1 Monitoring Blood-Brain Barrier Opening in Rats with A Preclinical Focused Ultrasound System
Abraham Kraegen edited this page 2025-09-26 10:10:57 +08:00


The brain has a extremely selective semipermeable blood barrier, termed the blood-brain barrier (BBB), which prevents the delivery of therapeutic macromolecular agents to the brain. The combination of MR-guided low-depth pulsed focused ultrasound (FUS) with microbubble pre-injection is a promising technique for non-invasive and BloodVitals test non-toxic BBB modulation. MRI can offer superior delicate-tissue distinction and varied quantitative assessments, akin to vascular permeability, BloodVitals SPO2 perfusion, and the spatial-temporal distribution of MRI distinction agents. Notably, contrast-enhanced MRI strategies with gadolinium-based mostly MR distinction brokers have been proven to be the gold commonplace for detecting BBB openings. This research outlines a comprehensive methodology involving MRI protocols and animal procedures for monitoring BBB opening in a rat model. The rat mannequin gives the added benefit of jugular vein catheter utilization, which facilitates rapid remedy administration. A stereotactic-guided preclinical FUS transducer facilitates the refinement and streamlining of animal procedures and MRI protocols. The resulting strategies are characterized by reproducibility and simplicity, eliminating the necessity for specialized surgical expertise. This research endeavors to contribute to the optimization of preclinical procedures with rat models and encourage additional investigation into the modulation of the BBB to enhance therapeutic interventions in neurological disorders.


Issue date 2021 May. To achieve extremely accelerated sub-millimeter resolution T2-weighted useful MRI at 7T by growing a 3-dimensional gradient and spin echo imaging (GRASE) with inside-quantity choice and variable flip angles (VFA). GRASE imaging has disadvantages in that 1) k-space modulation causes T2 blurring by limiting the variety of slices and 2) a VFA scheme results in partial success with substantial SNR loss. In this work, BloodVitals SPO2 accelerated GRASE with managed T2 blurring is developed to improve some extent unfold operate (PSF) and temporal sign-to-noise ratio (tSNR) with a lot of slices. Numerical and experimental research were performed to validate the effectiveness of the proposed methodology over regular and VFA GRASE (R- and V-GRASE). The proposed methodology, while reaching 0.8mm isotropic resolution, functional MRI compared to R- and V-GRASE improves the spatial extent of the excited quantity up to 36 slices with 52% to 68% full width at half most (FWHM) reduction in PSF but approximately 2- to 3-fold mean tSNR enchancment, thus leading to increased Bold activations.


We efficiently demonstrated the feasibility of the proposed methodology in T2-weighted functional MRI. The proposed methodology is very promising for cortical layer-specific functional MRI. Because the introduction of blood oxygen level dependent (Bold) distinction (1, 2), functional MRI (fMRI) has turn out to be one of many most commonly used methodologies for neuroscience. 6-9), during which Bold results originating from larger diameter draining veins could be considerably distant from the precise websites of neuronal activity. To concurrently achieve high spatial resolution whereas mitigating geometric distortion inside a single acquisition, inside-quantity choice approaches have been utilized (9-13). These approaches use slab selective excitation and BloodVitals device refocusing RF pulses to excite voxels within their intersection, BloodVitals wearable and limit the sector-of-view (FOV), by which the required number of part-encoding (PE) steps are lowered at the identical decision so that the EPI echo prepare size turns into shorter along the section encoding course. Nevertheless, the utility of the inside-quantity primarily based SE-EPI has been limited to a flat piece of cortex with anisotropic decision for masking minimally curved gray matter space (9-11). This makes it difficult to seek out purposes past primary visual areas particularly within the case of requiring isotropic excessive resolutions in other cortical areas.


3D gradient and spin echo imaging (GRASE) with internal-quantity selection, which applies multiple refocusing RF pulses interleaved with EPI echo trains along side SE-EPI, alleviates this problem by permitting for extended quantity imaging with excessive isotropic resolution (12-14). One major concern of using GRASE is picture blurring with a large level spread operate (PSF) within the partition course because of the T2 filtering impact over the refocusing pulse prepare (15, 16). To cut back the image blurring, a variable flip angle (VFA) scheme (17, 18) has been incorporated into the GRASE sequence. The VFA systematically modulates the refocusing flip angles so as to maintain the sign power throughout the echo train (19), thus increasing the Bold sign modifications in the presence of T1-T2 mixed contrasts (20, 21). Despite these benefits, VFA GRASE nonetheless results in important loss of temporal SNR (tSNR) due to diminished refocusing flip angles. Accelerated acquisition in GRASE is an appealing imaging possibility to scale back each refocusing pulse and EPI prepare length at the same time.


On this context, accelerated GRASE coupled with picture reconstruction strategies holds great potential for BloodVitals device both decreasing picture blurring or enhancing spatial volume along each partition and phase encoding instructions. By exploiting multi-coil redundancy in alerts, parallel imaging has been efficiently applied to all anatomy of the body and works for each 2D and 3D acquisitions (22-25). Kemper et al (19) explored a mixture of VFA GRASE with parallel imaging to increase quantity coverage. However, the restricted FOV, localized by only a few receiver coils, potentially causes high geometric issue (g-factor) values as a result of unwell-conditioning of the inverse drawback by together with the big number of coils which might be distant from the region of interest, BloodVitals device thus making it challenging to attain detailed signal evaluation. 2) sign variations between the identical section encoding (PE) strains across time introduce image distortions during reconstruction with temporal regularization. To address these points, Bold activation must be separately evaluated for both spatial and temporal characteristics. A time-sequence of fMRI pictures was then reconstructed under the framework of robust principal element analysis (k-t RPCA) (37-40) which may resolve presumably correlated data from unknown partially correlated pictures for reduction of serial correlations.