A common network of functional areas for attention and eye movements.

Functional magnetic resonance imaging (fMRI) and surface-based representations of brain activity were used to compare the functional anatomy of two tasks, one involving covert shifts of attention to peripheral visual stimuli, the other involving both attentional and saccadic shifts to the same stimuli. Overlapping regional networks in parietal, frontal, and temporal lobes were active in both tasks. This anatomical overlap is consistent with the hypothesis that attentional and oculomotor processes are tightly integrated at the neural level.

Hemispheric specialization in human dorsal frontal cortex and medial temporal lobe for verbal and nonverbal memory encoding.

The involvement of dorsal frontal and medial temporal regions during the encoding of words, namable line-drawn objects, and unfamiliar faces was examined using functional magnetic resonance imaging (fMRI). Robust dorsal frontal activations were observed in each instance, but lateralization was strongly dependent on the materials being encoded. Encoding of words produced left-lateralized dorsal frontal activation, whereas encoding of unfamiliar faces produced homologous right-lateralized activation. Encoding of namable objects, which are amenable to both verbal and nonverbal encoding, yielded bilateral dorsal frontal activation. A similar pattern of results was observed in the medial temporal lobe. These results indicate that regions in both hemispheres underlie human long-term memory encoding, and these regions can be engaged differentially according to the nature of the material being encoded.

Areas involved in encoding and applying directional expectations to moving objects.

Two experiments used functional magnetic resonance imaging (fMRI) to examine the cortical areas involved in establishing an expectation about the direction of motion of an upcoming object and applying that expectation to the analysis of the object. In Experiment 1, subjects saw a stationary cue that either indicated the direction of motion of a subsequent test stimulus (directional cue) or provided no directional information (neutral cue). Their task was to detect the presence of coherent motion in the test stimulus. The stationary directional cue produced larger modulations than the neutral cue, with respect to a passive viewing baseline, both in motion-sensitive areas such as left MT+ and the anterior intraparietal sulcus, as well as motion-insensitive areas such as the posterior intraparietal sulcus and the junction of the left medial precentral sulcus and superior frontal sulcus. Experiment 2 used an event-related fMRI technique to separate signals during the cue period, in which the expectation was encoded and maintained, from signals during the subsequent test period, in which the expectation was applied to the test object. Cue period activations from a stationary, directional cue included many of the same motion-sensitive and -insensitive areas from Experiment 1 that produced directionally specific modulations. Prefrontal activations were not observed during the cue period, even though the stationary cue information had to be translated into a format appropriate for influencing motion detection, and this format was maintained for the duration of the cue period (approximately 5 sec).

AUR Memorial Award. Two computer models for selection of optimal magnetic resonance imaging (MRI) pulse sequence timing.

Two computer modeling techniques have been developed that aid in the selection of optimal magnetic resonance imaging (MRI) pulse sequences and timing intervals for specific clinical situations. The "parameter sensitivity" technique provides a means of selecting three separate MRI scans which are individually sensitive to changes in each of the three NMR tissue parameters N, T1, and T2. The "contrast" technique allows selection of a single optimal MRI sequence using the expected changes in all three tissue parameters simultaneously. Excellent correlation is demonstrated between the models and images obtained in a normal volunteer and in a patient with multiple sclerosis. The two methods compliment each other; the parameter sensitivity method is most useful in situations where subtle changes in tissue parameters are expected, whereas the contrast method is suited to circumstances where large differences in tissue parameters are anticipated and the magnitude and direction of these changes are known.

Enhancement of red blood cell proton relaxation with chromium labeling.

Nuclear medicine has utilized chromium (Cr) for decades to label red blood cells (RBCs). The purpose of this project was to determine whether sufficient paramagnetic Cr could be bound to red cells to influence proton relaxation significantly. We demonstrated that the T1 and T2 of RBCs can be substantially shortened by labeling them with paramagnetic Cr. Proton relaxation enhancement occurs when red cells are incubated with sodium chromate (VI) over a concentration range of 0.10 mM to 31.6 mM. Labeling with Cr at a concentration of 31.6 mM shortened the T1 of packed cells from 714 msec to 33 msec, and the T2 from 117 msec to 24 msec, as compared with nonlabeled red cells. In vitro hemolysis was significantly increased after labeling at 31.6 mM, but not at lower concentrations. Cr-induced proton relaxation enhancement varied with RBCs from different species, temperature, pH, and length of incubation. T1 values of kidneys containing labeled red cells (303 msec), or labeled cells diluted 10-fold with nonlabeled cells (479 msec), were decreased compared with kidneys containing only nonlabeled cells (600 msec). Finally, preliminary data indicate that the signal intensity of perfused renal tissue is significantly influenced in vivo by infusion of Cr-labeled RBCs. This study demonstrated that Cr labeling of RBCs sufficiently enhances red cell proton relaxation to provide excised organs containing red cells, of which 10% have been Cr-labeled, with shorter T1 and T2 values than organs containing nonlabeled cells. In addition, the ability of labeled cells to alter signal intensity in vivo suggests that Cr may have the potential to become an MRI contrast agent.

AUR memorial award--1988. MRI enhancement of perfused tissues using chromium labeled red blood cells as an intravascular contrast agent.

It has been demonstrated that chromium (Cr) labeling significantly decreases the relaxation times of packed red blood cells (RBCs). In this study, the spin-lattice relaxation time (T1) of human red cells was shortened from 836 ms to 29 ms and the spin-spin relaxation time (T2) shortened from 134 ms to 18 ms, when the cells were labeled at a Cr incubation concentration of 50 mM. Labeling of canine cells at 50 mM resulted in a T1 of 36 ms and a T2 of 26 ms. A labeling concentration of 10 mM produced similar relaxation enhancement, with uptake of 47% of the available Cr, and was determined to be optimal. The enhancement of longitudinal and transverse relaxation rates (1/T1,-1/T2) per amount of hemoglobin-bound Cr are 6.9 s-1 mM-1 and 9.8 s-1 mM-1 respectively, different from those of a pure Cr+3 solution. Labeling cells at 10 mM decreased the survival half-time in vivo from 16.6 days to 4.7 days in dogs. No difference in red cell survival was found with the use of hetero-transfusion versus auto-transfusion of labeled RBCs. Significant shortening of the T1 (912 ms to 266 ms, P = .03) and T2 (90 ms to 70 ms, P = .006) of spleen and the T1 (764 ms to 282 ms, P = .005) and the T2 (128 ms to 86 ms, P = .005) of liver occurred when 10% of the RBC mass of dogs was exchanged with Cr labeled cells. Liver and spleen spin density changes (P greater than 0.23) and muscle spin density and relaxation changes (P greater than 0.4) were insignificant. The in vivo T1 of a canine spleen which had been infarcted did not change following transfusion with labeled cells, where the T1 of liver did shorten. We believe this preliminary study suggests that Cr labeled red cells may have the potential to become an intravascular magnetic resonance imaging contrast agent.

In vitro evaluation of MR hypointensity in Aspergillus colonies.

PURPOSE: To demonstrate that paramagnetic elements in fungal colonies can cause hypointensity in MR images. METHODS: Aspergillus fumigatus grown in vitro was imaged with CT and MR at the time of initial inoculation and 5 days later. CT and MR images, T2 values, scanning electron microscopy, energy-dispersive analysis, and furnace atomic absorption spectrometry were performed. RESULTS: After 5 days of growth, MR images of A fumigatus revealed curvilinear hypointensities on T2-weighted images corresponding to the fungal growth. Gradient-echo images revealed two distinct components of hypointensity with different calculated T2 values. Phase-angle-difference images revealed a phase shift characteristic of magnetic-susceptibility paramagnetic effects, which corresponded to the hypointense regions on gradient-echo images. Energy-dispersive analysis and furnace atomic absorption spectrometry confirmed the presence of paramagnetic elements. CONCLUSION: It was shown that in vitro A fumigatus concentrates metal elements contained within the nutrient broth. These focal collections of calculated T2 values are caused at least partly by magnetic susceptibility effects.

Improved determination of spin density, T1 and T2 from a three-parameter fit to multiple-delay-multiple-echo (MDME) NMR images.

A method is presented for simultaneously determining values of relative hydrogen spin density Nr, T1 and T2 from a single set of NMR image intensities acquired in a short imaging time. Present methods use separate acquisitions and data sets to determine all three parameters. In the method presented, multiple-echo data are collected at multiple delays in virtually the same imaging time used to obtain T1 and a T2-weighted Nr from a separate saturation recovery (SR) T1 measurement. All three parameters are then determined by a three-parameter fit of a derived signal intensity equation to these multiple-delay-multiple-echo (MDME) data. This provides an inherent correction of Nr for T1 and T2 weighting without the use of sequences with TD greater than 5T1, and without further data collection for a separate T2 measurement. It also provides an effective reduction in the noise of the separate T2 measurement. A three-parameter fit to MDME data appears to be superior to the separate T1 and T2 measurements currently used to determine all three parameters. Calculations performed on CrCl3 solutions produced T1 values from 21 ms to 3.4 s, T2 values from 6 to 714 ms, and standard errors as low as 0.33%, with a net imaging time of the order of that required for routine low-noise signal intensity imaging. The method could potentially be used in NMR spectroscopy to give similar benefits.

Analysis of encoding efficiency in MR imaging of velocity magnitude and direction.

The efficiency of balanced versus unbalanced techniques for phase-angle-based velocity magnitude and direction imaging is investigated. Methods having balanced flow-encoding gradients (gradients in positive and negative directions with a zero center of gravity) are compared with unbalanced methods. For three-dimensional imaging, a currently used balanced method is the six-point technique having opposed gradients pairs for each orthogonal direction. A currently used unbalanced method is a four-point null technique which has three orthogonal gradients and an additional acquisition having no specific flow encoding to correct the baseline (null) phase. In the gradient-limited case of slow flow and perfusion, the balanced method is predicted to have higher velocity magnitude-to-noise ratio per time (SNRV) by a factor of 1.63, with similar results for velocity direction. In the wraparound-limited case of faster flows and motions, similar results are found when a null acquisition is added to the balanced method. This results in a seven-point balanced method having an SNRV 1.51 times that of the four-point unbalanced method. If null phases are within the [-pi/2,pi/2] interval, this additional null acquisition is unnecessary. Other four-point methods are also considered. These results indicate that, in general, balanced methods have advantages over unbalanced methods for velocity imaging.

Arterial input functions from MR phase imaging.

A method is presented for obtaining high-sensitivity arterial input functions following bolus intravenous contrast agent administration. Arterial contrast agent is monitored by phase reconstruction of single-shot echo-planar images. During bolus injections of a gadolinium (Gd) agent in a baboon, data were acquired at the mid-abdominal aorta, and magnitude and phase-shift images were reconstructed. Pairwise image subtraction was used to minimize phase aliasing. The phase-based method is shown to have a significant potential improvement in sensitivity compared to the magnitude approach. The phase method also has a general linear response to concentration. This method may have potential utility in quantitative imaging of blood flow and contrast agent kinetics.

Signal-to-noise in phase angle reconstruction: dynamic range extension using phase reference offsets.

The dynamic range of phase-reconstructed magnetic resonance images is compared to that of magnitude-reconstructed images. From analysis of propagation of errors, the phase angle noise is phase-independent and given in radians by sigma ([I])/[I], the noise-to-signal ratio of the corresponding magnitude-reconstructed image. As the phase can range from minus pi to pi, the phase angle dynamic range is 2 pi times that of the signal magnitude. These results agree with experiment, verifying that the noise in the two receiver channels is uncorrelated. An artifact-free technique is presented for correcting phase spillover, which further extends the phase angle dynamic range. The reconstruction-based reference phase is adjusted on a local basis so that the boundary of phase wraparound is reconstructed near the center of the [- pi, pi] interval. For a particular flow study, the phase signal-to-noise was extended over twofold by spillover correction, to a value 15 times that of the magnitude signal-to-noise.

Rapid local rectangular views and magnifications: reduced phase encoding of orthogonally excited spin echoes.

A method is described for rapid, artifact-free imaging and magnification of small regions within a larger sample. This combines a rectangular window, reconstructed from a reduced number of phase-encoding steps, and confinement of spin echoes to a similar rectangular strip by orthogonal pi/2 and pi excitations. Phase encoding is along the width of the strip (along Y). Off-center strips are excited by offsetting the Y slice-selecting gradient, and the reconstruction window is kept coincident with excitation by similarly offsetting the Y phase-encoding gradient. The excited strip is centered in the reconstruction window by setting the radiofrequency transmitter on resonance. The method is shown to be useful for long narrow structures such as the spine where the acquisition time is reduced by over a factor of 5 determined by the image aspect ratio.

Addendum to "rapid local rectangular views and magnifications: reduced phase encoding of orthogonally excited spin echoes".

Attention is called to a previous work of Feinberg et al. on inner volume MRI, a work which was not known to the present authors when preparing a recent similar manuscript on imaging local fields of view. The rationale is discussed for tandemly offsetting the reconstruction window and excited volume.

Contrast-agent phase effects: an experimental system for analysis of susceptibility, concentration, and bolus input function kinetics.

A system is presented for experimental arterial input function (AIF) simulation and for accurate measurement of the concentration, susceptibility effects, and magnetic moment of paramagnetic MR contrast agents. Signal effects of contrast agents are evaluated with a stable, well-characterized, and precise experimental setup. A cylindrical phantom and a closed-loop circulating flow system were designed for AIF simulation, assessment of the physical determinants of contrast-agent phase effects, and measurement of contrast-agent properties under controlled conditions. A mathematical model of the AIF dynamics is proposed. From the experimental phase shift (delta phi), either the concentration or molar susceptibility, chiM, is determined. The linear dependence of delta phi on concentration and echo time (TE), the orientation dependence, and the lack of dependence on T1, T2, and diffusion time are proven precisely for water solutions under a wide variety of conditions. The measured effective magnetic moment of Gd+3, mu(eff), was 7.924 +/- 0.015 Bohr magnetons in agreement with the theoretical value of 7.937.

Cooperative T1 and T2 effects on contrast using a new driven inversion spin-echo (DISE) MRI pulse sequence.

A pulse sequence is presented for obtaining a single image with combined T1/T2 weighting. T2 relaxation is made to increase intensity, in cooperation with the effect of T1 relaxation, by providing T2 weighting with a 90 degrees-180 degrees-90 degrees driven inversion pulse triplet in an inversion recovery method. Unlike the inversion spin-echo method having a short inversion time (TI), signals in the new driven inversion spin-echo (DISE) method need not be negative and the most T1-sensitive region of the recovery curve can be used. Selecting sensitivity to one relaxation time does not degrade the sensitivity to the other relaxation time. T1 sensitivity is thus extended to longer echo times (TE intervals). T2 sensitivity is extended to longer TI intervals, and the combined T1/T2-weighted technique with intermediate TE and TI has highly cooperative and near-maximal T1 and T2 effects on contrast. Intensity is not multiplicatively degraded by T1 and T2 weighting so that the signal-to-noise of the combined T1/T2-weighted method is high. High intensity and T1 and T2 cooperatively occur for a much wider range of relaxation times, and especially for images heavily weighted to the pathologic intermediate and long T1 and T2 regime.

Simplified mathematical description of longitudinal recovery in multiple-echo sequences.

The intensity of multiple echoes separated by a time 2 tau has been modeled using the closed form of a finite geometric series. This eliminates long exponential series, introduces the number of echoes as an independent parameter, and corrects for the net T1 relaxation during the echo train. Other sequences having echo trains can be modeled similarly.

Dynamics and interactions of the anion channel in intact human erythrocytes: an electron paramagnetic resonance spectroscopic study employing a new membrane-impermeant bifunctional spin-label.

We have developed a new membrane-impermeant, bifunctional spin-labeling reagent, bis-(sulfo-N-succinimidyl) doxyl-2-spiro-4'-pimelate (BSSDP), and employed it in an electron paramagnetic resonance (EPR) study of the rotational diffusion of the anion-exchange channel (band 3) in intact human erythrocytes. BSSDP reacts in a covalent manner and with high specificity with the extracytoplasmic domain of band 3, forming a complex in which the spin-label is immobilized on the protein. The linear EPR spectrum of BSSDP-labeled intact erythrocytes is characteristic of a highly immobilized, spatially isolated nitroxide probe. The saturation-transfer EPR spectrum of the same sample indicates that the anion channel in intact erythrocytes exhibits rotational dynamics in the 0.1-1 ms correlation time range at 20 degrees C. Rotational dynamics in this motional domain are consistent with a strong interaction of the anion-exchange channel with the erythrocyte cytoskeleton. The saturation-transfer EPR spectrum of ghosts prepared from BSSDP-labeled erythrocytes indicates a significant increase in rotational mobility of the anion channel, suggesting a significant disruption on lysis of interactions between the anion channel and the cytoskeleton.

Diffusion MRI: precision, accuracy and flow effects.

After a decade of evolution and application of diffusion imaging, a large body of literature has been accumulated. It is in this context that the accuracy and precision of diffusion-weighted and quantitative diffusion MRI are reviewed. The emphasis of the review is on practical methods for clinical human imaging, particularly in the brain. The requirements for accuracy and precision are reviewed for various clinical and basic science applications. The methods of measuring and calculating diffusion effects with MRI are reviewed. The pulse gradient spin echo (PGSE) methods are emphasized as these methods are used most commonly in the clinical setting. Processing of PGSE data is reviewed. Various PGSE encoding schemes are also reviewed in terms of the accuracy and precision of isotropic and anisotropic diffusion measurements. The broad range of factors impacting the accuracy of the PGSE methods and other encoding schemes is then considered. Firstly, system inaccuracies such as background imaging gradients, gradient linearity, refocusing RF pulses, eddy currents, image misregistration, noise and dynamic range are considered. A second class of inaccuracies is contributed by the bulk effects of the imaged object, and include sample background gradients, subject motion of cerebrospinal fluid and organs, and aperiodic organ motion. A final category of potential inaccuracies is classified as being contributed by microscopic, biophysical tissue properties and include partial volume effects, anisotropy, restriction, diffusion distance, compartmentation, exchange, multiexponential diffusion decay, T2 weighting and microvascular perfusion. Finally, the application of diffusion methods to studies of blood flow in the microvasculature (i.e. the arterioles, capillaries and venules) are reviewed in detail, particularly in terms of feasibility and the stringent accuracy and precision requirements. Recent provocative studies examining the use of PGSE approaches to suppress microvascular signals in brain functional MRI (fMRI) are also reviewed.

Encoding of anisotropic diffusion with tetrahedral gradients: a general mathematical diffusion formalism and experimental results.

A diffusion imaging method with a tetrahedral sampling pattern has been developed for high-sensitivity diffusion analysis. The tetrahedral gradient pattern consists of four different combinations of x, y, and z gradients applied simultaneously at full strength to uniformly measure diffusion in four different directions. Signal-to-noise can be increased by up to a factor of about three using this approach, compared with diffusion measurements made using separately applied x, y, and z gradients. A mathematical formalism is presented describing six fundamental parameters: the directionally averaged diffusion coefficient D and diffusion element anisotropies eta and epsilon which are rotationally invariant, and diffusion ellipsoid orientation angles theta, phi, and omega which are rotationally variant. These six parameters contain all the information in the symmetric diffusion tensor D. Principal diffusion coefficients, reduced anisotropies, and other rotational invariants are further defined. It is shown that measurement of off-diagonal tensor elements is essential to assess anisotropy and orientation, and that the only parameter which can be measured with the orthogonal method is D. In cases of axial diffusion symmetry (e.g., fibers), the four tetrahedral diffusion measurements efficiently enable determination of D, eta, theta, and phi which contain all the diffusion information. From these four parameters, the diffusion parallel and perpendicular to the symmetry axis (D and D) and the axial anisotropy A can be determined. In more general cases, the six fundamental parameters can be determined with two additional diffusion measurements. Tetrahedral diffusion sequences were implemented on a clinical MR system. A muscle phantom demonstrates orientation independence of D, D, D, and A for large changes in orientation angles. Sample background gradients and diffusion gradient imbalances were directly measured and found to be insignificant in most cases.