title: Pulsed arterial spin labeling perfusion imaging at 3 T: estimating the number of subjects required in common designs of clinical trials.
abstract: Pulsed arterial spin labeling (PASL) is an increasingly common technique for noninvasively measuring cerebral blood flow (CBF) and has previously been shown to have good repeatability. It is likely to find a place in clinical trials and in particular the investigation of pharmaceutical agents active in the central nervous system. We aimed to estimate the sample sizes necessary to detect regional changes in CBF in common types of clinical trial design including (a) between groups, (b) a two-period crossover and (3) within-session single dosing. Whole brain CBF data were acquired at 3 T in two independent groups of healthy volunteers at rest; one of the groups underwent a repeat scan. Using these data, we were able to estimate between-groups, between-session and within-session variability along with regional mean estimates of CBF. We assessed the number of PASL tag-control image pairs that was needed to provide stable regional estimates of CBF and variability of regional CBF across groups. Forty tag-control image pairs, which take approximately 3 min to acquire using a single inversion label delay time, were adequate for providing stable CBF estimates at the group level. Power calculations based on the variance estimates of regional CBF measurements suggest that comparatively small cohorts are adequate. For example, detecting a 15% change in CBF, depending on the region of interest, requires from 7-15 subjects per group in a crossover design, 6-10 subjects in a within-session design and 20-41 subjects in a between-groups design. Such sample sizes make feasible the use of such CBF measurements in clinical trials of drugs.
authors.affiliation: Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, CF10 3AT Cardiff, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Murphy
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Harris
authors.forename: Ana
authors.initials: A
authors.lastname: Diukova
authors.forename: C John
authors.initials: CJ
authors.lastname: Evans
authors.forename: David J
authors.initials: DJ
authors.lastname: Lythgoe
authors.forename: Fernando
authors.initials: F
authors.lastname: Zelaya
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wise
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D015203:Reproducibility of Results; D018401:Sample Size; D012680:Sensitivity and Specificity; D013113:Spin Labels
chemical_list: D013113:Spin Labels