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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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).     

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.

     

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.     

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.     

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.     

Brain glucose utilization under high sensory activation: hypoactivation of prefrontal cortex

Brain glucose metabolism was studied, using positron emission tomography and [F-18]-2-deoxy-2-fluoro-D-glucose, in 13 healthy young adult men, at rest and under conditions of high visual and auditory stimulation with minor motor involvement. Despite high individual variations, the mean cerebral metabolic rate for glucose was highly increased during stimulation. Furthermore, the regional pattern of cerebral glucose utilization showed consistent differences between resting and activated states. Several brain areas, including temporal, motor-premotor and parieto-occipital cortices, and striatum, thalamus, and cerebellum showed a level of activation statistically comparable to that of mean gray. Significant preferential activation was found only in the visual cortex. By contrast, prefrontal and mesial cortical areas were relatively hypoactivated by the task. Inasmuch as prefrontal cortex is known to receive visual associative afferents, these observations are tentatively interpreted in terms of the "parallel" mode of information processing, along specific routes according to the environmental state.     

Determination of relative CMRO2 from CBF and BOLD changes: significant increase of oxygen consumption rate during visual stimulation.

The blood oxygenation level-dependent (BOLD) effect in functional magnetic resonance imaging depends on at least partial uncoupling between cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) changes. By measuring CBF and BOLD simultaneously, the relative change in CMRO2 can be estimated during neural activity using a reference condition obtained with known CMRO2 change. In this work, nine subjects were studied at a magnetic field of 1.5 T; each subject underwent inhalation of a 5% carbon dioxide gas mixture as a reference and two visual stimulation studies. Relative CBF and BOLD signal changes were measured simultaneously using the flow-sensitive alternating inversion recovery (FAIR) technique. During hypercapnia established by an end-tidal CO2 increase of 1.46 kPa, CBF in the visual cortex increased by 47.3 +/- 17.3% (mean +/- SD; n = 9), and deltaR2* was -0.478 +/- 0.147 sec(-1), which corresponds to BOLD signal change of 2.4 +/- 0.7% with a gradient echo time of 50 msec. During black/white visual stimulation reversing at 8 Hz, regional CBF increase in the visual cortex was 43.6 +/- 9.4% (n = 18), and deltaR2* was -0.114 +/- 0.086 sec(-1), corresponding to a BOLD signal change of 0.6 +/- 0.4%. Assuming that CMRO2 does not change during hypercapnia and that hemodynamic responses during hypercapnia and neural stimulation are similar, relative CMRO2 change was determined using BOLD biophysical models. The average CMRO2 change in the visual cortex ranged from 15.6 +/- 8.1% (n = 18) with significant cerebral blood volume (CBV) contribution to 29.6 +/- 18.8% without significant CBV contribution. A weak positive correlation between CBF and CMRO2 changes was observed, suggesting the CMRO2 increase is proportional to the CBF increase.     

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.     

Attempts to improve absolute quantification of cerebral blood flow in dynamic susceptibility contrast magnetic resonance imaging: a simplified T1-weighted steady-state cerebral blood volume approach

Background: Attempts to retrieve absolute values of cerebral blood flow (CBF) by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) have typically resulted in overestimations.

Purpose: To improve DSC-MRI CBF estimates by calibrating the DSC-MRI-based cerebral blood volume (CBV) with a corresponding T1-weighted (T1W) steady-state (ss) CBV estimate.

Material and Methods: 17 volunteers were investigated by DSC-MRI and ¹³³Xe SPECT. Steady-state CBV calculation, assuming no water exchange, was accomplished using signal values from blood and tissue, before and after contrast agent, obtained by T1W spin-echo imaging. Using steady-state and DSC-MRI CBV estimates, a calibration factor K = CBV(ss)/CBV(DSC) was obtained for each individual. Average whole-brain CBF(DSC) was calculated, and the corrected MRI-based CBF estimate was given by CBF(ss) = K×CBF(DSC).

Results: Average whole-brain SPECT CBF was 40.1±6.9 ml/min·100 g, while the corresponding uncorrected DSC-MRI-based value was 69.2±13.8 ml/min·100 g. After correction with the calibration factor, a CBF(ss) of 42.7±14.0 ml/min·100 g was obtained. The linear fit to CBF(ss)-versus-CBF(SPECT) data was close to proportionality (R = 0.52).

Conclusion: Calibration by steady-state CBV reduced the population average CBF to a reasonable level, and a modest linear correlation with the reference ¹³³Xe SPECT technique was observed. Possible explanations for the limited accuracy are, for example, large-vessel partial-volume effects, low post-contrast signal enhancement in T1W images, and water-exchange effects.