The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test-retest study

Abstract

Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed "The QUASAR reproducibility study". Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87+/-0.95 mm and rotations of 1.56+/-0.66 degrees . Mean gray matter CBF was 47.4+/-7.5 [ml/100 g/min] with a between-subject standard variation SD(b)=5.5 [ml/100 g/min] and a within-subject standard deviation SD(w)=4.7 [ml/100 g/min]. The corresponding repeatability was 13.0 [ml/100 g/min] and was found to be within the range of previous studies.

Figure 1

a) Error distributions for the displacement from the centre-of-mass of the image intensities in left-right (L-R), anterior-posterior (A-P) and foot-head (F-H) directions. b) Distribution of rotation errors around the image reference point. Bin-size for a & b = 0.25 [mm] & [degree] c) The axis of rotation in L-R, A-P and F-H directions. In green, red and blue are depicted the axis of rotation for MPRAGE 1-2, 1-3 and 2-3 registrations respectively. Notice the higher density of rotations around the L-R direction. d) Typical location of the registration reference point (centre-of-mass of the image intensity) around which the translation and rotation are defined.

Figure 2

CBF maps from three different subjects at three different sites. The upper row is from session 1 and the lower row is from session 2. Note the good match of location between the two scan sessions, a direct result of using automatic planning.

Figure 3

Perfusion maps registered to MNI space (N=275, 960 datasets). The upper row shows the CBF. The middle row shows arterial blood volume, where larger blood volumes can be seen corresponding to the location of feeding arteries. Finally in the lower row, the arterial transit time maps are shown, showing prolonged transit times in the regions between the perfusion territories of the anterior-, middle- and posterior cerebral arteries.

Figure 4

The mean gray matter CBF from all sites (N=28) are plotted in a) for all 4 ASL scan. In blue the values from within session 1 and in red from within session 2. In b) all the gray matter CBF test-retest values (N=191, 764 datasets) obtained within session 1 (blue), session 2 (green) and between sessions (red). c) shows the CBF difference versus mean for the same data. Dotted lines are 95% confidence interval and the solid lines are the mean difference. Note the narrower confidence interval within session 2 (no subject repositioning). compared to within session 1 (subject repositioning) and compared to between sessions (repositioning + physiological variation).