Absolute arterial cerebral blood volume quantification using inflow vascular-space-occupancy with dynamic subtraction magnetic resonance imaging

Abstract

In patients with steno-occlusive disease of the internal carotid artery (ICA), cerebral blood flow may be maintained by autoregulatory increases in arterial cerebral blood volume (aCBV). Therefore, characterizing aCBV may be useful for understanding hemodynamic compensation strategies. A new 'inflow vascular-space-occupancy with dynamic subtraction (iVASO-DS)' MRI approach is presented where aCBV (mL blood/100 mL parenchyma) is quantified without contrast agents using the difference between images with and without inflowing blood water signal. The iVASO-DS contrast mechanism is investigated (3.0 T, spatial resolution=2.4 x 2.4 x 5 mm(3)) in healthy volunteers (n=8; age=29+/-5 years), and patients with mild (n=7; age=72+/-8 years) and severe (n=10; age=73+/-8 years) ICA stenoses. aCBV was quantified in right and left hemispheres in controls, and, alongside industry standard dynamic susceptibility contrast (DSC), contralateral (cont), and ipsilateral (ips) to maximum stenosis in patients. iVASO contrast significantly correlated (R=0.67, P<0.01) with DSC-CBV after accounting for transit time discrepancies. Gray matter aCBV (mL/100 mL) was 1.60+/-0.10 (right) versus 1.61+/-0.20 (left) in controls, 1.59+/-0.38 (cont) and 1.65+/-0.37 (ips) in mild stenosis patients, and 1.72+/-0.18 (cont) and 1.58+/-0.20 (ips) in severe stenosis patients. aCBV was asymmetric (P<0.01) in 41% of patients whereas no asymmetry was found in any control. The potential of iVASO-DS for autoregulation studies is discussed in the context of existing hemodynamic literature.

Figure 1

(A) The inflow VASO with dynamic subtraction (iVASO-DS) pulse sequence. In the control preparation, two slice selective adiabatic inversion pulses are sequentially applied, followed by an inversion time (TI), and finally a 2D single-shot echo planar image gradient echo acquisition. In the control preparation, both blood and tissue magnetization are nonzero. After the control preparation, a null preparation is applied in which a nonselective adiabatic inversion is immediately followed by a slice-selective inversion (tissue ‘flip back'). The same TI is allowed, which corresponds to the time for the blood water magnetization to recover to zero. Control—null yields a CBVw map. (B) A snapshot in time of the tissue (gray) and inflowing blood (black) magnetization. This simulation has been performed for a representative TR/TI=1,492/914 ms. Note that tissue magnetization is only influenced by the readout excitation pulses, whereas the inflowing blood water magnetization is only influenced by an inversion pulse in alternate TRs.

Figure 2

Methodological study. Simulations demonstrating the effect of capillary arrival time (τ) and aCBV on iVASO-DS MR signal. (A) iVASO-DS signal versus τ for aCBV=1.5 mL/100 mL and TI=989 ms. MR signal is large for short τ but reduces at long τ. (B) iVASO-DS signal versus aCBV for three possible τ times. The simulations assume TI=989 ms. The signal is linear with aCBV, suggesting that an iVASO-DS image alone is proportional to aCBV. (C) Left to right: a representative control, null, difference, time-of-flight, and gray matter mask obtained from the methodological experiment. Voxels within the GM mask were used for aCBV quantification. (D) iVASO-DS CBVw images for varying TI (range 389 to 1,064 ms). The TR was adjusted to keep steady-state blood water nulled (see Table 1). (E) Gray matter aCBV as a function of TI. The gray data points represent all GM voxels and the line is the best fit line to these points. The measured aCBV is approximately linear with TI for the approximate range of capillary arrival times. The black data points show the measured aCBV for voxels with high SNR only. (F) The SNR of the iVASO-DS difference image as a function of TI.

Figure 3

Representative iVASO difference images and DSC-computed CBV, MTT, and CBF maps for three representative patients: PT8 (A), PT16 (B), and PT6 (C); see Table 3 for patient details and symptoms. Contralateral:ipsilateral (to maximum ICA stenosis burden) iVASO ratios are plotted against DSC-CBV ratios before (D) and after (E) MTT correction. Ipsilateral versus contralateral CBF (F) and iVASO aCBV (G) reveal a higher hemispheric correlation for CBF (R=0.88) compared with iVASO-measured aCBV (R=0.77) in patients.

Figure 4

(A) Histogram of all GM aCBV values for the healthy control group. (B) Box plots of iVASO aCBV for the healthy control (left), mild stenosis (middle), and severe stenosis (right) volunteers. Gray is right in controls and contralateral to maximum stenosis burden in patients. White is left in controls and ipsilateral to maximum stenosis burden in patients. The central black line is the group median, the edges of the boxes are the 25th and 75th percentiles, the whiskers extend to the most extreme data points and any statistically significant outliers are plotted as black crosses.