Flow-sensitive Alternating Inversion Recovery Research Articles

Effect of transit times on quantification of cerebral blood flow by the FAIR T(1)-difference approach.

The effect of finite transit times for the tagging bolus is known to be a significant error source for perfusion quantification using the flow-sensitive alternating inversion recovery (FAIR) technique. It is shown that, in the presence of transit times, both the slice-selective (SS) and nonselective (NS) inversion recovery experiments actually consist of an NS period followed by an SS period. This mixed process can be described using a newly defined time constant called the "switching time," which separates the two periods. Calculations predict that finite transit times always lead to decreased flow values in the signal-intensity-difference approach, but that the measured flows in the T(1)-difference approach may be decreased or increased. This theory well explains our recent experimental flow results on cat brain as a function of predelay. The results show the signal-intensity-difference method is superior over the T(1)-difference approach in terms of convenience and ease of quantification. Magn Reson Med 42:890-894, 1999.

Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex.

The aim of this study was to test the hypothesis that, within a specific cortical unit, fractional changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (CMR(O(2))) are coupled through an invariant relationship during physiological stimulation. This aim was achieved by simultaneously measuring relative changes in these quantities in human primary visual cortex (V1) during graded stimulation with patterns designed to selectively activate different populations of V1 neurons. Primary visual cortex was delineated individually in each subject by using phase-encoded retinotopic mapping. Flow-sensitive alternating inversion recovery MRI, in conjunction with blood oxygenation-sensitive MRI and hypercapnic calibration, was used to monitor CBF and CMR(O(2)). The stimuli used included (i) diffuse isoluminant chromatic displays; (ii) high spatial-frequency achromatic luminance gratings; and (iii) radial checkerboard patterns containing both color and luminance contrast modulated at different temporal rates. Perfusion responses to each pattern were graded by varying luminance and/or color modulation amplitudes. For all stimulus types, fractional changes in blood flow and oxygen uptake were found to be linearly coupled in a consistent ratio of approximately 2:1. The most potent stimulus produced CBF and CMR(O(2)) increases of 48 +/- 5% and 25 +/- 4%, respectively, with no evidence of a plateau for oxygen consumption. Estimation of aerobic ATP yields from the observed CMR(O(2)) increases and comparison with the maximum possible anaerobic ATP contribution indicate that elevated energy demands during brain activation are met largely through oxidative metabolism.

MR perfusion imaging in human brain using the UNFAIR technique. Un-inverted flow-sensitive alternating inversion recovery.

Pulsed arterial spin labeling magnetic resonance techniques have been developed recently to estimate cerebral blood flow (CBF). Flow-sensitive alternating inversion recovery (FAIR) is one such technique that has been implemented successfully in humans. Un-inverted FAIR (UNFAIR) is an alternative technique in which the flow-sensitive image is acquired following inversion of all spins outside the slice of interest, and the control image is acquired without any spin labeling. This approach is potentially more efficient than FAIR since the UNFAIR control image is entirely flow independent and need only be acquired once. Here, we describe implementation of the sequence on a clinical 1.5 T magnetic resonance system. Both FAIR and UNFAIR perfusion-weighted images were obtained from six normal volunteers. Wash-in/wash-out curves measured in cortical gray and white matter were practically identical for the two techniques, as predicted by our model.

Reperfusion in a gerbil model of forebrain ischemia using serial magnetic resonance FAIR perfusion imaging.

Existing methods for the quantitative measurement of the changing cerebral blood flow (CBF) during reperfusion suffer from poor spatial or temporal resolution. The aim of this study was to implement a recently developed MRI technique for quantitative perfusion imaging in a gerbil model of reperfusion. Flow-sensitive alternating inversion recovery (FAIR) is a noninvasive procedure that uses blood water as an endogenous tracer. Bilateral forebrain ischemia of 4 minutes' duration was induced in gerbils (n=8). A modified version of FAIR with improved time efficiency was used to provide CBF maps with a time resolution of 2.8 minutes after recirculation had been initiated. Quantitative diffusion imaging was also performed at intervals during the reperfusion period. On initiating recirculation after the transient period of ischemia, the FAIR measurements demonstrated either a symmetrical, bilateral pattern of flow impairment (n=4) or an immediate side-to-side difference that became apparent with respect to the cerebral hemispheres in the imaged slice (n=4). The flow in each hemisphere displayed a pattern of recovery close to the preocclusion level or, alternatively, returned to a lower level before displaying a delayed hypoperfusion and a subsequent slow recovery. The diffusion measurements during this latter response suggested the development of cell swelling during the reperfusion phase in the striatum. The CBF during the reperfusion period was monitored with a high time resolution, noninvasive method. This study demonstrates the utility of MRI techniques in following blood flow changes and their pathophysiological consequences.

Perfusion imaging using FAIR with a short predelay

It is shown theoretically that the flow-sensitive alternating inversion recovery (FAIR) signal intensity difference for flow quantification is independent of the length of the predelay between repeated measurements when assuming complete labeling in between scans. Theory also predicts that flows quantified using the concomitant T1 difference increase significantly with decreasing predelay, because the biexponential relaxation behavior after nonselective inversion is fitted as a monoexponential. The new equations include the effect of the unequal relaxation times of water in tissue (T1) and arterial blood (T1a). While this effect is significant for the signal-difference approach, it is negligible for the T1-difference procedure when using maximum inversion-recovery times shorter than 4 sec. Experiments on cat brain using the FAIR excluding radiation damping (FAIRER) pulse sequence at three different predelays (0.8, 2, and 5 sec) confirm the theoretical predictions. Magn Reson Med 41:1099–1107, 1999. © 1999 Wiley-Liss, Inc.

Perfusion imaging using FAIR with a short predelay.

It is shown theoretically that the flow-sensitive alternating inversion recovery (FAIR) signal intensity difference for flow quantification is independent of the length of the predelay between repeated measurements when assuming complete labeling in between scans. Theory also predicts that flows quantified using the concomitant T1 difference increase significantly with decreasing predelay, because the biexponential relaxation behavior after nonselective inversion is fitted as a monoexponential. The new equations include the effect of the unequal relaxation times of water in tissue (T1) and arterial blood (T1a). While this effect is significant for the signal-difference approach, it is negligible for the T1-difference procedure when using maximum inversion-recovery times shorter than 4 sec. Experiments on cat brain using the FAIR excluding radiation damping (FAIRER) pulse sequence at three different predelays (0.8, 2, and 5 sec) confirm the theoretical predictions.

Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation.

The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can be estimated during neural activity using a reference condition obtained with known CMRO2 change. In this work, nine subjects were studied at a magnetic field of 1.5 T; each subject underwent inhalation of a 5% carbon dioxide gas mixture as a reference and two visual stimulation studies. Relative CBF and BOLD signal changes were measured simultaneously using the flow-sensitive alternating inversion recovery (FAIR) technique. During hypercapnia established by an end-tidal CO2 increase of 1.46 kPa, CBF in the visual cortex increased by 47.3 +/- 17.3% (mean +/- SD; n = 9), and deltaR2* was -0.478 +/- 0.147 sec(-1), which corresponds to BOLD signal change of 2.4 +/- 0.7% with a gradient echo time of 50 msec. During black/white visual stimulation reversing at 8 Hz, regional CBF increase in the visual cortex was 43.6 +/- 9.4% (n = 18), and deltaR2* was -0.114 +/- 0.086 sec(-1), corresponding to a BOLD signal change of 0.6 +/- 0.4%. Assuming that CMRO2 does not change during hypercapnia and that hemodynamic responses during hypercapnia and neural stimulation are similar, relative CMRO2 change was determined using BOLD biophysical models. The average CMRO2 change in the visual cortex ranged from 15.6 +/- 8.1% (n = 18) with significant cerebral blood volume (CBV) contribution to 29.6 +/- 18.8% without significant CBV contribution. A weak positive correlation between CBF and CMRO2 changes was observed, suggesting the CMRO2 increase is proportional to the CBF increase.

Implementation of quantitative FAIR perfusion imaging with a short repetition time in time-course studies.

Flow-sensitive alternating inversion recovery (FAIR) is a pulsed arterial spin labeling magnetic resonance imaging method for perfusion quantification. In its standard implementation for quantification with full longitudinal relaxation between acquisitions, its use in time-course investigations of rapidly changing flow values is limited. The time efficiency can be improved by decreasing the repetition time but quantification becomes problematic. This situation is further complicated if a whole-body radiofrequency transmit coil is not used since fresh blood spins will flow in from outside the coil. To alleviate these problems, the use of global pre-saturation is proposed. The resulting expression for the flow signal depends on the relationship between the imaging parameters and the coil inflow time and can be significantly simplified under certain combinations of these parameters. With this implementation of FAIR, quantitative flow maps of gerbil brains were obtained with a 3 minute time resolution in a study of the effects of reperfusion. The pre-occlusion flow measurements were in good agreement with values obtained by the standard FAIR implementation and by other techniques, but the low values following occlusion were underestimated due to the increased transit times.

Implementation of quantitative FAIR perfusion imaging with a short repetition time in time‐course studies

Flow-sensitive alternating inversion recovery (FAIR) is a pulsed arterial spin labeling magnetic resonance imaging method for perfusion quantification. In its standard implementation for quantification with full longitudinal relaxation between acquisitions, its use in time-course investigations of rapidly changing flow values is limited. The time efficiency can be improved by decreasing the repetition time but quantification becomes problematic. This situation is further complicated if a whole-body radiofrequency transmit coil is not used since fresh blood spins will flow in from outside the coil. To alleviate these problems, the use of global pre-saturation is proposed. The resulting expression for the flow signal depends on the relationship between the imaging parameters and the coil inflow time and can be significantly simplified under certain combinations of these parameters. With this implementation of FAIR, quantitative flow maps of gerbil brains were obtained with a 3 minute time resolution in a study of the effects of reperfusion. The pre-occlusion flow measurements were in good agreement with values obtained by the standard FAIR implementation and by other techniques, but the low values following occlusion were underestimated due to the increased transit times. Magn Reson Med 41:829–840, 1999. © 1999 Wiley-Liss, Inc.

Perfusion imaging of the human lung using flow-sensitive alternating inversion recovery with an extra radiofrequency pulse (FAIRER)

Pulmonary perfusion is an important parameter in the evaluation of lung diseases such as pulmonary embolism. A noninvasive MR perfusion imaging technique of the lung is presented in which magnetically labeled blood water is used as an endogenous, freely diffusible tracer. The perfusion imaging technique is an arterial spin tagging method called Flow sensitive Alternating Inversion Recovery with an Extra Radiofrequency pulse (FAIRER). Seven healthy human volunteers were studied. High-resolution perfusion-weighted images with negligible artifacts were acquired within a single breathhold. Different patterns of signal enhancement were observed between the pulmonary vessels and parenchyma, which persists up to TI = 1400 ms. The T 1s of blood and lung parenchyma were determined to be 1.46s and 1.35 s, respectively.

MR perfusion imaging of pulmonary parenchyma using pulsed arterial spin labeling techniques: FAIRER and FAIR

Magnetic resonance imaging of pulmonary parenchyma perfusion using pulsed arterial spin labeling (ASL) techniques is presented. ASL uses magnetically labeled water as an endogenous, freely diffusible tracer. Presented are comparative results of ASL methods called Flow sensitive Alternating Inversion Recovery (FAIR), and FAIR with an Extra Radiofrequency pulse (FAIRER). Six healthy human volunteers were imaged. Perfusion-weighted images at different time delays, TI, were calculated from the subtraction of the control and tag images, which were acquired within a single breathhold. Detailed pulmonary structures can be visualized with negligible cardiac or respiratory motion artifacts. Different patterns of signal enhancement between the pulmonary vessels and parenchyma are shown in the perfusion images acquired at different TIs.J. Magn. Reson. Imaging 1999;9:483–487. © 1999 Wiley-Liss, Inc.

MR perfusion imaging of pulmonary parenchyma using pulsed arterial spin labeling techniques: FAIRER and FAIR

Magnetic resonance imaging of pulmonary parenchyma perfusion using pulsed arterial spin labeling (ASL) techniques is presented. ASL uses magnetically labeled water as an endogenous, freely diffusible tracer. Presented are comparative results of ASL methods called Flow sensitive Alternating Inversion Recovery (FAIR), and FAIR with an Extra Radiofrequency pulse (FAIRER). Six healthy human volunteers were imaged. Perfusion-weighted images at different time delays, TI, were calculated from the subtraction of the control and tag images, which were acquired within a single breathhold. Detailed pulmonary structures can be visualized with negligible cardiac or respiratory motion artifacts. Different patterns of signal enhancement between the pulmonary vessels and parenchyma are shown in the perfusion images acquired at different TIs.

Parameter estimation from Rician‐distributed data sets using a maximum likelihood estimator: Application to t1 and perfusion measurements

General expressions are presented to calculate the maximum likelihood (ML) estimator and corresponding Fisher matrix for Rician-distributed data sets. This estimator results in the most precise, unbiased estimations of T1 from magnitude data sets, even when low signal-to-noise ratios (<6) are present. By optimizing the sample point distributions for inversion-recovery experiments, a 32% increase in precision of the estimated T1 is obtained, compared with a linear sampling scheme. Perfusion rates are estimated from combined data sets of the slice- and nonslice-selective inversion-recovery experiments, as obtained with the flow-sensitive alternating inversion recovery (FAIR) technique. The ML estimator for the combined data set results in the most precise, unbiased estimations of the perfusion rate. Error analysis shows that very high signal-to-noise ratios are required for precise estimation of perfusion rates from FAIR experiments. Magn Reson Med 41:614–623, 1999. © 1999 Wiley-Liss, Inc.

Functional MRI of Human Brain during Breath Holding by BOLD and FAIR Techniques

BOLD (blood oxygenation level-dependent) and FAIR (flow-sensitive alternating inversion recovery) imaging techniques were used to investigate the oxygenation and hemodynamic responses of human brain during repeated challenges of breath holding and prolonged single breath holding. The effects of different breathing techniques on BOLD and FAIR image contrasts were carefully examined. With a periodic breath-holding paradigm of 30 s, global changes in gray matter were observable both in T*2-weighted and FAIR images. T*2-weighted images showed 1–4% relative signal intensity increases, while FAIR images demonstrated relative cerebral blood flow (CBF) increase up to 30–70%. The activated pixels depicted in FAIR images were about three times less than those seen in T*2-weighted images. With prolonged breath holding, it was observed that signal intensities in T*2-weighted and FAIR images were dependent on the breathing techniques used. Breath holding after expiration gave rise to immediate signal intensity increases in T*2-weighted and FAIR images, whereas breath holding performed after deep inspiration signals showed a biphasic change both in flow and T*2-weighted. T*2-weighted and FAIR signals showed a transient decrease before rising above the baseline level.

FAIR excluding radiation damping (FAIRER).

It is shown that the flow-sensitive alternating inversion recovery (FAIR) technique is complicated by the effect of radiation damping, leading to problems in calibrating this method on phantoms and to inaccuracies in measured flows. A modified scheme called FAIRER (FAIR excluding radiation damping) is proposed, which suppresses the damping effects by employing very weak magnetic field gradients (0.06 G/cm) during the inversion recovery, spin-echo, and predelay periods. Results on phantoms and in vivo on cat brain are presented that demonstrate that FAIRER effectively solves these problems.

Cocaine decreases cortical cerebral blood flow but does not obscure regional activation in functional magnetic resonance imaging in human subjects.

The authors used functional magnetic resonance imaging (fMRI) to determine whether acute intravenous (i.v.) cocaine use would change global cerebral blood flow (CBF) or visual stimulation-induced functional activation. They used flow-sensitive alternating inversion recovery (FAIR) scan sequences to measure CBF and blood oxygen level-dependent (BOLD) sensitive T2* scan sequences during visual stimulation to measure neuronal activation before and after cocaine and saline infusions. Cocaine (0.6 mg/kg i.v. over 30 seconds) increased heart rate and mean blood pressure and decreased end tidal carbon dioxide (CO2). All measures returned to baseline by 2 hours, the interinfusion interval, and were unchanged by saline. Flow-sensitive alternating inversion recovery imaging demonstrated that cortical gray matter CBF was unchanged after saline infusion (-2.4 +/- 6.5%) but decreased (-14.1 +/- 8.5%) after cocaine infusion (n = 8, P < 0.01). No decreases were detected in white matter, nor were changes found comparing BOLD signal intensity in cortical gray matter immediately before cocaine infusion with that measured 10 minutes after infusion. Visual stimulation resulted in comparable BOLD signal increases in visual cortex in all conditions (before and after cocaine and saline infusion). Despite a small (14%) but significant decrease in global cortical gray matter CBF after acute cocaine infusion, specific regional increases in BOLD imaging, mediated by neurons, can be measured reliably.

Multislice Imaging of Quantitative Cerebral Perfusion with Pulsed Arterial Spin-Labeling

A method is presented for multislice measurements of quantitative cerebral perfusion based on magnetic labeling of arterial spins. The method combines a pulsed arterial inversion, known as the FAIR (Flow-sensitive Alternating Inversion Recovery) experiment, with a fast spiral scan image acquisition. The short duration (22 ms) of the spiral data collection allows simultaneous measurement of up to 10 slices per labeling period, thus dramatically increasing efficiency compared to current single slice acquisition protocols. Investigation of labeling efficiency, suppression of unwanted signals from stationary as well as intraarterial spins, and the FAIR signal change as a function of inversion delay are presented. The assessment of quantitative cerebral blood flow (CBF) with the new technique is demonstrated and shown to require measurement of arterial transit time as well as suppression of intraarterial spin signals. CBF values measured on normal volunteers are consistent with results obtained from H2O15 positron emission tomography (PET) studies and other radioactive tracer approaches. In addition, the new method allows detection of activation-related perfusion changes in a finger-tapping experiment, with locations of activation corresponding well to those observed with blood oxygen level dependent (BOLD) fMRI.

Multislice imaging of quantitative cerebral perfusion with pulsed arterial spin labeling.

A method is presented for multislice measurements of quantitative cerebral perfusion based on magnetic labeling of arterial spins. The method combines a pulsed arterial inversion, known as the FAIR (Flow-sensitive Alternating Inversion Recovery) experiment, with a fast spiral scan image acquisition. The short duration (22 ms) of the spiral data collection allows simultaneous measurement of up to 10 slices per labeling period, thus dramatically increasing efficiency compared to current single slice acquisition protocols. Investigation of labeling efficiency, suppression of unwanted signals from stationary as well as intraarterial spins, and the FAIR signal change as a function of inversion delay are presented. The assessment of quantitative cerebral blood flow (CBF) with the new technique is demonstrated and shown to require measurement of arterial transit time as well as suppression of intraarterial spin signals. CBF values measured on normal volunteers are consistent with results obtained from H2O15 positron emission tomography (PET) studies and other radioactive tracer approaches. In addition, the new method allows detection of activation-related perfusion changes in a finger-tapping experiment, with locations of activation corresponding well to those observed with blood oxygen level dependent (BOLD) fMRI.

Multi-slice perfusion-based functional MRI using the FAIR technique: comparison of CBF and BOLD effects.

Perfusion-weighted imaging techniques employing blood water protons as an endogenous tracer have poor temporal resolution because each image should be acquired with an adequate spin 'tagging' time. Thus, perfusion-based functional magnetic resonance imaging studies are typically performed on a single slice. To alleviate this problem, a multi-slice flow-sensitive alternating inversion recovery technique has been developed. Following a single inversion pulse and a delay time, multi-slice echo-planar images are acquired sequentially without any additional inter-image delay. Thus, the temporal resolution of multi-slice FAIR is almost identical to that of single slice techniques. The theoretical background for multi-slice FAIR is described in detail. The multi-slice FAIR technique has been successfully applied to obtain three-slice cerebral blood flow based functional images during motor tasks. The relative CBF change in the contralateral motor/sensory area during unilateral thumb-digit opposition is 45.0+/-12.2% (n=9), while the blood oxygenation level dependent signal change is 1.5+/-0.4 SD%. Relative changes of the oxygen consumption rate can be estimated from CBF and BOLD changes using FAIR. The BOLD signal change is not correlated with the relative CBF increase, and thus caution should be exercised when interpreting the BOLD change as a quantitative index of the CBF change, especially in inter-subject comparisons.

Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps

We have recently demonstrated using functional magnetic resonance imaging the presence of synchronous low-frequency fluctuations of signal intensities from the resting human brain that have a high degree of temporal correlation (p < 0.0001) both within and across the sensorimotor cortex. A statistically significant overlap between the resting-state functional connectivity map and the task-activation map due to bilateral finger tapping was obtained. Similar results have been obtained in the auditory and visual cortex. Because the pulse sequence used for collecting data was sensitive to blood flow and blood oxygenation, these low-frequency fluctuations of signal intensity may have arisen from variations of both. The objective of this study was simultaneously to determine the contribution of the blood oxygenation level signal and the flow signal to physiological fluctuations in the resting brain using the flow-sensitive alternating inversion recovery pulse sequence. In all subjects, the functional connectivity maps obtained from BOLD had a greater coincidence with task-activation maps than the corresponding functional connectivity maps obtained from blood-flow signals at the same level of statistical significance. Results of this study suggest that while variations in blood flow might contribute to functional connectivity maps, BOLD signals play a dominant role in the mechanism that gives rise to functional connectivity in the resting human brain.