Fourier modeling of the BOLD response to a breath - hold task : 2 Optimization and

10 Article history: 11 Received 14 October 2015 12 Accepted 12 February 2016 13 Available online xxxx 145678 19 Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to adjust their caliber in order tomaintain a 20 steady supply of brain perfusion, and itmay provide a sensitive disease biomarker.Measurement of the blood ox21 ygen level dependent (BOLD) response to a hypercapnia-inducing breath-hold (BH) task has been frequently 22 used to map CVR noninvasively using functional magnetic resonance imaging (fMRI). However, the best model23 ing approach for the accurate quantification of CVRmaps remains an open issue. Here, we compare and optimize 24 Fouriermodels of the BOLD response to a BH taskwith a preparatory inspiration, and assess the test–retest repro25 ducibility of the associated CVR measurements, in a group of 10 healthy volunteers studied over two fMRI ses26 sions. Linear combinations of sine–cosine pairs at the BH task frequency and its successive harmonics were 27 added sequentially in a nested models approach, and were compared in terms of the adjusted coefficient of de28 termination and corresponding variance explained (VE) of the BOLD signal, as well as the number of voxels 29 exhibiting significant BOLD responses, the estimated CVR values, and their test–retest reproducibility. The 30 brain average VE increased significantly with the Fourier model order, up to the 3rd order. However, the number 31 of responsive voxels increased significantly only up to the 2nd order, and started to decrease from the 3rd order 32 onwards. Moreover, no significant relative underestimation of CVR values was observed beyond the 2nd order. 33 Hence, the 2nd order model was concluded to be the optimal choice for the studied paradigm. This model also 34 yielded the best test–retest reproducibility results, with intra-subject coefficients of variation of 12 and 16% 35 and an intra-class correlation coefficient of 0.74. In conclusion, our results indicate that a Fourier series set 36 consisting of a sine–cosine pair at the BH task frequency and its two harmonics is a suitable model for BOLD37 fMRI CVR measurements based on a BH task with preparatory inspiration, yielding robust estimates of this im38 portant physiological parameter. 39 © 2016 Published by Elsevier Inc. 40