference editing technique) while maintaining the superior Cr suppression and zero vulnerability to subtraction errors of previously proposed MQFs. The S/N enhancement results primarily from a significant reduction in transverse-relaxation losses, achieved by shortening the filter sequence by approximately 70%, first by altering the criterion that determines the initial evolution period and, second, by effectively eliminating the refocusing time prior to the start of acquisition. The altered evolution time criterion also leads to an increase in the intrinsic yield of the filter from 25 to 39%. The analysis of the filter design was verified in vitro on phantoms of GABA in D2O, and the maintenance of editing capability, i.e., Cr suppression by more than 1600, was demonstrated on rat brain extracts.

The response of the strongly coupled AB system of citrate to typical 1H MRS localization sequences.

The response of the strongly coupled AB system of citrate to the STEAM and PRESS spatial localization sequences is developed analytically and then verified experimentally at 2.35 T. At this field strength, the response predicted by the complete strong-coupling calculation is shown to differ greatly from that of the simpler weak-coupling approximation. It is shown that the strong-coupling effects induce a significant field-strength dependence in the time-dependent modulations of the response to either sequence. These effects are illustrated for the STEAM and PRESS responses at field strengths of 1.5, 2.35, and 4.7 T. Independent of the chosen sequence, the increase in the signal-to-noise (S/N) of the frequency response with increasing field strength is shown to be significantly less for the citrate system than for uncoupled spins. The factors which weaken the S/N dependence of the citrate AB signal with increasing field strength are quantified and discussed.