(E-187) Acute Lower Body Negative Pressure Changes Human Brain Tissue Perfusion and Stiffness in vivo Measured with MR Elastography

Understanding the relationship between brain tissue integrity and cardiovascular health offers many opportunities to improve health care interventions for aging patients. Brain tissue stiffness, measured with magnetic resonance elastography (MRE) can be used as a sensitive metric of brain health that decreases with increasing age and even further with neurodegenerative disease progression^1,2. Previous associations between brain stiffness and blood flow have been examined, but the relationships are not fully understood. Here, we use lower body negative pressure (LBNP) to observe the acute effects of decreased blood flow on brain stiffness in healthy young adults. LBNP is a method wherein negative pressure is applied below the iliac crest (hips) to reduce central venous pressure and venous return³, thus more of the subject’s blood remains in their lower body, which consequently decreases the blood flow in their brain. The decrease in brain blood flow in the brain may affect brain stiffness due to decreased intracranial pressure or changing mechanical properties of the arteries and perivascular tissue⁴. We use MRE while applying LBNP to measure brain stiffness changes, and also use arterial spin labeling (ASL), a non-invasive MRI technique measuring tissue perfusion that doesn’t require any type of injected contrast⁶. The objective of this study is to establish that applied LBNP induces a measurable change in brain stiffness and cerebral blood flow and to examine the association between both.

Sixteen subjects (4M/12F; 20-26 years old) were imaged using a Siemens 3T Prisma MRI scanner while utilizing a LBNP chamber. The LBNP chamber is custom-built, MRI-compatible, and has a skirt attachment, creating a seal at the subject’s iliac crest. A pneumatic actuator system and passive pillow driver (Resoundant, Rochester, MN) are used to deliver vibrations to the back of the head at 50 Hz, creating tissue displacements which are captured as phase with motion encoding gradients in the echoplanar imaging MRE sequence (2.5mm resolution; 48 slices; TR=6720ms; TE=70ms; FOV=240x240mm; 3.5 minutes per scan). Measured displacements are converted into maps of estimated brain stiffness through the nonlinear inversion algorithm⁷. ASL scans are collected using a multi-delay PCASL protocol with 2.5x2.5x2.3mm resolution as outlined in the Human Connectome Project⁸. A perfusion map is obtained from the data using FSL’s ASL processing toolbox, BASIL. Under baseline conditions, one 0.9mm isotropic T1 weighted scan is collected for anatomical segmentation, followed by a 5-minute ASL scan, and then a 3.5-minute MRE scan. The LBNP is then turned on and after a 1.5-minute adjustment period, the ASL and MRE scans are completed again in that order. Then the LBNP is turned off and after another 1.5-minute adjustment period, the ASL and MRE scans are repeated. After data collection, the regions of interest for grey and white matter are determined using FSL-FAST from T1 weighted anatomical images for ASL and MRE analysis.

Overall, we see that the application of LBNP for 10 minutes causes a decrease in blood flow and brain stiffness that can be reversed after returning to normal conditions (Figure 1). For the initial application of the LBNP condition, the decreases in both stiffness and perfusion in grey matter when LBNP is applied are strongly correlated (p< 0.001), and the recovery of both measures after LBNP is turned off is nearly significantly correlated (p=0.052). We can interpret this data to suggest that the change in stiffness from LBNP application is strongly related to the change in blood flow for two reasons. Since grey matter is more vascularized and therefore more highly perfused than white matter, which is evident in Figure 1A, it corroborates the strongest effects of LBNP on brain tissue stiffness being in grey matter as opposed to white matter (Table 1). Further, we found that grey matter has the greatest correlation between perfusion and stiffness, while the relationships in white matter are much weaker. This demonstrates that the changes in stiffness are proportional to the changes in perfusion as a result of LBNP, accounting for the physiological variation in each subject’s cerebral perfusion response to applied LBNP. Taken together, this suggests that there is a directly proportional relationship between the observable change in stiffness and perfusion and that a temporary change in both can be accomplished using LBNP. This ultimately provides an avenue to understand the intricate relationships between brain integrity and vascular health.

University of Delaware Research Foundation, R01-AG058853, and K01-AG054731.

[1] Hiscox LV, Johnson CL, McGarry MDJ, Perrins M, Littlejohn A, van Beek EJR, Roberts N, Starr JM. High-resolution magnetic resonance elastography reveals differences in subcortical gray matter viscoelasticity between young and healthy older adults. Neurobiol Aging. 2018 May;65:158-167. PMID: 29494862 DOI: 10.1016/j.neurobiolaging.2018.01.010. 

[2] Murphy MC, Huston J 3rd, Jack CR Jr, Glaser KJ, Manduca A, Felmlee JP, Ehman RL. Decreased brain stiffness in Alzheimer's disease determined by magnetic resonance elastography. J Magn Reson Imaging. 2011 Sep;34(3):494-8. PMID: 21751286 DOI: 10.1002/jmri.22707. 

[3] Crystal GJ, Salem MR. Lower Body Negative Pressure: Historical Perspective, Research Findings, and Clinical Applications. J Anesth Hist. 2015 Apr;1(2):49-54. PMID: 26205572 DOI: 10.1016/j.janh.2015.02.005. 

[4] Herthum H, Shahryari M, Tzschätzsch H, Schrank F, Warmuth C, Görner S, Hetzer S, Neubauer H, Pfeuffer J, Braun J, Sack I. Real-Time Multifrequency MR Elastography of the Human Brain Reveals Rapid Changes in Viscoelasticity in Response to the Valsalva Maneuver. Front Bioeng Biotechnol. 2021 May 5;9:666456. PMID: 34026743 DOI: 10.3389/fbioe.2021.666456. 

[5] Murphy MC, Huston J 3rd, Ehman RL. MR elastography of the brain and its application in neurological diseases. Neuroimage. 2019 Feb 15;187:176-183. PMID: 28993232 DOI: 10.1016/j.neuroimage.2017.10.008. 

[6] Petcharunpaisan S, Ramalho J, Castillo M. Arterial spin labeling in neuroimaging. World J Radiol. 2010 Oct 28;2(10):384-98. PMID: 21161024 DOI: 10.4329/wjr.v2.i10.384. 

[7] McGarry MD, Johnson CL, Sutton BP, Georgiadis JG, Van Houten EE, Pattison AJ, Weaver JB, Paulsen KD. Suitability of poroelastic and viscoelastic mechanical models for high and low frequency MR elastography. Med Phys. 2015 Feb;42(2):947-57. PMID: 25652507 DOI: 10.1118/1.4905048.

[8] Harms M et al. Extending the Human Connectome Project across ages: Imaging protocols for the Lifespan Development and Aging projects. Neuroimage. 2018 Dec;183:972-984. PMID: 30261308 DOI: 10.1016/j.neuroimage.2018.09.060.