Optimization of flow‐sensitive alternating inversion recovery (FAIR) for perfusion functional MRI of rodent brain

Arterial spin labeling (ASL) MRI provides a noninvasive method to image perfusion, and has been applied to map neural activation in the brain. Although pulsed labeling methods have been widely used in humans, continuous ASL with a dedicated neck labeling coil is still the preferred method in rodent brain functional MRI (fMRI) to maximize the sensitivity and allow multislice acquisition. However, the additional hardware is not readily available and hence its application is limited. In this study, flow‐sensitive alternating inversion recovery (FAIR) pulsed ASL was optimized for fMRI of rat brain. A practical challenge of FAIR is the suboptimal global inversion by the transmit coil of limited dimensions, which results in low effective labeling. By using a large volume transmit coil and proper positioning to optimize the body coverage, the perfusion signal was increased by 38.3% compared with positioning the brain at the isocenter. An additional 53.3% gain in signal was achieved using optimized repetition and inversion times compared with a long TR. Under electrical stimulation to the forepaws, a perfusion activation signal change of 63.7 ± 6.3% can be reliably detected in the primary somatosensory cortices using single slice or multislice echo planar imaging at 9.4 T. This demonstrates the potential of using pulsed ASL for multislice perfusion fMRI in functional and pharmacological applications in rat brain. Copyright © 2012 John Wiley & Sons, Ltd.     

Quantitative ASL muscle perfusion imaging using a FAIR-TrueFISP technique at 3.0 T

The feasibility of muscle perfusion imaging with diagnostic image quality was demonstrated using the FAIR-TrueFISP arterial spin labeling technique on a clinical 3.0 T whole-body scanner. In eight healthy volunteers (24 to 42 years old), quantitative perfusion maps of the forearm musculature were acquired before and after intense exercise. All measurements were carried out in a 3.0 T whole-body MR unit in combination with an eight-channel head coil. Pulsed arterial spin labeling and data recording were performed with an adapted FAIR-TrueFISP technique and quantitative perfusion maps were calculated on a pixel-by-pixel basis by means of the extended Bloch equations. Perfusion images with an in-plane resolution of 1 mm showed no significant distortions or blurring. Perfusion-time curves could be recorded with a temporal resolution of 6.4 s. Maximum perfusion in the musculature was found approximately 2 min after exercise, reaching values of up to 220 mL/min per 100 g of tissue with good delineation between the active muscles and the musculature not involved in the exercise. In conclusion, the TrueFISP pulsed arterial spin labeling technique allows patient-friendly assessment of muscular perfusion in a clinical whole-body scanner.     

Arterial spin labeling‐fast imaging with steady‐state free precession (ASL‐FISP): a rapid and quantitative perfusion technique for high‐field MRI

Arterial spin labeling (ASL) is a valuable non‐contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either echo‐planar imaging (EPI) or true fast imaging with steady‐state free precession (true FISP) readouts, which are prone to off‐resonance artifacts on high‐field MRI scanners. We have developed a rapid ASL‐FISP MRI acquisition for high‐field preclinical MRI scanners providing perfusion‐weighted images with little or no artifacts in less than 2 s. In this initial implementation, a flow‐sensitive alternating inversion recovery (FAIR) ASL preparation was combined with a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4 T (249 ± 38 and 241 ± 17 mL/min/100 g, respectively). The utility of this method was further demonstrated in the detection of significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL‐FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high‐field MRI scanners with minimal image artifacts. Copyright © 2014 John Wiley & Sons, Ltd.     

Fast volumetric imaging of bound and pore water in cortical bone using three‐dimensional ultrashort‐TE (UTE) and inversion recovery UTE sequences

We report the three‐dimensional ultrashort‐TE (3D UTE) and adiabatic inversion recovery UTE (IR‐UTE) sequences employing a radial trajectory with conical view ordering for bi‐component T₂* analysis of bound water (T₂*^BW) and pore water (T₂*^PW) in cortical bone. An interleaved dual‐echo 3D UTE acquisition scheme was developed for fast bi‐component analysis of bound and pore water in cortical bone. A 3D IR‐UTE acquisition scheme employing multiple spokes per IR was developed for bound water imaging. Two‐dimensional UTE (2D UTE) and IR‐UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n = 6) and volunteers (n = 6) using a 3‐T scanner. Bi‐component fitting of 3D UTE images of bovine samples showed a mean T₂*^BW of 0.26 ± 0.04 ms and T₂*^PW of 4.16 ± 0.35 ms, with fractions of 21.5 ± 3.6% and 78.5 ± 3.6%, respectively. The 3D IR‐UTE signal showed a single‐component decay with a mean T₂*^BW of 0.29 ± 0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR‐UTE sequences. Bi‐component fitting of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T₂*^BW of 0.32 ± 0.08 ms and T₂*^PW of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single‐component fitting of 3D IR‐UTE images showed a mean T₂*^BW of 0.35 ± 0.09 ms. The 3D UTE and 3D IR‐UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone. Copyright © 2016 John Wiley & Sons, Ltd.     

Effects of inversion time on inversion recovery prepared ultrashort echo time (IR‐UTE) imaging of bound and pore water in cortical bone

Water is present in cortical bone in different binding states. In this study we aimed to investigate the effects of inversion time (TI) on the signal from bound and pore water in cortical bone using an adiabatic inversion recovery prepared ultrashort echo time (IR‐UTE) sequence on a clinical 3 T scanner. In total ten bovine midshaft samples and four human tibial midshaft samples were harvested for this study. Each cortical sample was imaged with the UTE and IR‐UTE sequences with a TR of 300 ms and a series of TI values ranging from 10 to 240 ms. Five healthy volunteers were also imaged with the same sequence. Single‐ and bi‐component models were utilized to calculate the T₂* and relative fractions of short and long T₂* components. Bi‐component behavior of the signal from cortical bone was seen with the IR‐UTE sequence, except with a TI of around 80 ms, where the short T₂* component alone were seen and a mono‐exponential decay pattern was observed. In vivo imaging with the IR‐UTE sequence provided high contrast‐to‐noise images with direct visualization of bound water and reduced signal from long T₂ muscle and fat. Our preliminary results demonstrate that selective nulling of the pore water component can be achieved with the IR‐UTE sequence with an appropriate TI, allowing selective imaging of the bound water component in cortical bone in vivo using clinical MR scanners. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparison of perfusion MRI by flow-sensitive alternating inversion recovery and dynamic susceptibility contrast in rats with permanent middle cerebral artery occlusion

We compared cerebral blood flow (CBF) parameters obtained by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with those obtained by flow-sensitive alternating inversion recovery (FAIR) in brain regions with different perfusion levels in rats with permanent middle cerebral artery (MCA) occlusion. MCA occlusion was performed in 19 rats. T2-weighted MRI, FAIR and DSC-MRI were performed within 48 h after occlusion. CBF parameters were analyzed in regions of interest with either prolonged or less prolonged mean transit time (MTT). Ratios of ipsi- vs contralateral CBF values were calculated and tested for correlation and differences between FAIR and DSC-MRI. FAIR-aCBF ratios correlated significantly with DSC-rCBF ratios. The mean FAIR-aCBF ratio was significantly lower than mean DSC-rCBF ratio in the area with prolonged MTT. In the area with less prolonged MTT, the mean FAIR-aCBF ratio and mean DSC-rCBF values did not differ significantly. We conclude that FAIR correlates with DSC-MRI if perfusion is preserved. FAIR provides lower CBF values than DSC-MRI if perfusion is reduced and MTT is prolonged. This probable underestimation of perfusion may be caused by transit delays. Care should be taken when quantifying CBF with FAIR and when comparing the results of FAIR- and DSC-MRI in areas with hypoperfusion.     

A comparison of arterial spin labeling perfusion MRI and DCE‐MRI in human prostate cancer

Perfusion MRI has the potential to provide pathophysiological biomarkers for the evaluating, staging and therapy monitoring of prostate cancer. The objective of this study was to explore the feasibility of noninvasive arterial spin labeling (ASL) to detect prostate cancer in the peripheral zone and to investigate the correlation between the blood flow (BF) measured by ASL and the pharmacokinetic parameters K^trans (forward volume transfer constant), k_ep (reverse reflux rate constant between extracellular space and plasma) and v_e (the fractional volume of extracellular space per unit volume of tissue) measured by dynamic contrast‐enhanced (DCE) MRI in patients with prostate cancer. Forty‐three consecutive patients (ages ranging from 49 to 86 years, with a median age of 74 years) with pathologically confirmed prostate cancer were recruited. An ASL scan with four different inversion times (TI = 1000, 1200, 1400 and 1600 ms) and a DCE‐MRI scan were performed on a clinical 3.0 T GE scanner. BF, K^trans, k_ep and v_e maps were calculated. In order to determine whether the BF values in the cancerous area were statistically different from those in the noncancerous area, an independent t‐test was performed. Spearman's bivariate correlation was used to assess the relationship between BF and the pharmacokinetic parameters K^trans, k_ep and v_e. The mean BF values in the cancerous areas (97.1 ± 30.7, 114.7 ± 28.7, 102.3 ± 22.5, 91.2 ± 24.2 ml/100 g/min, respectively, for TI = 1000, 1200, 1400, 1600 ms) were significantly higher (p < 0.01 for all cases) than those in the noncancerous regions (35.8 ± 12.5, 42.2 ± 13.7, 53.5 ± 19.1, 48.5 ± 13.5 ml/100 g/min, respectively). Significant positive correlations (p < 0.01 for all cases) between BF and the pharmacokinetic parameters K^trans, k_ep and v_e were also observed for all four TI values (r = 0.671, 0.407, 0.666 for TI = 1000 ms; 0.713, 0.424, 0.698 for TI = 1200 ms; 0.604, 0.402, 0.595 for TI = 1400 ms; 0.605, 0.422, 0.548 for TI = 1600 ms). It can be seen that the quantitative ASL measurements show significant differences between cancerous and benign tissues, and exhibit strong to moderate correlations with the parameters obtained using DCE‐MRI. These results show the promise of ASL as a noninvasive alternative to DCE‐MRI. Copyright © 2014 John Wiley & Sons, Ltd.     

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.     

Whole‐brain perfusion imaging with balanced steady‐state free precession arterial spin labeling

Recently, balanced steady‐state free precession (bSSFP) readout has been proposed for arterial spin labeling (ASL) perfusion imaging to reduce susceptibility artifacts at a relatively high spatial resolution and signal‐to‐noise ratio (SNR). However, the main limitation of bSSFP‐ASL is the low spatial coverage. In this work, methods to increase the spatial coverage of bSSFP‐ASL are proposed for distortion‐free, high‐resolution, whole‐brain perfusion imaging. Three strategies of (i) segmentation, (ii) compressed sensing (CS) and (iii) a hybrid approach combining the two methods were tested to increase the spatial coverage of pseudo‐continuous ASL (pCASL) with three‐dimensional bSSFP readout. The spatial coverage was increased by factors of two, four and six using each of the three approaches, whilst maintaining the same total scan time (5.3 min). The number of segments and/or CS acceleration rate (R) correspondingly increased to maintain the same bSSFP readout time (1.2 s). The segmentation approach allowed whole‐brain perfusion imaging for pCASL‐bSSFP with no penalty in SNR and/or total scan time. The CS approach increased the spatial coverage of pCASL‐bSSFP whilst maintaining the temporal resolution, with minimal impact on the image quality. The hybrid approach provided compromised effects between the two methods. Balanced SSFP‐based ASL allows the acquisition of perfusion images with wide spatial coverage, high spatial resolution and SNR, and reduced susceptibility artifacts, and thus may become a good choice for clinical and neurological studies. Copyright © 2015 John Wiley & Sons, Ltd.     

Lipid suppression via double inversion recovery with symmetric frequency sweep for robust 2D‐GRAPPA‐accelerated MRSI of the brain at 7 T

This work presents a new approach for high‐resolution MRSI of the brain at 7 T in clinically feasible measurement times. Two major problems of MRSI are the long scan times for large matrix sizes and the possible spectral contamination by the transcranial lipid signal. We propose a combination of free induction decay (FID)‐MRSI with a short acquisition delay and acceleration via in‐plane two‐dimensional generalised autocalibrating partially parallel acquisition (2D‐GRAPPA) with adiabatic double inversion recovery (IR)‐based lipid suppression to allow robust high‐resolution MRSI. We performed Bloch simulations to evaluate the magnetisation pathways of lipids and metabolites, and compared the results with phantom measurements. Acceleration factors in the range 2–25 were tested in a phantom. Five volunteers were scanned to verify the value of our MRSI method in vivo. GRAPPA artefacts that cause fold‐in of transcranial lipids were suppressed via double IR, with a non‐selective symmetric frequency sweep. The use of long, low‐power inversion pulses (100 ms) reduced specific absorption rate requirements. The symmetric frequency sweep over both pulses provided good lipid suppression (>90%), in addition to a reduced loss in metabolite signal‐to‐noise ratio (SNR), compared with conventional IR suppression (52–70%). The metabolic mapping over the whole brain slice was not limited to a rectangular region of interest. 2D‐GRAPPA provided acceleration up to a factor of nine for in vivo FID‐MRSI without a substantial increase in g‐factors (<1.1). A 64 × 64 matrix can be acquired with a common repetition time of ~1.3 s in only 8 min without lipid artefacts caused by acceleration. Overall, we present a fast and robust MRSI method, using combined double IR fat suppression and 2D‐GRAPPA acceleration, which may be used in (pre)clinical studies of the brain at 7 T. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

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.     

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.     

Bone mineral 31P and matrix‐bound water densities measured by solid‐state 31P and 1H MRI

Bone is a composite material consisting of mineral and hydrated collagen fractions. MRI of bone is challenging because of extremely short transverse relaxation times, but solid‐state imaging sequences exist that can acquire the short‐lived signal from bone tissue. Previous work to quantify bone density via MRI used powerful experimental scanners. This work seeks to establish the feasibility of MRI‐based measurement on clinical scanners of bone mineral and collagen‐bound water densities, the latter as a surrogate of matrix density, and to examine the associations of these parameters with porosity and donors’ age. Mineral and matrix‐bound water images of reference phantoms and cortical bone from 16 human donors, aged 27–97 years, were acquired by zero‐echo‐time 31‐phosphorus (³¹P) and 1‐hydrogen (¹H) MRI on whole body 7T and 3T scanners, respectively. Images were corrected for relaxation and RF inhomogeneity to obtain density maps. Cortical porosity was measured by micro‐computed tomography (μCT), and apparent mineral density by peripheral quantitative CT (pQCT). MRI‐derived densities were compared to X‐ray‐based measurements by least‐squares regression. Mean bone mineral ³¹P density was 6.74 ± 1.22 mol/l (corresponding to 1129 ± 204 mg/cc mineral), and mean bound water ¹H density was 31.3 ± 4.2 mol/l (corresponding to 28.3 ± 3.7 %v/v). Both ³¹P and bound water (BW) densities were correlated negatively with porosity (³¹P: R² = 0.32, p < 0.005; BW: R² = 0.63, p < 0.0005) and age (³¹P: R² = 0.39, p < 0.05; BW: R² = 0.70, p < 0.0001), and positively with pQCT density (³¹P: R² = 0.46, p < 0.05; BW: R² = 0.50, p < 0.005). In contrast, the bone mineralization ratio (expressed here as the ratio of ³¹P density to bound water density), which is proportional to true bone mineralization, was found to be uncorrelated with porosity, age or pQCT density. This work establishes the feasibility of image‐based quantification of bone mineral and bound water densities using clinical hardware. Copyright © 2014 John Wiley & Sons, Ltd.     

Feasibility of measuring prostate perfusion with arterial spin labeling

Prostate perfusion has the potential to become an important pathophysiological marker for the monitoring of disease progression or the assessment of the therapeutic response of prostate cancer. The feasibility of arterial spin labeling, an MRI approach for the measurement of perfusion without an exogenous contrast agent, is demonstrated in the prostate for the first time. Although various arterial spin labeling methods have been demonstrated previously in highly perfused organs, such as the brain and kidneys, the prospect of obtaining such measurements in the prostate is challenging because of the relatively low blood flow, long transit times, susceptibility‐induced image distortion and local motion. However, despite these challenges, this study demonstrates that, with a whole‐body transmit coil and external receiver array, global prostate perfusion can be measured with arterial spin labeling at 3 T. In five healthy subjects with a mean age of 44 years, the mean total prostate blood flow was measured to be 25.8 ± 7.1 mL/100 cm³/min, with an estimated bolus duration and arterial transit time of 884 ± 209 ms and 721 ± 131 ms, respectively. Copyright © 2012 John Wiley & Sons, Ltd.     

Evaluation of segmented 3D acquisition schemes for whole‐brain high‐resolution arterial spin labeling at 3 T

Recent technical developments have significantly increased the signal‐to‐noise ratio (SNR) of arterial spin labeled (ASL) perfusion MRI. Despite this, typical ASL acquisitions still employ large voxel sizes. The purpose of this work was to implement and evaluate two ASL sequences optimized for whole‐brain high‐resolution perfusion imaging, combining pseudo‐continuous ASL (pCASL), background suppression (BS) and 3D segmented readouts, with different in‐plane k‐space trajectories. Identical labeling and BS pulses were implemented for both sequences. Two segmented 3D readout schemes with different in‐plane trajectories were compared: Cartesian (3D GRASE) and spiral (3D RARE Stack‐Of‐Spirals). High‐resolution perfusion images (2 × 2 × 4 mm³) were acquired in 15 young healthy volunteers with the two ASL sequences at 3 T. The quality of the perfusion maps was evaluated in terms of SNR and gray‐to‐white matter contrast. Point‐spread‐function simulations were carried out to assess the impact of readout differences on the effective resolution. The combination of pCASL, in‐plane segmented 3D readouts and BS provided high‐SNR high‐resolution ASL perfusion images of the whole brain. Although both sequences produced excellent image quality, the 3D RARE Stack‐Of‐Spirals readout yielded higher temporal and spatial SNR than 3D GRASE (spatial SNR = 8.5 ± 2.8 and 3.7 ± 1.4; temporal SNR = 27.4 ± 12.5 and 15.6 ± 7.6, respectively) and decreased through‐plane blurring due to its inherent oversampling of the central k‐space region, its reduced effective T_E and shorter total readout time, at the expense of a slight increase in the effective in‐plane voxel size. Copyright © 2014 John Wiley & Sons, Ltd.     

MR fingerprinting ASL: Sequence characterization and comparison with dynamic susceptibility contrast (DSC) MRI

MR Fingerprinting (MRF)‐based Arterial‐Spin‐Labeling (ASL) has the potential to measure multiple parameters such as cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T₁ in a single scan. However, the previous reports have only demonstrated a proof‐of‐principle of the technique but have not examined the performance of the sequence in the context of key imaging parameters. Furthermore, there has not been a study to directly compare the technique to clinically used perfusion method of dynamic‐susceptibility‐contrast (DSC) MRI. The present report consists of two studies. In the first study (N = 8), we examined the dependence of MRF‐ASL sequence on TR time pattern. Ten different TR patterns with a range of temporal characteristics were examined by both simulations and experiments. The results revealed that there was a significance dependence of the sequence performance on TR pattern (p < 0.001), although there was not a single pattern that provided dramatically improvements. Among the TR patterns tested, a sinusoidal pattern with a period of 125 TRs provided an overall best estimation in terms of spatial consistency. These experimental observations were consistent with those of numerical simulations. In the second study (N = 8), we compared MRF‐ASL results with those of DSC MRI. It was found that MRF‐ASL and DSC MRI provided highly comparable maps of cerebral blood flow (CBF) and bolus‐arrival‐time (BAT), with spatial correlation coefficients of 0.79 and 0.91, respectively. However, in terms of quantitative values, BAT obtained with MRF‐ASL was considerably lower than that from DSC (p < 0.001), presumably because of the differences in tracer characteristics in terms of diffusible versus intravascular tracers. Test–retest assessment of MRF‐ASL MRI revealed that the spatial correlations of parametric maps were 0.997, 0.962, 0.746 and 0.863 for B₁⁺, T₁, CBF, and BAT, respectively. MRF‐ASL is a promising technique for assessing multiple perfusion parameters simultaneously without contrast agent.     

Measuring perfusion and bioenergetics simultaneously in mouse skeletal muscle: a multiparametric functional‐NMR approach

A totally noninvasive set‐up was developed for comprehensive NMR evaluation of mouse skeletal muscle function in vivo. Dynamic pulsed arterial spin labeling‐NMRI perfusion and blood oxygenation level‐dependent (BOLD) signal measurements were interleaved with ³¹P NMRS to measure both vascular response and oxidative capacities during stimulated exercise and subsequent recovery. Force output was recorded with a dedicated ergometer. Twelve exercise bouts were performed. The perfusion, BOLD signal, pH and force–time integral were obtained from mouse legs for each exercise. All reached a steady state after the second exercise, justifying the pointwise summation of the last 10 exercises to compensate for the limited ³¹P signal. In this way, a high temporal resolution of 2.5 s was achieved to provide a time constant for phosphocreatine (PCr) recovery (τ_PCr). The higher signal‐to‐noise ratio improved the precision of τ_PCr measurement [coefficient of variation (CV) = 16.5% vs CV = 49.2% for a single exercise at a resolution of 30 s]. Inter‐animal summation confirmed that τ_PCr was stable at steady state, but shorter (89.3 ± 8.6 s) than after the first exercise (148 s, p < 0.05). This novel experimental approach provides an assessment of muscle vascular response simultaneously to energetic function in vivo. Its pertinence was illustrated by observing the establishment of a metabolic steady state. This comprehensive tool offers new perspectives for the study of muscle pathology in mice models. Copyright © 2010 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.     

Fast quantitative three‐dimensional ultrashort echo time (UTE) Cones magnetic resonance imaging of major tissues in the knee joint using extended sprial sampling

The purpose of this study is to investigate the effect of extending the spiral sampling window on quantitative 3D ultrashort echo time (UTE) Cones imaging of major knee joint tissues including articular cartilage, menisci, tendons and ligaments at 3 T. Nine cadaveric human whole knee specimens were imaged on a 3 T clinical MRI scanner. A series of quantitative 3D UTE Cones imaging biomarkers including T₂*, T₁, adiabatic T_1ρ, magnetization transfer ratio (MTR) and macromolecular fraction (MMF) were estimated using spiral sampling trajectories with various durations. Errors in UTE MRI biomarkers as a function of sampling time were evaluated using a nonstretched spiral trajectory as a reference standard. No significant differences were observed by increasing the spiral sampling window from 1116 to 2232 μs in the calculated T₂*, T₁, adiabatic T_1ρ, MTR and MMF, as all P‐values were over .05 as assessed by ANOVA with two‐sided Dunnett's test. Although extending the sampling window results in signal loss for short T₂ components, there was limited effect on the calculated quantitative biomarkers, with error percentages typically smaller than 5% in all the evaluated tissues. The total scan time can be reduced by up to 54% with quantification errors of less than 5% in any evaluated major tissue in the knee joint, suggesting that 3D UTE Cones MRI techniques can be greatly accelerated by using a longer spiral sampling window without causing additional quantitative bias.     

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.