title: Fourier modeling of the BOLD response to a breath-hold task: Optimization and reproducibility.
abstract: Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to adjust their caliber in order to maintain a steady supply of brain perfusion, and it may provide a sensitive disease biomarker. Measurement of the blood oxygen level dependent (BOLD) response to a hypercapnia-inducing breath-hold (BH) task has been frequently used to map CVR noninvasively using functional magnetic resonance imaging (fMRI). However, the best modeling approach for the accurate quantification of CVR maps remains an open issue. Here, we compare and optimize Fourier models of the BOLD response to a BH task with a preparatory inspiration, and assess the test-retest reproducibility of the associated CVR measurements, in a group of 10 healthy volunteers studied over two fMRI sessions. Linear combinations of sine-cosine pairs at the BH task frequency and its successive harmonics were added sequentially in a nested models approach, and were compared in terms of the adjusted coefficient of determination and corresponding variance explained (VE) of the BOLD signal, as well as the number of voxels exhibiting significant BOLD responses, the estimated CVR values, and their test-retest reproducibility. The brain average VE increased significantly with the Fourier model order, up to the 3rd order. However, the number of responsive voxels increased significantly only up to the 2nd order, and started to decrease from the 3rd order onwards. Moreover, no significant relative underestimation of CVR values was observed beyond the 2nd order. Hence, the 2nd order model was concluded to be the optimal choice for the studied paradigm. This model also yielded the best test-retest reproducibility results, with intra-subject coefficients of variation of 12 and 16% and an intra-class correlation coefficient of 0.74. In conclusion, our results indicate that a Fourier series set consisting of a sine-cosine pair at the BH task frequency and its two harmonics is a suitable model for BOLD-fMRI CVR measurements based on a BH task with preparatory inspiration, yielding robust estimates of this important physiological parameter.
authors.affiliation: Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal. Electronic address: joanasequeirapinto@tecnico.ulisboa.pt.
authors.forename: Joana
authors.initials: J
authors.lastname: Pinto
authors.affiliation: Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal; Biomedical Imaging Research Center, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: João
authors.initials: J
authors.lastname: Jorge
authors.affiliation: Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal; Healthcare Sector, Siemens, S.A., Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Sousa
authors.affiliation: Imaging Department, Hospital da Luz, Lisbon, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Vilela
authors.affiliation: Institute for Systems and Robotics, Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Figueiredo
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D062485:Breath Holding; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003198:Computer Simulation; D005260:Female; D005583:Fourier Analysis; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D008955:Models, Cardiovascular; D008959:Models, Neurological; D015233:Models, Statistical; D010092:Oximetry / Q000379:methods; D010100:Oxygen / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D010100:Oxygen
keywords: BOLD; Breath holding; CVR; Hypercapnia; Modeling; Reproducibility