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

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

High-resolution fMRI using multislice partial k-space GR-EPI with cubic voxels.

The premises of this work are: 1) the limit of spatial resolution in fMRI is determined by anatomy of the microcirculation; 2) because of cortical gray matter tortuosity, fMRI experiments should (in principle) be carried out using cubic voxels; and 3) the noise in fMRI experiments is dominated by low-frequency BOLD fluctuations that are a consequence of spontaneous neuronal events and are pixel-wise dependent. A new model is proposed for fMRI contrast which predicts that the contrast-to-noise ratio (CNR) tends to be independent of voxel dimensions (in the absence of partial voluming of activated tissue), TE, and scanner bandwidth. These predictions have been tested at 3 T, and results support the model. Scatter plots of fMRI signal intensities and low-frequency fluctuations for activated pixels in a finger-tapping paradigm demonstrated a linear relationship between signal and noise that was independent of TE. The R(2) value was about 0.9 across eight subjects studied. The CNR tended to be constant across pixels within a subject but varied across subjects: CNR = 3.2 +/- 1.0. fMRI statistics at 20- and 40-ms TE values were indistinguishable, and TE values as short as 10 ms were used successfully. Robust fMRI data were obtained across all subjects using 1 x 1 x 1 mm(3) cubic voxels with 10 contiguous slices, although 1.5 x 1.5 x 1.5 mm(3) was found to be optimum. Magn Reson Med 46:114-125, 2001.     

Quantifying the intra- and extravascular contributions to spin-echo fMRI at 3 T.

Functional MRI (fMRI) by means of spin-echo (SE) techniques provides an interesting alternative to gradient-echo methods because the contrast is based primarily on dynamic averaging associated with the blood oxygenation level-dependent (BOLD) effect. In this article the contributions from different brain compartments to BOLD signal changes in SE echo planar imaging (EPI) are investigated. To gain a better understanding of the underlying mechanisms that cause the fMRI contrast, two experiments are presented: First, the intravascular contribution is decomposed into two fractions with different regimes of flow by means of diffusion-weighting gradient schemes which are either flow-compensated, or will maximally dephase moving spins. Second, contributions from the intra- and extravascular space are selectively suppressed by combining flow-weighting with additional refocusing pulses. The results indicate two qualitatively different components of flowing blood which contribute to the BOLD contrast and a nearly equal share in functional signal from the intra- and extravascular compartments at TE approximately 80 ms and 3 T. Combining these results, there is evidence that at least one-half of the functional signal originates from the parenchyma in SE fMRI at 3 T. The authors suggest the use of flow-compensated diffusion weighting for SE fMRI to improve the sensitivity to the parenchyma.     

Theoretical noise model for oxygenation-sensitive magnetic resonance imaging.

Contrast-to-noise ratio (CNR) in blood oxygenation level-dependent (BOLD) based functional MRI (fMRI) studies is a fundamental parameter to determine statistical significance and therefore to map functional activation in the brain. The CNR is defined here as BOLD contrast with respect to temporal fluctuation. In this study, a theoretical noise model based on oxygenation-sensitive MRI signal formation is proposed. No matter what the noise sources may be in the signal acquired by a gradient-echo echo-planar imaging pulse sequence, there are only three noise elements: apparent spin density fluctuations, S(0)(t); transverse relaxation rate fluctuations, R(2) (*)(t); and thermal noise, n(t). The noise contributions from S(0)(t), R(2) (*)(t), and n(t) to voxel time course fluctuations were evaluated as a function of echo time (TE) at 3 T. Both noise contributions caused by S(0)(t) and R(2) (*)(t) are significantly larger than that of thermal noise when TE = 30 ms. In addition, the fluctuations between S(0)(t) and R(2) (*)(t) are cross-correlated and become a noise factor that is large enough and cannot be ignored. The experimentally measured TE dependences of noise, temporal signal-to-noise ratio, and BOLD CNR in finger-tapping activation regions were consistent with the proposed model. Furthermore, the proposed theoretical models not only unified previously proposed BOLD CNR models, but also provided mechanisms for interpreting apparent controversies and limitations that exist in the literature.     

A comparison between blood oxygenation level-dependent and cerebral blood volume contrast in the rat cerebral and cerebellar somatosensoric cortex during electrical paw stimulation

PURPOSE: To implement and optimize cerebral blood volume (CBV)-weighted functional magnetic resonance imaging (fMRI) in the rat cerebral and cerebellar cortex during electrical paw stimulation. MATERIALS AND METHODS: fMRI of the cerebral and cerebellar cortex was performed during electrical paw stimulation on a 7-T MRI system (MRRS, Guilford, UK) comparing the blood oxygenation level-dependent (BOLD) and CBV-weighted contrast with different ultrasmall particles of iron oxide (USPIO) contrast doses (NC100150, 30 mg Fe/mL; Amersham Health, Oslo, Norway) and different TE. RESULTS: Doses of 15 and 20 mg/kg USPIO at TE = T*2 or TE = 14 msec almost doubled the contrast-to-noise ratio (CNR) of the activated areas in the cerebral cortex without affecting the overall signal-to-noise ratio (SNR) or the incidence of activation (100%). In the cerebellum the SNR decreased significantly with an increasing contrast dose. At a dose of 15 mg/kg, the CNR was slightly smaller than the CNR measured in the BOLD images, but the activation incidence seemed to be doubled. At 20 mg/kg, the CNR was slightly increased, but the activation incidence was lower. At both contrast doses the venous artifacts disappeared. CONCLUSION: A USPIO contrast dose of 20 mg/kg proved to be beneficial for fMRI in the rat, even though it affected the CNR and SNR in the cerebral and the cerebellar cortex differentially.     

Extravascular proton-density changes as a non-BOLD component of contrast in fMRI of the human spinal cord.

The fractional signal intensity change (Delta S/S) observed during activation in T(2)-weighted fMRI of the spinal cord has previously been shown to depend linearly on the echo time (TE) but to have a positive value of roughly 2.5% extrapolated to zero TE. In this study we investigated the origin of this finding by measuring the Delta S/S in spinal fMRI with very short TEs. Our results demonstrate that the Delta S/S does not approach zero, but has a value as high as 3.3% at TE = 11 ms. At TEs > 33 ms we observed the linear relationship between Delta S/S and TE as in previous studies. These data demonstrate that there is a non-BOLD contribution to signal changes observed in spinal fMRI. We hypothesize that this contribution is a local proton density increase due to increased water exudation from capillaries with increased blood flow during neuronal activation, and term this effect "signal enhancement by extravascular protons" (SEEP).     

Disparity of activation onset in sensory cortex from simultaneous auditory and visual stimulation: Differences between perfusion and blood oxygenation level-dependent functional magnetic resonance imaging

PURPOSE: To compare the temporal behaviors of perfusion and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in the detection of timing differences between distinct brain areas, and determine potential latency differences between stimulus onset and measurable fMRI signal in sensory cortices. MATERIALS AND METHODS: Inversion recovery (IR) spin-echo echo-planar imaging (EPI) and T2*-weighted gradient-echo EPI sequences were used for perfusion- and BOLD-weighted experiments, respectively. Simultaneous auditory and visual stimulations were employed in an event-related (ER) paradigm. Signal time courses were averaged across 40 repeated trials to evaluate the onset of activation and to determine potential differences of activation latency between auditory and visual cortices and between these scanning methods. RESULTS: Temporal differences between visual and auditory areas ranged from 90-200 msec (root-mean-square (RMS) = 134 msec) and from -80 to 930 msec (RMS = 604 msec) in perfusion and BOLD measurements, respectively. The temporal variability detected with BOLD sequences was larger between subjects and was significantly greater than that in the perfusion response (P < 0.04). The measured time to half maximum (TTHM) values for perfusion imaging (visual, 3260 +/- 710 msec; auditory, 3130 +/- 700 msec) were earlier than those in BOLD responses (visual, 3770 +/- 430 msec; auditory, 3360 +/- 460 msec). CONCLUSION: The greater temporal variability between brain areas detected with BOLD could result from differences in the venous contributions to the signal. The results suggest that perfusion methods may provide more accurate timing information of neuronal activities than BOLD-based imaging.     

Spatial and temporal characteristics of physiological noise in fMRI at 3T

RATIONALE AND OBJECTIVES: Physiological noise in blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) has been shown to have characteristics similar to the BOLD signal itself, suggesting that it may have a vascular dependence. In this study, we evaluated the influence of physiological noise in fMRI as revealed by the differences in vasculature sensitivity of gradient-echo echo-planar imaging (GE-EPI) and spin-echo EPI (SE-EPI). MATERIALS AND METHODS: The contribution of physiological noise to the fMRI signal during activation of the visual cortex was assessed by comparing its temporal characteristics with respect to echo time (TE), using both GE-EPI and SE-EPI. The correlation of the noise in fMRI with apparent diffusion coefficient (ADC) and the number of components required to describe its variance, as determined by principal-component analysis (PCA), were also assessed. RESULTS: The SE-EPI data were less affected by a TE-dependence of noise, in contrast to the apparent physiological noise in GE-EPI. Voxel-wise analysis revealed that total apparent noise increased as ADC values increased, and the relationship was different for GE-EPI and SE-EPI. PCA revealed that while the number of components characterizing the noise in SE-EPI data increased in a TE-dependent manner, approaching that of white noise at long echo time, the number of components from GE-EPI data was TE-independent. CONCLUSIONS: The difference in sensitivities to physiological noise between SE-EPI and GE-EPI suggests that extravascular BOLD processes around draining veins contribute significantly to physiological noise in BOLD fMRI, and the suppression of this noise component may enhance SE-EPI BOLD sensitivity at higher fields.     

Fuzzy clustering of gradient-echo functional MRI in the human visual cortex. Part II: Quantification

Fuzzy cluster analysis (FCA) is a new exploratory method for analyzing fMRI data. Using simulated functional MRI (fMRI) data, the performance of FCA, as implemented in the software package Evident, was tested and a quantitative comparison with correlation analysis is presented. Furthermore, the fMRI model fit allows separation and quantification of flow and blood oxygen level dependent (BOLD) contributions in the human visual cortex. In gradient-recalled echo fMRI at 1.5 T (TR = 60 ms, TE = 42 ms, radiofrequency excitation flip angle [?] = 10^°–60^°) total signal enhancement in the human visual cortex, ie, flow-enhanced BOLD plus inflow contributions, on average varies from 5% to 10% in or close to the visual cortex (average cerebral blood volume [CBV] = 4%) and from 10% to 20% in areas containing medium-sized vessels (ie, average CBV = 12% per voxel), respectively. Inflow enhancement, however, is restricted to intravascular space (= CBV) and increases with increasing radiofrequency (RF) flip angle, whereas BOLD contributions may be obtained from a region up to three times larger and, applying an unspoiled gradient-echo (GRE) sequence, also show a flip angle dependency with a minimum at approximately 30^°. This result suggests that a localized hemodynamic response from the microvasculature at 1.5 T maybe extracted via fuzzy clustering. In summary, fuzzy clustering of fMRI data, as realized in the Evident software, is a robust and efficient method to (a) separate functional brain activation from noise or other sources resulting in time-dependent signal changes as proven by simulated fMRI data analysis and in vivo data from the visual cortex, and (b) allows separation of different levels of activation even if the temporal pattern is indistinguishable. Combining fuzzy cluster separation of brain activation with appropriate model calculations allows quantification of flow and (flow-enhanced) BOLD contributions in areas with different vascularization.     

T1rho contrast in functional magnetic resonance imaging.

The application of T1 in the rotating frame (T1rho) to functional MRI in humans was studied at 3 T. Increases in neural activity increased parenchymal T1rho. Modeling suggested that cerebral blood volume mediated this increase. A pulse sequence named spin-locked echo planar imaging (SLEPI) that produces both T1rho and T2* contrast was developed and used in a visual functional MRI (fMRI)experiment. Spin-locked contrast significantly augments the T2* blood oxygen level-dependent (BOLD) contrast in this sequence. The total functional contrast generated by the SLEPI sequence (1.31%) was 54% larger than the contrast (0.85%) obtained from a conventional gradient-echo EPI sequence using echo times of 30 ms. Analysis of image SNR revealed that the spin-locked preparation period of the sequence produced negligible signal loss from static dephasing effects. The SLEPI sequence appears to be an attractive alternative to conventional BOLD fMRI, particularly when long echo times are undesirable, such as when studying prefrontal cortex or ventral regions, where static susceptibility gradients often degrade T2*-weighted images.     

Quantifying the blood oxygenation level dependent effect in cerebral blood volume-weighted functional MRI at 9.4T.

In cerebral blood volume (CBV)-weighted functional MRI (fMRI) employing superparamagnetic contrast agent, iron dose and blood oxygenation level dependent (BOLD) contamination are two important issues for experimental design and CBV quantification. Both BOLD and CBV-weighted fMRI are based upon the susceptibility effect, to which spin-echo and gradient-echo sequences have different sensitivities. In the present study, CBV-weighted fMRI was conducted using spin-echo and gradient-echo sequences at 9.4T by systematically changing the doses of contrast agent. Results suggest that BOLD contamination is a significant component in CBV-weighted fMRI at high field, particularly when relatively low dose of contrast agent is administered. A mathematical model was developed to quantify the extravascular (EV) BOLD effect. With a TE of 35 ms, the EV BOLD effect was estimated to account for 76+/-12% of the observed spin-echo fMRI signal at 9.4T. These data suggest that correcting BOLD effect may be necessary for accurately quantifying activation-induced CBV changes at high field.     

Spatiotemporal dynamics of the BOLD fMRI signals: toward mapping submillimeter cortical columns using the early negative response.

The existence of the early-negative blood-oxygenation-level-dependent (BOLD) response is controversial and its practical utility for mapping brain functions with columnar spatial specificity remains questionable. To address these issues, gradient-echo BOLD fMRI studies were performed at 4.7 T and 9.4 T using the well-established orientation column model in the cat visual cortex. A robust transient early-negative BOLD response was consistently observed in anesthetized cat (-0.35 +/- 0.09%, mean +/- SD, n = 8 at 2.9 +/- 0.5 sec poststimulus onset for 4.7 T, TE = 31 ms; -0.29 +/- 0.10%, n = 4 at 3.0 +/- 0.8 sec poststimulus onset for 9.4 T, TE = 12 ms). In addition to its temporal evolution, the BOLD response also evolved dynamically in the spatial domain. The initially spatially localized early-negative signal appeared to dynamically drain from the active sites toward large vessels, followed by a wave of the delayed positive signal, which exhibited similar spatiotemporal dynamics. Only the early-negative BOLD response within 2 sec of the stimulus onset (not the entire dip) yielded columnar layouts without differential subtraction. The functional maps of two orthogonal orientations using the first 2-sec dip were indeed complementary. On the other hand, the delayed positive BOLD response appeared diffused and extended beyond the active sites. It was thus less suitable to resolve columnar layouts. These results have implications for the design and interpretation of the BOLD fMRI at columnar resolution. Magn Reson Med 44:231-242, 2000.     

Systematic investigation of balanced steady-state free precession for functional MRI in the human visual cortex at 3 Tesla.

Previous studies have applied balanced steady-state free precession (bSSFP) to functional brain imaging. Methods that exploit the strong frequency dependence of the MR signal in the bSSFP transition band are strongly affected by field inhomogeneity and frequency drifts. Recent bSSFP studies using "on-resonance" (in the bSSFP passband) acquisition claimed that higher sensitivity was achieved compared to traditional fMRI methods. However, the contrast mechanism that generates activation-related signal changes in bSSFP imaging is not yet fully understood. We performed a systematic study of on-resonance bSSFP signal behavior using a multiecho balanced SSFP sequence with different TRs at 3 Tesla. We conclude that intravoxel dephasing, or the off-resonance averaged steady state, dominates the bSSFP signal decay and determines the bSSFP fMRI contrast. Experimental findings were confirmed by simulations based on existing theories for signal formation around blood vessels in inhomogeneous tissues. The activation-induced signal change in on-resonance bSSFP increases with TE, and the TE dependence of the contrast-to-noise ratio (CNR) in bSSFP is similar to that in gradient echo-planar imaging (GE-EPI). However, GE-EPI has a significantly higher CNR efficiency.     

Functional MRI using regularized parallel imaging acquisition.

Parallel MRI techniques reconstruct full-FOV images from undersampled k-space data by using the uncorrelated information from RF array coil elements. One disadvantage of parallel MRI is that the image signal-to-noise ratio (SNR) is degraded because of the reduced data samples and the spatially correlated nature of multiple RF receivers. Regularization has been proposed to mitigate the SNR loss originating due to the latter reason. Since it is necessary to utilize static prior to regularization, the dynamic contrast-to-noise ratio (CNR) in parallel MRI will be affected. In this paper we investigate the CNR of regularized sensitivity encoding (SENSE) acquisitions. We propose to implement regularized parallel MRI acquisitions in functional MRI (fMRI) experiments by incorporating the prior from combined segmented echo-planar imaging (EPI) acquisition into SENSE reconstructions. We investigated the impact of regularization on the CNR by performing parametric simulations at various BOLD contrasts, acceleration rates, and sizes of the active brain areas. As quantified by receiver operating characteristic (ROC) analysis, the simulations suggest that the detection power of SENSE fMRI can be improved by regularized reconstructions, compared to unregularized reconstructions. Human motor and visual fMRI data acquired at different field strengths and array coils also demonstrate that regularized SENSE improves the detection of functionally active brain regions.     

Source of nonlinearity in echo-time-dependent BOLD fMRI.

Stimulation-induced changes in transverse relaxation rates can provide important insight into underlying physiological changes in blood oxygenation level-dependent (BOLD) contrast. It is often assumed that BOLD fractional signal change (DeltaS/S) is linearly dependent on echo time (TE). This relationship was evaluated at 9.4 T during visual stimulation in cats with gradient-echo (GE) and spin-echo (SE) echo-planar imaging (EPI). The TE dependence of GE DeltaS/S is close to linear in both the parenchyma and large vessel area at the cortical surface for TEs of 6-20 ms. However, this dependence is nonlinear for SE studies in the TE range of 16-70 ms unless a diffusion-weighting of b = 200 s/mm(2) is applied. This behavior is not caused by inflow effects, T(2)* decay during data acquisition in SE-EPI, or extravascular spin density changes. Our results are explained by a two-compartment model in which the extravascular contribution to DeltaS/S vs. TE is linear, while the intravascular contribution can be nonlinear depending on the magnetic field strength and TE. At 9.4 T, the large-vessel IV signal can be minimized by using long TE and/or moderate diffusion weighting. Thus, stimulation-induced relaxation rate changes should be carefully determined, and their physiological meanings should be interpreted with caution.     

Spin-echo fMRI in humans using high spatial resolutions and high magnetic fields.

The Hahn spin-echo (HSE)-based BOLD effect at high magnetic fields is expected to provide functional images that originate exclusively from the microvasculature. The blood contribution that dominates HSE BOLD contrast at low magnetic fields (e.g., 1.5 T), and degrades specificity, is highly attenuated at high fields because the apparent T(2) of venous blood in an HSE experiment decreases quadratically with increasing magnetic field. In contrast, the HSE BOLD contrast is believed to arise from the microvasculature and increase supralinearly with the magnetic field strength. In this work we report the results of detailed and quantitative evaluations of HSE BOLD signal changes for functional imaging in the human visual cortex at 4 and 7 T. This study used high spatial resolution, afforded by the increased signal-to-noise ratio (SNR) of higher field strengths and surface coils, to avoid partial volume effects (PVEs), and demonstrated increased contrast-to-noise ratio (CNR) and spatial specificity at the higher field strengths. The HSE BOLD signal changes induced by visual stimulation were predominantly linearly dependent on the echo time (TE). They increased in magnitude almost quadratically in going from 4 to 7 T when the blood contribution was suppressed using Stejskal-Tanner gradients that suppress signals from the blood due to its inhomogeneous flow and higher diffusion constant relative to tissue. The HSE signal changes at 7 T were modeled accurately using a vascular volume of 1.5%, in agreement with the capillary volume of gray matter. Furthermore, high-resolution acquisitions indicate that CNR increased with voxel sizes < 1 mm(3) due to diminishing white matter or cerebrospinal fluid-space vs. gray matter PVEs. It was concluded that the high-field HSE functional MRI (fMRI) signals originated largely from the capillaries, and that the magnitude of the signal changes associated with brain function reached sufficiently high levels at 7 T to make it a useful approach for mapping on the millimeter to submillimeter spatial scale.     

Dual-Echo Interleaved Echo-Planar Imaging of the Brain

An interleaved echo-planar imaging (EPI) technique is described that provides images from 20 sections of the brain at two echo times (27 and 84 ms) in 1:05. Six echoes per image per repetition are collected in 24 repetitions of the pulse sequence. MR images of the brain obtained from five volunteers using the dual-echo EPI sequence, fast spin-echo (FSE), and conventional dual-echo spin-echo were evaluated qualitatively for diagnostic use and quantitatively for relative signal-to-noise ratio (SNR), contrast, and contrast-to-noise ratios (CNR).     

血管外质子信号增强颈髓功能成像序列参数优化

目的通过优化成像参数,获得一种较高质量的利用血管外质子信号增强的颈髓功能成像。方法采用GRE-echoplan序列中的一种新的血管外质子信号增强(SEEP)磁共振功能成像技术,按TR、TE时间的相关关系,通过固定TR改变TE,同时通过选择使用呼吸门控或心电门控,是否加饱和带等不同参数下获得颈髓功能成像,比较上述不同参数下颈髓fMRI成像的影像质量,包括信噪比、显示激活区部位是否清晰、确定,是否可重复。结果采用SEEP成像技术能实现颈髓功能成像,TR 1065s与TE 45s时能获得较高质量的颈髓功能成像,使用心电门控较不使用心电门控图像质量明显提高,加前饱和带可减少呼吸与吞咽所致的伪影,呼吸门控对图像质量无明显影响。结论 GRE-echo plan序列的SEEP成像技术经优化技术参数后能获得较高质量的颈髓功能成像。     

Transient relationships among BOLD, CBV, and CBF changes in rat brain as detected by functional MRI.

The transient relationship between arterial cerebral blood flow (CBF(A)) and total cerebral blood volume (CBV(T)) was determined in the rat brain. Five rats anesthetized with urethane (1.2 g/kg) were examined under graded hypercapnia conditions (7.5% and 10% CO(2) ventilation). The blood oxygenation level-dependent (BOLD) contrast was determined by a gradient-echo echo-planar imaging (GE-EPI) pulse sequence, and CBV(T) changes were determined after injection of a monocrystalline iron oxide nanocolloid (MION) contrast agent using an iron dose of 12 mg/kg. The relationship between CBV(T) and CBF(A) under transient conditions is similar to the power law under steady-state conditions. In addition, the transient relationship between CBV(T) and CBF(A) is region-specific. Voxels with > or =15% BOLD signal changes from hypercapnia (7.5% CO(2) ventilation) have a larger power index (alpha = 3.26), a larger maximum possible BOLD response (M = 0.85), and shorter T(*)(2) (32 ms) caused by deoxyhemoglobin, compared to voxels with <15% BOLD signal changes (alpha = 1.82, M = 0.16, and T(*)(2) = 169 ms). It is suggested that the biophysical model of the BOLD signal can be extended under the transient state, with a caution that alpha and M values are region-specific. To avoid overestimation of the cerebral metabolic rate of oxygen changes seen using fMRI, caution should be taken to not include voxels with large veins and a large BOLD signal.     

Quantitative assessment of blood inflow effects in functional MRI signals

Functional MRI (fMRI) signal dependence on changes in blood flow velocities were analyzed for both conventional and echo-planar (EPI) gradient-echo pulse sequences. As the flow velocity increases, the fMRI signal increases monotonically in spoiled gradient-echo sequences, while the fMRI signal may increase or decrease in conventional refocused gradient-echo sequences. A larger flip angle generates a larger inflow contribution to the fMRI signal. For conventional gradient-echo sequences, the inflow contribution to the fMRI images is dominated by the cortical draining veins, while its effect on capillaries is generally small and may be negligible in the spoiled sequences. For EPI gradient-echo sequences, the contribution from inflow effects is relatively small, as compared with the blood oxygen level-dependent (BOLD) contribution, to the fMRI signal, not only for capillaries but also for the cortical draining veins.