Paced respiration with end-expiration technique offers superior BOLD signal repeatability for breath-hold studies.

As a simple, non-invasive method of blood oxygenation level-dependent (BOLD) signal calibration, the breath-hold task offers considerable potential for the quantification of neuronal activity from functional magnetic resonance imaging (fMRI) measurements. With an aim to improve the precision of this calibration method, the impact of respiratory rate control on the BOLD signal achieved with the breath-hold task was investigated. In addition to self-paced breathing, three different computer-paced breathing rates were imposed during the periods between end-expiration breath-hold blocks. The resulting BOLD signal timecourses and statistical activation maps were compared in eleven healthy human subjects. Results indicate that computer-paced respiration produces a larger peak BOLD signal increase with breath-hold than self-paced breathing, in addition to lower variability between trials. This is due to the more significant post-breath-hold signal undershoot present in self-paced runs, a characteristic which confounds the definition of baseline and is difficult to accurately model. Interestingly, the specific respiratory rate imposed between breath-hold periods generally does not have a statistically significant impact on the BOLD signal change. This result can be explained by previous reports of humans adjusting their inhalation depth to compensate for changes in rate, with the end-goal of maintaining homeostatic ventilation. The advantage of using end-expiration relative to end-inspiration breath-hold is apparent in view of the high repeatability of the BOLD signal in the present study, which does not suffer from the previously reported high variability associated with uncontrolled inspiration depth when using the end-inspiration technique.

Velocity selective radiofrequency pulse trains.

The incorporation of velocity-encoding gradient pulses in RF-pulse trains is proposed and examined. Velocity selective perturbation is shown to be analogous in many respects to the well established use of trains of short RF-pulses for chemical shift selective perturbation. Velocity selective perturbation is viable in a biomedical setting only if additional RF refocusing pulses are inserted between the individual RF-pulse elements. Aspects of velocity selective excitation saturation and inversion are examined, and new inversion pulse trains proposed. The selective perturbation of both flowing and stationary spins is demonstrated in phantoms and possible biomedical applications of these pulse trains are discussed.

Fast T2-mapping with snapshot flash imaging.

It has been shown recently that quantitative T2-maps may be measured by acquisition of a series of at least eight T2-weighted SNAPSHOT FLASH images. These measurements require a relaxation delay of 10-15 s after each T2-weighted image for the complete relaxation of the spin system. This results in long measuring times. The method presented in this paper allows a considerable reduction of the measuring time by combining the T2-sequence with a fast T1-measurement. Quantitative T1- and T2-maps may be acquired simultaneously in less than 30 s. The method was tested in a phantom experiment. In an in vivo application, relaxation times of different tissues in the abdomen of a rat were measured.

Simultaneous detection of changes in perfusion and BOLD contrast.

A new functional magnetic resonance imaging (fMRI) technique for simultaneous detection (SIDE) of changes in perfusion and blood oxygenation level dependent (BOLD) contrast is described. Perfusion contrast is generated by using magnetically labeled endogenous water proton spins as a freely diffusible tracer. A single slice-selective inversion pulse is combined with dual echo echo-planar imaging to generate a spin-echo (SE) image sensitive to changes in perfusion and a gradient-echo (GE) image sensitive to changes in both perfusion and BOLD contrast. The SIDE technique was applied to detect functional changes induced by a visual search task. A theoretical analysis is provided to calculate quantitative maps of changes in cerebral blood flow (DeltaCBF) and effective transverse relaxation time (DeltaT(2)*) from the corresponding signal changes in the SE and GE images. Since SE an GE images are generated from the same longitudinal magnetization, no errors due to spatial or temporal mismatch can arise in the quantification of DeltaCBF and DeltaT(2)*.

The effect of transient hypercapnia on task-related changes in cerebral blood flow and blood oxygenation in awake normal humans: a functional magnetic resonance imaging study.

It has recently been reported in alpha-chloralose anesthetized rats that the hemodynamic response to somatosensory stimulation almost doubled following transient hypercapnia (THC). In principle, this effect could be employed to enhance the sensitivity of perfusion-based fMRI experiments. To investigate whether a comparable effect was detectable in awake normal humans, changes in cerebral blood flow (DeltaCBF) and the effective transverse relaxation time (DeltaT(2)*) induced by a visual search task were measured in 10 healthy volunteers before and after THC. Concerning DeltaT(2)* no significant differences were found, whereas in four subjects DeltaCBF was significantly decreased (p < 0.01) following THC. These results demonstrate no increase in the CBF response following THC for awake humans. We conclude that the most likely explanation for this discrepancy with the earlier results obtained with animals is an as yet unknown mechanism of modulation of the cholinergic system by the anesthesia.

Subanesthetic isoflurane affects task-induced brain activation in a highly specific manner: a functional magnetic resonance imaging study.

BACKGROUND: Functional magnetic resonance imaging of blood oxygenation level-dependent signal changes offers a very promising approach to investigate activated neural networks during anesthesia. METHODS: Sixteen healthy male volunteers, assigned into two groups of eight subjects (isoflurane group, control group), were investigated by functional magnetic resonance imaging during different experimental conditions. The isoflurane group successively breathed air (baseline condition), isoflurane in air (0.42 vol% inspiratory; isoflurane condition) and air again (recovery condition) while performing a visual search task, whereas the control group breathed air during all experimental conditions. Functional magnetic resonance images were acquired during the entire experimental session. In addition, reaction times and error rates were recorded. RESULTS: A significant isoflurane-related decrease (z > 3.1 corresponding to P < 0.001) in task-induced brain activation was found in three distinct cortical regions: the right anterio-superior insula (Talairach coordinates: x = 32, y = 22, z = 8) and the banks of the left and right intraparietal sulcus (Talairach coordinates: x = -34, y = -36, z = 32; x = 22, y = -60, z = 41, respectively). Subcortical structures (lateral geniculate nucleus) and the primary cortices (motor cortex, visual cortex) were not affected. All measured parameters indicated a nearly complete recovery of the affected networks within 5 min. CONCLUSIONS: Our findings indicate that subanesthetic isoflurane affected task-induced activation in specific neural networks rather than causing a global decrease in functional activation.

Investigating the dependence of BOLD contrast on oxidative metabolism.

Most functional magnetic resonance imaging (fMRI) studies are based on measuring the changes in the blood oxygenation level-dependent (BOLD) contrast that arise from a complex interplay between cerebral hemodynamics and oxidative metabolism. To separate these effects, we consecutively applied two different stimuli: visual stimulation (black/white checkerboard alternating with a frequency of 8 Hz) and hypercapnia (inspiration of 5% CO2). Changes in cerebral blood flow (deltaCBF) and the effective transverse relaxation time (T2*) were measured in an interleaved manner by combining a previously described spin-labeling technique with BOLD-based fMRI. In six healthy volunteers, T2* was significantly longer during hypercapnia than during visual stimulation, whereas the corresponding deltaCBF values were the same at the given level of significance (P<0.01). This finding is explained by a significant increase in oxygen consumption under visual stimulation. The average T2* changes in the visual cortex related to cerebral hemodynamics and oxidative metabolism were 10.6+/-3.0% and -4.7+/-1.2%, respectively, resulting in a net increase of 5.9+/-2.3%. Although the hemodynamic effect is dominant, the increase in oxidative metabolism gives rise to a significant decrease in BOLD contrast. The calculated average change in the cerebral metabolic rate of oxygen (CMRO2), 4.4+/-1.1% (N = 6), is in excellent agreement with previous results obtained by positron emission tomography.

BASE imaging: a new spin labeling technique for measuring absolute perfusion changes.

A new technique for magnetic resonance imaging of absolute perfusion changes that uses magnetically labeled tissue water proton spins as a freely diffusible tracer is described. It consists of unprepared basis (BA) images that serve as a reference and selective (SE) inversion prepared images that are sensitive to perfusion changes. In the present study, the BASE technique was applied to functional neuroimaging. BA and SE images were alternatingly and repeatedly acquired during periods of visual stimulation and control. Visual stimulation was achieved with an alternating black/white checkerboard operating at a frequency of 8 Hz. Maps of the absolute cerebral blood flow changes (deltaCBF) were calculated from the image intensities of the corresponding BA and SE images. The individual mean values of deltaCBF measured in five healthy volunteers ranged from 69 +/- 18 to 99 +/- 26 ml/min/100 g. Since the BASE technique does not require nonselective spin inversion, it can be used with small transmit/receive head coils (e.g., surface coils). In addition, the BASE technique is robust against a mismatch of the inversion and detection slice profiles.

Optimisation of the 3D MDEFT sequence for anatomical brain imaging: technical implications at 1.5 and 3 T.

An algorithm for the optimisation of 3D Modified Driven Equilibrium Fourier Transform (MDEFT) sequences for T1-weighted anatomical brain imaging is presented. Imaging parameters are optimised for a clinical whole body scanner and a clinical head scanner operating at 1.5 and 3 T, respectively. In vivo studies show that the resulting sequences allow for the whole brain acquisition of anatomical scans with an isotropic resolution of 1 mm and high contrast-to-noise ratio (CNR) in an acceptable scan time of 12 min. Typical problems related to the scanner-specific hardware configurations are discussed in detail, especially the occurrence of flow artefacts in images acquired with head transmit coils and the enhancement of scalp intensities in images acquired with phased array receive coils. It is shown both theoretically and experimentally that these problems can be avoided by using spin tagging and fat saturation.

Quantification of regional blood volumes by rapid T1 mapping.

A new method is presented for the quantitative determination of regional blood volumes in vivo. It is based on rapid quantitative T1 mapping by Snapshot FLASH MRI combined with the injection of an intravascular MR contrast agent. Regional blood volumes in four different tissues of the rat (skeletal muscle, heart, liver, kidney) were determined in an in vivo experiment.

Quantitative magnetic resonance imaging of perfusion using magnetic labeling of water proton spins within the detection slice.

A technique for noninvasive quantitative magnetic resonance imaging of perfusion is presented. It relies on using endogenous water as a freely diffusible tracer. Tissue water proton spins are magnetically labeled by slice-selective inversion, and longitudinal relaxation within the slice is detected using a fast gradient echo magnetic resonance imaging technique. Due to blood flow, nonexcited spins are washed into the slice resulting in an acceleration of the longitudinal relaxation process. Incorporating this phenomenon into the Bloch equation yields an expression that allows quantification of perfusion on the basis of a slice-selective and a nonselective inversion recovery experiment. Based on this technique, quantitative parameter maps of the regional cerebral blood flow (rCBF) were obtained from eight rats. Evaluation of regions of interest within the cerebral hemispheres yielded an average rCBF value of 104 +/- 21 ml/min/100 g, which increased to 219 +/- 30 ml/min/100 g during hypercapnia. The measured rCBF values are in good agreement with previously reported literature values.

Sequential effects of propofol on functional brain activation induced by auditory language processing: an event-related functional magnetic resonance imaging study.

BACKGROUND: We have investigated the effect of propofol on language processing using event-related functional magnetic resonance imaging (MRI). METHODS: Twelve healthy male volunteers underwent MRI scanning at a magnetic field strength of 3 Tesla while performing an auditory language processing task. Functional images were acquired from the perisylvian cortical regions that are associated with auditory and language processing. The experiment consisted of three blocks: awake state (block 1), induction of anaesthesia with 3 mg kg(-1) propofol (block 2), and maintenance of anaesthesia with 3 mg kg(-1) h(-1) propofol (block 3). During each block normal sentences and pseudo-word sentences were presented in random order. The subjects were instructed to press a button to indicate whether a sentence was made up of pseudo-words or not. All subjects stopped responding during block two. The data collected before and after the subjects stopped responding during this block were analyzed separately. In addition, propofol plasma concentrations were measured and the effect-site concentrations of propofol were calculated. RESULTS: During wakefulness, language processing induced brain activation in a widely distributed temporofrontal network. Immediately after unresponsiveness, activation disappeared in frontal areas but persisted in both temporal lobes (block 2 second half, propofol effect-site concentration: 1.51 microg ml(-1)). No activation differences related to the task were observed during block 3 (propofol effect-site concentration: 4.35 microg ml(-1)). CONCLUSION: Our findings suggest sequential effects of propofol on auditory language processing networks. Brain activation firstly declines in the frontal lobe before it disappears in the temporal lobe.

A qualitative test of the balloon model for BOLD-based MR signal changes at 3T.

The aim of this study was to adapt the balloon model for BOLD-based MR signal changes to a magnetic field strength of 3T and to examine its validity. The simultaneous measurement of BOLD and diffusion-weighted BOLD responses was performed. The amplitude of the BOLD peak was found to be similar for all subjects when a short visual stimulus of 6 sec was used. The rise-time to the BOLD peak and the shape and depth of the poststimulus undershoot varied significantly. A fit of the experimental BOLD responses was found to be possible by use of parameters within a reasonable physiological range. The relations between these parameters and their influence on the modeled BOLD responses is discussed. A prediction of the balloon model is the occurrence of a BOLD overshoot, i.e., a lag between the changes of the blood volume and the blood flow after the start of the stimulation. Experimental evidence for the existence of a BOLD overshoot is presented.

Calculation of signal intensities in hybrid sequences for fast NMR imaging.

A number of techniques that recently have been used for fast NMR-imaging are based on a hybrid sequence of echo planar imaging (EPI) and FLASH imaging: after each NMR excitation several k-space lines are measured. The complete k-space is covered by performance of several excitations. It has been observed that there is usually an optimal hybrid sequence that maximizes the signal-to-noise ratio. In this work, a method is presented that allows a determination of the optimal sequence as a function of the relaxation times T1 and T2*.

Compensation of diffusion effects in T2 measurements.

Measurements of the transverse relaxation time T2 are usually conducted with the Carr Purcell Meiboom Gill (CPMG) pulse sequence, which causes T2-weighted magnetization. Diffusion effects are a common source of error in measurements of this kind, because the incoherent motion of spins in external magnetic field gradients distorts T2 weighting of the transverse magnetization. As a result, inaccurate T2-values are obtained. In this work, we present a method which completely compensates for the effect of diffusion.

Human rapid acquisition with relaxation enhancement imaging at 8 T without specific absorption rate violation.

A standard fast imaging sequence, rapid acquisition with relaxation enhancement (RARE), has been applied to human magnetic resonance at 8 T. RARE is known for its speed, good contrast and high RF power content. Highly T2 weighted images, the hallmark of RARE imaging, were acquired from the human brain. It is demonstrated that while T2 values may be reduced at 8 T, high quality RARE images could still be acquired at this field strength. Most importantly however, it is demonstrated that RARE images could be acquired without violating specific absorption rate (SAR) guidelines. Since it is well known that T2 weighted images are of significant value in clinical diagnosis, the implementation of RARE at this field strength will provide ultra high field MRI (UHFMRI) with a valuable imaging protocol at this field strength without exceeding SAR limitations.

Quantitative magnetic resonance imaging of capillary water permeability and regional blood volume with an intravascular MR contrast agent.

A novel method is presented to simultaneously measure the permeability surface area product of water (PS), also known as capillary diffusion capacity, and the regional blood volume (RBV). It is based on magnetic resonance imaging of the longitudinal relaxation times of tissue and blood at different concentrations of an intravascular MR contrast agent. PS and RBV were measured in vivo in different regions of the brain and the skeletal muscle of the rat. The average PS values (n = 5) obtained in cerebral cortex, corpus callosum, hippocampus, thalamus, jaw muscle, and tongue muscle were 3.31 +/- 0.20, 1.81 +/- 0.25, 3.37 +/- 0.36, 3.68 +/- 0.44, 10.6 +/- 1.1, and 14.1 +/- 2.51 ml x min(-1) x g(-1), respectively. The corresponding average RBV values were 1.63 +/- 0.18, 1.22 +/- 0.25, 3.30 +/- 0.37, 3.03 +/- 0.36, 1.66 +/- 0.30, and 1.38 +/- 0.33 ml x 100 g(-1). These results are in good agreement with previously reported literature values obtained by means of autoradiography.

In vivo measurement of partial oxygen pressure in large vessels and in the reticuloendothelial system using fast 19F-MRI.

Quantitative in vivo 19F-MRI was performed in a rat model to monitor partial oxygen pressure (pO2) using a perfluorocarbon (PFC) emulsion as contrast agent. On Days 1, 4, and 8 postinjection of the PFC emulsion, transaxial T1 and pO2 maps were acquired of the abdomen of rats that were consecutively ventilated with pure oxygen, air, and a mixture of 10% oxygen and 90% nitrogen. The images had a resolution of 0.75 mm x 0.75 mm x 2 mm and a total acquisition time of 24 min. In these images it was possible to distinguish between different vessels and hepatic and splenic tissue in the selected imaging plane. Serial 19F-MRI measurements on the different days postinjection of the PFC allowed to determine separately the pO2 of arterial and venous blood and the intracellular pO2 in macrophages of the liver and spleen.

MDEFT imaging of the human brain at 8 T.

T1-weighted images of the human brain obtained with the MDEFT sequence at 8 T are presented. These images are characterized by an excellent contrast and good signal to noise ratio. Importantly, results were obtained with adiabatic spin inversion and demonstrate that such pulses can be used even in the ultra high frequency (> 300 MHz) range. It is thus possible to obtain high quality results at this field strength without violating SAR guidelines.