Short-term cerebral blood flow reduction induced “apparent” brain tissue density reduction
Qiu Ge1, Wei Peng1, Yong Zhang2, Yu-Feng Zhang1, Thomas Liu3, Xuchu Weng1, and Ze Wang1

1Hangzhou Normal University, Hangzhou, China, People's Republic of, 2GE Healthcare, MR Research China, Beijing, Shanghai, China, People's Republic of, 3University of California San Diego, San Diego, CA, United States

Synopsis

MRI-identified short-term brain tissue changes have been in debate because of the lack of solid evidence of neurogenesis. Cerebral blood flow (CBF) has been traced as one contributing factor. We used caffeine to modulate CBF and to subsequently examine brain tissue change using MRI. Both CBF reduction and grey matter decrease were observed after caffeine ingestion, which were further related to each other in some brain regions. The data provide direct evidence for the CBF contribution to the short-term apparent tissue changes.

Introduction

Claiming the MRI-identified brain tissue change as a result of neurogenesis is now being challenged because neurogenesis in adult human brain has only been evidenced in very limited regions [1, 2]. One confounding factor that may contribute to the apparent tissue change is cerebral blood flow (CBF), which can change both MR parameters of tissue and tissue volume. While previous research has reported concurrent CBF and tissue volume changes, no one has explicitly assessed this “coincidence” by manipulating CBF in the healthy brain in a short time while keeping other conditions the same. In this study, we used caffeine to directly alter CBF and subsequently examined the CBF-tissue density interactions. We chose caffeine because it is well known to have robust effects of reducing CBF [3, 4].

Methods

All experiment procedures were approved by local IRB. 50 caffeine naïve healthy subjects (25 males and 25 females, age: 22.76±2.22 years, no medications, no more than 1 cup of coffee and 1 cup of tea in the week prior to the experiment) were recruited with written signed consent forms. All participants attended two imaging scan sessions before and after taking a 200 mg caffeine pill in two days with exactly 24 hours apart. The order of being caffeine free or taking caffeine prior to scan was counter-balanced. For each session, a high-resolution T1-weighted structural MRI and a six-minute resting brain perfusion MRI (using a GE product 3D BS-PCASL sequence (6 shots, 40 axial slices, TR=4690ms, TE=10.9ms, FOV=220x220 mm2, slice thickness=3.4mm, labeling time=1.5s, post label delay=1525ms, bandwidth=62.50Khz, matrix=512x512)) were acquired. Pre-post caffeine grey matter difference was examined using the state-of-art longitudinal voxel-based morphometry (VBM) analysis method [5] implemented in SPM12. CBF maps were spatially normalized into the MNI space using the registration information obtained from the mid-term structural image (created during the longitudinal VBM). Pre-post CBF difference was assessed using paired-t test. Correlation between tissue difference and CBF difference was calculated at each voxel in the standard brain space.

Results

Fig. 1 shows the observed effects of caffeine on CBF and tissue volume. Caffeine intake caused a global CBF reduction (Fig. 1A. voxel-wise P<0.05 with FWE correction). The whole brain mean CBF reduction was 15.3 ml/100g/min. Grey matter volume reduction after taking caffeine was observed in hippocampus, orbito-frontal cortex, ventral striatum, anterior cingulate cortex (ACC), insula, and superior temporal cortex (Fig. 1B). After regressing out the pre-post caffeine CBF difference from the tissue density difference, no significant caffeine induced tissue density change was found (Fig. 1C). Fig. 2 shows the correlation between the pre-post CBF difference and tissue density difference. Significant correlation was demonstrated in hippocampus, fusiform, visual cortex, putamen, prefrontal cortex, and lateral parietal cortex.

Conclusion and Dissusion

We proved that CBF reduction attribute short-term apparent brain tissue density reduction. Although linear correlations between CBF reduction and tissue density reduction were only observed in several brain regions, our data showed that after regressing out CBF effects, the apparent tissue changes went away. Altogether, our data should raise cautions of reporting short-term brain tissue density changes as a result of neurogenesis, rather the observed apparent tissue “changes” should be corrected for CBF alterations.

Acknowledgements

Work supported by Natural Science Foundation of Zhejiang Province Grant LZ15H180001, the Youth 1000 Talent Program of China, and Hangzhou Qianjiang Endowed Professor Program.

References

1. Ernst, A., et al., Cell, 2014. 156(5): p. 1072-1083. 2. Bhardwaj, R.D., et al., PNAS, 2006. 103(33): p. 12564-12568. 3. Addicott, M.A., et al., Hum Brain Map, 2009. 30(10): p. 3102-3114. 4. Mutsaerts, H.J.M.M., et al., Magnetic Resonance Materials in Physics, 2015. 5. Ashburner and Ridgway, Symmetric diffeomorphic modeling of longtudinal structural MRI. Frontiers in Neuroscience, 2013. 6.

Figures

Fig. 1. Caffeine-induced CBF reduction (A), and grey matter tissue indensity reduction (B), which disappeared after regressing out the CBF reduction (C).

Fig.2. Correlations between CBF changes and grey matter tissue changes after taking caffeine pill.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
0419