Steady pulsed imaging and labeling scheme for noninvasive perfusion imaging

Abstract

Purpose: A steady pulsed imaging and labeling (SPIL) scheme is proposed to obtain high-resolution multislice perfusion images of mice brain using standard preclinical MRI equipment.

Theory and methods: The SPIL scheme repeats a pulsed arterial spin labeling (PASL) module together with a short mixing time to extend the temporal duration of the generated PASL bolus to the total experimental time. Multislice image acquisition takes place during the mixing times. The mixing time is also used for magnetization recovery following image acquisition. The new scheme is able to yield multislice perfusion images rapidly. The perfusion kinetic curve can be measured by a multipulsed imaging and labeling (MPIL) scheme, i.e., acquiring single-slice ASL signals before reaching steady-state in the SPIL sequence.

Results: When applying the SPIL method to normal mice, and to mice with unilateral ischemia, high-resolution multislice (five slices) CBF images could be obtained in 8 min. Perfusion data from ischemic mice showed clear CBF reductions in ischemic regions. The SPIL method was also applied to postmortem mice, showing that the method is free from magnetization transfer confounds.

Conclusion: The new SPIL scheme provides for robust measurement of CBF with multislice imaging capability in small animals.

Keywords: arterial spin labeling (ASL); cerebral blood flow (CBF); multipulsed imaging and labeling (MPIL); perfusion; pulsed arterial spin labeling (PASL); steady pulsed imaging and labeling (SPIL); un-inverted flow-sensitive alternating inversion recovery (UNFAIR).

Figure 1

Steady pulsed imaging and labeling (SPIL). (A) The SPIL sequence is composed of a series of label-transfer modules (LTMs), each containing two adiabatic inversion pulses, and followed by a mixing time (t_mix) to enable the labeled water spins to perfuse into the tissue in the image slice. During the mixing time, an image acquisition (FSE sequence) is applied. (B) Illustration of the inversion slab positions, with respect to the image slice. (C) The time diagram of the MPIL scheme. The LEM identical to the one in the SPIL sequence is repeated periodically every t_mix. Following the labeling duration, a single slice image is recorded. (D) Illustration of the inversion slab positions, with respect to the image slices, for the MPIL sequence.

Figure 2

SPIL kinetics. (A) The Arterial Input Function (AIF) and (B) corresponding perfusion signal (ΔM/M₀) for SPIL. The bolus duration of the UNFAIR LEM was assumed to be 6 s. The T₁ relaxation time of arterial blood is assumed to be 2.8 s. The labeling efficiency was set to 0.9. An effective T_1,eff =1 s and ATT = 0.1 s were used. The mixing time was set to 1 s. (C) The typical Arterial Input Function (AIF) for MPIL with the parameters used in Figure A and B. The corresponding time course of the MPIL sequence with four LTMs is plotted on the top of the figure. (D) The simulated perfusion kinetic curves for the single slice SPIL with 1, 2, and 4 LEMs, respectively. When the number of LTMs is set to one, the MPIL sequence is the UNFAIR sequence.

Figure 3

Post-mortem SPIL results. (A) Control images (M_control). Only three slices located at −3 mm, 0 mm, and 3mm from the isocenter of the magnet are shown. (B, C) Difference images (ΔM/M_control) recorded using the SPIL scheme, with slab margins of 2 mm (B) and 6 mm (C). The mixing time is 1 s, NAV=8, with five slices with a slice thickness of 1 mm, and a slice gap of 0.5 mm (total slice package 7 mm).

Figure 4

Experimental perfusion kinetic curves, with respect to total labeling time, for MPIL with one LTM, i.e., the UNFAIR sequence (A), and four LTMs (B). Data from healthy adult mouse brains. Solid lines are theoretical fitting curves. The T_1,eff = 0.85 s, ATT = 0.12 s, and a labeling efficiency α=0.8 was obtained for the fitting. The labeling duration was assumed to be 6 s.

Figure 5

Representative multi-slice perfusion maps (middle row) of a normal mouse brain acquired using the SPIL scheme. Five slices with a slice thickness of 1 mm were acquired. The mixing time was 1 s. The M_control images are shown above the perfusion images for comparison (top row). The CBF maps were calculated by assuming a labeling efficiency of 0.9, T_1a=2.8 s, and T_1,eff=0.85 s.

Figure 6

Bilateral symmetry of CBF for three brain regions in five mice: cortex (green triangle), hippocampus (red circle), and thalamus (blue diamond). Error bars represent the in-ROI standard derivations. Typical ROIs for the three brain regions are illustrated in the figure inset.

Figure 7

Typical ΔM maps from a healthy mouse brain recorded with SPIL (A) and FAIR (B) techniques. The bottom row shows quantitative CBF maps acquired with SPIL (C) and FAIR (D) techniques.

Figure 8

Representative multi-slice perfusion maps (bottom row) on postnatal mouse brain with a stroke model, acquired using SPIL. The T₂-weighted images (TE= 60 ms) are shown above the perfusion images for comparison (top row). Five slices with a slice thickness of 1 mm and a slice gap of 0.1 mm were applied.