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.     

Simultaneous multi‐slice spin‐ and gradient‐echo dynamic susceptibility‐contrast perfusion‐weighted MRI of gliomas

Although combined spin‐ and gradient‐echo (SAGE) dynamic susceptibility‐contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T₁‐shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo‐planar imaging (EPI) sequence with simultaneous multi‐slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi‐band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR₂*(t) and ΔR₂(t) curves were derived to calculate dynamic signal‐to‐noise ratio (dSNR), ΔR₂*‐ and ΔR₂‐based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal‐appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal‐appearing gray matter were not statistically significant between the two protocols. ΔR₂*‐ and ΔR₂‐rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.     

High‐sensitivity cerebral perfusion mapping in mice by kbGRASE‐FAIR at 9.4 T

The combination of flow‐sensitive alternating inversion recovery (FAIR) and single‐shot k‐space‐banded gradient‐ and spin‐echo (kbGRASE) is proposed here to measure perfusion in the mouse brain with high sensitivity and stability. Signal‐to‐noise ratio (SNR) analysis showed that kbGRASE‐FAIR boosts image and temporal SNRs by 2.01 ± 0.08 and 2.50 ± 0.07 times, respectively, when compared with standard single‐shot echo planar imaging (EPI)‐FAIR implemented in our experimental systems, although the practically achievable spatial resolution was slightly reduced. The effects of varying physiological parameters on the precision and reproducibility of cerebral blood flow (CBF) measurements were studied following changes in anesthesia regime, capnia and body temperature. The functional MRI time courses with kbGRASE‐FAIR showed a more stable response to 5% CO₂ than did those with EPI‐FAIR. The results establish kbGRASE‐FAIR as a practical and robust protocol for quantitative CBF measurements in mice at 9.4 T. Copyright © 2010 John Wiley & Sons, Ltd.     

Cerebrovascular MRI: a review of state‐of‐the‐art approaches,methods and techniques

Cerebrovascular imaging is of great interest in the understanding of neurological disease. MRI is a non‐invasive technology that can visualize and provide information on: (i) the structure of major blood vessels; (ii) the blood flow velocity in these vessels; and (iii) the microcirculation, including the assessment of brain perfusion. Although other medical imaging modalities can also interrogate the cerebrovascular system, MR provides a comprehensive assessment, as it can acquire many different structural and functional image contrasts whilst maintaining a high level of patient comfort and acceptance. The extent of examination is limited only by the practicalities of patient tolerance or clinical scheduling limitations. Currently, MRI methods can provide a range of metrics related to the cerebral vasculature, including: (i) major vessel anatomy via time‐of‐flight and contrast‐enhanced imaging; (ii) blood flow velocity via phase contrast imaging; (iii) major vessel anatomy and tissue perfusion via arterial spin labeling and dynamic bolus passage approaches; and (iv) venography via susceptibility‐based imaging. When designing an MRI protocol for patients with suspected cerebral vascular abnormalities, it is appropriate to have a complete understanding of when to use each of the available techniques in the ‘MR angiography toolkit’. In this review article, we: (i) overview the relevant anatomy, common pathologies and alternative imaging modalities; (ii) describe the physical principles and implementations of the above listed methods; (iii) provide guidance on the selection of acquisition parameters; and (iv) describe the existing and potential applications of MRI to the cerebral vasculature and diseases. The focus of this review is on obtaining an understanding through the application of advanced MRI methodology of both normal and abnormal blood flow in the cerebrovascular arteries, capillaries and veins. Copyright © 2015 John Wiley & Sons, Ltd.     

Pushing the limits of high‐resolution functional MRI using a simple high‐density multi‐element coil design

Recent studies have shown that functional MRI (fMRI) can be sensitive to the laminar and columnar organization of the cortex based on differences in the spatial and temporal characteristics of the blood oxygenation level‐dependent (BOLD) signal originating from the macrovasculature and the neuronal‐specific microvasculature. Human fMRI studies at this scale of the cortical architecture, however, are very rare because the high spatial/temporal resolution required to explore these properties of the BOLD signal are limited by the signal‐to‐noise ratio. Here, we show that it is possible to detect BOLD signal changes at an isotropic spatial resolution as high as 0.55 mm at 7 T using a high‐density multi‐element surface coil with minimal electronics, which allows close proximity to the head. The coil comprises of very small, 1 × 2‐cm², elements arranged in four flexible modules of four elements each (16‐channel) that can be positioned within 1 mm from the head. As a result of this proximity, tissue losses were five‐fold greater than coil losses and sufficient to exclude preamplifier decoupling. When compared with a standard 16‐channel head coil, the BOLD sensitivity was approximately 2.2‐fold higher for a high spatial/temporal resolution (1 mm isotropic/0.4 s), multi‐slice, echo planar acquisition, and approximately three‐ and six‐fold higher for three‐dimensional echo planar images acquired with isotropic resolutions of 0.7 and 0.55 mm, respectively. Improvements in parallel imaging performance (geometry factor) were up to around 1.5‐fold with increasing acceleration factor, and improvements in fMRI detectability (temporal signal‐to‐noise ratio) were up to around four‐fold depending on the distance to the coil. Although deeper lying structures may not benefit from the design, most fMRI questions pertain to the neocortex which lies within approximately 4 cm from the surface. These results suggest that the resolution of fMRI (at 7 T) can approximate levels that are closer to the spatial/temporal scale of the fundamental functional organization of the human cortex using a simple high‐density coil design for high sensitivity. Copyright © 2012 John Wiley & Sons, Ltd.     

Transit time mapping in the mouse brain using time‐encoded pCASL

The cerebral blood flow (CBF) is a potential biomarker for neurological disease. However, the arterial transit time (ATT) of the labeled blood is known to potentially affect CBF quantification. Furthermore, ATT could be an interesting biomarker in itself, as it may reflect underlying macro‐ and microvascular pathologies. Currently, no optimized magnetic resonance imaging (MRI) sequence exists to measure ATT in mice. Recently, time‐encoded labeling schemes have been implemented in rats and humans, enabling ATT mapping with higher signal‐to‐noise ratio (SNR) and shorter scan time than multi‐delay arterial spin labeling (ASL). In this study, we show that time‐encoded pseudo‐continuous arterial spin labeling (te‐pCASL) also enables transit time measurements in mice. As an optimal design that takes the fast blood flow in mice into account, time encoding with 11 sub‐boli of 50 ms is proposed to accurately probe the inflow of labeled blood. For perfusion imaging, a separate, traditional pCASL scan was employed. From the six studied brain regions, the hippocampus showed the shortest ATT (169 ± 11 ms) and the auditory/visual cortex showed the longest (284 ± 16 ms). Furthermore, ATT was found to be preserved in old wild‐type mice. In a mouse with an induced carotid artery occlusion, prolongation of ATT was shown. In conclusion, this study shows the successful implementation of te‐pCASL in mice, making it possible, for the first time, to measure ATT in mice in a time‐efficient manner.     

The capability of detecting small vessels beyond the conventional MRI sensitivity using iron‐based contrast agent enhanced susceptibility weighted imaging

Imaging brain microvasculature is important in cerebrovascular diseases. However, there is still a lack of non‐invasive, non‐radiation, and whole‐body imaging techniques to investigate them. The aim of this study is to develop an ultra‐small superparamagnetic iron oxide (USPIO) enhanced susceptibility weighted imaging (SWI) method for imaging micro‐vasculature in both animal (~10 μm in rat) and human brain. We hypothesized that the USPIO‐SWI technique could improve the detection sensitivity of the diameter of small subpixel vessels 10‐fold compared with conventional MRI methods. Computer simulations were first performed with a double‐cylinder digital model to investigate the theoretical basis for this hypothesis. The theoretical results were verified using in vitro phantom studies and in vivo rat MRI studies (n = 6) with corresponding ex vivo histological examinations. Additionally, in vivo human studies (n = 3) were carried out to demonstrate the translational power of the USPIO‐SWI method. By directly comparing the small vessel diameters of an in vivo rat using USPIO‐SWI with the small vessel diameters of the corresponding histological slide using laser scanning confocal microscopy, 13.3‐fold and 19.9‐fold increases in SWI apparent diameter were obtained with 5.6 mg Fe/kg and 16.8 mg Fe/kg ferumoxytol, respectively. The USPIO‐SWI method exhibited its excellent ability to detect small vessels down to about 10 μm diameter in rat brain. The in vivo human study unveiled hidden arterioles and venules and demonstrated its potential in clinical practice. Theoretical modeling simulations and in vitro phantom studies also confirmed a more than 10‐fold increase in the USPIO‐SWI apparent diameter compared with the actual small vessel diameter size. It is feasible to use SWI blooming effects induced by USPIO to detect small vessels (down to 10 μm in diameter for rat brain), well beyond the spatial resolution limit of conventional MRI methods. The USPIO‐SWI method demonstrates higher potential in cerebrovascular disease investigations.     

Multiband diffusion‐weighted MRI of the eye and orbit free of geometric distortions using a RARE‐EPI hybrid

Diffusion‐weighted imaging (DWI) provides information on tissue microstructure. Single‐shot echo planar imaging (EPI) is the most common technique for DWI applications in the brain, but is prone to geometric distortions and signal voids. Rapid acquisition with relaxation enhancement [RARE, also known as fast spin echo (FSE)] imaging presents a valuable alternative to DWI with high anatomical accuracy. This work proposes a multi‐shot diffusion‐weighted RARE‐EPI hybrid pulse sequence, combining the anatomical integrity of RARE with the imaging speed and radiofrequency (RF) power deposition advantage of EPI. The anatomical integrity of RARE‐EPI was demonstrated and quantified by center of gravity analysis for both morphological images and diffusion‐weighted acquisitions in phantom and in vivo experiments at 3.0 T and 7.0 T. The results indicate that half of the RARE echoes in the echo train can be replaced by EPI echoes whilst maintaining anatomical accuracy. The reduced RF power deposition of RARE‐EPI enabled multiband RF pulses facilitating simultaneous multi‐slice imaging. This study shows that diffusion‐weighted RARE‐EPI has the capability to acquire high fidelity, distortion‐free images of the eye and the orbit. It is shown that RARE‐EPI maintains the immunity to B₀ inhomogeneities reported for RARE imaging. This benefit can be exploited for the assessment of ocular masses and pathological changes of the eye and the orbit.     

Three‐dimensional inversion recovery manganese‐enhanced MRI of mouse brain using super‐resolution reconstruction to visualize nuclei involved in higher brain function

The visualization of activity in mouse brain using inversion recovery spin echo (IR‐SE) manganese‐enhanced MRI (MEMRI) provides unique contrast, but suffers from poor resolution in the slice‐encoding direction. Super‐resolution reconstruction (SRR) is a resolution‐enhancing post‐processing technique in which multiple low‐resolution slice stacks are combined into a single volume of high isotropic resolution using computational methods. In this study, we investigated, first, whether SRR can improve the three‐dimensional resolution of IR‐SE MEMRI in the slice selection direction, whilst maintaining or improving the contrast‐to‐noise ratio of the two‐dimensional slice stacks. Second, the contrast‐to‐noise ratio of SRR IR‐SE MEMRI was compared with a conventional three‐dimensional gradient echo (GE) acquisition. Quantitative experiments were performed on a phantom containing compartments of various manganese concentrations. The results showed that, with comparable scan times, the signal‐to‐noise ratio of three‐dimensional GE acquisition is higher than that of SRR IR‐SE MEMRI. However, the contrast‐to‐noise ratio between different compartments can be superior with SRR IR‐SE MEMRI, depending on the chosen inversion time. In vivo experiments were performed in mice receiving manganese using an implanted osmotic pump. The results showed that SRR works well as a resolution‐enhancing technique in IR‐SE MEMRI experiments. In addition, the SRR image also shows a number of brain structures that are more clearly discernible from the surrounding tissues than in three‐dimensional GE acquisition, including a number of nuclei with specific higher brain functions, such as memory, stress, anxiety and reward behavior. Copyright © 2014 John Wiley & Sons, Ltd.     

SPECT显像在NPC放疗后所致脑损伤中的初步应用

目的 评价单光子发射型电子计算机断层（ＳＰＥＣＴ）脑血流灌注显像在鼻咽癌（ＮＰＣ）放射治疗后放射性脑损伤中的临床价值。方法 采用ＳＰＥＣＴ脑血流灌注显像检查,对１６例鼻咽癌放射治疗后有放射性脑损伤症状的患者和８例示经放疗的鼻咽癌患者作半定时分析对测量结果作统计学分析。１６例放射性脑损伤患者同期做电子计算机体层检查（ＣＴ）对比。结果 １６例有放射性脑损伤症状的鼻咽癌患者双侧颞叶局部脑血流灌注（ｒＣＢＦ）在横断面层面－放射性曲线相应部位上可见局部放射性下降峰或曲线变窄小,峰值降低,其曲线局部下降峰值与鼻咽癌放疗效量的生物效应剂量（ＢＥＤ）值呈正相关（ｒ＝０．８９７６,Ｐ〈０．０１）。８例未经放疗的鼻咽癌患者,在横断面图像上其双侧颞叶局部脑血流灌注的层面－放射性曲线大致呈正态分布曲线,未见异常的局部下降峰或曲线变窄小     

Time‐efficient measurement of multi‐phase arterial spin labeling MR signal in white matter

White matter (WM) perfusion has great potential as a physiological biomarker in many neurological diseases. Although it has been demonstrated previously that arterial spin labeling magnetic resonance imaging (ASL‐MRI) enables the detection of the perfusion‐weighted signal in most voxels in WM, studies of cerebral blood flow (CBF) in WM by ASL‐MRI are relatively scarce because of its particular challenges, such as significantly lower perfusion and longer arterial transit times relative to gray matter (GM). Recently, ASL with a spectroscopic readout has been proposed to enhance the sensitivity for the measurement of WM perfusion. However, this approach suffers from long acquisition times, especially when acquiring multi‐phase ASL datasets to improve CBF quantification. Furthermore, the potential increase in the signal‐to‐noise ratio (SNR) by spectroscopic readout compared with echo planar imaging (EPI) readout has not been proven experimentally. In this study, we propose the use of time‐encoded pseudo‐continuous ASL (te‐pCASL) with single‐voxel point‐resolved spectroscopy (PRESS) readout to quantify WM cerebral perfusion in a more time‐efficient manner. Results are compared with te‐pCASL with a conventional EPI readout for both WM and GM perfusion measurements. Perfusion measurements by te‐pCASL PRESS and conventional EPI showed no significant difference for quantitative WM CBF values (Student's t‐test, p = 0.19) or temporal SNR (p = 0.33 and p = 0.81 for GM and WM, respectively), whereas GM CBF values (p = 0.016) were higher using PRESS than EPI readout. WM CBF values were found to be 18.2 ± 7.6 mL/100 g/min (PRESS) and 12.5 ± 5.5 mL/100 g/min (EPI), whereas GM CBF values were found to be 77.1 ± 11.2 mL/100 g/min (PRESS) and 53.6 ± 9.6 mL/100 g/min (EPI). This study demonstrates the feasibility of te‐pCASL PRESS for the quantification of WM perfusion changes in a highly time‐efficient manner, but it does not result in improved temporal SNR, as does traditional te‐pCASL EPI, which remains the preferred option because of its flexibility in use.     

Post‐ischaemic activation of kinases in the pre‐conditioning‐like cardioprotective effect of the platelet‐activating factor

Aim: Platelet‐activating factor (PAF) triggers cardiac pre‐conditioning against ischemia/reperfusion injury. The actual protection of ischaemic pre‐conditioning occurs in the reperfusion phase. Therefore, we studied in this phase the kinases involved in PAF‐induced pre‐conditioning. Methods: Langendorff‐perfused rat hearts underwent 30 min of ischaemia and 2 h of reperfusion (group 1, control). Before ischaemia, group 2 hearts were perfused for 19 min with PAF (2 × 10^?11 m ); groups 3–5 hearts were co‐infused during the initial 20 min of reperfusion, with the protein kinase C (PKC) inhibitor chelerythrine (5 × 10^?6 m ) or the phosphoinositide 3‐kinase (PI3K) inhibitor LY294002 (5 × 10^?5 m ) and atractyloside (2 × 10^?5 m ), a mitochondrial permeability transition pore (mPTP) opener respectively. Phosphorylation of PKCε, PKB/Aκt, GSK‐3β and ERK1/2 at the beginning of reperfusion was also checked. Left ventricular pressure and infarct size were determined. Results: PAF pre‐treatment reduced infarct size (33 ± 4% vs. 64 ± 5% of the area at risk of control hearts) and improved pressure recovery. PAF pre‐treatment enhanced the phosphorylation/activation of PKCε, PKB/Aκt and the phosphorylation/inactivation of GSK‐3β at reperfusion. Effects on ERK1/2 phosphorylation were not consistent. Infarct‐sparing effect and post‐ischaemic functional improvement induced by PAF pre‐treatment were abolished by post‐ischaemic infusion of either chelerythrine, LY294002 or atractyloside. Conclusions: The cardioprotective effect exerted by PAF pre‐treatment involves activation of PKC and PI3K in post‐ischaemic phases and might be mediated by the prevention of mPTP opening in reperfusion via GSK‐3β inactivation.     

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.     

A model‐based reconstruction for undersampled radial spin‐echo DTI with variational penalties on the diffusion tensor

Radial spin‐echo diffusion imaging allows motion‐robust imaging of tissues with very low T₂ values like articular cartilage with high spatial resolution and signal‐to‐noise ratio (SNR). However, in vivo measurements are challenging, due to the significantly slower data acquisition speed of spin‐echo sequences and the less efficient k‐space coverage of radial sampling, which raises the demand for accelerated protocols by means of undersampling. This work introduces a new reconstruction approach for undersampled diffusion‐tensor imaging (DTI). A model‐based reconstruction implicitly exploits redundancies in the diffusion‐weighted images by reducing the number of unknowns in the optimization problem and compressed sensing is performed directly in the target quantitative domain by imposing a total variation (TV) constraint on the elements of the diffusion tensor. Experiments were performed for an anisotropic phantom and the knee and brain of healthy volunteers (three and two volunteers, respectively). Evaluation of the new approach was conducted by comparing the results with reconstructions performed with gridding, combined parallel imaging and compressed sensing and a recently proposed model‐based approach. The experiments demonstrated improvements in terms of reduction of noise and streaking artifacts in the quantitative parameter maps, as well as a reduction of angular dispersion of the primary eigenvector when using the proposed method, without introducing systematic errors into the maps. This may enable an essential reduction of the acquisition time in radial spin‐echo diffusion‐tensor imaging without degrading parameter quantification and/or SNR. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

Improvement of accuracy of diffusion MRI using real‐time self‐gated data acquisition

Diffusion‐weighted and diffusion tensor MR imaging (DWI, DTI) techniques are generally performed with signal averaging of multiple measurements to improve the signal‐to‐noise ratio (SNR) and the accuracy of the diffusion measurement. Any discrepancy in the images between different averages causes errors which reduce the accuracy of the diffusion MRI measurements. In this report, a motion artifact reduction scheme with a real‐time self‐gated (RTSG) data acquisition for diffusion MRI using two‐dimensional echo planar imaging (2D EPI) is described. A subject's translational and rotational motions during application of the diffusion gradients induce an additional phase term and a shift of the echo‐peak position in the k‐space, respectively. These motions also reduce the magnitude of the echo‐peak. Based on these properties, we present a new scheme which monitors the position and the magnitude of the largest echo‐peak in the k‐space. The position and the magnitude of each average is compared to those of early averaging shot to determine if the differences are within or beyond the given threshold values. Motion corrupted data are reacquired in real time. Our preliminary results using RTSG indicate an improvement of both SNR and the accuracy of diffusion MRI measurements. Copyright © 2009 John Wiley & Sons, Ltd.     

Three‐dimensional whole‐brain perfusion quantification using pseudo‐continuous arterial spin labeling MRI at multiple post‐labeling delays: accounting for both arterial transit time and impulse response function

Measurement of the cerebral blood flow (CBF) with whole‐brain coverage is challenging in terms of both acquisition and quantitative analysis. In order to fit arterial spin labeling‐based perfusion kinetic curves, an empirical three‐parameter model which characterizes the effective impulse response function (IRF) is introduced, which allows the determination of CBF, the arterial transit time (ATT) and T_1,eff. The accuracy and precision of the proposed model were compared with those of more complicated models with four or five parameters through Monte Carlo simulations. Pseudo‐continuous arterial spin labeling images were acquired on a clinical 3‐T scanner in 10 normal volunteers using a three‐dimensional multi‐shot gradient and spin echo scheme at multiple post‐labeling delays to sample the kinetic curves. Voxel‐wise fitting was performed using the three‐parameter model and other models that contain two, four or five unknown parameters. For the two‐parameter model, T_1,eff values close to tissue and blood were assumed separately. Standard statistical analysis was conducted to compare these fitting models in various brain regions. The fitted results indicated that: (i) the estimated CBF values using the two‐parameter model show appreciable dependence on the assumed T_1,eff values; (ii) the proposed three‐parameter model achieves the optimal balance between the goodness of fit and model complexity when compared among the models with explicit IRF fitting; (iii) both the two‐parameter model using fixed blood T₁ values for T_1,eff and the three‐parameter model provide reasonable fitting results. Using the proposed three‐parameter model, the estimated CBF (46 ± 14 mL/100 g/min) and ATT (1.4 ± 0.3 s) values averaged from different brain regions are close to the literature reports; the estimated T_1,eff values (1.9 ± 0.4 s) are higher than the tissue T₁ values, possibly reflecting a contribution from the microvascular arterial blood compartment.     

Volumetric imaging of myelin in vivo using 3D inversion recovery‐prepared ultrashort echo time cones magnetic resonance imaging

Direct myelin imaging is promising for characterization of multiple sclerosis (MS) brains at diagnosis and in response to therapy. In this study, a 3D inversion recovery‐prepared ultrashort echo time cones (IR‐UTE‐Cones) sequence was used for both morphological and quantitative imaging of myelin on a clinical 3 T scanner. Myelin powder phantoms with different myelin concentrations were imaged with the 3D UTE‐Cones sequence and it showed a strong correlation between concentrations and UTE‐Cones signals, demonstrating the ability of the UTE‐Cones sequence to directly image myelin in the brain. Quantitative myelin imaging with multi‐echo IR‐UTE‐Cones sequences show similar T₂* values for a D₂O‐exchanged myelin phantom (T₂* = 0.33 ± 0.04 ms), ex vivo brain specimens (T₂* = 0.20 ± 0.04 ms) and in vivo healthy volunteers (T₂* = 0.254 ± 0.023 ms), further confirming the feasibility of 3D IR‐UTE‐Cones sequences for direct myelin imaging in vivo. In ex vivo MS brain study, signal loss is observed in MS lesions, which was confirmed with histology. For the in vivo study, the lesions in MS patients also show myelin signal loss using the proposed direct myelin imaging method, demonstrating the clinical potential for MS diagnosis. Furthermore, the measured IR‐UTE‐Cones signal intensities show a significant difference between normal‐appearing white matter in MS patients and normal white matter in volunteers, which cannot be found in clinical used T₂‐FLAIR sequences. Thus, the proposed 3D IR‐UTE‐Cones sequence showed clinical potential for MS diagnosis with the capability of direct myelin detection of the whole brain.