Flow Alternating Inversion Recovery Research Articles

On the application of pseudo-continuous arterial spin labeled MRI for pulmonary perfusion imaging

PurposeTo evaluate different approaches for the effective assessment of pulmonary perfusion with a pseudo-continuous arterial spin labeled (pCASL) MRI. Materials and methodsFour different approaches were evaluated: 1) Cardiac-triggered inferior vena cava (IVC) labeling; 2) IVC labeling with cardiac-triggered acquisition; 3) Right pulmonary artery (RPA) labeling with cardiac-triggered acquisition; and 4) Cardiac-triggered RPA labeling with background suppression (BGS). Each approach was evaluated in 5 healthy volunteers (n = 20) using coefficient of variation (COV) across averages. Approach 4 was also compared against a flow alternating inversion recovery (FAIR). ResultsThe IVC labeling (Approach 1) achieved perfusion-weighted images of both lungs, although this approach was more sensitive to variations in heart rate. Cardiac-triggered acquisitions using IVC (Approach 2) and RPA (Approach 3) labeling improved signal consistencies, but were incompatible with BGS. The cardiac-triggered RPA labeling with BGS (Approach 4) achieved a COV of 0.34 ± 0.03 (p < 0.05 compared to IVC labeling approaches) and resulted in perfusion value of 434 ± 64 mL/100 g/min, which was comparable to 451 ± 181 mL/100 g/min measured by FAIR (p = 0.82). DiscussionPulmonary perfusion imaging using pCASL-MRI is highly sensitive to cardiac phase, and requires approaches to minimize flow-induced signal variations. Cardiac-triggered RPA labeling with BGS achieves reduced COV and enables robust pulmonary perfusion imaging.

A split-label design for simultaneous measurements of perfusion in distant slices by pulsed arterial spin labeling.

PurposeMultislice arterial spin labeling (ASL) MRI acquisitions are currently challenging in skeletal muscle because of long transit times, translating into low‐perfusion SNR in distal slices when large spatial coverage is required. However, fiber type and oxidative capacity vary along the length of healthy muscles, calling for multislice acquisitions in clinical studies. We propose a new variant of flow alternating inversion recovery (FAIR) that generates sufficient ASL signal to monitor exercise‐induced perfusion changes in muscle in two distant slices.MethodsLabel around and between two 7‐cm distant slices was created by applying the presaturation/postsaturation and selective inversion modules selectively to each slice (split‐label multislice FAIR). Images were acquired using simultaneous multislice EPI. We validated our approach in the brain to take advantage of the high resting‐state perfusion, and applied it in the lower leg muscle during and after exercise, interleaved with a single‐slice FAIR as a reference.ResultsWe show that standard multislice FAIR leads to an underestimation of perfusion, while the proposed split‐label multislice approach shows good agreement with separate single‐slice FAIR acquisitions in brain, as well as in muscle following exercise.ConclusionSplit‐label FAIR allows measuring muscle perfusion in two distant slices simultaneously without losing sensitivity in the distal slice.

Exploring label dynamics of velocity-selective arterial spin labeling in the kidney.

PurposeVelocity‐selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR).MethodsArterial spin labeling data were acquired in 7 subjects, using free‐breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior–posterior velocity‐encoding direction. Cortical perfusion‐weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported.ResultsIn contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was ≤ 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 ± 79 ms, P < .05). Finally, the average cortical renal blood flow measured with cutoff velocities of 5 cm/s (398 ± 84 mL/min/100 g) and 10 cm/s (472 ± 160 mL/min/100 g) were similar to renal blood flow measured with FAIR (441 ± 84 mL/min/100 g) (P > .05) with good correlations on subject level.ConclusionVelocity‐selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time‐efficient, single‐time‐point, free‐breathing renal perfusion measurements, despite lower tSNR than FAIR.

Multi-organ comparison of flow-based arterial spin labeling techniques: Spatially non-selective labeling for cerebral and renal perfusion imaging.

PurposeFlow‐based arterial spin labeling (ASL) techniques provide a transit‐time insensitive alternative to the more conventional spatially selective ASL techniques. However, it is not clear which flow‐based ASL technique performs best and also, how these techniques perform outside the brain (taking into account eg, flow‐dynamics, field‐inhomogeneity, and organ motion). In the current study we aimed to compare 4 flow‐based ASL techniques (ie, velocity selective ASL, acceleration selective ASL, multiple velocity selective saturation ASL, and velocity selective inversion prepared ASL [VSI‐ASL]) to the current spatially selective reference techniques in brain (ie, pseudo‐continuous ASL [pCASL]) and kidney (ie, pCASL and flow alternating inversion recovery [FAIR]).MethodsBrain (n = 5) and kidney (n = 6) scans were performed in healthy subjects at 3T. Perfusion‐weighted signal (PWS) maps were generated and ASL techniques were compared based on temporal SNR (tSNR), sensitivity to perfusion changes using a visual stimulus (brain) and robustness to respiratory motion by comparing scans acquired in paced‐breathing and free‐breathing (kidney).ResultsIn brain, all flow‐based ASL techniques showed similar tSNR as pCASL, but only VSI‐ASL showed similar sensitivity to perfusion changes. In kidney, all flow‐based ASL techniques had comparable tSNR, although all lower than FAIR. In addition, VSI‐ASL showed a sensitivity to B1‐inhomogeneity. All ASL techniques were relatively robust to respiratory motion.ConclusionIn both brain and kidney, flow‐based ASL techniques provide a planning‐free and transit‐time insensitive alternative to spatially selective ASL techniques. VSI‐ASL shows the most potential overall, showing similar performance as the golden standard pCASL in brain. However, in kidney, a reduction of B1‐sensitivity of VSI‐ASL is necessary to match the performance of FAIR.

Hyperpolarized 13 C,15 N2 -urea T2 relaxation changes in acute kidney injury.

To investigate the correlation between renal ischemia and 13 C-urea T2 relaxation rate in an acute kidney injury (AKI) rat model. Six rats subjected to unilateral renal ischemia were investigated. Creatinine clearance, urine output, plasma creatinine as well as blood-urea nitrogen (BUN) values were acquired before and after the procedure. 1 H T2* mapping was acquired using blood oxygenation level dependent (BOLD) MRI and hyperpolarized 13 C-urea T2 mapping was acquired using a 2D golden-angle radial approach. Kidney perfusion was estimated using noncontrast flow alternating inversion recovery arterial spin labeling. All rats showed clinical signs of AKI with increased plasma creatinine and increased BUN. Whole kidney 13 C-urea T2 significantly decreased 26% (P = 0.001) 24 h after reperfusion. A significantly different (3.7 times steeper; P = 0.008) osmolality gradient was observed in the contralateral kidney (P = 0.008; R2 = 0.86) compared with the postischemic kidney (P = 0.0004, R2 =0.97). Whole kidney T2* signal (P = 0.14) and T2* gradient (P = 0.26) was similar between the two kidneys. Oxygen availability dependency on 13 C-urea T2 was investigated by means of the correlation between the BOLD and T2 signals; a statistically significant difference (P = 0.03) was found in the contralateral kidney (P = 0.0001; R2 = 0.95), but not in the postischemic kidney (P = 0.31; R2 = 0.25). We demonstrate that hyperpolarized [13 C,15 N2 ]urea T2 relaxation correlates with renal oxygen tension ( T2*) in the healthy contralateral kidney, but not in the postischemic kidney. The whole kidney T2 relaxation difference between the postischemic and contralateral kidney may originate from altered blood volume in the postischemic kidney. Magn Reson Med 80:696-702, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Non-contrast quantitative pulmonary perfusion using flow alternating inversion recovery at 3 T: A preliminary study

PurposeTo demonstrate the initial feasibility of non-contrast quantitative pulmonary perfusion imaging at 3T using flow alternating inversion recovery (FAIR), and to evaluate the intra-session and inter-session reliability of FAIR measurements at 3T. Materials and methodsNine healthy volunteers were imaged using our own implementation of FAIR pulse sequence at 3T. Quantitative FAIR perfusion, both with and without larger pulmonary vessels, was correlated with global phase contrast (PC) measured blood flow in the right pulmonary artery (RPA). The same volunteers were also imaged with SPECT perfusion using technetium-99m-macroaggregated albumin and relative dispersion (RD) was assessed between FAIR and SPECT perfusion. Four additional healthy volunteers were evaluated for FAIR repeatability, using intra-class correlation coefficient (ICC) and Bland-Altman analysis. p<0.05 was considered statistically significant. ResultsFAIR perfusion across all subjects was 858±605mL/100g/min (with vessels) and 629±294mL/100g/min (without vessels) and correlated significantly with the PC measured blood flow in the RPA (r=0.62, p<0.01 with vessels; r=0.73, p<0.001 without vessels). The median RD of FAIR perfusion across all subjects was 0.73 (with vessels) and 0.49 (without vessels), compared against 0.23 with SPECT perfusion. The intra/inter-session ICC of FAIR perfusion with vessels was 0.95/0.59 and improved to 0.96/0.72, when vessels were removed. ConclusionsNon-contrast quantitative pulmonary perfusion imaging using FAIR is feasible at 3T. This may serve as a reliable method to assess regional lung perfusion at 3T to characterize and monitor treatment response in chronic lung disease without the concerns of repeated exposure to ionizing radiation or the accumulation of exogenous contrast agent.

Optimization of simultaneous multislice EPI for concurrent functional perfusion and BOLD signal measurements at 7T.

PurposeTo overcome limitations of previous ultra‐high‐field arterial spin labeling (ASL) techniques concerning temporal resolution and brain coverage by utilizing the simultaneous multi‐slice (SMS) approach.MethodsAn optimized, flow‐alternating inversion recovery quantitative imaging of perfusion using a single subtraction II scheme was developed that tackles the challenges of 7 tesla (T) ASL. The implementation of tailored labeling radiofrequency pulses reduced the effect of transmit field ( B1+) inhomogeneities. The proposed approach utilizes an SMS echo‐planar imaging (EPI) readout to efficiently achieve large brain coverage.ResultsA pulsed ASL (PASL) technique with large brain coverage is described and optimized that can be applied at temporal resolutions below 2.5 s, similar to those achievable at 1.5 and 3T magnetic field strength. The influences of within‐ and through‐slice acceleration factors and reconstruction parameters on perfusion and blood‐oxygenation‐level‐dependent (BOLD)‐signal image and temporal signal‐to‐noise ratio (SNR) are presented. The proposed approach yielded twice the brain coverage as compared to conventional PASL at 7T, without notable loss in image quality.ConclusionThe presented SMS EPI PASL at 7T overcomes current limitations in SNR, temporal resolution, and spatial coverage for functional perfusion and BOLD signal as well as baseline perfusion measurements. Magn Reson Med 78:121–129, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Functional and anatomical characterization of brown adipose tissue in heart failure with blood oxygen level dependent magnetic resonance.

Recent studies have suggested that brown adipose tissue (BAT) plays an important role in obesity, insulin resistance and heart failure. The characterization of BAT in vivo, however, has been challenging. No technique to comprehensively image BAT anatomy and function has been described. Moreover, the impact on BAT of the neuroendocrine activation seen in heart failure has only recently begun to be evaluated in vivo. The aim of this study was to use MRI to characterize the impact of heart failure on the morphology and function of BAT. Mice subjected to permanent ligation of the left coronary artery were imaged with MRI 6 weeks later. T2 weighted MRI of BAT volume and blood oxygen level dependent MRI of BAT function were performed. T2 * maps of BAT were obtained at multiple time points before and after administration of the β3 adrenergic agonist CL 316 243 (CL). Blood flow to BAT was studied after CL injection using the flow alternating inversion recovery (FAIR) approach. Excised BAT tissue was analyzed for lipid droplet content and for uncoupling protein 1 (UCP1) mRNA expression. BAT volume was significantly lower in heart failure (51 ± 1 mm(3) versus 65 ± 3 mm(3) ; p < 0.05), and characterized by a reduction in lipid globules and a fourfold increase in UCP1 mRNA (p < 0.05). CL injection increased BAT T2 * in healthy animals but not in mice with heart failure (24 ± 4% versus 6 ± 2%; p < 0.01), consistent with an increase in flow in control BAT. This was confirmed by a significant difference in the FAIR response in BAT in control and heart failure mice. Heart failure results in the chronic activation of BAT, decreased BAT lipid stores and decreased BAT volume, and it is associated with a marked decrease in ability to respond to acute physiological stimuli. This may have important implications for substrate utilization and overall metabolic homeostasis in heart failure. Copyright © 2016 John Wiley & Sons, Ltd.

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 × 468µm(2) , 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.

Basal and hypercapnia-altered cerebrovascular perfusion predict mild cognitive impairment in aging rodents

With increasing age, a subset of otherwise healthy individuals undergoes impairments in learning and memory that have been termed mild cognitive impairment (MCI). The enhanced neuronal activity associated with learning and memory requires increased cerebral blood flow (CBF) to specific brain regions. However, the interactions between cerebral blood flow and MCI remain unclear. In this study, we address whether baseline or hypercapnia-induced (increased blood CO2 levels) changes in CBF are modified with age, and whether these measures are predictive of cognitive status in rodents. Adult and aged rats were evaluated using a hippocampally-dependent task in a water maze. Aged rats were classified as memory-impaired or memory-intact based on performance comparisons with adult rats. Cerebral blood flow was assessed using flow-alternating inversion recovery (FAIR) magnetic resonance imaging (MRI), before and after breathing 10% CO2. The transition period between CO2 concentrations was examined with blood oxygen level dependent (BOLD) MRI. Separation of aged animals into memory-intact and impaired categories revealed increased basal perfusion in the dorsal hippocampus of memory-impaired versus memory-intact aged animals. Linear regression revealed that higher hippocampal perfusion was correlated with impaired memory in aged animals, and a logistic regression indicated that hippocampal perfusion predicted spatial memory ability. Several brain regions of aged rats demonstrated an attenuation of the perfusion increase normally observed in adult rats under hypercapnia. Memory-impaired animals were the primary contributor to this effect, as their perfusion response to hypercapnia was significantly reduced compared to adult animals. Aged, memory-intact animals were not significantly different from adults. BOLD MRI demonstrated a reduced response in aged animals to hypercapnia, with impaired animals being the primary contributor to the effect. A logistic regression model based on basal and hypercapnia perfusion correctly predicted cognitive status in 83.3% of animals tested. Our results indicate that age-related changes in vascular reactivity and perfusion are important contributing factors in memory impairment.

In vivo perfusion, T1, and T2 measurements in the female pelvis during the normal menstrual cycle: A feasibility study

To quantify T(1), T(2), and regional tissue perfusion in uterine tissues, with MR imaging in clinically feasible imaging times, using echo planar imaging (EPI) techniques over a single menstrual cycle. A total of 24 healthy ovulating women were scanned; however, complete data sets through the menstrual cycle were not obtained from all women. Three scans were performed to coincide prospectively with the follicular, periovulatory, and luteal phases of the cycle. T(1) and perfusion were measured simultaneously using flow alternating inversion recovery (FAIR), while T(2) was measured using a single Hahn spin-echo (SE) EPI sequence. Between the follicular and periovulatory phases, statistically significant increases (P < 0.05) were seen for the T(2) of the endometrium and perfusion of the myometrium as well as the T(2)/T(1) ratio for both endometrium and myometrium. A statistically significant decrease was seen in the endometrial T(2) between the periovulatory and luteal phases of the cycle. Tissue differentiation was achieved using the parameters measured, with T(1) and T(2) being statistically greater for the endometrium than for the myometrium, and endometrial perfusion being statistically lower than myometrial perfusion. These results show the feasibility of using these techniques to measure T(1), T(2), and perfusion in uterine tissues and of extending this work to study pathological conditions.

Arterial spin labeling blood flow magnetic resonance imaging for the characterization of metastatic renal cell carcinoma 1

This study sought to assess the feasibility of arterial spin labeling (ASL) blood flow (BF) magnetic resonance imaging (MRI) for the study of metastatic renal cell carcinoma (RCC) in the body, where the respiratory, cardiac, and peristaltic motions present challenges when applying ASL. ASL was performed using a background-suppressed single-section flow-alternating inversion recovery (FAIR) preparation and a single-shot fast spin-echo imaging sequence on a 3.0-T whole body imager. Tumor BF was evaluated for 26 patients with RCC metastatic to the liver, bone, lung, or lymph nodes before VEGF receptor inhibitor therapy. Two cases with tumor size change after treatment were also scanned 1 month after therapy. For validation, kidney cortex BF in five normal volunteers was measured with the same technique and compared with literature values. ASL was successfully performed in all normal volunteers and in 20 of 26 patients. The six failures resulted from a systematic error, which can be avoided in future studies. For normal volunteers, measured kidney cortex BF was 275 +/- 14 mL/min/100 g, a value consistent with the literature. ASL determined tumor BF averaged across tumor volume and subjects was 194 mL/min/100 g (intersubject SD = 100), resulting in high perfusion signal and conspicuity of lesions. Bright signal was also seen in large vessels and occasionally in bowel. In the two cases studied 1 month after therapy, ASL perfusion changes were consistent with tumor size changes. With background suppression, ASL MRI is a feasible method for quantifying BF in patients with renal cell carcinoma. This technique may be useful for evaluating tumor response to antiangiogenic agents.

Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat

Plastic changes in motor cortex capillary structure and function were examined in three separate experiments in adult rats following prolonged exercise. The first two experiments employed T-two-star (T 2*)-weighted and flow-alternating inversion recovery (FAIR) functional magnetic resonance imaging to assess chronic changes in blood volume and flow as a result of exercise. The third experiment used an antibody against the CD61 integrin expressed on developing capillaries to determine if motor cortex capillaries undergo structural modifications. In experiment 1, T 2*-weighted images of forelimb regions of motor cortex were obtained following 30 days of either repetitive activity on a running wheel or relative inactivity. The proton signal intensity was markedly reduced in the motor cortex of exercised animals compared with that of controls. This reduction was not attributable to alterations of vascular iron levels. These results are therefore most consistent with increased capillary perfusion or blood volume of forelimb regions of motor cortex. FAIR images acquired during experiment 2 under normocapnic and hypercapnic conditions indicated that resting cerebral blood flow was not altered under normal conditions but was elevated in response to high levels of CO 2, suggesting that prolonged exercise increases the size of a capillary reserve. Finally, the immunohistological data indicated that exercise induces robust growth of capillaries (angiogenesis) within 30 days from the onset of the exercise regimen. Analysis of other regions failed to find any changes in perfusion or capillary structure suggesting that this motor activity-induced plasticity may be specific to motor cortex. These data indicate that capillary growth occurs in motor areas of the cerebral cortex as a robust adaptation to prolonged motor activity. In addition to capillary growth, the vascular system also experiences heightened flow under conditions of activation. These changes are chronic and observable even in the anesthetized animal and are measurable using noninvasive techniques.

Simultaneous BOLD/perfusion measurement using dual-echo FAIR and UNFAIR: sequence comparison at 1.5T and 3.0T

Functional MRI (fMRI) studies designed for simultaneously measuring Blood Oxygenation Level Dependent (BOLD) and Cerebral Blood Flow (CBF) signal often employ the standard Flow Alternating Inversion Recovery (FAIR) technique. However, some sensitivity is lost in the BOLD data due to inherent T1 relaxation. We sought to minimize the preceding problem by employing a modified UN-inverted FAIR (UNFAIR) technique, which (in theory) should provide identical CBF signal as FAIR with minimal degradation of the BOLD signal. UNFAIR BOLD maps acquired from human subjects ( n = 8) showed significantly higher mean z-score of ∼17% ( p < 0.001), and number of activated voxels at 1.5T. On the other hand, the corresponding FAIR perfusion maps were superior to the UNFAIR perfusion maps as reflected in a higher mean z-score of ∼8% ( p = 0.013), and number of activated voxels. The reduction in UNFAIR sensitivity for perfusion is attributed to increased motion sensitivity related to its higher background signal, and, T2 related losses from the use of an extra inversion pulse. Data acquired at 3.0T demonstrating similar trends are also presented.