Impact of ROI definition on visual stimulation based cerebral vascular reactivity fMRI with a special focus on applications in Cerebral Amyloid Angiopathy.

Cerebral vascular reactivity quantified using BOLD fMRI in conjuncture with a visual stimulus has been proven to be a potent and early marker for cerebral amyloid angiopathy. This work investigates the influence of different post-processing methods on the outcome of such vascular reactivity measurements. Three methods for defining the region-of-interest (ROI) over which the reactivity is measured, are investigated: structural (transformed V1), functional (template based on the activation of a subset of subjects) and percentile (11.5 cm 3 most responding voxels). Evaluation is done both in a test-retest experiment in healthy volunteers (N= 12), as well as in 27 Dutch-type CAA patients and 33 age and sex matched control subjects. The results show that the 3 methods select a different subset of voxels, although all three lead to similar outcome measures in healthy subjects. However, in (severe) pathology the percentile method lead to higher reactivity measures than the other two, due to circular analysis or 'double dipping' by defining a subject-specific ROI based on the strongest responses within each subject. Furthermore, while different voxels are included in the presence of lesions, this does not necessarily result in different outcome measures. In conclusion, to avoid bias created by the method, either a structural or a functional method is recommended. Both of these methods provide similar reactivity measures, although the functional ROI appears to be less reproducible between studies, since slightly different sub-sets of voxels were found to be included. On the other hand, the functional method did include fewer lesion voxels than the structural method.