Functional magnetic resonance imaging based on changes in vascular space occupancy.

During brain activation, local control of oxygen delivery is facilitated through microvascular dilatation and constriction. A new functional MRI (fMRI) methodology is reported that is sensitive to these microvascular adjustments. This contrast is accomplished by eliminating the blood signal in a manner that is independent of blood oxygenation and flow. As a consequence, changes in cerebral blood volume (CBV) can be assessed through changes in the remaining extravascular water signal (i.e., that of parenchymal tissue) without need for exogenous contrast agents or any other invasive procedures. The feasibility of this vascular space occupancy (VASO)-dependent functional MRI (fMRI) approach is demonstrated for visual stimulation, breath-hold (hypercapnia), and hyperventilation (hypocapnia). During visual stimulation and breath-hold, the VASO signal shows an inverse correlation with the stimulus paradigm, consistent with local vasodilatation. This effect is reversed during hyperventilation. Comparison of the hemodynamic responses of VASO-fMRI, cerebral blood flow (CBF)-based fMRI, and blood oxygenation level-dependent (BOLD) fMRI indicates both arteriolar and venular temporal characteristics in VASO. The effect of changes in water exchange rate and partial volume contamination with CSF were calculated to be negligible. At the commonly-used fMRI resolution of 3.75 x 3.75 x 5 mm(3), the contrast-to-noise-ratio (CNR) of VASO-fMRI was comparable to that of CBF-based fMRI, but a factor of 3 lower than for BOLD-fMRI. Arguments supporting a better gray matter localization for the VASO-fMRI approach compared to BOLD are provided.     

Vascular space occupancy-dependent functional MRI by tissue suppression

PURPOSE: To measure the cerebral blood volume (CBV) dynamics during neural activation, a novel technique named vascular space occupancy (VASO)-based functional MRI (fMRI) was recently introduced for noninvasive CBV detection. However, its application is limited because of its low contrast-to-noise ratio (CNR) due to small signal change from the inverted blood. MATERIALS AND METHODS: In this study a new approach-VASO with tissue suppression (VAST)-is proposed to enhance CNR. This technique is compared with VASO and blood oxygenation level-dependent (BOLD) fMRI in block-design and event-related visual experiments. RESULTS: Based on acquired T(1) maps, 75.3% of the activated pixels detected by VAST are located in the cortical gray matter. Temporal characteristics of functional responses obtained by VAST were consistent with that of VASO. Although the baseline signal was decreased by the tissue suppression, the CNR of VAST was about 43% higher than VASO. CONCLUSION: With the improved sensitivity, VAST fMRI provides a useful alternative for mapping the spatial/temporal features of regional CBV changes during brain activation. However, the technical imperfectness of VAST, such as the nonideal inversion efficiency and physiological contaminations, limits its application to precise CBV quantification.     

Novel approach to the measurement of absolute cerebral blood volume using vascular-space-occupancy magnetic resonance imaging.

Quantitative determination of cerebral blood volume (CBV) is important for understanding brain physiology and pathophysiology. In this work, a novel approach is presented for accurate measurement of absolute CBV (aCBV) using vascular-space-occupancy (VASO) MRI, a blood-nulling pulse sequence, in combination with the T(1) shortening property of Gd-DTPA. Two VASO images with identical imaging parameters are acquired before and after contrast agent injection, resulting in a subtracted image that reflects the amount of blood present in the brain, i.e., CBV. With an additional normalizing factor, aCBV in units of milliliters of blood per 100 mL of brain can be estimated. Experimental results at 1.5 and 3 T systems showed that aCBV maps with high spatial resolution can be obtained with high reproducibility. The averaged aCBV values in gray and white matter were 5.5 +/- 0.2 and 1.4 +/- 0.1 mL of blood/100 mL of brain, respectively. Compared to dynamic susceptibility contrast techniques, VASO MRI is based upon a relatively straightforward theory and the calculation of CBV does not require measurement of an arterial input function. In comparison with previous pre/postcontrast difference approaches, VASO MRI provides maximal signal difference between pre- and postcontrast situation and does not require the use of whole blood for signal normalization.     

Effect of inflow of fresh blood on vascular‐space‐occupancy (VASO) contrast

In vascular‐space‐occupancy (VASO)‐MRI, cerebral blood volume (CBV)‐weighted contrast is generated by applying a nonselective inversion pulse followed by imaging when blood water magnetization is zero. An uncertainty in VASO relates to the completeness of blood water nulling. Specifically, radio frequency (RF) coils produce a finite inversion volume, rendering the possibility of fresh, non‐nulled blood. Here, VASO‐functional MRI (fMRI) was performed for varying inversion volume and TR using body coil RF transmission. For thin inversion volume thickness (δ_tot < 10 mm), VASO signal changes were positive (ΔS/S = 2.1–2.6%). Signal changes were negative and varied in magnitude for intermediate inversion volumes (δ_tot = 100–300 mm), yet did not differ significantly (P > 0.05) for δ_tot > 300 mm. These data suggest that blood water is in steady state for δ_tot > 300 mm. In this appropriate range, long‐TR VASO data converged to a less negative value (ΔS/S = –1.4% ± 0.2%) than short‐TR data (ΔS/S = –2.2% ± 0.2%), implying that cerebral blood flow or transit‐state effects may influence VASO contrast at short TR. Magn Reson Med 61:473–480, 2009. © 2009 Wiley‐Liss, Inc.     

Inflow‐based vascular‐space‐occupancy (iVASO) MRI

Vascular‐space‐occupancy (VASO) MRI, a blood nulling approach for assessing changes in cerebral blood volume (CBV), is hampered by low signal‐to‐noise ratio (SNR) because only 10–20% of tissue signal is recovered when using nonselective inversion for blood nulling. A new approach, called inflow‐VASO (iVASO), is introduced in which only blood flowing into the slice has experienced inversion, thereby keeping tissue and cerebrospinal fluid (CSF) signal in the slice maximal and reducing CSF partial volume effects. SNR increases of 198% ± 12% and 334% ± 9% (mean ± SD, n = 7) with respect to VASO were found at TR values of 5s and 2s, respectively. When using inflow approaches, data interpretation is complicated by the fact that signal changes are affected by vascular transit times. An optimal TR‐range (1.5–2.5s) was derived in which the iVASO response during activation predominantly reflects arterial/arteriolar CBV (CBV_a) changes. In this TR‐range, perfusion contributions to the signal change are negligible because arterial label has not yet undergone capillary exchange, and arterial and precapillary blood signals are nulled. For TR = 2s, the iVASO signal change upon visual stimulation corresponded to a CBV_a increase of 58% ± 7%, in agreement with arteriolar CBV changes previously reported. The onset of the hemodynamic response for iVASO occurred 1.2 ± 0.5s (n = 7) faster than for conventional VASO. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

CBF, BOLD, CBV, and CMRO(2) fMRI signal temporal dynamics at 500-msec resolution

PURPOSE: To investigate the temporal dynamics of blood oxygenation level-dependent (BOLD), cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO(2)) changes due to forepaw stimulation with 500-msec resolution in a single setting. MATERIALS AND METHODS: Forepaw stimulation and hypercapnic challenge on rats were studied. CBF and BOLD functional MRI (fMRI) were measured using the pseudo-continuous arterial spin-labeling technique at 500-msec resolution. CBV fMRI was measured using monocrystalline iron-oxide particles following CBF and BOLD measurements in the same animals. CMRO(2) change was estimated via the biophysical BOLD model with hypercapnic calibration. Percent changes and onset times were analyzed for the entire forepaw somatosensory cortices and three operationally defined cortical segments, denoted Layers I-III, IV-V, and VI. RESULTS: BOLD change was largest in Layers I-III, whereas CBF, CBV, and CMRO(2) changes were largest in Layers IV-V. Among all fMRI signals in all layers, only the BOLD signal in Layers I-III showed a poststimulus undershoot. CBF and CBV dynamics were similar. Closer inspection showed that CBV increased slightly first (P < 0.05), but was slow to peak. CBF increased second, but peaked first. BOLD significantly lagged both CBF and CBV (P < 0.05). CONCLUSION: This study provides important temporal dynamics of multiple fMRI signals at high temporal resolution in a single setting.     

VASO-based calculations of CBV change: accounting for the dynamic CSF volume

The goal of the vascular space occupancy (VASO) imaging technique is to use selective nulling of the blood signal to infer relative changes in cerebral blood volume (CBV). In accordance with recent work, we show that changes in the local CSF fraction (x(c)) with activation can significantly impact the VASO signal, thereby limiting our ability to infer DeltaCBV from DeltaVASO alone. Here we calculate CBV change using a VASO-based method which ACcounts for the Dynamic Cerebrospinal (ACDC) fluid fraction. By combining data from two separate VASO acquisitions that eliminate either the blood signal (VASO(b)) or the CSF signal (VASO(c)), a nonlinear least-squares optimization may then be used to simultaneously solve for the relative changes in CBV and CSF with activation. The method is applied across the whole brain during a breath-holding task, offering insight into the relationship between changes in CBV and x(c) associated with global vasodilatation. Calculations of mean changes in CBV in different volumes of interest obtained from the proposed method compare much better with previous (gold-standard) PET data than traditional VASO methods that do not account for a nonzero Deltax(c) with activation. This confirms the necessity of incorporating the dynamic CSF volume into VASO-based calculations of DeltaCBV.     

Estimating cerebral blood volume with expanded vascular space occupancy slice coverage

A model for quantifying cerebral blood volume (CBV) based on the vascular space occupancy (VASO) technique and varying the extent of blood nulling yielding task‐related signal changes with various amounts of blood oxygenation level‐dependent (BOLD) and VASO weightings was previously described. Challenges associated with VASO include limited slice coverage and the confounding inflow of fresh blood. In this work, an approach that extends the previous model to multiple slices and accounts for the inflow effect is described and applied to data from a multiecho sequence simultaneously acquiring VASO, cerebral blood flow (CBF), and BOLD images. This method led to CBV values (7.9 ± 0.3 and 5.6 ± 0.3 ml blood/100 ml brain during activation [CBV_ACT] and rest [CBV_REST], respectively) consistent with previous studies using similar visual stimuli. Furthermore, an increase in effective blood relaxation (0.65 ± 0.01) compared to the published value (0.62) was detected, likely reflecting inflow of fresh blood. Finally, cerebral metabolic rate of oxygen (CMRO₂) estimates using a multiple compartment model without assumption of CBV_REST led to estimates (18.7 ± 17.0%) that were within published ranges. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Applications and limitations of whole-brain MAGIC VASO functional imaging.

This work extends the multiple acquisitions with global inversion cycling vascular space occupancy (MAGIC VASO) method to human whole-brain functional magnetic resonance imaging (fMRI) at 3.0 Tesla and demonstrates the need to consider the dynamic contribution of cerebrospinal fluid (CSF) to the relative VASO signal change (DeltaVASO/VASO). Simulations were performed to determine the optimal slice number between global inversions, and correction factors were obtained to account for incomplete blood nulling in particular slices. The necessity of an accurate estimate of resting cerebral blood volume (CBV(rest)) is discussed in the context of DeltaCBV/CBV calculations. A three-compartment model is proposed to include both the resting and changing fractional CSF contribution (x(c,rest) and Deltax(c), respectively) to DeltaVASO/VASO. A MAGIC VASO sequence that provides whole-brain coverage is demonstrated using a paradigm comprised of visual, motor, and auditory stimulation. Activated regions are quantitatively compared in the corresponding blood oxygenation level-dependent (BOLD) images. Estimates of the minimum DeltaCBV/CBV resulting from motor and visual stimulation were comparable to previous findings at 17 +/- 8% (N = 8) and 19 +/- 9% (N = 6), respectively. The absence of VASO activation for auditory stimulation and evidence of activation-induced decreases in CSF volume fraction around the insula and superior temporal gyrus support the possibility of a Deltax(c) contribution to the VASO signal. Without specific knowledge of the CSF components (x(c,rest) and Deltax(c)), inference of DeltaCBV/CBV from DeltaVASO/VASO is severely limited.     

On the measurement of absolute cerebral blood volume (CBV) using vascular‐space‐occupancy (VASO) MRI

Recently, a vascular‐space‐occupancy (VASO) MRI technique was developed for quantitative assessment of cerebral blood volume (CBV). This method uses the T₁‐shortening effect of gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) with imaging parameters chosen that null the precontrast blood magnetization but allow the postcontrast blood magnetization to recover to equilibrium. A key advantage of VASO CBV estimation is that it provides a straightforward procedure for converting MR signals to absolute physiologic values. However, as with other T₁‐based steady‐state approaches, several important factors need to be considered that influence the accuracy of CBV values obtained with VASO MRI. Here, the transverse relaxation (T₂/T) effect in VASO MRI was investigated using multiecho spin‐echo and gradient‐echo experiments, resulting in underestimation of CBV by 14.9% ± 1.1% and 16.0% ± 2.5% for spin echo (TE = 10 ms) and gradient echo (TE = 6 ms), respectively. In addition, the influence of contrast agent clearance was studied by acquiring multiple postcontrast VASO images at 2.2‐min intervals, which showed that the concentration of Gd‐DTPA in the first 14 min (single dose) was sufficient for the blood magnetization to fully recover to equilibrium. Finally, the effect of vascular Gd‐DTPA leakage was assessed for scalp tissue, and signal extrapolation as a function of postinjection time was demonstrated to be useful in minimizing the associated errors. Specific recommendations for VASO MRI acquisition and processing strategies are provided. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.     

Effects of CBV,CBF, and blood‐brain barrier permeability on accuracy of PASL and VASO measurement

Cerebral blood flow, cerebral blood volume (CBV), and water permeability through blood‐brain barrier are important hemodynamic parameters in brain physiology. Pulsed arterial spin labeling and vascular‐space occupancy techniques have been used to measure regional cerebral blood flow and CBV, respectively. However, these techniques generally ignore the effects of one hemodynamic parameter on the measurement of others. For instance, the influences of CBV changes on arterial spin labeling or the permeability effects on vascular‐space occupancy typically were not accounted for in the quantification of blood flow or volume. In the current work, the biophysical effects of CBV on pulsed arterial spin labeling and permeability on vascular‐space occupancy signals are evaluated using a general two‐compartment model. The dependence of these effects on the T₁ at various field strengths is also assessed by simulations. Results indicate that CBV has negligible to small influences on pulsed arterial spin labeling signal (<6.6% at 3 T) and permeability effects are negligible on vascular‐space occupancy signal (<0.1% at 3 T) under normal physiologic conditions. In addition, CBV effect on pulsed arterial spin labeling is further diminished at high field strengths, but residual blood contamination in vascular‐space occupancy signal may be enhanced at high fields due to the reduced difference between extra‐ and intravascular T₁ values. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Magnetization transfer enhanced vascular‐space‐occupancy (MT‐VASO) functional MRI

Vascular‐space‐occupancy (VASO) MRI is a novel technique that uses blood signal nulling to detect blood volume alterations through changes in tissue signal. VASO has relatively low signal to noise ratio (SNR) because only 10–20% of tissue signal remain at the time of blood nulling. Here, it is shown that by adding a magnetization transfer (MT) prepulse it is possible to increase SNR either by attenuating the initial tissue magnetization when the MT pulse is placed before inversion, or, accelerating the recovery process when the pulse is applied after the inversion. To test whether the MT pulse would affect the blood nulling time in VASO, MT effects in blood were measured both ex vivo in a bovine blood phantom and in vivo in human brain. Such effects were found to be sufficiently small (< 2.5%) under a saturation power ≤ 3 μT, length = 500 ms, and frequency offset ≥40 ppm to allow use of the same nulling time. Subsequently, functional MRI experiments using MT‐VASO were performed in human visual cortex at 3 Tesla. The relative signal changes in MT‐VASO were of the same magnitude as in VASO, while the contrast to noise ratio (CNR) was enhanced by 44 ± 12% and 36 ± 11% respectively. Therefore, MT‐VASO should provide a means for increasing inherently low CNR in VASO experiments while preserving the CBV sensitivity. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Implementation of vascular‐space‐occupancy MRI at 7T

Vascular‐space‐occupancy (VASO) MRI exploits the difference between blood and tissue T₁ to null blood signal and measure cerebral blood volume changes using the residual tissue signal. VASO imaging is more difficult at higher field because of sensitivity loss due to the convergence of tissue and blood T₁ values and increased contamination from blood‐oxygenation‐level‐dependent (BOLD) effects. In addition, compared to 3T, 7T MRI suffers from increased geometrical distortions, e.g., when using echo‐planar‐imaging, and from increased power deposition, the latter especially problematic for the spin‐echo‐train sequences commonly used for VASO MRI. Third, non‐steady‐state blood spin effects become substantial at 7T when only a head coil is available for radiofrequency transmit. In this study, the magnetization‐transfer‐enhanced‐VASO approach was applied to maximize tissue‐blood signal difference, which boosted signal‐to‐noise ratio by 149% ± 13% (n = 7) compared to VASO. Second, a 3D fast gradient‐echo sequence with low flip‐angle (7°) and short echo‐time (1.8 ms) was used to minimize the BOLD effect and to reduce image distortion and power deposition. Finally, a magnetization‐reset technique was combined with a motion‐sensitized‐driven‐equilibrium approach to suppress three types of non‐steady‐state spins. Our initial functional MRI results in normal human brains at 7T with this optimized VASO sequence showed better signal‐to‐noise ratio than at 3T. Magn Reson Med 69:1003–1013, 2013. © 2012 Wiley Periodicals, Inc.     

3D single‐shot VASO using a maxwell gradient compensated GRASE sequence

The vascular space occupancy (VASO) method was recently proposed as a functional MRI (fMRI) method that is capable of detecting activation‐related changes in blood volume (CBV), without the need for a blood‐pool contrast agent. In the present work we introduce a new whole‐brain VASO technique that is based on a parallel‐accelerated single‐shot 3D GRASE (gradient and spin echo) readout. The GRASE VASO sequence employs a flow‐compensated correction scheme for concomitant Maxwell gradients which is necessary to avoid smearing artifacts that may occur due to violation of the Carr–Purcell–Meiboom–Gill (CPMG) condition for off‐resonance excitation. Experiments with 6 min of visual‐motor stimulation were performed on eight subjects. At P < 0.01, average percent signal change and t‐score for visual stimulation were ?3.11% and ?8.42, respectively; activation in left and right motor cortices and supplementary motor area was detected with ?2.75% and ?6.70, respectively. Sensitivity and signal changes are comparable to those of echo‐planar imaging (EPI)‐based single‐slice VASO, as indicated by additional visual‐task experiments (?3.39% and ?6.93). The method makes it possible to perform whole‐brain cognitive activation studies based on CBV contrast. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

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.     

Bicuculline-induced brain activation in mice detected by functional magnetic resonance imaging.

Dynamic measurements of local changes in relative cerebral blood volume (CBV(rel)) during a pharmacological stimulation paradigm were performed in mice. Using magnetite nanoparticles as an intravascular contrast agent, high-resolution CBV(rel) maps were obtained. Intravenous administration of the GABA(A) antagonist bicuculline prompted increases in local CBV(rel) as assessed by MRI with a high spatial resolution of 0.2 x 0.2 mm(2) and a temporal resolution of 21 s. Signal changes occurred 20-30 s after the onset of drug infusion in the somatosensory and motor cortex, followed by other cortical and subcortical structures. The magnitudes of the CBV(rel) increases were 18% +/- 4%, 46% +/- 14%, and 67% +/- 7%, as compared to prestimulation values for the cortex, and 9% +/- 3%, 25% +/- 4%, and 36% +/- 7% for the caudate putamen for bicuculline doses of 0.6, 1.25, and 1.5 mg/kg, respectively. On-line monitoring of transcutaneous carbon dioxide tension PtcCO(2) reflecting arterial PaCO(2) did not show any alteration during the stimulation paradigm. One of five of the mice receiving the highest bicuculline dose, and three of seven receiving the intermediate dose displayed a different cortical response pattern. After a CBV(rel) increase of 40% lasting for approximately 1 min, significant CBV(rel)reductions by 80% have been observed. Subcortical structures did not display this behavior. The present study suggests that this noninvasive approach of functional MRI (fMRI) can be applied to study drug-induced brain activation by central nervous system (CNS) drugs in mice under normal and pathological situations.     

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.     

Multiple acquisitions with global inversion cycling (MAGIC): a multislice technique for vascular-space-occupancy dependent fMRI.

Recently, a new fMRI technique, termed vascular-space-occupancy (VASO), was introduced that uses T1-based blood nulling to detect cerebral blood volume (CBV) changes during brain activity. However, similar to other T1-preparation methods, this technique is hampered by the fact that there is only one zero-crossing on the relaxation curve, presently limiting its application to single-slice studies. A multislice VASO-fMRI method is presented that employs a series of nonselective 180 degrees pulses to periodically invert the magnetization and maintain it around zero, while acquiring slices in between. The effects of magnetization transfer and signal contamination by stimulated echoes are discussed. Solutions to reduce the effect of T1-signal decay as a function of slice number are provided. Phantom data show excellent agreement between experiments and numerical simulations. Multislice VASO-fMRI images of visual stimulation show effective blood nulling in all slices and appropriate functional activations in all volunteers (n=4).     

Signal-to-noise analysis of cerebral blood volume maps from dynamic NMR imaging studies

The use of cerebral blood volume (CBV) maps generated from dynamic MRI studies tracking the bolus passage of paramagnetic contrast agents strongly depends on the signal-to-noise ratio (SNR) of the maps. The authors present a semianalytic model for the noise in CBV maps and introduce analytic and Monte Carlo techniques for determining the effect of experimental parameters and processing strategies upon CBV-SNR. CBV-SNR increases as more points are used to estimate the baseline signal level. For typical injections, maps made with 10 baseline points have 34% more noise than those made with 50 baseline points. For a given peak percentage signal drop, an optimum TE can be chosen that, in general, is less than the baseline T2. However, because CBV-SNR is relatively insensitive to TE around this optimum value, choosing TE ≈ T2 does not sacrifice much SNR for typical doses of contrast agent. The TR that maximizes spin-echo CBV-SNR satisfies TR/T1 ≈ 1.26, whereas as short a TR as possible should be used to maximize gradient-echo CBV-SNR. In general, CBV-SNR is maximized for a given dose of contrast agent by selecting as short an input bolus duration as possible. For image SNR exceeding 20–30, the Γ-fitting procedure adds little extra noise compared with simple numeric integration. However, for noisier input images, as can be the case for high resolution echo-planar images, the covarying parameters of the Γ-variate fit broaden the distribution of the CBV estimate and thereby decrease CBV-SNR. The authors compared the analytic noise predicted by their model with that of actual patient data and found that the analytic model accounts for roughly 70% of the measured variability of CBV within white matter regions of interest.     

Functional MRI using steady-state arterial water labeling

Flow-sensitive functional MRI (fMRI) was performed using steady-state arterial water labeling (SS-AWL). Arterial water labeling was accomplished by flow induced adiabatic fast passage. The signal intensity of the visual cortex in arterial water labeled images decreased by ?1.4% during visual stimulation of the brain. Acquisition of arterial water unlabeled and labeled images allows measurement of relative cerebral blood flow increase during brain activation. During visual stimulation, cerebral blood flow in the visual cortex increased by 17 to 35% as measured by SS-AWL. Quantitation of brain activation in terms of a physiological parameter using SS-AWL will facilitate comparative fMRI studies under different conditions.