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.     

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.     

Theoretical and experimental investigation of the VASO contrast mechanism.

Vascular space occupancy (VASO)-dependent functional MRI (fMRI) is a blood-nulling technique capable of generating microvascular cerebral blood volume (CBV)-weighted images. It is shown that at high magnetic field (3.0T) and high spatial resolution (1.89 x 1.89 x 3 mm(3)), the VASO signal changes are too large (6-7%) to originate from CBV effects alone. Additional contributions are investigated theoretically and experimentally as a function of MRI parameters (TR and TE), as well as the signal-to-noise ratio, (SNR) and spatial resolution. First, it is found that an arterial spin labeling (ASL) contribution causes large negative VASO signal changes at short TR. Second, even at high fMRI spatial resolution, CSF volume contributions (7-13%) cause VASO signal changes to become more negative, most noticeably at long TR and TE. Third, white matter (WM) effects reduce signal changes at lower spatial resolution. The VASO technique has been tested using different stimulus paradigms and field strengths (1-3), giving results consistent with comparable tasks investigated using BOLD and cerebral blood flow (CBF)-based techniques. Finally, simulations show that a mixture of fresh and steady-state blood may significantly alter signal changes at short TR (< or =3 s), permitting larger VASO signal changes than expected under pure steady-state conditions. Thus, many competing effects contribute to VASO contrast and care should be taken during interpretation.     

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.     

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.     

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).     

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.     

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.     

Vascular filters of functional MRI: spatial localization using BOLD and CBV contrast.

The spatial distributions of functional activation of rat somatosensory cortex by forepaw stimulation were quantitatively compared using blood oxygen level dependent (BOLD) signal and signal weighted by cerebral blood volume (CBV). The BOLD contrast to noise (CNR) distribution showed a significant dorsal shift with respect to the CBV method at fields strengths of 2 T (0.69 +/- 0.09 mm) and 4.7 T (0.44 +/- 0.15 mm). These shifts were attributed to the gradient of resting state blood volume across somatosensory cortex and the different CNR characteristics of the two image methods. The underlying principles suggest that the CBV method has a more uniform sensitivity to percent changes in functional indicators (blood volume or deoxygenated hemoglobin) across regions of variable resting state CBV. Magn Reson Med 42:591-598, 1999.     

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.     

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.     

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.     

Comparison of TCA and ICA techniques in fMRI data processing

PURPOSE: To make a quantitative comparison of temporal cluster analysis (TCA) and independent component analysis (ICA) techniques in detecting brain activation by using simulated data and in vivo event-related functional MRI (fMRI) experiments. MATERIALS AND METHODS: A single-slice MRI image was replicated 150 times to simulate an fMRI time series. An event-related brain activation pattern with five different levels of intensity and Gaussian noise was superimposed on these images. Maximum contrast-to-noise ratio (CNR) of the signal change ranged from 1.0 to 2.0 by 0.25 increments. In vivo visual stimulation fMRI experiments were performed on a 1.9 T magnet. Six human volunteers participated in this study. All imaging data were analyzed using both TCA and ICA methods. RESULTS: Both simulated and in vivo data have shown that no statistically significant difference exists in the activation areas detected by both ICA and TCA techniques when CNR of fMRI signal is larger than 1.75. CONCLUSION: TCA and ICA techniques are comparable in generating functional brain maps in event-related fMRI experiments. Although ICA has richer features in exploring the spatial and temporal information of the functional images, the TCA method has advantages in its computational efficiency, repeatability, and readiness to average data from group subjects     

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.     

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.     

Spatial correlations of laminar BOLD and CBV responses to rat whisker stimulation with neuronal activity localized by Fos expression.

The spatial relationship between a measured fMRI signal and its underlying neuronal activity remains unclear. One obstacle is the localization of neuronal activity; another is the spatial resolution of fMRI. In the present study, high-resolution BOLD and CBV fMRI experiments (voxel size: 156 x 156 x 2000 microm3) were conducted in the rat whisker barrel cortex at 3 T; neuronal activity across cortical layers was mapped using the Fos expression technique. Results show that BOLD response is weighted by blood volume and that pixels with high BOLD response can be located at the cortical surface or in deep layers, depending on local vasculature. In contrast to BOLD response, the pixels with high CBV response were consistently clustered in the deep cortical layers. Percentage-CBV change in cortical layers IV-V was 7.3 +/- 1.5%, which was significantly higher than in layers I-III (4.1 +/- 0.9%) and VI (4.3 +/- 0.7%) (mean +/- SEM). The laminar distribution of CBV response correlates well with neuronal activity localized by Fos expression. We conclude that neuronal activity can be inferred from CBV fMRI data with high spatial accuracy. The data indicate that both intracolumn functional connectivity and neurovascular coupling can be studied using CBV fMRI.     

Spin-echo MRI underestimates functional changes in microvascular cerebral blood plasma volume using exogenous contrast agent.

While most functional MRI studies using exogenous contrast agent employ gradient-echo (GE) signal, spin echo (SE) imaging would represent an attractive alternative if its detection power were more comparable with GE imaging. This study demonstrates that SE methods systematically underestimate functional changes in microvascular cerebral blood plasma volume (CBV), so that SE detection power in brain tissue cannot match that provided by GE signal. Empirically, the in vivo response of SE-CBV was about 40% smaller than that of GE-CBV in rat brain at low basal values of CBV, a result that is consistent with physics predictions under the simplifying assumption of uniform vessel dilation. However, increasing values of basal CBV were associated with monotonically increasing mean vessel sizes and monotonically decreasing GE to SE ratios of functional changes in CBV (fCBV). This result suggests the presence of large but weakly reactive conduit vessels at high basal values of CBV. Hence, we conclude that GE imaging is the method of choice for functional MRI (fMRI) using exogenous contrast agent in most cases, although SE methods may represent a more spatially linear representation of underlying neural activity that becomes most apparent in regions with high basal CBV, such as the cortical surface.     

Vascular space occupancy (VASO) cerebral blood volume‐weighted MRI identifies hemodynamic impairment in patients with carotid artery disease

Purpose

To assess the role of vascular space occupancy (VASO) magnetic resonance imaging (MRI), a noninvasive cerebral blood volume (CBV)‐weighted technique, for evaluating CBV reactivity in patients with internal carotid artery (ICA) stenosis.

Materials and Methods

VASO reactivity, defined as a signal change in response to hypercapnic stimulus (4‐second exhale, 14‐second breath‐hold), was measured in the left and right ICA flow territories in patients (n = 10) with varying degrees of unilateral and bilateral ICA stenosis and in healthy volunteers (n = 10).

Results

Percent VASO reactivity was more negative (P < 0.01) bilaterally in patients (ipsilateral: ?3.6 ± 1.5%; contralateral: ?3.4 ± 1.2%) compared with age‐matched controls (left: ?1.9 ± 0.6%; right: ?1.9 ± 0.8%). Owing to the nature of the VASO contrast mechanism, this more negative VASO reactivity was attributed to autoregulatory CBV effects in patients. A postbreath‐hold overshoot, which was absent in healthy volunteers, was observed unilaterally in a subset of patients.

Conclusion

More negative VASO reactivity was observed in patients with ICA stenosis and may be a marker of autoregulatory effects. Furthermore, the postbreath‐hold overshoot observed in patients is consistent with compensatory microvascular vasoconstriction and may be a marker of hemodynamic impairment. Based on the results of this feasibility study, VASO should be useful for identifying CBV adjustments in patients with steno‐occlusive disease of the ICA. J. Magn. Reson. Imaging 2009;29:718–724. © 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.     

BOLD and CBV-weighted functional magnetic resonance imaging of the rat somatosensory system.

A multislice spin echo EPI sequence was used to obtain functional MR images of the entire rat brain with blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) contrast at 11.7 T. Maps of activation incidence were created by warping each image to the Paxinos rat brain atlas and marking the extent of the activated area. Incidence maps for BOLD and CBV were similar, but activation in draining veins was more prominent in the BOLD images than in the CBV images. Cerebellar activation was observed along the surface in BOLD images, but in deeper regions in the CBV images. Both effects may be explained by increased signal dropout and distortion in the EPI images after administration of the ferumoxtran-10 contrast agent for CBV fMRI. CBV-weighted incidence maps were also created for 10, 20, and 30 mg Fe/kg doses of ferumoxtran-10. The magnitude of the average percentage change during stimulation increased from 4.9% with the 10 mg Fe/kg dose to 8.7% with the 30-mg Fe/kg dose. Incidence of activation followed a similar trend.