Flow-sensitive Alternating Inversion Recovery Research Articles

Consensus-based technical recommendations for clinical translation of renal ASL MRI

ObjectivesThis study aimed at developing technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5 T and 3 T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-centre clinical studies.MethodsAn international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting.ResultsFifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labelling with a single-slice spin-echo EPI readout with background suppression and a simple but robust quantification model.DiscussionThis approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data become available, since the renal ASL literature is rapidly expanding.

Comparison of multi-delay FAIR and pCASL labeling approaches for renal perfusion quantification at 3T MRI

ObjectiveTo compare the most commonly used labeling approaches, flow-sensitive alternating inversion recovery (FAIR) and pseudocontinuous arterial spin labeling (pCASL), for renal perfusion measurement using arterial spin labeling (ASL) MRI.MethodsMulti-delay FAIR and pCASL were performed in 16 middle-aged healthy volunteers on two different occasions at 3T. Relative perfusion-weighted signal (PWS), temporal SNR (tSNR), renal blood flow (RBF), and arterial transit time (ATT) were calculated for the cortex and medulla in both kidneys. Bland–Altman plots, intra-class correlation coefficient, and within-subject coefficient of variation were used to assess reliability and agreement between measurements.ResultsFor the first visit, RBF was 362 ± 57 and 140 ± 47 mL/min/100 g, and ATT was 0.47 ± 0.13 and 0.70 ± 0.10 s in cortex and medulla, respectively, using FAIR; RBF was 201 ± 72 and 84 ± 27 mL/min/100 g, and ATT was 0.71 ± 0.25 and 0.86 ± 0.12 s in cortex and medulla, respectively, using pCASL. For both labeling approaches, RBF and ATT values were not significantly different between visits. Overall, FAIR showed higher PWS and tSNR. Moreover, repeatability of perfusion parameters was better using FAIR.DiscussionThis study showed that compared to (balanced) pCASL, FAIR perfusion values were significantly higher and more comparable between visits.

Neurite orientation dispersion and density imaging for evaluating the severity of neonatal hypoxic-ischemic encephalopathy in rats

PurposeTo evaluate the utility of neurite orientation dispersion and density imaging (NODDI) for longitudinally assessing neonatal hypoxic-ischemic (HI) encephalopathy severity with 7.0 T magnetic resonance imaging. MethodsThirteen 8-day-old Wistar rats underwent unilateral ligation of the left common carotid artery followed by mild (1 h; n = 6) or severe (2 h; n = 7) hypoxic exposure (8% O2, 34 °C). Diffusion-weighted, T2-weighted (T2W), and flow-sensitive alternating inversion recovery images were obtained with a horizontal 7.0 T scanner at 1, 24, 72, and 168 h after HI insult. The fractional anisotropy (FA), apparent diffusion coefficient (ADC), intracellular volume fraction (ICVF), isotropic volume fraction (ISO), orientation dispersion index (ODI), and cerebral blood flow (CBF) values were calculated for each group (mild and severe) at each time point (1, 24, 72, and 168 h). ICVF, ISO, and ODI were the NODDI parameters. ResultsLeft hemisphere brain damage was identified as slight hyperintensity on T2W images after 1 h in both groups. In the severe group only, the signal hyperintensity increased time-dependently over 168 h. The ADC and CBF were not significantly different between the groups within any region. The ICVF and ODI were significantly higher in the severe vs. mild group at various points between 1 and 168 h (cortex, striatum, or white matter), whereas the FA was significantly higher in the mild vs. severe group at 168 h (cortex and white matter). The ISO was higher in the severe vs. mild group at 72 h (striatum) and 168 h (all regions), while the ISO was significantly higher in the mild vs. severe group at 24 h (all regions). ConclusionHere, ODI, a NODDI metric, identified early differences between mild and severe HI injuries. Our findings support the potential utility of NODDI for determining neonatal HI encephalopathy severity in rats.

Optimal repetition time for free breathing myocardial arterial spin labeling.

The aim of this study was to improve the scan efficiency of ASL in the myocardium. Free breathing FAIR-ASL scans with different TRs were compared, while keeping the acquisition time constant. Scans were named by the trigger pulse that started each acquisition: every two (TP1), four (TP2) and six (TP3) cardiac cycles. TP2 offered the best alternative with a coefficient of variation of 17.15% intrasession and 36.85% intersession. Mean MBF increased by 0.22±0.41ml/g/min with mild stress.

Non-invasive assessment of placental perfusion in vivo using arterial spin labeling (ASL) MRI: A preclinical study in rats

IntroductionNon-invasive assessment of placental perfusion is of great interest to characterize placental function in clinical practice. This article proposes a strictly non-invasive MRI technique using ASL to quantify placental blood flow in vivo. The aim of this study was to develop a fMRI tool to quantify placental blood flow (PBF) in rat, by using arterial spin labeling (ASL) MRI at 4.7 T. Materials and methodsMRI was performed with a dedicated magnet for small animals, in pregnant rats on day 20 of the 22-day gestation period. A Look-Locker flow-sensitive alternating inversion recovery gradient echo sequence was developed as ASL technique (TE: 1.55 ms; TR: 3.5 ms, TI: 56 ms, deltaTI: 56 ms, FA: 20°, Matrix: 128 × 128, 8 segments, 4 Nex). Labeling was performed with global and slice-selective inversions, and T1 map was obtained for each mode of inversion. PBF was then derived from a compartmental model of the variation of T1 between global and slice-selective inversions. ResultsThe full protocol was completed and ASL image post-processing was successful in 18 rats. Forty-seven placentas were analyzed, with a mean PBF of 147 ± 70 ml/min/100 g of placenta, consistent with published values of placental perfusion using invasive techniques. ConclusionASL MRI is feasible for the quantification of PBF in rats at 4.7 T. This technique, which requires no administration of contrast media, could have implications for non-invasive longitudinal and in vivo animal studies and may be useful for the management of human pregnancies.

Coupling between cerebral blood flow and cerebral blood volume: Contributions of different vascular compartments.

A better understanding of the coupling between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is vital for furthering our understanding of the BOLD response. The aim of this study was to measure CBF‐CBV coupling in different vascular compartments during neural activation. Three haemodynamic parameters were measured during a visual stimulus. Look‐Locker flow‐sensitive alternating inversion recovery was used to measure changes in CBF and arterial CBV (CBVa) using sequence parameters optimized for each contrast. Changes in total CBV (CBVtot) were measured using a gadolinium‐based contrast agent technique. Haemodynamic changes were extracted from a region of interest based on voxels that were activated in the CBF experiments. The CBF‐CBVtot coupling constant α tot was measured as 0.16 ± 0.14 and the CBF‐CBVa coupling constant α a was measured as 0.65 ± 0.24. Using a two‐compartment model of the vasculature (arterial and venous), the change in venous CBV (CBVv) was predicted for an assumed value of baseline arterial and venous blood volume. These results will enhance the accuracy and reliability of applications that rely on models of the BOLD response, such as calibrated BOLD.

Robust kidney perfusion mapping in pediatric chronic kidney disease using single-shot 3D-GRASE ASL with optimized retrospective motion correction.

To develop a robust renal arterial spin labeling (ASL) acquisition and processing strategy for mapping renal blood flow (RBF) in a pediatric cohort with severe kidney disease. A single-shot background-suppressed 3D gradient and spin-echo (GRASE) flow-sensitive alternating inversion recovery (FAIR) ASL acquisition method was used to perform 2 studies. First, an evaluation of the feasibility of single-shot 3D-GRASE and retrospective noise reduction methods was performed in healthy volunteers. Second, a pediatric cohort with severe chronic kidney disease underwent single-shot 3D-GRASE FAIR ASL and RBF was quantified following several retrospective motion correction pipelines, including image registration and threshold-free weighted averaging. The effect of motion correction on the fit errors of saturation recovery (SR) images (required for RBF quantification) and on the perfusion-weighted image (PWI) temporal signal-to-noise ratio (tSNR) was evaluated, as well as the intra- and inter-session repeatability of renal longitudinal relaxation time (T1 ) and RBF. The mean cortical and/or functional renal parenchyma RBF in healthy volunteers and CKD patients was 295 ± 97 and 95 ± 47 mL/100 g/min, respectively. Motion-correction reduced image artefacts in both T1 and RBF maps, significantly reduced SR fit errors, significantly increased the PWI tSNR and improved the improved the repeatability of T1 and RBF in the pediatric patient cohort. Single-shot 3D-GRASE ASL combined with retrospective motion correction enabled repeatable non-invasive RBF mapping in the first pediatric cohort with severe kidney disease undergoing ASL scans.

Perfusion of the placenta assessed using arterial spin labeling and ferumoxytol dynamic contrast enhanced magnetic resonance imaging in the rhesus macaque.

To investigate the correspondence between arterial spin labeling (ASL) flow-sensitive alternating inversion recovery (FAIR) and ferumoxytol DCE MRI for the assessment of placental intervillous perfusion. Ten pregnant macaques in late second trimester were imaged at 3 T using a 2D ASL FAIR, with and without outer-volume saturation pulses used to control the bolus width, and a 3D ferumoxytol DCE-MRI acquisition. The ASL tagged/control pairs were averaged, subtracted, and normalized to create perfusion ratio maps. Contrast arrival time and uptake slope were estimated by fitting the DCE data to a sigmoid function. Macaques (N = 4) received interleukin-1β to induce inflammation and disrupt perfusion. The FAIR tag modification with outer-volume saturation reduced the median ASL ratio percentage compared with conventional FAIR (0.64% ± 1.42% versus 0.71% ± 2.00%; P < .05). Extended ferumoxytol arrival times (34 ± 25 seconds) were observed across the placenta. No significant DCE signal change was measured in fetal tissue ( 0.6% ± 3.0%; P = .52) or amniotic fluid (1.9% ± 8.8%; P = .59). High ASL ratio was significantly correlated with early arrival time and high uptake slope (P < .05), but ASL signal was not above noise in late-DCE-enhancing regions. No significant differences were observed in perfusion measurements between the interleukin-1β and controls (P > .05). The ASL-FAIR and ferumoxytol DCE-MRI methods are feasible to detect early blood delivery to the macaque placenta. Outer volume saturation reduced the high macrovascular ASL signal. Interleukin-1β exposure did not alter placental intervillous perfusion. An endogenous-labeling perfusion technique is limited due to extended transit times for flow within the placenta beyond the immediate vicinity of the maternal spiral arteries.

Ultra-high-field arterial spin labelling MRI for non-contrast assessment of cortical lesion perfusion in multiple sclerosis

ObjectivesTo assess the feasibility of using an optimised ultra-high-field high-spatial-resolution low-distortion arterial spin labelling (ASL) MRI acquisition to measure focal haemodynamic pathology in cortical lesions (CLs) in multiple sclerosis (MS).MethodsTwelve MS patients (eight female, mean age 50 years; range 35–64 years) gave informed consent and were scanned on a 7 Tesla Philips Achieva scanner. Perfusion data were collected at multiple post-labelling delay times using a single-slice flow-sensitive alternating inversion recovery ASL protocol with a balanced steady-state free precession readout scheme. CLs were identified using a high-resolution Phase-Sensitive Inversion Recovery (PSIR) scan. Significant differences in perfusion within CLs compared to immediately surrounding normal appearing grey matter (NAGMlocal) and total cortical normal appearing grey matter (NAGMcortical) were assessed using paired t-tests.ResultsForty CLs were identified in PSIR scans that overlapped with the ASL acquisition coverage. After excluding lesions due to small size or intravascular contamination, 27 lesions were eligible for analysis. Mean perfusion was 40 ± 25 ml/100 g/min in CLs, 53 ± 12 ml/100 g/min in NAGMlocal, and 53 ± 8 ml/100 g/min in NAGMcortical. CL perfusion was significantly reduced by 23 ± 9% (mean ± SE, p = 0.013) and 26 ± 9% (p = 0.006) relative to NAGMlocal and NAGMcortical perfusion, respectively.ConclusionThis is the first ASL MRI study quantifying CL perfusion in MS at 7 Tesla, demonstrating that an optimised ASL acquisition is sensitive to focal haemodynamic pathology previously observed using dynamic susceptibility contrast MRI. ASL requires no exogenous contrast agent, making it a more appropriate tool to monitor longitudinal perfusion changes in MS, providing a new window to study lesion development.Key Points• Perfusion can be quantified within cortical lesions in multiple sclerosis using an optimised high spatial resolution arterial spin Labelling MRI acquisition at ultra-high-field.• The majority of cortical lesions assessed using arterial spin labelling are hypo-perfused compared to normal appearing grey matter, in agreement with dynamic susceptibility contrast MRI literature.• Arterial spin labelling MRI, which does not involve the injection of a contrast agent, is a safe and appropriate technique for repeat scanning of an individual patient.

Motion-corrected multiparametric renal arterial spin labelling at 3 T: reproducibility and effect of vasodilator challenge

ObjectivesWe investigated the feasibility and reproducibility of free-breathing motion-corrected multiple inversion time (multi-TI) pulsed renal arterial spin labelling (PASL), with general kinetic model parametric mapping, to simultaneously quantify renal perfusion (RBF), bolus arrival time (BAT) and tissue T1.MethodsIn a study approved by the Health Research Authority, 12 healthy volunteers (mean age, 27.6 ± 18.5 years; 5 male) gave informed consent for renal imaging at 3 T using multi-TI ASL and conventional single-TI ASL. Glyceryl trinitrate (GTN) was used as a vasodilator challenge in six subjects. Flow-sensitive alternating inversion recovery (FAIR) preparation was used with background suppression and 3D-GRASE (gradient and spin echo) read-out, and images were motion-corrected. Parametric maps of RBF, BAT and T1 were derived for both kidneys. Agreement was assessed using Pearson correlation and Bland-Altman plots.ResultsInter-study correlation of whole-kidney RBF was good for both single-TI (r2 = 0.90), and multi-TI ASL (r2 = 0.92). Single-TI ASL gave a higher estimate of whole-kidney RBF compared to multi-TI ASL (mean bias, 29.3 ml/min/100 g; p <0.001). Using multi-TI ASL, the median T1 of renal cortex was shorter than that of medulla (799.6 ms vs 807.1 ms, p = 0.01), and mean whole-kidney BAT was 269.7 ± 56.5 ms. GTN had an effect on systolic blood pressure (p < 0.05) but the change in RBF was not significant.ConclusionsFree-breathing multi-TI renal ASL is feasible and reproducible at 3 T, providing simultaneous measurement of renal perfusion, haemodynamic parameters and tissue characteristics at baseline and during pharmacological challenge.Key points• Multiple inversion time arterial spin labelling (ASL) of the kidneys is feasible and reproducible at 3 T.• This approach allows simultaneous mapping of renal perfusion, bolus arrival time and tissue T1during free breathing.• This technique enables repeated measures of renal haemodynamic characteristics during pharmacological challenge.

Intracranial compliance is associated with symptoms of orthostatic intolerance in chronic fatigue syndrome.

Symptoms of orthostatic intolerance (OI) are common in Chronic Fatigue Syndrome (CFS) and similar disorders. These symptoms may relate to individual differences in intracranial compliance and cerebral blood perfusion. The present study used phase-contrast, quantitative flow magnetic resonance imaging (MRI) to determine intracranial compliance based on arterial inflow, venous outflow and cerebrospinal fluid flow along the spinal canal into and out of the cranial cavity. Flow-sensitive Alternating Inversion Recovery (FAIR) Arterial Spin Labelling was used to measure cerebral blood perfusion at rest. Forty patients with CFS and 10 age and gender matched controls were scanned. Severity of symptoms of OI was determined from self-report using the Autonomic Symptom Profile. CFS patients reported significantly higher levels of OI (p < .001). Within the patient group, higher severity of OI symptoms were associated with lower intracranial compliance (r = -.346, p = .033) and higher resting perfusion (r = .337, p = .038). In both groups intracranial compliance was negatively correlated with cerebral perfusion. There were no significant differences between the groups in intracranial compliance or perfusion. In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS.

Evaluation of 2D Imaging Schemes for Pulsed Arterial Spin Labeling of the Human Kidney Cortex

A number of imaging readout schemes are proposed for renal arterial spin labeling (ASL) to quantify kidney cortex perfusion, including gradient echo-based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo-based schemes of spin-echo echo-planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these two-dimensional (2D) imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Ten healthy volunteers with normal renal function were scanned using each 2D multi-slice imaging scheme, in combination with a respiratory triggered flow-sensitive alternating inversion recovery (FAIR) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion-weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. For each imaging scheme, the renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100g/min, GE-EPI: 222 ± 18 mL/100g/min, SE-EPI: 201 ± 36 mL/100g/min, and TSE: 200 ± 20 mL/100g/min). Perfusion was found to be higher for GE-based readouts when compared with SE-based readouts, with significantly higher measured perfusion for the bFFE readout when compared with all other schemes (p < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI when compared with all other schemes (p < 0.05), the SE-EPI readout gave the highest tSNR, and was found to be the most reproducible scheme for the assessment of kidney cortex, with a coefficient of variation (CoV) of 17.2%, whilst minimizing variability of the perfusion-weighted signal across slices for whole-kidney perfusion assessment. For the assessment of kidney cortex perfusion using 2D readout schemes, SE-EPI provides optimal tSNR, minimal variability across slices, and repeatable data acquired in a short scan time with low specific absorption rate.

Consistency of Multiple Renal Functional MRI Measurements Over 18 Months.

Identification of patients with progressive chronic kidney disease (CKD) and those likely to respond to candidate therapeutics is urgently needed. Functional MRI measurements have shown promise. However, knowledge about the consistency of the measurements is essential to conduct longitudinal studies. To investigate the consistency of repeated functional MRI measurements in healthy subjects. Prospective, longitudinal study. Seventeen healthy subjects were examined on two different occasions, 18 months apart. Multiple gradient-recalled-echo, 2D navigator-gated flow-sensitive alternating inversion recovery True-FISP and spin-echo planar diffusion-weighted sequences were used on a 3T scanner. Images were acquired on two different scanner configurations. Blood oxygenation level-dependent (BOLD) R2*, arterial spin labeling (ASL) perfusion-derived blood flow (BF) and apparent diffusion coefficient (ADC) maps were analyzed using a custom image processing toolbox. Regions of interest (ROIs) were placed on renal cortex, medulla, and whole kidney. Multiple researchers were involved in defining the ROIs. Intra- and intersubject coefficients of variation (CV) and Bland-Altman plots were used to measure consistency and evaluate bias in the measurements. A nonparametric Wilcoxon test was used to compare differences between two timepoints. The intrasubject CV for R2* and ADC were 6.8% and 5.3% with small (-3.8 and 5.3%) bias, respectively, comparing baseline and 18-month data. Intrasubject CV for renal cortex BF was higher (18.7%) compared to R2* and ADC, but comparable to prior literature values over shorter durations. It also exhibited a larger bias (-15.4%) between two timepoints and significantly lower values (P = 0.022) at 18-month data. All three MRI parameters over 18 months, even with a scanner upgrade and involving multiple observers, showed good consistency. These results are useful for the interpretation of longitudinal data and support the use of these methods to monitor progression in patients with CKD. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:514-521.

Quantitative assessment of cerebral venous blood T2 in mouse at 11.7T: Implementation, optimization, and age effect.

To develop a non-contrast-agent MRI technique to quantify cerebral venous T2 in mice. We implemented and optimized a T2 -relaxation-under-spin-tagging (TRUST) sequence on an 11.7 Tesla animal imaging system. A flow-sensitive-alternating-inversion-recovery (FAIR) module was used to generate control and label images, pair-wise subtraction of which yielded blood signals. Then, a T2 -preparation module was applied to produce T2 -weighted images, from which blood T2 was quantified. We conducted a series of technical studies to optimize the imaging slice position, inversion slab thickness, post-labeling delay (PLD), and repetition time. We also performed three physiological studies to examine the venous T2 dependence on hyperoxia (N = 4), anesthesia (N = 3), and brain aging (N = 5). Our technical studies suggested that, for efficient data acquisition with minimal bias in estimated T2 , a preferred TRUST protocol was to place the imaging slice at the confluence of sagittal sinuses with an inversion-slab thickness of 2.5-mm, a PLD of 1000 ms and a repetition time of 3.5 s. Venous T2 values under normoxia and hyperoxia (inhaling pure oxygen) were 26.9 ± 1.7 and 32.3 ± 2.2 ms, respectively. Moreover, standard isoflurane anesthesia resulted in a higher venous T2 compared with dexmedetomidine anesthesia (N = 3; P = 0.01) which is more commonly used in animal functional MRI studies to preserve brain function. Venous T2 exhibited a decrease with age (N = 5; P < 0.001). We have developed and optimized a noninvasive method to quantify cerebral venous blood T2 in mouse at 11.7 T. This method may prove useful in studies of brain physiology and pathophysiology in animal models. Magn Reson Med 80:521-528, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Demonstration of velocity selective myocardial arterial spin labeling perfusion imaging in humans.

Transit delay is a potential source of error in cardiac arterial spin-labeled (ASL) in heart failure or with collateral circulation. This study demonstrates the feasibility of using transit delay insensitive velocity selective ASL and compares its performance with flow-sensitive alternating inversion recovery (FAIR) ASL. Velocity selective labeling was achieved using an adiabatic BIR8 preparation. FAIR and velocity-selective ASL (VSASL) with various velocity cutoffs (VC = 10-40 cm/s) and labeling directions (anterior-posterior X, lateral-septal Y, and apical-basal Z) were carried out in 10 healthy volunteers (1F/9M age 23-30 y). Myocardial blood flow (MBF) and temporal signal-to-noise (TSNR) were measured. VSASL sensitivity to perfusion decreased with increasing VC . At low VC (<5 cm/s), spurious labeling of myocardium occurs and overestimates MBF. MBF measured with FAIR (1.12 ± 0.26 ml/g/min) and VASL (1.26 ± 0.27 ml/g/min) at VC of 10 cm/s in Z were comparable (TOST with difference of 0.30 ml/g/min, P = 0.049). TSNR was 2.8 times larger using FAIR (13.62 ± 5.25) than in VSASL (4.87 ± 1.58). VSASL was insensitive to perfusion in the Y direction. X and Z performed similarly with TSNR of 4.17 ± 2.32 and 3.97 ± 0.56, respectively. VSASL is a promising alternative to FAIR ASL in the heart and is well suited for scenarios when transit delays are long. Magn Reson Med 80:272-278, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Multiple boli arterial spin labeling for high signal-to-noise rodent brain perfusion imaging.

A systematic method is proposed for optimizing a promising preclinical arterial spin labeling (ASL) sequence based on the use of a train of adiabatic radiofrequency pulses labeling successive boli of blood water. The sequence optimization is performed and evaluated using brain imaging experiments in mice and in rats. It involves the investigation of several parameters, ranging from the number of adiabatic pulses and labeling duration to the properties of the adiabatic hyperbolic secant pulses (ie, amplitude and frequency modulation). Species-dependent parameters are identified, allowing for robust fast optimization protocols to be introduced. The resulting optimized multiple boli ASL (mbASL) sequence provides with significantly higher average signal-to-noise ratios (SNR) per voxel volume than currently encountered in ASL studies (278 mm-3 in mice and 172 mm-3 in rats). Comparing with the commonly used flow-sensitive alternating inversion recovery technique (FAIR), mbASL-to-FAIR SNR ratios reach 203% for mice and 725% for rats. When properly optimized, mbASL can offer a robust, high SNR ASL alternative for rodent brain perfusion studies Magn Reson Med 79:1020-1030, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Quantitative single breath-hold renal arterial spin labeling imaging at 7T.

To evaluate the feasibility of quantitative single breath-hold renal arterial spin labeling (ASL) imaging at 7T. A single-shot fast spin echo FAIR (flow-sensitive alternating inversion recovery) method was used to perform two studies. First, a multi-delay perfusion study was performed to estimate the spin labeling temporal bolus width achievable with a local transceiver array coil at 7T. Second, with a conservatively defined bolus width, a quantitative perfusion study was performed using the single subtraction approach. To address issues of B1+ inhomogeneity/efficiency and excessive short-term specific absorption rates, various strategies were used, such as dynamic radiofrequency shimming and optimization. A conservative temporal bolus width of 600 ms determined from the multi-delay study was applied for single-subtraction imaging to measure the renal blood flow in the cortex and medulla: 303 ± 31.8 and 91.3 ± 15.2 (mL/100 g/min), respectively. The estimated spatial and temporal signal-to-noise ratios of renal perfusion measurements were 3.8 ± 0.7 and 2.4 ± 0.6 for the cortex, and 2.2 ± 0.6 and 1.4 ± 0.2 for the medulla. With proper management of field strength specific challenges, quantitative renal ASL imaging can be achieved at 7T within a single breath-hold. Magn Reson Med 79:815-825, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Quantification of Mouse Renal Perfusion Using Arterial Spin Labeled MRI at 1 T

Quantitative measurement of renal perfusion in murine models provides important information on the organ physiology and disease states. The 1-T desktop magnetic resonance imaging has a small footprint and a self-contained fringe field. This resultant flexibility in siting makes the system ideal for preclinical imaging research. Our objective was to evaluate the capability of the 1-T desktop magnetic resonance imaging to measure mouse renal perfusion without the administration of exogenous contrast agents. We implemented a flow-sensitive alternating inversion recovery (FAIR)-based arterial spin labeling sequence with a mouse volume coil on a 1-T desktop magnetic resonance scanner. The validity of the implementation was tested by comparing obtained renal perfusion results with literature values for normal mice and challenging the technique with mice treated with furosemide, a blood vessel vasoconstrictor drug. The measured cortical and medullary perfusions were quantified to be 402 ± 95 and 184 ± 52 mL/100 g/min, respectively, in agreement with literature values. The ratio of cortical to medullary renal blood flow was between 2 and 3 and was independent of the mouse weight. As expected, upon furosemide injection, a decrease (~50%) in cortical perfusion was observed in the mice population, at 1 hour post injection compared to baseline (P < 0.0001), which returned to baseline after 24 hours (P = 0.68). We reported the successful application of FAIR-based arterial spin labeling for noncontrast perfusion measurement of mouse kidneys using a 1-T desktop scanner. The easy implementation of FAIR sequence on a 1-T desktop scanner offers the potential for longitudinal perfusion studies in limited access areas such as behind the barrier in mouse facilities and in multimodality preclinical imaging laboratories without the administration of exogenous contrast agents.

MRI-based quantification of renal perfusion in mice: Improving sensitivity and stability in FAIR ASL

PurposeThe importance of the orientation of the selective inversion slice in relation to the anatomy in flow-sensitive alternating inversion recovery arterial spin labeling (FAIR ASL) kidney perfusion measurements is demonstrated by comparing the standard FAIR scheme to a scheme with an improved slice selective control experiment. MethodsA FAIR ASL method is used. The selective inversion preparation slice is set perpendicular to the measurement slice to decrease the unintended labeling of arterial spins in the control experiment. A T1*-based quantification method compensates for the effects of the imperfect inversion on the edge of the selective inversion slice. The quantified perfusion values are compared to the standard experiment with parallel orientation of imaging and selective inversion slice. ResultsPerfusion maps acquired with the perpendicular inversion slice orientation show higher sensitivity compared to the parallel orientation. The T1*-based quantification method removes artifacts arising from imperfect inversion slice profiles. The stability is improved. ConclusionAdjusting the labeling technique to the anatomy is of high importance. Improved sensitivity and reproducibility could be demonstrated. The proposed method provides a solution to the problem of FAIR ASL measurements of renal perfusion in coronal view.

Longitudinal evaluation of perfusion changes in acute and chronic renal allograft rejection using arterial spin labeling in translational mouse models.

To examine the longitudinal changes of renal perfusion due to acute and chronic renal allograft rejection by using arterial spin labeling (ASL) MRI in translational mouse models of isogenic and allogenic kidney transplantation (ktx). Acute rejection was induced by allogenic ktx of C57BL/6 (B6)-kidney grafts to BALB/c-recipients with prolonged cold ischemia (CIT) of 60 minutes (n = 13). To induce chronic rejection BALB/c-kidneys were transplanted into B6-recipients with short CIT of 30 minutes (n = 22). Isogenic grafts without rejection (n = 14 with prolonged, n = 9 with short CIT) and normal kidneys (n = 22) were used for comparison. Perfusion was measured on a 7T small-animal magnetic resonance imaging (MRI) scanner using flow-sensitive alternating inversion recovery (FAIR) ASL-sequences at day 1 and 6 (acute) or at week 3 and 6 (chronic) after surgery. Histological analyses of grafts included inflammation, vascular changes, and fibrosis. In the acute ktx model, ASL showed perfusion impairment in isogenic and allogenic kidney grafts. Perfusion of allografts further decreased until day 6 and remained stable in isografts without rejection (allogenic ktx 62 ± 21 vs. isogenic ktx 181 ± 39 ml/min/100g, P < 0.01). In the chronic ktx model, perfusion in isografts was similar to normal kidneys over the entire observation period. Perfusion was severely reduced in allografts compared to isografts (week 3: 28 ± 7 vs. 310 ± 46 ml/min/100g, P < 0.001, week 6: 32 ± 5 vs. 367 ± 72 ml/min/100g, P < 0.001). Histological analysis revealed severe inflammation, vascular occlusion, and rejection in allografts. Chronic rejection grafts showed endothelialitis, peritubular capillaritis, interstitial fibrosis, and tubular atrophy. ASL allows longitudinal assessment of renal perfusion impairment due to acute and chronic renal allograft rejection in translational mouse models. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1664-1672.