Influence of baseline hematocrit and hemodilution on BOLD fMRI activation.

Current understanding of blood oxygenation level dependent (BOLD) fMRI physiology predicts a close relationship between BOLD signal and blood hematocrit level. However, neither this relationship nor its effect on BOLD percent activation (BPA) has been empirically examined in man. To that end, BPA in primary visual cortex in response to photic stimulation was determined in a group of 24 normal subjects. A positive linear relationship between BPA and hematocrit was seen, particularly in men. To evaluate the effect of change in hematocrit on BPA, 9 men were studied before and following isotonic saline hemodilution, resulting in an average 6% reduction in hematocrit and an 8-31% reduction in BPA. No significant change in the number of activated pixels was seen. A model of predicted BPA as a function of hematocrit and vessel size was developed, and results from this model closely mirrored the empiric data. These results suggest that hematocrit significantly influences the magnitude of BPA and that such baseline factors should be accounted for when comparing BOLD data across groups of subjects, particularly in the many instances in which hematocrit may vary systematically. Such instances include several disease states as well as studies involving sex differences, drug administration, stress and other factors. Finally, the robust agreement between predicted and empiric data serves to validate a semiquantitative approach to the analysis of BOLD fMRI data.     

Mapping of the cerebral response to acetazolamide using graded asymmetric spin echo EPI

Cerebral vascular reactivity in different regions of the rat brain was quantitatively characterized by spatial and temporal measurements of blood oxygenation level-dependent (BOLD)-fMRI signals following intravenous administration of the carbonic anhydrase inhibitor acetazolamide: this causes cerebral vasodilatation through a cerebral extracellular acidosis that spares neuronal metabolism and vascular smooth muscle function, thus separating vascular and cerebral metabolic events. An asymmetric spin echo-echo planar imaging (ASE-EPI) pulse sequence sensitised images selectively to oxygenation changes in the microvasculature; use of a surface coil receiver enhanced image signal-to-noise ratios (SNRs). Image SNRs and hardware integrity were verified by incorporating quality assurance procedures; cardiorespiratory stability in the physiological preparations were monitored and maintained through the duration of the experiments. These conditions made it possible to apply BOLD contrast fMRI to map regional changes in cerebral perfusion in response to acetazolamide administration. Thus, fMRI findings demonstrated cerebral responses to acetazolamide that directly paralleled the known physiological actions of acetazolamide and whose time courses were similar through all regions of interest, consistent with acetazolamide's initial distribution in brain plasma, where it affects cerebral haemodynamics by acting at cerebral capillary endothelial cells. However, marked variations in the magnitude of the responses suggested relative perfusion deficits in the hippocampus and white matter regions correlating well with their relatively low vascularity and the known vulnerability of the hippocampus to ischaemic damage.     

Mapping of the cerebral response to hypoxia measured using graded asymmetric spin echo EPI

Graded asymmetric spin echo-echo planar imaging (ASE-EPI) was used to measure transient alterations in cerebral oxygenation resulting from 60 seconds of anoxia in alpha-chloralose anaesthetised rats. The anoxic period induced a transient fall ( approximately 1 min) in signal intensity followed by a prolonged signal overshoot consistent with an autoregulatory response to oxygen deprivation. The magnitude of signal response, integrated over the entire brain, increased linearly with the echo asymmetry (t(ge)). However, that increase in sensitivity was offset by a reduced signal to noise ratio and quality of the image data. The responses of four regions of interest within the brain to the anoxic stimulus, and the effect of increasing the echo asymmetry, were compared. A comparable magnitude of signal decrease was observed in all brain regions except the superficial cortex that included pial vessels. As t(ge) was incremented differences in signal attenuation between regions became more pronounced. The signal overshoot observed upon restoration of normal breathing gases showed similar trends, producing similar normalised vascular responses for all regions of interest studied. Different regions of interest showed comparable time courses of the signal overshoot suggesting that similar autoregulatory vascular mechanisms operate in all brain regions. These findings additionally show that the use of graded ASE-EPI produced a characteristic profile of maximum signal change measured during and following the anoxic period for each brain region. They suggest that the shape of this profile was determined by the local vasculature within each region of interest; this feature could be exploited in activation studies to eliminate regions with significant signal changes originating from large draining vessels. Finally, the consistent physiological response observed, when the overshoot was compared to the magnitude of the signal drop, demonstrated that modification of the spin echo offset parameter did not mask or detrimentally alter the signal change resulting from the underlying physiological perturbation.     

A comparison of fast spin echo and gradient field echo sequences

Optimal angle, fast repeat time, gradient field echo imaging techniques such as FISP (Fast Imaging with Steady Precession) and FLASH (Fast Low Angle Shot) often fail to discriminate disease from healthy tissue for two main reasons. First, T1 and T2 of the affected tissue may increase such that the ratio of T1 to T2 remains nearly unchanged, hence there is no contrast change with FISP. Second, T2 weighted gradient field echo images suffer severely from T2* signal and resolution loss leading to a reduction in C/N. Although FLASH imaging with two separate angles can, in principle, extract the longer T1 tumors, contrast is often not good. To overcome the inhomogeneity and contrast problems, we have implemented a FAst optimal angle spin-echo sequence with a short TE(FATE). For the first echo, FATE has the same contrast properties as FLASH with a slight decrease in signal intensity. The advantage is that the intensity of the signal does not suffer from T2* signal decay, hence improved contrast and disease detection via T2 weighted FATE images is possible. Contrast-to-noise in lesion detection is also considered for CE FAST (Contrast Enhanced Fast), a T2-weighted version of FISP, and HYBRID.     

Recovery of signal loss due to an in-plane susceptibility gradient in the gradient echo EPI through acquisition of extended phase-encoding lines

In gradient echo imaging the in-plane susceptibility gradient causes an echo shift which results in signal loss. The loss of signal becomes more severe in gradient echo EPI, due to the low amplitude of the gradient which is applied in the phase-encoding direction during a long echo train. As the readout gradient amplitude is set to be very high in gradient echo EPI, the echo shift in the readout direction is negligible compared to that in the phase-encoding direction. Traditionally, a z-shimming technique has been applied to the phase-encoding direction of gradient echo EPI to restore the lost signal. This technique, however, requires a significant increase of scan time, as is also the case with the through-plane z-shimming technique. A new approach that allows one to restore the lost signal is to acquire additional phase-encoding lines beyond the regular phase-encoding range. The extension of the phase-encoding lines prior to the regular phase-encoding range exploits the delay time for optimum echo time of the BOLD sensitivity. Therefore, scan time is increased only for the extended phase-encoding lines posterior to the regular phase-encoding range. This technique has been confirmed experimentally by imaging human subject's heads at 3T.     

Cervical spine MR imaging using multislice gradient echo imaging: comparison with cardiac gated spin echo

Forty-one patients with suspected cervical spine disorders were studied using multislice gradient echo imaging (GE) technique, with a 1.5-T system. The images were compared to cardiac-gated spin echo (CGSE) images in the diagnosis of suspected cord and spinal disorders. Images were graded for ability to detect cord lesion, cord-CSF contrast, CSF-bone contrast and contrast between CSF and extradural abnormality. The signal-to-noise ratio and contrast-to-noise ratio were used to compare images. There was 44% decrease in contrast between cord lesion and normal cord on GE when compared to CGSE, except for spinal cord hemorrhage. There was a 40% improvement between bone and CSF contrast on GE compared to CGSE. GE images were significantly better qualitatively as well as quantitatively in the detection of extradural lesions. This effect was more marked in axial plane where CGSE images are extremely suboptimal. CGSE images are better than GE for spinal cord lesions, while GE are superior in the diagnosis of degenerative disease in the cervical spine.     

Properties of the HYSCORE spin echo signal

In hyperfine sublevel correlation spectroscopy (HYSCORE), the finite duration of the microwave pulses leads to an incomplete inversion of the electron spin magnetization by the third pulse, which results in a significant admixture of stimulated ESEEM to HYSCORE ESEEM. This virtually unavoidable contribution of stimulated ESEEM seriously hampers the analysis of the modulation amplitudes in HYSCORE. In this work, we analyze the properties of the spin echo signals contributing to the composite HYSCORE signal. Based on this analysis, we propose the strategies of HYSCORE data acquisition and processing that allow one to practically eliminate the contribution of the stimulated echo and make the HYSCORE ESEEM analyzable in quantitative terms.     

The properties of spin echo signal in ferromagnetic domain walls

The domain-wall enhanced spin echo amplitude was calculated for the case of unequal lengths of the exciting pulses. The values thus obtained were compared with results of experiments performed on pure iron powder. Good agreement was obtained at exact resonance, but discrepancies were observed when frequency of exciting pulses differed from the NMR frequency. Special measurements were carried out in order to obtain the value of rf. field intensity inside the powder particles and the maximum enhancement factor related to this value was calculated.     

Underwater asymmetric acoustic transmission structure using the medium with gradient change of impedance

We propose an underwater asymmetric acoustic transmission structure comprised of two media each with a gradient change of acoustic impedance. By gradually increasing the acoustic impedances of the media, the propagating direction of the acoustic wave can be continuously bent, resulting in allowing the acoustic wave to pass through along the positive direction and blocking acoustic waves from the negative one. The main advantages of this structure are that the asymmetric transmission effect of this structure can be realized and enhanced more easily in water. We investigate both numerically and experimentally the asymmetric transmission effect. The experimental results show that a highly efficient asymmetric acoustic transmission can be yielded within a remarkable broadband frequency range, which agrees well with the numerical prediction. It is of potential practical significance for various underwater applications such as reducing vibration and noise.     

Self-diffusion measurements in EuB6 using the pulsed gradient spin echo NMR technique

Self-diffusion process in EuB₆ was studied using the pulsed gradient spin echo NMR technique. At 1.7 K, zero-field value of the self-diffusion parameter, k, was found to be (66 ± 4) × 10^-6 (μs)^-3, while that with 5 kG polarizing field turned out to be (3 ± 0.6) × 10^-6 (μs)^-3.     

Analysis of the magic asymmetric gradient stimulated echo sequence with shaped gradients

Recently a 13-interval magic asymmetrical gradient stimulated echo (MAGSTE) sequence has been proposed for accurate displacement measurements in the presence of spatially varying background gradients. In this paper, the commonly used trapezoidal and sine shaped gradients are studied for the MAGSTE sequence, and the magic asymmetrical gradient ratio and b-factor are provided. The derivation enables the MAGSTE sequence to be implemented on systems with non-negligible gradient rise times.     

Field strength influences on gradient recalled echo MRI signal compartment frequency shifts

Different trends of echo time dependent gradient recalled echo MRI signals in different brain regions have been attributed to signal compartments in image voxels. It remains unclear how variations in gradient recalled echo MRI signals change as a function of MRI field strength, and how data processing may impact signal compartment parameters. We used two popular quantitative susceptibility mapping methods of processing raw phase images (Laplacian and path-based unwrapping with V-SHARP) and expressed values in the form of induced frequency shifts (in Hz) in six specific brain regions at 3T and 7T. We found the frequency shift curves to vary with echo time, and a good overlap between 3T and 7T mean frequency shift curves was present. However, the amount of variation across participants was greater at 3T, and we were able to obtain better compartment model fits of the signal at 7T. We also found the temporal trends in the signal and compartment frequency shifts to change with the method used to process images. The inter-participant averaged trends were consistent between 3T and 7T for each quantitative susceptibility pipeline. However, signal compartment frequency shifts generated using different pipelines may not be comparable.     

Dependence of BOLD signal change on tactile stimulus intensity in SI of primates

Recently, we have demonstrated that the fine-digit topography (millimeter sized) previously identified in the primary somatosensory cortex (SI), using electrophysiology and intrinsic signal optical imaging, can also be mapped with submillimeter resolution using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging at high field. In the present study, we have examined the dependence of BOLD signal response on stimulus intensity in two subregions of SI, Areas 3b and 1. In a region(s)-of-interest (ROI) analysis of Area 3b, BOLD signal amplitude increased linearly with increasing amplitude of an 8-Hz vibrotactile stimulus, and BOLD signal was sustained throughout the stimulation period. In contrast, in Area 1, a significant BOLD signal response was only observed with more intense stimuli, and ROI analysis of the dependence of BOLD response showed no significant dependence on stimulus intensity. In addition, activation was not sustained throughout the period of stimulation. Differing responses of Areas 3b and 1 suggest potentially divergent roles for subregions of SI cortices in vibrotactile intensity encoding. Moreover, this study underscores the importance of imaging at small spatial scales. In this case, such high-resolution imaging allows differentiation between area-specific roles in intensity encoding and identifies anatomic targets for detailed electrophysiological studies of somatosensory neuronal populations with different coding properties. These experiments illustrate the value of nonhuman primates for characterizing the dependence of the BOLD signal response on stimulus parameters and on underlying neural response properties.     

Improved diffusion measurement in heterogeneous systems using the magic asymmetric gradient stimulated echo (MAGSTE) technique

A magic asymmetric gradient stimulated echo (MAGSTE) sequence was recently proposed to improve molecular diffusion measurements in the presence of spatially varying background gradients. Its effectiveness has been demonstrated previously with simulated background gradients and in phantoms that contain bulk susceptibility differences. In this study, we investigated the MAGSTE technique in microscopically heterogeneous systems, and compared it with the conventional bipolar pulsed gradient stimulated echo (bPGSTE) sequence. We demonstrated that the MASGTE measurements, compared to the bPGSTE method, varied significantly less when the diffusion encoding/decoding interval (delta) was changed. In addition, the MAGSTE technique provided good characterization of the surface area-to-volume ratio for heterogeneous systems investigated in this study. In sum, this study showed that the MAGSTE technique provided diffusion measurements superior to those of the bPGSTE sequence, especially in the presence of severe heterogeneous background gradients.     

Acquisition of pure-phase diffusion spectra using oscillating-gradient spin echo

Oscillating-gradient spin echo (OGSE) diffusion experiments have long been used to measure the short-time apparent diffusion coefficient, D(app)(t), in the presence of restricted diffusion, as well as the spectrum of the slow-motion velocity autocorrelation function. In this work, we focus on two previously unexplored aspects of OGSE experiments: convection compensation and acquisition of pure-phase diffusion spectra in the presence of homonuclear scalar couplings. We demonstrate that convection compensation afforded by single-echo OGSE compares well with that in double-echo convection-compensated PGSE experiments. We also show that, in the presence of homonuclear scalar couplings, setting the OGSE echo time to 1/2J enables acquisition of pure-phase diffusion spectra and yields more reliable D estimates than mixed-phase PGSE or OGSE spectra. Pure-phase OGSE acquisition is also compatible with measurements of the apparent diffusion coefficient at an arbitrary diffusion time. These features of OGSE can be valuable in diffusion measurements of scalar-coupled small-molecule probes in cellular and other heterogeneous systems.