Arterial Spin Labelling (ASL) is a non-invasive MRI technique for the quantification of tissue perfusion using freely diffusible intrinsic tracer. Measurement of regional cerebral blood flow (CBF) with ASL can be performed by different acquisition methods. The aim of this study was to compare the replicability of relative CBF acquired by single TI 3D pulsed arterial spin labelling (3D-PASL), multi-TI 3D-PASL and 2D pseudo-continuous arterial spin labelling (2D-pCASL) prior to use in clinical research.

This study was approved by the institutional review board and written consent was obtained. Ten healthy adult females (aged 20 to 37 years; average 25.1 years; median 24 years) were invited for MRI scan 1 week apart with a follow up scan done 2 to 3 months later. All individuals had normal body mass index and were scanned on a 3T MR scanner (MAGNETOM Skyra, Siemens Healthcare) with a 32-channel phased-array receive-only head coil. High-resolution anatomical images were acquired using sagittal 3D MPRAGE and coronal T2-weighted 3D SPACE. All individuals were scanned with single and multi-TI 3D-PASL ASL using FAIR labelling with Q2TIPS and 2D-pCASL with PICORE QUIPPS II.

ASL images were post-processed by FMRIB Software Library (FSL, www.fmrib.ox.ac.uk/fsl) for motion correction and smoothing. Anatomical whole-brain mask was created for each subject to linearly and non-linearly register MPRAGE to standard space (MNI152 template). Relative CBF image was registered to the MNI152 template through linear and non-linear registration of the M0 image to MPRAGE using FSL. Custom Matlab scripts (Mathworks, MA, USA) were used to calculate the mean CBF in the 59 areas of the cerebral hemispheres based on Harvard-Oxford atlas, including whole-brain CBF value. The cerebellum was excluded as 2D-pCASL had limited coverage. Calculated CBF values were compared with age-matched reference range values published for adults as there is known variation of CBF with age. The statistical analysis on IBM SPSS Statistics version 19 included one-way analysis of variance (ANOVA - Bonferroni post hoc test) to compare the CBF values acquired by different ASL acquisition methods. To check replicability and reliability of the ASL techniques, the first set of ASL scans were compared with those done 1 week later and follow-up scans done 2 to 3 months later. The significance level was set as p≤0.05.

The mean whole brain CBF values obtained with single TI 3D-PASL, multi-TI 3D-PASL and 2D-pCASL at baseline, 1 week later and 2 to 3 months later are presented in Table 1 to 2 and Figures 1 to 3.

Correlation coefficient of all scans at baseline with those done at 1 week is 0.77 while correlation coefficient of all scans done at baseline with those done at 2 to 3 months is 0.62 and correlation coefficient for scans at 1 week with those done at 2 to 3 months is 0.55.

Correlation coefficient between single-TI and multi-TI 3D-PASL is 0.53, between single-TI 3D-PASL and 2D-pCASL is 0.52, between multi-TI 3D-PASL and 2D-pCASL is 0.31.

There was no statistical difference between baseline scans and those done 1 week later as well as in those done 2 to 3 months later (all p values>0.2).

One-way ANOVA statistical analysis also showed no significant difference in the CBF values obtained by single-TI 3D-PASL, multi-TI 3D-PASL and 2D-pCASL (all p values>0.2).

In our study, CBF measurements of healthy subjects using single TI 3D-PASL is 56.02±6.66 mL/100g/min, using multi-TI 3D-PASL is 51.74±5.58 mL/100g/min and 51.40±7.05 mL/100g/min using 2D-pCASL. The published literature shows that the normal range of 3D-PASL CBF for adults is between 36.2-63.3 mL/100g/min ^{1, 2} and 2D-pCASL is between 40-100 mL/100g/min ³. Our values agree with the published normal range of CBF values in adults. Scans repeated 1 week and 2 to 3 months later demonstrated good replicability of all 3 ASL techniques.

3D ASL offers better spatial localization of areas of interest compared to 2D-pCASL and is able to provide whole brain coverage. Multi-TI 3D-PASL enables detailed quantification of cerebral perfusion across different time points as compared to single-TI and potentially may be useful in patients with altered perfusion such as vascular stenosis when the optimal TI may be longer than usual.

This study demonstrates that ASL is a promising non-invasive technique for quantitation of cerebral perfusion with good replicability.