*3.5. MRI Relative Cerebral Blood Flow*

Representative relative cerebral blood flow (rCBF) images in five regions of interest: cortex, striatum, hippocampus (HC), caudate-putamen (CPu), and basolateral amygdala (BLA) from two 1mm consecutive slices (approximately, Bregma −1.5 mm and −2.5 mm) are presented in Figure 5. No statistically significant differences in rCBF were observed (Figure 6A). However, 3xTg-AD female mice survivors had increased rCBF in the cortex and hippocampus compared with their NTg counterparts (Student t-test *p* < 0.05). In particular, genotype per sex interaction effects were observed in cortical rCBF (GxS, F(1,27) = 4.545, *p* = 0.044).

**Figure 5.** MRI arterial spin labeling (ASL)—relative cerebral blood flow in regions of interest. (**A**) Global cerebral blood flow and five regions of interest were examined in the present study from two different sections (Bregma −1.5 mm, −2.5 mm). Cortex; striatum; caudate putamen (CPu); basolateral amygdala (BLA); hippocampus (HC). (**B**) Representative images from rCBF maps superimposed to T2w-image from NTg male, NTg female, 3xTg-AD male, and 3xTg-AD female.

**Figure 6.** MRI-ASL—relative cerebral blood flow. (**A**) Mean relative blood flow in cortex and hippocampus. (**B**) Hemisphere relative cerebral blood flow asymmetry. Results are the mean ± SEM. Bars illustrate the genotype groups, as indicated in the abscissae. Symbols are used to illustrate individual values of males (black, left panel) and females (red, right panel). Left hemisphere: blue; right hemisphere: purple. In green: the no-survivors. Genotype (G) and sex (S) effects and GxS interaction were analyzed by 2x2 factorial ANOVA analysis, \* *p* < 0.05 (above line). Student *t*-test comparisons: \* *p* < 0.05 vs. the corresponding NTg group; Paired *t*-test in asymmetry between right/left hemispheres: @ *p* <0.05, @@@ *p* < 0.001.
