Multimodal MRI Quantification of Cerebral Hemodynamics

Data processing of TRUST and PC MRI followed methods used previously (21 (link),34 (link),40 (link)). Briefly, for TRUST MRI data, after motion correction and pair-wise subtraction between control and tag images, a preliminary region-of-interest (ROI) was manually drawn to include the superior sagittal sinus. To further define the venous voxels, four voxels with the highest signals in the difference images in the ROI were chosen as the final mask for spatial averaging. The venous blood signals were then fitted to a monoexponential function to obtain T₂. The T₂ was in turn converted to Y_v via a calibration plot obtained by in vitro bovine blood experiments under controlled oxygenation, temperature, and Hct conditions (40 (link)). For PC MRI data, a ROI was manually drawn on the targeted artery of each PC MRI scans based on the magnitude image. The operator was instructed to trace the boundary of the targeted artery without including adjacent vessels. The phase signals, i.e. velocity values, within the mask were summed to yield the blood flow of each artery. To account for brain size differences, the unit volume CBF (in ml/100 g/min) was obtained by normalizing the total CBF (in ml/min) of all four arteries to the intracranial mass (in gram), which was estimated from the high resolution T₁-MPRAGE image using the software FSL (FMRIB Software Library, Oxford University). OEF was calculated from Y_a and Y_v.
Several reproducibility indices were calculated for each of the physiologic parameters evaluated. Intra-session Coefficient of Variation (CoV) was calculated as:
$$Co{V}_{\text{intra–session}}=\frac{1}{I\cdot J}\sum _i\sum _j\frac{\mid M_{ij1}-M_{ij2}\mid }{\sqrt{2}\cdot Mean(M_{ij1},M_{ij2})}$$
where M_ij1 and M_ij2 represent measurement #1 and #2, respectively of Subject #i (i = 1, 2, …, I) in Session #j (j = 1, 2, …, J). Inter-session CoV was calculated as:
$$Co{V}_{\text{inter–session}}=\frac{1}{I\cdot K}\sum _i\sum _k\frac{S{D}_j\left(M_{ijk}\right)}{Mea{n}_j\left(M_{ijk}\right)}$$
where SD stands for standard deviation.
Inter-subject CoV was calculated as:
$$Co{V}_{\text{inter–subject}}=\frac{1}{I\cdot K}\sum _j\sum _k\frac{S{D}_i\left(M_{ijk}\right)}{Mea{n}_i\left(M_{ijk}\right)}$$
Compared to intra-session CoV, the value of inter-session is expected to contain additional variance due to subject repositioning and day-to-day differences in physiologic states. These contributions can be calculated as $\sqrt{Co{V}_{i\text{nter–session}}^2-Co{V}_{\text{intra–session}}^2}$ . Similarly, compared to inter-session CoV, inter-subject CoV contains additional inter-subject physiologic differences. These contributions can be calculated as $\sqrt{Co{V}_{i\text{nter–subject}}^2-Co{V}_{\text{inter–session}}^2}$ .
Additionally, since CBF quantification involves manual ROI selection, inter-rater reliability of CBF measurement was evaluated by having two raters (PL and FX) analyze the same datasets independently and calculating the correlation of the CBF values.
Relationships between physiologic parameters were evaluated with Pearson correlation and mixed effect model. In all analyses, a p < 0.05 is considered statistically significant.