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Continuous arterial spin labeling (CASL) measurements over a range of post-labeling delay (PLD) times can be interpreted to estimate cerebral blood flow (CBF) and arterial transit time (deltaa) with good spatial and temporal resolution. In this work, we present an in vivo demonstration of Hadamard-encoded continuous arterial spin labeling (H-CASL); an efficient method of imaging the inflow of short boli of labeled blood water in the brain at multiple PLD times. We present evidence that H-CASL is viable for in vivo application in the rat brain and can improve the precision of deltaa estimation in 2/3 of the imaging time required for standard multi-PLD CASL. Based on these findings, we propose that H-CASL may have application as an efficient prescan for optimization of ASL imaging parameters to improve the precision of CBF estimation.

Perfusion maps, which are calculated from dynamic-susceptibility contrast (DSC)-MRI data by deconvolution of the arterial input function (AIF), are commonly used to predict tissue infarction in acute stroke. However, since the AIF is commonly measured in a major artery, there can be perfusion measurement errors associated with bolus delay/dispersion. Although methods to account for delay-related errors have been proposed, the effect of dispersion is more difficult to deal with and is usually left uncorrected. This study presents an assessment of the delay-dispersion relationship in a group of patients. Although a significant correlation was observed with one of the bolus delay definitions used, the estimation of the dispersion from the degree of delay was unreliable. Importantly, the dispersion observed in many patients was sufficient to result in substantial perfusion errors. The results are compared with previous numerical simulations, and their implications for the assessment and management of acute stroke are discussed.

Although selective vulnerability and delayed neuronal death following global ischemia have been recognized in both the human and animal brain, the underlying mechanisms of cell damage are not fully understood. In this study we investigated the time-dependent changes of the apparent diffusion coefficient (ADC) of water and cerebral blood flow (CBF) in a classic animal model of selective vulnerability and delayed neuronal death, using magnetic resonance (MR) diffusion- and perfusion-weighted imaging. CBF was monitored using the noninvasive MR arterial spin labeling method called flow-sensitive alternating inversion recovery (FAIR). Bilateral common carotid occlusion was induced for 5 min, followed by 10 hr of reperfusion in a gerbil model. The most notable finding was that the lateral portion of the striatum in the basal ganglia exhibited a prolonged and gradual ADC decrease throughout the study following reperfusion. This pattern was not exhibited within the cortex. It is suggested that regions known to exhibit so-called delayed cell death progress to infarction via a gradual process that can be monitored by MR diffusion-weighted imaging (DWI).

Multiple-slice perfusion imaging by continuous arterial spin labeling (CASL) is made possible by amplitude modulation (AM) of the labeling RF pulse, but perfusion sensitivity is reduced relative to the single-slice technique. A computer model of the Bloch equations for velocity driven adiabatic fast passage was developed to elucidate the compromised sensitivity to perfusion of the AM control technique for CASL. Calculations were performed over ranges of RF pulse amplitude, B-1; magnetic field gradient, G; phase, phi, and frequency, f, of the modulation function; velocity, v, and relaxation times, T-1 and T-2, of blood. It was found that unless f > 2 pi B-1, phi determines the performance of the AM control; excessively high B-1 or v reduces the efficiency of the AM control; and T, relaxation dominates if f is too great. In vivo, in rat brain (n = 5) at 2.35 T, the sensitivity of the AM technique to perfusion was 70% of the sensitivity of single-slice CASL.

Velocity-driven adiabatic fast passage (AFP) is commonly employed for perfusion imaging by continuous arterial spin labeling (CASL). The degree of inversion of protons in blood determines the sensitivity of CASL to perfusion. For this study, a computer model of the modified Bloch equations was developed to establish the optimum conditions for velocity-driven AFP. Natural variations in blood velocity over the course of the cardiac cycle were found to result in significant variations in the degree of inversion. However, the mean degree of inversion was similar to that for blood moving at a constant velocity, equal to the time-averaged mean, at peak velocities and heart rates within normal ranges. A train of RF pulses instead of a continuous RF pulse for labeling was found to result in a highly nonlinear dependence of the degree of inversion on RF duty cycle. This may have serious implications for the quantification of perfusion.

Oligemic regions, in which the cerebral blood flow is reduced without impaired energy metabolism, have the potential to evolve toward infarction and remain a target for therapy. The aim of this study was to investigate this oligemic region using various MRI parameters in a rat model of focal oligemia. This model has been designed specifically for remote-controlled occlusion from outside an MRI scanner. Wistar rats underwent remote partial MCAO using an undersize 0.2 mm nylon monofilament with a bullet-shaped tip. Cerebral blood flow (CBF(ASL)), using an arterial spin labeling technique, the apparent diffusion coefficient of water (ADC), and the relaxation times T(1) and T(2) were acquired using an 8.5 T vertical magnet. Following occlusion there was a decrease in CBF(ASL) to 35 +/- 5% of baseline throughout the middle cerebral artery territory. During the entire period of the study there were no observed changes in the ADC. On occlusion, T(2) rapidly decreased in both cortex and basal ganglia and then normalized to the preocclusion values. T(1) values rapidly increased (within approximately 7 min) on occlusion. In conclusion, this study demonstrates the feasibility of partially occluding the middle cerebral artery to produce a large area of oligemia within the MRI scanner. In this region of oligemic flow we detect a rapid increase in T(1) and decrease in T(2). These changes occur before the onset of vasogenic edema. We attribute the acute change in T(2) to increased amounts of deoxyhemoglobin; the mechanisms underlying the change in T(1) require further investigation.

Dynamic susceptibility contrast (DSC) MRI is now increasingly used for measuring perfusion in many different applications. The quantification of DSC data requires the measurement of the arterial input function (AIF) and the deconvolution of the tissue concentration time curve. One of the most accepted deconvolution methods is the use of singular value decomposition (SVD). Simulations were performed to evaluate the effects on DSC quantification of the presence of delay and dispersion in the estimated AIF. Both delay and dispersion were found to introduce significant underestimation of cerebral blood flow (CBF) and overestimation of mean transit time (MTT). While the error introduced by the delay can be corrected by using the information of the arrival time of the bolus, the correction for the dispersion is less straightforward and requires a model for the vasculature.

Single-shot diffusion-weighted echo-planar imaging (EPI) is typically used for most clinical diffusion studies due to its low sensitivity to patient motion. Although the Nyquist ghost artifact in EPI can be substantially reduced, there is frequently a residual ghost with low signal intensity. As reported in this study, this residual ghost can produce severe artifacts when maps of the apparent diffusion coefficient (ADC) are calculated from single-shot echo-planar images. The artifacts presented in this paper appear as regions of apparently low ADC which simulate regions of reduced diffusion, but are in fact generated by b-value dependent Nyquist ghosts of the orbits. Data acquired in vivo were used to demonstrate that these artifacts can be avoided by including standard methods of spatial presaturation or fluid-suppression in the diffusion-weighted EPI protocol. In addition, phantom studies were used to illustrate how phase and amplitude variations in the ghost generate the artifacts and theoretical expressions, derived elsewhere, were used to provide a detailed understanding of the artifacts observed in vivo. The level of Nyquist ghost reported for the current generation of commercial scanners suggests that this is a general phenomenon which should be a consideration in all EPI-based diffusion studies. Magn Reson Med 42:385-392, 1999. (C) 1999 Wiley-Liss, Inc.

This study examined the relationship between magnetic resonance diffusion imaging and autoradiographic markers of cerebral blood flow (99mTc-hexamethylpropylene amine oxime) and cerebral hypoxia (125I-iodoazomycin arabinoside) in a rat model of stroke. Middle cerebral artery occlusion in the rat was performed using an intraluminal suture approach. Diffusion, hypoxia, and blood flow maps were acquired 2 hr following occlusion, and were compared with T2 images and histology at 7 hr. Two hours following middle cerebral artery occlusion the lesion distributions from the diffusion maps and hypoxic autoradiographs were similar. The blood flow threshold for increased uptake of the hypoxic marker was approximately 34 +/- 7% of the normal flow. The combination of diffusion or hypoxic images with perfusion maps allowed differentiation between four regions: 1) normal tissue; 2) a region of decreased perfusion but normal diffusion and normal uptake of hypoxic marker; 3) a region of decreased perfusion, decreased diffusion and increased uptake of hypoxic marker; 4) a region of decreased perfusion, decreased diffusion and low uptake of hypoxic marker. The areas for increased uptake of hypoxic marker and decreased diffusion are equivalent, indicating similar blood flow thresholds. Regions of oligaemic misery perfusion, ischaemic misery perfusion and lesion core may be delineated with the combination of diffusion or hypoxic images and perfusion maps.

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.

The importance of diffusion-weighted MRI in the assessment of acute stroke is well-recognized, and quantitative maps of the apparent diffusion coefficient (ADC) are now widely used. Echoplanar imaging provides a robust method of acquiring diffusion-weighted images free of motion artifact. However, initial experience with clinical MRI systems indicates that calculation of artifact-free ADC maps from a series of echo-planar diffusion-weighted images is not necessarily straight-forward. One of the problems is that frequency shifts resulting from eddy currents can cause misregistration of base diffusion-weighted images. In this study, an on-line correction method that overcomes this problem is described, and phantom and human images that demonstrate the validity of the technique are presented. The method uses a non-phase-encoded reference scan to correct the phase of each echo in the echo train, and can provide ADC maps that are free of misregistration artifacts, without the need for off-line postprocessing.

For the in vivo measurement of the apparent diffusion coefficient (ADC), it is desirable for the total imaging time to be as short as possible. One technique is based on a TurboFLASH acquisition in which the diffusion gradients are inserted into a driven equilibrium Fourier transform (DEFT) combination of hard pulses. However, this sequence has the disadvantage that eddy current-induced inhomogeneities lead to incomplete refocusing of the magnetization during the diffusion preparation and to incorrect ADC values. A modification to the sequence is suggested that eliminates this error by phase-cycling the second 90 degrees pulse of the preparation. This study also investigates the effect of a reduced delay time between acquisitions on the accuracy of the measurement. The quality of the TurboFLASH sequence is demonstrated by experimental validation on an agar phantom and in vivo on the rat brain using a high-field (8.5 T) system. Reduction of the interexperiment delay time is shown to be achievable to a certain degree without compromising the measurement accuracy.

The effects of white and gray matter diffusion anisotropy on ischemic lesion delineation have been studied in the rat model of middle cerebral artery occlusion. Apparent diffusion coefficient (ADC) maps obtained by conventional pulsed gradient spin echo diffusion-weighted imaging (PGSE-DWI) were compared with maps of the trace of the diffusion tensor in both normal and occluded animals. Diffusion tensor trace maps were derived from the average of the ADC maps from three separate experiments with diffusion weighting along three orthogonal axes, and also from a single-scan method. A marked degree of diffusion anisotropy was observed in both cortical gray matter and white matter from ADC maps of the control animals. In the occluded animals, the systematic effects of anisotropy on ADC and lesion area influenced the delineation of the ischemic territory in the PGSE-DWI ADC maps. However, the two trace methods eliminated these effects and gave consistent ischemic lesion depiction, despite the use of differing diffusion times in the two measurements.

In this high resolution magnetic resonance spectroscopic study of experimental allergic encephalomyelitis (EAE) and Semliki Forest virus (SFV) infection of the Biozzi AB/H mouse, marked increases in the initially low levels of N-trimethyl compounds in the spinal cord were observed during probable demyelinating episodes. There was also a pronounced and reproducible modulation of the levels of taurine and myo-inositol during acute and again during chronic relapsing EAE. The ratio of N-acetyl-aspartate to creatine in the spinal cord of mice infected with the mutant M9 strain of SFV decreased to approximately 70% of that seen in normal mice.

Diffusion-weighted images of the rat brain were obtained using the pulsed-gradient spinecho method. An attempt was made to extract perfusion-related parameters from signal intensity data taken from the caudate-putamen region of the images, by using a nonlinear least-squares calculation to fit the Le Bihan biexponential expression (Le Bihan et al., Radiology, 168, 497 (1988)) to the data. The perfusion-related parameters could not be obtained with sufficient accuracy to be useful, although the perfusion-weighted images appear to contain meaningful qualitative information. An analysis of the perfusion model is presented and shows why the Le Bihan pseudo-diffusion coefficient is particularly difficult to measure with reasonable accuracy. © 1992 Academic Press, Inc.

We report here how magnetic resonance imaging can be used to gain definitive information about tissue pathology by the combined use of spin-echo and gradient-echo sequences. We also show how artifacts arising from respiratory motion can be eliminated by using a simple respiratory gating technique. © 1990 Academic Press, Inc.

A novel method for measuring the longitudinal relaxation time of arterial blood (T1a) is presented. Knowledge of T1a is essential for accurately quantifying cerebral perfusion using arterial spin labeling (ASL) techniques. The method is based on the flow-sensitive alternating inversion recovery (FAIR) pulsed ASL (PASL) approach. We modified the standard FAIR acquisition scheme by incorporating a global saturation pulse at the beginning of the recovery period. With this approach the FAIR tissue signal difference has a simple monoexponential dependence on the recovery time, with T1a as the time constant. Therefore, FAIR measurements performed over a range of recovery times can be fitted to a monoexponential recovery curve and T1a can be calculated directly. This eliminates many of the difficulties associated with the measurement of T1a. Experiments performed in vivo in the mouse at 2.35T produced a mean value of 1.51 s for T1a, consistent with previously published values. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc.

Diffusion tensor fiber tracking potentially can give information about in vivo brain connectivity. However, this technique is difficult to validate due to the lack of a gold standard. Fiber tracking reliability will depend on the quality of the data and on the robustness of the algorithms used. Information about the effects of various anatomical and image acquisition parameters on fiber tracking reliability may be used in the design of imaging sequences and of tracking algorithms. In this study, tracking was performed on two different simulated models to study the effects on tracking quality of SNR, anisotropy, curvature, fiber cross-section, background anisotropy, step size, and interpolation. Tracking was also performed on volunteer data to assess the relevance of the simulations to real data. Our results show that, in general, tracking with high SNR and high anisotropy using interpolation and a low step size gives the most reliable results. Partial volume effects are shown to have a detrimental effect when the background is anisotropic and when tracking narrow fibers. The results derived from real data show similar trends and thus support the findings of the simulations. These simulations may therefore help to determine which structures can be tracked for a given image quality.

Bolus tracking data obtained with paramagnetic intravascular tracers are commonly analyzed and quantified by the direct measurement of properties of the tissue concentration-time curve (e.g., time to peak (TTP)). The measurement of these “summary parameters” is used as an accessible alternative approach to the complex deconvolution procedure, and provides indirect measures of perfusion. However, summary parameters do not take into account differences in arterial input functions (AIFs) or residue functions (R(t)) between patients or studies. Simulations were performed to assess the variability of summary parameters over a realistic range of AIFs and for differing R(t), to establish whether they can be used as reliable measures of tissue perfusion status. Results showed that the value of each summary parameter investigated is highly dependent upon both the AIF and R(t). The referencing of summary parameters to their corresponding value in the AIF or in normal tissue is a method commonly used to normalize results, but this approach did not lead to any measures that were independent of both the AIF and R(t) in this study. The results presented here show that the use of summary parameters requires considerable caution, since tissue or patient types can easily be incorrectly classified due to the effect of variations in patient AIF and R(t). Magn Reson Med 47:61‐67, 2002. © 2002 Wiley-Liss, Inc.

A new method for measuring cerebral blood flow (CBF) and cerebral blood volume (CBV) noninvasively using MRI is presented. The approach is based on the technique of arterial spin labelling (ASL), in which CBF-based contrast is generated by controlled modulation of the longitudinal magnetization of the blood. The proposed method also uses differences in T2 between tissue and blood to differentiate the two compartments and allow assessment of the relative size of each. Two successive EPI images are acquired following spin preparation using either a slice-selective or global inversion pulse, and the technique is therefore referred to as double-echo FAIR (DEFAIR). DEFAIR is demonstrated in the normal gerbil brain and during hypothermia, where reductions of both CBF and CBV are known to occur. It is also shown theoretically that this method can be extended to include a measurement of oxygen extraction fraction. The main drawbacks of the technique are the long acquisition time and relatively low sensitivity to hemodynamic changes compared to conventional qualitative T-weighted BOLD contrast, which may limit its applicability and practical use in monitoring functional cerebral activation. However, the technique can be used repetitively in longer-term time course studies due to its noninvasive and quantitative nature. Magn Reson Med 45:853–863, 2001. © 2001 Wiley-Liss, Inc.

Localized q-space imaging was used to obtain water displacement profiles from mouse brain. These profiles take the form of unidirectional diffusive displacement probability distributions. Two groups of mice were studied, a normal group and a group in which surgery had been performed to produce a unilateral reduction in the supply of blood to the forebrain, q-Space measurements were made both in vivo and postmortem, The displacement profiles were characterized using the summary parameter prob[d < 10], which is the proportion of water molecules that undergo a net diffusive displacement that is less than +/-10 mu m, during the diffusion period (50 ms). The range of prob[d < 10] values in the normal group was 0.71 to 0.77 in vivo compared with 0.78 to 0.87 in the impaired hemisphere of the surgically treated group, An increase in prob[d < 10] occurred postmortem to yield values in the range 0.79 to 0.81 and 0.80 to 0.89 in the normal and surgically treated group, respectively, These observations are consistent with the diffusion-weighted image intensity changes that occur after a period of ischemia.

Two children with Canavan's Disease, an autosomal recessive leukodystrophy, were studied by localized 1H spectroscopy. The N-acetylaspartate (NAA) signal intensity was high relative to other metabolite signals, and the signal intensity from choline-containing compounds was low. These findings are discussed in relation to a possible role for NAA in normal myelination.

Phosphorus-31 liver spectra were recorded from 6 controls and 12 patients with liver disease using TR values of 0.5 and 5 s and a pulse angle of 45°. One of the control subjects was also examined at seven TR values ranging from 0.5 to 20 s. Spectra from one additional patient were collected at TRs of 0.5, 1, and 2 s only. There was a significant increase in the mean ratio of peak areas phosphomonoesters (PME)/β-ATP in 9 of the 13 patients and a decrease in phosphodiesters (PDE)/β-ATP in 3 of the patients, compared with controls, at the longer TR values. The saturation factors for PME and PDE were greater than those for Pi and β-ATP, and spectral abnormalities in disease were often more evident as the TR value was increased from 0.5 to 5 s. Acquisition parameters need to be chosen with a knowledge of the impact that saturation effects have on metabolite quantification and Spectral Contrast. © 1991 Academic Press, Inc.

We observe linewidths of 0.1-0.4 ppm in 31P spectra of human muscle, liver, and brain. T2 measurements of muscle phosphocreatine, together with previous brain studies, indicate that further improvements in linewidth to 0.02-0.05 ppm might often be achieved, but in some lesions magnetic susceptibility variations may limit spectral resolution.

31P NMR spectra of the rat liver were recorded in vivo at 2.35 and 8.5 T. There was a large peak in the phosphodiester region of spectra obtained at 2.35 T which was much reduced at 8.5 T. The peak at 2.35 T is unlikely to be primarily from free cytosolic phosphodiesters, which would not be expected to display such a marked field dependence.

The elevated levels of brain histidine in histidinaemic mice are detected in vivo by 1H NMR at 8.5 and 1.9 T. The concentrations determined from the in vivo spectra correlate well with subsequent analytical determinations. This technique is discussed in relation to monitoring phenylalaninc in humans with phenylketonuria. © 1986 Academic Press, Inc.

1H NMR was used to detect lactate accumulation in the intact gerbil brain postmortem. The lactate concentration was estimated from the spectra by comparison to signals from N-acetylaspartate, creatine + phosphocreatine, and water. The effects of T2, phase modulation, and solvent suppression were taken into account. The estimated concentrations were compared to determinations performed on the same brains after extraction. The lactate concentration estimated from the intact brain spectra was between 70 and 90% of the values determined in vitro, on the extracts, depending on the concentration standard used. If N-acetylaspartate was used as the standard then the proportion of detected lactate (92%) was not significantly different from 100%.