BOLD background gradient contributions in diffusion‐weighted fMRI—comparison of spin‐echo and twice‐refocused spin‐echo sequences

The interaction (‘cross terms’) between diffusion‐weighting gradients and susceptibility‐induced background gradient fields around vessels has an impact on apparent diffusion coefficient (ADC) measurements and diffusion‐weighted functional magnetic resonance imaging (DFMRI) experiments. Monte‐Carlo (MC) simulations numerically integrating the Bloch equations for a large number of random walks in a vascular model were used to investigate to what extent such interactions would influence the extravascular signal change as well as the ADC change observed in DFMRI experiments. The vascular model consists of a set of independent, randomly oriented, infinite cylinders whose internal magnetic susceptibility varies as the state changes between rest and activation. In such a network, the cross terms result in the observation of a functional increase in ADC accompanied by a descending percent signal change with increasing diffusion weighting. It is shown that the twice‐refocused spin‐echo sequence permits sufficient yet not total suppression of such effects compared to the standard Stejskal‐Tanner spin‐echo diffusion weighting under experimentally relevant conditions. Copyright © 2010 John Wiley & Sons, Ltd.     

Spatial location and strength of BOLD activation in high-spatial-resolution fMRI of the motor cortex: a comparison of spin echo and gradient echo fMRI at 7 T

The increased blood oxygenation level‐dependent contrast‐to‐noise ratio at ultrahigh field (7 T) has been exploited in a comparison of the spatial location and strength of activation in high‐resolution (1.5 mm isotropic) gradient echo (GE) and spin echo (SE), echo planar imaging data acquired during the execution of a simple motor task in five subjects. SE data were acquired at six echo times from 30 to 55 ms. Excellent fat suppression was achieved in the SE echo planar images using slice‐selective gradient reversal. Threshold‐free cluster enhancement was used to define regions of interest (ROIs) containing voxels showing significant stimulus‐locked signal changes from the GE and average SE data. These were used to compare the signal changes and spatial locations of activated regions in SE and GE data. T₂ and T₂* values were measured, with means of 48.3 ± 1.1 ms and 36.5 ± 3.4 ms in the SE ROI. In addition, we identified a dark band in SE images of the motor cortex corresponding to a region in which T₂ and T₂* were significantly lower than in the surrounding grey matter. The fractional SE signal change in the ROI was found to vary linearly as a function of TE, with a slope that was dependent on the particular ROI assessed: the mean ΔR₂ value was found to be 0.85 ± 0.11 s^–1 for the SE ROI and ?0.37 ± 0.05 s^–1 for the GE ROI. The fractional signal change relative to the shortest TE revealed that the largest signal change occurred at a TE of 45 ms outside of the dark band. At this TE, the ratio of the fractional signal change in GE and SE data was found to be 0.48 ± 0.05. Phase maps produced from high‐resolution GE images spanning the right motor cortex were used to identify veins. The GE ROI was found to contain 18% more voxels overlying the venous mask than the SE ROI. Copyright © 2011 John Wiley & Sons, Ltd.     

Measurement of parenchymal extravascular R2* and tissue oxygen extraction fraction using multi‐echo vascular space occupancy MRI at 7 T

Parenchymal extravascular R₂* is an important parameter for quantitative blood oxygenation level‐dependent (BOLD) studies. Total and intravascular R₂* values and changes in R₂* values during functional stimulations have been reported in a number of studies. The purpose of this study was to measure absolute extravascular R₂* values in human visual cortex and to estimate the intra‐ and extravascular contributions to the BOLD effect at 7 T. Vascular space occupancy (VASO) MRI was employed to separate out the extravascular tissue signal. Multi‐echo VASO and BOLD functional MRI (fMRI) with visual stimulation were performed at 7 T for R₂* measurement at a spatial resolution of 2.5 × 2.5 × 2.5 mm³ in healthy volunteers (n = 6). The ratio of changes in extravascular and total R₂* (ΔR₂*) was used to estimate the extravascular fraction of the BOLD effect. Extravascular R₂* values were found to be 44.66 ± 1.55 and 43.38 ± 1.51 s^–1 (mean ± standard error of the mean, n = 6) at rest and activation, respectively, in human visual cortex at 7 T. The extravascular BOLD fraction was estimated to be 91 ± 3%. The parenchymal oxygen extraction fraction (OEF) during activation was estimated to be 0.24 ± 0.01 based on the R₂* measurements, indicating an approximately 37% decrease compared with OEF at rest. Copyright © 2014 John Wiley & Sons, Ltd.     

A multi‐compartmental SE‐BOLD interpretation for stimulus‐related signal changes in diffusion‐weighted functional MRI

A new interpretation is proposed for stimulus‐induced signal changes in diffusion‐weighted functional MRI. T₂‐weighted spin‐echo echo‐planar images were acquired at different diffusion‐weightings while visual stimulation was presented to human volunteers. The amplitudes of the positive stimulus‐correlated response and post‐stimulus undershoot (PSU) in the functional time‐courses were found to follow different trends as a function of b‐value. Data were analysed using a three‐compartment signal model, with one compartment being purely vascular and the other two dominated by fast‐ and slow‐diffusing molecules in the brain tissue. The diffusion coefficients of the tissue were assumed to be constant throughout the experiments. It is shown that the stimulus‐induced signal changes can be decomposed into independent contributions originating from each of the three compartments. After decomposition, the fast‐diffusion phase displays a substantial PSU, while the slow‐diffusion phase demonstrates a highly reproducible and stimulus‐correlated time‐course with minimal undershoot. The decomposed responses are interpreted in terms of the spin‐echo blood oxygenation level dependent (SE‐BOLD) effect, and it is proposed that the signal produced by fast‐ and slow‐diffusing molecules reflect a sensitivity to susceptibility changes in arteriole/venule‐ and capillary‐sized vessels, respectively. This interpretation suggests that diffusion‐weighted SE‐BOLD imaging may provide subtle information about the haemodynamic and neuronal responses. Copyright © 2009 John Wiley & Sons, Ltd.     

Post‐contractile BOLD contrast in skeletal muscle at 7 T reveals inter‐individual heterogeneity in the physiological responses to muscle contraction

Muscle blood oxygenation‐level dependent (BOLD) contrast is greater in magnitude and potentially more influenced by extravascular BOLD mechanisms at 7 T than it is at lower field strengths. Muscle BOLD imaging of muscle contractions at 7 T could, therefore, provide greater or different contrast than at 3 T. The purpose of this study was to evaluate the feasibility of using BOLD imaging at 7 T to assess the physiological responses to in vivo muscle contractions. Thirteen subjects (four females) performed a series of isometric contractions of the calf muscles while being scanned in a Philips Achieva 7 T human imager. Following 2 s maximal isometric plantarflexion contractions, BOLD signal transients ranging from 0.3 to 7.0% of the pre‐contraction signal intensity were observed in the soleus muscle. We observed considerable inter‐subject variability in both the magnitude and time course of the muscle BOLD signal. A subset of subjects (n = 7) repeated the contraction protocol at two different repetition times (T_R: 1000 and 2500 ms) to determine the potential of T₁‐related inflow effects on the magnitude of the post‐contractile BOLD response. Consistent with previous reports, there was no difference in the magnitude of the responses for the two T_R values (3.8 ± 0.9 versus 4.0 ± 0.6% for T_R = 1000 and 2500 ms, respectively; mean ± standard error). These results demonstrate that studies of the muscle BOLD responses to contractions are feasible at 7 T. Compared with studies at lower field strengths, post‐contractile 7 T muscle BOLD contrast may afford greater insight into microvascular function and dysfunction.     

Asymmetric spin‐echo (ASE) spiral improves BOLD fMRI in inhomogeneous regions

Functional MRI (fMRI) is of limited use in areas such as the orbitofrontal and inferior temporal lobes due to the presence of local susceptibility‐induced field gradients (SFGs), which result in severe image artifacts. Several techniques have been developed to reduce these artifacts, the most common being the dual‐echo spiral sequences (spiral‐in/out and spiral‐in/in). In this study, a new multiple spiral acquisition technique was developed, in which the later spiral acquisitions are acquired asymmetrically with the peak of a spin‐echo causing increased R₂‐weighting but matched R₂′‐weighting. This sequence, called asymmetric spin‐echo (ASE) spiral, has demonstrated significant improvements in minimizing the signal loss and increasing the image quality as well as optimal blood‐oxygen‐level‐dependent (BOLD)‐weighting. The ASE spiral is compared to conventional spiral‐out using both signal‐to‐noise ratio (SNR) and whole brain fMRI activation volumes from a breath‐hold task acquired at 4 Tesla. The ASE dual spiral has exhibited SNR increases of up to 300% in areas where strong SFGs are present. As a result, the ASE spiral is highly efficient for recovering lost activation in areas of SFGs, as demonstrated by a 16% increase in the total number of activated voxels over the whole brain. Post spin‐echo ASE spiral images have decreasing SNR due to R₂ signal losses, however the increase in R₂‐weighting leads to a higher percentage of signal changes producing ASE spiral images with equivalent contrast‐to‐noise ratio (CNR) for each echo. The use of this sequence allows for recovery of BOLD activation in areas of SFG without sacrificing the CNR over the whole brain. Copyright © 2009 John Wiley & Sons, Ltd.     

Probing metabolite diffusion at ultra‐short time scales in the mouse brain using optimized oscillating gradients and “short”‐echo‐time diffusion‐weighted MRS

Measuring diffusion at ultra‐short time scales may yield information about short‐range intracellular structure and cytosol viscosity. However, reaching such time scales usually requires oscillating gradients, which in turn imply long echo times T_E. Here we propose a new kind of stretched oscillating gradient that allows us to increase diffusion‐weighting b while preserving spectral and temporal properties of the gradient modulation. We used these optimized gradients to measure metabolite diffusion in the mouse brain down to effective diffusion times of 1 ms while keeping T_E relatively short (60 ms). At such T_E, a significant macromolecule signal could still be observed and used as an internal reference of approximately null diffusivity, which proved critical to discard datasets corrupted by some motion artifact. The methods introduced here may be useful to improve the accuracy and precision of metabolite apparent diffusion coefficient measurements with oscillating gradients.     

Multiple‐echo diffusion tensor acquisition technique (MEDITATE) on a 3T clinical scanner

This article describes the concepts and implementation of an MRI method, the multiple‐echo diffusion tensor acquisition technique (MEDITATE), which is capable of acquiring apparent diffusion tensor maps in two scans on a 3T clinical scanner. In each MEDITATE scan, a set of RF pulses generates multiple echoes, the amplitudes of which are diffusion weighted in both magnitude and direction by a pattern of diffusion gradients. As a result, two scans acquired with different diffusion weighting strengths suffice for accurate estimation of diffusion tensor imaging (DTI) parameters. The MEDITATE variation presented here expands previous MEDITATE approaches to adapt to the clinical scanner platform, such as exploiting longitudinal magnetization storage to reduce T₂ weighting. Fully segmented multi‐shot Cartesian encoding is used for image encoding. MEDITATE was tested on isotropic (agar gel), anisotropic diffusion phantoms (asparagus) and in vivo skeletal muscle in healthy volunteers with cardiac gating. Comparisons of accuracy were performed with standard twice‐refocused spin echo (TRSE) DTI in each case and good quantitative agreement was found between diffusion eigenvalues, mean diffusivity and fractional anisotropy derived from TRSE DTI and from the MEDITATE sequence. Orientation patterns were correctly reproduced in both isotropic and anisotropic phantoms, and approximately for in vivo imaging. This illustrates that the MEDITATE method of compressed diffusion encoding is feasible on the clinical scanner platform. With future development and employment of appropriate view‐sharing image encoding, this technique may be used in clinical applications requiring time‐sensitive acquisition of DTI parameters such as dynamical DTI in muscle. Copyright © 2013 John Wiley & Sons, Ltd.     

Diffusion‐prepared stimulated‐echo turbo spin echo (DPsti‐TSE): An eddy current‐insensitive sequence for three‐dimensional high‐resolution and undistorted diffusion‐weighted imaging

In this study, we present a new three‐dimensional (3D), diffusion‐prepared turbo spin echo sequence based on a stimulated‐echo read‐out (DPsti‐TSE) enabling high‐resolution and undistorted diffusion‐weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti‐TSE and diffusion‐weighted echo planar imaging (DW‐EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High‐resolution and undistorted DPsti‐TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole‐prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10^?3 versus (1.60 ± 0.02) × 10^?3 mm²/s]. High‐resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10^?3 mm²/s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti‐TSE can serve as a robust 3D diffusion‐weighted sequence and is an attractive alternative to the traditional two‐dimensional DW‐EPI approaches.     

Implementation of spin‐echo blood oxygen level‐dependent (BOLD) functional MRI in birds

The advent of high‐field MRI systems has allowed the implementation of blood oxygen level‐dependent functional MRI (BOLD fMRI) on small animals. An increased magnetic field improves the signal‐to‐noise ratio and thus allows an improvement in the spatial resolution. However, it also increases susceptibility artefacts in the commonly acquired gradient‐echo images. This problem is particularly prominent in songbird MRI because of the presence of numerous air cavities in the skull of birds. These T₂*‐related image artefacts can be circumvented using spin‐echo BOLD fMRI. In this article, we describe the implementation of spin‐echo BOLD fMRI in zebra finches, a small songbird of 15–25 g, extensively studied in the behavioural neurosciences of birdsong. Because the main topics in this research domain are song perception and song learning, the protocol implemented used auditory stimuli. Despite the auditory nature of the stimuli and the weak contrast‐to‐noise ratio of spin‐echo BOLD fMRI compared with gradient‐echo BOLD fMRI, we succeeded in detecting statistically significant differences in BOLD responses triggered by different stimuli. This study shows that spin‐echo BOLD fMRI is a viable approach for the investigation of auditory processing in the whole brain of small songbirds. It can also be applied to study auditory processing in other small animals, as well as other sensory modalities. Copyright © 2010 John Wiley & Sons, Ltd.     

Three‐dimensional ultrashort echo time cones T1ρ (3D UTE‐cones‐T1ρ) imaging

We report a novel three‐dimensional (3D) ultrashort echo time (UTE) sequence employing Cones trajectory and T_1ρ preparation (UTE‐Cones‐T_1ρ) for quantitative T_1ρ assessment of short T₂ tissues in the musculoskeletal system. A basic 3D UTE‐Cones sequence was combined with a spin‐locking preparation pulse for T_1ρ contrast. A relatively short TR was used to decrease the scan time, which required T₁ measurement and compensation using 3D UTE‐Cones data acquisitions with variable TRs. Another strategy to reduce the total scan time was to acquire multiple Cones spokes (N_sp) after each T_1ρ preparation and fat saturation. Four spin‐locking times (TSL = 0–20 ms) were acquired over 12 min, plus another 7 min for T₁ measurement. The 3D UTE‐Cones‐T_1ρ sequence was compared with a two‐dimensional (2D) spiral‐T_1ρ sequence for the imaging of a spherical CuSO₄ phantom and ex vivo meniscus and tendon specimens, as well as the knee and ankle joints of healthy volunteers, using a clinical 3‐T scanner. The CuSO₄ phantom showed a T_1ρ value of 76.5 ± 1.6 ms with the 2D spiral‐T_1ρ sequence, as well as 85.7 ± 3.6 and 89.2 ± 1.4 ms for the 3D UTE‐Cones‐T_1ρ sequences with N_sp of 1 and 5, respectively. The 3D UTE‐Cones‐T_1ρ sequence provided shorter T_1ρ values for the bovine meniscus sample relative to the 2D spiral‐T_1ρ sequence (10–12 ms versus 16 ms, respectively). The cadaveric human Achilles tendon sample could only be imaged with the 3D UTE‐Cones‐T_1ρ sequence (T_1ρ = 4.0 ± 0.9 ms), with the 2D spiral‐T_1ρ sequence demonstrating near‐zero signal intensity. Human studies yielded T_1ρ values of 36.1 ± 2.9, 18.3 ± 3.9 and 3.1 ± 0.4 ms for articular cartilage, meniscus and the Achilles tendon, respectively. The 3D UTE‐Cones‐T_1ρ sequence allows volumetric T_1ρ measurement of short T₂ tissues in vivo.     

In vivo GABA T2 determination with J‐refocused echo time extension at 7 T

A method to measure the T₂ relaxation time of GABA with spectral editing techniques is proposed. Spectral editing techniques can be used to unambiguously extract signals of low concentration J‐coupled spins such as γ‐aminobutyric acid (GABA) from overlapping resonances such as creatine and macromolecules. These sequences, however, generally have fixed and relatively long echo times. Therefore, for the absolute quantification of the edited spectrum, the T₂ relaxation time must be taken into account. To measure the T₂ relaxation time, the signal intensity has to be obtained at multiple echo times. However, on a coupled spin system such as GABA this is challenging, since the signal intensity of the target resonances is modulated not only by T₂ decay but also by the J‐coupling, which strongly influences the shapes and amplitudes of the edited signals, depending on the echo time. Here, we propose to refocus the J‐modulation of the edited signal at different echo times by using chemical shift selective refocusing. In this way the echo time can be arbitrarily extended while preserving the shape of the edited signal. The method was applied in combination with the MEGA‐sLASER editing technique to measure the in vivo T₂ relaxation time of GABA (87 ± 11 ms, n = 10) and creatine (109 ± 8 ms, n = 10) at 7 T. The T₁ relaxation time of these metabolites in a single subject was also determined (GABA, 1334 ± 158 ms; Cr, 1753 ± 12 ms). The T₂ decay curve of coupled spin systems can be sampled in an arbitrary fashion without the need for signal shape correction. Furthermore, the method can be applied with any spectral editing technique. The shortest echo time of the method is limited by the echo time of the spectral editing technique. Copyright © 2013 John Wiley & Sons, Ltd.     

Evaluation of normal cadaveric Achilles tendon and enthesis with ultrashort echo time (UTE) magnetic resonance imaging and indentation testing

Entheses are regions where tendons and ligaments attach to bone, and are the primary target in seronegative and other diseases of the musculoskeletal (MSK) system. MRI has been widely used for visualizing features of inflammatory and degenerative MSK disease; however, normal tendons and entheses have short transverse relaxation times (T₂), and show little or no signal with conventional clinical MRI pulse sequences, making it difficult to investigate their MR properties. In this study we examined the normal MR morphology of the cadaveric Achilles tendon and enthesis at 3 T using novel three‐dimensional ultrashort echo time (3D UTE) Cones sequences, and at 11.7 T using conventional MRI sequences. We also studied the MR properties of the Achilles tendon and enthesis including T₂*, T₁, and magnetization transfer ratio (MTR). In addition, MT modeling of macromolecular proton fractions was investigated using 3D UTE Cones sequences at 3 T. Indentation testing was performed to investigate the mechanical properties of the tendons and entheses, and this was followed by histological examination. In total five specimens (<50 years) were investigated. On average, tendons and entheses respectively had T₂* values of 0.93 ± 0.48 ms and 2.77 ± 0.79 ms, T₁ values of 644 ± 22 ms and 780 ± 55 ms, MTRs of 0.373 ± 0.03 and 0.244 ± 0.009 with an MT power of 1000° and frequency offset of 2 kHz, and macromolecular proton fractions of 18.0 ± 2.2% and 13.9 ± 1.9%. Compared with the tendon, the enthesis generally had a longer T₂*, a longer T₁, a lower MTR, and a lower macromolecular proton fraction as well as both a higher Young's modulus and stiffness. Results from this study are likely to provide a useful baseline for identifying deviations from the normal in seronegative arthritis and other disease of the entheses.     

Bi‐exponential 23Na T2* component analysis in the human brain

The purpose of this study was to measure the sodium transverse relaxation time T₂* in the healthy human brain. Five healthy subjects were scanned with 18 echo times (TEs) as short as 0.17 ms. T₂* values were fitted on a voxel‐by‐voxel basis using a bi‐exponential model. Data were also analysed using a continuous distribution fit with a region of interest‐based inverse Laplace transform. Average T₂* values were 3.4 ± 0.2 ms and 23.5 ± 1.8 ms in white matter (WM) for the short and long components, respectively, and 3.9 ± 0.5 ms and 26.3 ± 2.6 ms in grey matter (GM) for the short and long components, respectively, using the bi‐exponential model. Continuous distribution fits yielded results of 3.1 ± 0.3 ms and 18.8 ± 3.2 ms in WM for the short and long components, respectively, and 2.9 ± 0.4 ms and 17.2 ± 2 ms in GM for the short and long components, respectively. ²³Na T₂* values of the brain for the short and long components for various anatomical locations using ultra‐short TEs are presented for the first time.     

Fast low‐angle shot diffusion tensor imaging with stimulated echo encoding in the muscle of rabbit shank

In the past, spin‐echo (SE) echo planar imaging(EPI)‐based diffusion tensor imaging (DTI) has been widely used to study the fiber structure of skeletal muscles in vivo. However, this sequence has several shortcomings when measuring restricted diffusion in small animals, such as its sensitivity to susceptibility‐related distortions and a relatively short applicable diffusion time. To address these limitations, in the current work, a stimulated echo acquisition mode (STEAM) MRI technique, in combination with fast low‐angle shot (FLASH) readout (turbo‐STEAM MRI), was implemented and adjusted for DTI in skeletal muscles. Signal preparation using stimulated echoes enables longer effective diffusion times, and thus the detection of restricted diffusion within muscular tissue with intracellular distances up to 100 µm. Furthermore, it has a reduced penalty for fast T₂ muscle signal decay, but at the expense of 50% signal loss compared with a SE preparation. Turbo‐STEAM MRI facilitates high‐resolution DTI of skeletal muscle without introducing susceptibility‐related distortions. To demonstrate its applicability, we carried out rabbit in vivo measurements on a human whole‐body 3 T scanner. DTI parameters of the shank muscles were extracted, including the apparent diffusion coefficient, fractional anisotropy, eigenvalues and eigenvectors. Eigenvectors were used to calculate maps of structural parameters, such as the planar index and the polar coordinates θ and ? of the largest eigenvector. These parameters were compared between three muscles. θ and ? showed clear differences between the three muscles, reflecting different pennation angles of the underlying fiber structures. Fiber tractography was performed to visualize and analyze the architecture of skeletal pennate muscles. Optimization of tracking parameters and utilization of T₂‐weighted images for improved muscle boundary detection enabled the determination of additional parameters, such as the mean fiber length. The presented results support the applicability of turbo‐STEAM MRI as a promising method for quantitative DTI analysis and fiber tractography in skeletal muscles. Copyright © 2013 John Wiley & Sons, Ltd.     

Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2O exchange study

Inversion recovery ultrashort echo time (IR‐UTE) imaging holds the potential to directly characterize MR signals from ultrashort T₂ tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR‐UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T₂* signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D₂O exchange model and explored the potential of IR‐UTE imaging for the quantification of ultrashort T₂* signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D₂O. Long T₂ MR signals were measured using a clinical proton density‐weighted fast spin echo (PD‐FSE) sequence. IR‐UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T₂ signals (TI_null). Then, at this TI_null, images with echo times (TEs) of 0.01–4 ms were acquired to measure the T₂* values of STCs. The PD‐FSE signal dropped to near zero after 24 h of immersion in D₂O. A wide range of TI_null values were used at different time points (240–330 ms for white matter and 320–350 ms for gray matter at TR = 1000 ms) because the T₁ values of the long T₂ tissue components changed significantly. The T₂* values of STCs were 200–300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D₂O or H₂O), and showed minimal changes after sequential immersion. The ultrashort T₂* signals seen on IR‐UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D₂O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.     

Feasibility of quantitative ultrashort echo time (UTE)‐based methods for MRI of peripheral nerve

Peripheral nerves are a composite tissue consisting of neurovascular elements packaged within a well‐organized extracellular matrix. Their composition, size, and anatomy render nerves a challenging medical imaging target. In contrast to morphological MRI, which represents the predominant approach to nerve imaging, quantitative MRI sequences can provide information regarding tissue composition. Here, we applied standard clinical Carr‐Purcell‐Meiboom‐Gill (CPMG) and experimental three‐dimensional (3D) ultrashort echo time (UTE) Cones sequences for quantitative nerve imaging including T₂ measurement with single‐component analysis, T₂* measurement with single‐component and bi‐component analyses, and magnetization transfer ratio (MTR) analysis. We demonstrated the feasibility and the high quality of single‐component T₂*, bi‐component T₂*, and MTR approaches to analyze nerves imaged with clinically deployed 3D UTE Cones pulse sequences. For 24 single fascicles from eight nerves, we measured a mean single‐component T₂* of 22.6 ±8.9 ms, and a short T₂* component (STC) with a mean T₂* of 1.7 ±1.0 ms and a mean fraction of (6.74 ±4.31)% in bi‐component analysis. For eight whole nerves, we measured a mean single‐component T₂* of 16.7 ±2.2 ms, and an STC with a mean T₂* of 3.0 ±1.0 ms and a mean fraction of (15.56 ±7.07)% in bi‐component analysis. For nine fascicles from three healthy nerves, we measured a mean MTR of (25.2 ±1.9)% for single fascicles and a mean MTR of (23.6 ±0.9)% for whole nerves. No statistically significant correlation was observed between any MRI parameter and routine histological outcomes, perhaps due to the small sample size and lack of apparent sample pathology. Overall, we have successfully demonstrated the feasibility of measuring quantitative MR outcomes ex vivo, which might reflect features of nerve structure and macromolecular content. These methods should be validated comprehensively on a larger and more diverse set of nerve samples, towards the interpretation of in vivo outcomes. These approaches have new and broad implications for the management of nerve disease, injury, and repair.     

Three‐dimensional echo planar spectroscopic imaging for differentiation of true progression from pseudoprogression in patients with glioblastoma

Accurate differentiation of true progression (TP) from pseudoprogression (PsP) in patients with glioblastomas (GBMs) is essential for planning adequate treatment and for estimating clinical outcome measures and future prognosis. The purpose of this study was to investigate the utility of three‐dimensional echo planar spectroscopic imaging (3D‐EPSI) in distinguishing TP from PsP in GBM patients. For this institutional review board approved and HIPAA compliant retrospective study, 27 patients with GBM demonstrating enhancing lesions within six months of completion of concurrent chemo‐radiation therapy were included. Of these, 18 were subsequently classified as TP and 9 as PsP based on histological features or follow‐up MRI studies. Parametric maps of choline/creatine (Cho/Cr) and choline/N‐acetylaspartate (Cho/NAA) were computed and co‐registered with post‐contrast T₁‐weighted and FLAIR images. All lesions were segmented into contrast enhancing (CER), immediate peritumoral (IPR), and distal peritumoral (DPR) regions. For each region, Cho/Cr and Cho/NAA ratios were normalized to corresponding metabolite ratios from contralateral normal parenchyma and compared between TP and PsP groups. Logistic regression analyses were performed to obtain the best model to distinguish TP from PsP. Significantly higher Cho/NAA was observed from CER (2.69 ± 1.00 versus 1.56 ± 0.51, p = 0.003), IPR (2.31 ± 0.92 versus 1.53 ± 0.56, p = 0.030), and DPR (1.80 ± 0.68 versus 1.19 ± 0.28, p = 0.035) regions in TP patients compared with those with PsP. Additionally, significantly elevated Cho/Cr (1.74 ± 0.44 versus 1.34 ± 0.26, p = 0.023) from CER was observed in TP compared with PsP. When these parameters were incorporated in multivariate regression analyses, a discriminatory model with a sensitivity of 94% and a specificity of 87% was observed in distinguishing TP from PsP. These results indicate the utility of 3D‐EPSI in differentiating TP from PsP with high sensitivity and specificity.     

Characterization of the response of taurine protons to PRESS at 9.4 T for Resolving choline and Determining taurine T2

Point‐resolved spectroscopy (PRESS), characterized by two TEs (TE₁ and TE₂), can be employed to perform animal magnetic resonance spectroscopy (MRS) studies at 9.4 T. Taurine (Tau) and choline (Cho) are relevant metabolites that can be measured by MRS. In this work, the response of the J‐coupled protons of Tau as a function of PRESS TE₁ and TE₂ was characterized at 9.4 T to achieve two objectives. The first was to determine two TE₁ and TE₂ combinations that could be used to obtain T₂‐corrected measures of Tau (3.42 ppm) that were minimally influenced by J coupling. The second was to exploit the Tau J coupling to find a timing combination that minimized the 3.25‐ppm Tau signal to enable the Cho (3.22 ppm) resonance to be resolved from the overlapping Tau signal. The response of Tau protons was investigated both numerically and experimentally. It was numerically determined that the timings {TE₁, TE₂} = {17 ms, 10 ms} and {TE₁, TE₂} = {80 ms, 70 ms} yielded similar 3.42‐ppm Tau resonance areas (5% difference), rendering them suitable for Tau T₂ determination. {TE₁, TE₂} = {25 ms, 50 ms} was found to yield minimal 3.25‐ppm Tau signal, reducing its interference with Cho. The efficacy of the timings was demonstrated on phantom solutions and in vivo in four Sprague Dawley rats. LCModel was employed to analyse the in vivo spectra and Tau T₂ values were estimated by fitting the Tau peak areas obtained with {TE₁, TE₂} = {17 ms, 10 ms} and {TE₁, TE₂} = {80 ms, 70 ms} to a monoexponentially decaying function. An average Tau T₂ of 106 ms (standard deviation, 12 ms) was obtained. LCModel analysis of rat spectra obtained with {TE₁, TE₂} = {25 ms, 50 ms} demonstrated negligible levels of Tau signal, compared with that obtained with short TE.     

Rapid multi‐echo measurement of brain metabolite T2 values at 7 T using a single‐shot spectroscopic Carr–Purcell–Meiboom–Gill sequence and prior information

We present a method for the robust and accurate estimation of brain metabolite transverse relaxation times (T₂) from multiple spin‐echo data acquired with a single‐shot Carr–Purcell–Meiboom–Gill (CPMG) spectroscopic sequence. Each acquired echo consists of a small number of complex time‐domain data points. The amplitudes of the spectral components in each echo are calculated by solving a set of linear equations in which previously estimated frequencies and linewidths serve as prior information. These priors are obtained from a short MRS experiment in which a large number of time‐domain data points are acquired, and are subsequently estimated using linear prediction with singular value decomposition (LPSVD) processing. We show that this process can be used to accurately and rapidly measure the T₂ values for the main singlet resonances in single‐volume MRS measurements in the brain. The proposed method can be generalized to any set of MRS experiments comprising repeated measurements of amplitude changes, e.g. as a function of an experimental parameter, such as TE, inversion time or diffusion weighting. Copyright © 2013 John Wiley & Sons, Ltd.