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.     

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.     

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.     

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.     

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 (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.

     

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.     

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.     

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.     

Simultaneous measurement of cerebral blood flow and transit time with turbo dynamic arterial spin labeling (Turbo-DASL): application to functional studies

A turbo dynamic arterial spin labeling method (Turbo-DASL) was developed to simultaneously measure cerebral blood flow (CBF) and blood transit time with high temporal resolution. With Turbo-DASL, images were repeatedly acquired with a spiral readout after small-angle excitations during pseudocontinuous arterial spin labeling and control periods. Turbo-DASL experiments at 9.4 T without and with diffusion gradients were performed on rats anesthetized with isoflurane or α-chloralose. We determined blood transit times from carotid arteries to cortical arterial vessels (TT(a) ) from data obtained without diffusion gradients and to capillaries (TT(c) ) from data obtained with diffusion gradients. Cerebral arterial blood volume (CBV(a) ) was also calculated. At the baseline condition, both CBF and CBV(a) in the somatosensory cortical area were 40-50% less in rats with α-chloralose than in rats with isoflurane, while TT(a) and TT(c) were similar for both anesthetics. Absolute CBF and CBV(a) were positively correlated, while CBF and TT(c) were slightly negatively correlated. During forepaw stimulation, CBF increase was 15 ± 3% (n = 7) vs. 60 ± 7% (n = 5), and CBV(a) increase was 19 ± 9% vs. 46 ± 17% under isoflurane vs. α-chloralose anesthesia, respectively; CBF vs. CBV(a) changes were highly correlated. However, TT(a) and TT(c) were not significantly changed during stimulation. Our results support that arterial CBV increase plays a major role in functional CBF changes.     

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.     

Influence of the compliance of the neck arteries and veins on the measurement of intracranial volume change by phase‐contrast MRI

Purpose

To assess the influence of arterial and venous vascular compliances in the neck region on the measurement of the change in intracranial volume during the cardiac cycle.

Materials and Methods

Arterial and venous blood flows were imaged by MRI phase contrast at two different locations, one close to the skull base (upper) and one 2–3 cm lower, around C3 level (lower). Maximal intracranial volume change (ICVC) measurements were derived from the momentary difference between the arterial inflow and venous outflow rates at the upper and lower locations separately to assess the influence of the compliances of the vessel segments bounded by the two different imaging locations. Imaging location for the craniospinal cerebrospinal fluid flow was a constant variable in this experiment.

Results

The systolic ICVC obtained using the lower location was consistently larger than when using the upper location. Comparison between arterial and venous flow dynamics revealed a much larger changes in flow dynamic and lumen areas in the veins compared with the arteries, which explain the large venous influence on the intracranial volume change measurement.

Conclusion

Arterial inflow and venous outflow should be sampled at a level close to the skull base (C1–C2) to minimize the influence of the compliance of arteries and the collapsibility of veins for a reliable measurement of ICVC. J. Magn. Reson. Imaging 2009;30:878–883. © 2009 Wiley‐Liss, Inc.