Effects of deep respiration on cerebrospinal fluid flow in 4th ventricle

2096 

Abstract Submission 

Kian Wong¹, Chun Siong Soon¹, Yicun Wang², Jeff Duyn², Michael Chee¹

¹Centre for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore, ²National Institutes of Health, Bethesda, MD

Kian Wong  
Centre for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore
Singapore, Singapore

Chun Siong Soon  
Centre for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore
Singapore, Singapore

Yicun Wang  
National Institutes of Health
Bethesda, MD

Jeff Duyn  
National Institutes of Health
Bethesda, MD

Michael Chee  
Centre for Sleep and Cognition, Yong Loo Lin School of Medicine, National University of Singapore
Singapore, Singapore

Accumulation of neurotoxic brain metabolites contributes to the development of Alzheimer's Disease (Darst et al., 2021). Clearance of these substances is enhanced during sleep particularly deep sleep through increased transfer from brain through interstitial spaces and then into the CSF. Enhancing CSF flow might thus be beneficial (Burman & Alperin, 2023). Recent work has shown that slower and deep breathing can increase CSF oscillations and flow. CSF flow in the ventricles can be quantified with high temporal resolution (Chen et al., 2015; Dreha-Kulaczewski et al., 2015; Yildiz et al., 2017), including a steady-state free precession (SSFP) sequence (Wang et al., 2022) by measuring the shift and distortion in frequency tags. We examined the replicability of this method with a guided breathing paradigm in young adults before examining if the breathing-induced increases in CSF flow are attenuated in older adults.

Five healthy participants (mean age 24.8 years; 1 male) were studied using an IRB approved protocol. Each participant underwent five 7min 58s task runs during which breathing was guided by an expanding (inhalation) or contracting (exhalation) circle. Interspersed between 86 normal breaths (2.5s inhale, 2.5s exhale) were 6 deep breaths (4s inhale, 4s exhale; larger circle). Deep breaths were separated by either 10 or 20 normal breaths (Fig. 1).
MRI scans were conducted on a 3T Prisma Scanner (Siemens Healthineers, Erlangen, Germany) using a 32-channel head and neck receiver array. Participants undertook two runs of a T2* weighted multiband (sms = 4) EPI sequence, and three using an SSFP sequence (TR 6ms; TE 3ms; flip angle 45°; slice thickness 3mm; FOV 240mm; matrix size 192 x 108; resolution 1.3mm x 1.3mm; frame rate 216ms). A hi-res (1mm isovoxel) structural MPRAGE scan was also acquired.
For the SSFP sequence, a shim offset was introduced following B0 shimming to create the tags, and the frequency shift was tuned to position a tag in the 4th ventricle (Wang et. al., 2022). Tag profiles (Fig 1b) were extracted across time. Offset values for each breathing epoch were baseline-corrected to the 1 second period preceding the breath. Area under the curve for the breathing-related tag distortions were calculated and normalized to the event duration to obtain the offset distance per second, which provided a surrogate measure of CSF movement. The offset distance per second for deep vs normal breaths were compared by repeated measures t-tests.

Deep breaths showed significantly higher offset distance per second than normal breaths (paired t-test: t = -2.85, p<.05). This indicates that the change in CSF flow rate is not just a linear function of breath duration, but also depth of breathing, as can be seen in Fig 2.

In this preliminary work, we demonstrated how CSF flow can be increased during guided breathing by increasing breath duration and depth, where deeper breathing elicited substantially higher volume of ventricular CSF flow. This could potentially benefit brain metabolite waste clearance (Burman & Alperin, 2023). Additionally, the change in CSF flow may be accompanied by a change in BOLD signal, which we plan to verify in the acquired multiband EPI scans.

Anatomy and Functional Systems ¹

Physiology, Metabolism and Neurotransmission Other ²

Cerebro Spinal Fluid (CSF)

Other - Respiration