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.     

Characterizing pulmonary blood flow distribution measured using arterial spin labeling

The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head‐down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% (p < 0.005). Head‐down tilt significantly reduced the lognormal scale parameter (p = 0.01) but not the shape parameter or GSD. The RD increased post‐tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels. Copyright © 2009 John Wiley & Sons, Ltd.     

Comparison of relative cerebral blood flow maps using pseudo-continuous arterial spin labeling and single photon emission computed tomography

Pseudo‐continuous arterial spin labeling (PCASL) MRI is a relatively new arterial spin labeling technique and has the potential to extend the cerebral blood flow (CBF) measurement to all tissue types, including white matter. However, the arterial transit time (δ_a) for white matter is not well established and a limited number of reports using multi‐delay methods have yielded inconsistent findings. In this study, we used a different approach and measured white matter δ_a (mean ± standard deviation, 1541 ± 173 ms) by determining the arrival times of exogenous contrast agent in a bolus tracking experiment. The data also confirmed δ_a of gray matter to be 912 ± 209 ms. In the second part of this study, we used these parameters in PCASL kinetic models and compared relative CBF (rCBF, with respect to the whole brain) maps with those measured using a single photon emission computed tomography (SPECT) technique. It was found that the use of tissue‐specific δ_a in the PCASL model was helpful in improving the correspondence between the two modalities. On a regional level, the gray/white matter CBF ratios were 2.47 ± 0.39 and 2.44 ± 0.18 for PCASL and SPECT, respectively. On a single‐voxel level, the variance between the modalities was still considerable, with an average rCBF difference of 0.27. Copyright © 2011 John Wiley & Sons, Ltd.     

The importance of RF bandwidth for effective tagging in pulsed arterial spin labeling MRI at 9.4T

The movement towards MRI at higher field strengths (>7T) has enhanced the appeal of arterial spin labeling (ASL) for many applications due to improved SNR of the measurements. Greater field strength also introduces increased magnetic susceptibility effects resulting in marked B₀ field inhomogeneity. Although B₀ field perturbations can be minimised by shimming over the imaging volume, marked field inhomogeneity is likely to remain within the labeling region for pulsed ASL (PASL). This study highlights a potential source of error in cerebral blood flow quantification using PASL at high field. We show that labeling efficiency in flow‐sensitive alternating inversion recovery (FAIR) displayed marked sensitivity to the RF bandwidth of the inversion pulse in a rat model at 9.4T. The majority of preclinical PASL studies have not reported the bandwidth of the inversion pulse. We show that a high bandwidth pulse of > = 15 kHz was required to robustly overcome the field inhomogeneity in the labeling region at high field strength, which is significantly greater than the inversion bandwidth ~2–3 kHz used in previous studies. Unless SAR levels are at their limit, we suggest the use of a high bandwidth labeling pulse for most PASL studies. Copyright © 2012 John Wiley & Sons, Ltd.     

Timing dependence of peripheral pulse‐wave‐triggered pulsed arterial spin labeling

Arterial spin labeling (ASL) has been developed into a useful technique that is capable of quantifying noninvasively local cerebral blood flow (CBF) using the water molecules in arterial blood as diffusible tracers. Pulsed ASL (PASL) is more strongly affected than continuous ASL (CASL) by cardiac pulsation, because the tag bolus is shorter than the cardiac cycle in most cases. No reports have yet clarified the effects of multiple cardiac phases on the quantification of CBF in PASL when triggering is used. Fourteen subjects participated in this study. Peripheral pulse‐wave‐triggered (PPWT)‐ASL was performed at various time points at the carotid artery (delay 0 ms, second point, foot, peak and tail) and compared with nontriggered (NT)‐ASL. Regions of interest (ROIs) were applied based on the anterior, middle and posterior cerebral artery (ACA, MCA, PCA) territories, and CBFs were compared among different time points and ROIs. PPWT‐ASL strongly affects CBF values compared with NT‐ASL in ACA and MCA territories, especially when measured at the foot of the carotid artery flow phase. CBF_NT was assumed to lie approximately between the minimum and maximum CBFs, with clear statistical significance in several ROIs at several time points of PPWT‐ASL, and CBF_NT was assumed to resemble ‘randomly triggered’ PPWT‐ASL. In conclusion, PPWT‐ASL strongly affects CBF values compared with NT‐ASL, particularly at the foot of the carotid artery flow in ACA and MCA territories. Copyright © 2013 John Wiley & Sons, Ltd.     

Look‐Locker FAIR TrueFISP for arterial spin labelling on mouse at 9.4 T

Pulsed arterial spin labelling remains a non‐invasive and highly used method for the study of rodent cerebral blood flow (CBF). Flow‐sensitive alternating inversion recovery (FAIR) is one of the most commonly used MR‐sequences for this purpose and exists with many different strategies to record the images. This study investigates Look‐Locker (LL) TrueFISP readout for FAIR as an alternative to the standard EPI readout, which is provided by the manufacturer. The aim was to show the improved image quality using TrueFISP and to verify the reproducibility of the determination of the cerebral blood flow values. The measurement of many inversion points also allowed to investigate the influence of the correct blood relaxation rate on the fit of the CBF data. For the LL‐FAIR TrueFISP an in‐house written method was created. The method was tested on a group of C57BL/6 mice at the field strength of 9.4 T. The results show CBF maps with less distortion than for EPI and the values found are in good agreement with the literature. A comparison of the CBF values found with EPI and LL‐TrueFISP shows very small differences, most being not significant. In conclusion, the method presented gives equivalent CBF maps in comparison to standard FAIR‐EPI. Both methods have the same measurement time. TrueFISP has the advantage to EPI of producing undistorted images over larger areas of the mouse brain. It is advisable to check the value of the blood relaxation rate by measurement or to estimate it as a fitting parameter.     

Background suppression in arterial spin labeling MRI with a separate neck labeling coil

In arterial spin labeling (ASL) MRI to measure cerebral blood flow (CBF), pair-wise subtraction of temporally adjacent non-labeled and labeled images often can not completely cancel the background static tissue signal because of temporally fluctuating physiological noise. While background suppression (BS) by inversion nulling improves CBF temporal stability, imperfect pulses compromise CBF contrast. Conventional BS techniques may not be applicable in small animals because the arterial transit time is short. This study presents a novel approach of BS to overcome these drawbacks using a separate 'neck' radiofrequency coil for ASL and a 'brain' radiofrequency coil for BS with the inversion pulse placed before spin labeling. The use of a separate 'neck' coil for ASL should also improve ASL contrast. This approach is referred to as the inversion-recovery BS with the two-coil continuous ASL (IR-cASL) technique. The temporal and spatial contrast-to-noise characteristics of basal CBF and CBF-based fMRI of hypercapnia and forepaw stimulation in rats at 7 Tesla were analyzed. IR-cASL yielded two times better temporal stability and 2.0-2.3 times higher functional contrast-to-noise ratios for hypercapnia and forepaw stimulation compared with cASL without BS in the same animals. The Bloch equations were modified to provide accurate CBF quantification at different levels of BS and for multislice acquisition where different slices have different degree of BS and residual degree of labeling. Improved basal CBF and CBF-based fMRI sensitivity should lead to more accurate CBF quantification and should prove useful for imaging low CBF conditions such as in white matter and stroke.     

Pain response measured with arterial spin labeling

The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level‐dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is another imaging approach in which the magnetically labeled arterial water is used as an endogenous tracer that allows for direct measurement of cerebral blood flow. In this study, we assessed the pain response in the brain using a pulsed‐continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised. Copyright © 2013 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.     

Quantitative mouse renal perfusion using arterial spin labeling

Information on renal perfusion is essential for the diagnosis and prognosis of kidney function. Quantification using gadolinium chelates is limited as a result of filtration through renal glomeruli and safety concerns in patients with kidney dysfunction. Arterial spin labeling MRI is a noninvasive technique for perfusion quantification that has been applied to humans and animals. However, because of the low sensitivity and vulnerability to motion and susceptibility artifacts, its application to mice has been challenging. In this article, mouse renal perfusion was studied using flow‐sensitive alternating inversion recovery at 7 T. Good perfusion image quality was obtained with spin‐echo echo‐planar imaging after controlling for respiratory, susceptibility and fat artifacts by triggering, high‐order shimming and water excitation, respectively. High perfusion was obtained in the renal cortex relative to the medulla, and signal was absent in scans carried out post mortem. Cortical perfusion increased from 397 ± 36 (mean ± standard deviation) to 476 ± 73 mL/100 g/min after switching from 100% oxygen to carbogen with 95% oxygen and 5% carbon dioxide. The perfusion in the medulla was 2.5 times lower than that in the cortex and changed from 166 ± 41 mL/100 g/min under oxygen to 203 ± 40 mL/100 g/min under carbogen. T₁ decreased in both the cortex (from 1570 ± 164 to 1377 ± 72 ms, p < 0.05) and medulla (from 1788 ± 107 to 1573 ± 144 ms, p < 0.05) under carbogen relative to 100% oxygen. The results showed the potential of the use of ASL for perfusion quantification in mice and in models of renal diseases. Copyright © 2013 John Wiley & Sons, Ltd.     

Robust arterial transit time and cerebral blood flow estimation using combined acquisition of Hadamard‐encoded multi‐delay and long‐labeled long‐delay pseudo‐continuous arterial spin labeling: a simulation and in vivo study

Arterial transit time (ATT) prolongation causes an error of cerebral blood flow (CBF) measurement during arterial spin labeling (ASL). To improve the accuracy of ATT and CBF in patients with prolonged ATT, we propose a robust ATT and CBF estimation method for clinical practice. The proposed method consists of a three‐delay Hadamard‐encoded pseudo‐continuous ASL (H‐pCASL) with an additional‐encoding and single‐delay with long‐labeled long‐delay (1dLLLD) acquisition. The additional‐encoding allows for the reconstruction of a single‐delay image with long‐labeled short‐delay (1dLLSD) in addition to the normal Hadamard sub‐bolus images. Five different images (normal Hadamard 3 delay, 1dLLSD, 1dLLLD) were reconstructed to calculate ATT and CBF. A Monte Carlo simulation and an in vivo study were performed to access the accuracy of the proposed method in comparison to normal 7‐delay (7d) H‐pCASL with equally divided sub‐bolus labeling duration (LD). The simulation showed that the accuracy of CBF is strongly affected by ATT. It was also demonstrated that underestimation of ATT and CBF by 7d H‐pCASL was higher with longer ATT than with the proposed method. Consistent with the simulation, the 7d H‐pCASL significantly underestimated the ATT compared to that of the proposed method. This underestimation was evident in the distal anterior cerebral artery (ACA; P = 0.0394) and the distal posterior cerebral artery (PCA; 2 P = 0.0255). Similar to the ATT, the CBF was underestimated with 7d H‐pCASL in the distal ACA (P = 0.0099), distal middle cerebral artery (P = 0.0109), and distal PCA (P = 0.0319) compared to the proposed method. Improving the SNR of each delay image (even though the number of delays is small) is crucial for ATT estimation. This is opposed to acquiring many delays with short LD. The proposed method confers accurate ATT and CBF estimation within a practical acquisition time in a clinical setting.     

Quantification of myocardial blood flow and flow reserve in rats using arterial spin labeling MRI: comparison with a fluorescent microsphere technique

To quantify noninvasively myocardial blood flow (MBF) and MBF reserve in isoflurane‐anesthetized rats using the Look‐Locker flow‐alternating inversion recovery gradient‐echo arterial spin labeling technique (LLFAIRGE‐ASL), and to compare the results with the fluorescent microsphere (FM) technique. Male Wistar rats (weight = 200–240 g, n = 21) were anesthetized with 2.0% isoflurane. Hemodynamic parameters were recorded. In seven rats, MBF was assessed on a Bruker Biospec 4.7T MR system using an ECG‐ and respiration‐gated LLFAIRGE‐ASL (pixel size = 234 × 468µm², TE = 1.52ms) at rest and during adenosine infusion (140 µg/kg/min). A mixture of 200 000 FM was injected into a second group of rats at rest and during adenosine infusion (n = 7 each), under similar physiologic conditions. Hearts and skeletal muscle samples were processed for fluorescence spectroscopy. Two‐tailed unpaired, paired Student's t‐test and ANOVA were used to compare groups. MBF measured with LLFAIRGE‐ASL was 5.2 ± 1.0 mL/g/min at rest and 13.3 ± 3.0 mL/g/min during adenosine infusion. Results obtained with fluorescent microspheres yielded 5.9 ± 2.3 mL/g/min (nonsignificant vs. LLFAIRGE‐ASL, p = 0.9) at rest and 13.1 ± 2.1 mL/g/min (nonsignificant vs. LLFAIRGE‐ASL, p = 0.4) during adenosine infusion. Myocardial blood flow reserve measured using LLFAIRGE‐ASL and FM were not significantly different (2.5 ± 0.6 vs. 2.4 ± 0.9, respectively; p = 0.8). Hemodynamic parameters during the experiments were not different between the groups. The myocardial blood flow reserve determined under isoflurane anesthesia was 2.5 ± 0.6, which was not different from the value obtained with FM. LLFAIRGE‐ASL provided MBF maps with high spatial resolution in rats under isoflurane anesthesia. LLFAIRGE‐ASL is a noninvasive measure to assess myocardial blood flow reserve and provides an interesting tool for cardiovascular research. Copyright © 2011 John Wiley & Sons, Ltd.     

Influence of different isoflurane anesthesia protocols on murine cerebral hemodynamics measured with pseudo‐continuous arterial spin labeling

Arterial spin labeling (ASL)‐MRI can noninvasively map cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), potential biomarkers of cognitive impairment and dementia. Mouse models of disease are frequently used in translational MRI studies, which are commonly performed under anesthesia. Understanding the influence of the specific anesthesia protocol used on the measured parameters is important for accurate interpretation of hemodynamic studies with mice. Isoflurane is a frequently used anesthetic with vasodilative properties. Here, the influence of three distinct isoflurane protocols was studied with pseudo‐continuous ASL in two different mouse strains. The first protocol was a free‐breathing set‐up with medium concentrations, the second a free‐breathing set‐up with low induction and maintenance concentrations, and the third a set‐up with medium concentrations and mechanical ventilation. A protocol with the vasoconstrictive anesthetic medetomidine was used as a comparison. As expected, medium isoflurane anesthesia resulted in significantly higher CBF and lower CVR values than medetomidine (median whole‐brain CBF of 157.7 vs 84.4 mL/100 g/min and CVR of 0.54 vs 51.7% in C57BL/6 J mice). The other two isoflurane protocols lowered the CBF and increased the CVR values compared with medium isoflurane anesthesia, without obvious differences between them (median whole‐brain CBF of 138.9 vs 131.7 mL/100 g/min and CVR of 10.0 vs 9.6%, in C57BL/6 J mice). Furthermore, CVR was shown to be dependent on baseline CBF, regardless of the anesthesia protocol used.     

An account of the discrepancy between MRI and PET cerebral blood flow measures. A high-field MRI investigation

There is controversy concerning the discrepancy between absolute cerebral blood flow (CBF) values measured using positron emission tomography (PET) and magnetic resonance imaging (MRI). To gain insight into this problem, the increased signal-to-noise ratio (SNR) and extended T(1) relaxation times of blood and tissue at 3.0 T were exploited to perform pulsed arterial spin labeling (PASL) MRI measurements as a function of spatial resolution and post-labeling delay. The results indicate that, when using post-labeling delays shorter than 1500 ms, MRI gray matter flow values may become as high as several times the correct CBF values owing to tissue signal contamination by remaining arterial blood water label. For delays above 1500 ms, regional PASL-based CBF values (n = 5; frontal gray matter: 48.8 +/- 3.3(SD) ml/100 g/min; occipital gray matter: 49.3 +/- 4.5 ml/100 g/min) comparable with PET-based measurements can be obtained by using spatial resolutions comparable with PET (5-7.5 mm in-plane). At very high resolution (2.5 x 2.5 x 3 mm(3)), gray matter CBF values were found to increase by 10-20%, a consequence attributed to reduction in partial volume effects with cerebrospinal fluid and white matter. The recent availability of MRI field strengths of 3.0 T and higher will facilitate the use of MRI-based CBF measurements in the clinic.     

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.     

In vivo quantification of hyperoxic arterial blood water T1

Normocapnic hyperoxic and hypercapnic hyperoxic gas challenges are increasingly being used in cerebrovascular reactivity (CVR) and calibrated functional MRI experiments. The longitudinal arterial blood water relaxation time (T_1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma‐dissolved O₂ (pO₂) and increased oxygen bound to hemoglobin in arteries (Y_a) and veins (Y_v). The dependence of T_1a on Y_a and Y_v has been elegantly characterized ex vivo; however, the combined influence of pO₂, Y_a and Y_v on T_1a in vivo under normal ventilation has not been reported. Here, T_1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T₁‐dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n = 14; age, 31.5 ± 7.2 years) were scanned using pseudo‐continuous ASL in combination with room air (RA; 21% O₂/79% N₂), hypercapnic normoxic (HN; 5% CO₂/21% O₂/74% N₂) and hypercapnic hyperoxic (HH; 5% CO₂/95% O₂) gas administration. HH T_1a was calculated by requiring that the HN and HH cerebral blood flow (CBF) change be identical. The HH protocol was then repeated in patients (n = 10; age, 61.4 ± 13.3 years) with intracranial stenosis to assess whether an HH T_1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T_1a decreased from 1.65 s at baseline to 1.49 ± 0.07 s during HH. In patients, CBF values in the affected flow territory for the HH condition were increased relative to baseline CBF values and were within the physiological range (RA CBF = 36.6 ± 8.2 mL/100 g/min; HH CBF = 45.2 ± 13.9 mL/100 g/min). It can be concluded that hyperoxic (95% O₂) 3‐T arterial blood T_1aHH = 1.49 ± 0.07 s relative to a normoxic T_1a of 1.65 s. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

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.     

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.