Cerebrovascular reactivity in the developing brain: influence of sex and maturation

The brain is energetically expensive and maintenance of normal cerebral metabolism is critically dependent on the regulation of cerebral blood flow (CBF). In addition to buffering changes in blood pressure and meeting local metabolic needs, the cerebrovasculature has an exquisite sensitivity to even small changes in the partial pressure of arterial CO2 (PaCO2 ). This response is termed cerebrovascular reactivity (CVR) and reflects the functional capacity of the cerebrovasculature to dilate and constrict, for example in response to flucations in PaCO2 (Ainslie & Duffin, 2009). When used in clinical settings, CVR has been used to evaluate cerebrovascular function in at-risk populations, such as in stroke and hypertensive patients (Ainslie & Duffin, 2009). A multitude of studies have investigated CVR in adults; however, studies investigating CBF and CVR in children are scarce. Maturation, unique developmental trajectories for males and females, and high cerebral metabolic demands greatly affect the regulation of CBF in children. As such, data on CBF and CVR are crucial in the pediatric population for the understanding of overall brain development and function throughout the formative years. A recent Journal of Physiology article by Leung et al. (2016) utilized powerful and quantitative techniques – arterial spin labelling (ASL) and blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) – to characterize the developmental trajectories of CBF and CVR in grey (GM) and white matter (WM) in healthy children and young adults. Accordingly, this investigation highlighted the importance of accounting for age-related cerebrovascular changes when assessing developmental changes in CBF and CVR. A cohort of 17 males and 17 females (aged 9–30 years) underwent a CVR challenge using a novel prospective end-tidal forcing system capable of targeting specific end-tidal O2 and CO2 levels (PETO2 and PETCO2 , respectively) on a breath-by-breath basis. This challenge consisted of four blocks of alternating 60 s of normoxic (PETO2 = 100 mHg) isocapnia (PETCO2 = 40 mmHg) and 45 s of normoxic (PETO2 = 100 mHg) hypercapnia (PETCO2 = 45 mmHg); the protocol was terminated by a 60 s period of normoxic isocapnia resulting in a total time of 8 min. Together with the CVR challenge, imaging data were collected for 8 min with a single-shot T2∗-weighted echo-planar imaging sequence. T1-weighted anatomical images with isotropic 1.0 mm voxel size were collected for co-registration and segmentation of GM and WM regions. Moreover, a pulsed ASL sequence was utilized to obtain baseline CBF data. The CVR values were created by temporally aligning PETCO2 waveform and the corresponding BOLD MRI datasets, followed by a resampling of the PETCO2 data. A linear regression between the two resulted in CVR values for each voxel on the CVR map represented as % MR signal mmHg (CO2). The CVR and CBF maps were then coregistered in order to calculate the global mean reactivity and mean CBF in the GM and WM for each subject. Primary results from this investigation indicate that CVR in GM and WM increases ( 55 % in GM, 51 % in WM) in children aged 9–14.7 years and decreases ( 27 % in GM, 26 % in