Comparing two MRI methods to assess fundamental sex differences in resting cerebral blood flow

Abstract

Background: Cerebral blood flow (CBF) is a critical measurement for understanding healthy brain physiology prior to aging or neurologic diseases. Patterns of stroke and neurologic pathologies are often sex-specific. Therefore, it is important to understand basic sex differences in CBF, which are often associated with poor brain outcomes. Furthermore, prior literature examining sex differences in CBF is confounded by age, comorbidities, medications, lack of control of menstrual cycle and/or hormonal contraceptive use, and methodological discrepancies. The objective of this study was to compare two different magnetic resonance imaging (MRI) methods of quantifying CBF in young adults while controlling for the aforementioned confounding factors. We hypothesized that females would display higher CBF than males, and that there would be a high reliability between Arterial Spin Labeling (ASL) and 4D Flow MRI. Methods: 30 males and 26 females (23 ± 4yr) were studied on a single MRI (3T) visit. Subjects were fasted 8 hours and withheld caffeine, exercise, and NSAIDs for at least 24 hours. Females were not taking hormonal contraception and were studied on days 1-7 of the menstrual cycle. Microvascular CBF (mL/100g/min) was assessed via pseudo-continuous ASL (pcASL) while 4D Flow MRI acquired with Phase Contrast Vastly undersampled Isotropic Projection Reconstruction (PC VIPR) yielded macrovascular flow via the larger cerebral arteries, summing the internal carotid arteries and basilar artery for total CBF (mL/min). A T1-weighted MRI scan was used to provide brain volumes, allowing CBF from PC VIPR to be normalized and compared to ASL (mL/100g/min). The scans were taken consecutively, with subjects breathing normoxic gas while hemodynamics and end tidal CO2 were monitored. Regression analysis was used to determine reliability of two measures to test a sex difference in CBF. Results: Linear regression analysis demonstrated reliability between measurements of resting CBF via ASL and PC VIPR (p<0.001, R2=0.621). However, ASL measured significantly higher blood flows than PC VIPR in females (63.40 ± 8.55 vs. 56.47 ± 8.48 mL/100g/min, p<0.001) while male subjects had similar flows measured by both methods (45.75 ± 9.39 vs. 46.69 ± 8.19 mL/100g/min, p=0.464). Females displayed an increase in resting CBF compared to males, being 27.8% and 17.3% higher in the ASL and PC VIPR flow measurements (both p<0.001), respectively. Conclusions: These results demonstrate that ASL and PC VIPR CBF display a strong correlation, and that females have greater resting CBF compared to males that is detected by both MRI methods of quantification. However, ASL resulted in greater flow measurements in females, resulting in larger differences being observed (27.8% versus 17.3%). This discrepancy in CBF quantification warrants further investigation to determine the optimal mode of CBF measurement and comparison. Funding by NIH (HL150361). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.