Comparison of static and dynamic MRI techniques for the measurement of regional cerebral blood volume.

Two different acquisition and processing strategies to determine the regional cerebral blood volume (rCBV) with magnetic resonance imaging (MRI) are compared. The first method is based on the acquisition of the signal time course during a bolus administration of a contrast agent (dynamic method). The second method evaluates signal changes before and after the contrast agent injection (static method), assuming the contrast agent remains primarily intravascular in the brain after the first pass. Both methods were applied to the same data sets, acquired with either echoplanar imaging (EPI, n = 18) or fast low-angle shot (FLASH, n = 28) techniques. A voxel-by-voxel correlation between the static and dynamic method yielded a correlation coefficient of 0.76 +/- 0.06 for the EPI and 0.71 +/- 0.10 for the FLASH measurements. The static method was less sensitive and showed higher standard deviations for rCBV than the dynamic method. With the development of truly intravascular contrast agents, the static perfusion MRI method, which can be performed with higher signal-to-noise ratio and higher spatial resolution, may become an alternative to ultra-fast MRI for measuring rCBV.     

Time-dependent changes in image contrast in brain tumors after gadolinium-DTPA

Time-dependent changes in the contrast enhancement of tumor tissue, tumor necrosis, perifocal edema, and normal brain tissue after IV injection of 0.1 mmol gadolinium-DTPA/kg body weight were studied with spin-echo technique (SE 800/35) in 15 patients with intracranial tumors. Using a region of interest technique, we determined the signal-intensity values of these tissues before and at fixed times up to 68.5 min after administration of the contrast agent. In tumor tissue, the 8.5 min postinjection (p.i.) scan showed a significant increase in signal intensity. The signal intensity of the tumor tissue remained significantly higher than precontrast levels throughout the entire period of observation, decreasing only slightly toward the end of the examination (48.5 and 68.5 min p.i.). Central tumor necrosis exhibited a delayed uptake of the contrast agent, with a maximum signal intensity between 48.5 and 68.5 min p.i. In perifocal edema and normal brain tissue, slight increases in signal intensity after injection of gadolinium-DTPA were measured (statistically significant in the case of edema). This effect, however, was not visually detectable. The present study shows that after one injection, scans with excellent tumor visualization can be obtained between 8.5 and 38.5 min p.i. and with diagnostically valid enhancement at least up to 68.5 min p.i.     

Biexponential modeling of multigradient-echo MRI data of the brain.

Functional MRI (fMRI) using fast multigradient-echo acquisition methods allows the quantitative determination of the relevant parameter T2*. Previously, the TE-dependent signal decay has been modeled with a monoexponential function despite the complex composition of the brain. In this study, biexponential modeling was used to evaluate the relaxation of brain parenchyma and blood separate from that of cerebrospinal fluid. Single-shot multigradient-echo data acquired with spiral or EPI techniques were analyzed. In phantom experiments the biexponential method proved to be accurate. Compared to the biexponential procedure, the monoexponential model overestimated T2* (72.2 msec vs. 65.3 msec) and underestimated DeltaT2* (2.96 msec vs. 3.19 msec) during visual stimulation. The biexponential method may allow intrinsic correction for partial volume effects due to cerebrospinal fluid. The activation-induced parameter changes are detected with a sensitivity equal to that of a monoexponential method. The resulting T2* and DeltaT2* values describe the experimental data more accurately.     

Correcting partial volume artifacts of the arterial input function in quantitative cerebral perfusion MRI.

To quantify cerebral perfusion with dynamic susceptibility contrast MRI (DSC-MRI), one needs to measure the arterial input function (AIF). Conventionally, one derives the contrast concentration from the DSC sequence by monitoring changes in either the amplitude or the phase signal on the assumption that the signal arises completely from blood. In practice, partial volume artifacts are inevitable because a compromise has to be reached between the temporal and spatial resolution of the DSC acquisition. As the concentration of the contrast agent increases, the vector of the complex blood signal follows a spiral-like trajectory. In the case of a partial-volume voxel, the spiral is located around the static contribution of the surrounding tissue. If the static contribution of the background tissue is disregarded, estimations of the contrast concentration will be incorrect. By optimizing the correspondence between phase information and amplitude information one can estimate the origin of the spiral, and thereupon correct for partial volume artifacts. This correction is shown to be accurate at low spatial resolutions for phantom data and to improve the AIF determination in a clinical example. Magn Reson Med 45:477-485, 2001.     

Thin-section, three-dimensional Fourier transform, steady-state free precession MR imaging of the brain.

The authors evaluated a three-dimensional Fourier transform implementation of a very short repetition time (TR) (24 msec), steady-state free precession (SSFP) pulse sequence for clinical imaging of the brain and compared it with a conventional two-dimensional Fourier transform long TR/echo time (TE) spin-echo sequence. First, the optimal flip angle of 10 degrees for generating images with contrast similar to that of long TR/TE spin-echo images was determined. Then, 29 patients with suspected brain lesions were studied with both techniques. Although the SSFP images did not exhibit the magnetic susceptibility artifacts that plague other rapid-imaging techniques, the conspicuity of most parenchymal lesions was often less than that on the spin-echo images. Also, the visibility of paramagnetic effects, such as the low signal intensity of brain iron, was less obvious at SSFP imaging. These substantial limitations may relegate the SSFP sequence to an adjunctive role, perhaps mainly demonstration of the cystic nature of mass lesions, because of its extreme sensitivity to slow flow.     

Macroscopic susceptibility in ultra high field MRI

PURPOSE: Magnetic susceptibility provides the basis for functional studies and image artifacts in MRI. In this work, magnetic susceptibility and the associated artifacts were analyzed at 8 T in phantoms and in the human head. METHOD: A mineral oil phantom was constructed in which three cylindrical air-filled tubes were inserted. This phantom was analyzed with gradient-recalled echo and SE imaging techniques acquired using varying TEs and receiver bandwidths. To visualize the presence of magnetic susceptibility artifacts in the head at 8 T, near axial, coronal, and sagittal GE images were also acquired from human volunteers. RESULTS: The use of gradient-recalled echo imaging resulted in the production of significant magnetic susceptibility artifacts. These artifacts could be readily visualized in phantom samples containing air-filled cylindrical tubes. In the human head, susceptibility artifacts produced significant image distortion in the skull base region. In this area, susceptibility artifacts often resulted in the complete loss of MR signal. Magnetic susceptibility artifacts were manifested as bands of varying signal intensity in the frontal lobe and temporal bone region. In addition, they produced clear distortions in the appearance of brain vasculature and seemed to accentuate the relative size of venous structures within the brain. CONCLUSION: When using gradient-recalled echo imaging in combination with relatively long TE values, magnetic susceptibility artifacts can be severe at 8 T. These artifacts could be reduced by increasing receiver bandwidths and by lowering effective TEs. As ultra high field MRI provides a fertile ground for the study of susceptibility artifacts in MRI, improvements obtained at this field strength will have a direct impact on studies performed at lower field strengths.     

BOLD contrast sensitivity enhancement and artifact reduction with multiecho EPI: parallel-acquired inhomogeneity-desensitized fMRI.

Functional MRI (fMRI) generally employs gradient-echo echo-planar imaging (GE-EPI) to measure blood oxygen level-dependent (BOLD) signal changes that result from changes in tissue relaxation time T(*) (2) between activation and rest. Since T(*) (2) strongly varies across the brain and BOLD contrast is maximal only where the echo time (TE) equals the local T(*) (2), imaging at a single TE is a compromise in terms of overall sensitivity. Furthermore, the long echo train makes EPI very sensitive to main field inhomogeneities, causing strong image distortion. A method is presented that uses accelerated parallel imaging to reduce image artifacts and acquire images at multiple TEs following a single excitation, with no need to increase TR. Sensitivity gains from the broadened T(*) (2) coverage are optimized by pixelwise weighted echo summation based on local T(*) (2) or contrast-to-noise ratio (CNR) measurements. The method was evaluated using an approach that allows differential BOLD CNR to be calculated without stimulation, as well as with a Stroop experiment. Results obtained at 3 T showed that BOLD sensitivity improved by 11% or more in all brain regions, with larger gains in areas typically affected by strong susceptibility artifacts. The use of parallel imaging markedly reduces image distortion, and hence the method should find widespread application in functional brain imaging.     

On the synchronization of transcranial magnetic stimulation and functional echo-planar imaging

PURPOSE: To minimize artifacts in echo-planar imaging (EPI) of human brain function introduced by simultaneous transcranial magnetic stimulation (TMS). MATERIALS AND METHODS: Distortions due to TMS pulses (0.25 msec, 2.0 T) were studied at 2.0 T before and during EPI. RESULTS: Best results were obtained if both the EPI section orientation and the frequency-encoding gradient were parallel to the plane of the TMS coil. Under these conditions, a TMS pulse caused image distortions when preceding the EPI sequence by less than 100 msec. Recordings with a magnetic field gradient pick-up coil revealed transient magnetic fields after TMS, which are generated by eddy currents in the TMS coil. TMS during image acquisition completely spoiled all transverse magnetizations and induced disturbances ranging from image corruption to mild image blurring, depending on the affected low and high spatial frequencies. Simultaneous TMS and radio-frequency (RF) excitation gave rise to T1-dependent signal changes that lasted for several seconds and yielded pronounced false-positive activations during functional brain mapping. CONCLUSION: To ensure reliable and robust combinations, TMS should be applied at least 100 msec before EPI while completely avoiding any pulses during imaging.     

Multiecho coarse voxel acquisition for neurofeedback fMRI

“Real‐time” functional magnetic resonance imaging is starting to be used in neurofeedback applications, enabling individuals to regulate their brain activity for therapeutic purposes. These applications use two‐dimensional multislice echo planar or spiral readouts to image the entire brain volume, often with a much smaller region of interest within the brain monitored for feedback purposes. Given that such brain activity should be sampled rapidly, it is worthwhile considering alternative functional magnetic resonance imaging pulse sequences that trade spatial resolution for temporal resolution. We developed a prototype sequence localizing a column of magnetization by outer volume saturation, from which densely sampled transverse relaxation time decays are obtained at coarse voxel locations using an asymmetric gradient echo train. For 5 × 20 × 20 mm3 voxels, 256 echoes are sampled at ～1 msec and then combined in weighted summation to increase functional magnetic resonance imaging signal contrast. This multiecho coarse voxel pulse sequence is shown experimentally at 1.5 T to provide the same signal contrast to noise ratio as obtained by spiral imaging for a primary motor cortex region of interest, but with potential for enhanced temporal resolution. A neurofeedback experiment also illustrates measurement and calculation of functional magnetic resonance imaging signals within 1 sec, emphasizing the future potential of the approach. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Simultaneous perfusion and BOLD imaging using reverse spiral scanning at 3T: characterization of functional contrast and susceptibility artifacts.

Reverse spiral scanning with arterial spin-labeling was developed at 3T to simultaneously detect perfusion and BOLD signals in the brain by subtracting or adding the control and labeled images, respectively, in the same dataset. BOLD contrast was improved with the longer effective echo time achieved in the reverse spiral scan compared to conventional forward spiral scans. Susceptibility artifacts near air-tissue interfaces in the brain were substantially reduced in the reverse spiral images due to their early data acquisition time and, hence, less signal attenuation. Brain activation experiments with the reverse spiral scan were performed on normal subjects and were compared to forward spiral imaging in the same subjects. The experiments demonstrated that reverse spiral imaging was able to detect perfusion and BOLD signals simultaneously and reliably, even in the brain regions with severe susceptibility-induced local gradients, while forward spiral scans were either not optimal for detecting the two functional signals at the same time or were vulnerable to susceptibility artifacts.     

Detection with echo-planar MR imaging of transit of susceptibility contrast medium in a rat model of regional brain ischemia.

Gradient-refocused echo-planar magnetic resonance (MR) images (TE = 18 msec) were acquired in rats during bolus injection of iron oxide particles, and the first pass of the contrast agent through the brain was monitored. In control rats, contrast agent (0.1 mmol/kg iron) produced significant signal-intensity (SI) reduction over the right hemisphere and similar declines over the left. SI loss occurred first in the cortex and basal ganglia and later in the periventricular regions, along the midline, and in the thalamic zone. Sequential volume-localized proton spectra acquired during transit of 0.02 mmol/kg iron showed substantial reduction in SI, slight asymmetric broadening, and no change in chemical shift of the water resonance. In rats with unilateral occlusion of the middle cerebral artery, peak reduction in ischemic brain SI was to 70% +/- 9% of control, while normal brain SI was reduced to 18% +/- 2% (P less than .01), allowing distinction of the ischemic regions. The presence and location of injury were confirmed with diffusion-weighted imaging and postmortem vital staining. These results demonstrate abnormal transit profiles in a rat model of regional brain ischemia. Evaluation of dynamic contrast delivery patterns may provide unique information in early brain ischemia.     

Evaluation of potential gastrointestinal contrast agents for echoplanar MR imaging

Although the diagnostic application of echoplanar imaging (EPI) has until now been limited, recent technical advances provide anatomic resolution and signal-to-noise ratios comparable to that of conventional MR imaging. The purpose of this study was to investigate approved aqueous gastrointestinal contrast agents for use in abdominal EPI. Conventional and echoplanar MR imaging experiments were performed with 1.0 Tesla whole body systems. Phantom measurements of Gastrografin, barium sulfate suspension, oral gadopentetate dimeglumine, water, and saline were performed. Signal intensity (SI) of aqueous oral barium sulfate and iodine based CT contrast agents was lower on conventional spin-echo (SE), Flash, and Turbo-Flash images than on EP images. The contrast agents exhibited higher SI on T2-weighted SE PE images and TI-time dependence on inversion recovery EP-images. The barium sulfate suspension was administered in volunteers to obtain information about bowel lumen enhancement and susceptibility artifacts. Oral administration of the aqueous barium sulfate suspension increased bowel lumen signal and reduced susceptibility artifacts. Approved aqueous gastrointestinal contrast media or flavored saline with long relaxation times may serve as safe, simple, and effective gastrointestinal contrast agents in abdominal EPI. Correspondence to: P. Reimer     

BOLD Signal in memory paradigms in hippocampal region depends on echo time

Purpose:

To evaluate the hypothesis that the entire hippocampus might be affected by susceptibility artifacts. Previous studies described susceptibility artifacts in the amygdala and the anterior hippocampus.

Materials and Methods:

We investigated 20 subjects with a verbal memory paradigm aiming at testing two different TEs (45 vs. 64 msec) at 1.5 T for hippocampal blood oxygenation level‐dependent (BOLD) activity. T2* maps were calculated from the normalized mean echo‐planar imaging (EPI) of the two echo times (TEs).

Results:

Within the hippocampal region of interest (ROI), the amount of suprathreshold voxels was significantly higher at TE = 64 msec compared to TE = 45 msec. When corrected for multiple comparisons (family‐wise error [FWE] in a small volume of interest, P < 0.05) we no longer found significant activations at TE = 45 msec, while a significant number of voxels remained after the small volume correction (P < 0.05, FWE) within the ROI at TE = 64 msec.

Conclusion:

Although a shorter TE demonstrates advantages, a TE of 45 msec leads to a significant loss of BOLD signal detection in memory functional magnetic resonance imaging (fMRI) studies when compared to 64 msec. We assume that the hippocampal region, even the anterior part, is not strongly affected by susceptibility gradients. J. Magn. Reson. Imaging 2013;37:1064–1071. © 2012 Wiley Periodicals, Inc.     

Improving high-resolution MR bold venographic imaging using a T1 reducing contrast agent.

Recently, a new imaging method was proposed by Reichenbach et al (Radiology 1997;204:272-277) to image small cerebral venous vessels specifically. This method, referred to as high-resolution blood oxygen level-dependent venography (HRBV), relies on the susceptibility difference between the veins and the brain parenchyma. The resulting phase difference between the vessels and the brain parenchyma leads to signal losses over and above the usual T2* effect. At 1.5 T, a rather long TE (roughly 40 msec) is required for this cancellation to become significant, leading to enhanced susceptibility artifacts and a long data acquisition time. In this study, we examine the utility of incorporating a clinically available T1 reducing contrast agent, Omniscan (Sanofi Winthrop Pharmaceuticals, NY, NY), with the HRBV imaging approach to reduce susceptibility artifacts and imaging time while maintaining the visibility of cerebral veins. Using a double-dose injection of Omniscan, we were able to reduce TE from 40 to 25 msec. This led to a decrease in TR from 57 to 42 msec, allowing a 26% reduction in data acquisition time while maintaining the visibility of cerebral venous vessels and reducing susceptibility artifacts. J. Magn. Reson. Imaging 1999;10:118-123, 1999.     

Exogenous contrast agent improves sensitivity of gradient-echo functional magnetic resonance imaging at 9.4 T.

Relative to common clinical magnetic field strengths, higher fields benefit functional brain imaging both by providing additional signal for high-resolution applications and by improving the sensitivity of endogenous contrast due to the blood oxygen level dependent (BOLD) mechanism, which has limited detection power at low magnetic fields relative to the use of exogenous contrast agent. This study evaluates the utility of iron oxide contrast agent for gradient echo functional MRI at 9.4 T in rodents using cocaine and methylphenidate as stimuli. Relative to the BOLD method, the use of high iron doses and short echo times provided a roughly twofold global increase in functional sensitivity, while also suppressing large vessel signal and reducing susceptibility artifacts. Furthermore, MRI measurements of the functional percentage change in cerebral blood volume (CBV) showed excellent agreement with results obtained at much lower magnetic field strengths, demonstrating that MRI estimates of this quantity are roughly independent of magnetic field when appropriate techniques are employed. The derived field dependencies for relative sensitivity and MRI estimates of the percentage change in CBV suggest that the benefits provided by exogenous agents will persist even at much higher magnetic fields than 9.4 T.     

Functional brain imaging using a blood oxygenation sensitive steady state.

Blood oxygenation level dependent (BOLD) functional MRI (fMRI) is an important method for functional neuroimaging that is sensitive to changes in blood oxygenation related to brain activation. While BOLD imaging has good spatial coverage and resolution relative to other neuroimaging methods (such as positron emission tomography (PET)), it has significant limitations relative to other MRI techniques, including poor spatial resolution, low signal levels, limited contrast, and image artifacts. These limitations derive from the coupling of BOLD functional contrast to sources of image degradation. This work presents an alternative method for fMRI that may over-come these limitations by establishing a blood oxygenation sensitive steady-state (BOSS) that inverts the signal from deoxygenated blood relative to the water signal. BOSS fMRI allows the imaging parameters to be optimized independently of the functional contrast, resulting in fewer image artifacts and higher signal-to-noise ratio (SNR). In addition, BOSS fMRI has greater functional contrast than BOLD. BOSS fMRI requires careful shimming and multiple acquisitions to obtain a precise alignment of the magnetization to the SSFP frequency response.     

Multislice T1-weighted hybrid rare in CNS imaging: Assessment of magnetization transfer effects and artifacts

Using a T1-weighted hybrid rapid acquisition with relaxation enhancement (RARE) MR sequence that implements an echo-to-view mapping scheme termed “low-high profile order,” we evaluated signal intensity changes in different brain tissues as a function of number of slices, interslice gap, and echo train length (ETL). We also measured phase-encode and frequency-encode noise as well as blurring artifacts along the phase-encode direction as a function of ETL. Off-resonance magnetization transfer effects were demonstrated to be responsible for signal intensities changes in white matter and gray matter when using multislice techniques. These effects are amplified by increasing the number of slices and ETL. Due to the nature of the implemented echo-to-view mapping scheme, no on-resonance magnetization transfer effects were observed from the intraslice echo train. Selective background (white matter and gray matter) suppression in multislice T1-weighted hybrid RARE, secondary to off-resonance magnetization transfer effects, may provide better contrast resolution of enhancing central nervous system (CNS) lesions at much shorter scan time as compared to conventional spin-echo T1-weighted sequences. This improvement in contrast resolution as a function of ETL may be limited by worsening phase-encode noise and blurring artifacts.     

Gradient-echo MR imaging of the cervical spine: evaluation of extradural disease

A prospective study was undertaken on 204 consecutive patients comparing low flip angle gradient-echo and T1-weighted spin-echo techniques in the MR evaluation of cervical extradural disease. Four patient groups were studied with varying gradient-echo TEs (6 or 13 msec) and flip angles (10 degrees or 60 degrees). Images were evaluated independently for contrast behavior and anatomy, then directly compared for conspicuity of lesions. The FLASH sequences (especially with a 10 degrees flip angle) produced better conspicuity of disease in half the imaging time. T1-weighted spin-echo sequences were more sensitive to marrow changes and intradural disease. The short TE sequence (6 msec) did not produce any diagnostic advantage over the longer TE sequence (13 msec). A fast and sensitive MR examination for cervical extradural disease combines a sagittal T1-weighted spin-echo acquisition with sagittal and axial FLASH 10 degrees sequences.     

In vivo fluorine-19 MR imaging: Relaxation enhancement with Gd-DTPA

The lack of a naturally occurring background signal from fluorine in magnetic resonance (MR) imaging makes fluorinated compounds potentially attractive candidates for tissue-specific MR contrast agents. Problems associated with the in vivo use of fluorinated compounds are toxicity, which limits the amount of agent that can be used; multiple resonance lines; and an excessively long T1, which leads to long sequence TRs and consequently long imaging times. Many fluorinated agents also possess complex MR spectra that result in chemical shift artifacts if not corrected. The authors demonstrate the use of an extracellular fluorinated agent with a single MR peak for selective imaging of a brain abscess in an animal model and show that the image signal per unit of acquisition time can be enhanced through the use of a T1 relaxation agent, gadolinium diethylenetriamine-pentaacetic acid (DTPA). Trifluoromethylsulfonate was administered at a fluorine-19 dose of 4 mmol/kg, and fluorine images of the induced abscess were acquired before and after the injection of a standard dose of Gd-DTPA (0.1 mmol/kg); non—section-selected projection images were used. Typical imaging times were less than 5 minutes. The signal enhancement factor achieved was approximately four (4.0 ± 0.8) with use of a 500/12 (TR msec/TE msec) spinecho sequence.     

A comparison of fast MR scan techniques for cerebral activation studies at 1.5 Tesla

To evaluate the sensitivity of fast, gradient-echo MR scan techniques in their ability to detect blood oxygenation level dependent (BOLD) signal changes in task activation studies, three dedicated fast scan techniques, each with whole-brain coverage, were compared during a 3-min finger tapping paradigm on nine normal volunteers on a clinical 1.5 T scanner. Multislice (2D) single-shot spiral, 3D spiral, and multislice (2D) single-shot EPI scan techniques were done with similar temporal and spatial resolutions on each of the volunteers in random order. After image registration and statistical analysis, the sensitivity to detect activation was evaluated for the techniques by calculating t scores and number of activated voxels in predetermined regions of interest, including the contralateral primary sensorimotor cortex, the premotor region, the parietal region, the supplementary motor area, and the ipsilateral cerebellum. Baseline images acquired with the three techniques were qualitatively comparable and had a similar effective spatial resolution of around 5 × 5 × 5 mm³, as determined from autocorrelation analysis. The anatomical coverage was somewhat reduced (4 less slices per volume) with EPI at the identical temporal resolution of 1.76 s for all techniques. The use of multislice 2D spiral scan for motor cortex fMRI experiments provided for a superior overall temporal stability, and an increased sensitivity compared with multislice 2D EPI, and 3D spiral scan. The difference in sensitivity between multislice 2D spiral and EPI scans was small, in particular in the case of a ramp-sampled version of EPI. The difference in performance is attributed mainly to the difference in scan-to-scan stability.