Supplemental Methods and Results, Appendix E-1

Supplemental Methods and Results, Appendix e-1

SUPPLEMENTAL METHODS

MRI Sequence details

Table e-1.

Sequence / TE/TR (ms) / Flip angle (°) / Other parameters / Slice thickness (mm) / FOV (cm) [acquisition matrix]
2D SPGR / 3.5 / 200 / 18 / 4 / 24 [128 x 128]
EPI fMRI / 30 / 2000 / 70 / 4 / 24 [64 x 64]
3D inversion prepared T1 / 2.5 / 6 / 8 / TI = 650ms / 1 / 24 [256 x 256]
T2 FLAIR / 140 / 9000 / 90 / TI = 2250ms / 3.5 / 24 [256 x 256]
T2* GRE / 20 / 1200 / 18 / 3.5 / 24 [256 x 256]
PD/T2 FSE / 85 / 3500 / 90 / TE1=9 ms (min);
ETL = 12 / 3.5 / 24 [256 x 256]

Abbreviations

TE/TR: echo time/repetition time.

TI: inversion time.

FOV: field of view.

SPGR: spoiled gradient echo.

EPI: echo planar imaging.

FLAIR: fluid attenuated inversion recovery.

GRE:gradient recall echo.

PD/T2: proton density / transverse relaxation time.

FSE: fast spin echo.

ETL: echo train length.

Determination of the volume of activated brain regions

The volume of activated brain was determined for each task (visual and motor) within specified regions encompassing primary visual cortex (for the visual task) and primary motor and primary sensory cortex (for the motor task). For the visual task the region of interest encompassed the banks of the calcarine sulcus. For the motor task the region of interest encompassed the primary motor cortex of the left hemisphere (that is, the precentral sulcus—Brodmann area 4) and the primary sensory area (the postcentral gyrus, Brodmann areas 3, 1 and 2), extending from the lateral surface to the midline and from the vertex of the brain to the the level of the superior aspect of the lateral ventricles caudally, and excluding the gap of the central sulcus (Tjandra et al, Neuroimage 2005;27:393-401). These regions were drawn on each subject’s high-resolution T1-weighted MRI. Subject brains were then coregistered to the MNI template using FSL, and the numbers of activated voxels in each group were counted with the regions of interest. By this method, in the visual task the CAA subjects activated 28.2 cm3 of primary visual cortex while the non-CAA control subjects activated 41.5 cm3 of primary visual cortex. In the motor task the CAA subjects activated 21.2 cm3 of primary motor and sensory cortex while the healthy control subjects activated 61.3 cm3 of primary motor and sensory cortex.
SUPPLEMENTAL RESULTS

Table e-2. Multivariable analyses controlling for hypertension

Model dependent (outcome) variable / Model 1 (not including hypertension)* / Model 2 (including hypertension)*
CAA (vs. control) / CAA / Hypertension
β coefficient
(95% CI) / β coefficient
(95% CI) / β coefficient
(95% CI)
Occipital BOLD fMRI amplitude (visual task) / -0.99
(-0.29, -1.69) / -1.35
(-0.52, -2.18) / 0.64
(-0.19, 1.47)

Legend: Results of linear mixed models of BOLD fMRI amplitude, with (model 1) vs. without (model 2) controlling for hypertension. A random effects term was included for each case-control pair, to account for the paired experimental design. The relationship between CAA and BOLD fMRI amplitude persisted, and if anything was strengthened, after adjustment for hypertension. Additionally, hypertension was not associated with occipital BOLD fMRI amplitude in univariate analysis (3.01 ± 1.19% in hypertensives compared to 3.12 ± 1.05% in normotensives, p=0.75).

Table e-3. Differences between CAA with Inflammation (n=4) and CAA Without Inflammation (n=14)

Characteristic / CAA with inflammation (n=4) / CAA without inflammation (n=14) / Control
(n=18)
Visual BOLD fMRI amplitude (% from baseline) / 1.93±1.21* / 2.76±0.94* / 3.57±0.94
Motor BOLD fMRI amplitude (% from baseline) / 1.61±0.98 / 1.97±0.70 / 2.39±0.97
PCA CO2 reactivity (% change per mmHg) / 0.95±0.20* / 1.97±1.80 / 3.30±2.31
MCA CO2 reactivity (% change per mmHg) / 2.77±0.62 / 2.33±1.78 / 3.56±1.77
VEP P100 amplitude (microvolts) / 7.88±2.0** / 4.76±2.02 / 4.82±2.78

Legend: Because of poor temporal bone windows, PCA CO2 reactivity index was missing in 2 patients with CAA with inflammation, 2 patients with CAA without inflammation, and 4 controls. MCA CO2 reactivity index was missing in 2 patients with CAA with inflammation, 3 patients with CAA without inflammation, and 4 controls.

*Different from controls, p<0.05.

*Different between CAA with inflammation vs. CAA without inflammation, p<0.05.