Noise reduction in multi-slice arterial spin tagging imaging.

Attenuating the static signal in arterial spin tagging (ASSIST) was initially developed for 3D imaging of cerebral blood flow. To enable the simultaneous collection of cerebral blood flow and BOLD data, a multi-slice version of ASSIST is proposed. As with the 3D version, this sequence uses multiple inversion pulses during the tagging period to suppress the static signal. To maintain background suppression in all slices, the multi-slice sequence applies additional inversion pulses between slice acquisitions. The utility of the sequence was demonstrated by simultaneously acquiring ASSIST and BOLD data during a functional task and by collecting resting-state ASSIST data over a large number of slices. In addition, the temporal stability of the perfusion signal was found to be 60% greater at 3 T compared to 1.5 T, which was attributed to the insensitivity of ASSIST to physiologic noise.

Measuring the effects of indomethacin on changes in cerebral oxidative metabolism and cerebral blood flow during sensorimotor activation.

The work presented here uses combined blood oxygenation level-dependent (BOLD) and arterial spin tagging (AST) approaches to study the effect of indomethacin on cerebral blood flow (CBF) and oxygen consumption (CMRO(2)) increases during motor activation. While indomethacin reduced the CBF increase during activation, it did not significantly affect the CMRO(2) increase during activation. The ratio of the activation-induced CBF increase in the presence and absence of indomethacin was 0.54 +/- 0.08 (+/-SEM, n = 8, P < 0.001), while the ratio of the CMRO(2) increase in the presence and absence of the drug was 1.02 +/- 0.08 (+/-SEM, N = 8, ns). Potential difficulties in estimating CMRO(2) changes from combined BOLD/AST data are discussed.

Supracondylar extension fracture of the humerus in children. Manipulative reduction, immobilisation and fixation using a U-shaped plaster slab with the elbow in full extension.

We present a method of manipulative reduction, immobilisation and fixation using a U-shaped plaster with the elbow in extension for extension-type supracondylar fractures of the humerus in children. When the elbow is in full extension, both the extensor and the flexor muscles are neutralised during manipulative reduction and the carrying angle can be easily assessed thus preventing cubitus varus, the most common complication. In order to evaluate the efficiency of this method, we compared the clinical results of the new method with those of conventional treatment. In a group of 95 children who sustained an extension-type supracondylar fracture of the humerus, 49 were treated by the new method and 46 by the conventional method, reduction and immobilisation in a plaster slab with the elbow in flexion. Reduction and immobilisation were easily achieved and reliably maintained by one manipulation for all the children treated by the new method. In 12 children treated by the conventional method, the initial reduction failed and in seven secondary displacement of the distal fragment occurred during the period of immobilisation in plaster. All required a second or third manipulation. Of the 46 children, 28 (60.9%) had developed cubitus varus at a mean follow-up of 4.6 years when treated by the conventional method. None of the children treated by the new method developed cubitus varus. The mean score, according to the Hospital for Special Surgery (HSS) elbow scoring system, was 91 points using the new method and 78 with the conventional method. The results were statistically significant with regard to the incidence of cubitus varus and the elbow score (p < 0.01) suggesting that the new method is reliable and gives a satisfactory outcome.

H(2)(15)O PET validation of steady-state arterial spin tagging cerebral blood flow measurements in humans.

Steady-state arterial spin tagging approaches can provide quantitative images of CBF, but have not been validated in humans. The work presented here compared CBF values measured using steady-state arterial spin tagging with CBF values measured in the same group of human subjects using the H(2)(15)O IV bolus PET method. Blood flow values determined by H(2)(15)O PET were corrected for the known effects of incomplete extraction of water across the blood brain barrier. For a cortical strip ROI, blood flow values determined using arterial spin tagging (64+/-12 cc/100 g/min) were not statistically different from corrected blood flow values determined using H(2)(15)O PET (67+/-13 cc/100 g/min). However, for a central white matter ROI, blood flow values determined using arterial spin tagging were significantly underestimated compared to corrected blood flow values determined using H(2)(15)O PET. This underestimation could be caused by an underestimation of the arterial transit time for white matter regions.

Noise reduction in 3D perfusion imaging by attenuating the static signal in arterial spin tagging (ASSIST).

Phase-encoded multishot SPIRAL approaches were used to acquire true 3D cerebral blood flow images of the human head using arterial spin tagging approaches. Multiple-inversion background suppression techniques, which suppress phase noise due to interacquisition fluctuations in the static magnetic field, reduced the temporal standard deviation of true 3D delta M images acquired using arterial spin tagging approaches by approximately 50%. Background suppressed arterial spin tagging (ASSIST) approaches were used to obtain high-resolution isotropic true 3D cerebral blood flow images, and to obtain true 3D activation images during cognitive (working memory) tasks. Magn Reson Med 44:92-100, 2000. Published 2000 Wiley-Liss, Inc.

Quantitation of regional cerebral blood flow increases during motor activation: A multislice, steady-state, arterial spin tagging study.

Steady-state arterial spin tagging approaches were used to construct multislice images of relative cerebral blood flow changes during finger-tapping tasks. Statistically significant increases in cerebral blood flow were observed in primary sensorimotor cortex in all seven subjects. The mean volume of the activated region in the contralateral primary sensorimotor cortex was 0.9 cm(3), and the mean increase in cerebral blood flow in the activated area was 54% +/- 11%. Although the extended spatial coverage is advantageous for activation studies, the intrinsic sensitivity of the multislice approach is smaller than the intrinsic sensitivity of the single-slice, arterial spin tagging approach. Magn Reson Med 42:404-407, 1999. Published 1999 Wiley-Liss, Inc.

Investigation of low frequency drift in fMRI signal.

Low frequency drift (0.0-0.015 Hz) has often been reported in time series fMRI data. This drift has often been attributed to physiological noise or subject motion, but no studies have been done to test this assumption. Time series T*2-weighted volumes were acquired on two clinical 1.5 T MRI systems using spiral and EPI readout gradients from cadavers, a normal volunteer, and nonhomogeneous and homogeneous phantoms. The data were tested for significant differences (P = 0.001) from Gaussian noise in the frequency range 0.0-0.015 Hz. The percentage of voxels that were significant in data from the cadaver, normal volunteer, nonhomogeneous and homogeneous phantoms were 13.7-49.0%, 22.1-61.9%, 46.4-68.0%, and 1.10%, respectively. Low frequency drift was more pronounced in regions with high spatial intensity gradients. Significant drifting was present in data acquired from cadavers and nonhomogeneous phantoms and all pulse sequences tested, implying that scanner instabilities and not motion or physiological noise may be the major cause of the drift.

Quantitation of regional cerebral blood flow increases in prefrontal cortex during a working memory task: a steady-state arterial spin-tagging study.

Steady-state arterial spin-tagging MRI approaches were used to quantitate regional cerebral blood flow increases in prefrontal cortex during a working memory ("two-back") task in six normal subjects. Statistically significant increases in cerebral blood flow in prefrontal cortex were observed in all six subjects: the average increase in cerebral blood flow in activated prefrontal cortex regions was 22 +/- 5 cc/100 g/min (23 +/- 7%). The results demonstrate that spin-tagging approaches can be used to follow focal activation in prefrontal cortex during cognitive tasks.

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

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

Increasing striatal iron content associated with normal aging.

Free-radical-mediated mechanisms may contribute to neuronal damage in Parkinson's disease (PD), other neurodegenerative conditions also associated with aging, and the aging process itself. Cytotoxic free radicals are generated in the brain by oxidation/reduction reactions that are catalyzed by transition metals such as iron. Any regional increase in brain iron concentration may increase the potential for local free-radical formation. The purpose of this study was to determine the relationship between age and basal ganglia iron content in 20 normal individuals ranging from 24 to 79 years of age. We used an in vivo magnetic resonance method to quantify the effects of paramagnetic centers sequestered inside cellular membranes, thereby enabling the determination of a quantitative index of local brain iron content. We observed a strong direct relationship between age and regional iron content in the putamen (r = 0.76, p < 0.0001) and caudate (r = 0.69, p < 0.001), but not in the globus pallidus (r = 0.32, p = 0.17) or thalamus (r = 0.13, p = 0.58). In conclusion, striatal iron content increases with advancing age. This increase may increase the probability of free-radical formation in the striatum, therefore representing a risk factor for the development of neurodegenerative disorders such as PD in which nigrostriatal neurons may be affected by increased oxidant stress.

Increased basal ganglia iron in striatonigral degeneration: in vivo estimation with magnetic resonance.

BACKGROUND: As many as 20% of individuals with the clinical diagnosis of Parkinson's disease (PD) do not have the characteristic neuropathologic features of PD at post mortem. The striatonigral degeneration (SND) subtype of multiple system atrophy is one of the categories of pathology which may be incorrectly diagnosed as PD on the basis of clinical presentation. SND may be associated with increased iron deposition in the putamen which can be detected with magnetic resonance imaging. METHODS: We have estimated regional brain iron content in a patient with probable SND, using a novel imaging method developed in our laboratory, and have compared the results in this patient to those which we have previously reported in patients with PD and in age-matched controls. RESULTS: We observed that putamenal iron content was increased in our SND patient, beyond the 95% confidence limit for inclusion in the PD group, even when considering clinical severity. In contrast, pallidal and thalamic iron were within the PD range. CONCLUSIONS: The demonstration of increased putamenal iron content may be a useful adjunctive investigative procedure in patients with suspected SND.

Quantitation of regional cerebral blood flow increases during motor activation: a steady-state arterial spin tagging study.

Steady-state arterial spin tagging MRI approaches were used to quantitate regional cerebral blood flow increases during finger tapping tasks in seven normal subjects. Statistically significant increases in cerebral blood flow were observed in the contralateral primary sensorimotor cortex in all seven subjects and in the supplementary motor area in five subjects. The intrinsic spatial resolution of the cerebral blood flow images was approximately 4 mm. If no spatial filtering was applied, the average increase in cerebral blood flow in the activated primary sensorimotor cortex was 60 +/- 10 cc/100 g/min (91 +/- 32%). If the images were filtered to a spatial resolution of 15 mm, the average increase in cerebral blood flow in the activated primary sensorimotor cortex was 23 +/- 7 cc/100 g/min (42 +/- 15%), in agreement with previously reported 133Xe and PET results.

Effect of magnetization transfer on the measurement of cerebral blood flow using steady-state arterial spin tagging approaches: a theoretical investigation.

A simple four-compartment model for magnetization transfer was used to obtain theoretical expressions for the relationship between regional cerebral blood flow and delta M, the change in longitudinal magnetization of brain water spins when arterial water spins are perturbed. The theoretical relationship can be written in two forms, depending on the approach used to normalize delta M. Using the first approach, the calculation of cerebral blood flow requires a knowledge of R1(omega 1, delta omega), the longitudinal relaxation rate observed in the presence of continuous off-resonance RF irradiation. Using the second approach, the calculation of cerebral blood flow requires a knowledge of R1(omega 1, delta omega), where R1(omega 1, delta omega) is given by the product of R1(omega 1, delta omega) and the fractional steady-state longitudinal water magnetization in the presence of off-resonance RF irradiation. If the off-resonance RF irradiation used for arterial tagging does not produce appreciable magnetization transfer effects, R1(omega 1, delta omega) can be approximated by the longitudinal relaxation rate measured in the absence of off-resonance RF irradiation, R1obs. Theoretical expressions obtained by using the four-component model for magnetization transfer are compared with equivalent expressions obtained by using two-compartment models.

Correction for vascular artifacts in cerebral blood flow values measured by using arterial spin tagging techniques.

"Vascular" artifacts can have substantial effects on human cerebral blood flow values calculated by using arterial spin tagging approaches. One vascular artifact arises from the contribution of "tagged" arterial water spins to the observed change in brain water MR signal. This artifact can be reduced if large bipolar gradients are used to "crush" the MR signal from moving arterial water spins. A second vascular artifact arises from relaxation of "tagged" arterial blood during transit from the tagging plane to the capillary exchange site in the imaging slice. This artifact can be corrected if the arterial transit times are measured by using "dynamic" spin tagging approaches. The mean transit time from the tagging plane to capillary exchange sites in a gray matter region of interest was calculated to be approximately 0.94 s. Cerebral blood flow values calculated for seven normal volunteers agree reasonably well with values calculated by using radioactive tracer approaches.

Perfusion imaging of the human brain at 1.5 T using a single-shot EPI spin tagging approach.

Single-shot echo planar imaging (EPI) techniques have been applied, in conjunction with arterial spin tagging approaches, to obtain images of cerebral blood flow in a single axial slice in the human brain. Serial studies demonstrate that cerebral blood flow images acquired in 8 min are reproducible, with a statistical precision of approximately +/-10 cc/100 g/min. The average value of cerebral blood flow in the slice is 51 +/- 11 cc/100 g/min for six normal subjects. The cerebral blood flow images contain two types of artifact, probably due to arterial and venous blood volume contributions, which must be overcome before the arterial spin tagging approach can be used for routine clinical studies.

Estimation of brain iron in vivo by means of the interecho time dependence of image contrast.

An imaging protocol for a quantitative estimation of disease-induced variations in brain iron is proposed and then validated, first, on a phantom and second, on a group of 11 healthy volunteers. The relative estimate of brain iron is achieved from a rate difference image that measures the enhancement, delta R2app, of the transverse relaxation rate of water protons brought about by the heterogeneous accumulation of iron in the glial cells. At 1.5 T, the phantom study demonstrates, over the range 0-6 A/m, a linear dependence of delta R2app on the magnetization difference between microspheres and a paramagnetic gel, with a sensitivity of approximately 2 s-1 A-1 m. In the group of healthy volunteers (mean age 33 +/- 7 years) devoid of disease-related or appreciable age-related accumulations of iron, the precision of delta R2app was still sufficient to distinguish the globus pallidus and the putamen from all of the other iron-containing brain structures in a manner that was significant at the 99% confidence level.

Basal ganglia iron content in Parkinson's disease measured with magnetic resonance.

The possibility of using magnetic resonance (MR) to evaluate the severity of the pathological changes of Parkinson's disease (PD) is suggested by the known accumulation of iron in the basal ganglia in PD and the reduced signal evident from this area with conventional T2-weighted MR imaging. To improve the specificity of MR for the measurement of tissue iron content, we have developed a method that quantifies the effects of paramagnetic centers sequestered inside cellular membranes, based on the echo time dependence of the decay of transverse magnetization caused by the local field inhomogeneities which are due to intracellular iron. This method enables an index of local tissue iron content to be calculated for structures of the basal ganglia. We report here the application of this method to a series of patients with PD (n = 12) and of normal, age-matched controls (n = 13). Our objective was to determine whether this measurement of basal ganglia iron concentration correlates with the presence and severity of PD. We observed a significant increase in iron content in both the putamen and pallidum in PD as well as a correlation with the severity of clinical symptomatology. More severely affected patients had a higher iron content in both of these structures. Our results suggest that this MR measurement may provide a noninvasive method of measuring the severity of the pathological changes underlying PD.

Estimation of the iron concentration in excised gray matter by means of proton relaxation measurements.

To validate their correlation with tissue iron concentration, proton transverse relaxation measurements have been made at 2.35 T (100 MHz) in 25 samples of excised, frozen, but unfixed human gray matter tissue obtained from the globus pallidus, putamen, caudate, thalamus, and cortex of five postmortem brains free of neurological disease. The iron concentration was independently measured, using atomic absorption spectroscopy. The proton transverse relaxation measurements exploited the interecho time dependence of the apparent transverse relaxation rate, R2app, obtained from a Carr-Purcell-Meiboom-Gill (CPMG) sequence. An empirical semilogarithmic relationship between R2app and the interecho time provided a measure of the relaxation enhancement due to iron, namely, a slope p, which demonstrated a significant correlation (r = 0.78, P < 0.001) with tissue iron concentration. Moreover, a simple rate difference, delta R2app, determined between interecho time values of 6 and 60 ms, was also found to correlate significantly with iron concentration (r = 0.81, P < 0.001). Both of the foregoing correlations were better than that of R2app itself. When the tissue samples were subdivided into brain structure groups, the intergroup differences in rho reflected their known differences in iron accumulation and correlated with those of the mean group iron content, determined by atomic absorption spectrometry.

Relaxation enhancement of the transverse magnetization of water protons in paramagnetic suspensions of red blood cells.

The enhancement of the water proton transverse relaxation, delta R2, brought about by a difference between intra and extracellular paramagnetic susceptibilities in a suspension of red blood cells (RBC) has been evaluated both experimentally and theoretically in terms of (i) the refocusing interval, delta 180, of a CPMG pulse sequence, (ii) the difference in paramagnetic susceptibility, and (iii) the shape of the cell surface. At a hematocrit of 45, the increase in the relaxation enhancement, delta R2, with increasing delta 180, was a factor of two greater for the naturally biconcave RBC, than for the quasi-spherical RBC in hypotonic suspensions. This difference could be modeled in terms of a transmembrane correlation time, tau = 5.5 ms, across an RBC surface characterized by a demagnetizing factor which differs by 0.13 from that of a sphere. The increase in delta R2 with increasing magnetization difference between the RBC and its surroundings was found to be marginally less than quadratic, both experimentally and from the model.