Additional file 1 of Pilot study of repeated blood-brain barrier disruption in patients with mild Alzheimer’s disease with an implantable ultrasound device
Creators: name: Epelbaum, Stéphane
name: Burgos, Ninon
name: Canney, Michael
name: Matthews, Dawn
name: Houot, Marion
name: Santin, Mathieu D.
name: Desseaux, Carole
name: Bouchoux, Guillaume
name: Stroer, Sebastian
name: Martin, Cyril
name: Habert, Marie-Odile
name: Levy, Marcel
name: Bah, Aicha
name: Martin, Karine
name: Delatour, Benoît
name: Riche, Maximilien
name: Dubois, Bruno
name: Belin, Lisa
name: Carpentier, Alexandre
Publisher: name: figshare
Year: 2022
Subjects: Space Science
Medicine
Cell Biology
Neuroscience
Mental Health

description: Additional file 1. Supplementary analyses at the global scale. Fig. S1. Baseline amyloid load for each participant in regional SUVRs and in target (implant) region (ROI1). All participants had a positive amyloid load in the region targeted by the sonication except for Patient 10 (threshold of 1.1 assumed for amyloid positivity). Fig. S2. Violin plots representing the distribution of the annualized percent changes (APC) in PET uptake for the current study ("BOREAL", n=9) and reference cohort ("ADNI", n=45) populations. The APC were computed for both the cognitive (left) amyloid PET (middle) and FDG PET (right) in the large (top) and small (bottom) regions of interest for PET imaging. No statistical difference was observed between BOREAL and ADNI (Kruskal-Wallis H-test with the Benjamini-Hochberg procedure to correct for multiple testing). Fig. S3. Typical Gd-DOTA concentration map obtained after a successful sonication session. Images are reoriented in order to contain the central axis of the implanted ultrasound implant (shown in pink). The implant region of interest covering brain tissues in the white and gray matter targeted by the ultrasound beam is shown in green. A non-sonicated control region defined in the contralateral hemisphere is also shown. Fig. S4. Acoustic field simulated in the brain for the SonoCloud-1 device at a nominal pressure of 1.03 MPa. The nominal pressure is calibrated in water at the natural focus (red cross) during manufacturing. The acoustic field in brain is evaluated from the measurement in water and considering an attenuation of 0.6 dB/cm/MHz. Table S1. Evaluation of BBB-disruption efficacy with metrics computed from T1 maps acquired after sonication. The differences of Gd-DOTA marked with * are above the criterion for detectable BBB disruption (2 times the standard deviation of all control ROIs, i.e. 13.9 μg). Table S2. Regional standardized uptake value ratios (SUVR) obtained for the amyloid and FDG PET tracers at M0, M4 and M8, presented as average ± standard deviation. The amyloid uptake remained on average stable between M0 and M8 (no statistical difference according to the Wilcoxon signed rank test), while the FDG uptake decreased on average between M0 and M8 (significant difference in the left cortex, and in both the left and right angular + supramarginal + superior temporal gyri according to the Wilcoxon signed rank test after correction for multiple comparisons following the Benjamini-Hochberg procedure). L: left, R: right. Table S3. Comparison of the BOREAL and ADNI populations. No statistical difference exists in terms of age and mini mental state examination (MMSE) score (Kruskal-Wallis H-test) between the BOREAL and ADNI populations, nor in terms of regional PET standardized uptake value ratio (SUVR) at baseline and annualized percent change (APC) computed in both the large and small regions of interest (Kruskal-Wallis H-test with the Benjamini-Hochberg procedure to correct for multiple testing). L: left, R: right.