A novel method of quantifying hemodynamic delays to improve hemodynamic response, and CVR estimates in CO2 challenge fMRI

Elevated carbon dioxide (CO2) in breathing air is widely used as a vasoactive stimulus to assess cerebrovascular functions under hypercapnia (i.e., “stress test” for the brain). Blood-oxygen-level-dependent (BOLD) is a contrast mechanism used in functional magnetic resonance imaging (fMRI). BOLD is used to study CO2-induced cerebrovascular reactivity (CVR), which is defined as the voxel-wise percentage BOLD signal change per mmHg change in the arterial partial pressure of CO2 (PaCO2). Besides the CVR, two additional important parameters reflecting the cerebrovascular functions are the arrival time of arterial CO2 at each voxel, and the waveform of the local BOLD signal. In this study, we developed a novel analytical method to accurately calculate the arrival time of elevated CO2 at each voxel using the systemic low frequency oscillations (sLFO: 0.01-0.1 Hz) extracted from the CO2 challenge data. In addition, 26 candidate hemodynamic response functions (HRF) were used to quantitatively describe the temporal brain reactions to a CO2 stimulus. We demonstrated that our approach improved the traditional method by allowing us to accurately map three perfusion-related parameters: the relative arrival time of blood, the hemodynamic response function, and CVR during a CO2 challenge.

0011 The Influence of Obstructive Sleep Apnea Severity and Sex on Cerebral Perfusion

Introduction Obstructive Sleep Apnea (OSA) has been shown to initiate a pathological cascade negatively affecting the cardiovascular system, including cerebral circulation. There is limited data on OSA effects on regional brain function, though reduced global cerebral blood flow (CBF) has been observed among patients with OSA. However, there are few precise assessments. We hypothesized that regional CBF values are altered in OSA, and that sex influences the hypothesized relationship. Methods Participants from the NYU Center for Brain Health cohort (n=68; 57.4% female; mean age=66.32±6.84), representing cognitively healthy volunteers with OSA (AHI4% > 5/hr) and without, from several NIA-supported studies, completed evaluations including clinical, structural & functional high-resolution arterial spin labeling 3 tesla MRI scans. Hippocampal and temporal cortex CBF was assessed at baseline and after CO2 challenge using a rebreathing protocol. Analyses were completed using one-way ANCOVA controlling for age and BMI. Results More men had OSA (82.8% vs 56.4%). Men without OSA showed a larger change in CBF after challenge in left (t=2.6, p=0.014) and right (t=2.4, p=0.021) hippocampus. Although the main analyses by severity level only boarded significance, pairwise comparisons indicated men with severe OSA (AHI4%>30/hr) exhibited a larger change in CBF after challenge in the hippocampus overall compared to those with mild OSA (AHI4%5–15/hr; p=0.015) and without OSA (p=0.017). Women with severe OSA showed a reduced change in CBF after challenge in the right hippocampus compared to those with mild (p=0.016), moderate (AHI4%16–29/hr; p=0.008), and without OSA (p=0.015). Conclusion This study suggests a possible differential effect of OSA severity and sex on regional CBF in response to a CO2 challenge, specifically in the hippocampus. Further studies will examine cognitive consequences of these sex-specific hippocampal perfusion abnormalities in OSA. Support NIH/NIA (1R01HL118624) Osorio, RS 07/01/13-04/30/17 Sleep Disordered Breathing in normal elderly and risk for Alzheimer’s disease (AD).NIH/NIA (R01AG056031S1) Osorio, RS 8/01/2019-7/31/2020 Sleep Aging and Risk for Alzheimer’s disease - Research Supplement to Promote Diversity in Health-Related Research

Brain Functional Connectivity Correlates of Response in the 7.5% CO2 Inhalational Model of Generalized Anxiety Disorder: A Pilot Study

Background The 7.5% CO2 inhalational model can be used to explore potential treatments for generalized anxiety disorder. However, it is unknown how inter-individual variability in the functional architecture of negative affective valence systems might relate to anxiogenic response in this model. Methods A total of 13 healthy volunteers underwent functional magnetic resonance imaging during a passive emotional face perception task. We explored task-evoked functional connectivity in the potential threat system through generalized psychophysiological interaction analysis. Within 7 days, these participants underwent prolonged 7.5% CO2 inhalation, and results from the generalized psychophysiological interaction analysis were correlated with CO2 outcome measures. Results Functional connectivity between ventromedial prefrontal cortex and right amygdala positively correlated with heart rate and subjective anxiety, while connectivity between midcingulate cortex and left amygdala negatively correlated with anxiety during CO2 challenge. Conclusions Response to CO2 challenge correlated with task-evoked functional connectivity in the potential threat system. Further studies should assess whether this translates into clinical populations.