Aging and Sex Differences in Brain Volume and Cerebral Blood Flow

How do regional brain volume ratios and cerebral blood flow (CBF, mL/min) change with aging, and are there sex differences? This study aimed to comprehensively evaluate the relationships between regional brain volume ratios and CBF in healthy brains. The study participants were healthy volunteers who underwent three-dimensional T1-weighted MRI, time-of-flight MR angiography, and four-dimensional (4D) flow MRI between 2020 and 2022. The brain was automatically segmented into 21 brain subregions from 3D T1-weighted MRI, and CBF in 16 major intracranial arteries were measured by 4D flow MRI. The relationships between segmented brain volume ratios and CBFs around the circle of Willis were comprehensively investigated in each decade and sex. This study included 129 healthy volunteers (mean age ± SD, 48.2 ± 16.8; range, 22-92 years; 43 males and 86 females). The association was strongest between the cortical gray matter volume ratio and total outflow of the intracranial major arteries distal to the circle of Willis (Pearson's correlation coefficient, r: 0.425). In addition, the mean flow of the total inflow and outflow around the circle of Willis were significantly greater in women than men, and significant left-right differences were observed in CBFs even on the peripheral side of the circle of Willis. Moreover, the correlation was strongest between the left cortical gray matter volume ratio and the combined flows of the left anterior and posterior cerebral arteries distal to the circle of Willis (r: 0.486). There was a trend toward greater total intracranial CBF, especially among women in their 40s and younger, who had a larger cortical gray matter volume. This finding may be one of the reasons for the approximately twofold higher incidence of cerebral aneurysms and subarachnoid hemorrhage, and a threefold higher incidence of migraine headaches.