Bespoke magnetic field design for a magnetically shielded cold atom interferometer.

Quantum sensors based on cold atoms are being developed which produce measurements of unprecedented accuracy. Due to shifts in atomic energy levels, quantum sensors often have stringent requirements on their internal magnetic field environment. Typically, background magnetic fields are attenuated using high permeability magnetic shielding, with the cancelling of residual and introduction of quantisation fields implemented with coils inside the shield. The high permeability shield, however, distorts all magnetic fields, including those generated inside the sensor. Here, we demonstrate a solution by designing multiple coils overlaid on a 3D-printed former to generate three uniform and three constant linear gradient magnetic fields inside the capped cylindrical magnetic shield of a cold atom interferometer. The fields are characterised in-situ and match their desired forms to high accuracy. For example, the uniform transverse field, Bx, deviates by less than 0.2% over more than 40% of the length of the shield. We also map the field directly using the cold atoms and investigate the potential of the coil system to reduce bias from the quadratic Zeeman effect. This coil design technology enables targeted field compensation over large spatial volumes and has the potential to reduce systematic shifts and noise in numerous cold atom systems.

Microstructural imaging of the human brain with a 'super-scanner': 10 key advantages of ultra-strong gradients for diffusion MRI.

The key component of a microstructural diffusion MRI 'super-scanner' is a dedicated high-strength gradient system that enables stronger diffusion weightings per unit time compared to conventional gradient designs. This can, in turn, drastically shorten the time needed for diffusion encoding, increase the signal-to-noise ratio, and facilitate measurements at shorter diffusion times. This review, written from the perspective of the UK National Facility for In Vivo MR Imaging of Human Tissue Microstructure, an initiative to establish a shared 300 mT/m-gradient facility amongst the microstructural imaging community, describes ten advantages of ultra-strong gradients for microstructural imaging. Specifically, we will discuss how the increase of the accessible measurement space compared to a lower-gradient systems (in terms of Δ, b-value, and TE) can accelerate developments in the areas of 1) axon diameter distribution mapping; 2) microstructural parameter estimation; 3) mapping micro-vs macroscopic anisotropy features with gradient waveforms beyond a single pair of pulsed-gradients; 4) multi-contrast experiments, e.g. diffusion-relaxometry; 5) tractography and high-resolution imaging in vivo and 6) post mortem; 7) diffusion-weighted spectroscopy of metabolites other than water; 8) tumour characterisation; 9) functional diffusion MRI; and 10) quality enhancement of images acquired on lower-gradient systems. We finally discuss practical barriers in the use of ultra-strong gradients, and provide an outlook on the next generation of 'super-scanners'.

Global signal modulation of single-trial fMRI response variability: Effect on positive vs negative BOLD response relationship.

In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses.

Investigating intrinsic connectivity networks using simultaneous BOLD and CBF measurements.

When the sensory cortex is stimulated and directly receiving afferent input, modulations can also be observed in the activity of other brain regions comprising spatially distributed, yet intrinsically connected networks, suggesting that these networks support brain function during task performance. Such networks can exhibit subtle or unpredictable task responses which can pass undetected by conventional general linear modelling (GLM). Additionally, the metabolic demand of these networks in response to stimulation remains incompletely understood. Here, we recorded concurrent BOLD and CBF measurements during median nerve stimulation (MNS) and compared GLM analysis with independent component analysis (ICA) for identifying the spatial, temporal and metabolic properties of responses in the primary sensorimotor cortex (S1/M1), and in the default mode (DMN) and fronto-parietal (FPN) networks. Excellent spatial and temporal agreement was observed between the positive BOLD and CBF responses to MNS detected by GLM and ICA in contralateral S1/M1. Values of the change in cerebral metabolic rate of oxygen consumption (Δ%CMRO2) and the Δ%CMRO2/Δ%CBF coupling ratio were highly comparable when using either GLM analysis or ICA to extract the contralateral S1/M1 responses, validating the use of ICA for estimating changes in CMRO2. ICA identified DMN and FPN network activity that was not detected by GLM analysis. Using ICA, spatially coincident increases/decreases in both BOLD and CBF signals to MNS were found in the FPN/DMN respectively. Calculation of CMRO2 changes in these networks during MNS showed that the Δ%CMRO2/Δ%CBF ratio is comparable between the FPN and S1/M1 but is larger in the DMN than in the FPN, assuming an equal value of the parameter M in the DMN, FPN and S1/M1. This work suggests that metabolism-flow coupling may differ between these two fundamental brain networks, which could originate from differences between task-positive and task-negative fMRI responses, but might also be due to intrinsic differences between the two networks.

Evidence that the negative BOLD response is neuronal in origin: a simultaneous EEG-BOLD-CBF study in humans.

Unambiguous interpretation of changes in the BOLD signal is challenging because of the complex neurovascular coupling that translates changes in neuronal activity into the subsequent haemodynamic response. In particular, the neurophysiological origin of the negative BOLD response (NBR) remains incompletely understood. Here, we simultaneously recorded BOLD, EEG and cerebral blood flow (CBF) responses to 10 s blocks of unilateral median nerve stimulation (MNS) in order to interrogate the NBR. Both negative BOLD and negative CBF responses to MNS were observed in the same region of the ipsilateral primary sensorimotor cortex (S1/M1) and calculations showed that MNS induced a decrease in the cerebral metabolic rate of oxygen consumption (CMRO2) in this NBR region. The ∆CMRO2/∆CBF coupling ratio (n) was found to be significantly larger in this ipsilateral S1/M1 region (n=0.91±0.04, M=10.45%) than in the contralateral S1/M1 (n=0.65±0.03, M=10.45%) region that exhibited a positive BOLD response (PBR) and positive CBF response, and a consequent increase in CMRO2 during MNS. The fMRI response amplitude in ipsilateral S1/M1 was negatively correlated with both the power of the 8-13 Hz EEG mu oscillation and somatosensory evoked potential amplitude. Blocks in which the largest magnitude of negative BOLD and CBF responses occurred therefore showed greatest mu power, an electrophysiological index of cortical inhibition, and largest somatosensory evoked potentials. Taken together, our results suggest that a neuronal mechanism underlies the NBR, but that the NBR may originate from a different neurovascular coupling mechanism to the PBR, suggesting that caution should be taken in assuming the NBR simply represents the neurophysiological inverse of the PBR.

Spatial location and strength of BOLD activation in high-spatial-resolution fMRI of the motor cortex: a comparison of spin echo and gradient echo fMRI at 7 T.

The increased blood oxygenation level-dependent contrast-to-noise ratio at ultrahigh field (7 T) has been exploited in a comparison of the spatial location and strength of activation in high-resolution (1.5 mm isotropic) gradient echo (GE) and spin echo (SE), echo planar imaging data acquired during the execution of a simple motor task in five subjects. SE data were acquired at six echo times from 30 to 55 ms. Excellent fat suppression was achieved in the SE echo planar images using slice-selective gradient reversal. Threshold-free cluster enhancement was used to define regions of interest (ROIs) containing voxels showing significant stimulus-locked signal changes from the GE and average SE data. These were used to compare the signal changes and spatial locations of activated regions in SE and GE data. T(2) and T(2)* values were measured, with means of 48.3 ± 1.1 ms and 36.5 ± 3.4 ms in the SE ROI. In addition, we identified a dark band in SE images of the motor cortex corresponding to a region in which T(2) and T(2)* were significantly lower than in the surrounding grey matter. The fractional SE signal change in the ROI was found to vary linearly as a function of TE, with a slope that was dependent on the particular ROI assessed: the mean ΔR(2) value was found to be 0.85 ± 0.11 s(-1) for the SE ROI and -0.37 ± 0.05 s(-1) for the GE ROI. The fractional signal change relative to the shortest TE revealed that the largest signal change occurred at a TE of 45 ms outside of the dark band. At this TE, the ratio of the fractional signal change in GE and SE data was found to be 0.48 ± 0.05. Phase maps produced from high-resolution GE images spanning the right motor cortex were used to identify veins. The GE ROI was found to contain 18% more voxels overlying the venous mask than the SE ROI.

Mapping human somatosensory cortex in individual subjects with 7T functional MRI.

Functional magnetic resonance imaging (fMRI) is now routinely used to map the topographic organization of human visual cortex. Mapping the detailed topography of somatosensory cortex, however, has proven to be more difficult. Here we used the increased blood-oxygen-level-dependent contrast-to-noise ratio at ultra-high field (7 Tesla) to measure the topographic representation of the digits in human somatosensory cortex at 1 mm isotropic resolution in individual subjects. A "traveling wave" paradigm was used to locate regions of cortex responding to periodic tactile stimulation of each distal phalangeal digit. Tactile stimulation was applied sequentially to each digit of the left hand from thumb to little finger (and in the reverse order). In all subjects, we found an orderly map of the digits on the posterior bank of the central sulcus (postcentral gyrus). Additionally, we measured event-related responses to brief stimuli for comparison with the topographic mapping data and related the fMRI responses to anatomical images obtained with an inversion-recovery sequence. Our results have important implications for the study of human somatosensory cortex and underscore the practical utility of ultra-high field functional imaging with 1 mm isotropic resolution for neuroscience experiments. First, topographic mapping of somatosensory cortex can be achieved in 20 min, allowing time for further experiments in the same session. Second, the maps are of sufficiently high resolution to resolve the representations of all five digits and third, the measurements are robust and can be made in an individual subject. These combined advantages will allow somatotopic fMRI to be used to measure the representation of digits in patients undergoing rehabilitation or plastic changes after peripheral nerve damage as well as tracking changes in normal subjects undergoing perceptual learning.

Investigating the effect of blood susceptibility on phase contrast in the human brain.

Recent work has shown a dramatic contrast between GM and WM in gradient echo phase images at high field (7 T). Although this contrast is key to the exploitation of phase in imaging normal and pathological tissue, its origin remains contentious. Several sources for this contrast have been considered including iron content, myelin, deoxy-hemoglobin, or water-macromolecule interactions. Here we quantify the contribution of intravascular dHb to the GM/WM contrast in the human brain at 7 T by modulating the susceptibility of the blood using a paramagnetic contrast agent. By carrying out high resolution, dynamic, gradient echo imaging before, during and after the injection of the contrast agent, we were able to follow the change in GM/WM phase contrast and to monitor simultaneously the susceptibility of the blood. Using these data in conjunction with the known susceptibility of venous blood we estimate the upper bound for the relative contribution of dHb in the vasculature to the measured GM/WM phase contrast to be 0.48 Hz for GM close to the pial surface, and 0.27 Hz for deeper GM. These values are up to 20% of the GM/WM phase difference observed in the human brain at 7 T. Furthermore, we found that the fractional blood volume differences required to account for the observed GM/WM phase contrast are 1.3% and 0.7% for GM close to the pial surface and for deeper GM, respectively.

Water proton T1 measurements in brain tissue at 7, 3, and 1.5 T using IR-EPI, IR-TSE, and MPRAGE: results and optimization.

METHOD: This paper presents methods of measuring the longitudinal relaxation time using inversion recovery turbo spin echo (IR-TSE) and magnetization-prepared rapid gradient echo (MPRAGE) sequences, comparing and optimizing these sequences, reporting T1 values for water protons measured from brain tissue at 1.5, 3, and 7 T. T1 was measured in cortical grey matter and white matter using the IR-TSE, MPRAGE, and inversion recovery echo planar imaging (IR-EPI) pulse sequences. RESULTS: In four subjects the T1 of white and grey matter were found to be 646+/-32 and 1,197+/-134 ms at 1.5 T, 838+/-50 and 1,607+/-112 ms at 3T, and 1,126+/-97, and 1,939+/-149 ms at 7 T with the MPRAGE sequence. The T1 of the putamen was found to be 1,084+/-63 ms at 1.5 T, 1,332+/-68 ms at 3T, and 1,644+/-167 ms at 7 T. The T1 of the caudate head was found to be 1,109+/- 66 ms at 1.5 T, 1,395+/-49 ms at 3T, and 1,684+/-76 ms at 7 T. DISCUSSION: There was a trend for the IR-TSE sequence to underestimate T1 in vivo. The sequence parameters for the IR-TSE and MPRAGE sequences were also optimized in terms of the signal-to-noise ratio (SNR) in the fitted T1. The optimal sequence for IR-TSE in terms of SNR in the fitted T1 was found to have five readouts at TIs of 120, 260, 563, 1,221, 2,647, 5,736 ms and TR of 7 s. The optimal pulse sequence for MPRAGE with readout flip angle = 8 degrees was found to have five readouts at TIs of 160, 398, 988, 2,455, and 6,102 ms and a TR of 9 s. Further optimization including the readout flip angle suggests that the flip angle should be increased, beyond levels that are acceptable in terms of power deposition and point-spread function.

Measurement of electric fields induced in a human subject due to natural movements in static magnetic fields or exposure to alternating magnetic field gradients.

A dual dipole electric field probe has been used to measure surface electric fields in vivo on a human subject over a frequency range of 0.1-800 Hz. The low-frequency electric fields were induced by natural body movements such as walking and turning in the fringe magnetic fields of a 3 T magnetic resonance whole-body scanner. The rate-of-change of magnetic field (dB/dt) was also recorded simultaneously by using three orthogonal search coils positioned near to the location of the electric field probe. Rates-of-change of magnetic field for natural body rotations were found to exceed 1 T s(-1) near the end of the magnet bore. Typical electric fields measured on the upper abdomen, head and across the tongue for 1 T s(-1) rate of change of magnetic field were 0.15+/-0.02, 0.077+/-0.003 and 0.015+/-0.002 V m(-1) respectively. Electric fields on the abdomen and chest were measured during an echo-planar sequence with the subject positioned within the scanner. With the scanner rate-of-change of gradient set to 10 T m(-1) s(-1) the measured rate-of-change of magnetic field was 2.2+/-0.1 T s(-1) and the peak electric field was 0.30+/-0.01 V m(-1) on the chest. The values of induced electric field can be related to dB/dt by a 'geometry factor' for a given subject and sensor position. Typical values of this factor for the abdomen or chest (for measured surface electric fields) lie in the range of 0.10-0.18 m. The measured values of electric field are consistent with currently available numerical modelling results for movement in static magnetic fields and exposure to switched magnetic field gradients.

Modeling and optimization of Look-Locker spin labeling for measuring perfusion and transit time changes in activation studies taking into account arterial blood volume.

This work describes a new compartmental model with step-wise temporal analysis for a Look-Locker (LL)-flow-sensitive alternating inversion-recovery (FAIR) sequence, which combines the FAIR arterial spin labeling (ASL) scheme with a LL echo planar imaging (EPI) measurement, using a multireadout EPI sequence for simultaneous perfusion and T*(2) measurements. The new model highlights the importance of accounting for the transit time of blood through the arteriolar compartment, delta, in the quantification of perfusion. The signal expected is calculated in a step-wise manner to avoid discontinuities between different compartments. The optimal LL-FAIR pulse sequence timings for the measurement of perfusion with high signal-to-noise ratio (SNR), and high temporal resolution at 1.5, 3, and 7T are presented. LL-FAIR is shown to provide better SNR per unit time compared to standard FAIR. The sequence has been used experimentally for simultaneous monitoring of perfusion, transit time, and T*(2) changes in response to a visual stimulus in four subjects. It was found that perfusion increased by 83 +/- 4% on brain activation from a resting state value of 94 +/- 13 ml/100 g/min, while T*(2) increased by 3.5 +/- 0.5%.

Using forward calculations of the magnetic field perturbation due to a realistic vascular model to explore the BOLD effect.

This paper assesses the reliability of the infinite cylinder model used previously in the literature to simulate blood oxygenation level dependent (BOLD) signal changes. A three-dimensional finite element method was applied to a realistic model of the cortical vasculature, and the results compared with those generated from a simple model of the vasculature as a set of independent, randomly oriented, infinite cylinders. The realistic model is based on scanning electron microscopy measurements of the terminal vascular bed in the superficial cortex of the rat. Good agreement is found between the two models with regard to the extravascular R(2)* and R(2) dependence on the cerebral blood volume and blood oxygenation fraction. Using the realistic model, it is also possible to gain further understanding of the relative importance of intravascular and extravascular BOLD contrast. A simple parameterisation of the dependence of the relaxation rates on relative cerebral blood volume and blood-tissue susceptibility difference was carried out, allowing discussion of the variation in the form of the haemodynamic response with field strength.

Measurement of electric fields due to time-varying magnetic field gradients using dipole probes.

The operation of dipole probes in measuring electric fields in conductive media exposed to temporally varying magnetic fields is discussed. The potential measured by the probe can be thought of as originating from two contributions to the electric field, namely the gradient of the scalar electric potential and the temporal derivative of the magnetic vector potential. Using this analysis, it is shown that the exact form of the wire paths employed when using electric field probes to measure the effects of temporally varying magnetic fields is very important and this prediction is verified via simple experiments carried out using different probe geometries in a cylindrical sample exposed to a temporally varying, uniform magnetic field. Extending this work, a dipole probe has been used to measure the electric field induced in a cylindrical sample by gradient coils as used in magnetic resonance imaging (MRI). Analytic solutions for the electric field in an infinite cylinder are verified by comparison with experimental measurements. Deviations from the analytic solutions of the electric field for the x-gradient coil due to the finite length of the sample cylinder are also demonstrated.

Magnetic-field-induced vertigo: a theoretical and experimental investigation.

Vertigo-like sensations or apparent perception of movement are reported by some subjects and operators in and around high field whole body magnetic resonance body scanners. Induced currents (which modulate the firing rate of the vestibular hair cell), magneto-hydrodynamics (MDH), and tissue magnetic susceptibility differences have all been proposed as possible mechanisms for this effect. In this article, we examine the theory underlying each of these mechanisms and explore resulting predictions. Experimental evidence is summarised in the following findings: 30% of subjects display a postural sway response at a field-gradient product of 1 T(2)m(-1); a determining factor for experience of vertigo is the total unipolar integrated field change over a period greater than 1 s; the perception of dizziness is not necessarily related to a high value of the rate of change of magnetic field; eight of ten subjects reported sensations ranging from mild to severe when exposed to a magnetic field change of the order of 4.7 T in 1.9 s; no subjects reported any response when exposed to 50 ms pulses of dB/dt of 2 Ts(-1) amplitude. The experimental evidence supports the hypothesis that magnetic-field related vertigo results from both magnetic susceptibility differences between vestibular organs and surrounding fluid, and induced currents acting on the vestibular hair cells. Both mechanisms are consistent with theoretical predictions.

Theoretical optimization of multi-echo fMRI data acquisition.

Simulations are used to optimize multi-echo fMRI data acquisition for detection of BOLD signal changes in this study. Optimal sequence design (echo times and sampling period (receiver bandwidth)) and the variation in sensitivity between tissues with different baseline T*(2) are investigated, taking into account the effects of physiological noise and non-exponential signal decay. In the case of a single echo, for normally distributed, uncorrelated noise, the results indicate that the sampling period should be made as long as possible (so as to produce an acceptable level of image distortion), up to a maximum sampling period of 3T*(2), (i.e. optimum TE = 1.5T*(2)). Combining the signal from multiple echoes using weighted summation improves the contrast-to-noise ratio (CNR), at a reduced optimum echo interval. If the BOLD effect causes a constant change in relaxation rate, DeltaR*(2), independent of the tissue R*(2), then a multi-echo acquisition causes considerable variation in sensitivity to BOLD signal changes with tissue T*(2), so that if the sequence is optimized for a target tissue T*(2) it will be more sensitive to BOLD signal changes in tissues with shorter T*(2) values. Fitting for DeltaR*(2) reduces the CNR, and when using this approach, the shortest echo time interval should be used, down to a limit of about 0.3T*(2), and as many echoes as possible within the constraints of TR or hardware limitations should be collected. It is also shown that the optimal sequence will remain optimum or close to optimum irrespective of whether there are physiological noise contributions.

Intermolecular multiple quantum coherences at high magnetic field: the nonlinear regime.

Experiments have been carried at magnetic-field strengths of 9.4, 14.1, and 17.6 T to explore the evolution of intermolecular multiple quantum coherences in the nonlinear regime where the system evolves for times that are much greater than the characteristic time of action of the long-range dipolar field, tau(d). The results show the expected Bessel function form of the recorded signal as a function of time of evolution, with evident zeros and sign changes. As expected, the rate of signal evolution increases at higher-field strengths as a result of the increased equilibrium magnetization. A numerical method for calculating the evolution of magnetization under the action of the distant dipolar field, relaxation, and diffusion that is based on Fourier analysis of the magnetization distribution has been applied to the correlated two-dimensional spectroscopy revamped by asymmetric z-gradient echo detection sequence in the nonlinear regime and shown to produce results that are in good agreement with experimental data acquired at different magnetic fields and rates of spatial modulation. Experiments and simulations have also been used to explore the evolution of magnetization in a mixture of two interacting spin species in the nonlinear regime.

Optimizing the sequence parameters for double-quantum CRAZED imaging.

The evolution of magnetization during repeated application of the double-quantum-(DQ)-CRAZED sequence is analyzed, with the aim of identifying sequence parameters that maximize sensitivity to signal produced by the distant dipole field (DDF). Phase cycling schemes that allow cancellation of signals following undesired coherence pathways are also described. Simulations and imaging experiments carried out at 3 T on phantoms and the human head were used to verify the analysis. The results indicate that in the absence of phase cycling, the DDF-related signal-to-noise ratio (SNR) per unit time is maximized using TR=2.05 T1, along with values of the RF flip angles (alpha approximately 90 degrees and beta approximately 60 degrees ), and echo time (TE=T2) that have previously been shown to maximize the DDF-related signal at long TR. However, with TR=2.05 T1 there can also be a significant signal contribution due to stimulated echo effects (up to 40% of the signal for water at 3 T and TE=70 ms). Using a two-step phase cycle, the stimulated echo signal is eliminated and the maximum SNR per unit time occurs for TR=2.76 T1. It is also demonstrated that sensitivity to signal changes caused by small variations in T2 is maximized by setting TE=2T2.

Actively shielded multi-layer gradient coil designs with improved cooling properties.

In standard cylindrical gradient coils consisting of a single layer of wires, a limiting factor in achieving very large magnetic field gradients is the rapid increase in coil resistance with efficiency. This is a particular problem in small-bore scanners, such as those used for MR microscopy. By adopting a multi-layer design in which the coil wires are allowed to spread out into multiple layers wound at increasing radii, a more favourable scaling of resistance with efficiency is achieved, thus allowing the design of more powerful gradient coils with acceptable resistance values. Previously this approach has been applied to the design of unshielded, longitudinal, and transverse gradient coils. Here, the multi-layer approach has been extended to allow the design of actively shielded multi-layer gradient coils, and also to produce coils exhibiting enhanced cooling characteristics. An iterative approach to modelling the steady-state temperature distribution within the coil has also been developed. Results indicate that a good level of screening can be achieved in multi-layer coils, that small versions of such coils can yield higher efficiencies at fixed resistance than conventional two-layer (primary and screen) coils, and that performance improves as the number of layers of increases. Simulations show that by optimising multi-layer coils for cooling it is possible to achieve significantly higher gradient strengths at a fixed maximum operating temperature. A four-layer coil of 8 mm inner diameter has been constructed and used to test the steady-state temperature model.

Measuring the change in CBV upon cortical activation with high temporal resolution using look-locker EPI and Gd-DTPA.

A method of simultaneously measuring the changes in cerebral blood volume (CBV) and T(*) (2) that occur on brain activation with high temporal resolution was developed. The method involves measuring the change in the longitudinal relaxation time (T(1)) that occurs following a bolus injection of Gd-DTPA and converting this measurement to a change in blood volume assuming fast exchange. The sequence was optimized for the measurement of changes in CBV with high temporal resolution. A change in CBV of 27 +/- 4% on activation of the primary visual cortex (V1) was measured across four subjects. The time course of changes in T(*) (2) showed a poststimulus undershoot (P = 0.008) corresponding approximately to a period over which CBV was still elevated above baseline, but falling (P = 0.01). The effects of perfusion, nonfulfillment of the assumption of fast exchange and of intrinsic T(1) changes on activation on the model used to calculate the change in CBV are discussed.