## 2 Materials and Methods
### Monitoring the Distribution of F&S and Omniscan in the Mouse Brain  
The Hamilton syringe (25 \(\upmu\)L, Hamilton Co., Reno, NV, USA) with the needle (25 Gauge) was mounted onto the injection pump using the stereotactic manipulator ([PERSON], New York, NY, USA). A small cranial burr hole was drilled through the skull using a variable speed dental drill (with a 1 mm drill bit). Five microliters of beta-amyloid (1-42), HiLyte(tm) Fluor 488-labeled (AnaSpec Inc., Fremont, CA, USA) at a rate of 0.1 \(\upmu\)L/min was injected into the right lateral ventricle (AP-1.0 mm; ML--1.4 mm; DV-3.5 mm). The needle was left in the ventricle for 10 min and then removed at a rate of 1 mm/min to prevent the reflux of \(\mathrm{F}\alpha\beta\). The burr hole and scalp incision were closed with bone wax (Ethicon, Somerville, NJ, USA) and with cyanoacrylate glue (Henkel Consumer Adhesive Inc. Scottsdale, AZ, USA), respectively. The real time and ex vivo optical study of the distribution of \(\mathrm{F}\alpha\beta\) was performed immediately (for in vivo) and 1 h (for ex vivo) after intraventricular injection of \(\mathrm{F}\alpha\beta\) in mice with IBBB and OBBB. The 1 h was selected as the time of OBBB, which was established in our previous studies [23,24]. The imaging was performed using homemade optical instrument based on the monochrome camera ac A2040-90 um (Basler AG, Ahrensburg, Germany) and 50 mm 2.8 C-mount CCTV objective lens (Tamron, Saitama, Japan) The lens was attached to the camera with 15 mm extension tube to ensure macro imaging with 23.3 to 31.8 mm field of view depending of the lens focusing ring adjustment. The lens was mounted on the vertical manual translation stage (Standa, Vilnius, Lithuania) above a Petridish where samples were submerged in a buffer solution. The top surface of each sample was covered with 25 \(\times\) 50 \(\times\) 0.17 mm cover glass. The slider with filter sets (49019, 49002, Chroma Technology, Bellows Falls, VT, USA) was placed just below the objective lens. Each filter set was illuminated with homemade condensers with 1 W LEDs (635 nm for 49019; and 460 nm for 49002) to ensure uniform illumination over the camera field of view. Led illuminators were synchronized with camera \"fire\" output. The camera resolution was 2048 \(\times\) 2048 pixels at 12 bit grayscale. Images were ac-quired in a dark room at constant exposure time of 200 ms and other settings kept unchanged for all samples. An image acquisition and processing were performed with custom software developed using the N I Vision and LabVIEW software (National Instruments, Austin, TX, USA) and the FIJI open source image processing package [35]. Image processing procedures were identical for each pair of images (control and laser treated sample) for each channel to ensure an accurate comparison of the fluorescence intensity. The analysis of F\(\alpha\beta\) in the brain slices was carried out on a fluorescence microscopic system described above. For a quantitative analysis of the intensity signal from F\(\alpha\beta\), ImageJ was used for image data processing and analysis. The intensity of fluorescence for each slide was integrated over a rectangular region of interest bounding brain slice. The integral value was divided by slice area. The areas of brain slices were calculated using the plugin \"Analyze Particles\" in the \"Analyze\" tab, which calculates the total area of F\(\alpha\beta\) fluorescence intensity tissue elements--the indicator \"Total Area\". In all cases, 10 regions of interest were analyzed. The distribution of the MRI contrast agent Omniscan(r) (GE Health Care, Chicago, IL, USA, 0.1 mmol/kg) in the mouse brain after its injection into the cortex (AP--1.06 mm; DV--1.0 mm; ML--1.5 mm) was studied during 2 h using an ultra-high-field tomography BioSpec 117/16 USR (11 T, Bruker, Karlsruhe, Germany).