Menstrual hormone fluctuations matter for neurofluid imaging: BOLD-CSF coupling links to estradiol
Poster No:
2107
Submission Type:
Abstract Submission
Authors:
Merel van der Thiel1, Noa van der Knaap1, Brendan Williams2, Joana Pinto3, Laura Lewis4
Institutions:
1Maastricht University Medical Center, Maastricht, the Netherlands, 2University of Reading, Reading, United Kingdom, 3University of Oxford, Oxford, Oxfordshire, 4Massachusetts Institute of Technology, Cambridge, MA
First Author:
Co-Author(s):
Introduction:
Despite half the population experiencing menstruation, its influence on neurophysiology remains understudied. Menstrual hormones – such as estrogen, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) – have been shown to influence vascular tone [1], cardiovascular output [2] and functional connectivity [3]. These vascular dynamics drive cerebrospinal fluid (CSF) flow through cerebral blood volume (CBV) changes [4], suggesting that menstrual hormones may also affect CSF movement.
CSF is essential for clearing brain waste [5]. Women face a higher risk of Alzheimer's disease (AD), potentially linked to a reduced brain waste clearance of proteins like amyloid-beta [6,7]. This emphasizes the need to investigate how hormone-driven vascular changes influence CSF dynamics via CBV alterations. BOLD-CSF coupling, measurable with fMRI [4], can offer insights into the interplay between hemodynamics and CSF flow.
This study examined how menstrual hormones (FSH, LH, 17β-estradiol, and progesterone) influence neurofluid dynamics by analyzing their relationship with BOLD-CSF coupling across the menstrual cycle in a naturally cycling woman.
CSF is essential for clearing brain waste [5]. Women face a higher risk of Alzheimer's disease (AD), potentially linked to a reduced brain waste clearance of proteins like amyloid-beta [6,7]. This emphasizes the need to investigate how hormone-driven vascular changes influence CSF dynamics via CBV alterations. BOLD-CSF coupling, measurable with fMRI [4], can offer insights into the interplay between hemodynamics and CSF flow.
This study examined how menstrual hormones (FSH, LH, 17β-estradiol, and progesterone) influence neurofluid dynamics by analyzing their relationship with BOLD-CSF coupling across the menstrual cycle in a naturally cycling woman.
Methods:
Subject:
We analyzed data from the 28andMe study (OpenNeuro ds0026748)[3], which imaged a 23-year-old female with regular menstrual cycles and no hormone-based medication for a year. Resting-state fMRI and T1-weighted images were acquired daily on 3T MRI (Prisma, Siemens) for 30 days (Fig.1).
Image analysis:
Anatomical images: Cortical gray matter (cGM) was automatically segmented from the T1-weighted image at day 30 using Freesurfer (v7.4.1) and coregistered to each day's fMRI images (FLIRT, FSL, v6.0.1).
fMRI processing: CSF timeseries were extracted from the fMRI signal in the central canal (CSF ROI)(Fig.1).
fMRI data were motion corrected (MCFLIRT, FSL) and distortion corrected (FEAT, FSL) using fieldmaps [8].
BOLD-CSF coupling: Average CSF and BOLD timeseries were extracted from the CSF ROI and cGM mask respectively (Fig.1). The timeseries were normalized (% signal change), detrended, and temporally filtered (0.01-0.1Hz). The maximum absolute cross-correlation between CSF and BOLD was calculated across time lags (-20 to 20s) using Matlab (2019b, Mathworks)[4].
Hormone assessment: Serum levels of menstrual hormones were quantified as previously reported [3](Fig.2).
Statistics: Partial Pearson's correlations were calculated between menstrual hormones and daily BOLD-CSF cross-correlations and lags, adjusting for mean framewise displacement and CSF ROI size (IBM SPSS v25).
We analyzed data from the 28andMe study (OpenNeuro ds0026748)[3], which imaged a 23-year-old female with regular menstrual cycles and no hormone-based medication for a year. Resting-state fMRI and T1-weighted images were acquired daily on 3T MRI (Prisma, Siemens) for 30 days (Fig.1).
Image analysis:
Anatomical images: Cortical gray matter (cGM) was automatically segmented from the T1-weighted image at day 30 using Freesurfer (v7.4.1) and coregistered to each day's fMRI images (FLIRT, FSL, v6.0.1).
fMRI processing: CSF timeseries were extracted from the fMRI signal in the central canal (CSF ROI)(Fig.1).
fMRI data were motion corrected (MCFLIRT, FSL) and distortion corrected (FEAT, FSL) using fieldmaps [8].
BOLD-CSF coupling: Average CSF and BOLD timeseries were extracted from the CSF ROI and cGM mask respectively (Fig.1). The timeseries were normalized (% signal change), detrended, and temporally filtered (0.01-0.1Hz). The maximum absolute cross-correlation between CSF and BOLD was calculated across time lags (-20 to 20s) using Matlab (2019b, Mathworks)[4].
Hormone assessment: Serum levels of menstrual hormones were quantified as previously reported [3](Fig.2).
Statistics: Partial Pearson's correlations were calculated between menstrual hormones and daily BOLD-CSF cross-correlations and lags, adjusting for mean framewise displacement and CSF ROI size (IBM SPSS v25).
·Figure 1. Example of bottom slice positioning (A), region of interest delineation (B-C), BOLD and CSF timeseries (D) and acquisition parameters (E). FOV, field of view; cGM, cortical gray matter.
Results:
Weaker BOLD-CSF coupling (i.e., less negative anti-correlations) was only significantly correlated with higher 17β-estradiol levels (r=.439, p=.019)(Fig.2).
·Figure 2. The participant’s hormone fluctuations, including menstrual cycle phase, ovarian and uterine cycle. 17β-estradiol concentrations (purple) and BOLD-CSF coupling (blue) are correlated.
Conclusions:
This study explored the relationship between menstrual cycle hormones and neurofluid dynamics and found that higher estrogen (17β-estradiol) levels are associated with reduced BOLD-CSF coupling.
Estrogen increases cerebral blood flow (CBF) by lowering cerebrovascular resistance and enhancing cardiac output [1,9], likely inducing vasodilation. Vasodilation may reduce BOLD fluctuation amplitude [10], contributing to weaker BOLD-CSF coupling.
Estradiol is also linked to increased parenchymal volume and a corresponding reduced relative CSF volume [11], creating a potential imbalance between CSF and CBV that could further explain our observations. Additionally, estradiol-driven CSF volume loss may redistribute CSF and reduce central canal flow, thereby lowering the measured BOLD-CSF coupling values.
Future research with a larger sample will examine within- and between-subject variability, incorporating menstrual cycle differences.
To conclude, this study highlights how estradiol fluctuations impact BOLD-CSF coupling, emphasizing the need to consider hormonal influences in neurofluid research. Future research should further examine whether hormonal shifts and neurofluid dynamics contribute to altered waste clearance and heightened AD risk in women.
Estrogen increases cerebral blood flow (CBF) by lowering cerebrovascular resistance and enhancing cardiac output [1,9], likely inducing vasodilation. Vasodilation may reduce BOLD fluctuation amplitude [10], contributing to weaker BOLD-CSF coupling.
Estradiol is also linked to increased parenchymal volume and a corresponding reduced relative CSF volume [11], creating a potential imbalance between CSF and CBV that could further explain our observations. Additionally, estradiol-driven CSF volume loss may redistribute CSF and reduce central canal flow, thereby lowering the measured BOLD-CSF coupling values.
Future research with a larger sample will examine within- and between-subject variability, incorporating menstrual cycle differences.
To conclude, this study highlights how estradiol fluctuations impact BOLD-CSF coupling, emphasizing the need to consider hormonal influences in neurofluid research. Future research should further examine whether hormonal shifts and neurofluid dynamics contribute to altered waste clearance and heightened AD risk in women.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Novel Imaging Acquisition Methods:
BOLD fMRI
Non-BOLD fMRI
Physiology, Metabolism and Neurotransmission:
Cerebral Metabolism and Hemodynamics 1
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Aging
Blood
Cerebral Blood Flow
Cerebro Spinal Fluid (CSF)
Degenerative Disease
FUNCTIONAL MRI
MRI
NORMAL HUMAN
Other - women's health, menstrual cycle
1|2Indicates the priority used for review
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