Decoupling between cerebral blood volume and CSF in cognitive impairment is linked to brain volume
Poster No:
183
Submission Type:
Abstract Submission
Authors:
Riya Mahajan1, Adam Wright1, Qiuting Wen2, Andrew Saykin2, Shannon Risacher2, Yunjie Tong1
Institutions:
1Purdue University, West Lafayette, IN, 2Indiana University School of Medicine, Indianapolis, IN
First Author:
Co-Author(s):
Introduction:
Cerebrospinal fluid (CSF) is crucial for eliminating misfolded proteins from the brain1, but the mechanisms driving CSF dynamics in the human brain remain incompletely understood. Prior research demonstrates a tight coupling between CSF motion and cerebral blood volume (CBV), directly linked to low-frequency (LFO) hemodynamic oscillations2-4. In cognitive impairment (CI), there is a reduction in brain volume due to loss of neurons, gray and white matter, and ventricular expansion5. A resting-state fMRI (rs-fMRI) study showed reduced coupling between the CBV and CSF dynamics in CI individuals6. To build upon this study, we investigate how reduced brain volume in CI may alter the coupling between CBV and CSF dynamics. We hypothesize that a reduced brain volume weakens the driving force of brain pulsations, which may lower the coupling between CBV and CSF dynamics. Neurodegenerative diseases like Alzheimer's disease (AD) accelerate brain atrophy5, possibly resulting in a more pronounced decoupling.
Methods:
This study analyzed 40 participants, with 15 excluded due to poor image quality. The remaining 25 participants (10 female, 15 male, aged 51-87) included 12 cognitively normal (CN) and 14 with CI. MRI data were obtained using a 3T SIEMENS MRI scanner: T1W images (res = 1.2 x 1.1 x 1.1 mm3, TR/TE = 2300/2.98 ms) and rs-fMRI (res = 2.5 × 2.5 × 2.5 mm3, TR/TE = 1200/29 ms).
Rs-fMRI were slice time corrected, motion corrected, and spatially smoothed. The global mean signal (GMS) was extracted from the whole brain excluding ventricles. CSF inflow signal was extracted with ROIs manually defined on the first slice (near the cerebellum) of non-motion corrected rs-fMRI. The selected voxel's time series had a maximum skewness > 0.5 to enhance sensitivity to CSF inflow effect. The GMS and CSF signals were linearly detrended, oversampled to 10 Hz sampling frequency, and band-pass filtered (0.01 to 0.1 Hz) using a zero delay, 4th-order Butterworth filter.
The GMS signal's time derivative (d(GMS)/dt) can be used to assess the effect of hemodynamic oscillations in the brain, as CSF movement occurs during CBV oscillations3. The d(GMS)/dt was multiplied by -1, and negative values were set to zero to restrict the analysis to inflow. The coupling strength was quantified by calculating the maximal cross-correlation coefficients between the -d(GMS)/dt and CSF signals. Volumetric brain analysis was completed using the vol2Brain 1.0 software analysis7 and brain tissue volume (gray + white matter) was normalized to the total intracranial volume.
Spearman correlation quantified the associations between -d(GMS)/dt-CSF coupling and normalized brain volume, with respect to cognition and biological sex. Group-level comparisons of cognition and biological sex with -d(GMS)/dt-CSF coupling, and normalized brain volumes were performed using a student's t-test. p<0.05 was regarded as significant.
Rs-fMRI were slice time corrected, motion corrected, and spatially smoothed. The global mean signal (GMS) was extracted from the whole brain excluding ventricles. CSF inflow signal was extracted with ROIs manually defined on the first slice (near the cerebellum) of non-motion corrected rs-fMRI. The selected voxel's time series had a maximum skewness > 0.5 to enhance sensitivity to CSF inflow effect. The GMS and CSF signals were linearly detrended, oversampled to 10 Hz sampling frequency, and band-pass filtered (0.01 to 0.1 Hz) using a zero delay, 4th-order Butterworth filter.
The GMS signal's time derivative (d(GMS)/dt) can be used to assess the effect of hemodynamic oscillations in the brain, as CSF movement occurs during CBV oscillations3. The d(GMS)/dt was multiplied by -1, and negative values were set to zero to restrict the analysis to inflow. The coupling strength was quantified by calculating the maximal cross-correlation coefficients between the -d(GMS)/dt and CSF signals. Volumetric brain analysis was completed using the vol2Brain 1.0 software analysis7 and brain tissue volume (gray + white matter) was normalized to the total intracranial volume.
Spearman correlation quantified the associations between -d(GMS)/dt-CSF coupling and normalized brain volume, with respect to cognition and biological sex. Group-level comparisons of cognition and biological sex with -d(GMS)/dt-CSF coupling, and normalized brain volumes were performed using a student's t-test. p<0.05 was regarded as significant.
Results:
The -d/dt(GMS)-CSF coupling showed significant positive association with brain volume across all participants (r = 0.408, p = 0.043). This coupling was significantly positively associated with brain volume in CI patients (r = 0.555, p = 0.049), but not in CN patients (r = 0.252, p = 0.430). There was no significant difference in the coupling between CN and CI groups (t-test, p = 0.462). A significant difference (t-test, p = 0.008) was observed in the brain volumes between CN and CI, where the CI group had smaller brain volumes.
Conclusions:
Our results suggest a significant positive correlation between the -d(GMS)/dt-CSF and brain volume in CI. This could indicate that a reduced brain volume weakens the interaction between CBV and CSF dynamics and impair a major driving force of CSF movement. This could lead to reduced CSF flow and an accelerated accumulation of toxic proteins, ultimately leading to greater atrophy and accelerating progression of neurodegenerative diseases like AD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Lifespan Development:
Aging
Novel Imaging Acquisition Methods:
BOLD fMRI 2
Keywords:
Aging
Cerebro Spinal Fluid (CSF)
Cognition
Degenerative Disease
FUNCTIONAL MRI
MRI
1|2Indicates the priority used for review
Provide references using author date format
[2] Fultz, N. E. (2019), 'Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep'. Science, 366, 628–631
[3] Yang, H.-C. (2022), 'Coupling between cerebrovascular oscillations and CSF flow fluctuations during wakefulness: An fMRI study'. Journal of Cerebral Blood Flow and Metabolism, 42, 1091–1103
[4] Nair, V.V. (2022), 'Human CSF movement influenced by vascular low frequency oscillations and respiration'. Frontiers in Physiology, 13
[5] Blinkouskaya, Y. (2021), 'Brain Shape Changes Associated With Cerebral Atrophy in Healthy Aging and Alzheimer’s Disease'. Frontiers in Mechanical Engineering, 7
[6] Han, F. (2021), 'Reduced coupling between cerebrospinal fluid flow and global brain activity is linked to Alzheimer disease–related pathology'. PLOS Biology 19, e3001233–e3001233
[7] Manjón, J. V. (2022), 'vol2Brain: A New Online Pipeline for Whole Brain MRI Analysis'. Frontiers in Neuroinformatics,16