Joseph Alisch1, Nikkita Khattar1, Richard Wonjoong Kim1, Abinand C. Rejimon1, Luis E. Cortina1, Wenshu Qian1, Mustapha Bouhrara1, and Richard G. Spencer1
1NIA, NIH, Baltimore, MD, United States
Synopsis
Cerebral
blood flow (CBF) has been shown to decline with age and differs between men and
women. However, limited work has been conducted on cognitively unimpaired
subjects. Furthermore, most investigations focus on gray matter (GM), with few results
reported for white matter (WM), in which CBF is lower and represents a particularly
challenging measurement. We investigate associations of age and sex with CBF in
GM and WM regions in a cohort of cognitively unimpaired subjects across a wide
age range. We find significant correlations
between CBF and age, as well as sexual dimorphism of CBF, in critical brain
structures.
PURPOSE
Our main goals are to
characterize the regional differences between cerebral blood flow (CBF) in
white matter (WM) and gray matter (GM), measured using the pseudo-continuous
arterial spin labeling (pCASL) technique (1), and age and sex in a cohort of cognitively unimpaired subjects
across a wide age range, and to provide reference values for CBF in critical WM
and GM structures. METHODS
Subjects and MRI
Our
study cohort consisted of 77 cognitively unimpaired participants (48.8 ± 19.0
years, age range of 22-88 years) incorporating 30 women (47.4 ± 18.9 years) and
47 men (49.7 ± 19.2 years). Age was not
statistically different between men and women. For each participant, pCASL imaging
datasets for CBF mapping were acquired (1). Datasets consisted of control,
labeled, and proton density (PD) images that were acquired with incorporation
of background suppression, FoV of 220 mm x 210 mm x 120 mm, and spatial
resolution of 2.5 mm x 2.5 mm x 5 mm with reconstruction to 1 mm x 1 mm x 1 mm.
Other experimental parameters were: TE of 15 ms, TR of 7.5 s, labeling duration
of 1.8 s, post-labeling duration of 2 s, and 30 signal averages.
Image processing and statistical analysis
For each participant, a whole-brain
CBF map was generated from the pCASL dataset using the NESMA analysis to
improve accuracy and precision in CBF determination (2). The PD image was nonlinearly registered to the MNI space and the
computed transformation matrix was then applied to the corresponding CBF map.
FAST segmentation was performed on PD images to generate WM masks and cortical
GM masks. Six WM and GM regions of interest (ROIs) were defined from the MNI
structural atlas using the FAST-derived WM and GM masks; these ROIs correspond
to the whole brain, and the frontal, parietal, temporal and occipital lobes, as
well as the cerebellum. Within each WM and GM ROI, the mean CBF value was
calculated. The registration, segmentation, and ROI analyses were performed
using FSL software (3). Finally, for each ROI, the effect of CBF was investigated using linear
regression with the mean CBF value within the ROI as the dependent variable and
sex and age as the independent variables. RESULTS & DISCUSSION
Figure 1 shows representative CBF
maps derived from pCASL imaging datasets. These NESMA-filtered images exhibited
excellent detail (2). Results are shown for three slices covering the main brain
structures and for seven participants of different ages. Visual inspection of
CBF maps indicate an overall decrease in CBF with age, especially in the GM
brain regions. Regression analysis quantified these changes in CBF in GM (Fig.
2) and WM (Fig. 3) regions. As expected, the GM CBF values were higher than the
WM CBF values. We also observed variations in these age- and sex-related
differences across different brain regions, as expected. Further, various cortical
GM regions investigated exhibited a statistically significant (p
< 0.05), or close to significant (p < 0.1), decline in CBF
with age (Table 1), in agreement with recent studies (4, 5).
Interestingly, the WM regions exhibited increasing trends of CBF with age; this
association was significant in all brain regions studied except the temporal
lobes (Table 1). We provisionally attribute this increase of CBF with age in WM
to increasing oligodendrocyte metabolic demand for maintenance of myelin
homeostasis (6, 7).
Sex differences in CBF were
statistically significant in most GM and WM regions studied (Table 1). Our
results indicate that women exhibit, overall, higher mean CBF values than males
(Fig. 4), in agreement with recent work (4).
This may be accounted for by differential endocrine regulation of CBF between
the sexes (4).
In addition, recent studies have also
indicated greater myelin content in women as compared to men (6, 7).
Thus, greater CBF in women could reflect increased oligodendrocyte metabolic
demand for myelin synthesis. CONCLUSIONS
Our results
provide evidence for statistically significant associations between age and sex,
and CBF, in a large sample of well-characterized cognitively unimpaired adults.
The GM regions exhibit overall statistically significant decreasing CBF with
age while WM exhibited increasing trends. Finally, women showed higher CBF
values than men in all brain structures investigated.Acknowledgements
This work was supported by the Intramural Research Program of the National Institute on Aging of the National Institutes of Health.
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